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Greetings and welcome to the

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National Heart,

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Lung and Blood Institute NHLBI

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Workshop on Neurodevelopmental

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Disorders and Sleep.

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I'm Doctor Lawrence Bazer,

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a program Officer in the

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National Center

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on Sleep Disorders Research

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Branch of NHLBI,

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and I'm the organizer

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of this event.

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Over the next couple of days,

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we look forward to hearing from

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our panel

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of experts about the current

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state of the science in this

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rapidly developing field

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and important issues for further

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investigation.

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This slide charts the the the

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the continuing development of

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and brought

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interest in this research area

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and chose the approximately 4

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fold increase in

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publications in this area over

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the past 20 years in Pub Med.

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Also,

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the significance significant

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increase in

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application grant applications

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to NIH on neurodevelopment

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disorders and their

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symptoms over the past

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20 years over that.

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That same period of time.

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Additional indications of

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interest include the some 480

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people registered

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for this workshop.

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I really appreciate your

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participation, everybody who's

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joining,

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and the fact that several

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different NIH institutes and

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centers were involved in

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this workshop,

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either in its development and

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its

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conception, actually

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carrying it out.

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So National Institute of

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Environmental Health Sciences,

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Child Health Institute,

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Human Genome Research Institute,

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NINDS and Neurological Sciences

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Institute,

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as well as National Institutes

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of Mental Health.

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Many thanks to my Co chair is

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Doctor Jared Salton from Brown

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University in the

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EP Bradley Hospital Sleep

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Research Laboratory at Brown and

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Lucia Pesciotto

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from Washington State University

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along with my NIH program

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officer colleagues.

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And special thanks to our

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workshop support team who have

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done a wonderful

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job in getting this workshop

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together and are helping support

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it today.

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So thanks everybody involved in

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the conception and development

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and execution

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of this workshop.

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A few meeting logistics to start

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off, attendees will be muted and

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your cameras

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will be off.

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The chat functionality in

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Microsoft Teams has actually

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been disabled.

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You can't use that,

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but participants can post

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questions in

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the Q&

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A function in Microsoft Teams

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and we're

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going to try and leave a minute

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or two at the end of the

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speaker's talks so we can

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maybe answer one question in

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that period of time.

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If your question is directed to

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a particular speaker,

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maybe you can include their

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name, the name of that speaker

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in your question.

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Questions can also be answered

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online by the speakers after

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their talk is over.

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They can respond to those

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questions and there will

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actually be also a 30 minute

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discussion session at the end of

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the day to address any remaining

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or additional

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questions that might come up

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throughout the course of the

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presentation.

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Stay the workshop support time

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will will again provide a

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warning at about 17 or 18

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minutes after the speakers start

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their talk to try and leave some

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time at the

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end of the talk for a question

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or two the workshop is being

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recorded.

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To enable closed captioning,

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click the CC icon located at the

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bottom

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of your team screen.

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Thanks again to

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everybody participating.

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And I'll turn to my Co chair,

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Jared Sal and from Brown

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University for a

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few introductory remarks about

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the goals and objectives of this

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workshop.

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Thanks, Jared.

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Thank you Larry, and,

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and thank you Lucia for for

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going with us,

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with me,

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and thank you for everyone for

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being here.

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This is going to be a really

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exciting couple of days and I

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just wanted to

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overview a couple of goals for

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our workshop.

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What Lucy and I really were

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hoping to accomplish over the

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next day or two is to

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survey what we know about sleep

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in nerve developmental

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disorders,

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but really what we don't know.

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And so hopefully we're going to

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be be filling in some gaps for

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you,

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but also revealing a number of

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gaps that are apparent.

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This includes both across the

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the type and presentation of

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nerve developmental

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disorders,

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how they progress on across the

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human

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lifespan,

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but also how they translate to

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animal

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models so that we can better

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identify preclinical targets

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that might be

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applicable to clinical studies.

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We want to promote a better

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understanding of the development

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of sleeping circadian

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regulation across typical

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development and how that

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developmental process helps us

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understand the trajectories of

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neurodevelopmental disorders.

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We hope that we can identify

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some factors that might

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distinguish vulnerability and

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resilience to differences in

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sleep and sleep loss that might

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occur across the

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lifespan and how individuals

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with neurodevelopmental

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disorders might be

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differentially responsive to

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these factors.

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And then more broadly,

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we hope to establish a dialogue

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and

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collaboration both between the

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sleep and circadian field and

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then the

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neurodevelopmental field so that

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the 2 fields can come together

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to really move

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the science forward and address

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new and unanswered questions in

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this area.

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We have an amazing slate of

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speakers from both of these

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fields, again,

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focusing both on human work,

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but also on animal models that

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might

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underlie some of the conditions

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that we're going to speak about.

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And I don't want to

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hold up any more time.

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So I'm going to turn it back to

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Larry to introduce our first

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speaker.

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And thank you everyone

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for for being here.

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Thanks, Jared.

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And let's keep those objectives

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in mind when we go through the

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talks in the

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workshop today and and think

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about how the talks are kind of

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addressing those

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objectives.

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So introducing the first speaker

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to considerable honor, then to

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introduce.

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Beth Mallow is the keynote

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speaker for this workshop.

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And she's clearly a widely

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recognized expert in this field.

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She's professor of neurology and

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Pediatrics,

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the director of the Vanderbilt

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Sleep Division,

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holds the Brewery Endowed Chair

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and Child and Cognitive

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Childhood development,

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and serves as the vice chair for

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clinical research in the

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Department of Neurology

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at Vanderbilt University

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Medical School.

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Her research focuses on the

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interface of sleep and epilepsy,

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autism and related or just

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orders of neurodevelopment and

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improving health and

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quality of life for individuals

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with intellectual and

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developmental

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disabilities across

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the lifespan.

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And she's going to provide us an

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overview that will set kind of

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the framework and

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the context for the rest of the

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talks we're going to hear in the

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next couple of

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days.

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Thanks, Beth.

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Thank you.

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I really appreciate having this

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honor to set the stage for our

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workshop the next

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two days, next, next slide.

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I just wanted to quickly go

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through my disclosures and

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acknowledgments.

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I consult for Neuron

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Pharmaceuticals.

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I am gonna briefly mention some

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off label uses of medications

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for sleep in the

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conditions that we're gonna be

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covering or some of the

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conditions we're gonna be

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covering.

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There's there's very little as

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you can imagine that has been

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approved by FDA in

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this area and I know I'm greatly

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appreciative of my grant support

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from

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multiple sources.

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Next,

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what I'm gonna try to do in the

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next few

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minutes is set the tone,

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set the stage for what we're

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going to be

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hearing about in much more

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detail over the next two days.

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I'd like to characterize the

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types of and causes of sleep

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problems common in

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individuals with ND,

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DS neurodevelopmental

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conditions.

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I put this photo in deliberately

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because I say individuals, not

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00:07:28,257 --> 00:07:28,950
children,

305
00:07:28,950 --> 00:07:30,619
because children grow up.

306
00:07:30,619 --> 00:07:32,585
And this is one of my young

307
00:07:32,585 --> 00:07:34,822
adult patients with autism and

308
00:07:34,822 --> 00:07:35,791
intellectual

309
00:07:35,791 --> 00:07:36,591
disability.

310
00:07:36,591 --> 00:07:38,233
He also has sleep apnea,

311
00:07:38,233 --> 00:07:40,414
and that's his mom as well with

312
00:07:40,414 --> 00:07:40,695
us.

313
00:07:41,129 --> 00:07:43,253
And this is something that is

314
00:07:43,253 --> 00:07:45,427
really important to recognize

315
00:07:45,427 --> 00:07:46,401
that it is a

316
00:07:46,401 --> 00:07:47,207
trajectory,

317
00:07:47,207 --> 00:07:49,537
it is a developmental continuum

318
00:07:49,537 --> 00:07:50,138
between

319
00:07:50,138 --> 00:07:52,186
children and adults and also

320
00:07:52,186 --> 00:07:53,942
young adults and teens.

321
00:07:54,509 --> 00:07:55,977
And so we'll do that.

322
00:07:55,977 --> 00:07:58,352
We'll talk about the impact of

323
00:07:58,352 --> 00:07:59,806
improving sleep on

324
00:07:59,806 --> 00:08:02,150
neurodevelopment and also on

325
00:08:02,150 --> 00:08:04,666
aspects related to well-being in

326
00:08:04,666 --> 00:08:07,164
the individual and their family

327
00:08:07,164 --> 00:08:07,889
members.

328
00:08:08,256 --> 00:08:09,780
And then I'll highlight

329
00:08:09,780 --> 00:08:11,812
treatments as well as gaps for

330
00:08:11,812 --> 00:08:12,828
further study.

331
00:08:12,828 --> 00:08:13,395
Next.

332
00:08:16,565 --> 00:08:18,022
Lots of things happen in our

333
00:08:18,022 --> 00:08:19,564
first year of life and we see

334
00:08:19,564 --> 00:08:20,468
that in the EEG.

335
00:08:20,468 --> 00:08:22,404
We see that in progression of

336
00:08:22,404 --> 00:08:24,455
the different sleep stages and

337
00:08:24,455 --> 00:08:25,207
going more

338
00:08:25,207 --> 00:08:25,941
from R.E.M.

339
00:08:25,941 --> 00:08:26,808
to non R.E.M.

340
00:08:26,808 --> 00:08:28,719
And all different changes that

341
00:08:28,719 --> 00:08:30,357
we see that reflect brain

342
00:08:30,357 --> 00:08:31,012
activity.

343
00:08:31,413 --> 00:08:33,405
And I just want to point out

344
00:08:33,405 --> 00:08:35,302
that sleep is critical for

345
00:08:35,302 --> 00:08:36,251
development,

346
00:08:36,251 --> 00:08:37,225
especially for

347
00:08:37,225 --> 00:08:38,687
memory and learning.

348
00:08:38,687 --> 00:08:40,355
And that's what we'll be

349
00:08:40,355 --> 00:08:42,143
focusing on a lot in this

350
00:08:42,143 --> 00:08:42,858
workshop.

351
00:08:43,525 --> 00:08:44,271
For example,

352
00:08:44,271 --> 00:08:46,312
we know that when there's higher

353
00:08:46,312 --> 00:08:46,695
sleep

354
00:08:46,695 --> 00:08:48,350
efficiency in the first few

355
00:08:48,350 --> 00:08:50,100
years of life, where there's

356
00:08:50,100 --> 00:08:51,600
more advanced executive

357
00:08:51,600 --> 00:08:52,703
function later on,

358
00:08:52,703 --> 00:08:54,403
we know that when there are

359
00:08:54,403 --> 00:08:54,970
frequent

360
00:08:54,970 --> 00:08:55,838
night wakings,

361
00:08:55,838 --> 00:08:57,434
it translates into poorer

362
00:08:57,434 --> 00:08:58,073
cognitive

363
00:08:58,073 --> 00:08:58,624
function,

364
00:08:58,624 --> 00:09:00,510
while fewer night wakings have

365
00:09:00,510 --> 00:09:01,076
resulted

366
00:09:01,076 --> 00:09:02,385
in better performance

367
00:09:02,385 --> 00:09:03,445
on memory tasks.

368
00:09:03,445 --> 00:09:06,024
Next slide across the spectrum

369
00:09:06,024 --> 00:09:08,516
of developmental conditions,

370
00:09:08,516 --> 00:09:10,649
there are prominent sleep

371
00:09:10,649 --> 00:09:13,344
disturbances and these can vary

372
00:09:13,344 --> 00:09:15,257
somewhat according to

373
00:09:15,257 --> 00:09:18,002
the condition I've just listed 5

374
00:09:18,002 --> 00:09:20,734
conditions here we'll also hear

375
00:09:20,734 --> 00:09:21,263
about

376
00:09:21,263 --> 00:09:23,999
ADHD, we'll hear about epilepsy,

377
00:09:23,999 --> 00:09:26,735
we'll hear about Rett syndrome.

378
00:09:26,735 --> 00:09:28,145
So this is not an

379
00:09:28,145 --> 00:09:29,804
exhaustive chart I.

380
00:09:29,804 --> 00:09:31,803
I put it up to show you that,

381
00:09:31,803 --> 00:09:34,009
for example, in Smith McGinnis,

382
00:09:34,009 --> 00:09:36,091
there's more insomnia and also

383
00:09:36,091 --> 00:09:37,479
daytime sleepiness,

384
00:09:37,479 --> 00:09:39,547
while in Down syndrome there's

385
00:09:39,547 --> 00:09:41,616
more obstructive sleep apnea.

386
00:09:41,850 --> 00:09:43,602
So the more plus signs,

387
00:09:43,602 --> 00:09:45,887
the more that problem exists.

388
00:09:46,421 --> 00:09:48,188
And there's just a lot of

389
00:09:48,188 --> 00:09:50,279
overlap in terms of the sleep

390
00:09:50,279 --> 00:09:51,793
problems that we see

391
00:09:51,793 --> 00:09:53,194
in these conditions.

392
00:09:53,194 --> 00:09:55,739
But each condition has its own

393
00:09:55,739 --> 00:09:57,265
unique signature.

394
00:09:57,265 --> 00:09:58,437
Next slide,

395
00:09:58,437 --> 00:10:01,712
I also wanted to emphasize the

396
00:10:01,712 --> 00:10:02,804
impact of

397
00:10:02,804 --> 00:10:05,974
sleep on emotional regulation,

398
00:10:05,974 --> 00:10:08,691
core symptoms and daytime

399
00:10:08,691 --> 00:10:09,778
behavior.

400
00:10:09,778 --> 00:10:12,006
And this isn't really important

401
00:10:12,006 --> 00:10:14,135
because we know that sleeping

402
00:10:14,135 --> 00:10:15,383
better in and of

403
00:10:15,383 --> 00:10:16,506
itself reflects

404
00:10:16,506 --> 00:10:17,852
in better health.

405
00:10:17,852 --> 00:10:18,617
We can control

406
00:10:18,617 --> 00:10:19,654
our weight better.

407
00:10:19,654 --> 00:10:20,659
It helps with

408
00:10:20,659 --> 00:10:22,590
cardiovascular outcomes.

409
00:10:23,224 --> 00:10:25,660
It prevents or it ameliorates

410
00:10:25,660 --> 00:10:28,096
the development of diabetes.

411
00:10:28,096 --> 00:10:29,414
If we're if we're sleeping

412
00:10:29,414 --> 00:10:30,732
better, we know all that.

413
00:10:31,132 --> 00:10:33,705
However, in this population,

414
00:10:33,705 --> 00:10:36,066
NDD's, neurodevelopmental

415
00:10:36,066 --> 00:10:37,105
disorders,

416
00:10:37,105 --> 00:10:40,033
there's a huge impact that sleep

417
00:10:40,033 --> 00:10:42,013
can make on emotional

418
00:10:42,013 --> 00:10:43,144
regulation.

419
00:10:43,511 --> 00:10:45,872
So I think of it as as sleep is

420
00:10:45,872 --> 00:10:47,015
a great reset.

421
00:10:47,015 --> 00:10:48,188
We all know, right,

422
00:10:48,188 --> 00:10:49,959
what it's like when we don't

423
00:10:49,959 --> 00:10:50,719
sleep well,

424
00:10:50,719 --> 00:10:52,528
when we're sleep deprived for

425
00:10:52,528 --> 00:10:53,588
whatever reason.

426
00:10:54,389 --> 00:10:56,282
Maybe we're doing too much with

427
00:10:56,282 --> 00:10:57,993
work or family or whatever,

428
00:10:57,993 --> 00:10:59,986
burning the candle at both ends,

429
00:10:59,986 --> 00:11:00,795
so to speak.

430
00:11:01,262 --> 00:11:03,264
And we're grumpy, we're grouchy.

431
00:11:03,264 --> 00:11:05,053
We're more apt to send that

432
00:11:05,053 --> 00:11:07,160
snarky e-mail that we'll regret

433
00:11:07,160 --> 00:11:07,635
later.

434
00:11:08,036 --> 00:11:11,538
And this is where we see it even

435
00:11:11,538 --> 00:11:13,508
more in the NDDS.

436
00:11:13,742 --> 00:11:16,020
The kids, the adults with NDDS,

437
00:11:16,020 --> 00:11:18,436
they really have a lot of issues

438
00:11:18,436 --> 00:11:18,813
with

439
00:11:18,813 --> 00:11:20,686
emotional regulation when

440
00:11:20,686 --> 00:11:22,484
they're sleep deprived.

441
00:11:22,484 --> 00:11:24,392
And we see this actually borne

442
00:11:24,392 --> 00:11:26,279
out by functional MRI studies

443
00:11:26,279 --> 00:11:27,255
that show that

444
00:11:27,255 --> 00:11:29,179
when people are sleep deprived

445
00:11:29,179 --> 00:11:30,765
and they're looking, for

446
00:11:30,765 --> 00:11:31,359
example,

447
00:11:31,359 --> 00:11:33,284
at aversive stimuli like bugs,

448
00:11:33,284 --> 00:11:34,696
crawling or whatever,

449
00:11:34,696 --> 00:11:36,616
they have increased activation

450
00:11:36,616 --> 00:11:37,832
of their amygdala.

451
00:11:38,333 --> 00:11:39,934
They also have decreased

452
00:11:39,934 --> 00:11:41,573
connectivity between the

453
00:11:41,573 --> 00:11:42,871
prefrontal cortex,

454
00:11:42,871 --> 00:11:44,739
which keeps centers like the

455
00:11:44,739 --> 00:11:46,785
amygdala in check when they're

456
00:11:46,785 --> 00:11:47,876
sleep deprived.

457
00:11:47,876 --> 00:11:51,246
So that's one area.

458
00:11:51,546 --> 00:11:54,182
The other is core symptoms.

459
00:11:54,182 --> 00:11:56,051
And this is work that one of my

460
00:11:56,051 --> 00:11:57,957
postdocs, Olivia Veitch, did at

461
00:11:57,957 --> 00:11:59,187
Vanderbilt with us.

462
00:11:59,621 --> 00:12:01,645
She looked at more than 2000

463
00:12:01,645 --> 00:12:03,637
children with autism in the

464
00:12:03,637 --> 00:12:05,260
genetic Simon Simplex

465
00:12:05,260 --> 00:12:07,073
collection and found that

466
00:12:07,073 --> 00:12:08,849
severity scores for core

467
00:12:08,849 --> 00:12:10,698
symptoms like repetitive

468
00:12:10,698 --> 00:12:12,767
behavior restricted interest.

469
00:12:13,535 --> 00:12:15,256
Social interactions were

470
00:12:15,256 --> 00:12:17,302
increased when when children

471
00:12:17,302 --> 00:12:19,274
were sleeping less than or

472
00:12:19,274 --> 00:12:21,292
equal to hours per night and

473
00:12:21,292 --> 00:12:23,501
then the other area is daytime

474
00:12:23,501 --> 00:12:24,679
behavior and we

475
00:12:24,679 --> 00:12:26,902
find that when we improve sleep

476
00:12:26,902 --> 00:12:28,673
either with supplemental

477
00:12:28,673 --> 00:12:29,484
melatonin.

478
00:12:29,484 --> 00:12:31,685
Behavioral sleep education this

479
00:12:31,685 --> 00:12:33,499
results, this is our work

480
00:12:33,499 --> 00:12:35,023
results in decreased

481
00:12:35,023 --> 00:12:37,096
core symptoms, improved mood,

482
00:12:37,096 --> 00:12:39,027
improved parenting stress.

483
00:12:39,694 --> 00:12:41,646
Parents feel more confident as

484
00:12:41,646 --> 00:12:43,306
parents and children have

485
00:12:43,306 --> 00:12:44,899
greater quality of life

486
00:12:44,899 --> 00:12:46,367
when you improve sleep.

487
00:12:46,367 --> 00:12:46,574
So,

488
00:12:46,574 --> 00:12:48,626
so think of it like all these

489
00:12:48,626 --> 00:12:49,404
drugs that

490
00:12:49,404 --> 00:12:51,605
we use to treat irritability and

491
00:12:51,605 --> 00:12:53,875
aggression in these populations.

492
00:12:54,742 --> 00:12:56,340
They all have side effects,

493
00:12:56,340 --> 00:12:58,221
but if we can improve someone's

494
00:12:58,221 --> 00:12:58,646
sleep,

495
00:12:58,646 --> 00:13:00,426
that can not only impact their

496
00:13:00,426 --> 00:13:02,383
health, but all of these issues.

497
00:13:02,383 --> 00:13:02,680
And I,

498
00:13:02,680 --> 00:13:04,196
I think that's really huge and

499
00:13:04,196 --> 00:13:04,752
that's why

500
00:13:04,752 --> 00:13:05,487
I'm so excited.

501
00:13:05,487 --> 00:13:06,895
We're doing this

502
00:13:06,895 --> 00:13:08,656
workshop right now.

503
00:13:08,656 --> 00:13:09,424
Next slide.

504
00:13:11,926 --> 00:13:13,150
There's many different

505
00:13:13,150 --> 00:13:14,929
contributors to sleep problems.

506
00:13:14,929 --> 00:13:16,658
And I'll just say that often

507
00:13:16,658 --> 00:13:18,687
times we emphasize what I put in

508
00:13:18,687 --> 00:13:19,067
here,

509
00:13:19,067 --> 00:13:20,907
read some of these biological,

510
00:13:20,907 --> 00:13:22,871
not that they're not important,

511
00:13:22,871 --> 00:13:24,661
and we're going to hear a lot

512
00:13:24,661 --> 00:13:26,574
about animal models, genetics,

513
00:13:26,574 --> 00:13:27,719
various other areas

514
00:13:27,719 --> 00:13:29,043
in the talks to come.

515
00:13:29,644 --> 00:13:31,646
I just want to make a plug for

516
00:13:31,646 --> 00:13:33,648
the holistic nature of sleep.

517
00:13:33,648 --> 00:13:36,610
And remember that, for example,

518
00:13:36,610 --> 00:13:39,463
a lot of individuals with NDD

519
00:13:39,463 --> 00:13:39,954
have

520
00:13:39,954 --> 00:13:42,802
coexisting medical conditions,

521
00:13:42,802 --> 00:13:45,527
whether it be sleep apnea or

522
00:13:45,527 --> 00:13:46,694
seizures or

523
00:13:46,694 --> 00:13:48,316
reflux or eczema,

524
00:13:48,316 --> 00:13:51,252
or the psychiatric conditions,

525
00:13:51,252 --> 00:13:52,133
anxiety,

526
00:13:52,133 --> 00:13:53,752
depression, ADHD,

527
00:13:53,752 --> 00:13:56,296
all that can contribute to

528
00:13:56,296 --> 00:13:57,372
disordered

529
00:13:57,372 --> 00:13:57,939
sleep.

530
00:13:58,139 --> 00:13:59,830
And then you throw on the

531
00:13:59,830 --> 00:14:01,901
medicines that we use to treat

532
00:14:01,901 --> 00:14:03,144
these conditions,

533
00:14:03,144 --> 00:14:04,487
like the stimulating

534
00:14:04,487 --> 00:14:06,056
antidepressants and the

535
00:14:06,056 --> 00:14:08,229
stimulants for ADHD and seizure

536
00:14:08,229 --> 00:14:08,650
meds,

537
00:14:08,650 --> 00:14:10,756
and you can see where sleep can

538
00:14:10,756 --> 00:14:12,387
definitely take a toll.

539
00:14:12,687 --> 00:14:14,576
So that's one area I wanted to

540
00:14:14,576 --> 00:14:16,504
make sure we kept in mind over

541
00:14:16,504 --> 00:14:17,725
the next two days.

542
00:14:17,725 --> 00:14:18,768
The other is the

543
00:14:18,768 --> 00:14:20,461
behavioral environmental.

544
00:14:20,828 --> 00:14:23,129
A lot of people feel that that

545
00:14:23,129 --> 00:14:25,481
NDDS, individuals with NDD are

546
00:14:25,481 --> 00:14:26,734
not going to do

547
00:14:26,734 --> 00:14:28,241
well with behavioral

548
00:14:28,241 --> 00:14:29,370
interventions.

549
00:14:29,370 --> 00:14:30,606
They need something stronger,

550
00:14:30,606 --> 00:14:31,372
they need a drug.

551
00:14:31,372 --> 00:14:33,445
But actually some of these

552
00:14:33,445 --> 00:14:35,677
individuals do really well,

553
00:14:35,677 --> 00:14:37,900
almost better than typically

554
00:14:37,900 --> 00:14:40,330
developing individuals because

555
00:14:40,330 --> 00:14:41,950
they love routines.

556
00:14:41,950 --> 00:14:44,044
So we see that in autism, for

557
00:14:44,044 --> 00:14:46,181
example, and these strategies

558
00:14:46,181 --> 00:14:47,655
for a sleep habits,

559
00:14:47,655 --> 00:14:48,681
sleep hygiene,

560
00:14:48,681 --> 00:14:51,025
sleep interventions can be very

561
00:14:51,025 --> 00:14:51,826
successful.

562
00:14:52,193 --> 00:14:53,881
Limited, being light too late in

563
00:14:53,881 --> 00:14:55,611
the day, but getting it early in

564
00:14:55,611 --> 00:14:56,097
the day,

565
00:14:56,097 --> 00:14:57,788
limiting those screens, limiting

566
00:14:57,788 --> 00:14:59,413
caffeine, all those things can

567
00:14:59,413 --> 00:14:59,901
be very,

568
00:14:59,901 --> 00:15:00,702
very important.

569
00:15:00,702 --> 00:15:02,070
Increasing exercise.

570
00:15:02,537 --> 00:15:03,554
And then there is that

571
00:15:03,554 --> 00:15:04,572
biological component.

572
00:15:04,572 --> 00:15:05,760
And I'm not going to dwell on

573
00:15:05,760 --> 00:15:06,931
that too much here because I

574
00:15:06,931 --> 00:15:07,809
know you're going to

575
00:15:07,809 --> 00:15:08,449
hear about it in

576
00:15:08,449 --> 00:15:09,210
the talks to come.

577
00:15:09,544 --> 00:15:12,593
I do want to emphasize on the

578
00:15:12,593 --> 00:15:15,116
importance of genetics,

579
00:15:15,116 --> 00:15:18,159
not just the clock genes that

580
00:15:18,159 --> 00:15:21,603
share both impact in NDDS and in

581
00:15:21,603 --> 00:15:22,357
sleep,

582
00:15:22,357 --> 00:15:25,520
but also arousal dysregulation

583
00:15:25,520 --> 00:15:28,263
and melatonin processing.

584
00:15:28,263 --> 00:15:30,812
We can go to the next slide in

585
00:15:30,812 --> 00:15:32,767
arousal dysregulation.

586
00:15:32,767 --> 00:15:34,705
We know that the HPA axis is

587
00:15:34,705 --> 00:15:36,750
dysregulated in both insomnia

588
00:15:36,750 --> 00:15:38,373
and neurodevelopmental

589
00:15:38,373 --> 00:15:39,134
conditions,

590
00:15:39,134 --> 00:15:41,334
and this is an association with

591
00:15:41,334 --> 00:15:42,043
increased

592
00:15:42,043 --> 00:15:43,244
daytime stressors.

593
00:15:43,244 --> 00:15:44,895
So if there are more stressors

594
00:15:44,895 --> 00:15:46,357
on the individual and they

595
00:15:46,357 --> 00:15:47,482
they're starting to

596
00:15:47,482 --> 00:15:48,919
have more irritability and

597
00:15:48,919 --> 00:15:50,675
aggression and meltdowns during

598
00:15:50,675 --> 00:15:51,185
the day,

599
00:15:51,185 --> 00:15:52,830
that can translate into higher

600
00:15:52,830 --> 00:15:54,255
cortisol levels at night,

601
00:15:54,255 --> 00:15:55,790
which interferes with sleep.

602
00:15:55,790 --> 00:15:57,946
And then if you're not sleeping

603
00:15:57,946 --> 00:15:59,730
well, you wake up already

604
00:15:59,730 --> 00:16:00,728
dysregulated.

605
00:16:00,728 --> 00:16:02,870
And you can see there's like a

606
00:16:02,870 --> 00:16:05,056
wheel that we put together off

607
00:16:05,056 --> 00:16:06,367
one of our papers

608
00:16:06,367 --> 00:16:08,518
showing this vicious circle of

609
00:16:08,518 --> 00:16:10,126
becoming more and more

610
00:16:10,126 --> 00:16:12,173
dysregulated related as the

611
00:16:12,173 --> 00:16:13,875
day and evening goes on.

612
00:16:14,976 --> 00:16:17,647
And then in autonomic function,

613
00:16:17,647 --> 00:16:20,305
we see additional evidence for

614
00:16:20,305 --> 00:16:20,748
over

615
00:16:20,748 --> 00:16:23,255
arousal or hyper arousal with

616
00:16:23,255 --> 00:16:24,552
this was work.

617
00:16:24,552 --> 00:16:26,748
We did it at Vanderbilt with one

618
00:16:26,748 --> 00:16:28,189
of our PhD students.

619
00:16:28,623 --> 00:16:30,919
Even when you go to sleep,

620
00:16:30,919 --> 00:16:33,362
kids with autism had higher

621
00:16:33,362 --> 00:16:34,629
resting heart

622
00:16:34,629 --> 00:16:36,675
rates than kids who are

623
00:16:36,675 --> 00:16:38,633
typically developing.

624
00:16:38,633 --> 00:16:40,521
Even when they went to sleep and

625
00:16:40,521 --> 00:16:41,915
those daytime stressors

626
00:16:41,915 --> 00:16:42,704
disappeared,

627
00:16:42,704 --> 00:16:44,501
they still showed evidence for

628
00:16:44,501 --> 00:16:45,340
over arousal.

629
00:16:45,340 --> 00:16:46,852
And we also see this with heart

630
00:16:46,852 --> 00:16:48,158
rate variability and other

631
00:16:48,158 --> 00:16:48,609
studies.

632
00:16:49,110 --> 00:16:49,668
Next,

633
00:16:49,668 --> 00:16:52,989
I want to talk a moment about

634
00:16:52,989 --> 00:16:54,248
melatonin.

635
00:16:55,583 --> 00:16:58,152
It's a hypnotic as well as a

636
00:16:58,152 --> 00:17:00,701
stabilizer of the circadian

637
00:17:00,701 --> 00:17:01,456
rhythm.

638
00:17:01,456 --> 00:17:03,875
So hypnotic is MT1 receptors,

639
00:17:03,875 --> 00:17:06,440
Chronobiotic or stabilizing of

640
00:17:06,440 --> 00:17:07,295
circadian

641
00:17:07,295 --> 00:17:09,330
rhythms is MT2 receptors.

642
00:17:09,530 --> 00:17:11,132
This is the melatonin we make in

643
00:17:11,132 --> 00:17:11,733
our bodies,

644
00:17:11,733 --> 00:17:13,077
not the ones that we buy at

645
00:17:13,077 --> 00:17:14,562
stores, which I'll talk about

646
00:17:14,562 --> 00:17:14,869
next.

647
00:17:15,336 --> 00:17:17,348
And there's a lot of variability

648
00:17:17,348 --> 00:17:19,286
in melatonin in these NDDS and

649
00:17:19,286 --> 00:17:19,674
they,

650
00:17:19,674 --> 00:17:21,239
the levels may be normal,

651
00:17:21,239 --> 00:17:23,166
they may be decreased inverted

652
00:17:23,166 --> 00:17:23,745
in Smith

653
00:17:23,745 --> 00:17:25,130
McGinnis, for example,

654
00:17:25,130 --> 00:17:26,938
where you get more melatonin

655
00:17:26,938 --> 00:17:27,648
during the

656
00:17:27,648 --> 00:17:29,473
day and not as much at night,

657
00:17:29,473 --> 00:17:31,343
which is backwards and can in

658
00:17:31,343 --> 00:17:32,053
contribute

659
00:17:32,053 --> 00:17:33,352
to their insomnia and

660
00:17:33,352 --> 00:17:34,589
daytime sleepiness.

661
00:17:35,256 --> 00:17:36,870
I wanted to emphasize a lot of

662
00:17:36,870 --> 00:17:38,517
people say, well, if melatonin

663
00:17:38,517 --> 00:17:39,560
levels are normal,

664
00:17:39,560 --> 00:17:40,208
the child is

665
00:17:40,208 --> 00:17:41,396
sleeping fine, right?

666
00:17:41,396 --> 00:17:43,765
And it, it actually isn't there.

667
00:17:43,765 --> 00:17:45,635
There are kids with normal

668
00:17:45,635 --> 00:17:47,909
melatonin levels who still have

669
00:17:47,909 --> 00:17:49,303
a lot of insomnia.

670
00:17:49,303 --> 00:17:51,067
And the reason that is,

671
00:17:51,067 --> 00:17:53,516
is that it's not just replacing

672
00:17:53,516 --> 00:17:53,674
a

673
00:17:53,674 --> 00:17:54,528
deficiency,

674
00:17:54,528 --> 00:17:57,000
but we we are seeing impacts on

675
00:17:57,000 --> 00:17:57,478
those

676
00:17:57,478 --> 00:17:59,483
receptors even with normal

677
00:17:59,483 --> 00:18:00,948
endogenous levels.

678
00:18:01,716 --> 00:18:03,749
And then when we treat kids

679
00:18:03,749 --> 00:18:05,442
where we give them the

680
00:18:05,442 --> 00:18:07,288
supplemental melatonin,

681
00:18:07,288 --> 00:18:09,457
we see improvements in sleep.

682
00:18:09,791 --> 00:18:11,387
I think one of the things

683
00:18:11,387 --> 00:18:12,882
driving this is a small

684
00:18:12,882 --> 00:18:14,962
literature on how melatonin may

685
00:18:14,962 --> 00:18:16,824
also act as an anxiolytic and

686
00:18:16,824 --> 00:18:18,855
mitigate that hyper arousal and

687
00:18:18,855 --> 00:18:20,034
anxiety and hyper

688
00:18:20,034 --> 00:18:20,990
arousal are two

689
00:18:20,990 --> 00:18:22,136
different things.

690
00:18:23,171 --> 00:18:23,467
And,

691
00:18:23,467 --> 00:18:25,291
and this may explain why

692
00:18:25,291 --> 00:18:26,507
melatonin works

693
00:18:26,507 --> 00:18:28,770
better in ND DS because we know

694
00:18:28,770 --> 00:18:31,154
that our our individuals with ND

695
00:18:31,154 --> 00:18:32,346
DS have anxiety

696
00:18:32,346 --> 00:18:34,676
often times and they often times

697
00:18:34,676 --> 00:18:36,686
have that inability to shut

698
00:18:36,686 --> 00:18:37,952
their brain down

699
00:18:37,952 --> 00:18:39,253
that over arousal.

700
00:18:39,587 --> 00:18:39,928
Next,

701
00:18:39,928 --> 00:18:41,887
and Speaking of supplemental

702
00:18:41,887 --> 00:18:42,657
melatonin,

703
00:18:42,657 --> 00:18:44,229
this is the number one,

704
00:18:44,229 --> 00:18:46,123
I'm going to call it a drug

705
00:18:46,123 --> 00:18:46,894
because it

706
00:18:46,894 --> 00:18:48,029
really is a drug.

707
00:18:48,029 --> 00:18:51,049
It needs to be regulated by the

708
00:18:51,049 --> 00:18:52,900
FDA in my opinion,

709
00:18:52,900 --> 00:18:55,901
but I do acknowledge that it is

710
00:18:55,901 --> 00:18:59,062
the most studied medication that

711
00:18:59,062 --> 00:19:00,741
we have and this

712
00:19:00,741 --> 00:19:03,482
is in case series randomized

713
00:19:03,482 --> 00:19:05,146
trials, reviews.

714
00:19:05,413 --> 00:19:06,897
Improved sleep latency,

715
00:19:06,897 --> 00:19:09,019
time to fall asleep with minimal

716
00:19:09,019 --> 00:19:09,350
side

717
00:19:09,350 --> 00:19:09,851
effects.

718
00:19:10,785 --> 00:19:11,987
Not surprisingly,

719
00:19:11,987 --> 00:19:13,942
supplemental melatonin when

720
00:19:13,942 --> 00:19:14,956
combined with

721
00:19:14,956 --> 00:19:17,138
behavioral interventions is the

722
00:19:17,138 --> 00:19:19,229
most effective and one of the

723
00:19:19,229 --> 00:19:20,094
most common

724
00:19:20,094 --> 00:19:21,876
types of melatonin is the

725
00:19:21,876 --> 00:19:23,231
immediate release.

726
00:19:23,231 --> 00:19:25,178
But there are prolonged release

727
00:19:25,178 --> 00:19:27,234
perhaps including the one that I

728
00:19:27,234 --> 00:19:28,069
consult with

729
00:19:28,069 --> 00:19:28,515
Neuron,

730
00:19:28,515 --> 00:19:30,348
which they make a tiny micro

731
00:19:30,348 --> 00:19:30,872
tablet.

732
00:19:30,872 --> 00:19:33,032
And I just wanted to emphasize

733
00:19:33,032 --> 00:19:35,235
that that has these have shown

734
00:19:35,235 --> 00:19:36,777
promise in improving

735
00:19:36,777 --> 00:19:38,366
night Wakings in their

736
00:19:38,366 --> 00:19:40,723
developmental conditions because

737
00:19:40,723 --> 00:19:42,049
the the immediate

738
00:19:42,049 --> 00:19:44,235
release only has a duration of

739
00:19:44,235 --> 00:19:45,620
action of an hour,

740
00:19:45,620 --> 00:19:47,649
but the prolonged release is

741
00:19:47,649 --> 00:19:49,736
time released throughout the

742
00:19:49,736 --> 00:19:50,258
night.

743
00:19:50,258 --> 00:19:52,460
So I think that has promised in

744
00:19:52,460 --> 00:19:54,095
night wakings as well.

745
00:19:54,095 --> 00:19:54,538
Next,

746
00:19:54,538 --> 00:19:57,357
I just wanted to also emphasize

747
00:19:57,357 --> 00:19:58,266
before we

748
00:19:58,266 --> 00:20:00,830
move away from melatonin that

749
00:20:00,830 --> 00:20:03,355
there's a lot of controversy

750
00:20:03,355 --> 00:20:05,339
about melatonin right

751
00:20:05,339 --> 00:20:07,809
now because of overdoses and

752
00:20:07,809 --> 00:20:10,426
mixing it with CBD, baking it

753
00:20:10,426 --> 00:20:11,779
into brownies.

754
00:20:13,347 --> 00:20:16,098
Mixing it with Benadryl and the,

755
00:20:16,098 --> 00:20:18,665
the issue here I think is not

756
00:20:18,665 --> 00:20:19,020
the

757
00:20:19,020 --> 00:20:21,528
melatonin as much as the fact

758
00:20:21,528 --> 00:20:23,691
that it's not regulated.

759
00:20:23,691 --> 00:20:24,164
So it's,

760
00:20:24,164 --> 00:20:26,050
it's kind of like the Wild West

761
00:20:26,050 --> 00:20:26,294
and

762
00:20:26,294 --> 00:20:27,900
others like Judy Owens have

763
00:20:27,900 --> 00:20:29,030
spoken about this.

764
00:20:29,030 --> 00:20:30,174
I think the concerns

765
00:20:30,174 --> 00:20:31,032
are very real.

766
00:20:31,465 --> 00:20:33,490
My biggest concern is I don't

767
00:20:33,490 --> 00:20:35,487
want to throw the proverbial

768
00:20:35,487 --> 00:20:36,771
baby out with the

769
00:20:36,771 --> 00:20:38,652
bathwater because melatonin

770
00:20:38,652 --> 00:20:40,855
really works very well in a lot

771
00:20:40,855 --> 00:20:42,276
of individuals with

772
00:20:42,276 --> 00:20:44,502
NDDS for the reasons I mentioned

773
00:20:44,502 --> 00:20:46,346
and I as part of a science

774
00:20:46,346 --> 00:20:48,049
communication project I

775
00:20:48,049 --> 00:20:49,939
did through the Allen Aldis

776
00:20:49,939 --> 00:20:51,670
Center for Communicating

777
00:20:51,670 --> 00:20:52,320
Science,

778
00:20:52,320 --> 00:20:53,359
I was getting a

779
00:20:53,359 --> 00:20:55,022
graduate studies there.

780
00:20:55,990 --> 00:20:58,525
I designed a safety video and

781
00:20:58,525 --> 00:21:01,113
blogs to help families figure

782
00:21:01,113 --> 00:21:02,897
out on their own if

783
00:21:02,897 --> 00:21:05,477
melatonin was right for their

784
00:21:05,477 --> 00:21:07,168
child with autism.

785
00:21:07,168 --> 00:21:09,017
And I think it extends to all

786
00:21:09,017 --> 00:21:11,100
ADDNDDS and maybe even typically

787
00:21:11,100 --> 00:21:12,206
developing kits.

788
00:21:12,206 --> 00:21:12,978
But I want to make

789
00:21:12,978 --> 00:21:14,008
these available to you.

790
00:21:14,008 --> 00:21:15,971
The QR code takes you to the

791
00:21:15,971 --> 00:21:18,145
video and the posts on Medium.

792
00:21:18,813 --> 00:21:21,772
And I think there's a build if

793
00:21:21,772 --> 00:21:24,911
you can go to those next, next,

794
00:21:24,911 --> 00:21:25,620
right?

795
00:21:25,820 --> 00:21:27,517
So a typical scenario,

796
00:21:27,517 --> 00:21:29,730
you can do one more families

797
00:21:29,730 --> 00:21:30,758
will come to

798
00:21:30,758 --> 00:21:32,259
me in clinic, right?

799
00:21:32,259 --> 00:21:33,706
And they will say,

800
00:21:33,706 --> 00:21:35,796
Johnny is sleeping great.

801
00:21:35,796 --> 00:21:37,064
He takes melatonin.

802
00:21:37,064 --> 00:21:38,099
He's doing wonderfully.

803
00:21:38,099 --> 00:21:39,105
And I'm, I'm like,

804
00:21:39,105 --> 00:21:40,334
and why are you here?

805
00:21:40,334 --> 00:21:41,502
Why are you in my clinic?

806
00:21:41,502 --> 00:21:42,536
What's going on?

807
00:21:42,870 --> 00:21:43,258
And oh,

808
00:21:43,258 --> 00:21:45,021
his pediatrician said we had to

809
00:21:45,021 --> 00:21:45,306
stop

810
00:21:45,306 --> 00:21:46,213
melatonin because

811
00:21:46,213 --> 00:21:47,174
it was dangerous.

812
00:21:47,475 --> 00:21:48,155
So I owe,

813
00:21:48,155 --> 00:21:50,016
I spend most of the time

814
00:21:50,016 --> 00:21:51,178
educating them

815
00:21:51,178 --> 00:21:53,180
on the safety of melatonin.

816
00:21:53,180 --> 00:21:55,290
I try to make sure that the

817
00:21:55,290 --> 00:21:57,839
family is using AUS P designated

818
00:21:57,839 --> 00:21:59,353
brand because this

819
00:21:59,353 --> 00:22:01,714
means it's the next best thing

820
00:22:01,714 --> 00:22:03,524
to being FDA approved.

821
00:22:04,458 --> 00:22:05,744
They, the company,

822
00:22:05,744 --> 00:22:07,943
the dietary supplement company

823
00:22:07,943 --> 00:22:08,529
submits

824
00:22:08,529 --> 00:22:10,519
their data to the FDA to get

825
00:22:10,519 --> 00:22:12,851
this designation and it looks at

826
00:22:12,851 --> 00:22:13,434
purity,

827
00:22:13,434 --> 00:22:15,369
it looks at bioavailability.

828
00:22:15,369 --> 00:22:16,584
Because you may have read

829
00:22:16,584 --> 00:22:17,920
there's all these different

830
00:22:17,920 --> 00:22:19,206
melatonin brands that are

831
00:22:19,206 --> 00:22:20,577
all over the map in terms of

832
00:22:20,577 --> 00:22:21,409
bioavailability.

833
00:22:21,409 --> 00:22:22,761
So you know that you're getting

834
00:22:22,761 --> 00:22:23,678
a reputable product,

835
00:22:23,678 --> 00:22:25,061
you know you're getting what the

836
00:22:25,061 --> 00:22:25,579
label says.

837
00:22:25,913 --> 00:22:27,880
Natural and Nature Made are the

838
00:22:27,880 --> 00:22:29,572
two companies with the USP

839
00:22:29,572 --> 00:22:30,418
designation.

840
00:22:30,418 --> 00:22:31,452
So I recommend them.

841
00:22:31,752 --> 00:22:35,845
Next slide and I did want to

842
00:22:35,845 --> 00:22:40,483
touch on other medicines have a

843
00:22:40,483 --> 00:22:42,129
very small

844
00:22:42,129 --> 00:22:43,431
database.

845
00:22:43,431 --> 00:22:46,042
So the only medicine that's been

846
00:22:46,042 --> 00:22:48,373
approved by the FDA that I'm

847
00:22:48,373 --> 00:22:50,204
aware of for sleep in

848
00:22:50,204 --> 00:22:52,750
children is Tasmeltian which is

849
00:22:52,750 --> 00:22:54,475
a melatonin agonist.

850
00:22:54,475 --> 00:22:56,122
It was approved in Smith

851
00:22:56,122 --> 00:22:58,365
McGinnis syndrome and also a non

852
00:22:58,365 --> 00:22:59,346
24 hour sleep

853
00:22:59,346 --> 00:23:00,114
wake cycle.

854
00:23:00,948 --> 00:23:02,406
The other ones that are bold

855
00:23:02,406 --> 00:23:03,957
have some studies but they're

856
00:23:03,957 --> 00:23:04,385
sparse.

857
00:23:05,419 --> 00:23:06,607
We studied gabapentin

858
00:23:06,607 --> 00:23:07,455
at Vanderbilt.

859
00:23:07,455 --> 00:23:08,589
We like it a lot.

860
00:23:08,589 --> 00:23:09,470
It doesn't interact

861
00:23:09,470 --> 00:23:10,257
with other meds.

862
00:23:10,257 --> 00:23:12,793
It it also may work so well

863
00:23:12,793 --> 00:23:15,568
because it it treats restless

864
00:23:15,568 --> 00:23:17,865
legs and restless sleep

865
00:23:17,865 --> 00:23:19,074
and the alpha

866
00:23:19,074 --> 00:23:20,935
adrenergic agonist.

867
00:23:20,935 --> 00:23:23,019
And also there's a recent study

868
00:23:23,019 --> 00:23:24,750
of Doxepin have all shown

869
00:23:24,750 --> 00:23:25,372
promise.

870
00:23:25,372 --> 00:23:28,336
But these are all case series,

871
00:23:28,336 --> 00:23:30,411
20 to 30 kids total,

872
00:23:30,411 --> 00:23:32,546
so very small numbers.

873
00:23:32,546 --> 00:23:33,748
We need more studies.

874
00:23:33,948 --> 00:23:35,382
CBD has been studied.

875
00:23:35,382 --> 00:23:37,354
It was shown not to work in a

876
00:23:37,354 --> 00:23:39,573
randomized trial of 150, did not

877
00:23:39,573 --> 00:23:40,821
show improvement.

878
00:23:40,821 --> 00:23:42,479
And then these other drugs that

879
00:23:42,479 --> 00:23:44,005
we use a lot like Trazodone,

880
00:23:44,005 --> 00:23:45,259
have not been studied.

881
00:23:45,259 --> 00:23:47,341
They need to be studied getting

882
00:23:47,341 --> 00:23:49,259
studies in these about drugs

883
00:23:49,259 --> 00:23:50,698
that are generic and

884
00:23:50,698 --> 00:23:52,846
that have been out there a while

885
00:23:52,846 --> 00:23:54,696
are you know not oftentimes

886
00:23:54,696 --> 00:23:56,203
fundable by by anyone

887
00:23:56,203 --> 00:23:57,938
industry isn't interested.

888
00:23:57,938 --> 00:23:59,112
So that's a challenge

889
00:23:59,112 --> 00:24:00,174
we can talk about.

890
00:24:00,975 --> 00:24:03,263
And then I will mention the

891
00:24:03,263 --> 00:24:06,052
benzodiazepines are very helpful

892
00:24:06,052 --> 00:24:06,313
in

893
00:24:06,313 --> 00:24:08,598
sleepwalking sleep terrors,

894
00:24:08,598 --> 00:24:11,026
but not in the typical night

895
00:24:11,026 --> 00:24:12,153
wakings that

896
00:24:12,153 --> 00:24:13,487
we normally see.

897
00:24:14,021 --> 00:24:15,744
So you want to keep that in mind

898
00:24:15,744 --> 00:24:16,390
next slide.

899
00:24:18,492 --> 00:24:21,061
And I wanted to just mention the

900
00:24:21,061 --> 00:24:23,631
practice pathways very quickly.

901
00:24:24,565 --> 00:24:26,867
We can really encourage people

902
00:24:26,867 --> 00:24:29,170
to screen for sleep problems,

903
00:24:29,170 --> 00:24:30,547
identify these are

904
00:24:30,547 --> 00:24:32,961
pediatricians, identify medical

905
00:24:32,961 --> 00:24:34,909
Co occurring conditions.

906
00:24:35,342 --> 00:24:36,553
Start with behavioral

907
00:24:36,553 --> 00:24:37,244
strategies.

908
00:24:37,244 --> 00:24:39,046
If a family is willing and able,

909
00:24:39,046 --> 00:24:40,848
and I do want to put a plug in,

910
00:24:40,848 --> 00:24:42,627
we're doing a study sponsored by

911
00:24:42,627 --> 00:24:43,851
our sleep foundation.

912
00:24:44,285 --> 00:24:45,665
It does work to do these

913
00:24:45,665 --> 00:24:46,987
behavioral strategies.

914
00:24:46,987 --> 00:24:48,078
The challenge is how

915
00:24:48,078 --> 00:24:49,223
to disseminate them.

916
00:24:49,723 --> 00:24:50,557
For example,

917
00:24:50,557 --> 00:24:52,841
we really lean on our therapists

918
00:24:52,841 --> 00:24:53,127
and

919
00:24:53,127 --> 00:24:55,327
community practices to work with

920
00:24:55,327 --> 00:24:57,570
families, and we're having a lot

921
00:24:57,570 --> 00:24:58,833
of success there,

922
00:24:58,833 --> 00:25:00,625
like behavioral therapists

923
00:25:00,625 --> 00:25:01,936
teaching families.

924
00:25:01,936 --> 00:25:04,057
Sleep medicines should be used

925
00:25:04,057 --> 00:25:05,786
sparingly, hopefully, to

926
00:25:05,786 --> 00:25:07,875
facilitate these strategies.

927
00:25:08,175 --> 00:25:10,461
And if someone has epilepsy or

928
00:25:10,461 --> 00:25:12,878
ADHD, that's a good time to try

929
00:25:12,878 --> 00:25:13,814
to choose a

930
00:25:13,814 --> 00:25:16,261
medicine that can help sleep and

931
00:25:16,261 --> 00:25:17,484
that condition.

932
00:25:17,484 --> 00:25:19,086
And we have these wonderful tool

933
00:25:19,086 --> 00:25:20,725
kits we developed at the Kennedy

934
00:25:20,725 --> 00:25:21,288
Center for

935
00:25:21,288 --> 00:25:22,679
things like sleep studies in

936
00:25:22,679 --> 00:25:23,524
adults and kids.

937
00:25:23,524 --> 00:25:24,391
Next slide.

938
00:25:24,592 --> 00:25:26,193
I think this is my last slide.

939
00:25:26,193 --> 00:25:27,261
Yeah, you have less time.

940
00:25:27,261 --> 00:25:29,096
Yeah, 'cause I wanna wrap up.

941
00:25:29,697 --> 00:25:30,487
So basically,

942
00:25:30,487 --> 00:25:32,433
these are my future directions.

943
00:25:33,634 --> 00:25:35,069
Sleep problems are common.

944
00:25:35,069 --> 00:25:36,804
Take a holistic approach.

945
00:25:36,804 --> 00:25:37,531
Remember the

946
00:25:37,531 --> 00:25:39,106
developmental trajectory.

947
00:25:39,406 --> 00:25:40,944
We'll be hearing more about

948
00:25:40,944 --> 00:25:42,710
neurobiological underpinnings.

949
00:25:43,711 --> 00:25:45,779
We need more research on how do

950
00:25:45,779 --> 00:25:47,350
we implement behavioral

951
00:25:47,350 --> 00:25:48,716
strategies and also

952
00:25:48,716 --> 00:25:50,799
how do we combine medicines and

953
00:25:50,799 --> 00:25:52,867
behavioral strategies with the

954
00:25:52,867 --> 00:25:53,487
input of

955
00:25:53,487 --> 00:25:55,155
individuals and families.

956
00:25:55,155 --> 00:25:56,462
I think that's critical and I

957
00:25:56,462 --> 00:25:57,797
hope we hear a lot about that

958
00:25:57,797 --> 00:25:58,626
over the next two

959
00:25:58,626 --> 00:25:58,859
days.

960
00:25:59,093 --> 00:26:00,345
We need to hear from our

961
00:26:00,345 --> 00:26:01,781
families what they need and

962
00:26:01,781 --> 00:26:03,163
what's important to them.

963
00:26:03,464 --> 00:26:04,859
Thank you very much for your

964
00:26:04,859 --> 00:26:06,333
attention, and I'm excited to

965
00:26:06,333 --> 00:26:07,501
hear the speakers that

966
00:26:07,501 --> 00:26:07,868
follow.

967
00:26:09,970 --> 00:26:10,738
Thanks so much, Beth.

968
00:26:10,738 --> 00:26:12,171
I think this addresses a lot of

969
00:26:12,171 --> 00:26:13,500
the questions that people on

970
00:26:13,500 --> 00:26:13,974
this call

971
00:26:13,974 --> 00:26:15,379
probably have about treatment,

972
00:26:15,379 --> 00:26:16,293
both behavioral and

973
00:26:16,293 --> 00:26:17,111
pharmacological.

974
00:26:17,511 --> 00:26:18,148
So we need to,

975
00:26:18,148 --> 00:26:19,641
we don't have time for questions

976
00:26:19,641 --> 00:26:20,014
on now,

977
00:26:20,014 --> 00:26:20,648
unfortunately.

978
00:26:20,648 --> 00:26:22,250
Hopefully we can entertain

979
00:26:22,250 --> 00:26:24,285
questions at the end of the day,

980
00:26:24,285 --> 00:26:26,286
hopefully or put them in the in

981
00:26:26,286 --> 00:26:28,266
the Q& A of anybody online and

982
00:26:28,266 --> 00:26:29,256
maybe Beth can

983
00:26:29,256 --> 00:26:31,058
answer them online afterwards.

984
00:26:31,892 --> 00:26:33,722
So the next section is common

985
00:26:33,722 --> 00:26:34,795
human disorders.

986
00:26:34,795 --> 00:26:36,747
And it's wonderful to have Shu

987
00:26:36,747 --> 00:26:38,872
Buckley from National Institutes

988
00:26:38,872 --> 00:26:40,000
of Mental Health

989
00:26:40,000 --> 00:26:41,849
serving as the moderator for

990
00:26:41,849 --> 00:26:43,103
that that session.

991
00:26:43,470 --> 00:26:44,702
So Shu, please

992
00:26:44,702 --> 00:26:46,373
start the session.

993
00:26:46,373 --> 00:26:48,676
Hi, hi, great to be here.

994
00:26:48,676 --> 00:26:49,774
Thank you, Beth,

995
00:26:49,774 --> 00:26:51,893
that was fantastic star to our

996
00:26:51,893 --> 00:26:52,246
day.

997
00:26:52,246 --> 00:26:54,503
I'm Shoe Buckley and been at the

998
00:26:54,503 --> 00:26:56,160
NIMH studying sleep and

999
00:26:56,160 --> 00:26:57,818
neurodevelopment for a

1000
00:26:57,818 --> 00:26:58,485
long time.

1001
00:26:58,485 --> 00:27:00,059
I'm very happy to be serving as

1002
00:27:00,059 --> 00:27:00,821
the moderator.

1003
00:27:01,155 --> 00:27:02,879
This next session session will

1004
00:27:02,879 --> 00:27:04,174
feature several common

1005
00:27:04,174 --> 00:27:05,292
neurodevelopmental

1006
00:27:05,292 --> 00:27:05,859
disorders.

1007
00:27:06,226 --> 00:27:07,668
They're likely polygenic in

1008
00:27:07,668 --> 00:27:09,246
origin and they're often they

1009
00:27:09,246 --> 00:27:10,497
present with a variety

1010
00:27:10,497 --> 00:27:11,646
of symptoms, including

1011
00:27:11,646 --> 00:27:12,533
sleep disorders.

1012
00:27:13,067 --> 00:27:14,300
So the first lecture you're

1013
00:27:14,300 --> 00:27:15,661
going to hear is from Heather

1014
00:27:15,661 --> 00:27:16,036
Joseph.

1015
00:27:16,036 --> 00:27:17,695
She is an assistant professor of

1016
00:27:17,695 --> 00:27:19,406
psychiatry and Pediatrics at the

1017
00:27:19,406 --> 00:27:20,648
University of Pittsburgh

1018
00:27:20,648 --> 00:27:21,475
Medical Center.

1019
00:27:21,976 --> 00:27:23,853
Her research focuses on early

1020
00:27:23,853 --> 00:27:25,648
detection of inattention in

1021
00:27:25,648 --> 00:27:26,313
neonates,

1022
00:27:26,313 --> 00:27:28,377
infants and toddlers at risk for

1023
00:27:28,377 --> 00:27:30,094
ADHD and identification of

1024
00:27:30,094 --> 00:27:31,085
protective and

1025
00:27:31,085 --> 00:27:32,286
resilience factors.

1026
00:27:32,486 --> 00:27:34,670
Her talk today is on treatments

1027
00:27:34,670 --> 00:27:36,323
for ADHD, including non

1028
00:27:36,323 --> 00:27:38,192
pharmacologic approaches.

1029
00:27:40,995 --> 00:27:41,462
All right.

1030
00:27:41,462 --> 00:27:43,627
So it's a pleasure to be here

1031
00:27:43,627 --> 00:27:45,835
today and to talk to you very

1032
00:27:45,835 --> 00:27:47,434
briefly about such a

1033
00:27:47,434 --> 00:27:49,823
broad topic of ADHD Co occurring

1034
00:27:49,823 --> 00:27:52,037
sleep problems and and try to

1035
00:27:52,037 --> 00:27:53,107
start to talk

1036
00:27:53,107 --> 00:27:54,933
about non pharmacological

1037
00:27:54,933 --> 00:27:55,809
treatments.

1038
00:27:56,610 --> 00:27:58,000
So I have no conflicts of

1039
00:27:58,000 --> 00:27:59,757
interest to disclose and I will

1040
00:27:59,757 --> 00:28:00,948
share a few findings

1041
00:28:00,948 --> 00:28:02,548
and ongoing studies that have

1042
00:28:02,548 --> 00:28:04,014
been funded by NIH and the

1043
00:28:04,014 --> 00:28:05,085
Klingenstein Third

1044
00:28:05,085 --> 00:28:06,286
Generation Foundation.

1045
00:28:07,254 --> 00:28:09,224
So my objectives for today is to

1046
00:28:09,224 --> 00:28:11,246
provide a very brief overview of

1047
00:28:11,246 --> 00:28:11,625
ADHD,

1048
00:28:11,625 --> 00:28:13,570
review common Co occurring sleep

1049
00:28:13,570 --> 00:28:15,564
problems with ADHD and introduce

1050
00:28:15,564 --> 00:28:16,063
the non

1051
00:28:16,063 --> 00:28:17,860
pharmacological interventions

1052
00:28:17,860 --> 00:28:19,099
for sleep and ADHD.

1053
00:28:19,533 --> 00:28:21,187
And I will focus primarily on

1054
00:28:21,187 --> 00:28:22,669
adolescents and children.

1055
00:28:24,571 --> 00:28:25,620
So ADHD is a common

1056
00:28:25,620 --> 00:28:27,136
neurodevelopmental disorder

1057
00:28:27,136 --> 00:28:28,876
affecting one in nine children

1058
00:28:28,876 --> 00:28:30,480
in the US and it's associated

1059
00:28:30,480 --> 00:28:32,008
with significant impairment

1060
00:28:32,008 --> 00:28:32,913
across multiple

1061
00:28:32,913 --> 00:28:34,365
domains, including health,

1062
00:28:34,365 --> 00:28:35,482
social functioning,

1063
00:28:35,482 --> 00:28:36,884
academic and occupational.

1064
00:28:37,351 --> 00:28:38,266
And importantly,

1065
00:28:38,266 --> 00:28:39,967
as many as 2/3 of individuals

1066
00:28:39,967 --> 00:28:40,554
that have

1067
00:28:40,554 --> 00:28:42,218
ADHD in childhood continue to

1068
00:28:42,218 --> 00:28:43,920
meet full diagnostic criteria

1069
00:28:43,920 --> 00:28:44,858
into adulthood.

1070
00:28:45,225 --> 00:28:47,201
And even those who don't don't

1071
00:28:47,201 --> 00:28:49,153
meet full diagnostic criteria

1072
00:28:49,153 --> 00:28:50,297
continue to have

1073
00:28:50,297 --> 00:28:51,765
significant impairment.

1074
00:28:53,867 --> 00:28:55,409
ADHD is associated with a

1075
00:28:55,409 --> 00:28:57,369
variety of genes, environmental

1076
00:28:57,369 --> 00:28:57,938
factors,

1077
00:28:57,938 --> 00:28:59,423
and differences in brain

1078
00:28:59,423 --> 00:29:00,908
structure and function.

1079
00:29:00,908 --> 00:29:02,610
But there is no single cause of

1080
00:29:02,610 --> 00:29:04,292
ADHD, and each factor that has

1081
00:29:04,292 --> 00:29:05,245
been found to be

1082
00:29:05,245 --> 00:29:06,964
associated really only accounts

1083
00:29:06,964 --> 00:29:08,446
for a small portion of the

1084
00:29:08,446 --> 00:29:09,016
variance.

1085
00:29:09,817 --> 00:29:10,292
However,

1086
00:29:10,292 --> 00:29:11,995
we do know that ADHD runs in

1087
00:29:11,995 --> 00:29:12,786
families and

1088
00:29:12,786 --> 00:29:13,954
is highly heritable.

1089
00:29:16,056 --> 00:29:18,392
So here I share with you the DSM

1090
00:29:18,392 --> 00:29:20,727
criteria for ADHD in childhood.

1091
00:29:20,727 --> 00:29:22,703
It's required that the children

1092
00:29:22,703 --> 00:29:24,657
have 6 symptoms of inattentive

1093
00:29:24,657 --> 00:29:25,699
or hyperactive,

1094
00:29:25,699 --> 00:29:26,341
impulsive,

1095
00:29:26,341 --> 00:29:28,116
and if they have a combined

1096
00:29:28,116 --> 00:29:29,036
presentation,

1097
00:29:29,036 --> 00:29:31,067
it's 6 symptoms in each category

1098
00:29:31,067 --> 00:29:32,370
and falling into the

1099
00:29:32,370 --> 00:29:33,607
neurodevelopmental

1100
00:29:33,607 --> 00:29:34,174
category.

1101
00:29:34,174 --> 00:29:36,166
These symptoms really are

1102
00:29:36,166 --> 00:29:38,078
onsetting in childhood,

1103
00:29:38,078 --> 00:29:40,601
so they must be present prior to

1104
00:29:40,601 --> 00:29:43,096
age 12 and that there are clear

1105
00:29:43,096 --> 00:29:44,384
symptoms in two

1106
00:29:44,384 --> 00:29:46,927
or more domains to more settings

1107
00:29:46,927 --> 00:29:49,389
of impairment and functioning.

1108
00:29:50,824 --> 00:29:52,598
When you enter adulthood,

1109
00:29:52,598 --> 00:29:54,931
the symptom criteria is lessened

1110
00:29:54,931 --> 00:29:55,295
to 5

1111
00:29:55,295 --> 00:29:56,830
instead of 6 symptoms.

1112
00:29:57,064 --> 00:29:58,725
And partly that's trying to

1113
00:29:58,725 --> 00:30:00,169
account for some of the

1114
00:30:00,169 --> 00:30:01,802
developmental changes and

1115
00:30:01,802 --> 00:30:03,537
maybe the appropriateness or

1116
00:30:03,537 --> 00:30:05,378
inappropriateness at times of

1117
00:30:05,378 --> 00:30:06,140
some of the

1118
00:30:06,140 --> 00:30:08,008
symptoms in the DSM for adults.

1119
00:30:08,809 --> 00:30:09,898
So for example,

1120
00:30:09,898 --> 00:30:11,766
these are the inattentive

1121
00:30:11,766 --> 00:30:12,513
symptoms.

1122
00:30:12,513 --> 00:30:14,396
If you look through some of

1123
00:30:14,396 --> 00:30:16,544
these easily distracted, loses

1124
00:30:16,544 --> 00:30:17,117
things,

1125
00:30:17,117 --> 00:30:19,353
doesn't listen when spoken to.

1126
00:30:19,353 --> 00:30:21,121
Some of that may be present in

1127
00:30:21,121 --> 00:30:22,890
childhood and into adulthood.

1128
00:30:23,190 --> 00:30:23,657
However,

1129
00:30:23,657 --> 00:30:25,526
when you're looking at the more

1130
00:30:25,526 --> 00:30:27,371
hyperactive, impulsive symptoms,

1131
00:30:27,371 --> 00:30:28,911
some of these things are a

1132
00:30:28,911 --> 00:30:29,563
little bit

1133
00:30:29,563 --> 00:30:31,398
more easy to see in children and

1134
00:30:31,398 --> 00:30:33,104
and by adulthood you've had a

1135
00:30:33,104 --> 00:30:33,634
lot more

1136
00:30:33,634 --> 00:30:34,368
compensation.

1137
00:30:34,368 --> 00:30:36,076
You might not be getting out of

1138
00:30:36,076 --> 00:30:37,154
your seat when it's

1139
00:30:37,154 --> 00:30:38,005
inappropriate.

1140
00:30:38,572 --> 00:30:40,243
So there's just a little bit

1141
00:30:40,243 --> 00:30:41,832
more wiggle room for adult

1142
00:30:41,832 --> 00:30:42,809
diagnosis here.

1143
00:30:44,645 --> 00:30:46,298
So the relation between sleep

1144
00:30:46,298 --> 00:30:47,781
and ADHD is multifaceted.

1145
00:30:47,781 --> 00:30:48,783
There are three,

1146
00:30:48,783 --> 00:30:50,851
there are potentially 3 separate

1147
00:30:50,851 --> 00:30:52,252
relations between them.

1148
00:30:52,886 --> 00:30:54,152
So just for example,

1149
00:30:54,152 --> 00:30:55,972
you might have ADHD symptoms

1150
00:30:55,972 --> 00:30:56,557
that are

1151
00:30:56,557 --> 00:30:58,198
impairing one's ability to

1152
00:30:58,198 --> 00:30:59,874
organize themselves around

1153
00:30:59,874 --> 00:31:01,228
bedtime and get into

1154
00:31:01,228 --> 00:31:01,995
bed on time.

1155
00:31:02,196 --> 00:31:04,040
That might be resulting in

1156
00:31:04,040 --> 00:31:06,210
shortened sleep duration, more

1157
00:31:06,210 --> 00:31:07,801
variable sleep onset,

1158
00:31:07,801 --> 00:31:09,718
or you may have sleep sleep

1159
00:31:09,718 --> 00:31:11,602
disorder primarily that is

1160
00:31:11,602 --> 00:31:13,340
resulting in poor sleep

1161
00:31:13,340 --> 00:31:14,974
and more inattentive or

1162
00:31:14,974 --> 00:31:17,151
cognitive impairments that may

1163
00:31:17,151 --> 00:31:18,312
present as ADHD

1164
00:31:18,312 --> 00:31:18,946
symptoms.

1165
00:31:19,313 --> 00:31:21,008
And then the third option is

1166
00:31:21,008 --> 00:31:22,798
perhaps that there's a common

1167
00:31:22,798 --> 00:31:24,218
underlying 'cause that

1168
00:31:24,218 --> 00:31:26,036
is linking both sleep and ADHD

1169
00:31:26,036 --> 00:31:27,829
symptoms, like for depression

1170
00:31:27,829 --> 00:31:29,189
might be one example.

1171
00:31:32,092 --> 00:31:33,999
So when we think about the sleep

1172
00:31:33,999 --> 00:31:35,651
problems presenting as ADHD

1173
00:31:35,651 --> 00:31:36,263
symptoms,

1174
00:31:36,263 --> 00:31:37,584
it's really important,

1175
00:31:37,584 --> 00:31:39,126
as the first talk kind of

1176
00:31:39,126 --> 00:31:39,866
alluded to,

1177
00:31:39,866 --> 00:31:41,294
that individuals who are

1178
00:31:41,294 --> 00:31:43,050
presenting for ADHD diagnosis

1179
00:31:43,050 --> 00:31:44,504
are evaluated for sleep

1180
00:31:44,504 --> 00:31:45,046
concerns,

1181
00:31:45,046 --> 00:31:46,222
and there should be

1182
00:31:46,222 --> 00:31:47,274
consideration of

1183
00:31:47,274 --> 00:31:49,003
whether there's an underlying

1184
00:31:49,003 --> 00:31:50,831
sleep problem that is actually

1185
00:31:50,831 --> 00:31:51,745
presenting and

1186
00:31:51,745 --> 00:31:53,247
confounding the diagnosis.

1187
00:31:54,181 --> 00:31:54,929
For example,

1188
00:31:54,929 --> 00:31:56,590
obstructive sleep apnea is

1189
00:31:56,590 --> 00:31:57,484
almost always

1190
00:31:57,484 --> 00:31:59,219
associated with inattention,

1191
00:31:59,219 --> 00:32:00,997
and restless leg syndrome is

1192
00:32:00,997 --> 00:32:01,822
present with

1193
00:32:01,822 --> 00:32:03,674
about 1/4 of the children with

1194
00:32:03,674 --> 00:32:05,437
restless leg syndrome having

1195
00:32:05,437 --> 00:32:06,760
symptoms that appear

1196
00:32:06,760 --> 00:32:07,394
like ADHD.

1197
00:32:08,061 --> 00:32:09,620
It's also true that individuals

1198
00:32:09,620 --> 00:32:11,161
with ADHD do have higher rates

1199
00:32:11,161 --> 00:32:11,932
of these sleep

1200
00:32:11,932 --> 00:32:12,432
disorders.

1201
00:32:12,432 --> 00:32:14,968
So it's not just One Direction.

1202
00:32:14,968 --> 00:32:16,883
There are also greater risk for

1203
00:32:16,883 --> 00:32:17,871
these symptoms,

1204
00:32:17,871 --> 00:32:19,790
even if it's not just the sleep

1205
00:32:19,790 --> 00:32:21,708
disorder presenting like ADHD.

1206
00:32:23,510 --> 00:32:25,079
So sleep problems are common

1207
00:32:25,079 --> 00:32:26,737
amongst individuals with ADHD

1208
00:32:26,737 --> 00:32:27,881
across the lifespan

1209
00:32:27,881 --> 00:32:28,877
and they really do

1210
00:32:28,877 --> 00:32:29,983
begin in childhood.

1211
00:32:30,817 --> 00:32:32,695
There you can see that across

1212
00:32:32,695 --> 00:32:34,424
childhood, adolescents and

1213
00:32:34,424 --> 00:32:35,155
adulthood,

1214
00:32:35,155 --> 00:32:37,161
the rates of sleep problems are

1215
00:32:37,161 --> 00:32:39,140
70 to 80% for individuals with

1216
00:32:39,140 --> 00:32:40,460
ADHD as compared to

1217
00:32:40,460 --> 00:32:41,469
20 to 45% in the

1218
00:32:41,469 --> 00:32:42,729
general population.

1219
00:32:44,298 --> 00:32:46,369
And adolescence is a period of

1220
00:32:46,369 --> 00:32:48,350
increased sleep difficulties

1221
00:32:48,350 --> 00:32:49,269
even amongst

1222
00:32:49,269 --> 00:32:50,971
individuals without ADHD.

1223
00:32:51,271 --> 00:32:53,122
And this is often due to more

1224
00:32:53,122 --> 00:32:55,205
transitions to independence with

1225
00:32:55,205 --> 00:32:56,376
less oversight on

1226
00:32:56,376 --> 00:32:57,420
sleep schedules,

1227
00:32:57,420 --> 00:32:59,246
shift in biological timing,

1228
00:32:59,246 --> 00:33:01,223
and competing demands for their

1229
00:33:01,223 --> 00:33:02,916
schedules, so after school

1230
00:33:02,916 --> 00:33:04,284
activities and early

1231
00:33:04,284 --> 00:33:05,485
school start times.

1232
00:33:06,253 --> 00:33:07,742
But adolescents with ADHD

1233
00:33:07,742 --> 00:33:09,319
experience even more sleep

1234
00:33:09,319 --> 00:33:10,957
problems than their peers,

1235
00:33:10,957 --> 00:33:12,510
including delayed onset of

1236
00:33:12,510 --> 00:33:14,361
sleep, shorter sleep duration,

1237
00:33:14,361 --> 00:33:15,487
poor sleep quality,

1238
00:33:15,487 --> 00:33:17,372
more variability in their sleep

1239
00:33:17,372 --> 00:33:17,798
timing

1240
00:33:17,798 --> 00:33:19,633
and greater daytime sleepiness.

1241
00:33:21,768 --> 00:33:23,538
There's also some evidence to

1242
00:33:23,538 --> 00:33:25,039
suggest that ADHD may be

1243
00:33:25,039 --> 00:33:26,039
associated with

1244
00:33:26,039 --> 00:33:27,614
disturbances and circadian

1245
00:33:27,614 --> 00:33:29,098
rhythms, such as greater

1246
00:33:29,098 --> 00:33:30,644
tendency for eveningness

1247
00:33:30,644 --> 00:33:32,224
later, which is, you know,

1248
00:33:32,224 --> 00:33:33,967
having later bedtimes, later

1249
00:33:33,967 --> 00:33:34,715
wait times,

1250
00:33:34,715 --> 00:33:36,290
and later peak arousal for

1251
00:33:36,290 --> 00:33:37,684
individuals with ADHD.

1252
00:33:40,554 --> 00:33:42,079
And a meta analysis of of So

1253
00:33:42,079 --> 00:33:43,643
when we think about children

1254
00:33:43,643 --> 00:33:44,257
with ADHD,

1255
00:33:44,257 --> 00:33:45,933
there's a meta analysis done to

1256
00:33:45,933 --> 00:33:47,645
kind of look at parent reported

1257
00:33:47,645 --> 00:33:48,528
sleep problems.

1258
00:33:49,062 --> 00:33:50,686
And there are several things

1259
00:33:50,686 --> 00:33:52,577
that were reported by parents of

1260
00:33:52,577 --> 00:33:53,700
children with ADHD

1261
00:33:53,700 --> 00:33:55,394
more frequently than children

1262
00:33:55,394 --> 00:33:57,311
than parents of children without

1263
00:33:57,311 --> 00:33:57,671
ADHD.

1264
00:33:58,004 --> 00:34:00,082
And the largest difference was

1265
00:34:00,082 --> 00:34:01,675
in bedtime resistance.

1266
00:34:05,412 --> 00:34:07,407
So insomnia is a common clinical

1267
00:34:07,407 --> 00:34:09,193
concern for individuals with

1268
00:34:09,193 --> 00:34:10,150
ADHD and their

1269
00:34:10,150 --> 00:34:12,037
parents of young children with

1270
00:34:12,037 --> 00:34:13,987
ADHD presenting to the clinic.

1271
00:34:13,987 --> 00:34:15,684
We hear a lot about sleep

1272
00:34:15,684 --> 00:34:17,924
problems, particularly insomnia.

1273
00:34:18,525 --> 00:34:20,020
And not only, you know, in the

1274
00:34:20,020 --> 00:34:21,497
first talk, we also mentioned

1275
00:34:21,497 --> 00:34:22,362
like insomnia is

1276
00:34:22,362 --> 00:34:23,943
associated with many things that

1277
00:34:23,943 --> 00:34:25,155
these sleep problems are

1278
00:34:25,155 --> 00:34:26,166
disrupting not just

1279
00:34:26,166 --> 00:34:26,666
the child,

1280
00:34:26,666 --> 00:34:27,897
but their family and the

1281
00:34:27,897 --> 00:34:28,769
parenting stress

1282
00:34:28,769 --> 00:34:30,220
and parenting functioning and

1283
00:34:30,220 --> 00:34:31,071
self competency.

1284
00:34:31,471 --> 00:34:33,018
So we also see that it's

1285
00:34:33,018 --> 00:34:34,992
associated with increased ADHD

1286
00:34:34,992 --> 00:34:36,176
symptom severity,

1287
00:34:36,176 --> 00:34:37,861
risk for other psychiatric

1288
00:34:37,861 --> 00:34:39,387
concerns, mental health

1289
00:34:39,387 --> 00:34:40,647
symptoms, anxiety,

1290
00:34:40,647 --> 00:34:42,115
depression or even ODD.

1291
00:34:42,582 --> 00:34:44,864
And it is related to poorer ADHD

1292
00:34:44,864 --> 00:34:46,837
treatment response and then

1293
00:34:46,837 --> 00:34:47,788
worse health

1294
00:34:47,788 --> 00:34:49,734
related quality of life for

1295
00:34:49,734 --> 00:34:51,825
children and their families.

1296
00:34:53,493 --> 00:34:55,866
So one example from my work is

1297
00:34:55,866 --> 00:34:58,286
that the we examined 2 cohorts

1298
00:34:58,286 --> 00:34:59,900
of individuals with

1299
00:34:59,900 --> 00:35:02,382
and without ADHD as new parents

1300
00:35:02,382 --> 00:35:03,904
and their infants.

1301
00:35:03,904 --> 00:35:06,133
And so really I'm looking at the

1302
00:35:06,133 --> 00:35:08,140
heritability of ADHD and how

1303
00:35:08,140 --> 00:35:08,642
family

1304
00:35:08,642 --> 00:35:10,108
factors might predict

1305
00:35:10,108 --> 00:35:12,170
differences in child outcomes

1306
00:35:12,170 --> 00:35:13,947
and trying to find early

1307
00:35:13,947 --> 00:35:15,649
signals of risk for ADHD.

1308
00:35:16,116 --> 00:35:17,562
But when we followed these

1309
00:35:17,562 --> 00:35:18,952
children longitudinally,

1310
00:35:18,952 --> 00:35:20,671
we were able to look at parents

1311
00:35:20,671 --> 00:35:22,318
and and what factors might be

1312
00:35:22,318 --> 00:35:23,056
different in

1313
00:35:23,056 --> 00:35:24,691
parents with and without ADHD.

1314
00:35:26,126 --> 00:35:27,116
So in our sample,

1315
00:35:27,116 --> 00:35:28,966
we found that parents with ADHD

1316
00:35:28,966 --> 00:35:29,563
and their

1317
00:35:29,563 --> 00:35:31,115
Co parents reported greater

1318
00:35:31,115 --> 00:35:32,936
parenting distress in the first

1319
00:35:32,936 --> 00:35:33,934
year postpartum.

1320
00:35:34,534 --> 00:35:35,992
And we wanted to examine what

1321
00:35:35,992 --> 00:35:37,378
factors might be predicting

1322
00:35:37,378 --> 00:35:38,405
parenting distress.

1323
00:35:39,573 --> 00:35:41,639
One of the largest things we saw

1324
00:35:41,639 --> 00:35:43,577
here was that in this sample,

1325
00:35:43,577 --> 00:35:45,323
parents with ADHD and their

1326
00:35:45,323 --> 00:35:47,431
partners had significantly worse

1327
00:35:47,431 --> 00:35:48,815
sleep quality in the

1328
00:35:48,815 --> 00:35:50,217
first year postpartum.

1329
00:35:50,584 --> 00:35:52,377
So not just the individual with

1330
00:35:52,377 --> 00:35:54,270
ADHD, but you could imagine that

1331
00:35:54,270 --> 00:35:54,921
if someone

1332
00:35:54,921 --> 00:35:56,315
with a sleep disorder or

1333
00:35:56,315 --> 00:35:58,030
difficulties is in and out of

1334
00:35:58,030 --> 00:35:59,626
the room or disrupting the

1335
00:35:59,626 --> 00:36:00,329
environment,

1336
00:36:00,329 --> 00:36:02,069
that their partner would also

1337
00:36:02,069 --> 00:36:02,729
have worse

1338
00:36:02,729 --> 00:36:03,063
sleep.

1339
00:36:03,697 --> 00:36:06,092
And so these parents and their

1340
00:36:06,092 --> 00:36:07,884
partners with ADHD had

1341
00:36:07,884 --> 00:36:10,003
significantly worse sleep

1342
00:36:10,003 --> 00:36:11,573
quality than parents

1343
00:36:11,573 --> 00:36:12,672
without ADHD.

1344
00:36:12,973 --> 00:36:14,012
And this is in the

1345
00:36:14,012 --> 00:36:15,108
postpartum period.

1346
00:36:15,108 --> 00:36:16,482
So as you can see,

1347
00:36:16,482 --> 00:36:18,987
the mean for the parents without

1348
00:36:18,987 --> 00:36:19,613
ADHD is

1349
00:36:19,613 --> 00:36:21,748
3, which is still not great.

1350
00:36:22,382 --> 00:36:23,581
It which is to kind of be

1351
00:36:23,581 --> 00:36:25,058
expected when you have a young

1352
00:36:25,058 --> 00:36:25,452
infant.

1353
00:36:26,820 --> 00:36:28,435
But what was interesting here is

1354
00:36:28,435 --> 00:36:30,089
that when we considered sleep in

1355
00:36:30,089 --> 00:36:30,657
the model,

1356
00:36:30,657 --> 00:36:32,179
it was associated with greater

1357
00:36:32,179 --> 00:36:33,193
parenting distress.

1358
00:36:33,693 --> 00:36:34,760
And interestingly,

1359
00:36:34,760 --> 00:36:36,583
the association between parent

1360
00:36:36,583 --> 00:36:37,130
ADHD and

1361
00:36:37,130 --> 00:36:39,005
parenting distress was no longer

1362
00:36:39,005 --> 00:36:39,766
significant.

1363
00:36:40,166 --> 00:36:41,431
So this cross-sectional

1364
00:36:41,431 --> 00:36:42,779
association supports the

1365
00:36:42,779 --> 00:36:44,070
possibility that sleep

1366
00:36:44,070 --> 00:36:45,711
quality may mediate the effect

1367
00:36:45,711 --> 00:36:47,407
of ADHD on parenting distress.

1368
00:36:49,009 --> 00:36:50,833
So to shift in the time that I

1369
00:36:50,833 --> 00:36:52,820
have left to talk about some non

1370
00:36:52,820 --> 00:36:53,813
pharmacological

1371
00:36:53,813 --> 00:36:55,520
interventions that have been

1372
00:36:55,520 --> 00:36:57,139
studied in adolescents and

1373
00:36:57,139 --> 00:36:58,385
children with ADHD.

1374
00:36:59,586 --> 00:37:00,700
For adolescents,

1375
00:37:00,700 --> 00:37:02,985
a large majority of the research

1376
00:37:02,985 --> 00:37:03,557
that is

1377
00:37:03,557 --> 00:37:05,714
starting to come online here is

1378
00:37:05,714 --> 00:37:07,999
focusing on cognitive behavioral

1379
00:37:07,999 --> 00:37:08,428
based

1380
00:37:08,428 --> 00:37:09,415
interventions,

1381
00:37:09,415 --> 00:37:11,731
which have been found to improve

1382
00:37:11,731 --> 00:37:12,165
sleep

1383
00:37:12,165 --> 00:37:14,113
and associated mental health

1384
00:37:14,113 --> 00:37:16,106
symptoms in individuals even

1385
00:37:16,106 --> 00:37:17,103
without ADHD.

1386
00:37:17,103 --> 00:37:18,241
So as you can see,

1387
00:37:18,241 --> 00:37:19,863
the there's two published

1388
00:37:19,863 --> 00:37:20,707
studies that

1389
00:37:20,707 --> 00:37:22,646
I'm highlighting here from 2022

1390
00:37:22,646 --> 00:37:24,690
and 2024, as well as a third one

1391
00:37:24,690 --> 00:37:25,712
that is ongoing

1392
00:37:25,712 --> 00:37:27,475
without results yet that are

1393
00:37:27,475 --> 00:37:29,216
really trying to take these

1394
00:37:29,216 --> 00:37:30,183
evidence based

1395
00:37:30,183 --> 00:37:32,009
interventions for adolescents

1396
00:37:32,009 --> 00:37:33,945
and move them into adolescence

1397
00:37:33,945 --> 00:37:34,654
with ADHD.

1398
00:37:35,388 --> 00:37:37,321
And these studies have been

1399
00:37:37,321 --> 00:37:39,512
finding promising results with

1400
00:37:39,512 --> 00:37:40,827
moderate to large

1401
00:37:40,827 --> 00:37:42,410
sleep improvements and

1402
00:37:42,410 --> 00:37:44,461
improvements in other mental

1403
00:37:44,461 --> 00:37:46,366
health symptoms and daily

1404
00:37:46,366 --> 00:37:48,170
functioning and decreased

1405
00:37:48,170 --> 00:37:50,011
nighttime wakefulness and

1406
00:37:50,011 --> 00:37:51,705
daytime sleepiness for

1407
00:37:51,705 --> 00:37:53,173
school aged children.

1408
00:37:53,373 --> 00:37:54,986
There are nearly a dozen

1409
00:37:54,986 --> 00:37:57,112
randomized controlled trials of

1410
00:37:57,112 --> 00:37:58,278
behavioral sleep

1411
00:37:58,278 --> 00:38:00,347
interventions for children with

1412
00:38:00,347 --> 00:38:02,390
ADHD that support improvements

1413
00:38:02,390 --> 00:38:03,617
in sleep and ADHD

1414
00:38:03,617 --> 00:38:04,217
symptoms.

1415
00:38:04,484 --> 00:38:05,934
The majority of these

1416
00:38:05,934 --> 00:38:08,188
interventions are focused around

1417
00:38:08,188 --> 00:38:09,456
sleep hygiene and

1418
00:38:09,456 --> 00:38:11,330
strategies for common sleep

1419
00:38:11,330 --> 00:38:12,926
interfering behaviors,

1420
00:38:12,926 --> 00:38:14,980
and they've been found to have

1421
00:38:14,980 --> 00:38:16,869
reduced sleep problems with

1422
00:38:16,869 --> 00:38:18,198
moderate to severe

1423
00:38:18,198 --> 00:38:19,232
sleep problems.

1424
00:38:20,033 --> 00:38:22,770
And the other group is really

1425
00:38:22,770 --> 00:38:25,857
focused on supporting parents in

1426
00:38:25,857 --> 00:38:27,207
how to reduce

1427
00:38:27,207 --> 00:38:29,873
bedtime resistance and other

1428
00:38:29,873 --> 00:38:31,778
sleep difficulties.

1429
00:38:31,778 --> 00:38:33,426
So this there's a parenting

1430
00:38:33,426 --> 00:38:35,415
piece to it, especially when the

1431
00:38:35,415 --> 00:38:36,783
children are probably

1432
00:38:36,783 --> 00:38:38,429
a little younger and have a

1433
00:38:38,429 --> 00:38:40,172
little more control over the

1434
00:38:40,172 --> 00:38:41,354
sleep environment.

1435
00:38:44,257 --> 00:38:46,053
There is one study that looked

1436
00:38:46,053 --> 00:38:47,954
at weighted blankets as another

1437
00:38:47,954 --> 00:38:48,628
option for

1438
00:38:48,628 --> 00:38:50,565
sleep interventions for children

1439
00:38:50,565 --> 00:38:51,231
with ADHD.

1440
00:38:51,231 --> 00:38:52,330
The mean age for

1441
00:38:52,330 --> 00:38:53,566
the sample was 9.

1442
00:38:53,900 --> 00:38:55,702
And the weighted blanket did

1443
00:38:55,702 --> 00:38:57,548
have a significant impact on

1444
00:38:57,548 --> 00:38:58,405
total sleep,

1445
00:38:58,405 --> 00:38:59,501
sleep efficiency,

1446
00:38:59,501 --> 00:39:01,307
and wake after sleep onset,

1447
00:39:01,307 --> 00:39:03,133
but it did not improve sleep

1448
00:39:03,133 --> 00:39:04,110
onset latency.

1449
00:39:05,045 --> 00:39:06,717
And there's some evidence that

1450
00:39:06,717 --> 00:39:08,425
perhaps it was more beneficial

1451
00:39:08,425 --> 00:39:09,449
for children that

1452
00:39:09,449 --> 00:39:11,108
were a little bit older, 11 to

1453
00:39:11,108 --> 00:39:12,807
14, and that children with the

1454
00:39:12,807 --> 00:39:13,486
inattentive

1455
00:39:13,486 --> 00:39:14,472
presentation might

1456
00:39:14,472 --> 00:39:15,622
have benefited more.

1457
00:39:17,123 --> 00:39:18,960
The one other study I wanted to

1458
00:39:18,960 --> 00:39:20,560
highlight here is ongoing,

1459
00:39:20,560 --> 00:39:22,278
and it's a novel intervention

1460
00:39:22,278 --> 00:39:23,997
called Power Down for Sleep,

1461
00:39:23,997 --> 00:39:25,869
which is a sensory based bedtime

1462
00:39:25,869 --> 00:39:27,368
intervention that teaches

1463
00:39:27,368 --> 00:39:28,268
parents a deep

1464
00:39:28,268 --> 00:39:29,859
pressure massage and guided

1465
00:39:29,859 --> 00:39:31,805
mantra to help settling for bed.

1466
00:39:32,105 --> 00:39:33,409
And this intervention is being

1467
00:39:33,409 --> 00:39:34,742
tested and developed by Doctor

1468
00:39:34,742 --> 00:39:35,408
Hartman at the

1469
00:39:35,408 --> 00:39:36,509
University of Pittsburgh.

1470
00:39:37,177 --> 00:39:38,571
And although the study is

1471
00:39:38,571 --> 00:39:40,334
ongoing, families have reported

1472
00:39:40,334 --> 00:39:41,414
that they like the

1473
00:39:41,414 --> 00:39:42,143
intervention,

1474
00:39:42,143 --> 00:39:43,752
that they feel that it's low

1475
00:39:43,752 --> 00:39:44,384
burden and

1476
00:39:44,384 --> 00:39:45,941
seem to be seeing aspects of

1477
00:39:45,941 --> 00:39:47,305
sleep and falling asleep

1478
00:39:47,305 --> 00:39:48,555
improving in just two

1479
00:39:48,555 --> 00:39:48,888
weeks.

1480
00:39:51,891 --> 00:39:53,554
So the last thing that I was

1481
00:39:53,554 --> 00:39:55,493
going to share with you today is

1482
00:39:55,493 --> 00:39:56,463
another ongoing

1483
00:39:56,463 --> 00:39:56,830
study.

1484
00:39:56,830 --> 00:39:59,527
So this is an NIH sponsored R34

1485
00:39:59,527 --> 00:40:02,193
and the goal of this is really

1486
00:40:02,193 --> 00:40:03,703
to see if we can

1487
00:40:03,703 --> 00:40:05,105
intervene early.

1488
00:40:05,105 --> 00:40:06,647
So ADHD symptoms and sleep

1489
00:40:06,647 --> 00:40:08,339
problems both present before

1490
00:40:08,339 --> 00:40:09,909
school entry and can lead

1491
00:40:09,909 --> 00:40:10,792
to a cascade of

1492
00:40:10,792 --> 00:40:12,145
negative consequences.

1493
00:40:12,378 --> 00:40:14,134
So our team wondered if early

1494
00:40:14,134 --> 00:40:15,996
preventative interventions for

1495
00:40:15,996 --> 00:40:16,616
preschool

1496
00:40:16,616 --> 00:40:18,492
aged children and their parents

1497
00:40:18,492 --> 00:40:20,225
could improve both sleep and

1498
00:40:20,225 --> 00:40:21,154
ADHD symptoms,

1499
00:40:21,154 --> 00:40:22,839
and possibly even before the

1500
00:40:22,839 --> 00:40:24,524
onset of an ADHD diagnosis.

1501
00:40:26,259 --> 00:40:28,343
So to do that we are combining 2

1502
00:40:28,343 --> 00:40:30,296
evidence based interventions.

1503
00:40:30,897 --> 00:40:32,135
So parent behavioral

1504
00:40:32,135 --> 00:40:34,089
interventions are gold standard

1505
00:40:34,089 --> 00:40:35,602
treatment for childhood

1506
00:40:35,602 --> 00:40:37,388
ADHD in the preschool age and

1507
00:40:37,388 --> 00:40:39,337
have been found to be effective

1508
00:40:39,337 --> 00:40:40,406
in reducing ADHD

1509
00:40:40,406 --> 00:40:40,970
symptoms,

1510
00:40:40,970 --> 00:40:42,896
parenting distress and improve

1511
00:40:42,896 --> 00:40:43,409
overall

1512
00:40:43,409 --> 00:40:45,044
parent child relationships.

1513
00:40:45,645 --> 00:40:47,890
And the sleep piece here we are

1514
00:40:47,890 --> 00:40:50,181
combining elements of the Sleep

1515
00:40:50,181 --> 00:40:51,584
Well intervention.

1516
00:40:51,584 --> 00:40:52,335
So I'll share a

1517
00:40:52,335 --> 00:40:53,486
little bit about that.

1518
00:40:54,020 --> 00:40:55,634
So Sleep Well is a brief

1519
00:40:55,634 --> 00:40:57,495
behavioral intervention for

1520
00:40:57,495 --> 00:40:58,391
toddlers and

1521
00:40:58,391 --> 00:41:00,527
preschoolers who have caregivers

1522
00:41:00,527 --> 00:41:02,514
reporting poor sleep problems

1523
00:41:02,514 --> 00:41:03,062
for the

1524
00:41:03,062 --> 00:41:03,463
child.

1525
00:41:04,130 --> 00:41:06,169
And this intervention has been

1526
00:41:06,169 --> 00:41:08,178
developed and tested by Ariel

1527
00:41:08,178 --> 00:41:09,702
Williamson and it was

1528
00:41:09,702 --> 00:41:11,662
really adapted with community

1529
00:41:11,662 --> 00:41:13,387
engagement, meant to be a

1530
00:41:13,387 --> 00:41:14,974
comprehensive model to

1531
00:41:14,974 --> 00:41:16,678
address poor sleep health

1532
00:41:16,678 --> 00:41:18,280
behaviors, insomnia and

1533
00:41:18,280 --> 00:41:19,813
insufficient sleep in

1534
00:41:19,813 --> 00:41:21,845
toddlers and preschoolers with

1535
00:41:21,845 --> 00:41:23,938
an emphasis on strategies that

1536
00:41:23,938 --> 00:41:24,217
are

1537
00:41:24,217 --> 00:41:26,110
accessible and acceptable to

1538
00:41:26,110 --> 00:41:27,700
individuals living in a

1539
00:41:27,700 --> 00:41:29,289
disadvantaged context.

1540
00:41:32,792 --> 00:41:34,981
So combining that with COPE,

1541
00:41:34,981 --> 00:41:37,143
which is coping with a DHDA

1542
00:41:37,143 --> 00:41:38,264
commonly used

1543
00:41:38,264 --> 00:41:40,613
parent behavioral intervention

1544
00:41:40,613 --> 00:41:42,612
that has been adapted for

1545
00:41:42,612 --> 00:41:44,370
several ADHD clinical

1546
00:41:44,370 --> 00:41:46,520
trials across preschool and

1547
00:41:46,520 --> 00:41:47,874
early childhood.

1548
00:41:48,341 --> 00:41:50,368
We are able to infuse the sleep

1549
00:41:50,368 --> 00:41:52,108
well content into the COPE

1550
00:41:52,108 --> 00:41:53,179
session format,

1551
00:41:53,179 --> 00:41:55,198
which includes success oriented

1552
00:41:55,198 --> 00:41:56,792
homework, some videotape

1553
00:41:56,792 --> 00:41:58,585
vignettes for the parents,

1554
00:41:58,585 --> 00:42:00,665
brainstorming with the therapist

1555
00:42:00,665 --> 00:42:02,061
around strategies for

1556
00:42:02,061 --> 00:42:03,656
implementing the skills

1557
00:42:03,656 --> 00:42:05,224
that were taught in that

1558
00:42:05,224 --> 00:42:07,026
session, and then assigning

1559
00:42:07,026 --> 00:42:08,294
specific homework.

1560
00:42:09,662 --> 00:42:10,826
So in this study,

1561
00:42:10,826 --> 00:42:12,931
we are implementing it in five

1562
00:42:12,931 --> 00:42:13,633
pediatric

1563
00:42:13,633 --> 00:42:15,798
practices by 6 behavioral health

1564
00:42:15,798 --> 00:42:18,017
specialists that are embedded in

1565
00:42:18,017 --> 00:42:18,571
each of

1566
00:42:18,571 --> 00:42:20,273
the primary care offices.

1567
00:42:20,740 --> 00:42:22,268
It will enroll 30,

1568
00:42:22,268 --> 00:42:25,056
it'll enroll 50 preschoolers and

1569
00:42:25,056 --> 00:42:25,578
their

1570
00:42:25,578 --> 00:42:27,262
parents and the ages

1571
00:42:27,262 --> 00:42:29,115
of the three to five.

1572
00:42:29,449 --> 00:42:31,191
And these children are at risk

1573
00:42:31,191 --> 00:42:33,089
for ADHD, meaning that they have

1574
00:42:33,089 --> 00:42:33,920
elevated ADHD

1575
00:42:33,920 --> 00:42:35,435
symptoms, so four or more,

1576
00:42:35,435 --> 00:42:37,291
but they do not have to have an

1577
00:42:37,291 --> 00:42:37,590
ADHD

1578
00:42:37,590 --> 00:42:38,191
diagnosis.

1579
00:42:38,791 --> 00:42:40,628
And the families are being

1580
00:42:40,628 --> 00:42:42,592
randomized either to coping

1581
00:42:42,592 --> 00:42:43,029
only.

1582
00:42:43,029 --> 00:42:44,541
So the the standard parent

1583
00:42:44,541 --> 00:42:46,442
behavioral intervention or sleep

1584
00:42:46,442 --> 00:42:47,333
focused parent

1585
00:42:47,333 --> 00:42:48,742
behavioral intervention,

1586
00:42:48,742 --> 00:42:50,616
the Oasis intervention and it's

1587
00:42:50,616 --> 00:42:50,737
6

1588
00:42:50,737 --> 00:42:51,722
sessions and it's

1589
00:42:51,722 --> 00:42:52,939
delivered virtually.

1590
00:42:54,407 --> 00:42:55,978
So some of the parenting

1591
00:42:55,978 --> 00:42:58,112
strategies that are used are the

1592
00:42:58,112 --> 00:42:59,512
praise and attending

1593
00:42:59,512 --> 00:43:01,394
planned ignoring transitional

1594
00:43:01,394 --> 00:43:03,320
warnings when then statements

1595
00:43:03,320 --> 00:43:04,250
and incentive

1596
00:43:04,250 --> 00:43:04,784
systems.

1597
00:43:05,184 --> 00:43:07,209
The parents that are enrolled in

1598
00:43:07,209 --> 00:43:09,150
the standard parent behavioral

1599
00:43:09,150 --> 00:43:10,056
training will

1600
00:43:10,056 --> 00:43:11,453
also receive time out,

1601
00:43:11,453 --> 00:43:13,342
but time out was removed from

1602
00:43:13,342 --> 00:43:13,993
our sleep

1603
00:43:13,993 --> 00:43:16,028
enhanced version for the sake of

1604
00:43:16,028 --> 00:43:17,916
time and to include the sleep

1605
00:43:17,916 --> 00:43:18,698
strategies.

1606
00:43:19,299 --> 00:43:20,811
So our sleep strategies,

1607
00:43:20,811 --> 00:43:22,687
everyone receives the bedtime

1608
00:43:22,687 --> 00:43:23,269
routine,

1609
00:43:23,269 --> 00:43:25,228
which is refined throughout the

1610
00:43:25,228 --> 00:43:27,180
intervention and then a second

1611
00:43:27,180 --> 00:43:27,440
and

1612
00:43:27,440 --> 00:43:29,345
sometimes third sleep strategy

1613
00:43:29,345 --> 00:43:31,166
is selected with the parents

1614
00:43:31,166 --> 00:43:32,011
based on the

1615
00:43:32,011 --> 00:43:33,746
child's presenting problems.

1616
00:43:35,048 --> 00:43:37,092
So the Oasis clinical trial is

1617
00:43:37,092 --> 00:43:38,768
ongoing with 34 families

1618
00:43:38,768 --> 00:43:39,886
enrolled and 50

1619
00:43:39,886 --> 00:43:40,687
anticipated.

1620
00:43:40,687 --> 00:43:42,488
So stay tuned for results.

1621
00:43:45,625 --> 00:43:47,480
And just to kind of conclude

1622
00:43:47,480 --> 00:43:49,586
here, sleep problems are common

1623
00:43:49,586 --> 00:43:50,129
amongst

1624
00:43:50,129 --> 00:43:51,564
individuals with ADHD.

1625
00:43:51,898 --> 00:43:54,050
Behavioral interventions improve

1626
00:43:54,050 --> 00:43:56,069
both sleep and ADHD symptoms.

1627
00:43:56,569 --> 00:43:57,704
And what's next?

1628
00:43:58,271 --> 00:43:59,775
How do we make these evidence

1629
00:43:59,775 --> 00:44:01,472
based interventions scalable and

1630
00:44:01,472 --> 00:44:02,108
accessible?

1631
00:44:02,875 --> 00:44:04,746
And one thing of interest to me

1632
00:44:04,746 --> 00:44:06,476
really is can we reduce ADHD

1633
00:44:06,476 --> 00:44:07,280
symptoms and

1634
00:44:07,280 --> 00:44:08,984
associated impairment before

1635
00:44:08,984 --> 00:44:10,975
school entry by intervening with

1636
00:44:10,975 --> 00:44:11,784
sleep early?

1637
00:44:13,386 --> 00:44:15,710
So thank you to NIH for inviting

1638
00:44:15,710 --> 00:44:17,652
me to speak here for grant

1639
00:44:17,652 --> 00:44:18,324
support.

1640
00:44:18,324 --> 00:44:20,305
And then a special thank you to

1641
00:44:20,305 --> 00:44:21,327
the Oasis team.

1642
00:44:22,428 --> 00:44:23,666
Thank you, doctor Joseph,

1643
00:44:23,666 --> 00:44:25,193
we do have one question in the

1644
00:44:25,193 --> 00:44:25,498
chat,

1645
00:44:25,498 --> 00:44:26,979
but in the interest of time to

1646
00:44:26,979 --> 00:44:27,867
stay on schedule,

1647
00:44:27,867 --> 00:44:29,292
I think I'll just note it and

1648
00:44:29,292 --> 00:44:30,901
maybe we'll get to it at the end

1649
00:44:30,901 --> 00:44:31,504
of the day,

1650
00:44:31,504 --> 00:44:32,572
if that's OK with you.

1651
00:44:32,939 --> 00:44:35,126
Our next speaker is, oh, forgive

1652
00:44:35,126 --> 00:44:37,176
me, Dan, is Renee Shellhouse.

1653
00:44:37,176 --> 00:44:37,577
Dr.

1654
00:44:37,577 --> 00:44:39,102
Shellhouse is the David T

1655
00:44:39,102 --> 00:44:40,721
Blasting game professor of

1656
00:44:40,721 --> 00:44:42,215
neurology at Washington

1657
00:44:42,215 --> 00:44:43,783
University in Saint Louis.

1658
00:44:44,350 --> 00:44:46,023
Her research interests include

1659
00:44:46,023 --> 00:44:47,502
sleep as a marker of brain

1660
00:44:47,502 --> 00:44:48,755
function in newborns,

1661
00:44:48,755 --> 00:44:49,774
neonatal seizures,

1662
00:44:49,774 --> 00:44:51,190
and early life epilepsy.

1663
00:44:51,624 --> 00:44:53,641
Her talk today is on pediatric

1664
00:44:53,641 --> 00:44:55,367
epilepsy and sleep doctor

1665
00:44:55,367 --> 00:44:56,195
Shellhouse.

1666
00:45:00,099 --> 00:45:00,441
Hello,

1667
00:45:00,441 --> 00:45:02,193
Thank you so much for inviting

1668
00:45:02,193 --> 00:45:02,835
me and get

1669
00:45:02,835 --> 00:45:04,103
our screen set up here.

1670
00:45:05,405 --> 00:45:06,548
Thank you so much for the,

1671
00:45:06,548 --> 00:45:07,340
this opportunity.

1672
00:45:07,340 --> 00:45:07,792
And I'm,

1673
00:45:07,792 --> 00:45:09,536
I'm really thrilled that we're

1674
00:45:09,536 --> 00:45:09,942
having

1675
00:45:09,942 --> 00:45:11,579
this workshop today because I

1676
00:45:11,579 --> 00:45:12,902
think, well, we're, I'm

1677
00:45:12,902 --> 00:45:14,514
preaching to the converted,

1678
00:45:14,514 --> 00:45:16,210
but this is a really important

1679
00:45:16,210 --> 00:45:17,947
topic of, of sleep and medical

1680
00:45:17,947 --> 00:45:18,584
disorders.

1681
00:45:19,652 --> 00:45:21,788
These are my disclosures.

1682
00:45:24,123 --> 00:45:26,113
My objectives for this of this

1683
00:45:26,113 --> 00:45:27,939
talk are to talk with you a

1684
00:45:27,939 --> 00:45:29,495
little bit about sleep

1685
00:45:29,495 --> 00:45:31,364
disorders among children and

1686
00:45:31,364 --> 00:45:33,433
adults with severe epilepsies.

1687
00:45:33,699 --> 00:45:35,839
And this is a kind of epilepsy

1688
00:45:35,839 --> 00:45:37,336
that we bucket into.

1689
00:45:37,537 --> 00:45:39,270
Developmental and epileptic

1690
00:45:39,270 --> 00:45:41,379
encephalopathies are the DES and

1691
00:45:41,379 --> 00:45:41,774
think

1692
00:45:41,774 --> 00:45:43,647
about the reasons that people

1693
00:45:43,647 --> 00:45:45,758
with DES may be at high risk for

1694
00:45:45,758 --> 00:45:46,813
sleep disorders

1695
00:45:46,813 --> 00:45:48,609
and talk about the potential

1696
00:45:48,609 --> 00:45:50,443
impacts of treating abnormal

1697
00:45:50,443 --> 00:45:51,818
sleep Physiology for

1698
00:45:51,818 --> 00:45:53,152
people with epilepsy.

1699
00:45:54,587 --> 00:45:56,201
Before I launch into all of

1700
00:45:56,201 --> 00:45:58,162
that, I want to make a shout out

1701
00:45:58,162 --> 00:45:58,591
to the

1702
00:45:58,591 --> 00:46:00,383
American Epilepsy Society that

1703
00:46:00,383 --> 00:46:02,211
has really fantastic resources

1704
00:46:02,211 --> 00:46:03,429
available to any of

1705
00:46:03,429 --> 00:46:05,342
us about sleep and epilepsy that

1706
00:46:05,342 --> 00:46:06,880
can be very helpful for a

1707
00:46:06,880 --> 00:46:07,433
patient.

1708
00:46:08,868 --> 00:46:09,551
I would encourage you

1709
00:46:09,551 --> 00:46:10,169
to check that out.

1710
00:46:12,171 --> 00:46:14,108
I'm a child neurologist and I'm

1711
00:46:14,108 --> 00:46:15,108
an epilepsy Dr.

1712
00:46:15,108 --> 00:46:16,352
by training and interested in

1713
00:46:16,352 --> 00:46:17,210
neonatal neurology.

1714
00:46:17,210 --> 00:46:18,704
So what am I doing in a in a

1715
00:46:18,704 --> 00:46:19,612
sleep symposium?

1716
00:46:20,012 --> 00:46:21,429
I really think that over the

1717
00:46:21,429 --> 00:46:22,628
years, as my career has

1718
00:46:22,628 --> 00:46:23,149
advanced,

1719
00:46:23,149 --> 00:46:24,743
I've become convinced that sleep

1720
00:46:24,743 --> 00:46:26,278
is really the next frontier in

1721
00:46:26,278 --> 00:46:26,586
child

1722
00:46:26,586 --> 00:46:27,553
neurology research.

1723
00:46:28,988 --> 00:46:30,427
Treating sleep disorders in

1724
00:46:30,427 --> 00:46:31,787
typical children improves

1725
00:46:31,787 --> 00:46:33,092
behavior and quality of

1726
00:46:33,092 --> 00:46:34,662
life, and it also helps their

1727
00:46:34,662 --> 00:46:35,528
parents, right?

1728
00:46:37,130 --> 00:46:38,841
Sleep problems are highly

1729
00:46:38,841 --> 00:46:40,656
prevalent in children with

1730
00:46:40,656 --> 00:46:42,401
neurologic disorders and

1731
00:46:42,401 --> 00:46:43,955
abnormal sleep patterns

1732
00:46:43,955 --> 00:46:45,171
even in newborns.

1733
00:46:45,404 --> 00:46:46,924
And then in some of the work

1734
00:46:46,924 --> 00:46:48,582
that my team has done predicts

1735
00:46:48,582 --> 00:46:49,909
developmental outcomes.

1736
00:46:49,909 --> 00:46:51,991
So even in the first days of

1737
00:46:51,991 --> 00:46:54,352
life, we have an opportunity to

1738
00:46:54,352 --> 00:46:55,114
to study,

1739
00:46:55,114 --> 00:46:57,429
understand and parents identify

1740
00:46:57,429 --> 00:46:59,334
sleep disturbance as high

1741
00:46:59,334 --> 00:47:01,087
priority for research.

1742
00:47:01,888 --> 00:47:03,331
I think it's high time that we

1743
00:47:03,331 --> 00:47:04,854
address sleep as a key strategy

1744
00:47:04,854 --> 00:47:05,591
to improve the

1745
00:47:05,591 --> 00:47:06,826
outcomes for our patients.

1746
00:47:08,728 --> 00:47:09,971
Why am I focusing on the

1747
00:47:09,971 --> 00:47:11,397
developmental and epileptic

1748
00:47:11,397 --> 00:47:12,665
encephalopathies today?

1749
00:47:12,965 --> 00:47:15,112
Simply because epilepsy is a is

1750
00:47:15,112 --> 00:47:17,161
a very large topic and people

1751
00:47:17,161 --> 00:47:18,504
with the DE ES are

1752
00:47:18,504 --> 00:47:19,873
people who have very

1753
00:47:19,873 --> 00:47:21,174
severe epilepsies.

1754
00:47:21,174 --> 00:47:22,997
They have frequent disabling

1755
00:47:22,997 --> 00:47:24,523
seizures and associated

1756
00:47:24,523 --> 00:47:26,579
significant neurodevelopmental

1757
00:47:26,579 --> 00:47:27,413
disabilities.

1758
00:47:29,382 --> 00:47:30,885
Our parents in our in our

1759
00:47:30,885 --> 00:47:32,481
clinics tell us that sleep

1760
00:47:32,481 --> 00:47:33,953
disorders are a serious

1761
00:47:33,953 --> 00:47:34,420
concern.

1762
00:47:34,420 --> 00:47:35,807
They're very common among these

1763
00:47:35,807 --> 00:47:36,389
individuals.

1764
00:47:37,256 --> 00:47:39,007
There's a very high caregiver

1765
00:47:39,007 --> 00:47:40,438
burden related to those

1766
00:47:40,438 --> 00:47:41,060
seizures,

1767
00:47:41,060 --> 00:47:42,391
the neurodevelopmental

1768
00:47:42,391 --> 00:47:44,008
disabilities and the sleep

1769
00:47:44,008 --> 00:47:44,630
problems.

1770
00:47:45,932 --> 00:47:46,772
And so I would,

1771
00:47:46,772 --> 00:47:48,494
I would submit to you that the

1772
00:47:48,494 --> 00:47:49,068
interplay

1773
00:47:49,068 --> 00:47:50,797
between sleep frequent seizures

1774
00:47:50,797 --> 00:47:52,457
and a very abnormal EEG along

1775
00:47:52,457 --> 00:47:52,972
with the

1776
00:47:52,972 --> 00:47:54,580
neurodevelopmental impairment

1777
00:47:54,580 --> 00:47:56,053
positions the DES as ideal

1778
00:47:56,053 --> 00:47:57,243
targets for proof of

1779
00:47:57,243 --> 00:47:58,778
principal sleep research.

1780
00:47:58,778 --> 00:48:00,313
We can make a difference here.

1781
00:48:00,313 --> 00:48:01,598
We can apply it into

1782
00:48:01,598 --> 00:48:02,949
broader communities.

1783
00:48:04,984 --> 00:48:06,197
One of the paradigms of

1784
00:48:06,197 --> 00:48:07,645
developmental and epileptic

1785
00:48:07,645 --> 00:48:09,255
encephalopathies is something

1786
00:48:09,255 --> 00:48:10,489
called Gervais syndrome.

1787
00:48:10,990 --> 00:48:12,715
These children appear to be

1788
00:48:12,715 --> 00:48:14,760
normal when they're first born,

1789
00:48:14,760 --> 00:48:16,744
but within the first year or so

1790
00:48:16,744 --> 00:48:18,842
of life, they begin to have very

1791
00:48:18,842 --> 00:48:19,432
frequent

1792
00:48:19,432 --> 00:48:20,648
disabling seizures,

1793
00:48:20,648 --> 00:48:22,090
and they go on to have

1794
00:48:22,090 --> 00:48:23,336
neurodevelopmental

1795
00:48:23,336 --> 00:48:24,136
disabilities.

1796
00:48:24,971 --> 00:48:26,962
Here's a parent survey of 76

1797
00:48:26,962 --> 00:48:29,069
families who had a child with

1798
00:48:29,069 --> 00:48:30,376
Gervais syndrome.

1799
00:48:30,376 --> 00:48:32,519
Median age of the child of 7.

1800
00:48:32,519 --> 00:48:34,942
5 years and 93% of those parents

1801
00:48:34,942 --> 00:48:35,548
monitor

1802
00:48:35,548 --> 00:48:37,609
their children during sleep,

1803
00:48:37,609 --> 00:48:39,496
with more than half by Co

1804
00:48:39,496 --> 00:48:40,553
sleeping with

1805
00:48:40,553 --> 00:48:41,354
that child.

1806
00:48:41,887 --> 00:48:43,201
The reasons for that are

1807
00:48:43,201 --> 00:48:44,708
manifold but include a high

1808
00:48:44,708 --> 00:48:45,992
incidence of something

1809
00:48:45,992 --> 00:48:47,180
called SUDEP or sudden

1810
00:48:47,180 --> 00:48:48,720
unexpected Death in epilepsy

1811
00:48:48,720 --> 00:48:50,096
patients for people with

1812
00:48:50,096 --> 00:48:51,030
Gervais syndrome.

1813
00:48:51,030 --> 00:48:52,722
So parents are concerned their

1814
00:48:52,722 --> 00:48:54,282
their children might die in

1815
00:48:54,282 --> 00:48:55,034
their sleep,

1816
00:48:55,034 --> 00:48:56,839
but also that there are a lot of

1817
00:48:56,839 --> 00:48:58,343
behavioral concerns around

1818
00:48:58,343 --> 00:48:59,038
sleeping in

1819
00:48:59,038 --> 00:49:00,673
people with Gervais syndrome.

1820
00:49:01,907 --> 00:49:03,192
Half of the parents reported

1821
00:49:03,192 --> 00:49:04,319
sleep disruptions due to

1822
00:49:04,319 --> 00:49:05,211
seizures at night.

1823
00:49:05,778 --> 00:49:07,461
But 3/4 of families also

1824
00:49:07,461 --> 00:49:09,460
reported non seizure related

1825
00:49:09,460 --> 00:49:11,317
nocturnal awakenings more

1826
00:49:11,317 --> 00:49:13,085
than three times per week.

1827
00:49:13,619 --> 00:49:14,648
That's a lot of sleep

1828
00:49:14,648 --> 00:49:16,053
disturbance for this patient

1829
00:49:16,053 --> 00:49:16,656
population.

1830
00:49:19,792 --> 00:49:21,794
In a hot off the presses paper

1831
00:49:21,794 --> 00:49:23,796
that just came out this week,

1832
00:49:23,796 --> 00:49:25,931
there are the study looked at 30

1833
00:49:25,931 --> 00:49:27,644
participants with Gervais

1834
00:49:27,644 --> 00:49:28,534
syndrome who

1835
00:49:28,534 --> 00:49:29,869
had a polysomnogram,

1836
00:49:29,869 --> 00:49:31,724
a mean age of just about 10

1837
00:49:31,724 --> 00:49:32,204
years.

1838
00:49:32,571 --> 00:49:34,523
And what this study showed was

1839
00:49:34,523 --> 00:49:36,409
that they also had activity.

1840
00:49:36,409 --> 00:49:38,379
It's an interesting study that

1841
00:49:38,379 --> 00:49:40,546
children who had tonic seizures,

1842
00:49:40,546 --> 00:49:42,652
they they stiffened during their

1843
00:49:42,652 --> 00:49:44,676
seizures had shorter REM sleep

1844
00:49:44,676 --> 00:49:45,351
duration.

1845
00:49:45,885 --> 00:49:47,721
Children who had convulsive

1846
00:49:47,721 --> 00:49:49,872
seizures, they had shaking with

1847
00:49:49,872 --> 00:49:51,190
their seizures had

1848
00:49:51,190 --> 00:49:53,034
shorter slow wave sleep and

1849
00:49:53,034 --> 00:49:54,126
three duration.

1850
00:49:54,994 --> 00:49:56,784
And even when the children were

1851
00:49:56,784 --> 00:49:57,997
not having seizures,

1852
00:49:57,997 --> 00:49:59,799
the abnormalities that show up

1853
00:49:59,799 --> 00:50:00,700
on their Eegs.

1854
00:50:00,700 --> 00:50:02,689
There's an example here on the

1855
00:50:02,689 --> 00:50:04,856
right with bursts of generalized

1856
00:50:04,856 --> 00:50:05,871
discharges are

1857
00:50:05,871 --> 00:50:07,573
associated with hypotenia.

1858
00:50:07,573 --> 00:50:08,941
So subtle respiratory events.

1859
00:50:10,009 --> 00:50:10,715
Interestingly,

1860
00:50:10,715 --> 00:50:12,178
over the last several years,

1861
00:50:12,178 --> 00:50:13,329
a new medication called

1862
00:50:13,329 --> 00:50:14,551
penfluoramine has become

1863
00:50:14,551 --> 00:50:16,182
available for dreadful syndrome

1864
00:50:16,182 --> 00:50:17,383
and it's very helpful in

1865
00:50:17,383 --> 00:50:18,484
controlling seizures.

1866
00:50:18,851 --> 00:50:21,267
It turns out that the hypotenuse

1867
00:50:21,267 --> 00:50:23,663
were much improved when a child

1868
00:50:23,663 --> 00:50:24,590
was treated

1869
00:50:24,590 --> 00:50:25,624
with lymphoma.

1870
00:50:25,624 --> 00:50:27,044
That's compared to not off that

1871
00:50:27,044 --> 00:50:27,593
medication.

1872
00:50:27,593 --> 00:50:28,427
That's interesting.

1873
00:50:29,328 --> 00:50:31,292
The overall apnea hypopnea index

1874
00:50:31,292 --> 00:50:33,235
or STB sleep disorder breathing

1875
00:50:33,235 --> 00:50:34,300
severity was not

1876
00:50:34,300 --> 00:50:35,701
reported in this paper.

1877
00:50:35,701 --> 00:50:36,347
So there's still

1878
00:50:36,347 --> 00:50:37,236
more work to do here.

1879
00:50:39,872 --> 00:50:41,567
There is a consensus guideline

1880
00:50:41,567 --> 00:50:43,358
on on how you manage people who

1881
00:50:43,358 --> 00:50:44,110
have Gervais

1882
00:50:44,110 --> 00:50:45,871
syndrome and one of the aspects

1883
00:50:45,871 --> 00:50:47,209
that is covered in that

1884
00:50:47,209 --> 00:50:48,314
guideline is sleep

1885
00:50:48,314 --> 00:50:49,648
related recommendations.

1886
00:50:50,049 --> 00:50:51,093
And in this and in the

1887
00:50:51,093 --> 00:50:52,518
development of this guidance,

1888
00:50:52,518 --> 00:50:54,032
there were physicians as well as

1889
00:50:54,032 --> 00:50:55,298
caregivers and people with

1890
00:50:55,298 --> 00:50:55,688
Gervais

1891
00:50:55,688 --> 00:50:56,088
syndrome.

1892
00:50:57,590 --> 00:50:59,180
Virtually all of them agreed

1893
00:50:59,180 --> 00:51:00,981
that sleep problems are seen in

1894
00:51:00,981 --> 00:51:01,794
a majority of

1895
00:51:01,794 --> 00:51:03,462
persons with Gervais syndrome.

1896
00:51:04,663 --> 00:51:05,886
100% of them agreed that

1897
00:51:05,886 --> 00:51:07,547
questions regarding sleep should

1898
00:51:07,547 --> 00:51:08,534
be routinely asked

1899
00:51:08,534 --> 00:51:10,127
as part of continuing care of a

1900
00:51:10,127 --> 00:51:11,771
person with this epilepsy type.

1901
00:51:13,506 --> 00:51:14,976
A formal sleep study should be

1902
00:51:14,976 --> 00:51:16,476
obtained if a clinical history

1903
00:51:16,476 --> 00:51:17,476
of a possible sleep

1904
00:51:17,476 --> 00:51:18,511
disorder is obtained.

1905
00:51:19,979 --> 00:51:20,780
They agreed on this.

1906
00:51:20,780 --> 00:51:22,103
Although I would say it's

1907
00:51:22,103 --> 00:51:23,832
interesting that it was not 100%

1908
00:51:23,832 --> 00:51:24,750
consensus that a

1909
00:51:24,750 --> 00:51:26,338
formal polysomnogram should be

1910
00:51:26,338 --> 00:51:28,017
obtained since that is the gold

1911
00:51:28,017 --> 00:51:28,721
standard for

1912
00:51:28,721 --> 00:51:30,389
diagnosing many sleep disorders.

1913
00:51:30,589 --> 00:51:32,110
So we need to think about that

1914
00:51:32,110 --> 00:51:33,352
and the accessibility of

1915
00:51:33,352 --> 00:51:34,593
polysomnography and the

1916
00:51:34,593 --> 00:51:36,228
acceptability of polysomnography

1917
00:51:36,228 --> 00:51:37,863
for people who have significant

1918
00:51:37,863 --> 00:51:39,365
neurodevelopmental disability.

1919
00:51:40,566 --> 00:51:42,082
Attention to sleep hygiene is,

1920
00:51:42,082 --> 00:51:43,636
is important to managing sleep

1921
00:51:43,636 --> 00:51:44,103
problems

1922
00:51:44,103 --> 00:51:45,009
associated Dravet,

1923
00:51:45,009 --> 00:51:46,461
just like we heard about for

1924
00:51:46,461 --> 00:51:46,772
ADHD.

1925
00:51:47,273 --> 00:51:48,601
I thought this was really

1926
00:51:48,601 --> 00:51:50,118
interesting that only 60% of

1927
00:51:50,118 --> 00:51:51,310
caregivers agree with

1928
00:51:51,310 --> 00:51:52,119
this statement,

1929
00:51:52,119 --> 00:51:53,846
hinting that that there's more,

1930
00:51:53,846 --> 00:51:55,520
more to this story that we need

1931
00:51:55,520 --> 00:51:56,816
to, we need to explore.

1932
00:51:57,450 --> 00:51:59,116
And melatonin we have heard

1933
00:51:59,116 --> 00:52:01,153
about already a couple of times,

1934
00:52:01,153 --> 00:52:02,986
certainly may be considered as

1935
00:52:02,986 --> 00:52:04,921
as one option for treatment for

1936
00:52:04,921 --> 00:52:05,858
sleep problems

1937
00:52:05,858 --> 00:52:07,126
with Dravet syndrome.

1938
00:52:08,627 --> 00:52:09,669
There are lots of other

1939
00:52:09,669 --> 00:52:10,529
kinds of epilepsy.

1940
00:52:10,529 --> 00:52:12,521
As I said at the very beginning,

1941
00:52:12,521 --> 00:52:14,572
the Rare Epilepsy Network funded

1942
00:52:14,572 --> 00:52:14,700
a

1943
00:52:14,700 --> 00:52:16,612
database where parents could go

1944
00:52:16,612 --> 00:52:18,060
in and provide a lot of

1945
00:52:18,060 --> 00:52:19,572
information about their

1946
00:52:19,572 --> 00:52:20,734
children with early

1947
00:52:20,734 --> 00:52:21,774
life epilepsies.

1948
00:52:22,141 --> 00:52:24,197
And parents reported a lot of

1949
00:52:24,197 --> 00:52:26,520
sleep problems in their in their

1950
00:52:26,520 --> 00:52:27,246
children.

1951
00:52:27,246 --> 00:52:28,122
So Geeta Gupta,

1952
00:52:28,122 --> 00:52:29,977
who was doing a postdoc with me

1953
00:52:29,977 --> 00:52:30,516
when she

1954
00:52:30,516 --> 00:52:31,511
wrote this paper,

1955
00:52:31,511 --> 00:52:33,378
looked at the number of parents

1956
00:52:33,378 --> 00:52:33,619
who

1957
00:52:33,619 --> 00:52:35,196
reported sleep concerns for

1958
00:52:35,196 --> 00:52:36,991
their children with early life

1959
00:52:36,991 --> 00:52:37,590
epilepsy.

1960
00:52:37,590 --> 00:52:39,188
And one of the things that was

1961
00:52:39,188 --> 00:52:40,717
interesting was that the the

1962
00:52:40,717 --> 00:52:41,427
number of of

1963
00:52:41,427 --> 00:52:42,863
kids who had sleep concerns

1964
00:52:42,863 --> 00:52:44,498
seemed to increase as children

1965
00:52:44,498 --> 00:52:45,097
got older,

1966
00:52:45,097 --> 00:52:46,597
which is opposite to typical

1967
00:52:46,597 --> 00:52:48,183
typically developing children

1968
00:52:48,183 --> 00:52:49,168
where as parents,

1969
00:52:49,168 --> 00:52:50,767
we are concerned about our our

1970
00:52:50,767 --> 00:52:52,292
baby's sleep when they don't

1971
00:52:52,292 --> 00:52:53,272
sleep through the

1972
00:52:53,272 --> 00:52:54,218
night when they're

1973
00:52:54,218 --> 00:52:55,007
young infants.

1974
00:52:55,007 --> 00:52:55,932
But it tends to get

1975
00:52:55,932 --> 00:52:56,809
better over time.

1976
00:52:57,176 --> 00:52:57,980
For these children,

1977
00:52:57,980 --> 00:52:59,371
they didn't get better over time

1978
00:52:59,371 --> 00:52:59,545
and

1979
00:52:59,545 --> 00:53:00,135
parents became

1980
00:53:00,135 --> 00:53:01,146
increasingly concerned.

1981
00:53:02,581 --> 00:53:04,126
We wondered whether it had

1982
00:53:04,126 --> 00:53:05,765
something to do with having

1983
00:53:05,765 --> 00:53:06,919
seizures at night,

1984
00:53:06,919 --> 00:53:08,585
and many of the children who

1985
00:53:08,585 --> 00:53:10,472
were included in this study did

1986
00:53:10,472 --> 00:53:11,323
have seizures

1987
00:53:11,323 --> 00:53:11,858
at night,

1988
00:53:11,858 --> 00:53:13,562
but that was not the primary

1989
00:53:13,562 --> 00:53:14,293
explanation

1990
00:53:14,293 --> 00:53:16,095
for the the increase the sleep

1991
00:53:16,095 --> 00:53:17,296
concerns over time.

1992
00:53:19,899 --> 00:53:21,593
There are a lot of reasons that

1993
00:53:21,593 --> 00:53:23,332
sleep seizures at night are bad

1994
00:53:23,332 --> 00:53:23,669
news,

1995
00:53:23,669 --> 00:53:25,412
but one of them is that seizures

1996
00:53:25,412 --> 00:53:26,338
can cause apnea.

1997
00:53:26,338 --> 00:53:28,031
Here's Here's simply an example

1998
00:53:28,031 --> 00:53:29,817
of a polysomnogram that happened

1999
00:53:29,817 --> 00:53:30,543
to capture a

2000
00:53:30,543 --> 00:53:31,310
tonic seizure.

2001
00:53:31,710 --> 00:53:34,089
The seizure is the dense spikes

2002
00:53:34,089 --> 00:53:36,440
that you can see in the middle

2003
00:53:36,440 --> 00:53:37,850
of the screen and

2004
00:53:37,850 --> 00:53:39,136
you see the apnea

2005
00:53:39,136 --> 00:53:40,953
indicated by the arrow.

2006
00:53:41,987 --> 00:53:43,670
Now OK, seizures

2007
00:53:43,670 --> 00:53:45,457
can cause apnea.

2008
00:53:45,991 --> 00:53:46,961
Does that mean that we don't

2009
00:53:46,961 --> 00:53:48,058
need to worry about other kinds

2010
00:53:48,058 --> 00:53:48,694
of apnea in these

2011
00:53:48,694 --> 00:53:49,094
children?

2012
00:53:49,094 --> 00:53:49,828
Of course not.

2013
00:53:51,030 --> 00:53:52,253
Absolutely does not mean we

2014
00:53:52,253 --> 00:53:53,684
should ignore concomitant sleep

2015
00:53:53,684 --> 00:53:54,700
disordered breathing.

2016
00:53:56,168 --> 00:53:57,053
Why do we pay so

2017
00:53:57,053 --> 00:53:58,270
much attention to it?

2018
00:53:59,271 --> 00:54:00,867
One one way to look at it is

2019
00:54:00,867 --> 00:54:02,675
that obstructive sleep apnea or

2020
00:54:02,675 --> 00:54:03,375
one form of

2021
00:54:03,375 --> 00:54:04,209
sleep disorder.

2022
00:54:04,209 --> 00:54:05,637
Breathing and epilepsy can

2023
00:54:05,637 --> 00:54:07,204
exacerbate each other make a

2024
00:54:07,204 --> 00:54:08,547
positive feedback loop.

2025
00:54:10,549 --> 00:54:12,851
We have intermittent arousals,

2026
00:54:12,851 --> 00:54:14,386
nocturnal seizures,

2027
00:54:14,386 --> 00:54:16,129
effects of anti seizure

2028
00:54:16,129 --> 00:54:18,524
medicines and behavior problems

2029
00:54:18,524 --> 00:54:19,992
that contribute to

2030
00:54:19,992 --> 00:54:22,434
sleep deprivation and contribute

2031
00:54:22,434 --> 00:54:24,773
to or have concomitant hypoxic

2032
00:54:24,773 --> 00:54:26,098
hypoxemic neuron

2033
00:54:26,098 --> 00:54:26,632
injury.

2034
00:54:27,032 --> 00:54:28,432
You get increase in neural

2035
00:54:28,432 --> 00:54:30,148
inflammation and what does that

2036
00:54:30,148 --> 00:54:30,369
do?

2037
00:54:30,836 --> 00:54:31,873
In a simplistic way,

2038
00:54:31,873 --> 00:54:32,993
it increases neuronal

2039
00:54:32,993 --> 00:54:33,739
excitability,

2040
00:54:33,739 --> 00:54:35,351
which is a problem for somebody

2041
00:54:35,351 --> 00:54:37,052
who already has epilepsy and has

2042
00:54:37,052 --> 00:54:37,743
neurons that

2043
00:54:37,743 --> 00:54:39,211
want to fire abnormal, right?

2044
00:54:39,745 --> 00:54:41,499
Then you have those abnormal

2045
00:54:41,499 --> 00:54:43,315
neuronal firing episodes in,

2046
00:54:43,315 --> 00:54:45,058
in epilepsy that causes more

2047
00:54:45,058 --> 00:54:46,961
seizures and can be associated

2048
00:54:46,961 --> 00:54:48,420
with central apnea and

2049
00:54:48,420 --> 00:54:49,655
with challenges with

2050
00:54:49,655 --> 00:54:50,889
airway muscle tone.

2051
00:54:51,457 --> 00:54:53,323
That airway muscle tone can be

2052
00:54:53,323 --> 00:54:55,361
from abnormality can be from the

2053
00:54:55,361 --> 00:54:56,061
underlying

2054
00:54:56,061 --> 00:54:57,736
epilepsy etiology, from the

2055
00:54:57,736 --> 00:54:59,508
seizures, from the medicines

2056
00:54:59,508 --> 00:55:00,899
that we that we give.

2057
00:55:01,100 --> 00:55:02,761
So lots of reasons to be

2058
00:55:02,761 --> 00:55:04,947
thinking about how can we break

2059
00:55:04,947 --> 00:55:06,639
this potential positive

2060
00:55:06,639 --> 00:55:08,711
feedback loop for somebody who

2061
00:55:08,711 --> 00:55:10,576
has both OSA and epilepsy.

2062
00:55:13,812 --> 00:55:15,361
The good news is that

2063
00:55:15,361 --> 00:55:17,310
obstructive sleep apnea is

2064
00:55:17,310 --> 00:55:19,785
treatable and that the treatment

2065
00:55:19,785 --> 00:55:21,220
might help seizures.

2066
00:55:21,487 --> 00:55:21,918
So in,

2067
00:55:21,918 --> 00:55:24,274
in this meta analysis that's now

2068
00:55:24,274 --> 00:55:24,790
from a

2069
00:55:24,790 --> 00:55:26,071
few years ago now,

2070
00:55:26,071 --> 00:55:28,267
they looked at people who were

2071
00:55:28,267 --> 00:55:28,560
had

2072
00:55:28,560 --> 00:55:30,829
epilepsy and were treated with C

2073
00:55:30,829 --> 00:55:32,938
pap or not treated with C pap

2074
00:55:32,938 --> 00:55:33,666
for their

2075
00:55:33,666 --> 00:55:35,334
obstructive sleep apnea.

2076
00:55:35,768 --> 00:55:37,498
And one of the outcomes was a

2077
00:55:37,498 --> 00:55:38,871
50% seizure reduction.

2078
00:55:38,871 --> 00:55:40,507
So that's a typical trial

2079
00:55:40,507 --> 00:55:42,642
endpoint for testing in medicine

2080
00:55:42,642 --> 00:55:44,043
is how many patients

2081
00:55:44,043 --> 00:55:45,830
have a 50% reduction in the

2082
00:55:45,830 --> 00:55:47,738
number of seizures that they

2083
00:55:47,738 --> 00:55:48,147
have.

2084
00:55:48,781 --> 00:55:50,783
What they found was for people

2085
00:55:50,783 --> 00:55:52,901
who were treated with C pap for

2086
00:55:52,901 --> 00:55:53,652
their OSA,

2087
00:55:53,652 --> 00:55:55,788
the odds ratio of reaching a 50%

2088
00:55:55,788 --> 00:55:57,656
seizure reduction was 6.12.

2089
00:55:58,691 --> 00:55:59,692
It did cross 1,

2090
00:55:59,692 --> 00:56:01,067
so not statistically

2091
00:56:01,067 --> 00:56:01,960
significant,

2092
00:56:01,960 --> 00:56:03,629
but really an interesting

2093
00:56:03,629 --> 00:56:05,030
tantalizing finding.

2094
00:56:06,065 --> 00:56:06,989
Additionally,

2095
00:56:06,989 --> 00:56:09,032
the odds of becoming seizure

2096
00:56:09,032 --> 00:56:09,835
free after

2097
00:56:09,835 --> 00:56:11,819
initiating C pap as compared

2098
00:56:11,819 --> 00:56:14,076
with not become not receiving C

2099
00:56:14,076 --> 00:56:14,440
pap,

2100
00:56:14,440 --> 00:56:16,570
that was an odds ratio of four

2101
00:56:16,570 --> 00:56:18,238
which was statistically

2102
00:56:18,238 --> 00:56:19,978
significant and I think

2103
00:56:19,978 --> 00:56:21,847
clinically very meaningful.

2104
00:56:23,148 --> 00:56:24,862
There are some additional

2105
00:56:24,862 --> 00:56:26,753
studies that have looked at

2106
00:56:26,753 --> 00:56:28,153
similar kinds of of

2107
00:56:28,153 --> 00:56:30,292
designs with outcomes of adults

2108
00:56:30,292 --> 00:56:32,411
with epilepsy who were treated

2109
00:56:32,411 --> 00:56:33,258
with C pap.

2110
00:56:33,892 --> 00:56:35,883
And here's one report where the

2111
00:56:35,883 --> 00:56:37,981
group that was treated with CPAP

2112
00:56:37,981 --> 00:56:38,964
had a 32 times

2113
00:56:38,964 --> 00:56:40,433
increased likelihood of

2114
00:56:40,433 --> 00:56:41,927
achieving a 50% seizure

2115
00:56:41,927 --> 00:56:43,868
reduction compared with those

2116
00:56:43,868 --> 00:56:44,136
who

2117
00:56:44,136 --> 00:56:45,471
did not receive CPAP.

2118
00:56:45,771 --> 00:56:47,473
So this is good news.

2119
00:56:47,473 --> 00:56:49,087
We know how to treat some people

2120
00:56:49,087 --> 00:56:50,683
who have OSA and happen to also

2121
00:56:50,683 --> 00:56:51,610
have epilepsy and

2122
00:56:51,610 --> 00:56:53,024
it can make a difference not

2123
00:56:53,024 --> 00:56:54,674
only in their general well-being

2124
00:56:54,674 --> 00:56:55,447
health and all

2125
00:56:55,447 --> 00:56:56,865
of the things that come with

2126
00:56:56,865 --> 00:56:58,310
obstructive sleep apnea, but

2127
00:56:58,310 --> 00:56:59,651
also with their seizures.

2128
00:57:00,753 --> 00:57:01,653
Why might that be?

2129
00:57:02,488 --> 00:57:02,795
Well,

2130
00:57:02,795 --> 00:57:04,815
lots of potential theories and I

2131
00:57:04,815 --> 00:57:05,257
showed

2132
00:57:05,257 --> 00:57:07,034
you that that initial diagram

2133
00:57:07,034 --> 00:57:08,627
about that feedback loop.

2134
00:57:09,027 --> 00:57:11,248
Another possibility is that the

2135
00:57:11,248 --> 00:57:13,593
the prevalence of EEG spikes may

2136
00:57:13,593 --> 00:57:14,399
be reduced

2137
00:57:14,399 --> 00:57:14,900
by Cpl.

2138
00:57:15,667 --> 00:57:17,600
So the the spikes on an EEG are

2139
00:57:17,600 --> 00:57:19,449
an indicator of a tendency to

2140
00:57:19,449 --> 00:57:20,405
make seizures.

2141
00:57:20,405 --> 00:57:21,617
So if you have fewer spikes,

2142
00:57:21,617 --> 00:57:22,952
you're probably less likely to

2143
00:57:22,952 --> 00:57:23,175
have

2144
00:57:23,175 --> 00:57:23,542
seizures.

2145
00:57:23,542 --> 00:57:26,612
So that that's one possibility.

2146
00:57:27,913 --> 00:57:29,886
Another option that we have for,

2147
00:57:29,886 --> 00:57:30,749
for research,

2148
00:57:30,749 --> 00:57:32,660
and I'm not going to dig deeply

2149
00:57:32,660 --> 00:57:34,618
into this, but just to give you

2150
00:57:34,618 --> 00:57:35,187
an idea,

2151
00:57:35,187 --> 00:57:36,863
is that for people who have

2152
00:57:36,863 --> 00:57:37,856
focal epilepsy,

2153
00:57:37,856 --> 00:57:39,584
who are being considered for

2154
00:57:39,584 --> 00:57:41,603
epilepsy surgery, where the, the

2155
00:57:41,603 --> 00:57:42,361
idea is to,

2156
00:57:42,361 --> 00:57:44,135
to surgically remove the area

2157
00:57:44,135 --> 00:57:46,133
that starts the vast majority of

2158
00:57:46,133 --> 00:57:47,132
their seizures.

2159
00:57:48,233 --> 00:57:49,887
Many of them have intracranial

2160
00:57:49,887 --> 00:57:50,769
EEG monitoring.

2161
00:57:50,769 --> 00:57:53,084
So long term monitoring whether

2162
00:57:53,084 --> 00:57:55,370
they're measuring EEG activity

2163
00:57:55,370 --> 00:57:56,742
directly from the

2164
00:57:56,742 --> 00:57:58,944
brain for many days on on end.

2165
00:57:59,745 --> 00:58:01,970
And what this group reported was

2166
00:58:01,970 --> 00:58:04,169
that the the rate of EEG spikes

2167
00:58:04,169 --> 00:58:05,517
was much higher in

2168
00:58:05,517 --> 00:58:06,218
non R.E.M.

2169
00:58:06,218 --> 00:58:07,286
than in wakefulness.

2170
00:58:08,353 --> 00:58:09,989
And this is something that we've

2171
00:58:09,989 --> 00:58:11,399
kind of known from from the

2172
00:58:11,399 --> 00:58:12,391
scalp EEG world as

2173
00:58:12,391 --> 00:58:12,658
well.

2174
00:58:14,593 --> 00:58:15,677
And that the spatial

2175
00:58:15,677 --> 00:58:17,196
distribution of the spikes,

2176
00:58:17,196 --> 00:58:18,712
so how much of the brain is

2177
00:58:18,712 --> 00:58:20,566
involved is larger in non R.E.M.

2178
00:58:20,566 --> 00:58:21,667
than in wakefulness.

2179
00:58:21,867 --> 00:58:22,747
On the other hand,

2180
00:58:22,747 --> 00:58:24,302
the spatial distribution of the

2181
00:58:24,302 --> 00:58:24,703
seizure

2182
00:58:24,703 --> 00:58:25,243
onset zone,

2183
00:58:25,243 --> 00:58:26,853
exactly where those seizures are

2184
00:58:26,853 --> 00:58:27,306
starting

2185
00:58:27,306 --> 00:58:28,828
in how far the seizure spreads,

2186
00:58:28,828 --> 00:58:30,339
there's not difference between

2187
00:58:30,339 --> 00:58:30,843
sleep and

2188
00:58:30,843 --> 00:58:31,376
wake state.

2189
00:58:31,376 --> 00:58:31,785
So I,

2190
00:58:31,785 --> 00:58:34,461
I present this just as one other

2191
00:58:34,461 --> 00:58:35,214
way that

2192
00:58:35,214 --> 00:58:37,628
we can evaluate in some detail

2193
00:58:37,628 --> 00:58:40,093
the impact of sleep Physiology

2194
00:58:40,093 --> 00:58:41,653
on brain function.

2195
00:58:43,655 --> 00:58:44,945
Then we think about how do we

2196
00:58:44,945 --> 00:58:46,191
treat people with epilepsy.

2197
00:58:46,191 --> 00:58:48,054
And just to state the absolute

2198
00:58:48,054 --> 00:58:50,090
obvious, epilepsy treatments can

2199
00:58:50,090 --> 00:58:50,662
cause or

2200
00:58:50,662 --> 00:58:52,331
exacerbate sleep disorders.

2201
00:58:52,531 --> 00:58:53,632
We know this, right?

2202
00:58:54,967 --> 00:58:56,563
We have lots and lots of anti

2203
00:58:56,563 --> 00:58:58,360
seizure medications and they can

2204
00:58:58,360 --> 00:58:59,371
cause somnolence.

2205
00:58:59,938 --> 00:59:02,741
Those are highlighted in blue

2206
00:59:02,741 --> 00:59:05,544
and they can cause insomnia.

2207
00:59:06,178 --> 00:59:07,142
So we need to pay close

2208
00:59:07,142 --> 00:59:08,340
attention to which medicines

2209
00:59:08,340 --> 00:59:09,281
we're prescribing and

2210
00:59:09,281 --> 00:59:10,626
what the side effects are for an

2211
00:59:10,626 --> 00:59:11,383
individual child.

2212
00:59:12,217 --> 00:59:13,888
Another option for treatment is

2213
00:59:13,888 --> 00:59:15,650
vagal nerve stimulation that can

2214
00:59:15,650 --> 00:59:16,421
be associated

2215
00:59:16,421 --> 00:59:17,831
with exacerbation of sleep

2216
00:59:17,831 --> 00:59:19,024
disordered breathing.

2217
00:59:20,826 --> 00:59:23,188
And about 1/3 of of people with

2218
00:59:23,188 --> 00:59:25,539
epilepsy treated with VNS have

2219
00:59:25,539 --> 00:59:25,931
SDB.

2220
00:59:25,931 --> 00:59:27,226
It doesn't matter if they're

2221
00:59:27,226 --> 00:59:28,567
children or adults, go true.

2222
00:59:29,468 --> 00:59:30,641
On the flip side,

2223
00:59:30,641 --> 00:59:32,481
VNS can also have positive

2224
00:59:32,481 --> 00:59:33,472
impact on the

2225
00:59:33,472 --> 00:59:33,959
spleen,

2226
00:59:33,959 --> 00:59:36,171
especially in situation and the

2227
00:59:36,171 --> 00:59:36,742
overall

2228
00:59:36,742 --> 00:59:38,911
distributions that break stages.

2229
00:59:40,112 --> 00:59:41,882
There's a nice systematic review

2230
00:59:41,882 --> 00:59:43,412
published in Epilepsy a few

2231
00:59:43,412 --> 00:59:44,149
years ago if

2232
00:59:44,149 --> 00:59:45,083
you're interested

2233
00:59:45,083 --> 00:59:46,018
in more details.

2234
00:59:49,388 --> 00:59:51,114
Treating epilepsy and curing the

2235
00:59:51,114 --> 00:59:52,624
seizures can improve sleep.

2236
00:59:52,624 --> 00:59:53,952
This shouldn't be a huge

2237
00:59:53,952 --> 00:59:55,589
surprise, but here's a a nice

2238
00:59:55,589 --> 00:59:56,662
study of 48 adults

2239
00:59:56,662 --> 00:59:58,330
who had temporal lobe epilepsy.

2240
00:59:58,330 --> 00:59:59,110
That they had the

2241
00:59:59,110 --> 01:00:00,165
temporal lobe removed.

2242
01:00:00,165 --> 01:00:01,847
The seizures got all better,

2243
01:00:01,847 --> 01:00:03,693
and every which way you survey

2244
01:00:03,693 --> 01:00:04,369
them about

2245
01:00:04,369 --> 01:00:05,088
their sleep,

2246
01:00:05,088 --> 01:00:06,936
things were better after their

2247
01:00:06,936 --> 01:00:07,306
their

2248
01:00:07,306 --> 01:00:08,407
epilepsy was cured.

2249
01:00:08,974 --> 01:00:10,457
If that's true for people with

2250
01:00:10,457 --> 01:00:11,643
temporal lobe epilepsy,

2251
01:00:11,643 --> 01:00:13,062
I would hypothesize it's also

2252
01:00:13,062 --> 01:00:14,579
true for others with epilepsy.

2253
01:00:17,215 --> 01:00:19,027
And I'll just leave you with one

2254
01:00:19,027 --> 01:00:20,877
other set of data to think about

2255
01:00:20,877 --> 01:00:21,687
is people who

2256
01:00:21,687 --> 01:00:22,521
are at risk for

2257
01:00:22,521 --> 01:00:23,689
developing epilepsy.

2258
01:00:24,690 --> 01:00:25,190
You know,

2259
01:00:25,190 --> 01:00:26,785
I study babies with neonatal

2260
01:00:26,785 --> 01:00:27,526
seizures and

2261
01:00:27,526 --> 01:00:29,287
follow them for the long run and

2262
01:00:29,287 --> 01:00:31,088
think a lot about the the impact

2263
01:00:31,088 --> 01:00:31,763
of having a

2264
01:00:31,763 --> 01:00:33,303
child with seizures on their

2265
01:00:33,303 --> 01:00:34,733
parents and their family.

2266
01:00:34,733 --> 01:00:36,187
And our our family partners have

2267
01:00:36,187 --> 01:00:36,868
asked us like,

2268
01:00:36,868 --> 01:00:38,324
are we ever going to sleep again

2269
01:00:38,324 --> 01:00:38,870
as parents?

2270
01:00:38,870 --> 01:00:40,143
Are these children going to be

2271
01:00:40,143 --> 01:00:40,906
able to sleep OK?

2272
01:00:41,573 --> 01:00:43,098
And I would say it's very clear

2273
01:00:43,098 --> 01:00:44,355
that we need to watch out

2274
01:00:44,355 --> 01:00:45,410
clinically for sleep

2275
01:00:45,410 --> 01:00:45,844
problems.

2276
01:00:46,712 --> 01:00:48,808
We had 116 parents of five year

2277
01:00:48,808 --> 01:00:50,538
old survival survivors of

2278
01:00:50,538 --> 01:00:51,783
neonatal seizures

2279
01:00:51,783 --> 01:00:53,960
who reported on their children's

2280
01:00:53,960 --> 01:00:56,117
sleep and their mean children's

2281
01:00:56,117 --> 01:00:57,022
sleep habits

2282
01:00:57,022 --> 01:00:58,850
questionnaire score was 45,

2283
01:00:58,850 --> 01:01:01,000
which is well above the healthy

2284
01:01:01,000 --> 01:01:01,693
cutoff of

2285
01:01:01,693 --> 01:01:03,328
41 and and LED to say us

2286
01:01:03,328 --> 01:01:05,555
concluding a nearly 2/3 of these

2287
01:01:05,555 --> 01:01:06,598
children's had

2288
01:01:06,598 --> 01:01:08,667
abnormal sleep at the age of 5.

2289
01:01:11,169 --> 01:01:13,003
About 1/4 of them screened

2290
01:01:13,003 --> 01:01:14,944
positive for sleep disorder

2291
01:01:14,944 --> 01:01:16,742
breathing on the the PS:

2292
01:01:16,742 --> 01:01:17,776
QSRBD subscale.

2293
01:01:19,044 --> 01:01:19,667
Interestingly,

2294
01:01:19,667 --> 01:01:21,036
children who have lower scores

2295
01:01:21,036 --> 01:01:21,446
on their

2296
01:01:21,446 --> 01:01:22,581
Vineland and their whipsy.

2297
01:01:22,581 --> 01:01:23,972
So children with lower IQ were

2298
01:01:23,972 --> 01:01:25,440
more likely to have symptoms of

2299
01:01:25,440 --> 01:01:26,151
sleep disorder

2300
01:01:26,151 --> 01:01:26,618
breathing.

2301
01:01:27,152 --> 01:01:28,504
And the question then I would

2302
01:01:28,504 --> 01:01:29,980
pose is could earlier diagnosis

2303
01:01:29,980 --> 01:01:30,789
and treatment of

2304
01:01:30,789 --> 01:01:32,300
the sleep problems have improved

2305
01:01:32,300 --> 01:01:33,267
their behavioral and

2306
01:01:33,267 --> 01:01:34,426
developmental outcomes?

2307
01:01:34,426 --> 01:01:36,104
And that's something that is a

2308
01:01:36,104 --> 01:01:37,655
tantalizing possibility and

2309
01:01:37,655 --> 01:01:38,230
something

2310
01:01:38,230 --> 01:01:39,664
that is is ripe for study.

2311
01:01:41,099 --> 01:01:42,344
So to conclude for you,

2312
01:01:42,344 --> 01:01:43,535
people with epilepsy,

2313
01:01:43,535 --> 01:01:44,976
just like people with ADHD,

2314
01:01:44,976 --> 01:01:45,937
as we just heard,

2315
01:01:45,937 --> 01:01:46,789
are at high risk

2316
01:01:46,789 --> 01:01:47,906
for sleep disorders.

2317
01:01:48,373 --> 01:01:49,959
Treatment of the sleep disorder

2318
01:01:49,959 --> 01:01:51,582
may improve seizure control and

2319
01:01:51,582 --> 01:01:52,210
vice versa,

2320
01:01:52,210 --> 01:01:53,849
seizure control helps with sleep

2321
01:01:53,849 --> 01:01:54,413
disorders.

2322
01:01:55,313 --> 01:01:56,368
Routine screening for and

2323
01:01:56,368 --> 01:01:57,574
treatment of sleep disorders

2324
01:01:57,574 --> 01:01:58,350
could make a real

2325
01:01:58,350 --> 01:01:59,802
difference for our patients and

2326
01:01:59,802 --> 01:02:00,552
their families.

2327
01:02:00,552 --> 01:02:02,211
And I think that the evidence

2328
01:02:02,211 --> 01:02:03,755
base has significant gaps.

2329
01:02:04,022 --> 01:02:05,559
But this is an area of research

2330
01:02:05,559 --> 01:02:06,933
that really holds important

2331
01:02:06,933 --> 01:02:07,492
promise to

2332
01:02:07,492 --> 01:02:08,894
generate actionable results,

2333
01:02:08,894 --> 01:02:10,074
which practice changing

2334
01:02:10,074 --> 01:02:10,896
implications in

2335
01:02:10,896 --> 01:02:11,830
the very near term.

2336
01:02:12,564 --> 01:02:14,258
So I think this is an exciting

2337
01:02:14,258 --> 01:02:16,046
place to be looking and we have

2338
01:02:16,046 --> 01:02:16,968
an awful lot of

2339
01:02:16,968 --> 01:02:18,558
work to do for those who are

2340
01:02:18,558 --> 01:02:20,205
interested in infants leave.

2341
01:02:20,205 --> 01:02:22,275
I'll just put on a quick plug to

2342
01:02:22,275 --> 01:02:23,992
to join us for an upcoming

2343
01:02:23,992 --> 01:02:25,510
conference where we're

2344
01:02:25,510 --> 01:02:27,568
going to be talking specifically

2345
01:02:27,568 --> 01:02:29,047
about Neil in Belgium.

2346
01:02:29,414 --> 01:02:30,115
Look at this year.

2347
01:02:31,416 --> 01:02:32,084
Thank you very much.

2348
01:02:33,251 --> 01:02:34,019
Thank you.

2349
01:02:34,019 --> 01:02:35,053
Thank you, Doctor Shellhouse.

2350
01:02:35,053 --> 01:02:36,599
That was really that

2351
01:02:36,599 --> 01:02:38,223
was a fabulous talk.

2352
01:02:38,223 --> 01:02:41,526
And I, I have a question.

2353
01:02:41,526 --> 01:02:44,568
I hadn't heard about C Pap

2354
01:02:44,568 --> 01:02:48,032
actually decreasing the spike

2355
01:02:48,032 --> 01:02:50,302
burden in any EGS.

2356
01:02:50,302 --> 01:02:52,278
And I wonder if you've thought

2357
01:02:52,278 --> 01:02:54,364
about potentially or if anybody

2358
01:02:54,364 --> 01:02:55,373
documented the

2359
01:02:55,373 --> 01:02:57,362
changes in maybe REM sleep and

2360
01:02:57,362 --> 01:02:59,396
did you end up with increasing

2361
01:02:59,396 --> 01:03:00,345
the REM sleep

2362
01:03:00,345 --> 01:03:02,389
ratio and you know, Rems to be

2363
01:03:02,389 --> 01:03:03,615
protected, right?

2364
01:03:03,615 --> 01:03:05,474
Because we know that REM sleep,

2365
01:03:05,474 --> 01:03:07,260
like wakefulness is protected

2366
01:03:07,260 --> 01:03:07,752
against

2367
01:03:07,752 --> 01:03:08,386
seizures.

2368
01:03:08,386 --> 01:03:09,836
And right, I don't know,

2369
01:03:09,836 --> 01:03:11,579
I don't know the answer from

2370
01:03:11,579 --> 01:03:11,890
that

2371
01:03:11,890 --> 01:03:13,647
particular study whether they

2372
01:03:13,647 --> 01:03:15,442
looked at the distribution of

2373
01:03:15,442 --> 01:03:16,495
sleeping stages.

2374
01:03:16,495 --> 01:03:18,159
But obviously the point of the

2375
01:03:18,159 --> 01:03:19,462
question and how are we

2376
01:03:19,462 --> 01:03:20,765
balancing out what are

2377
01:03:20,765 --> 01:03:22,484
what are sleep cycles look like

2378
01:03:22,484 --> 01:03:23,852
when we when we initiate

2379
01:03:23,852 --> 01:03:24,536
treatments?

2380
01:03:24,536 --> 01:03:25,070
It's something that

2381
01:03:25,070 --> 01:03:25,604
definitely should.

2382
01:03:25,604 --> 01:03:25,871
Yeah.

2383
01:03:26,271 --> 01:03:27,549
And also that you'd be more

2384
01:03:27,549 --> 01:03:28,874
likely to experience R.E.M.

2385
01:03:28,874 --> 01:03:30,221
for physiologic, I mean, apnea

2386
01:03:30,221 --> 01:03:31,414
during R.E. M., right, for

2387
01:03:31,414 --> 01:03:32,377
physiologic reasons.

2388
01:03:32,377 --> 01:03:33,745
So we'd be interrupting it.

2389
01:03:33,745 --> 01:03:35,801
So you you alleviate the OSA,

2390
01:03:35,801 --> 01:03:37,979
you end up with just naturally

2391
01:03:37,979 --> 01:03:38,850
more R.E.M.

2392
01:03:38,850 --> 01:03:39,561
and then sort of a

2393
01:03:39,561 --> 01:03:40,352
natural protectant.

2394
01:03:40,352 --> 01:03:41,347
So I think that would be an

2395
01:03:41,347 --> 01:03:42,454
interesting thing to look at.

2396
01:03:43,054 --> 01:03:43,755
Thank you.

2397
01:03:43,755 --> 01:03:44,946
Thank you so much for an

2398
01:03:44,946 --> 01:03:46,361
informative very as usual as

2399
01:03:46,361 --> 01:03:47,726
always and wonderful talk.

2400
01:03:49,261 --> 01:03:50,896
Now we have Doctor Pohm.

2401
01:03:50,896 --> 01:03:51,824
So thank you guys for

2402
01:03:51,824 --> 01:03:52,664
waiting patiently.

2403
01:03:53,298 --> 01:03:53,532
Dr.

2404
01:03:53,532 --> 01:03:55,212
Pohmes is an assistant professor

2405
01:03:55,212 --> 01:03:56,886
Pediatrics of Sleep Medicine at

2406
01:03:56,886 --> 01:03:57,102
the

2407
01:03:57,102 --> 01:03:58,774
University of Arizona Center for

2408
01:03:58,774 --> 01:03:59,843
Sleep, Circadian and

2409
01:03:59,843 --> 01:04:01,072
Neuroscience Research.

2410
01:04:01,806 --> 01:04:03,248
His research interests include

2411
01:04:03,248 --> 01:04:04,624
the cognitive and quality of

2412
01:04:04,624 --> 01:04:05,410
life effects of

2413
01:04:05,410 --> 01:04:06,956
sleep disorders in children with

2414
01:04:06,956 --> 01:04:08,213
special healthcare needs,

2415
01:04:08,213 --> 01:04:09,460
as well as identifying new

2416
01:04:09,460 --> 01:04:10,731
treatments to mitigate the

2417
01:04:10,731 --> 01:04:12,050
effects of sleep disorders

2418
01:04:12,050 --> 01:04:12,951
in this population.

2419
01:04:13,351 --> 01:04:15,124
So this talk is going to focus

2420
01:04:15,124 --> 01:04:16,188
on Down syndrome.

2421
01:04:16,488 --> 01:04:17,222
Doctor Combs.

2422
01:04:18,456 --> 01:04:19,215
OK, thank you very

2423
01:04:19,215 --> 01:04:20,058
much for having me.

2424
01:04:20,492 --> 01:04:22,607
You scared being you started

2425
01:04:22,607 --> 01:04:24,926
introducing me the first time,

2426
01:04:24,926 --> 01:04:25,931
but so yeah.

2427
01:04:25,931 --> 01:04:27,304
So I am excited to talk about

2428
01:04:27,304 --> 01:04:28,708
sleep problems in people with

2429
01:04:28,708 --> 01:04:29,434
Down syndrome.

2430
01:04:30,335 --> 01:04:31,628
I could talk about this all day,

2431
01:04:31,628 --> 01:04:32,637
but I've got 20 minutes,

2432
01:04:32,637 --> 01:04:33,807
which is probably a fortunate

2433
01:04:33,807 --> 01:04:34,573
for everyone here.

2434
01:04:38,810 --> 01:04:39,211
There we go.

2435
01:04:39,978 --> 01:04:40,920
So my disclosures,

2436
01:04:40,920 --> 01:04:42,585
I have research funding related

2437
01:04:42,585 --> 01:04:43,014
to Down

2438
01:04:43,014 --> 01:04:44,524
syndrome and sleep apnea from

2439
01:04:44,524 --> 01:04:46,120
NIH, NT Cory and then we're at

2440
01:04:46,120 --> 01:04:46,918
clinical trial

2441
01:04:46,918 --> 01:04:47,852
site for Eidorcia.

2442
01:04:48,453 --> 01:04:49,472
That's not particularly related

2443
01:04:49,472 --> 01:04:50,453
to this talk, but I disclosed

2444
01:04:50,453 --> 01:04:50,589
it.

2445
01:04:52,390 --> 01:04:53,725
So common sleep disorders.

2446
01:04:53,992 --> 01:04:54,682
So there are lots

2447
01:04:54,682 --> 01:04:55,493
of sleep disorders.

2448
01:04:56,528 --> 01:04:57,631
I'm going to focus on two of

2449
01:04:57,631 --> 01:04:58,880
them, but just to kind of paint

2450
01:04:58,880 --> 01:04:59,364
the broader

2451
01:04:59,364 --> 01:05:00,392
picture, obstructive sleep

2452
01:05:00,392 --> 01:05:01,690
apnea, probably everyone on this

2453
01:05:01,690 --> 01:05:01,933
call,

2454
01:05:01,933 --> 01:05:02,952
if you hear Down syndrome,

2455
01:05:02,952 --> 01:05:03,919
you should probably take

2456
01:05:03,919 --> 01:05:04,402
obstructive

2457
01:05:04,402 --> 01:05:04,869
sleep apnea.

2458
01:05:04,869 --> 01:05:06,461
In terms of sleep disorders,

2459
01:05:06,461 --> 01:05:07,747
restless leg syndrome,

2460
01:05:07,747 --> 01:05:08,506
parasomnias,

2461
01:05:08,506 --> 01:05:10,055
circadian rhythm disorders,

2462
01:05:10,055 --> 01:05:11,587
insufficient sleep are all

2463
01:05:11,587 --> 01:05:12,177
potential

2464
01:05:12,177 --> 01:05:13,769
issues are mostly either not

2465
01:05:13,769 --> 01:05:15,632
very well studied in people Down

2466
01:05:15,632 --> 01:05:16,214
syndrome.

2467
01:05:17,215 --> 01:05:18,561
And so in the interest I'm I'm

2468
01:05:18,561 --> 01:05:19,818
kind of glossing over them,

2469
01:05:19,818 --> 01:05:21,115
but that's not to say they're

2470
01:05:21,115 --> 01:05:21,786
not important.

2471
01:05:21,786 --> 01:05:22,787
And then insomnia,

2472
01:05:22,787 --> 01:05:24,269
I'm going to touch on very

2473
01:05:24,269 --> 01:05:25,123
briefly at the

2474
01:05:25,123 --> 01:05:25,323
end.

2475
01:05:27,058 --> 01:05:28,597
So obstructive sleep apnea in

2476
01:05:28,597 --> 01:05:30,295
people with Down syndrome, why,

2477
01:05:30,295 --> 01:05:31,081
why do we think

2478
01:05:31,081 --> 01:05:32,130
about this so much?

2479
01:05:32,564 --> 01:05:33,758
As early as infancy,

2480
01:05:33,758 --> 01:05:35,660
about one in three infants with

2481
01:05:35,660 --> 01:05:35,967
Down

2482
01:05:35,967 --> 01:05:37,788
syndrome have obstructive sleep

2483
01:05:37,788 --> 01:05:39,711
apnea that more or less steadily

2484
01:05:39,711 --> 01:05:40,372
progresses

2485
01:05:40,372 --> 01:05:42,073
over the course of your life.

2486
01:05:42,974 --> 01:05:45,366
So by childhood about half to 3

2487
01:05:45,366 --> 01:05:47,808
/4 have obstructive sleep apnea

2488
01:05:47,808 --> 01:05:49,147
and by adulthood

2489
01:05:49,147 --> 01:05:51,249
this is pushing essentially

2490
01:05:51,249 --> 01:05:53,726
almost everyone will have sleep

2491
01:05:53,726 --> 01:05:54,286
apnea.

2492
01:05:54,286 --> 01:05:56,567
So it's incredibly common and is

2493
01:05:56,567 --> 01:05:58,476
obviously a very important

2494
01:05:58,476 --> 01:05:58,990
issue.

2495
01:05:59,924 --> 01:06:00,461
Importantly,

2496
01:06:00,461 --> 01:06:01,927
many children with Down syndrome

2497
01:06:01,927 --> 01:06:02,294
and OSA

2498
01:06:02,294 --> 01:06:03,695
don't have typical OSA symptoms.

2499
01:06:03,695 --> 01:06:05,123
So loud snoring, gasping,

2500
01:06:05,123 --> 01:06:06,757
choking, all of those things

2501
01:06:06,757 --> 01:06:07,866
would clue you in.

2502
01:06:08,700 --> 01:06:10,365
Many parents don't report those

2503
01:06:10,365 --> 01:06:11,899
symptoms despite their child

2504
01:06:11,899 --> 01:06:13,104
having OSAOSA in kids

2505
01:06:13,104 --> 01:06:14,734
with Down syndrome tends to be

2506
01:06:14,734 --> 01:06:15,440
more severe,

2507
01:06:15,440 --> 01:06:16,940
so it's during about half of

2508
01:06:16,940 --> 01:06:18,695
cases, which is much higher than

2509
01:06:18,695 --> 01:06:19,244
typically

2510
01:06:19,244 --> 01:06:20,312
developing children.

2511
01:06:21,179 --> 01:06:22,846
Because of the lack of symptoms

2512
01:06:22,846 --> 01:06:24,119
and the incredibly high

2513
01:06:24,119 --> 01:06:24,783
prevalence,

2514
01:06:24,783 --> 01:06:26,071
universal screening with

2515
01:06:26,071 --> 01:06:27,834
polysynography is recommended by

2516
01:06:27,834 --> 01:06:28,219
age 4.

2517
01:06:28,953 --> 01:06:29,917
Unfortunately, we are

2518
01:06:29,917 --> 01:06:30,789
not great at this.

2519
01:06:30,789 --> 01:06:32,520
So in one study looking at this,

2520
01:06:32,520 --> 01:06:34,128
only 25% of kids had actually

2521
01:06:34,128 --> 01:06:34,793
had a sleep

2522
01:06:34,793 --> 01:06:35,593
study by age 4.

2523
01:06:36,695 --> 01:06:38,003
And from a clinical experience,

2524
01:06:38,003 --> 01:06:39,174
I would say that's probably

2525
01:06:39,174 --> 01:06:39,564
probably

2526
01:06:39,564 --> 01:06:39,931
accurate.

2527
01:06:39,931 --> 01:06:41,994
Maybe ideally we make it half by

2528
01:06:41,994 --> 01:06:42,767
age 5 or 6.

2529
01:06:43,234 --> 01:06:44,623
So there are many children with

2530
01:06:44,623 --> 01:06:45,954
Down syndrome who are hanging

2531
01:06:45,954 --> 01:06:46,504
out who are

2532
01:06:46,504 --> 01:06:47,005
undiagnosed.

2533
01:06:49,507 --> 01:06:50,712
Why is it so common in people

2534
01:06:50,712 --> 01:06:51,543
with Down syndrome?

2535
01:06:52,310 --> 01:06:53,527
I broadly think of it kind of in

2536
01:06:53,527 --> 01:06:53,945
two areas.

2537
01:06:53,945 --> 01:06:54,602
So the first,

2538
01:06:54,602 --> 01:06:55,613
anatomic structure.

2539
01:06:56,581 --> 01:06:57,735
So people with Down syndrome

2540
01:06:57,735 --> 01:06:59,046
tend to have a relatively small

2541
01:06:59,046 --> 01:06:59,384
airway.

2542
01:07:00,352 --> 01:07:01,783
So mid face hypoplasia means

2543
01:07:01,783 --> 01:07:03,401
kind of your airway is a little

2544
01:07:03,401 --> 01:07:04,289
bit set back and

2545
01:07:04,289 --> 01:07:04,689
smaller.

2546
01:07:04,689 --> 01:07:05,953
From that perspective,

2547
01:07:05,953 --> 01:07:07,839
people tend to have a relatively

2548
01:07:07,839 --> 01:07:08,193
large

2549
01:07:08,193 --> 01:07:09,915
tongue compared to the size of

2550
01:07:09,915 --> 01:07:10,662
their mouth.

2551
01:07:11,496 --> 01:07:12,253
And so that can lead to

2552
01:07:12,253 --> 01:07:13,328
obstruction from their tongue at

2553
01:07:13,328 --> 01:07:13,898
the tongue base.

2554
01:07:14,265 --> 01:07:15,329
And then adenotongs or

2555
01:07:15,329 --> 01:07:16,609
hypertrophy is also fairly

2556
01:07:16,609 --> 01:07:18,036
common in children with Down

2557
01:07:18,036 --> 01:07:18,470
syndrome.

2558
01:07:19,304 --> 01:07:20,616
The other big area in the area

2559
01:07:20,616 --> 01:07:22,048
that we focus our research on is

2560
01:07:22,048 --> 01:07:22,540
hypatonia.

2561
01:07:23,141 --> 01:07:24,415
So airway hypatonia is a known

2562
01:07:24,415 --> 01:07:25,507
thing in people with Down

2563
01:07:25,507 --> 01:07:25,944
syndrome.

2564
01:07:26,778 --> 01:07:28,226
So we all have decreased muscle

2565
01:07:28,226 --> 01:07:29,114
tone during sleep.

2566
01:07:29,447 --> 01:07:31,218
If you start off hypatonic and

2567
01:07:31,218 --> 01:07:32,517
go to more hypatonic,

2568
01:07:32,517 --> 01:07:34,235
that's when you see that that

2569
01:07:34,235 --> 01:07:35,954
spontaneous airway collapse,

2570
01:07:35,954 --> 01:07:37,472
which is obstructive sleep

2571
01:07:37,472 --> 01:07:39,263
apnea, effects of I was saying

2572
01:07:39,263 --> 01:07:40,158
in people with

2573
01:07:40,158 --> 01:07:40,989
Down syndrome,

2574
01:07:40,989 --> 01:07:42,944
these are really all of the kind

2575
01:07:42,944 --> 01:07:43,128
of

2576
01:07:43,128 --> 01:07:44,920
typical things that we've seen

2577
01:07:44,920 --> 01:07:45,697
in everyone.

2578
01:07:45,697 --> 01:07:47,509
This tends to be more of an

2579
01:07:47,509 --> 01:07:49,423
issue because it's kind of a

2580
01:07:49,423 --> 01:07:51,336
second additional decrease.

2581
01:07:51,536 --> 01:07:53,090
So for example, verbal IQ,

2582
01:07:53,090 --> 01:07:54,805
my collaborator Jamie showed

2583
01:07:54,805 --> 01:07:55,540
about a six

2584
01:07:55,540 --> 01:07:55,907
point.

2585
01:07:55,907 --> 01:07:57,161
So children of Down syndrome

2586
01:07:57,161 --> 01:07:58,581
without sleep apnea versus with

2587
01:07:58,581 --> 01:07:59,177
sleep apnea,

2588
01:07:59,177 --> 01:08:00,472
the children with sleep apnea

2589
01:08:00,472 --> 01:08:01,946
had a six point lower verbal IQ.

2590
01:08:03,248 --> 01:08:05,248
If your baseline OQ is 110,

2591
01:08:05,248 --> 01:08:07,603
that six points is not going to

2592
01:08:07,603 --> 01:08:08,286
be huge,

2593
01:08:08,286 --> 01:08:09,020
huge deal.

2594
01:08:09,020 --> 01:08:10,900
Obviously, it'd be better not

2595
01:08:10,900 --> 01:08:12,894
to, but when you're going from

2596
01:08:12,894 --> 01:08:13,558
45 to 39,

2597
01:08:13,558 --> 01:08:15,322
you can see really dramatic

2598
01:08:15,322 --> 01:08:16,926
effects in terms of your

2599
01:08:16,926 --> 01:08:18,196
adaptive function.

2600
01:08:18,830 --> 01:08:20,185
Like are you, are you staying in

2601
01:08:20,185 --> 01:08:21,032
a, in a group home?

2602
01:08:21,032 --> 01:08:22,337
Are you living with your parents

2603
01:08:22,337 --> 01:08:23,634
versus how, how independent you

2604
01:08:23,634 --> 01:08:23,968
can be.

2605
01:08:24,669 --> 01:08:25,959
So we know decreased adaptive

2606
01:08:25,959 --> 01:08:27,151
function if you have sleep

2607
01:08:27,151 --> 01:08:27,472
apnea,

2608
01:08:27,472 --> 01:08:28,573
decreased verbal fluency.

2609
01:08:28,940 --> 01:08:30,613
Interestingly, in adulthood,

2610
01:08:30,613 --> 01:08:31,967
Alzheimer's disease is

2611
01:08:31,967 --> 01:08:32,644
incredibly

2612
01:08:32,644 --> 01:08:33,828
prevalent for people

2613
01:08:33,828 --> 01:08:35,013
with Down syndrome.

2614
01:08:35,447 --> 01:08:37,013
There are some studies in adults

2615
01:08:37,013 --> 01:08:38,466
without Down syndrome showing

2616
01:08:38,466 --> 01:08:39,117
that there's

2617
01:08:39,117 --> 01:08:39,996
increased amyloid,

2618
01:08:39,996 --> 01:08:41,351
suggesting obstructed sleep

2619
01:08:41,351 --> 01:08:41,853
apnea can

2620
01:08:41,853 --> 01:08:43,111
complete can contribute to

2621
01:08:43,111 --> 01:08:44,646
Alzheimer's Alzheimer's disease

2622
01:08:44,646 --> 01:08:45,290
development.

2623
01:08:47,091 --> 01:08:48,281
This is not an area that's been

2624
01:08:48,281 --> 01:08:49,394
very well studied so far in,

2625
01:08:49,394 --> 01:08:50,295
in people Down syndrome.

2626
01:08:51,129 --> 01:08:52,552
We know quality of life goes

2627
01:08:52,552 --> 01:08:53,858
down as this common sleep

2628
01:08:53,858 --> 01:08:54,432
disorders,

2629
01:08:54,432 --> 01:08:55,876
your quality of life takes a

2630
01:08:55,876 --> 01:08:56,701
fairly big hit.

2631
01:08:56,701 --> 01:08:58,289
And there's also some a little

2632
01:08:58,289 --> 01:08:59,860
bit of data showing that even

2633
01:08:59,860 --> 01:09:00,672
cardiovascular

2634
01:09:00,672 --> 01:09:01,105
effects.

2635
01:09:01,105 --> 01:09:01,388
So you,

2636
01:09:01,388 --> 01:09:02,343
you have decreased left

2637
01:09:02,343 --> 01:09:02,841
ventricular

2638
01:09:02,841 --> 01:09:03,174
function.

2639
01:09:05,643 --> 01:09:06,731
So what can we do about

2640
01:09:06,731 --> 01:09:07,912
obstructive sleep apnea?

2641
01:09:07,912 --> 01:09:09,168
So all of the kind of common

2642
01:09:09,168 --> 01:09:10,597
treatments that I'm gonna touch

2643
01:09:10,597 --> 01:09:10,782
on.

2644
01:09:11,516 --> 01:09:13,279
So the alternative treatments,

2645
01:09:13,279 --> 01:09:15,091
so standard Endoton selectomy,

2646
01:09:15,091 --> 01:09:15,453
CPAP,

2647
01:09:15,453 --> 01:09:16,937
most people are typically

2648
01:09:16,937 --> 01:09:18,822
familiar with these alternative

2649
01:09:18,822 --> 01:09:19,491
therapies.

2650
01:09:19,858 --> 01:09:21,102
So myofunctional therapy is

2651
01:09:21,102 --> 01:09:22,326
essentially speech therapy

2652
01:09:22,326 --> 01:09:23,361
exercises that try to

2653
01:09:23,361 --> 01:09:24,839
increase your airway muscle tone

2654
01:09:24,839 --> 01:09:25,763
during the daytime,

2655
01:09:25,763 --> 01:09:27,244
with the idea being that if your

2656
01:09:27,244 --> 01:09:28,665
airway muscle tone is stronger

2657
01:09:28,665 --> 01:09:29,234
in the day,

2658
01:09:29,234 --> 01:09:30,584
at night it will hopefully be

2659
01:09:30,584 --> 01:09:31,236
stronger too.

2660
01:09:31,970 --> 01:09:33,393
There is one study of this doing

2661
01:09:33,393 --> 01:09:34,529
one week of myofunctional

2662
01:09:34,529 --> 01:09:35,573
therapy for a group of

2663
01:09:35,573 --> 01:09:36,608
kids with Down syndrome.

2664
01:09:37,475 --> 01:09:39,175
The baseline HI and follow up HI

2665
01:09:39,175 --> 01:09:40,860
were essentially the same so no

2666
01:09:40,860 --> 01:09:41,513
difference.

2667
01:09:42,247 --> 01:09:43,515
anti-inflammatory medication.

2668
01:09:43,515 --> 01:09:44,560
There's some evidence

2669
01:09:44,560 --> 01:09:46,144
Montelukast and and Flonase can

2670
01:09:46,144 --> 01:09:46,451
help,

2671
01:09:46,451 --> 01:09:47,384
especially for mild

2672
01:09:47,384 --> 01:09:48,219
OSA in children.

2673
01:09:48,953 --> 01:09:50,146
There are two retrospective

2674
01:09:50,146 --> 01:09:51,230
studies looking at these

2675
01:09:51,230 --> 01:09:52,223
specific to kids with

2676
01:09:52,223 --> 01:09:52,824
Down syndrome.

2677
01:09:53,124 --> 01:09:54,259
That too had no benefits.

2678
01:09:55,994 --> 01:09:57,690
GLP one medications tirzepatide

2679
01:09:57,690 --> 01:09:59,090
was recently approved for

2680
01:09:59,090 --> 01:10:00,098
obstructive sleep

2681
01:10:00,098 --> 01:10:01,132
apnea in in adults.

2682
01:10:02,634 --> 01:10:04,451
There is no data for people with

2683
01:10:04,451 --> 01:10:05,303
Down syndrome.

2684
01:10:05,570 --> 01:10:06,207
I think this is

2685
01:10:06,207 --> 01:10:06,971
fairly promising.

2686
01:10:06,971 --> 01:10:08,193
I've actually had a handful of

2687
01:10:08,193 --> 01:10:09,007
patients in clinic,

2688
01:10:09,007 --> 01:10:10,030
my adult patients who are

2689
01:10:10,030 --> 01:10:10,808
already taking it.

2690
01:10:11,910 --> 01:10:12,610
So we will see what

2691
01:10:12,610 --> 01:10:13,311
happens with that.

2692
01:10:13,311 --> 01:10:13,943
So that I think

2693
01:10:13,943 --> 01:10:14,913
that's very promising.

2694
01:10:15,580 --> 01:10:17,346
There's no data for it at all in

2695
01:10:17,346 --> 01:10:19,094
Down syndrome in the more of it

2696
01:10:19,094 --> 01:10:19,884
this time and

2697
01:10:19,884 --> 01:10:20,852
dental approaches.

2698
01:10:21,052 --> 01:10:23,224
So things like palate expansion

2699
01:10:23,224 --> 01:10:25,454
in younger kids where you use a

2700
01:10:25,454 --> 01:10:25,957
bar to

2701
01:10:25,957 --> 01:10:28,146
expand the the palate increases

2702
01:10:28,146 --> 01:10:30,194
your your airway dimensions.

2703
01:10:30,595 --> 01:10:32,144
For teens with most of their

2704
01:10:32,144 --> 01:10:33,500
adult teeth, you can use

2705
01:10:33,500 --> 01:10:34,799
mandibular advancement

2706
01:10:34,799 --> 01:10:35,246
devices,

2707
01:10:35,246 --> 01:10:36,906
which is essentially a device

2708
01:10:36,906 --> 01:10:37,535
that pulls

2709
01:10:37,535 --> 01:10:39,203
you lower drop forward to open

2710
01:10:39,203 --> 01:10:40,371
up your airway more.

2711
01:10:41,105 --> 01:10:42,364
There are no studies specific to

2712
01:10:42,364 --> 01:10:43,336
this in people with Down

2713
01:10:43,336 --> 01:10:43,741
syndrome.

2714
01:10:44,876 --> 01:10:46,066
If you are not obese and have

2715
01:10:46,066 --> 01:10:47,115
mild OSA, it's probably a

2716
01:10:47,115 --> 01:10:47,912
reasonable option,

2717
01:10:47,912 --> 01:10:48,329
but again,

2718
01:10:48,329 --> 01:10:49,443
it's it's unstudied so I'm

2719
01:10:49,443 --> 01:10:49,914
willing to

2720
01:10:49,914 --> 01:10:50,373
mention it,

2721
01:10:50,373 --> 01:10:51,749
but there's no doubt either way.

2722
01:10:52,617 --> 01:10:53,720
Hypoglossal nerve simulation is

2723
01:10:53,720 --> 01:10:54,218
in the green.

2724
01:10:54,218 --> 01:10:55,517
So it is studied and then auto

2725
01:10:55,517 --> 01:10:56,713
oxy is something that we're

2726
01:10:56,713 --> 01:10:57,422
studying so I'm

2727
01:10:57,422 --> 01:10:58,623
gonna touch on that as well.

2728
01:11:01,593 --> 01:11:02,916
So adeno tonsillectomy is your

2729
01:11:02,916 --> 01:11:04,195
typical first line approach.

2730
01:11:04,462 --> 01:11:05,053
Unfortunately,

2731
01:11:05,053 --> 01:11:06,308
it's not especially effective

2732
01:11:06,308 --> 01:11:06,698
for kids

2733
01:11:06,698 --> 01:11:07,498
with Down syndrome.

2734
01:11:08,433 --> 01:11:09,910
So about half to 3/4 will have

2735
01:11:09,910 --> 01:11:11,416
residual objective sleep apnea

2736
01:11:11,416 --> 01:11:12,470
after tonsillectomy.

2737
01:11:13,271 --> 01:11:14,174
It does at least

2738
01:11:14,174 --> 01:11:15,473
decrease OSA severity.

2739
01:11:16,341 --> 01:11:16,749
And so,

2740
01:11:16,749 --> 01:11:18,665
and there's been many studies of

2741
01:11:18,665 --> 01:11:19,143
this at

2742
01:11:19,143 --> 01:11:19,786
this point,

2743
01:11:19,786 --> 01:11:21,646
but about half of children will

2744
01:11:21,646 --> 01:11:21,946
show

2745
01:11:21,946 --> 01:11:23,721
about a 50% reduction in their

2746
01:11:23,721 --> 01:11:24,549
OSA severity.

2747
01:11:26,284 --> 01:11:26,998
That tends to be a

2748
01:11:26,998 --> 01:11:27,752
fairly wide range.

2749
01:11:27,752 --> 01:11:29,739
So some kids do get completely

2750
01:11:29,739 --> 01:11:31,643
better, but some kids get no

2751
01:11:31,643 --> 01:11:32,323
benefits.

2752
01:11:33,224 --> 01:11:33,725
Unfortunately,

2753
01:11:33,725 --> 01:11:34,863
there's no way to predict who's

2754
01:11:34,863 --> 01:11:35,193
going to

2755
01:11:35,193 --> 01:11:35,911
be a great responder

2756
01:11:35,911 --> 01:11:36,594
that I'm aware of.

2757
01:11:36,594 --> 01:11:37,595
In terms of published data.

2758
01:11:37,996 --> 01:11:38,823
There are some other ENT

2759
01:11:38,823 --> 01:11:39,605
procedures that can be

2760
01:11:39,605 --> 01:11:40,031
considered.

2761
01:11:40,031 --> 01:11:41,132
I'm gonna gloss over those.

2762
01:11:43,167 --> 01:11:45,029
CPAP works great if you use it,

2763
01:11:45,029 --> 01:11:47,002
and I think everyone is aware of

2764
01:11:47,002 --> 01:11:47,372
that.

2765
01:11:47,372 --> 01:11:48,355
The big issue with this is

2766
01:11:48,355 --> 01:11:49,073
therapy adherence.

2767
01:11:50,108 --> 01:11:51,368
One study showed about 46%

2768
01:11:51,368 --> 01:11:52,713
adherence in kids with Down

2769
01:11:52,713 --> 01:11:53,211
syndrome.

2770
01:11:54,178 --> 01:11:55,319
This was people who are followed

2771
01:11:55,319 --> 01:11:55,747
in clinics.

2772
01:11:55,747 --> 01:11:56,963
There might be a selection bias

2773
01:11:56,963 --> 01:11:58,087
where these are kids who are

2774
01:11:58,087 --> 01:11:58,650
showing up to

2775
01:11:58,650 --> 01:11:59,199
clinic because

2776
01:11:59,199 --> 01:11:59,984
they're using CPAP.

2777
01:12:00,818 --> 01:12:02,046
One study in clinical trial

2778
01:12:02,046 --> 01:12:03,443
showed an average of two hours

2779
01:12:03,443 --> 01:12:03,955
per night.

2780
01:12:04,989 --> 01:12:06,001
If you're thinking they're

2781
01:12:06,001 --> 01:12:07,044
sleeping 8 to 10 hours per

2782
01:12:07,044 --> 01:12:07,325
night,

2783
01:12:07,325 --> 01:12:08,512
they're only treated about 20%

2784
01:12:08,512 --> 01:12:09,027
of the time.

2785
01:12:10,094 --> 01:12:12,078
So CPAP is fantastic if you use

2786
01:12:12,078 --> 01:12:13,979
it, but unfortunately for the

2787
01:12:13,979 --> 01:12:14,766
majority of

2788
01:12:14,766 --> 01:12:16,816
children who children and adults

2789
01:12:16,816 --> 01:12:17,969
who don't use it,

2790
01:12:17,969 --> 01:12:20,011
CPAP next to you does not do any

2791
01:12:20,011 --> 01:12:21,901
benefit for OSA hyperglobulin

2792
01:12:21,901 --> 01:12:23,074
nerve simulation.

2793
01:12:23,074 --> 01:12:24,515
So currently on the market is

2794
01:12:24,515 --> 01:12:25,510
the Inspire device.

2795
01:12:25,510 --> 01:12:26,925
So this is essentially A

2796
01:12:26,925 --> 01:12:28,731
pacemaker battery implanted in

2797
01:12:28,731 --> 01:12:29,814
your chest with a

2798
01:12:29,814 --> 01:12:31,168
wire that goes up to an

2799
01:12:31,168 --> 01:12:32,970
implanted lead right here that

2800
01:12:32,970 --> 01:12:34,052
uses electricity,

2801
01:12:34,052 --> 01:12:35,945
uses voltage to essentially push

2802
01:12:35,945 --> 01:12:37,762
your tongue forward to keep it

2803
01:12:37,762 --> 01:12:38,489
out of your

2804
01:12:38,489 --> 01:12:38,890
airway.

2805
01:12:39,791 --> 01:12:41,204
This has been FDA approved in

2806
01:12:41,204 --> 01:12:42,509
adults for a while at this

2807
01:12:42,509 --> 01:12:42,860
point.

2808
01:12:43,795 --> 01:12:45,101
This was approved

2809
01:12:45,101 --> 01:12:46,330
I believe 2023.

2810
01:12:46,330 --> 01:12:47,194
That's when the

2811
01:12:47,194 --> 01:12:48,633
clinical trial was done.

2812
01:12:48,633 --> 01:12:51,067
So there is a study that looked

2813
01:12:51,067 --> 01:12:53,649
at a 42 adolescent, so age 10 to

2814
01:12:53,649 --> 01:12:53,971
21,

2815
01:12:53,971 --> 01:12:56,413
baseline obstructive HI was 22,

2816
01:12:56,413 --> 01:12:58,776
which is severe OSA for kids.

2817
01:12:58,776 --> 01:13:00,542
Treatment got a little bit more

2818
01:13:00,542 --> 01:13:02,344
than 50% improved adherence was

2819
01:13:02,344 --> 01:13:03,448
excellent and they

2820
01:13:03,448 --> 01:13:05,091
did find quality of life from

2821
01:13:05,091 --> 01:13:06,451
approved significantly.

2822
01:13:07,051 --> 01:13:08,052
This is now on the market.

2823
01:13:08,052 --> 01:13:10,524
It's FDA approved to age 13 plus

2824
01:13:10,524 --> 01:13:13,058
I know there are ENT's out there

2825
01:13:13,058 --> 01:13:13,691
who are

2826
01:13:13,691 --> 01:13:16,095
implanting in younger patients,

2827
01:13:16,095 --> 01:13:18,481
but the FDA approval is age 13

2828
01:13:18,481 --> 01:13:19,197
and then

2829
01:13:19,197 --> 01:13:19,664
adoxy.

2830
01:13:19,664 --> 01:13:20,400
So this is a clinical

2831
01:13:20,400 --> 01:13:21,065
trial that we did.

2832
01:13:21,065 --> 01:13:23,159
So we did a smaller study

2833
01:13:23,159 --> 01:13:25,336
initially in 12 children.

2834
01:13:25,336 --> 01:13:25,518
So,

2835
01:13:25,518 --> 01:13:27,380
so adamoxydine is FDA approved

2836
01:13:27,380 --> 01:13:27,939
to age 6

2837
01:13:27,939 --> 01:13:28,473
for ADHD.

2838
01:13:28,773 --> 01:13:29,838
It's, it's generic,

2839
01:13:29,838 --> 01:13:31,576
fairly inexpensive increase of

2840
01:13:31,576 --> 01:13:32,407
norepinephrine,

2841
01:13:32,407 --> 01:13:34,114
which also happens to increase

2842
01:13:34,114 --> 01:13:34,512
airway

2843
01:13:34,512 --> 01:13:35,513
tone in non R.E.M.

2844
01:13:36,214 --> 01:13:37,840
oxybutynin the FDA approved down

2845
01:13:37,840 --> 01:13:39,517
to age 6 for overactive bladder,

2846
01:13:39,517 --> 01:13:41,132
it decreases muscarinic receptor

2847
01:13:41,132 --> 01:13:42,730
activity, which also happens to

2848
01:13:42,730 --> 01:13:43,554
increase airway

2849
01:13:43,554 --> 01:13:44,455
tone in REM sleep.

2850
01:13:45,389 --> 01:13:46,499
So we looked at the

2851
01:13:46,499 --> 01:13:47,725
combination of this.

2852
01:13:48,092 --> 01:13:49,550
There was a study in 2019 in

2853
01:13:49,550 --> 01:13:51,039
adults without Down syndrome

2854
01:13:51,039 --> 01:13:51,996
that showed about

2855
01:13:51,996 --> 01:13:52,964
an 80% improvement.

2856
01:13:52,964 --> 01:13:54,062
So we thought this might be

2857
01:13:54,062 --> 01:13:55,140
particularly effective for

2858
01:13:55,140 --> 01:13:56,300
children with Down syndrome

2859
01:13:56,300 --> 01:13:57,593
because airway hypatonia is such

2860
01:13:57,593 --> 01:13:58,626
such a critical issue for

2861
01:13:58,626 --> 01:13:59,370
obstructive sleep

2862
01:13:59,370 --> 01:13:59,971
apnea for them.

2863
01:14:01,339 --> 01:14:02,491
Interestingly enough,

2864
01:14:02,491 --> 01:14:04,181
we found about a 50% reduction

2865
01:14:04,181 --> 01:14:04,575
in OSA

2866
01:14:04,575 --> 01:14:05,076
severity.

2867
01:14:05,810 --> 01:14:08,045
This was 12 kids aged 6 to 17.

2868
01:14:08,346 --> 01:14:09,259
And you can see that the

2869
01:14:09,259 --> 01:14:10,352
individual participant level

2870
01:14:10,352 --> 01:14:10,782
data here.

2871
01:14:11,449 --> 01:14:13,499
So you can see that some people

2872
01:14:13,499 --> 01:14:15,153
responded fantastically,

2873
01:14:15,153 --> 01:14:17,261
so participant in the orange and

2874
01:14:17,261 --> 01:14:19,415
then some did not have nearly as

2875
01:14:19,415 --> 01:14:20,424
much benefits,

2876
01:14:20,424 --> 01:14:21,425
but on average,

2877
01:14:21,425 --> 01:14:23,427
it's about a 50% improvement.

2878
01:14:24,796 --> 01:14:26,763
We have an ongoing larger study

2879
01:14:26,763 --> 01:14:28,771
that will look at about 36 kids

2880
01:14:28,771 --> 01:14:30,001
over six months to

2881
01:14:30,001 --> 01:14:31,590
look to see if we improve

2882
01:14:31,590 --> 01:14:33,287
quality of life as well as

2883
01:14:33,287 --> 01:14:34,005
cognition.

2884
01:14:34,338 --> 01:14:36,140
That study's ongoing that will

2885
01:14:36,140 --> 01:14:37,942
hopefully conclude next year.

2886
01:14:37,942 --> 01:14:39,146
So we'll hopefully have results

2887
01:14:39,146 --> 01:14:40,311
of that to present next year.

2888
01:14:41,345 --> 01:14:42,980
So this is a promising therapy.

2889
01:14:42,980 --> 01:14:44,710
There is a somewhat similar

2890
01:14:44,710 --> 01:14:46,804
medication called 81 O nine that

2891
01:14:46,804 --> 01:14:47,785
is in clinical

2892
01:14:47,785 --> 01:14:49,642
trials in adults without Down

2893
01:14:49,642 --> 01:14:51,606
syndrome that uses a different

2894
01:14:51,606 --> 01:14:52,523
version of of

2895
01:14:52,523 --> 01:14:53,991
oxybutynin essentially.

2896
01:14:55,126 --> 01:14:56,488
And so this is, this is

2897
01:14:56,488 --> 01:14:58,302
promising, but further studies

2898
01:14:58,302 --> 01:14:59,330
need to be done.

2899
01:15:00,631 --> 01:15:01,693
Does OSA treatment improve OSA

2900
01:15:01,693 --> 01:15:02,740
associated adverse effects in

2901
01:15:02,740 --> 01:15:03,534
people Down syndrome?

2902
01:15:03,534 --> 01:15:05,036
This is the important question.

2903
01:15:06,070 --> 01:15:07,508
There is a little bit of data

2904
01:15:07,508 --> 01:15:09,133
that suggests that the answer is

2905
01:15:09,133 --> 01:15:09,640
probably,

2906
01:15:09,640 --> 01:15:10,346
unfortunately,

2907
01:15:10,346 --> 01:15:12,009
they're both very small studies.

2908
01:15:12,009 --> 01:15:13,854
So one was a a study of of CPAP

2909
01:15:13,854 --> 01:15:15,561
that happened to include six

2910
01:15:15,561 --> 01:15:16,414
kids that had

2911
01:15:16,414 --> 01:15:17,215
Down syndrome.

2912
01:15:18,049 --> 01:15:19,519
Parent reported quality of life

2913
01:15:19,519 --> 01:15:20,925
and their behavioral outcomes

2914
01:15:20,925 --> 01:15:21,652
were improved.

2915
01:15:22,587 --> 01:15:24,244
There is one study that included

2916
01:15:24,244 --> 01:15:24,934
children with

2917
01:15:24,934 --> 01:15:26,524
mucopolysaccharidesis or Down

2918
01:15:26,524 --> 01:15:26,997
syndrome,

2919
01:15:26,997 --> 01:15:28,669
which did to improve quality of

2920
01:15:28,669 --> 01:15:28,993
life.

2921
01:15:31,696 --> 01:15:33,268
There was a pilot study of

2922
01:15:33,268 --> 01:15:34,993
hypoglossal nerve simulation

2923
01:15:34,993 --> 01:15:36,534
that also showed really,

2924
01:15:36,534 --> 01:15:38,483
really promising results that if

2925
01:15:38,483 --> 01:15:40,371
you can effectively treat OSA,

2926
01:15:40,371 --> 01:15:42,023
you do improve all of those

2927
01:15:42,023 --> 01:15:43,674
associated adverse issues.

2928
01:15:43,674 --> 01:15:44,675
So it works.

2929
01:15:44,675 --> 01:15:46,005
Quality of life and beared

2930
01:15:46,005 --> 01:15:47,465
cognition, all of those seem

2931
01:15:47,465 --> 01:15:48,613
like it probably gets

2932
01:15:48,613 --> 01:15:49,013
better.

2933
01:15:49,013 --> 01:15:50,381
Again, this is a study of nine.

2934
01:15:51,549 --> 01:15:52,867
One of the historic issues has

2935
01:15:52,867 --> 01:15:54,167
been that if CPAP is the only

2936
01:15:54,167 --> 01:15:55,019
effective therapy,

2937
01:15:55,019 --> 01:15:56,257
it's very hard to do a trial

2938
01:15:56,257 --> 01:15:57,519
where you know that at least

2939
01:15:57,519 --> 01:15:58,556
half your participants

2940
01:15:58,556 --> 01:15:59,953
are not going to use your study,

2941
01:15:59,953 --> 01:16:01,076
your intervention to show

2942
01:16:01,076 --> 01:16:01,525
efficacy.

2943
01:16:02,260 --> 01:16:03,423
So as we get more effective

2944
01:16:03,423 --> 01:16:04,741
therapies, I'm optimistic that

2945
01:16:04,741 --> 01:16:05,663
we're going to start

2946
01:16:05,663 --> 01:16:06,831
seeing larger improvements.

2947
01:16:10,101 --> 01:16:11,302
So obstructive sleep Ave.

2948
01:16:11,302 --> 01:16:12,103
take home points.

2949
01:16:12,470 --> 01:16:13,504
OSA is common in people.

2950
01:16:13,504 --> 01:16:15,467
Down syndrome is associated with

2951
01:16:15,467 --> 01:16:16,981
a lot of worse outcomes,

2952
01:16:16,981 --> 01:16:17,675
cognition,

2953
01:16:17,675 --> 01:16:18,652
quality of life,

2954
01:16:18,652 --> 01:16:20,177
cardiovascular behavior.

2955
01:16:20,912 --> 01:16:21,857
Current OSA treatments are

2956
01:16:21,857 --> 01:16:22,975
effective for some people Down

2957
01:16:22,975 --> 01:16:23,347
syndrome,

2958
01:16:23,347 --> 01:16:23,948
but not not all.

2959
01:16:24,815 --> 01:16:25,586
And we have multiple new

2960
01:16:25,586 --> 01:16:26,403
treatments that are under

2961
01:16:26,403 --> 01:16:27,351
development that may be more

2962
01:16:27,351 --> 01:16:27,985
effective for people

2963
01:16:27,985 --> 01:16:28,619
with Down syndrome.

2964
01:16:29,287 --> 01:16:30,484
So I think this is a really

2965
01:16:30,484 --> 01:16:31,797
promising area and I'm really

2966
01:16:31,797 --> 01:16:32,657
optimistic that in

2967
01:16:32,657 --> 01:16:34,085
the next 5 to 10 years we'll see

2968
01:16:34,085 --> 01:16:35,543
a lot of dramatic improvement in

2969
01:16:35,543 --> 01:16:36,227
OSA treatment.

2970
01:16:38,195 --> 01:16:39,393
Turning briefly towards

2971
01:16:39,393 --> 01:16:40,773
insomnia, insomnia related

2972
01:16:40,773 --> 01:16:42,099
complaints are extremely

2973
01:16:42,099 --> 01:16:43,620
common in children and adults

2974
01:16:43,620 --> 01:16:44,669
with Down syndrome.

2975
01:16:45,670 --> 01:16:46,867
The big issue with this

2976
01:16:46,867 --> 01:16:48,300
literature is most of these

2977
01:16:48,300 --> 01:16:49,573
studies tend to kind of

2978
01:16:49,573 --> 01:16:51,148
focus on sleep problems, sleep

2979
01:16:51,148 --> 01:16:52,700
complaints, and don't tend to

2980
01:16:52,700 --> 01:16:53,878
use strict diagnostic

2981
01:16:53,878 --> 01:16:54,345
criteria.

2982
01:16:55,246 --> 01:16:56,550
This gets challenging to

2983
01:16:56,550 --> 01:16:58,161
interpret because obstructive

2984
01:16:58,161 --> 01:16:59,050
sleep apnea can

2985
01:16:59,050 --> 01:17:00,657
simply cause sleep complaints,

2986
01:17:00,657 --> 01:17:02,359
whereas a more rigorous kind of

2987
01:17:02,359 --> 01:17:02,853
insomnia

2988
01:17:02,853 --> 01:17:04,439
diagnosis would probably be a

2989
01:17:04,439 --> 01:17:05,423
lot more helpful.

2990
01:17:06,424 --> 01:17:07,024
So in sum,

2991
01:17:07,024 --> 01:17:08,564
if you talk to parents of

2992
01:17:08,564 --> 01:17:09,427
children with

2993
01:17:09,427 --> 01:17:10,544
Down syndrome, this

2994
01:17:10,544 --> 01:17:11,896
is a common complaint.

2995
01:17:12,263 --> 01:17:14,389
This is a very open area that I

2996
01:17:14,389 --> 01:17:16,639
think really needs to be studied

2997
01:17:16,639 --> 01:17:17,201
kind of

2998
01:17:17,201 --> 01:17:18,936
briefly to highlight this.

2999
01:17:18,936 --> 01:17:20,027
So my general approach to

3000
01:17:20,027 --> 01:17:21,272
insomnia in clinic is really

3001
01:17:21,272 --> 01:17:22,340
someone comes in with a

3002
01:17:22,340 --> 01:17:23,445
complaint about insomnia,

3003
01:17:23,445 --> 01:17:24,241
they can't sleep,

3004
01:17:24,241 --> 01:17:25,501
You need to figure out what's

3005
01:17:25,501 --> 01:17:26,923
causing that says that a medical

3006
01:17:26,923 --> 01:17:27,411
condition.

3007
01:17:27,411 --> 01:17:28,117
So sleep apnea,

3008
01:17:28,117 --> 01:17:29,565
restless legs or kidney rhythm

3009
01:17:29,565 --> 01:17:30,047
disorders

3010
01:17:30,047 --> 01:17:31,259
and just asthma, untreated

3011
01:17:31,259 --> 01:17:32,596
reflux, things like that and

3012
01:17:32,596 --> 01:17:33,217
treating the

3013
01:17:33,217 --> 01:17:34,631
underlying disorder might make

3014
01:17:34,631 --> 01:17:36,187
that insomnia complaint go away.

3015
01:17:37,355 --> 01:17:38,391
Conversely, more of

3016
01:17:38,391 --> 01:17:39,590
the primary insomnia.

3017
01:17:39,590 --> 01:17:41,004
So insomnia where nothing else

3018
01:17:41,004 --> 01:17:42,351
is causing it kind of splits

3019
01:17:42,351 --> 01:17:43,361
broadly in the sleep

3020
01:17:43,361 --> 01:17:44,595
association insomnia limit

3021
01:17:44,595 --> 01:17:45,954
setting disorder in kids and

3022
01:17:45,954 --> 01:17:46,731
then primary or

3023
01:17:46,731 --> 01:17:47,568
psycho physiologic

3024
01:17:47,568 --> 01:17:48,499
insomnia in adults.

3025
01:17:48,499 --> 01:17:49,707
And behavioral therapy,

3026
01:17:49,707 --> 01:17:50,968
as it's been mentioned,

3027
01:17:50,968 --> 01:17:51,791
can be extremely

3028
01:17:51,791 --> 01:17:52,870
effective for these.

3029
01:17:55,573 --> 01:17:57,230
And so I'm going to gloss over

3030
01:17:57,230 --> 01:17:58,776
to sleep onset association.

3031
01:17:59,777 --> 01:18:01,122
So parent rocking childlessly,

3032
01:18:01,122 --> 01:18:02,277
the classic of this limit

3033
01:18:02,277 --> 01:18:02,646
setting

3034
01:18:02,646 --> 01:18:04,084
insomnia is really just children

3035
01:18:04,084 --> 01:18:04,982
testing boundaries.

3036
01:18:05,783 --> 01:18:06,777
And this is far too broad a

3037
01:18:06,777 --> 01:18:07,984
topic to talk about treatment in

3038
01:18:07,984 --> 01:18:08,285
detail.

3039
01:18:08,753 --> 01:18:09,787
I'm going to touch a little bit.

3040
01:18:09,787 --> 01:18:10,622
So older children,

3041
01:18:10,622 --> 01:18:12,143
so teens and adults tend to have

3042
01:18:12,143 --> 01:18:12,523
more of

3043
01:18:12,523 --> 01:18:13,124
the, in some,

3044
01:18:13,124 --> 01:18:14,641
we have adults experienced where

3045
01:18:14,641 --> 01:18:14,925
it's,

3046
01:18:14,925 --> 01:18:15,781
I want to sleep and

3047
01:18:15,781 --> 01:18:16,727
I can't fall asleep.

3048
01:18:17,395 --> 01:18:18,134
Maybe I'm stressed,

3049
01:18:18,134 --> 01:18:19,263
I'm worried about something.

3050
01:18:21,265 --> 01:18:22,570
And so treatment for that is

3051
01:18:22,570 --> 01:18:24,005
really focused on perpetuating

3052
01:18:24,005 --> 01:18:24,435
factors.

3053
01:18:24,435 --> 01:18:25,639
And so predisposing factors,

3054
01:18:25,639 --> 01:18:26,670
your risk for insomnia.

3055
01:18:27,605 --> 01:18:28,910
So you might have underlying

3056
01:18:28,910 --> 01:18:30,147
genetic risk, family risk,

3057
01:18:30,147 --> 01:18:31,242
precipitating factors,

3058
01:18:31,242 --> 01:18:32,503
you're worried about it and

3059
01:18:32,503 --> 01:18:33,344
things like that.

3060
01:18:33,344 --> 01:18:34,245
These tend to go away.

3061
01:18:34,612 --> 01:18:35,834
And then the reason people have

3062
01:18:35,834 --> 01:18:37,084
chronic insomnia is usually not

3063
01:18:37,084 --> 01:18:37,648
active coping

3064
01:18:37,648 --> 01:18:38,237
strategies that

3065
01:18:38,237 --> 01:18:38,983
make things worse.

3066
01:18:39,817 --> 01:18:40,463
The classic is

3067
01:18:40,463 --> 01:18:41,385
people don't sleep.

3068
01:18:41,385 --> 01:18:42,286
They try to go to bed super

3069
01:18:42,286 --> 01:18:43,172
early and then they're not

3070
01:18:43,172 --> 01:18:43,888
sleepy so they can't

3071
01:18:43,888 --> 01:18:44,288
fall asleep.

3072
01:18:45,389 --> 01:18:46,803
That's probably the most common

3073
01:18:46,803 --> 01:18:48,014
one that people tend to do

3074
01:18:48,014 --> 01:18:48,993
cognitive behavioral

3075
01:18:48,993 --> 01:18:49,527
therapy for.

3076
01:18:49,527 --> 01:18:50,434
Insomnia is the gold

3077
01:18:50,434 --> 01:18:51,295
standard for this.

3078
01:18:52,196 --> 01:18:53,972
This is a package of a bunch of

3079
01:18:53,972 --> 01:18:54,832
interventions.

3080
01:18:55,132 --> 01:18:55,621
Importantly,

3081
01:18:55,621 --> 01:18:56,959
a lot of these things are things

3082
01:18:56,959 --> 01:18:57,168
like

3083
01:18:57,168 --> 01:18:57,902
sleep restriction.

3084
01:18:58,903 --> 01:19:00,627
These are really effective for

3085
01:19:00,627 --> 01:19:02,451
people with a broad level of of

3086
01:19:02,451 --> 01:19:03,040
cognitive

3087
01:19:03,040 --> 01:19:03,541
function.

3088
01:19:03,541 --> 01:19:06,154
And so I think could probably be

3089
01:19:06,154 --> 01:19:08,493
adapted for many adults with

3090
01:19:08,493 --> 01:19:09,747
Down syndrome.

3091
01:19:10,548 --> 01:19:11,649
There's no research on this.

3092
01:19:11,649 --> 01:19:12,994
And so I'm mentioning it in

3093
01:19:12,994 --> 01:19:14,470
hopes that someone is feeling

3094
01:19:14,470 --> 01:19:15,386
inspired to begin

3095
01:19:15,386 --> 01:19:15,820
doing it.

3096
01:19:16,153 --> 01:19:17,488
And so I'll end with kind of

3097
01:19:17,488 --> 01:19:18,823
future research directions.

3098
01:19:19,924 --> 01:19:20,471
Insomnia,

3099
01:19:20,471 --> 01:19:22,154
really rigorous studies are

3100
01:19:22,154 --> 01:19:23,027
lacking a lot

3101
01:19:23,027 --> 01:19:23,632
of, again,

3102
01:19:23,632 --> 01:19:25,629
they tend to be focused on sleep

3103
01:19:25,629 --> 01:19:27,205
complaints, kind of vague,

3104
01:19:27,205 --> 01:19:28,642
not specific diagnostic

3105
01:19:28,642 --> 01:19:29,266
criteria.

3106
01:19:30,267 --> 01:19:31,956
And so even doing studies trying

3107
01:19:31,956 --> 01:19:33,631
to window down, is this primary

3108
01:19:33,631 --> 01:19:34,171
insomnia,

3109
01:19:34,171 --> 01:19:35,706
this is insomnia due to sleep

3110
01:19:35,706 --> 01:19:37,278
apnea or needed Cbti or other

3111
01:19:37,278 --> 01:19:37,875
behavioral

3112
01:19:37,875 --> 01:19:39,247
interventions are probably

3113
01:19:39,247 --> 01:19:40,917
adaptable to individuals across

3114
01:19:40,917 --> 01:19:41,779
a wide range of

3115
01:19:41,779 --> 01:19:42,813
cognitive abilities.

3116
01:19:43,647 --> 01:19:44,944
This is completely unstudied as

3117
01:19:44,944 --> 01:19:46,020
far as I'm aware for Down

3118
01:19:46,020 --> 01:19:46,450
syndrome.

3119
01:19:47,485 --> 01:19:49,390
And then as it's been touched on

3120
01:19:49,390 --> 01:19:50,521
by other speakers,

3121
01:19:50,521 --> 01:19:52,373
medications are really commonly

3122
01:19:52,373 --> 01:19:53,090
prescribed.

3123
01:19:53,090 --> 01:19:55,120
There's really minimal data for

3124
01:19:55,120 --> 01:19:57,125
safety or FX advocacy specific

3125
01:19:57,125 --> 01:19:58,329
to Down syndrome,

3126
01:19:58,329 --> 01:19:59,897
obstructive sleep apnea.

3127
01:19:59,897 --> 01:20:00,937
So we, we need, we

3128
01:20:00,937 --> 01:20:02,266
need better therapies.

3129
01:20:02,500 --> 01:20:03,868
I think there's studies ongoing.

3130
01:20:04,768 --> 01:20:05,974
So maybe there's a role for

3131
01:20:05,974 --> 01:20:07,299
position medicine to identify

3132
01:20:07,299 --> 01:20:07,938
the right OSA

3133
01:20:07,938 --> 01:20:08,677
treatment for the

3134
01:20:08,677 --> 01:20:09,373
right patients.

3135
01:20:10,107 --> 01:20:11,582
We got a recent PECORI grant

3136
01:20:11,582 --> 01:20:13,250
that is starting this year that

3137
01:20:13,250 --> 01:20:14,111
will attempt to

3138
01:20:14,111 --> 01:20:14,945
do exactly that.

3139
01:20:14,945 --> 01:20:16,422
So we'll see if we can predict

3140
01:20:16,422 --> 01:20:18,029
if people are going to be better

3141
01:20:18,029 --> 01:20:18,983
responders to auto

3142
01:20:18,983 --> 01:20:20,451
oxy versus oxygen as therapies

3143
01:20:20,451 --> 01:20:21,919
based on their sleep studies,

3144
01:20:21,919 --> 01:20:23,354
their based on sleep studies.

3145
01:20:24,188 --> 01:20:25,930
And then broadly long term,

3146
01:20:25,930 --> 01:20:28,058
does treatment improve cognition

3147
01:20:28,058 --> 01:20:30,119
importantly lower Alzheimer risk

3148
01:20:30,119 --> 01:20:31,705
as individuals with Down

3149
01:20:31,705 --> 01:20:32,630
syndrome age,

3150
01:20:32,630 --> 01:20:34,375
the Alzheimer risk is very,

3151
01:20:34,375 --> 01:20:36,103
very important concern for

3152
01:20:36,103 --> 01:20:36,767
families.

3153
01:20:37,668 --> 01:20:39,069
So I will stop right there.

3154
01:20:42,339 --> 01:20:43,107
Thank you.

3155
01:20:43,107 --> 01:20:43,807
Thank you so much.

3156
01:20:43,807 --> 01:20:45,391
That was a great overview and

3157
01:20:45,391 --> 01:20:46,810
and pretty comprehensive.

3158
01:20:46,810 --> 01:20:47,876
We do have a question in the

3159
01:20:47,876 --> 01:20:49,123
chat and then if we have time, I

3160
01:20:49,123 --> 01:20:49,513
have one.

3161
01:20:50,147 --> 01:20:51,058
The question is,

3162
01:20:51,058 --> 01:20:52,750
can you please comment on the

3163
01:20:52,750 --> 01:20:53,450
feasibility

3164
01:20:53,450 --> 01:20:54,182
of PSG in the

3165
01:20:54,182 --> 01:20:55,419
pediatric population?

3166
01:20:55,419 --> 01:20:56,856
How often are valid PSG

3167
01:20:56,856 --> 01:20:58,828
assessments just not attainable

3168
01:20:58,828 --> 01:21:00,291
and is this greater or

3169
01:21:00,291 --> 01:21:02,169
lesser problem in NDD patients

3170
01:21:02,169 --> 01:21:04,168
recognizing that there are lots

3171
01:21:04,168 --> 01:21:04,361
of

3172
01:21:04,361 --> 01:21:05,863
different types of NDDS?

3173
01:21:06,630 --> 01:21:07,631
That's a great question.

3174
01:21:07,631 --> 01:21:08,496
I actually had a slide on that

3175
01:21:08,496 --> 01:21:09,261
and I took it out 'cause I

3176
01:21:09,261 --> 01:21:09,967
didn't get time to talk

3177
01:21:09,967 --> 01:21:10,234
about it.

3178
01:21:10,901 --> 01:21:11,104
So,

3179
01:21:11,104 --> 01:21:13,204
So the answer is from a clinic

3180
01:21:13,204 --> 01:21:14,012
perspective,

3181
01:21:14,012 --> 01:21:16,154
we do about 500 sleep studies a

3182
01:21:16,154 --> 01:21:16,707
year at

3183
01:21:16,707 --> 01:21:17,408
our clinic.

3184
01:21:17,908 --> 01:21:20,058
I would say we have less than 1%

3185
01:21:20,058 --> 01:21:22,054
get cancelled for propeeds so

3186
01:21:22,054 --> 01:21:22,880
they can be

3187
01:21:22,880 --> 01:21:23,214
done.

3188
01:21:24,148 --> 01:21:25,525
Some of my collaborators,

3189
01:21:25,525 --> 01:21:26,517
so Ignacio Tapia,

3190
01:21:26,517 --> 01:21:28,219
Chris Cello have looked at home

3191
01:21:28,219 --> 01:21:29,153
sleep tests for,

3192
01:21:29,153 --> 01:21:30,685
for children and adults with

3193
01:21:30,685 --> 01:21:32,362
Down syndrome depending on the

3194
01:21:32,362 --> 01:21:33,257
device you use.

3195
01:21:33,257 --> 01:21:33,981
Those were actually

3196
01:21:33,981 --> 01:21:34,592
very promising.

3197
01:21:35,426 --> 01:21:36,861
And so the kind of traditional

3198
01:21:36,861 --> 01:21:38,421
home sleep apnea tests that look

3199
01:21:38,421 --> 01:21:39,396
at airflow at home,

3200
01:21:39,396 --> 01:21:39,637
they,

3201
01:21:39,637 --> 01:21:41,021
they had fairly good success

3202
01:21:41,021 --> 01:21:41,565
with that.

3203
01:21:41,565 --> 01:21:42,455
And so I think there

3204
01:21:42,455 --> 01:21:43,300
are other options.

3205
01:21:44,468 --> 01:21:46,115
We would love to have an in lab

3206
01:21:46,115 --> 01:21:47,071
TST for children,

3207
01:21:47,071 --> 01:21:48,702
but also some it's not going to

3208
01:21:48,702 --> 01:21:49,807
happen for everyone.

3209
01:21:50,608 --> 01:21:52,095
I think looking at the home

3210
01:21:52,095 --> 01:21:53,496
sleep test is an entirely

3211
01:21:53,496 --> 01:21:55,179
reasonable option clinically.

3212
01:21:55,179 --> 01:21:56,247
We will do that sometimes.

3213
01:21:56,247 --> 01:21:57,876
Some of the other devices like

3214
01:21:57,876 --> 01:21:59,016
the more ring types,

3215
01:21:59,016 --> 01:22:00,090
devices that look at

3216
01:22:00,090 --> 01:22:01,354
cardiovascular, cardio,

3217
01:22:01,354 --> 01:22:02,453
pulmonary coupling,

3218
01:22:02,453 --> 01:22:03,781
I'm hesitant to recommend

3219
01:22:03,781 --> 01:22:05,135
because I don't know that

3220
01:22:05,135 --> 01:22:06,490
there's a lot of data to

3221
01:22:06,490 --> 01:22:08,211
support them and I think there's

3222
01:22:08,211 --> 01:22:09,595
a high risk of inaccurate

3223
01:22:09,595 --> 01:22:10,094
studies.

3224
01:22:10,861 --> 01:22:12,354
But anything that that looks at

3225
01:22:12,354 --> 01:22:13,681
airflow I think is entirely

3226
01:22:13,681 --> 01:22:14,665
reasonable and it's

3227
01:22:14,665 --> 01:22:15,933
probably relatively useful.

3228
01:22:16,767 --> 01:22:17,434
So thank you.

3229
01:22:18,302 --> 01:22:18,956
Yeah, it's a very

3230
01:22:18,956 --> 01:22:19,803
comprehensive answer.

3231
01:22:19,803 --> 01:22:20,271
Thank you.

3232
01:22:20,537 --> 01:22:22,131
So I do have this time for I I

3233
01:22:22,131 --> 01:22:23,869
am The auto oxy stuff is just so

3234
01:22:23,869 --> 01:22:24,575
exciting and

3235
01:22:24,575 --> 01:22:26,234
it's so great that you're doing

3236
01:22:26,234 --> 01:22:27,411
that Super promising.

3237
01:22:27,411 --> 01:22:29,396
I didn't catch whether or not

3238
01:22:29,396 --> 01:22:31,562
the kids who are enrolled in in

3239
01:22:31,562 --> 01:22:32,750
those trials are

3240
01:22:32,750 --> 01:22:34,783
the people with Down syndrome

3241
01:22:34,783 --> 01:22:37,001
who are enrolled if they had to

3242
01:22:37,001 --> 01:22:38,289
have a prior TNA.

3243
01:22:38,289 --> 01:22:39,827
So have you done the standard

3244
01:22:39,827 --> 01:22:41,341
sort of for them or are they

3245
01:22:41,341 --> 01:22:42,693
sort of folks who didn't

3246
01:22:42,693 --> 01:22:44,359
want to have the surgery or how

3247
01:22:44,359 --> 01:22:45,596
did how does that get?

3248
01:22:46,463 --> 01:22:47,898
That is a great question.

3249
01:22:47,898 --> 01:22:48,880
So for that study,

3250
01:22:48,880 --> 01:22:50,229
children with three plus

3251
01:22:50,229 --> 01:22:50,734
tonsils,

3252
01:22:50,734 --> 01:22:52,352
so like essentially very large

3253
01:22:52,352 --> 01:22:54,064
tonsils are not eligible unless

3254
01:22:54,064 --> 01:22:54,672
they get a

3255
01:22:54,672 --> 01:22:55,739
tonsillectomy first.

3256
01:22:56,507 --> 01:22:57,374
In that pilot study,

3257
01:22:57,374 --> 01:22:58,620
everyone had a tonsillectomy

3258
01:22:58,620 --> 01:22:59,109
before the

3259
01:22:59,109 --> 01:22:59,710
study anyways.

3260
01:22:59,710 --> 01:23:01,201
So they just all happened to

3261
01:23:01,201 --> 01:23:02,479
have had tonsillectomy,

3262
01:23:02,479 --> 01:23:03,325
which I think is

3263
01:23:03,325 --> 01:23:04,381
generally the case.

3264
01:23:04,381 --> 01:23:05,840
In our larger study,

3265
01:23:05,840 --> 01:23:08,087
I think we have maybe 10% that

3266
01:23:08,087 --> 01:23:08,686
haven't

3267
01:23:08,686 --> 01:23:10,087
had a tonsillectomy.

3268
01:23:10,087 --> 01:23:10,809
So I think we've just,

3269
01:23:10,809 --> 01:23:11,718
the reality is that they've

3270
01:23:11,718 --> 01:23:12,089
almost all

3271
01:23:12,089 --> 01:23:13,077
had a tonsillectomy before they

3272
01:23:13,077 --> 01:23:13,524
do the study.

3273
01:23:14,091 --> 01:23:14,457
And so,

3274
01:23:14,457 --> 01:23:16,118
and then how many of those sort

3275
01:23:16,118 --> 01:23:16,493
of had

3276
01:23:16,493 --> 01:23:18,093
resolution or I guess that's in

3277
01:23:18,093 --> 01:23:19,797
the paper, like where they were,

3278
01:23:19,797 --> 01:23:21,352
how well they responded before

3279
01:23:21,352 --> 01:23:22,700
they started the Idoloxy.

3280
01:23:24,168 --> 01:23:25,584
So we don't because we didn't

3281
01:23:25,584 --> 01:23:26,937
look at their tonsillectomy

3282
01:23:26,937 --> 01:23:27,538
beforehand.

3283
01:23:27,538 --> 01:23:28,739
So we, we do a baseline study.

3284
01:23:28,739 --> 01:23:28,979
So we,

3285
01:23:28,979 --> 01:23:30,134
we know what their status is

3286
01:23:30,134 --> 01:23:30,341
post

3287
01:23:30,341 --> 01:23:31,427
tonsillectomy, but we don't

3288
01:23:31,427 --> 01:23:32,578
really, we don't collect the

3289
01:23:32,578 --> 01:23:33,277
data on pre tons

3290
01:23:33,277 --> 01:23:33,596
like me,

3291
01:23:33,596 --> 01:23:34,912
just because a lot of them don't

3292
01:23:34,912 --> 01:23:35,713
necessarily have it.

3293
01:23:37,247 --> 01:23:37,981
Thank you.

3294
01:23:37,981 --> 01:23:38,916
Thank you so much.

3295
01:23:38,916 --> 01:23:39,616
Awesome work.

3296
01:23:40,451 --> 01:23:41,671
OK, we're gonna,

3297
01:23:41,671 --> 01:23:44,188
we are right on time and we are.

3298
01:23:44,188 --> 01:23:44,419
Oh,

3299
01:23:44,419 --> 01:23:46,871
we might have one more if we if

3300
01:23:46,871 --> 01:23:47,424
it's a

3301
01:23:47,424 --> 01:23:48,492
62nd question.

3302
01:23:51,028 --> 01:23:51,168
Oh,

3303
01:23:51,168 --> 01:23:52,696
this is just a comment about the

3304
01:23:52,696 --> 01:23:53,030
attoxy

3305
01:23:53,030 --> 01:23:54,313
slide looking like they're a

3306
01:23:54,313 --> 01:23:55,764
bunch of subjects who did a bit

3307
01:23:55,764 --> 01:23:56,467
worse with the

3308
01:23:56,467 --> 01:23:57,034
higher dose.

3309
01:23:57,334 --> 01:23:58,386
Was that reflecting

3310
01:23:58,386 --> 01:23:59,603
intolerability issue?

3311
01:23:59,870 --> 01:24:01,185
So they were less adherent with

3312
01:24:01,185 --> 01:24:01,905
the higher dose.

3313
01:24:02,940 --> 01:24:03,604
Is that something

3314
01:24:03,604 --> 01:24:04,308
you'd comment on?

3315
01:24:05,976 --> 01:24:06,744
I don't know that I can

3316
01:24:06,744 --> 01:24:07,796
officially answer that question

3317
01:24:07,796 --> 01:24:08,679
because it's such a small

3318
01:24:08,679 --> 01:24:08,846
study.

3319
01:24:09,346 --> 01:24:11,017
For the larger study we're using

3320
01:24:11,017 --> 01:24:11,749
the low dose.

3321
01:24:13,016 --> 01:24:14,423
So I think that there probably

3322
01:24:14,423 --> 01:24:15,954
is some we saw more side effects

3323
01:24:15,954 --> 01:24:16,720
with the higher

3324
01:24:16,720 --> 01:24:16,954
dose.

3325
01:24:16,954 --> 01:24:17,560
And so there's

3326
01:24:17,560 --> 01:24:18,555
probably some of that.

3327
01:24:19,423 --> 01:24:20,794
But because it essentially works

3328
01:24:20,794 --> 01:24:22,062
nightly, as long as they took

3329
01:24:22,062 --> 01:24:22,893
the medication the

3330
01:24:22,893 --> 01:24:23,717
night of the study,

3331
01:24:23,717 --> 01:24:25,062
they should have had advocacy.

3332
01:24:26,096 --> 01:24:27,315
I think there was one or two

3333
01:24:27,315 --> 01:24:28,742
that needed to take it like in a

3334
01:24:28,742 --> 01:24:29,099
liquid.

3335
01:24:29,099 --> 01:24:30,239
And so maybe they didn't finish

3336
01:24:30,239 --> 01:24:30,901
their whole dose.

3337
01:24:31,769 --> 01:24:33,167
But we based on that data,

3338
01:24:33,167 --> 01:24:34,876
that data we used the the lower

3339
01:24:34,876 --> 01:24:35,372
dose for

3340
01:24:35,372 --> 01:24:36,273
our larger study.

3341
01:24:37,274 --> 01:24:39,143
OK, OK, thank you very much.

3342
01:24:39,510 --> 01:24:41,028
We are gonna turn now

3343
01:24:41,028 --> 01:24:42,546
to our next speaker.

3344
01:24:43,447 --> 01:24:44,767
Demetrius Milonas is an

3345
01:24:44,767 --> 01:24:46,054
assistant professor of

3346
01:24:46,054 --> 01:24:47,751
psychology in the Department

3347
01:24:47,751 --> 01:24:49,461
of Psychiatry at Massachusetts

3348
01:24:49,461 --> 01:24:50,487
General Hospital.

3349
01:24:51,021 --> 01:24:52,870
His research interests include

3350
01:24:52,870 --> 01:24:54,070
the development and

3351
01:24:54,070 --> 01:24:55,459
implementation of new

3352
01:24:55,459 --> 01:24:57,423
analysis methods to neuroimaging

3353
01:24:57,423 --> 01:24:58,896
data, EE, GMEG and MRI.

3354
01:24:59,463 --> 01:25:01,179
His presentation will focus on

3355
01:25:01,179 --> 01:25:02,666
autism spectrum disorder.

3356
01:25:02,866 --> 01:25:05,738
So thank you so much for

3357
01:25:05,738 --> 01:25:09,523
inviting me today that So today

3358
01:25:09,523 --> 01:25:11,842
I'm going to speak

3359
01:25:11,842 --> 01:25:15,213
about sleep ET biomarkers in

3360
01:25:15,213 --> 01:25:18,546
autism and I don't have any

3361
01:25:18,546 --> 01:25:20,150
disclosures.

3362
01:25:21,618 --> 01:25:24,469
So we focus on sleep ET in our

3363
01:25:24,469 --> 01:25:26,798
work and we're trying to

3364
01:25:26,798 --> 01:25:29,126
establish links between

3365
01:25:29,126 --> 01:25:31,808
the underlying secretary and

3366
01:25:31,808 --> 01:25:33,190
manifestations

3367
01:25:33,190 --> 01:25:35,065
neurodevelopmental

3368
01:25:35,065 --> 01:25:35,899
disorder.

3369
01:25:35,899 --> 01:25:38,472
So today I'm going to speak how

3370
01:25:38,472 --> 01:25:40,336
we can study non sleep

3371
01:25:40,336 --> 01:25:42,539
oscillations to inform us

3372
01:25:42,539 --> 01:25:44,531
about the thermocortical

3373
01:25:44,531 --> 01:25:47,238
circuitry and how this is linked

3374
01:25:47,238 --> 01:25:48,846
to impaired sleep.

3375
01:25:49,046 --> 01:25:49,765
You notice,

3376
01:25:49,765 --> 01:25:51,712
and there is probably no need

3377
01:25:51,712 --> 01:25:52,316
for that

3378
01:25:52,316 --> 01:25:54,215
because the previous speakers

3379
01:25:54,215 --> 01:25:55,853
talked a lot about that,

3380
01:25:55,853 --> 01:25:56,759
but sleep is a

3381
01:25:56,759 --> 01:25:57,988
important problem.

3382
01:25:57,988 --> 01:26:00,274
You notice up to 80% of children

3383
01:26:00,274 --> 01:26:02,327
and adolescents report sleep

3384
01:26:02,327 --> 01:26:03,060
problems,

3385
01:26:03,060 --> 01:26:05,195
including difficulties falling

3386
01:26:05,195 --> 01:26:07,331
asleep or waking after sleep.

3387
01:26:07,331 --> 01:26:09,889
Oncids and importantly as Doctor

3388
01:26:09,889 --> 01:26:11,168
Malo mentioned,

3389
01:26:11,168 --> 01:26:13,139
these were sleep problems

3390
01:26:13,139 --> 01:26:15,387
actually are associated with

3391
01:26:15,387 --> 01:26:17,474
more severe core symptoms

3392
01:26:17,474 --> 01:26:19,810
and worse day day functioning.

3393
01:26:20,043 --> 01:26:21,691
So it's very important to

3394
01:26:21,691 --> 01:26:23,100
understand the neural

3395
01:26:23,100 --> 01:26:24,827
underpinnings of impaired

3396
01:26:24,827 --> 01:26:25,449
sleeping

3397
01:26:25,449 --> 01:26:27,229
autism and to develop novel

3398
01:26:27,229 --> 01:26:29,310
interventions, and also for the

3399
01:26:29,310 --> 01:26:30,854
existing interventions

3400
01:26:30,854 --> 01:26:32,688
to actually understand, like

3401
01:26:32,688 --> 01:26:34,424
melatonin, for example, to

3402
01:26:34,424 --> 01:26:36,093
understand how they act.

3403
01:26:36,994 --> 01:26:38,862
So I will go very briefly.

3404
01:26:39,730 --> 01:26:41,257
I will give a very brief

3405
01:26:41,257 --> 01:26:42,466
overview of sleep.

3406
01:26:43,467 --> 01:26:45,096
Just want to say that sleep is

3407
01:26:45,096 --> 01:26:46,670
not a monolithic phenomenon.

3408
01:26:46,670 --> 01:26:49,477
There are different stages

3409
01:26:49,477 --> 01:26:52,905
states of sleep and by using EG

3410
01:26:52,905 --> 01:26:54,011
actually.

3411
01:26:54,011 --> 01:26:56,154
So what you see on top is the

3412
01:26:56,154 --> 01:26:58,492
typical hypnogram of sleep with

3413
01:26:58,492 --> 01:26:59,850
a different sleep

3414
01:26:59,850 --> 01:27:02,141
stages and at the bottom is the

3415
01:27:02,141 --> 01:27:04,255
window in the brain activity

3416
01:27:04,255 --> 01:27:05,689
that EG can offer.

3417
01:27:05,956 --> 01:27:07,678
On the X axis is the time,

3418
01:27:07,678 --> 01:27:09,716
the 9 hours of sleep and the Y

3419
01:27:09,716 --> 01:27:10,327
axis are

3420
01:27:10,327 --> 01:27:11,395
the frequencies.

3421
01:27:11,595 --> 01:27:12,537
So using EG,

3422
01:27:12,537 --> 01:27:14,793
we can actually see that the

3423
01:27:14,793 --> 01:27:15,599
different

3424
01:27:15,599 --> 01:27:17,939
sleep stages are characterized

3425
01:27:17,939 --> 01:27:20,413
by different by different brain

3426
01:27:20,413 --> 01:27:21,371
activities.

3427
01:27:21,371 --> 01:27:22,920
So slow wave sleep here,

3428
01:27:22,920 --> 01:27:24,977
stage sleep is characterized by

3429
01:27:24,977 --> 01:27:25,309
this

3430
01:27:25,309 --> 01:27:26,258
increase in low

3431
01:27:26,258 --> 01:27:27,778
frequency oscillations.

3432
01:27:27,778 --> 01:27:29,713
You can see it here, even here.

3433
01:27:30,948 --> 01:27:33,107
And knowing about of sleep,

3434
01:27:33,107 --> 01:27:35,730
stage 2 and stage stay sleep are

3435
01:27:35,730 --> 01:27:36,386
aligned

3436
01:27:36,386 --> 01:27:38,977
very well with this increased of

3437
01:27:38,977 --> 01:27:40,976
increased power in Sigma

3438
01:27:40,976 --> 01:27:41,892
frequency.

3439
01:27:41,892 --> 01:27:44,144
This 12 to 15 Hertz activity,

3440
01:27:44,144 --> 01:27:46,396
you can see it very clearly.

3441
01:27:46,830 --> 01:27:48,702
And this is important because

3442
01:27:48,702 --> 01:27:50,812
this increases in power actually

3443
01:27:50,812 --> 01:27:51,735
reflect brain

3444
01:27:51,735 --> 01:27:52,491
oscillatory

3445
01:27:52,491 --> 01:27:54,004
oscillatory activity.

3446
01:27:54,004 --> 01:27:56,121
So this increases in low

3447
01:27:56,121 --> 01:27:58,733
frequency reflect slow waves,

3448
01:27:58,733 --> 01:28:00,444
slow oscillations.

3449
01:28:00,744 --> 01:28:03,113
And this increases in Sigma band

3450
01:28:03,113 --> 01:28:05,390
actually reflect spindles such

3451
01:28:05,390 --> 01:28:06,149
spindles.

3452
01:28:06,383 --> 01:28:09,098
And since this will be my main

3453
01:28:09,098 --> 01:28:11,961
characters, the main characters

3454
01:28:11,961 --> 01:28:13,624
of my talk today,

3455
01:28:13,624 --> 01:28:16,376
I will spend one more slide to

3456
01:28:16,376 --> 01:28:17,661
go over them.

3457
01:28:18,195 --> 01:28:20,887
So slow waves or slow psilations

3458
01:28:20,887 --> 01:28:22,065
are cortical,

3459
01:28:22,065 --> 01:28:23,984
cortical waves that are

3460
01:28:23,984 --> 01:28:26,624
generated in the cortex, in the

3461
01:28:26,624 --> 01:28:28,071
pyramidal cells,

3462
01:28:28,071 --> 01:28:29,206
in the cortex.

3463
01:28:29,906 --> 01:28:30,463
Spindles,

3464
01:28:30,463 --> 01:28:32,432
which are the hallmark of stage

3465
01:28:32,432 --> 01:28:32,876
2 slip

3466
01:28:32,876 --> 01:28:34,541
are generated in the salami

3467
01:28:34,541 --> 01:28:35,712
reticular nucleus.

3468
01:28:35,712 --> 01:28:37,833
And then we have sharp wave

3469
01:28:37,833 --> 01:28:39,769
rippers generated in the

3470
01:28:39,769 --> 01:28:40,817
hippocampus.

3471
01:28:41,018 --> 01:28:43,695
And these are the three non REM

3472
01:28:43,695 --> 01:28:45,422
sleep oscillations.

3473
01:28:45,689 --> 01:28:46,572
Importantly,

3474
01:28:46,572 --> 01:28:48,925
these oscillations are actually

3475
01:28:48,925 --> 01:28:50,822
synchronized, synchronized

3476
01:28:50,822 --> 01:28:53,210
altogether, so they don't act in

3477
01:28:53,210 --> 01:28:54,031
isolation.

3478
01:28:54,031 --> 01:28:56,088
So during non REM sleep,

3479
01:28:56,088 --> 01:28:58,812
this secretary is in a constant

3480
01:28:58,812 --> 01:28:59,603
dialogue

3481
01:28:59,603 --> 01:29:02,264
and I will spend one more slide

3482
01:29:02,264 --> 01:29:04,366
to focus on the thalamic

3483
01:29:04,366 --> 01:29:06,643
thalamocortical circuitry

3484
01:29:06,643 --> 01:29:09,383
because and explain why we think

3485
01:29:09,383 --> 01:29:12,098
that thalamic reticular nucleus

3486
01:29:12,098 --> 01:29:13,150
dysfunction

3487
01:29:13,150 --> 01:29:15,903
may contribute to both sleep and

3488
01:29:15,903 --> 01:29:18,055
wake symptoms in autism.

3489
01:29:18,288 --> 01:29:20,490
So this is this red structure.

3490
01:29:20,490 --> 01:29:22,665
Here is the thalamic reticular

3491
01:29:22,665 --> 01:29:25,032
nucleus which is a thin shell of

3492
01:29:25,032 --> 01:29:26,363
gabytic neurosis,

3493
01:29:26,363 --> 01:29:28,381
completely inhibitory and it

3494
01:29:28,381 --> 01:29:30,443
wraps around the lateral and

3495
01:29:30,443 --> 01:29:31,768
ventral thalamus.

3496
01:29:31,968 --> 01:29:34,301
So due to its strategic

3497
01:29:34,301 --> 01:29:36,887
location, TRN is actually

3498
01:29:36,887 --> 01:29:39,576
modulates thalamocortical

3499
01:29:39,576 --> 01:29:40,977
communication.

3500
01:29:41,411 --> 01:29:44,239
So during the day TRN actually

3501
01:29:44,239 --> 01:29:47,028
inhibits the incoming sensory

3502
01:29:47,028 --> 01:29:48,952
information or like

3503
01:29:48,952 --> 01:29:51,585
filters the incoming sensory

3504
01:29:51,585 --> 01:29:54,273
information leaving only the

3505
01:29:54,273 --> 01:29:56,193
salient the salient

3506
01:29:56,193 --> 01:29:59,109
stimuli to to come in and works

3507
01:29:59,109 --> 01:30:01,905
functions as a Searchlight of

3508
01:30:01,905 --> 01:30:02,966
attention.

3509
01:30:03,266 --> 01:30:05,859
So dysfunction of this inhibitor

3510
01:30:05,859 --> 01:30:08,511
reaction can actually lead to an

3511
01:30:08,511 --> 01:30:09,506
overflow of

3512
01:30:09,506 --> 01:30:11,878
sensory stimuli to the cortex

3513
01:30:11,878 --> 01:30:13,677
and over stimulation,

3514
01:30:13,677 --> 01:30:16,179
sensory sensitivities etcetera.

3515
01:30:16,713 --> 01:30:18,556
So during night the same

3516
01:30:18,556 --> 01:30:20,516
structure generates sleep

3517
01:30:20,516 --> 01:30:22,319
spindles by inhibiting

3518
01:30:22,319 --> 01:30:24,554
this thalamocortical neurons.

3519
01:30:24,821 --> 01:30:27,244
And there is a large large body

3520
01:30:27,244 --> 01:30:29,806
of literature showing that sleep

3521
01:30:29,806 --> 01:30:30,527
spindles

3522
01:30:30,527 --> 01:30:32,945
play a protective role in sleep

3523
01:30:32,945 --> 01:30:35,333
with the same idea that during

3524
01:30:35,333 --> 01:30:36,767
the sleep spindle

3525
01:30:36,767 --> 01:30:38,650
the cortical response to

3526
01:30:38,650 --> 01:30:40,895
external auditors stimuli is

3527
01:30:40,895 --> 01:30:42,339
quite suppressed.

3528
01:30:42,906 --> 01:30:43,702
So again,

3529
01:30:43,702 --> 01:30:46,436
this inhibition or dysfunction

3530
01:30:46,436 --> 01:30:46,710
of

3531
01:30:46,710 --> 01:30:49,443
thalamocortical circuitry might

3532
01:30:49,443 --> 01:30:51,648
leads to impaired sleep,

3533
01:30:51,648 --> 01:30:53,834
more awakenings both over

3534
01:30:53,834 --> 01:30:55,526
stimulation, sensor

3535
01:30:55,526 --> 01:30:57,913
sensitivities and impaired

3536
01:30:57,913 --> 01:30:58,555
sleep,

3537
01:30:58,555 --> 01:30:59,511
very common

3538
01:30:59,511 --> 01:31:01,424
phenotypes in autism.

3539
01:31:04,060 --> 01:31:06,243
So a main research test of mine

3540
01:31:06,243 --> 01:31:08,478
is developing methods to detect

3541
01:31:08,478 --> 01:31:09,199
spindles,

3542
01:31:09,199 --> 01:31:11,234
low waves and their coupling.

3543
01:31:11,568 --> 01:31:13,999
And I won't go into the details

3544
01:31:13,999 --> 01:31:16,480
here of these methods, although

3545
01:31:16,480 --> 01:31:17,841
I would love to,

3546
01:31:17,841 --> 01:31:20,110
but will take us a long time.

3547
01:31:20,110 --> 01:31:21,750
But these are examples of this

3548
01:31:21,750 --> 01:31:23,431
is an example of a spindle and

3549
01:31:23,431 --> 01:31:24,047
how we can

3550
01:31:24,047 --> 01:31:24,915
characterize it.

3551
01:31:25,615 --> 01:31:27,647
You know, the, the, the, the

3552
01:31:27,647 --> 01:31:29,514
duration, the features in

3553
01:31:29,514 --> 01:31:30,187
general,

3554
01:31:30,187 --> 01:31:32,283
these are slow waves detected

3555
01:31:32,283 --> 01:31:34,090
slow waves during sleep.

3556
01:31:34,491 --> 01:31:36,301
And this is what I talked about

3557
01:31:36,301 --> 01:31:38,212
the coordination of spindles and

3558
01:31:38,212 --> 01:31:38,929
slow waves.

3559
01:31:38,929 --> 01:31:41,379
So this is a spindle here riding

3560
01:31:41,379 --> 01:31:43,884
on top of of a on the upstate of

3561
01:31:43,884 --> 01:31:44,901
a slow wave.

3562
01:31:45,235 --> 01:31:47,486
And this is a cartoon now of the

3563
01:31:47,486 --> 01:31:48,471
same concept.

3564
01:31:48,705 --> 01:31:50,931
But we can actually quantify

3565
01:31:50,931 --> 01:31:53,214
this synchronization of slow

3566
01:31:53,214 --> 01:31:54,110
waves with

3567
01:31:54,110 --> 01:31:54,811
spindles.

3568
01:31:56,112 --> 01:31:57,261
If we do that,

3569
01:31:57,261 --> 01:31:59,712
like if we find spindles that

3570
01:31:59,712 --> 01:32:00,050
are

3571
01:32:00,050 --> 01:32:02,519
synchronized across the night,

3572
01:32:02,519 --> 01:32:04,988
we can actually calculate the

3573
01:32:04,988 --> 01:32:07,611
preferential coupling phase with

3574
01:32:07,611 --> 01:32:10,122
spindles peak during the phase

3575
01:32:10,122 --> 01:32:11,628
of the slow wave,

3576
01:32:11,628 --> 01:32:14,266
and we can actually evaluate how

3577
01:32:14,266 --> 01:32:16,894
consistent this synchronization

3578
01:32:16,894 --> 01:32:17,234
is.

3579
01:32:17,534 --> 01:32:19,783
And my point of this slide is

3580
01:32:19,783 --> 01:32:21,528
that we have all these

3581
01:32:21,528 --> 01:32:23,273
measurements that can

3582
01:32:23,273 --> 01:32:25,597
actually index the function of

3583
01:32:25,597 --> 01:32:27,611
thalamocortical security.

3584
01:32:27,611 --> 01:32:28,735
They can show us,

3585
01:32:28,735 --> 01:32:30,841
they can offer a glimpse of how

3586
01:32:30,841 --> 01:32:31,181
this

3587
01:32:31,181 --> 01:32:32,215
secretary works.

3588
01:32:33,950 --> 01:32:36,820
So we did the study.

3589
01:32:36,820 --> 01:32:39,815
We analysed data in 2022 from a

3590
01:32:39,815 --> 01:32:42,976
sleep study run by Masquita 2015

3591
01:32:42,976 --> 01:32:44,261
in boys with

3592
01:32:44,261 --> 01:32:47,130
autism from 9 to 17 years old.

3593
01:32:47,130 --> 01:32:50,078
That was an at home sleep study

3594
01:32:50,078 --> 01:32:52,699
using the sparse EGRE in 19

3595
01:32:52,699 --> 01:32:54,738
typically developing

3596
01:32:54,738 --> 01:32:57,704
children and adolescents and 18

3597
01:32:57,704 --> 01:32:59,809
children with autism.

3598
01:33:01,044 --> 01:33:02,628
Not surprisingly,

3599
01:33:02,628 --> 01:33:05,590
we found that sleep overall was

3600
01:33:05,590 --> 01:33:06,449
worse in

3601
01:33:06,449 --> 01:33:07,083
autism.

3602
01:33:07,617 --> 01:33:10,219
Kids spend more time in bed,

3603
01:33:10,219 --> 01:33:13,084
they had more awakenings after

3604
01:33:13,084 --> 01:33:13,657
sleep

3605
01:33:13,657 --> 01:33:14,214
onset,

3606
01:33:14,214 --> 01:33:16,785
and they took them longer a

3607
01:33:16,785 --> 01:33:17,928
longer time

3608
01:33:17,928 --> 01:33:19,296
to fall asleep.

3609
01:33:20,096 --> 01:33:21,970
All these reflected in poorer

3610
01:33:21,970 --> 01:33:23,133
sleep efficiency.

3611
01:33:24,167 --> 01:33:26,335
Again, not surprisingly,

3612
01:33:26,335 --> 01:33:28,661
based on what I mentioned

3613
01:33:28,661 --> 01:33:29,406
before,

3614
01:33:29,406 --> 01:33:31,905
we found that higher spindle

3615
01:33:31,905 --> 01:33:34,730
density actually predicted less

3616
01:33:34,730 --> 01:33:36,279
wake after sleep

3617
01:33:36,279 --> 01:33:36,813
onset.

3618
01:33:37,047 --> 01:33:39,811
So consistent to this protective

3619
01:33:39,811 --> 01:33:42,290
role of spindles against the

3620
01:33:42,290 --> 01:33:43,353
awakenings,

3621
01:33:43,353 --> 01:33:46,119
we found that more spindles were

3622
01:33:46,119 --> 01:33:48,625
associated with less wazzle.

3623
01:33:50,593 --> 01:33:52,942
We also found that in noticing

3624
01:33:52,942 --> 01:33:55,181
boys with autism had reduced

3625
01:33:55,181 --> 01:33:56,700
spindles in states

3626
01:33:56,700 --> 01:33:59,053
three sleep in slow wave sleep

3627
01:33:59,053 --> 01:34:00,896
in both frontal central

3628
01:34:00,896 --> 01:34:02,739
electrodes and when we

3629
01:34:02,739 --> 01:34:05,261
looked at the synchronization of

3630
01:34:05,261 --> 01:34:07,310
spindles with slow waves,

3631
01:34:07,310 --> 01:34:09,511
we found that in autism here

3632
01:34:09,511 --> 01:34:12,084
spindles speak later in the slow

3633
01:34:12,084 --> 01:34:13,049
wave phase.

3634
01:34:13,049 --> 01:34:14,137
This is a schematic

3635
01:34:14,137 --> 01:34:15,945
representation of the slow wave

3636
01:34:15,945 --> 01:34:17,287
of frontal and central

3637
01:34:17,287 --> 01:34:18,954
electrodes and with thread is

3638
01:34:18,954 --> 01:34:19,990
the autism group.

3639
01:34:19,990 --> 01:34:22,017
You can see that spindles

3640
01:34:22,017 --> 01:34:24,503
overall on average speak later

3641
01:34:24,503 --> 01:34:25,829
compared to the

3642
01:34:25,829 --> 01:34:28,272
typically developing peers and

3643
01:34:28,272 --> 01:34:30,364
the coordination was less

3644
01:34:30,364 --> 01:34:31,368
consistent.

3645
01:34:31,368 --> 01:34:34,103
So there was high variability at

3646
01:34:34,103 --> 01:34:36,906
the central electrodes in ASD in

3647
01:34:36,906 --> 01:34:37,607
autism.

3648
01:34:38,775 --> 01:34:41,016
And this is a small interim

3649
01:34:41,016 --> 01:34:43,386
summary of the study that we

3650
01:34:43,386 --> 01:34:45,248
found disrupted sleep

3651
01:34:45,248 --> 01:34:47,889
in autism a late this indices of

3652
01:34:47,889 --> 01:34:50,509
thalamocortical circuitry where

3653
01:34:50,509 --> 01:34:51,354
a typical

3654
01:34:51,354 --> 01:34:53,767
in autism and spindle density

3655
01:34:53,767 --> 01:34:56,405
was related as we expected with

3656
01:34:56,405 --> 01:34:57,427
less Guazo.

3657
01:34:57,894 --> 01:35:00,418
But the main caveat of or

3658
01:35:00,418 --> 01:35:03,711
limitation of the study was that

3659
01:35:03,711 --> 01:35:05,769
the sample size was

3660
01:35:05,769 --> 01:35:06,970
quite small.

3661
01:35:07,270 --> 01:35:09,109
And this is a common theme in

3662
01:35:09,109 --> 01:35:11,123
autism because I believe people

3663
01:35:11,123 --> 01:35:11,708
here can

3664
01:35:11,708 --> 01:35:13,742
appreciate how challenging sleep

3665
01:35:13,742 --> 01:35:15,826
studies are and sleep studies in

3666
01:35:15,826 --> 01:35:16,413
clinical

3667
01:35:16,413 --> 01:35:18,194
population are with you know

3668
01:35:18,194 --> 01:35:19,884
sensory sensitivities with

3669
01:35:19,884 --> 01:35:21,184
bedtime things with

3670
01:35:21,184 --> 01:35:23,205
sleep problems etcetera can be

3671
01:35:23,205 --> 01:35:24,754
even more challenging.

3672
01:35:24,754 --> 01:35:27,488
So this is a common theme notice

3673
01:35:27,488 --> 01:35:29,777
like small sample sizes in

3674
01:35:29,777 --> 01:35:30,393
sleep,

3675
01:35:30,393 --> 01:35:32,713
in sleep studies and if you

3676
01:35:32,713 --> 01:35:34,821
combine it with inherent

3677
01:35:34,821 --> 01:35:36,666
heterogeneity of the

3678
01:35:36,666 --> 01:35:37,443
disorder,

3679
01:35:37,443 --> 01:35:40,097
this is the perfect recipe for

3680
01:35:40,097 --> 01:35:41,071
how to put

3681
01:35:41,071 --> 01:35:42,857
it like mixed results

3682
01:35:42,857 --> 01:35:44,474
in the literature.

3683
01:35:45,575 --> 01:35:47,888
And this is what what we see a

3684
01:35:47,888 --> 01:35:49,045
lot in autism.

3685
01:35:49,045 --> 01:35:51,957
So our next step was to actually

3686
01:35:51,957 --> 01:35:53,912
try to use to turn to

3687
01:35:53,912 --> 01:35:56,052
wearability devices to

3688
01:35:56,052 --> 01:35:58,388
upscale our sleep studies.

3689
01:35:58,655 --> 01:36:00,687
And with the funding from the

3690
01:36:00,687 --> 01:36:02,158
Sandwich Foundation,

3691
01:36:02,158 --> 01:36:03,341
we started trying

3692
01:36:03,341 --> 01:36:04,594
wearable devices.

3693
01:36:04,594 --> 01:36:06,755
This is just an example of two

3694
01:36:06,755 --> 01:36:09,132
wearable devices sleep upon top.

3695
01:36:09,132 --> 01:36:11,477
This is developing this in

3696
01:36:11,477 --> 01:36:14,003
Switzerland And then three,

3697
01:36:14,003 --> 01:36:16,562
the device that's the device

3698
01:36:16,562 --> 01:36:19,285
that we opted using in in the

3699
01:36:19,285 --> 01:36:19,943
study.

3700
01:36:19,943 --> 01:36:23,578
We validated devices in the lab

3701
01:36:23,578 --> 01:36:27,308
and we embarked in a nationwide

3702
01:36:27,308 --> 01:36:28,151
study.

3703
01:36:29,219 --> 01:36:30,794
Before I go to that,

3704
01:36:30,794 --> 01:36:32,974
I want to say that they the

3705
01:36:32,974 --> 01:36:34,023
landscape of

3706
01:36:34,023 --> 01:36:36,322
wearable devices is emerging,

3707
01:36:36,322 --> 01:36:38,687
is growing and there is a lot

3708
01:36:38,687 --> 01:36:39,095
more

3709
01:36:39,095 --> 01:36:41,297
devices and very interesting

3710
01:36:41,297 --> 01:36:43,876
studies validating these devices

3711
01:36:43,876 --> 01:36:44,601
nowadays

3712
01:36:44,601 --> 01:36:45,301
actually.

3713
01:36:45,635 --> 01:36:47,478
So we embarked in this

3714
01:36:47,478 --> 01:36:49,405
nationwide study page.

3715
01:36:49,606 --> 01:36:52,201
Nicole and Tory are leading this

3716
01:36:52,201 --> 01:36:54,310
study where we ship this,

3717
01:36:54,310 --> 01:36:55,992
we ship these devices

3718
01:36:55,992 --> 01:36:57,514
all across the US.

3719
01:36:58,014 --> 01:36:59,023
We train,

3720
01:36:59,023 --> 01:37:02,470
they train families to use the

3721
01:37:02,470 --> 01:37:03,620
device at

3722
01:37:03,620 --> 01:37:06,753
night and we record 3 nights

3723
01:37:06,753 --> 01:37:10,319
from children to 12 to 19 years

3724
01:37:10,319 --> 01:37:10,894
old.

3725
01:37:12,262 --> 01:37:13,093
The first night is

3726
01:37:13,093 --> 01:37:14,063
an adaptation night.

3727
01:37:14,063 --> 01:37:15,061
The other two nights,

3728
01:37:15,061 --> 01:37:16,476
you know are the experimental

3729
01:37:16,476 --> 01:37:16,866
nights.

3730
01:37:17,133 --> 01:37:20,545
And we had quite a success here

3731
01:37:20,545 --> 01:37:23,941
with 76 children without these

3732
01:37:23,941 --> 01:37:24,507
men,

3733
01:37:24,507 --> 01:37:25,793
47 typically

3734
01:37:25,793 --> 01:37:28,044
developing children.

3735
01:37:28,978 --> 01:37:30,719
I have to say here,

3736
01:37:30,719 --> 01:37:33,162
I have to note that we had

3737
01:37:33,162 --> 01:37:34,384
support from

3738
01:37:34,384 --> 01:37:37,017
the Autism Science Foundation

3739
01:37:37,017 --> 01:37:39,982
and the QSONG to actually expand

3740
01:37:39,982 --> 01:37:41,558
this protocol is

3741
01:37:41,558 --> 01:37:44,202
to profound autism and Philan

3742
01:37:44,202 --> 01:37:47,093
McDermott syndrome syndrome and

3743
01:37:47,093 --> 01:37:48,398
also from the

3744
01:37:48,398 --> 01:37:51,222
Simons Foundation to expand our

3745
01:37:51,222 --> 01:37:54,108
protocol to include monogenetic

3746
01:37:54,108 --> 01:37:55,505
autism as well

3747
01:37:55,505 --> 01:37:57,385
like fragile legs and

3748
01:37:57,385 --> 01:37:59,175
the 16B11 deletion.

3749
01:37:59,509 --> 01:38:01,613
And as you can imagine,

3750
01:38:01,613 --> 01:38:04,518
we have a lot of influx of data

3751
01:38:04,518 --> 01:38:05,548
every day.

3752
01:38:05,815 --> 01:38:07,405
So we're using an open software

3753
01:38:07,405 --> 01:38:09,081
Luna and open software developed

3754
01:38:09,081 --> 01:38:09,919
by some percent

3755
01:38:09,919 --> 01:38:11,487
to actually do quality control.

3756
01:38:11,854 --> 01:38:13,661
And I give this out out because

3757
01:38:13,661 --> 01:38:15,215
it's important to use some

3758
01:38:15,215 --> 01:38:15,992
standardized

3759
01:38:15,992 --> 01:38:17,864
methods when we go like to these

3760
01:38:17,864 --> 01:38:19,603
larger data sets, these large

3761
01:38:19,603 --> 01:38:20,263
data sets.

3762
01:38:20,263 --> 01:38:21,325
And I want to show some

3763
01:38:21,325 --> 01:38:22,665
preliminary results on that.

3764
01:38:23,533 --> 01:38:25,443
Again, non not surprisingly,

3765
01:38:25,443 --> 01:38:27,261
we've found that kids with

3766
01:38:27,261 --> 01:38:28,171
autism spend

3767
01:38:28,171 --> 01:38:29,305
more time in bed.

3768
01:38:29,505 --> 01:38:30,816
They have reduced sleep

3769
01:38:30,816 --> 01:38:32,504
efficiency and increased wake

3770
01:38:32,504 --> 01:38:33,610
after sleep onset.

3771
01:38:33,810 --> 01:38:35,997
We didn't find any differences

3772
01:38:35,997 --> 01:38:37,747
in sleep onset latency,

3773
01:38:37,747 --> 01:38:39,938
but it's quite tricky actually

3774
01:38:39,938 --> 01:38:42,031
to measure this at home with

3775
01:38:42,031 --> 01:38:43,152
these devices.

3776
01:38:43,152 --> 01:38:44,887
I can get back to that later.

3777
01:38:47,056 --> 01:38:47,500
Again,

3778
01:38:47,500 --> 01:38:49,551
we found that lower spindle

3779
01:38:49,551 --> 01:38:50,159
density

3780
01:38:50,159 --> 01:38:52,435
predicted were sleep consistent

3781
01:38:52,435 --> 01:38:53,463
to this idea,

3782
01:38:53,463 --> 01:38:55,726
to this notion of spindles that

3783
01:38:55,726 --> 01:38:57,601
are protecting sleep from

3784
01:38:57,601 --> 01:38:58,501
awakenings.

3785
01:38:58,968 --> 01:39:00,829
And we found that either

3786
01:39:00,829 --> 01:39:03,048
measured by wake after sleep

3787
01:39:03,048 --> 01:39:04,474
onset or by sleep

3788
01:39:04,474 --> 01:39:06,034
fragmentation index,

3789
01:39:06,034 --> 01:39:08,592
this is an index showing that so

3790
01:39:08,592 --> 01:39:09,312
how many

3791
01:39:09,312 --> 01:39:10,993
transitions to lighter

3792
01:39:10,993 --> 01:39:12,215
sleep you have.

3793
01:39:12,215 --> 01:39:13,037
So again,

3794
01:39:13,037 --> 01:39:15,949
lower spindle density predicted

3795
01:39:15,949 --> 01:39:16,419
more

3796
01:39:16,419 --> 01:39:18,955
transitions to lighter slim.

3797
01:39:18,955 --> 01:39:21,447
And when we looked at the

3798
01:39:21,447 --> 01:39:23,783
spindle spindle density

3799
01:39:23,783 --> 01:39:26,829
initially we did not find any

3800
01:39:26,829 --> 01:39:30,113
differences typically developing

3801
01:39:30,113 --> 01:39:32,268
versus ASD children.

3802
01:39:32,268 --> 01:39:36,029
But when we broke it down by 6,

3803
01:39:36,029 --> 01:39:39,652
we found that maize in autism

3804
01:39:39,652 --> 01:39:40,276
have

3805
01:39:40,276 --> 01:39:43,146
reduced spindle density.

3806
01:39:43,146 --> 01:39:45,295
And I have to remind you here

3807
01:39:45,295 --> 01:39:47,489
that our initial study was in

3808
01:39:47,489 --> 01:39:48,851
boys with autism.

3809
01:39:48,851 --> 01:39:50,396
So that's a, that's

3810
01:39:50,396 --> 01:39:52,021
a replication here.

3811
01:39:52,255 --> 01:39:55,007
And there is a very interesting

3812
01:39:55,007 --> 01:39:56,959
interaction with sex,

3813
01:39:56,959 --> 01:39:59,718
sex effect that we need to wrap

3814
01:39:59,718 --> 01:40:01,230
our head around.

3815
01:40:04,067 --> 01:40:05,007
And finally,

3816
01:40:05,007 --> 01:40:07,428
I want to say that our goal is

3817
01:40:07,428 --> 01:40:07,670
to

3818
01:40:07,670 --> 01:40:08,814
actually target

3819
01:40:08,814 --> 01:40:10,340
these oscillations.

3820
01:40:10,540 --> 01:40:11,840
And last September,

3821
01:40:11,840 --> 01:40:13,805
I was funded by the American

3822
01:40:13,805 --> 01:40:14,577
Academy of

3823
01:40:14,577 --> 01:40:16,483
Sleep Medicine to use closed

3824
01:40:16,483 --> 01:40:18,711
loop auditory stimulation during

3825
01:40:18,711 --> 01:40:19,615
sleep class.

3826
01:40:20,216 --> 01:40:22,839
This is work led by my colleague

3827
01:40:22,839 --> 01:40:23,986
Brian Baxter.

3828
01:40:24,253 --> 01:40:26,633
What we do during class is

3829
01:40:26,633 --> 01:40:29,161
actually we monitor ongoing

3830
01:40:29,161 --> 01:40:30,660
brain activity.

3831
01:40:30,660 --> 01:40:32,195
You can sit here with the black

3832
01:40:32,195 --> 01:40:33,830
line and we're trying to target.

3833
01:40:34,864 --> 01:40:37,206
We were trying to target the

3834
01:40:37,206 --> 01:40:39,938
upstate of the slow waves with a

3835
01:40:39,938 --> 01:40:41,304
very short mild

3836
01:40:41,304 --> 01:40:43,773
auditory stimulus, pink noise.

3837
01:40:44,107 --> 01:40:46,540
And this here in this example

3838
01:40:46,540 --> 01:40:48,951
evokes a new cortical, a new

3839
01:40:48,951 --> 01:40:49,812
response,

3840
01:40:49,812 --> 01:40:51,305
slow wave response

3841
01:40:51,305 --> 01:40:52,548
and a spindle.

3842
01:40:53,049 --> 01:40:55,408
And this is working by Brian

3843
01:40:55,408 --> 01:40:57,902
showing that by targeting the

3844
01:40:57,902 --> 01:40:59,622
upstate of the slow

3845
01:40:59,622 --> 01:41:00,134
waves,

3846
01:41:00,134 --> 01:41:02,766
we're actually can elicit slow

3847
01:41:02,766 --> 01:41:03,292
waves

3848
01:41:03,292 --> 01:41:05,659
evokes the ways which is the

3849
01:41:05,659 --> 01:41:08,423
hallmark of slow way sleep of of

3850
01:41:08,423 --> 01:41:09,632
deeper sleep.

3851
01:41:10,099 --> 01:41:13,385
And we can also elicit increase

3852
01:41:13,385 --> 01:41:15,505
evoked Sigma power.

3853
01:41:15,772 --> 01:41:18,357
So we are developing our, our,

3854
01:41:18,357 --> 01:41:20,477
our algorithms right now

3855
01:41:20,477 --> 01:41:21,978
actually to, to,

3856
01:41:21,978 --> 01:41:24,382
to start to embark into this

3857
01:41:24,382 --> 01:41:26,919
study to try close repository

3858
01:41:26,919 --> 01:41:29,018
stimulation in children

3859
01:41:29,018 --> 01:41:30,386
with the autism.

3860
01:41:30,953 --> 01:41:32,877
And with that, I hope,

3861
01:41:32,877 --> 01:41:35,324
I want to summarize to say,

3862
01:41:35,324 --> 01:41:37,959
I hope I've convinced you that

3863
01:41:37,959 --> 01:41:40,329
by interrogating Sleepy G,

3864
01:41:40,329 --> 01:41:42,761
we can understand better the

3865
01:41:42,761 --> 01:41:45,508
circuitry that might contribute

3866
01:41:45,508 --> 01:41:47,103
to impaired sleep

3867
01:41:47,103 --> 01:41:47,970
in autism.

3868
01:41:48,304 --> 01:41:49,979
And importantly,

3869
01:41:49,979 --> 01:41:53,090
this can offer new biomarkers

3870
01:41:53,090 --> 01:41:54,377
that we can

3871
01:41:54,377 --> 01:41:57,500
target to we can target and to

3872
01:41:57,500 --> 01:42:00,055
improve sleep and weight

3873
01:42:00,055 --> 01:42:02,185
function in autism.

3874
01:42:02,819 --> 01:42:04,858
And I think I have maybe one

3875
01:42:04,858 --> 01:42:06,936
more minute I want to have a

3876
01:42:06,936 --> 01:42:08,791
teaser to speak a little

3877
01:42:08,791 --> 01:42:11,093
bit about the future directions.

3878
01:42:11,928 --> 01:42:14,255
We I talked mostly about the

3879
01:42:14,255 --> 01:42:16,332
slow waves and spindles,

3880
01:42:16,332 --> 01:42:18,948
but there is emerging literature

3881
01:42:18,948 --> 01:42:21,453
showing that there is an other

3882
01:42:21,453 --> 01:42:22,872
important rhythm

3883
01:42:22,872 --> 01:42:24,773
during non dream sleep,

3884
01:42:24,773 --> 01:42:27,482
the infra slow rhythm that lasts

3885
01:42:27,482 --> 01:42:28,244
around a

3886
01:42:28,244 --> 01:42:30,893
minute a period and is generated

3887
01:42:30,893 --> 01:42:32,548
by locus cellulose,

3888
01:42:32,548 --> 01:42:33,596
the source of

3889
01:42:33,596 --> 01:42:35,852
noradrenaline in the brain.

3890
01:42:36,252 --> 01:42:38,921
So during the high noradrenaline

3891
01:42:38,921 --> 01:42:40,923
in the in the thalamus,

3892
01:42:40,923 --> 01:42:43,247
this rhythm actually divides

3893
01:42:43,247 --> 01:42:45,704
sleep in periods of vigilance

3894
01:42:45,704 --> 01:42:47,230
that the brain is

3895
01:42:47,230 --> 01:42:48,898
more vigilant to the

3896
01:42:48,898 --> 01:42:51,537
environment, more prone to wake

3897
01:42:51,537 --> 01:42:53,069
up and periods of

3898
01:42:53,069 --> 01:42:55,387
consolidation where you find

3899
01:42:55,387 --> 01:42:58,004
abundance of these oscillations

3900
01:42:58,004 --> 01:42:59,609
that are linked to

3901
01:42:59,609 --> 01:43:01,344
memory consolidation.

3902
01:43:01,644 --> 01:43:02,178
Absolutely.

3903
01:43:02,378 --> 01:43:04,621
And I think this is a this is a

3904
01:43:04,621 --> 01:43:06,619
study showing that how this

3905
01:43:06,619 --> 01:43:07,950
intra slow rhythm

3906
01:43:07,950 --> 01:43:10,125
coordinates neural and cardiac

3907
01:43:10,125 --> 01:43:12,270
autonomic autonomic system as

3908
01:43:12,270 --> 01:43:13,823
well in audience and

3909
01:43:13,823 --> 01:43:14,323
humans.

3910
01:43:14,891 --> 01:43:16,870
This is quite understudy

3911
01:43:16,870 --> 01:43:19,229
understudied in humans and I

3912
01:43:19,229 --> 01:43:20,830
think by studying,

3913
01:43:20,830 --> 01:43:23,147
understanding this secretary

3914
01:43:23,147 --> 01:43:25,767
having a more fuller picture of

3915
01:43:25,767 --> 01:43:27,203
that and help us

3916
01:43:27,203 --> 01:43:29,105
understand why sleeping

3917
01:43:29,105 --> 01:43:31,173
impaired, you know this.

3918
01:43:32,108 --> 01:43:32,341
Yeah.

3919
01:43:32,341 --> 01:43:32,997
And with that,

3920
01:43:32,997 --> 01:43:34,544
I wanted to thank my Pi Diamond.

3921
01:43:34,544 --> 01:43:36,361
Not everybody in the lab,

3922
01:43:36,361 --> 01:43:38,447
the Lewis Centre and and our

3923
01:43:38,447 --> 01:43:39,415
sponsors and

3924
01:43:39,415 --> 01:43:41,651
of course our our participants.

3925
01:43:42,385 --> 01:43:42,885
Thank you.

3926
01:43:43,085 --> 01:43:44,086
Thank you for listening.

3927
01:43:45,087 --> 01:43:46,889
Oh, thank you Doctor Milan.

3928
01:43:46,889 --> 01:43:48,076
So we are right at

3929
01:43:48,076 --> 01:43:49,659
time, which is too bad.

3930
01:43:49,659 --> 01:43:51,185
I'll have to hold my questions

3931
01:43:51,185 --> 01:43:52,637
to the end because I have to

3932
01:43:52,637 --> 01:43:53,829
admit to being partial

3933
01:43:53,829 --> 01:43:54,492
when the main

3934
01:43:54,492 --> 01:43:55,665
character is Spindles.

3935
01:43:56,098 --> 01:43:56,264
OK,

3936
01:43:56,264 --> 01:43:57,902
we're going to move on to our

3937
01:43:57,902 --> 01:43:58,467
last talk

3938
01:43:58,467 --> 01:43:59,393
for this session,

3939
01:43:59,393 --> 01:44:01,124
and we'll just have to remember

3940
01:44:01,124 --> 01:44:01,571
all the

3941
01:44:01,571 --> 01:44:03,245
things we want to ask the other

3942
01:44:03,245 --> 01:44:04,974
speakers to the end of the day.

3943
01:44:05,508 --> 01:44:06,549
We're going to hear

3944
01:44:06,549 --> 01:44:07,810
from Jennifer Accardo.

3945
01:44:08,210 --> 01:44:10,217
She's an associate professor of

3946
01:44:10,217 --> 01:44:11,949
Pediatrics and director of

3947
01:44:11,949 --> 01:44:12,548
Virginia

3948
01:44:12,548 --> 01:44:14,046
Leadership Education in

3949
01:44:14,046 --> 01:44:16,185
Neurodevelopmental Disabilities,

3950
01:44:16,185 --> 01:44:16,652
or VA,

3951
01:44:16,652 --> 01:44:18,402
Lent or violent at Virginia

3952
01:44:18,402 --> 01:44:20,022
Commonwealth University.

3953
01:44:20,456 --> 01:44:22,393
Her research interests focus on

3954
01:44:22,393 --> 01:44:24,393
sleep problems in children with

3955
01:44:24,393 --> 01:44:26,379
neurodevelopmental disabilities,

3956
01:44:26,379 --> 01:44:27,496
autism, and ADHD.

3957
01:44:27,730 --> 01:44:29,287
Her talk today is on the effects

3958
01:44:29,287 --> 01:44:30,635
of medications on sleep and

3959
01:44:30,635 --> 01:44:31,233
symptoms of

3960
01:44:31,233 --> 01:44:32,663
neurodevelopmental disorders,

3961
01:44:32,663 --> 01:44:34,233
which is relevant to everything

3962
01:44:34,233 --> 01:44:34,537
we've

3963
01:44:34,537 --> 01:44:36,072
been talking about this morning.

3964
01:44:36,505 --> 01:44:37,373
Doctor Ricardo.

3965
01:44:38,908 --> 01:44:40,464
Thank you, Doctor Buckley,

3966
01:44:40,464 --> 01:44:42,427
and I very much appreciate being

3967
01:44:42,427 --> 01:44:42,979
asked to

3968
01:44:42,979 --> 01:44:44,033
speak at this very

3969
01:44:44,033 --> 01:44:45,381
interesting symposium.

3970
01:44:48,184 --> 01:44:48,892
All right,

3971
01:44:48,892 --> 01:44:50,927
no conflicts of interest and

3972
01:44:50,927 --> 01:44:51,654
basically

3973
01:44:51,654 --> 01:44:53,709
this entire talk is basically

3974
01:44:53,709 --> 01:44:55,948
off label with the exception of

3975
01:44:55,948 --> 01:44:57,393
the medication that

3976
01:44:57,393 --> 01:44:58,300
Doctor Mallow

3977
01:44:58,300 --> 01:44:59,695
referenced earlier.

3978
01:45:01,097 --> 01:45:03,540
I'm primarily A clinician and

3979
01:45:03,540 --> 01:45:05,860
that is the perspective I'm

3980
01:45:05,860 --> 01:45:07,837
going to bring to this

3981
01:45:07,837 --> 01:45:08,270
talk.

3982
01:45:08,971 --> 01:45:11,252
I wanted to start with this is

3983
01:45:11,252 --> 01:45:13,503
actually an citation from the

3984
01:45:13,503 --> 01:45:14,977
first issue of the

3985
01:45:14,977 --> 01:45:16,878
Journal of Clinical Sleep

3986
01:45:16,878 --> 01:45:18,247
Medicine in 2005,

3987
01:45:18,247 --> 01:45:20,072
the profile of the ideal

3988
01:45:20,072 --> 01:45:21,947
medication for sleep and

3989
01:45:21,947 --> 01:45:22,885
Pediatrics.

3990
01:45:24,787 --> 01:45:27,296
You'll notice ideally it would

3991
01:45:27,296 --> 01:45:29,694
take effect quickly, be very

3992
01:45:29,694 --> 01:45:30,893
bioavailable,

3993
01:45:30,893 --> 01:45:33,229
have both a long duration of

3994
01:45:33,229 --> 01:45:35,185
action so that it would

3995
01:45:35,185 --> 01:45:37,566
substantiate throughout the

3996
01:45:37,566 --> 01:45:39,052
night and also not

3997
01:45:39,052 --> 01:45:40,703
produce a hangover.

3998
01:45:41,337 --> 01:45:42,547
Minimal side effects,

3999
01:45:42,547 --> 01:45:43,675
no effects on sleep

4000
01:45:43,675 --> 01:45:44,507
architecture,

4001
01:45:44,507 --> 01:45:45,708
any palatable format.

4002
01:45:45,708 --> 01:45:47,762
Because one thing I've learned

4003
01:45:47,762 --> 01:45:49,861
from families of children with

4004
01:45:49,861 --> 01:45:50,980
autism over the

4005
01:45:50,980 --> 01:45:52,905
years is if a child does not

4006
01:45:52,905 --> 01:45:55,023
want to put something in their

4007
01:45:55,023 --> 01:45:55,518
mouth,

4008
01:45:55,518 --> 01:45:56,852
they truly will not.

4009
01:45:58,421 --> 01:46:00,635
This medication unfortunately

4010
01:46:00,635 --> 01:46:01,857
does not exist.

4011
01:46:03,426 --> 01:46:06,071
So many of my patients in sleep

4012
01:46:06,071 --> 01:46:08,785
and development lack the season

4013
01:46:08,785 --> 01:46:09,398
of All

4014
01:46:09,398 --> 01:46:10,685
Nature's Sleep,

4015
01:46:10,685 --> 01:46:13,060
and initially I was being a

4016
01:46:13,060 --> 01:46:14,203
little silly

4017
01:46:14,203 --> 01:46:16,525
putting this up in a reread

4018
01:46:16,525 --> 01:46:18,074
Macbeth recently.

4019
01:46:18,407 --> 01:46:20,329
But this this picture reminds me

4020
01:46:20,329 --> 01:46:22,174
of a resident's comment that I

4021
01:46:22,174 --> 01:46:22,912
had earlier

4022
01:46:22,912 --> 01:46:24,780
this week where someone told me

4023
01:46:24,780 --> 01:46:26,649
about medications I was using.

4024
01:46:26,649 --> 01:46:28,567
These medications are

4025
01:46:28,567 --> 01:46:30,486
dirty, and they are.

4026
01:46:30,486 --> 01:46:32,516
This is a somewhat dirty

4027
01:46:32,516 --> 01:46:34,850
business, the medication of

4028
01:46:34,850 --> 01:46:36,492
sleep in children.

4029
01:46:38,260 --> 01:46:40,247
My other disclaimer is some

4030
01:46:40,247 --> 01:46:42,048
years ago I was having a

4031
01:46:42,048 --> 01:46:43,999
conversation with another

4032
01:46:43,999 --> 01:46:46,220
pediatric sleep colleague more

4033
01:46:46,220 --> 01:46:47,670
about children with

4034
01:46:47,670 --> 01:46:48,738
disabilities.

4035
01:46:49,004 --> 01:46:50,187
We had a very nice conversation

4036
01:46:50,187 --> 01:46:51,356
and I thought we were wrapping

4037
01:46:51,356 --> 01:46:51,941
up and then he

4038
01:46:51,941 --> 01:46:53,057
took me aside and said, well,

4039
01:46:53,057 --> 01:46:53,943
what do you really do?

4040
01:46:54,443 --> 01:46:57,446
What is what is the I?

4041
01:46:57,446 --> 01:46:59,049
I think a lot of people are

4042
01:46:59,049 --> 01:47:00,927
looking for that break glass in

4043
01:47:00,927 --> 01:47:02,017
case of emergency

4044
01:47:02,017 --> 01:47:03,849
medication that unfortunately I

4045
01:47:03,849 --> 01:47:05,723
am not able to disclose because

4046
01:47:05,723 --> 01:47:06,388
I have not

4047
01:47:06,388 --> 01:47:07,490
figured it out yet.

4048
01:47:10,826 --> 01:47:12,503
So let's look at what some

4049
01:47:12,503 --> 01:47:14,413
people are actually doing And

4050
01:47:14,413 --> 01:47:15,664
Judy Owens and her

4051
01:47:15,664 --> 01:47:17,633
group had a couple of articles.

4052
01:47:17,633 --> 01:47:18,901
This was the more recent one.

4053
01:47:18,901 --> 01:47:20,905
There was also a 2003 looking at

4054
01:47:20,905 --> 01:47:22,503
primary care pediatrician

4055
01:47:22,503 --> 01:47:23,973
surveyed on medication

4056
01:47:23,973 --> 01:47:25,674
treatment and for insomnia.

4057
01:47:25,941 --> 01:47:28,157
This may not say specifically

4058
01:47:28,157 --> 01:47:30,654
children with neurodevelopmental

4059
01:47:30,654 --> 01:47:31,747
disabilities,

4060
01:47:31,747 --> 01:47:33,729
but realistically when she

4061
01:47:33,729 --> 01:47:36,212
looked at the characteristics of

4062
01:47:36,212 --> 01:47:37,920
the children who were

4063
01:47:37,920 --> 01:47:40,071
being prescribed medication,

4064
01:47:40,071 --> 01:47:41,991
many of them had autism,

4065
01:47:41,991 --> 01:47:44,214
intellectual disability, some

4066
01:47:44,214 --> 01:47:46,330
other, you know, ADHD, some

4067
01:47:46,330 --> 01:47:47,663
other condition.

4068
01:47:49,298 --> 01:47:52,238
So 28% over all of those child

4069
01:47:52,238 --> 01:47:54,939
psychiatry patients getting

4070
01:47:54,939 --> 01:47:57,139
medication treatment,

4071
01:47:57,139 --> 01:47:58,778
most commonly the

4072
01:47:58,778 --> 01:48:00,609
over the counters.

4073
01:48:00,609 --> 01:48:01,844
And at that time it was

4074
01:48:01,844 --> 01:48:03,380
antihistamine, melatonin and

4075
01:48:03,380 --> 01:48:04,313
various herbals.

4076
01:48:04,647 --> 01:48:06,533
And I believe some of those

4077
01:48:06,533 --> 01:48:08,350
percentages have flipped,

4078
01:48:08,350 --> 01:48:10,367
especially based on that more

4079
01:48:10,367 --> 01:48:12,139
recent IPSA International

4080
01:48:12,139 --> 01:48:14,123
Pediatric Sleep Association

4081
01:48:14,123 --> 01:48:15,525
review of melatonin,

4082
01:48:15,525 --> 01:48:17,541
that melatonin is now #1 for

4083
01:48:17,541 --> 01:48:18,260
better or

4084
01:48:18,260 --> 01:48:18,928
for worse.

4085
01:48:21,297 --> 01:48:24,070
I did find it very interesting

4086
01:48:24,070 --> 01:48:26,529
thinking about reasons why

4087
01:48:26,529 --> 01:48:28,137
prescribers used

4088
01:48:28,137 --> 01:48:31,042
medication and reasons why they

4089
01:48:31,042 --> 01:48:32,541
decided not to.

4090
01:48:33,075 --> 01:48:34,425
Can you get both

4091
01:48:34,425 --> 01:48:36,111
at kind of a first?

4092
01:48:36,111 --> 01:48:37,913
Then we tried other things.

4093
01:48:37,913 --> 01:48:38,747
They didn't help.

4094
01:48:39,048 --> 01:48:42,187
We get at family can't or won't

4095
01:48:42,187 --> 01:48:44,820
do other do other things.

4096
01:48:45,187 --> 01:48:47,729
We get at the behavioral changes

4097
01:48:47,729 --> 01:48:49,848
that I think Doctor Joseph

4098
01:48:49,848 --> 01:48:50,826
alluded to.

4099
01:48:50,826 --> 01:48:52,962
And some of the some of the

4100
01:48:52,962 --> 01:48:55,097
interventions can be hard.

4101
01:48:58,367 --> 01:49:00,493
Reasons not to use medication

4102
01:49:00,493 --> 01:49:02,671
for insomnia in children were

4103
01:49:02,671 --> 01:49:03,572
also pretty

4104
01:49:03,572 --> 01:49:04,073
robust.

4105
01:49:06,008 --> 01:49:08,029
I don't understand the second

4106
01:49:08,029 --> 01:49:10,091
one here, but control concern

4107
01:49:10,091 --> 01:49:11,513
about shorter long,

4108
01:49:11,513 --> 01:49:13,688
long term side effects may come

4109
01:49:13,688 --> 01:49:14,950
from a clinician,

4110
01:49:14,950 --> 01:49:17,033
may come from parents concerns

4111
01:49:17,033 --> 01:49:19,255
about giving the wrong message.

4112
01:49:20,556 --> 01:49:22,548
I don't know how many times I've

4113
01:49:22,548 --> 01:49:24,022
counseled parents about

4114
01:49:24,022 --> 01:49:24,727
behavioral

4115
01:49:24,727 --> 01:49:26,539
interventions and said, well,

4116
01:49:26,539 --> 01:49:28,163
and let's let's also try,

4117
01:49:28,163 --> 01:49:30,107
let's also try this other thing

4118
01:49:30,107 --> 01:49:31,914
to help you through the hard

4119
01:49:31,914 --> 01:49:32,301
part.

4120
01:49:32,835 --> 01:49:34,305
And at the follow up,

4121
01:49:34,305 --> 01:49:36,316
I hear the medication didn't

4122
01:49:36,316 --> 01:49:37,106
work well.

4123
01:49:37,339 --> 01:49:38,750
What about the changes that we

4124
01:49:38,750 --> 01:49:39,408
talked about?

4125
01:49:41,610 --> 01:49:43,455
Unsure of the best or most

4126
01:49:43,455 --> 01:49:45,769
appropriate medication to choose

4127
01:49:45,769 --> 01:49:47,216
is a real challenge

4128
01:49:47,216 --> 01:49:49,483
because there's frankly, spoiler

4129
01:49:49,483 --> 01:49:51,820
alert, not a lot of information.

4130
01:49:53,689 --> 01:49:54,461
Doctor Mallow,

4131
01:49:54,461 --> 01:49:55,994
I used to always put up the

4132
01:49:55,994 --> 01:49:56,392
Autism

4133
01:49:56,392 --> 01:49:57,814
Treatment Network insomnia

4134
01:49:57,814 --> 01:49:59,602
protocol, and I wanted to mix it

4135
01:49:59,602 --> 01:50:00,496
up a little bit

4136
01:50:00,496 --> 01:50:01,931
with something more recent.

4137
01:50:02,364 --> 01:50:04,509
But ultimately there's several

4138
01:50:04,509 --> 01:50:06,263
kind of expert consensus

4139
01:50:06,263 --> 01:50:07,870
protocols for what do

4140
01:50:07,870 --> 01:50:10,171
you do with the child with sleep

4141
01:50:10,171 --> 01:50:11,106
disturbance.

4142
01:50:11,106 --> 01:50:13,746
This particular 1 is out of

4143
01:50:13,746 --> 01:50:16,747
Lurie, so hello to my previous

4144
01:50:16,747 --> 01:50:18,147
presenter and

4145
01:50:18,147 --> 01:50:19,415
Mass General.

4146
01:50:19,815 --> 01:50:21,403
And all of these

4147
01:50:21,403 --> 01:50:23,585
protocols start with.

4148
01:50:24,286 --> 01:50:26,689
Are there other factors?

4149
01:50:26,689 --> 01:50:28,057
What else is going on?

4150
01:50:28,057 --> 01:50:29,781
Is there something physical that

4151
01:50:29,781 --> 01:50:31,269
is preventing sleep that is

4152
01:50:31,269 --> 01:50:32,261
irritating sleep?

4153
01:50:32,261 --> 01:50:33,019
Are there other

4154
01:50:33,019 --> 01:50:33,929
sleep conditions?

4155
01:50:36,532 --> 01:50:38,999
Is there adequate sleep hygiene,

4156
01:50:38,999 --> 01:50:41,527
which is not necessarily an easy

4157
01:50:41,527 --> 01:50:42,237
thing to

4158
01:50:42,237 --> 01:50:42,871
address?

4159
01:50:43,572 --> 01:50:45,488
I think the interesting twist in

4160
01:50:45,488 --> 01:50:47,207
the autism treatment network

4161
01:50:47,207 --> 01:50:47,943
protocol is

4162
01:50:47,943 --> 01:50:49,734
assessed parent willingness to

4163
01:50:49,734 --> 01:50:51,630
use these behavioral strategies

4164
01:50:51,630 --> 01:50:52,181
as well.

4165
01:50:53,515 --> 01:50:55,360
I think this gives us fairly

4166
01:50:55,360 --> 01:50:57,511
standard picture of what many of

4167
01:50:57,511 --> 01:50:58,721
us do in the real

4168
01:50:58,721 --> 01:50:59,121
world,

4169
01:50:59,121 --> 01:51:00,977
which is melatonin is often

4170
01:51:00,977 --> 01:51:01,390
first

4171
01:51:01,390 --> 01:51:02,051
Clonidine,

4172
01:51:02,051 --> 01:51:04,083
maybe Trazodone or hydroxyzine

4173
01:51:04,083 --> 01:51:04,760
or second

4174
01:51:04,760 --> 01:51:05,094
line.

4175
01:51:05,094 --> 01:51:06,979
I really do like gabapentin as

4176
01:51:06,979 --> 01:51:09,033
published by Doctor Robinson out

4177
01:51:09,033 --> 01:51:09,932
of Vanderbilt

4178
01:51:09,932 --> 01:51:10,939
those years ago,

4179
01:51:10,939 --> 01:51:12,945
and I don't know why that's not

4180
01:51:12,945 --> 01:51:13,268
more

4181
01:51:13,268 --> 01:51:14,909
widely showing up in these

4182
01:51:14,909 --> 01:51:16,739
protocols, but there we are.

4183
01:51:17,373 --> 01:51:19,157
I don't love seeing zolpidem at

4184
01:51:19,157 --> 01:51:20,309
the bottom of this,

4185
01:51:20,309 --> 01:51:21,944
but that's a different slide.

4186
01:51:23,112 --> 01:51:24,940
When do you want to think about

4187
01:51:24,940 --> 01:51:25,647
medication?

4188
01:51:27,416 --> 01:51:29,355
This kind of tracks back to some

4189
01:51:29,355 --> 01:51:30,386
sleep disorders.

4190
01:51:30,386 --> 01:51:32,582
I want to think about is this a

4191
01:51:32,582 --> 01:51:34,479
child who's getting enough

4192
01:51:34,479 --> 01:51:34,990
sleep?

4193
01:51:34,990 --> 01:51:36,387
Are they getting adequate

4194
01:51:36,387 --> 01:51:37,393
quality of sleep?

4195
01:51:37,393 --> 01:51:39,447
Quality is very quality can be

4196
01:51:39,447 --> 01:51:41,615
very difficult to measure and a

4197
01:51:41,615 --> 01:51:42,664
standard sleep

4198
01:51:42,664 --> 01:51:44,784
study isn't going to get at all

4199
01:51:44,784 --> 01:51:47,015
of all of my previous colleagues

4200
01:51:47,015 --> 01:51:48,270
kind of different

4201
01:51:48,270 --> 01:51:50,335
parameters in terms of spindle

4202
01:51:50,335 --> 01:51:51,573
density etcetera.

4203
01:51:53,142 --> 01:51:55,306
But like like in real estate,

4204
01:51:55,306 --> 01:51:57,546
location, location, location,

4205
01:51:57,546 --> 01:51:59,489
we can work with duration,

4206
01:51:59,489 --> 01:52:00,983
duration, duration,

4207
01:52:00,983 --> 01:52:03,215
appropriate timing of sleep in

4208
01:52:03,215 --> 01:52:05,422
terms of circadian, just like

4209
01:52:05,422 --> 01:52:06,488
with the DSM,

4210
01:52:06,488 --> 01:52:07,800
we don't just want

4211
01:52:07,800 --> 01:52:09,258
a sleep difference.

4212
01:52:09,491 --> 01:52:11,312
We want evidence that something

4213
01:52:11,312 --> 01:52:13,114
with sleep is interfering with

4214
01:52:13,114 --> 01:52:13,896
the reducing

4215
01:52:13,896 --> 01:52:15,297
the quality of function.

4216
01:52:15,297 --> 01:52:17,609
In order to be concerned about

4217
01:52:17,609 --> 01:52:19,979
this, I've in my developmental

4218
01:52:19,979 --> 01:52:20,769
practice,

4219
01:52:20,769 --> 01:52:22,701
I've run across plenty of

4220
01:52:22,701 --> 01:52:24,829
children who have odd sleep

4221
01:52:24,829 --> 01:52:26,642
schedules that are for

4222
01:52:26,642 --> 01:52:28,906
whatever reason not currently

4223
01:52:28,906 --> 01:52:30,312
bothering anyone.

4224
01:52:30,312 --> 01:52:32,701
They're homeschooling and it's

4225
01:52:32,701 --> 01:52:33,816
not an issue.

4226
01:52:35,818 --> 01:52:37,544
Other factors including families

4227
01:52:37,544 --> 01:52:39,313
and patients and shared decision

4228
01:52:39,313 --> 01:52:39,755
making.

4229
01:52:39,755 --> 01:52:41,133
Some families are seeking

4230
01:52:41,133 --> 01:52:42,291
medication actively.

4231
01:52:42,291 --> 01:52:44,525
Other families wanted on no

4232
01:52:44,525 --> 01:52:46,428
conditions whatsoever.

4233
01:52:46,428 --> 01:52:48,567
And I saw a young man earlier

4234
01:52:48,567 --> 01:52:50,296
this week who was using

4235
01:52:50,296 --> 01:52:52,401
melatonin whose goal was to

4236
01:52:52,401 --> 01:52:54,069
fall asleep without it.

4237
01:52:55,704 --> 01:52:57,658
But I think medication is a non

4238
01:52:57,658 --> 01:52:59,338
starter without addressing

4239
01:52:59,338 --> 01:53:00,242
significantly

4240
01:53:00,242 --> 01:53:01,410
interfering issues.

4241
01:53:02,111 --> 01:53:04,576
And my reminder slide here is

4242
01:53:04,576 --> 01:53:07,273
this is a picture of a Japanese

4243
01:53:07,273 --> 01:53:08,317
hikikomori,

4244
01:53:08,317 --> 01:53:10,781
a teenager or young adult who

4245
01:53:10,781 --> 01:53:13,213
has basically self-imposed A

4246
01:53:13,213 --> 01:53:14,690
hermit situation

4247
01:53:14,690 --> 01:53:17,421
where they are not leaving their

4248
01:53:17,421 --> 01:53:20,041
rooms, are often engaging in a

4249
01:53:20,041 --> 01:53:21,263
great deal of

4250
01:53:21,263 --> 01:53:22,264
screen time.

4251
01:53:24,633 --> 01:53:26,176
I would like to say we don't

4252
01:53:26,176 --> 01:53:27,817
have anything that extreme in

4253
01:53:27,817 --> 01:53:28,270
the US,

4254
01:53:28,270 --> 01:53:29,771
but I think we very much do.

4255
01:53:29,771 --> 01:53:31,478
And some of the people

4256
01:53:31,478 --> 01:53:33,452
experiencing this are not

4257
01:53:33,452 --> 01:53:35,978
neurotypical and fall under the

4258
01:53:35,978 --> 01:53:37,130
heading of this

4259
01:53:37,130 --> 01:53:38,514
of the symposium.

4260
01:53:38,514 --> 01:53:40,304
There is no I CD10 code for

4261
01:53:40,304 --> 01:53:42,265
hikikomori and this young man

4262
01:53:42,265 --> 01:53:43,685
actually seems to be

4263
01:53:43,685 --> 01:53:45,821
getting some sunlight which many

4264
01:53:45,821 --> 01:53:47,289
of my patients don't.

4265
01:53:47,956 --> 01:53:49,056
My point being,

4266
01:53:49,056 --> 01:53:51,384
there is no medication on earth

4267
01:53:51,384 --> 01:53:52,060
which is

4268
01:53:52,060 --> 01:53:54,106
going to moderate or improve

4269
01:53:54,106 --> 01:53:56,268
your sleep if you don't leave

4270
01:53:56,268 --> 01:53:57,833
your room and you're

4271
01:53:57,833 --> 01:53:58,925
in constant dim

4272
01:53:58,925 --> 01:54:00,235
light situations.

4273
01:54:00,903 --> 01:54:02,688
It is very challenging to use a

4274
01:54:02,688 --> 01:54:04,576
medication to improve sleep when

4275
01:54:04,576 --> 01:54:05,107
you have

4276
01:54:05,107 --> 01:54:06,793
almost unlimited screen time,

4277
01:54:06,793 --> 01:54:08,403
which applies to many of my

4278
01:54:08,403 --> 01:54:09,178
patients who

4279
01:54:09,178 --> 01:54:10,202
are not constantly

4280
01:54:10,202 --> 01:54:11,113
in their rooms.

4281
01:54:13,315 --> 01:54:15,091
Sorry about the soapbox

4282
01:54:15,091 --> 01:54:17,486
categories of sleep disorders.

4283
01:54:17,886 --> 01:54:20,408
The International Classification

4284
01:54:20,408 --> 01:54:22,336
of Sleep Disorders Third

4285
01:54:22,336 --> 01:54:24,426
addition gives us several

4286
01:54:24,426 --> 01:54:26,866
categories and I'm not going to

4287
01:54:26,866 --> 01:54:28,597
focus on all of them,

4288
01:54:28,597 --> 01:54:31,111
but I am going to hit insomnia a

4289
01:54:31,111 --> 01:54:33,278
little bit on sleep related

4290
01:54:33,278 --> 01:54:34,803
movement disorders

4291
01:54:34,803 --> 01:54:37,163
and a little bit with a nod to

4292
01:54:37,163 --> 01:54:39,502
Doctor Combs on sleep related

4293
01:54:39,502 --> 01:54:40,309
breathing

4294
01:54:40,309 --> 01:54:42,177
disorders with insomnia.

4295
01:54:42,444 --> 01:54:42,928
Again,

4296
01:54:42,928 --> 01:54:44,828
the first line often is

4297
01:54:44,828 --> 01:54:46,315
melatonin at this

4298
01:54:46,315 --> 01:54:46,793
point,

4299
01:54:46,793 --> 01:54:49,330
and part of the challenge there

4300
01:54:49,330 --> 01:54:49,985
is that

4301
01:54:49,985 --> 01:54:52,440
by the time I see somebody in a

4302
01:54:52,440 --> 01:54:55,033
sleep clinic tried melatonin and

4303
01:54:55,033 --> 01:54:55,924
it's more,

4304
01:54:55,924 --> 01:54:57,826
what exactly did you do?

4305
01:54:57,826 --> 01:54:58,794
How much did you take?

4306
01:54:58,794 --> 01:54:59,661
When did you take it?

4307
01:54:59,661 --> 01:55:00,696
What kind did you take?

4308
01:55:01,930 --> 01:55:03,547
Antihistamines are a bit less

4309
01:55:03,547 --> 01:55:05,202
popular, but if you don't ask

4310
01:55:05,202 --> 01:55:06,001
specifically,

4311
01:55:06,001 --> 01:55:07,674
you might miss that somebody's

4312
01:55:07,674 --> 01:55:09,267
using that to supplement the

4313
01:55:09,267 --> 01:55:10,405
effect of something

4314
01:55:10,405 --> 01:55:11,451
else or alternating

4315
01:55:11,451 --> 01:55:12,608
with something else.

4316
01:55:13,575 --> 01:55:14,752
Hydroxyzine is a

4317
01:55:14,752 --> 01:55:16,445
reasonable anxiolytic.

4318
01:55:16,445 --> 01:55:18,578
I'm increasingly using that for

4319
01:55:18,578 --> 01:55:20,826
my many anxious patients so that

4320
01:55:20,826 --> 01:55:21,950
that may have a

4321
01:55:21,950 --> 01:55:23,508
few different benefits

4322
01:55:23,508 --> 01:55:24,853
prescription wise.

4323
01:55:24,853 --> 01:55:27,124
We'll come to Clonidine in a

4324
01:55:27,124 --> 01:55:29,613
moment, Gabapentin and some of

4325
01:55:29,613 --> 01:55:30,692
the atypical

4326
01:55:30,692 --> 01:55:31,994
antidepressants.

4327
01:55:34,529 --> 01:55:36,994
I swiped this image from a

4328
01:55:36,994 --> 01:55:40,002
chapter that Roberta Lou did on

4329
01:55:40,002 --> 01:55:41,069
melatonin.

4330
01:55:41,670 --> 01:55:42,577
But again,

4331
01:55:42,577 --> 01:55:45,556
the darkness hormone you need to

4332
01:55:45,556 --> 01:55:46,208
not be

4333
01:55:46,208 --> 01:55:48,737
constantly exposed to bright

4334
01:55:48,737 --> 01:55:51,505
light in order to secrete this

4335
01:55:51,505 --> 01:55:52,981
mediated by the

4336
01:55:52,981 --> 01:55:55,523
retinal retinothalamic tract

4337
01:55:55,523 --> 01:55:58,409
heading to the Super chaosmatic

4338
01:55:58,409 --> 01:55:59,154
nuclei.

4339
01:56:03,992 --> 01:56:06,697
Coming back to the International

4340
01:56:06,697 --> 01:56:09,064
Pediatric Sleep Association

4341
01:56:09,064 --> 01:56:10,422
recommendations,

4342
01:56:10,422 --> 01:56:12,968
which were relatively recent,

4343
01:56:12,968 --> 01:56:15,666
you want to use this one caution

4344
01:56:15,666 --> 01:56:17,606
with children under 2.

4345
01:56:18,607 --> 01:56:21,255
The suggestion maybe a little

4346
01:56:21,255 --> 01:56:23,812
bit Contra we heard before,

4347
01:56:23,812 --> 01:56:26,363
not come to the sleep doctor

4348
01:56:26,363 --> 01:56:28,520
because you had to stop

4349
01:56:28,520 --> 01:56:29,551
melatonin.

4350
01:56:29,551 --> 01:56:30,619
It was working well.

4351
01:56:30,619 --> 01:56:32,877
But the idea to supervise use in

4352
01:56:32,877 --> 01:56:34,537
children with ND DS and

4353
01:56:34,537 --> 01:56:36,124
periodically reassess

4354
01:56:36,124 --> 01:56:38,293
whether children still need it.

4355
01:56:38,593 --> 01:56:40,814
I think that one of the great

4356
01:56:40,814 --> 01:56:43,315
needs and lacks in this field is

4357
01:56:43,315 --> 01:56:44,566
not just how to

4358
01:56:44,566 --> 01:56:46,496
put people on medication,

4359
01:56:46,496 --> 01:56:48,503
but how to take them off,

4360
01:56:48,503 --> 01:56:50,172
when to take them off.

4361
01:56:52,207 --> 01:56:54,176
Maximum dose 10 milligrams.

4362
01:56:54,176 --> 01:56:55,959
I think that this particular

4363
01:56:55,959 --> 01:56:57,922
paper suggested a range of two

4364
01:56:57,922 --> 01:56:58,380
to 10.

4365
01:56:58,380 --> 01:57:00,308
I've usually started kids on 0.

4366
01:57:00,308 --> 01:57:02,228
5 milligrams and I had a young

4367
01:57:02,228 --> 01:57:02,484
man

4368
01:57:02,484 --> 01:57:04,418
earlier this week who fessed up

4369
01:57:04,418 --> 01:57:06,077
to his mother to taking 40

4370
01:57:06,077 --> 01:57:07,289
milligrams because

4371
01:57:07,289 --> 01:57:09,057
the 10 wasn't quite doing it.

4372
01:57:09,057 --> 01:57:11,842
So he popped a few timing,

4373
01:57:11,842 --> 01:57:15,163
lack of long term safety data.

4374
01:57:16,331 --> 01:57:17,309
Doctor Mallow,

4375
01:57:17,309 --> 01:57:19,529
thank you for one of the follow

4376
01:57:19,529 --> 01:57:20,102
-ups to

4377
01:57:20,102 --> 01:57:21,921
try to address some of the

4378
01:57:21,921 --> 01:57:24,130
concerns about delay of puberty

4379
01:57:24,130 --> 01:57:25,841
and effects on HPA axis

4380
01:57:25,841 --> 01:57:27,957
with the follow up of children

4381
01:57:27,957 --> 01:57:29,829
treated with the pediatric

4382
01:57:29,829 --> 01:57:31,413
prolonged release and

4383
01:57:31,413 --> 01:57:33,535
the knowledge that at least in

4384
01:57:33,535 --> 01:57:34,950
that two year term,

4385
01:57:34,950 --> 01:57:37,059
the pubertal status and growth

4386
01:57:37,059 --> 01:57:38,887
were not really affected.

4387
01:57:45,727 --> 01:57:48,473
This is some information from

4388
01:57:48,473 --> 01:57:51,572
AUK review of Clonidine practice

4389
01:57:51,572 --> 01:57:52,734
prescribing

4390
01:57:52,734 --> 01:57:53,668
practices.

4391
01:57:55,737 --> 01:57:58,517
This one is pretty reasonable in

4392
01:57:58,517 --> 01:58:00,776
terms of onset of action.

4393
01:58:00,776 --> 01:58:02,509
In terms of duration of action,

4394
01:58:02,509 --> 01:58:04,287
for some of my patients it does

4395
01:58:04,287 --> 01:58:04,746
seem to

4396
01:58:04,746 --> 01:58:06,081
help not only with sleep

4397
01:58:06,081 --> 01:58:07,508
initiation but with sleep

4398
01:58:07,508 --> 01:58:08,250
maintenance.

4399
01:58:09,651 --> 01:58:11,887
It does tend to be R.E.M.

4400
01:58:11,887 --> 01:58:15,740
Suppressing and you can see what

4401
01:58:15,740 --> 01:58:17,426
the range is.

4402
01:58:18,293 --> 01:58:20,301
One of the things that we run

4403
01:58:20,301 --> 01:58:22,278
into with this medication as

4404
01:58:22,278 --> 01:58:23,832
well as others in the

4405
01:58:23,832 --> 01:58:25,982
world of sleep is that it seems

4406
01:58:25,982 --> 01:58:28,111
to be more effective initially

4407
01:58:28,111 --> 01:58:29,104
and over time

4408
01:58:29,104 --> 01:58:30,338
maybe not as much.

4409
01:58:31,973 --> 01:58:33,846
Many prescribers had concerns

4410
01:58:33,846 --> 01:58:34,943
about tolerance.

4411
01:58:36,511 --> 01:58:39,085
This being an alpha adrenergic

4412
01:58:39,085 --> 01:58:41,891
agonist, we also have effects on

4413
01:58:41,891 --> 01:58:43,118
hyper arousal

4414
01:58:43,118 --> 01:58:45,863
states which may be very helpful

4415
01:58:45,863 --> 01:58:47,923
for people with autism,

4416
01:58:47,923 --> 01:58:50,670
people who are chronically there

4417
01:58:50,670 --> 01:58:53,483
And I am short on time due to my

4418
01:58:53,483 --> 01:58:54,362
technical

4419
01:58:54,362 --> 01:58:55,464
difficulties.

4420
01:58:55,464 --> 01:58:56,507
So moving forward to

4421
01:58:56,507 --> 01:58:57,499
some side effects.

4422
01:58:57,732 --> 01:59:00,027
Constipation is not necessarily

4423
01:59:00,027 --> 01:59:02,068
minor, though it was in the

4424
01:59:02,068 --> 01:59:03,505
sample in children

4425
01:59:03,505 --> 01:59:04,172
with NDD.

4426
01:59:07,976 --> 01:59:10,001
In Doctor Robinson's paper on

4427
01:59:10,001 --> 01:59:12,155
gabapentin, this has been, I'd

4428
01:59:12,155 --> 01:59:12,514
say,

4429
01:59:12,514 --> 01:59:14,670
one of the more helpful ones in

4430
01:59:14,670 --> 01:59:16,618
terms of sleep maintenance.

4431
01:59:16,618 --> 01:59:17,619
Insomnia.

4432
01:59:18,753 --> 01:59:19,623
You can see some

4433
01:59:19,623 --> 01:59:20,655
irritability here.

4434
01:59:20,655 --> 01:59:22,177
You can see some changes in

4435
01:59:22,177 --> 01:59:23,191
sleep parameters.

4436
01:59:24,793 --> 01:59:26,528
One of the challenges here is

4437
01:59:26,528 --> 01:59:28,263
yes, it comes in a solution.

4438
01:59:28,530 --> 01:59:29,748
Yes, the solution

4439
01:59:29,748 --> 01:59:30,966
tastes terrible.

4440
01:59:32,567 --> 01:59:34,386
Restless leg syndrome

4441
01:59:34,386 --> 01:59:37,117
recommendations melatonin rides

4442
01:59:37,117 --> 01:59:39,407
again gabapentin at least

4443
01:59:39,407 --> 01:59:41,851
the ASM most recent practice

4444
01:59:41,851 --> 01:59:44,631
parameter recommended in adults

4445
01:59:44,631 --> 01:59:45,080
iron

4446
01:59:45,080 --> 01:59:47,240
supplementation low serum

4447
01:59:47,240 --> 01:59:49,794
ferritin is not diagnostic of

4448
01:59:49,794 --> 01:59:51,820
restless leg syndrome.

4449
01:59:51,820 --> 01:59:53,081
But for children who have

4450
01:59:53,081 --> 01:59:54,572
restless leg syndrome or more

4451
01:59:54,572 --> 01:59:55,857
commonly in the world of

4452
01:59:55,857 --> 01:59:57,374
developmental disabilities are

4453
01:59:57,374 --> 01:59:58,729
kind of restless and maybe

4454
01:59:58,729 --> 01:59:59,094
could.

4455
01:59:59,094 --> 02:00:00,629
And we want to try something.

4456
02:00:01,930 --> 02:00:03,678
Probably worth a try with

4457
02:00:03,678 --> 02:00:05,607
monitoring, with counseling

4458
02:00:05,607 --> 02:00:07,035
about side effects.

4459
02:00:08,537 --> 02:00:10,855
I was ready to go into a short

4460
02:00:10,855 --> 02:00:13,143
tirade about dopamine agonist

4461
02:00:13,143 --> 02:00:14,643
and the challenges

4462
02:00:14,643 --> 02:00:16,845
of disinhibition in children.

4463
02:00:16,845 --> 02:00:18,537
But now AASM is suggesting

4464
02:00:18,537 --> 02:00:20,011
against use for adults

4465
02:00:20,011 --> 02:00:20,749
routinely.

4466
02:00:21,349 --> 02:00:22,617
Interesting times.

4467
02:00:24,252 --> 02:00:26,424
Magnesium has been blowing up

4468
02:00:26,424 --> 02:00:27,622
right and left.

4469
02:00:28,924 --> 02:00:31,167
A small open label pilot study

4470
02:00:31,167 --> 02:00:33,261
in adults showed something,

4471
02:00:33,261 --> 02:00:35,276
but a recent ish systematic

4472
02:00:35,276 --> 02:00:37,641
review really didn't have a lot

4473
02:00:37,641 --> 02:00:38,633
of evidence.

4474
02:00:38,633 --> 02:00:40,422
And yet this is absolutely out

4475
02:00:40,422 --> 02:00:41,436
there for sleep.

4476
02:00:43,071 --> 02:00:44,506
Obstructive sleep apnea.

4477
02:00:46,775 --> 02:00:49,711
Nasal steroid sprays in the mix.

4478
02:00:51,346 --> 02:00:51,732
Again,

4479
02:00:51,732 --> 02:00:53,717
it's a little unclear when you

4480
02:00:53,717 --> 02:00:53,982
can

4481
02:00:53,982 --> 02:00:55,116
discontinue these.

4482
02:00:55,383 --> 02:00:56,451
Montelukast.

4483
02:00:56,451 --> 02:00:57,684
If you listen to the

4484
02:00:57,684 --> 02:00:59,287
otolaryngology consensus,

4485
02:00:59,287 --> 02:01:01,116
probably safe and affected for

4486
02:01:01,116 --> 02:01:02,457
mild to moderate OSA.

4487
02:01:03,625 --> 02:01:04,025
However,

4488
02:01:04,025 --> 02:01:05,518
there's a black box statement

4489
02:01:05,518 --> 02:01:05,827
about

4490
02:01:05,827 --> 02:01:07,062
neuropsychiatric effects.

4491
02:01:07,062 --> 02:01:08,842
There's fairly conflicting

4492
02:01:08,842 --> 02:01:10,588
evidence out in the world

4493
02:01:10,588 --> 02:01:12,334
whether they are a risk.

4494
02:01:12,334 --> 02:01:13,842
And if you counsel parents about

4495
02:01:13,842 --> 02:01:15,286
this, which you should because

4496
02:01:15,286 --> 02:01:16,104
they're going to

4497
02:01:16,104 --> 02:01:17,102
read about it anyway,

4498
02:01:17,102 --> 02:01:18,614
I find that many of them refuse

4499
02:01:18,614 --> 02:01:18,907
this.

4500
02:01:19,174 --> 02:01:20,575
I see Doctor Buckley is up.

4501
02:01:21,710 --> 02:01:22,774
Doctor Combs,

4502
02:01:22,774 --> 02:01:25,376
thank you so much for your work

4503
02:01:25,376 --> 02:01:26,047
in auto

4504
02:01:26,047 --> 02:01:26,381
oxy.

4505
02:01:26,381 --> 02:01:28,198
I am very intrigued and want to

4506
02:01:28,198 --> 02:01:30,124
investigate this further in some

4507
02:01:30,124 --> 02:01:30,485
of my

4508
02:01:30,485 --> 02:01:31,019
patients.

4509
02:01:31,653 --> 02:01:33,274
And I want to point out

4510
02:01:33,274 --> 02:01:34,996
following Doctor Mallows

4511
02:01:34,996 --> 02:01:37,292
mentioned that there is one FDA

4512
02:01:37,292 --> 02:01:39,554
approved medication for children

4513
02:01:39,554 --> 02:01:41,651
with sleep problems and it is

4514
02:01:41,651 --> 02:01:42,664
tassimilty on

4515
02:01:42,664 --> 02:01:44,833
specifically for Smith magenis.

4516
02:01:47,969 --> 02:01:50,402
A lot of times we get hung up on

4517
02:01:50,402 --> 02:01:52,607
side effects of medications.

4518
02:01:52,941 --> 02:01:54,812
I will say there are side

4519
02:01:54,812 --> 02:01:57,025
effects to sleep problems not

4520
02:01:57,025 --> 02:01:58,780
being treated and they

4521
02:01:58,780 --> 02:02:00,653
are often significant and

4522
02:02:00,653 --> 02:02:02,349
include familial sleep

4523
02:02:02,349 --> 02:02:03,351
deprivation,

4524
02:02:03,351 --> 02:02:05,521
safety risks for children who

4525
02:02:05,521 --> 02:02:07,823
are wandering and exploring at

4526
02:02:07,823 --> 02:02:08,590
night and

4527
02:02:08,590 --> 02:02:11,010
generally less pleasant behavior

4528
02:02:11,010 --> 02:02:11,993
by children.

4529
02:02:14,229 --> 02:02:16,731
I'm going to skip past some of

4530
02:02:16,731 --> 02:02:19,305
this quickly to say looking at

4531
02:02:19,305 --> 02:02:19,734
ADHD

4532
02:02:19,734 --> 02:02:20,739
medications,

4533
02:02:20,739 --> 02:02:23,400
thinking about medications that

4534
02:02:23,400 --> 02:02:24,172
are used

4535
02:02:24,172 --> 02:02:25,573
in kids with NDD.

4536
02:02:25,573 --> 02:02:26,999
Not specifically for sleep but

4537
02:02:26,999 --> 02:02:28,376
with potential side effects.

4538
02:02:28,743 --> 02:02:29,111
Yes,

4539
02:02:29,111 --> 02:02:31,947
stimulants can sometimes cause

4540
02:02:31,947 --> 02:02:32,514
sleep

4541
02:02:32,514 --> 02:02:34,132
difficulties, more

4542
02:02:34,132 --> 02:02:35,750
with long acting.

4543
02:02:35,750 --> 02:02:37,433
I don't think that's a reason

4544
02:02:37,433 --> 02:02:38,420
not to use them,

4545
02:02:38,420 --> 02:02:40,230
but is a reason to monitor with

4546
02:02:40,230 --> 02:02:41,456
seizure medications.

4547
02:02:41,456 --> 02:02:42,791
Shout out to doctor Schellhaas.

4548
02:02:43,692 --> 02:02:45,262
The thing I find fascinating is

4549
02:02:45,262 --> 02:02:46,762
the same medications can have

4550
02:02:46,762 --> 02:02:47,796
the opposite effect

4551
02:02:47,796 --> 02:02:49,030
depending on the child's

4552
02:02:49,030 --> 02:02:50,265
somnolence or insomnia.

4553
02:02:52,467 --> 02:02:54,306
SSRIs can trigger restless leg

4554
02:02:54,306 --> 02:02:55,470
syndrome symptoms,

4555
02:02:55,470 --> 02:02:57,053
which is important to know

4556
02:02:57,053 --> 02:02:59,042
should you be using those, which

4557
02:02:59,042 --> 02:02:59,974
many of us do.

4558
02:02:59,974 --> 02:03:02,351
And atypical antipsychotics come

4559
02:03:02,351 --> 02:03:04,579
with significant weight gain,

4560
02:03:04,579 --> 02:03:06,863
potential for obstructive sleep

4561
02:03:06,863 --> 02:03:09,272
apnea and sidebar potential kind

4562
02:03:09,272 --> 02:03:10,251
of metabolic

4563
02:03:10,251 --> 02:03:12,020
syndrome and directions.

4564
02:03:12,020 --> 02:03:13,558
There are more questions than

4565
02:03:13,558 --> 02:03:14,804
answers in the world of

4566
02:03:14,804 --> 02:03:16,157
medication for pediatric

4567
02:03:16,157 --> 02:03:16,458
sleep.

4568
02:03:16,791 --> 02:03:18,509
How do we integrate medication

4569
02:03:18,509 --> 02:03:19,915
use and behavioral sleep

4570
02:03:19,915 --> 02:03:21,029
strategies into an

4571
02:03:21,029 --> 02:03:22,265
effective and holistic

4572
02:03:22,265 --> 02:03:23,164
treatment plan?

4573
02:03:24,265 --> 02:03:26,031
We're we have expert guidance,

4574
02:03:26,031 --> 02:03:27,659
Is there kind of additional

4575
02:03:27,659 --> 02:03:28,503
evidence base

4576
02:03:28,503 --> 02:03:29,198
for rational

4577
02:03:29,198 --> 02:03:30,472
medication selection?

4578
02:03:30,472 --> 02:03:32,270
Where is our precision medicine

4579
02:03:32,270 --> 02:03:33,760
in the world of sleep for

4580
02:03:33,760 --> 02:03:34,476
Pediatrics?

4581
02:03:35,443 --> 02:03:37,045
What are acceptable formats?

4582
02:03:37,045 --> 02:03:38,878
Because some of my patients are

4583
02:03:38,878 --> 02:03:40,810
not going to swallow a pill or a

4584
02:03:40,810 --> 02:03:41,716
capsule and if

4585
02:03:41,716 --> 02:03:42,754
that tastes funny,

4586
02:03:42,754 --> 02:03:43,618
it is a no go.

4587
02:03:45,019 --> 02:03:47,182
Protocols for cessation,

4588
02:03:47,182 --> 02:03:49,962
issues of long term effects of

4589
02:03:49,962 --> 02:03:50,425
use,

4590
02:03:50,425 --> 02:03:51,392
measures of

4591
02:03:51,392 --> 02:03:53,328
effectiveness and Dr.

4592
02:03:53,328 --> 02:03:54,937
Combs Will medication for sleep

4593
02:03:54,937 --> 02:03:56,367
related breathing disorders

4594
02:03:56,367 --> 02:03:57,532
emerge as a treatment

4595
02:03:57,532 --> 02:03:57,899
option?

4596
02:03:57,899 --> 02:03:59,134
That would be wonderful.

4597
02:03:59,634 --> 02:04:01,572
Thank you so much for having me

4598
02:04:01,572 --> 02:04:03,487
and I very much appreciate all

4599
02:04:03,487 --> 02:04:04,572
the speakers and

4600
02:04:04,572 --> 02:04:05,740
I'm learning a lot.

4601
02:04:05,740 --> 02:04:06,307
Thank you.

4602
02:04:06,775 --> 02:04:07,693
Thank you so much,

4603
02:04:07,693 --> 02:04:08,510
Doctor Ricardo.

4604
02:04:08,510 --> 02:04:10,788
So we are about 90 seconds or

4605
02:04:10,788 --> 02:04:13,381
maybe even 120 seconds overtime.

4606
02:04:13,381 --> 02:04:15,428
So I think we're going to close

4607
02:04:15,428 --> 02:04:16,551
and go to break,

4608
02:04:16,551 --> 02:04:18,603
but I do have the questions in

4609
02:04:18,603 --> 02:04:20,655
the chat that we can revisit.

4610
02:04:20,655 --> 02:04:22,529
And I just think that was a

4611
02:04:22,529 --> 02:04:24,584
really fantastic way to round

4612
02:04:24,584 --> 02:04:25,860
out this morning.

4613
02:04:26,261 --> 02:04:28,196
So I think it's break time now.

4614
02:04:28,196 --> 02:04:30,865
It is to 130.

4615
02:04:30,865 --> 02:04:31,548
Thanks, you and

4616
02:04:31,548 --> 02:04:32,367
all the speakers.

4617
02:04:33,568 --> 02:04:33,751
OK,

4618
02:04:33,751 --> 02:04:34,944
welcome back to the

4619
02:04:34,944 --> 02:04:36,137
Neurodevelopmental

4620
02:04:36,137 --> 02:04:37,872
Disorders and Sleep workshop.

4621
02:04:38,606 --> 02:04:40,403
We're going into our third

4622
02:04:40,403 --> 02:04:42,477
session, which is population,

4623
02:04:42,477 --> 02:04:43,611
environmental and

4624
02:04:43,611 --> 02:04:44,813
other influences.

4625
02:04:45,313 --> 02:04:46,381
I'm Cindy Lawler.

4626
02:04:46,381 --> 02:04:48,385
I'm the Program Officer and the

4627
02:04:48,385 --> 02:04:50,431
Chief of Gene's Environment and

4628
02:04:50,431 --> 02:04:51,553
Health Branch at

4629
02:04:51,553 --> 02:04:53,191
the National Institute of

4630
02:04:53,191 --> 02:04:55,223
Environmental Health Sciences,

4631
02:04:55,223 --> 02:04:57,091
where I manage a portfolio of

4632
02:04:57,091 --> 02:04:58,938
grants seeking to understand

4633
02:04:58,938 --> 02:04:59,861
environmental

4634
02:04:59,861 --> 02:05:01,229
influences on autism.

4635
02:05:01,729 --> 02:05:02,897
I'm your moderator

4636
02:05:02,897 --> 02:05:04,065
for this session.

4637
02:05:04,365 --> 02:05:06,018
Our speakers will describe

4638
02:05:06,018 --> 02:05:08,096
challenges with sleep assessment

4639
02:05:08,096 --> 02:05:09,070
in people with

4640
02:05:09,070 --> 02:05:10,922
neurodevelopmental disorders,

4641
02:05:10,922 --> 02:05:12,774
the relationship of sleep to

4642
02:05:12,774 --> 02:05:14,566
developmental progression in

4643
02:05:14,566 --> 02:05:16,333
autism, and we'll also hear

4644
02:05:16,333 --> 02:05:17,445
about the use of

4645
02:05:17,445 --> 02:05:19,475
cohort studies for identifying a

4646
02:05:19,475 --> 02:05:21,288
variety of influences on how

4647
02:05:21,288 --> 02:05:22,584
these disorders are

4648
02:05:22,584 --> 02:05:23,151
manifest.

4649
02:05:23,818 --> 02:05:25,087
Our first speaker

4650
02:05:25,087 --> 02:05:26,654
is Jared Fallington.

4651
02:05:27,055 --> 02:05:27,941
He's one of the Co

4652
02:05:27,941 --> 02:05:29,123
chairs of this meeting.

4653
02:05:29,424 --> 02:05:31,440
He's an assistant professor in

4654
02:05:31,440 --> 02:05:33,648
the Department of Psychiatry and

4655
02:05:33,648 --> 02:05:34,062
Human

4656
02:05:34,062 --> 02:05:34,674
Behavior,

4657
02:05:34,674 --> 02:05:36,835
Ed Brown and Associate director

4658
02:05:36,835 --> 02:05:37,532
of the EP

4659
02:05:37,532 --> 02:05:39,625
Bradley Hospital Sleep Research

4660
02:05:39,625 --> 02:05:40,435
Laboratory,

4661
02:05:40,435 --> 02:05:42,450
A cognitive neuroscientist who

4662
02:05:42,450 --> 02:05:44,308
is studying sleep dependent

4663
02:05:44,308 --> 02:05:45,340
brain function

4664
02:05:45,340 --> 02:05:46,274
in typical and

4665
02:05:46,274 --> 02:05:47,742
atypical development.

4666
02:05:48,176 --> 02:05:50,003
His talk today is on sleep

4667
02:05:50,003 --> 02:05:51,877
assessments in challenging

4668
02:05:51,877 --> 02:05:52,814
populations.

4669
02:05:56,618 --> 02:05:58,213
Thank you so much and thank you

4670
02:05:58,213 --> 02:05:59,654
everyone for for attending.

4671
02:06:00,221 --> 02:06:00,755
Wonderful.

4672
02:06:01,022 --> 02:06:01,487
So again,

4673
02:06:01,487 --> 02:06:03,023
my name is Jared Salt and I'm

4674
02:06:03,023 --> 02:06:03,658
it's such a

4675
02:06:03,658 --> 02:06:05,114
privilege to share this this

4676
02:06:05,114 --> 02:06:06,547
incredible workshop and I'm

4677
02:06:06,547 --> 02:06:07,662
grateful for all the

4678
02:06:07,662 --> 02:06:08,763
speakers this morning.

4679
02:06:09,063 --> 02:06:10,566
My talk is not going to be a

4680
02:06:10,566 --> 02:06:11,532
data-driven talk,

4681
02:06:11,532 --> 02:06:13,179
although I'll try and hint at a

4682
02:06:13,179 --> 02:06:14,135
couple of things.

4683
02:06:14,335 --> 02:06:15,951
I'm really going to speak from

4684
02:06:15,951 --> 02:06:17,719
the lens of methodology and some

4685
02:06:17,719 --> 02:06:18,106
of the

4686
02:06:18,106 --> 02:06:19,717
difficulties that we face when

4687
02:06:19,717 --> 02:06:20,989
studying sleep in these

4688
02:06:20,989 --> 02:06:21,542
contexts.

4689
02:06:22,543 --> 02:06:23,149
As mentioned,

4690
02:06:23,149 --> 02:06:24,587
I'm a cognitive neuroscientist

4691
02:06:24,587 --> 02:06:24,779
who

4692
02:06:24,779 --> 02:06:26,257
studies how sleep and sleep loss

4693
02:06:26,257 --> 02:06:27,391
affect brain function in

4694
02:06:27,391 --> 02:06:28,383
neuropsychiatric and

4695
02:06:28,383 --> 02:06:29,751
neurodevelopmental conditions.

4696
02:06:29,751 --> 02:06:31,616
I'm incredibly grateful for the

4697
02:06:31,616 --> 02:06:33,421
NI HS support in this effort,

4698
02:06:33,421 --> 02:06:34,969
including an RO one that's

4699
02:06:34,969 --> 02:06:36,730
ongoing from NICHD as well as

4700
02:06:36,730 --> 02:06:38,126
funding from NIMHNIGMS

4701
02:06:38,126 --> 02:06:39,646
as well as as non federal

4702
02:06:39,646 --> 02:06:40,862
foundation funding.

4703
02:06:42,430 --> 02:06:44,003
And I think this is a great sort

4704
02:06:44,003 --> 02:06:45,412
of stepping to remind us the

4705
02:06:45,412 --> 02:06:46,067
scale of the

4706
02:06:46,067 --> 02:06:46,467
problem.

4707
02:06:46,467 --> 02:06:47,827
So I do a little bit of work in

4708
02:06:47,827 --> 02:06:49,177
neuropsychiatric conditions as

4709
02:06:49,177 --> 02:06:49,537
well as

4710
02:06:49,537 --> 02:06:50,772
neurodevelopmental disorders.

4711
02:06:50,772 --> 02:06:52,542
And when you look at the, the,

4712
02:06:52,542 --> 02:06:54,297
the amount of citations of of

4713
02:06:54,297 --> 02:06:54,842
studying

4714
02:06:54,842 --> 02:06:56,370
sleep in these conditions,

4715
02:06:56,370 --> 02:06:58,057
neurodevelopmental disorders

4716
02:06:58,057 --> 02:06:58,780
really lags

4717
02:06:58,780 --> 02:07:00,669
behind the psychiatry literature

4718
02:07:00,669 --> 02:07:01,849
for sleep research.

4719
02:07:01,849 --> 02:07:03,890
And I think some of this is, is,

4720
02:07:03,890 --> 02:07:05,715
you know, sort of trends and

4721
02:07:05,715 --> 02:07:06,888
interest in these

4722
02:07:06,888 --> 02:07:07,335
topics,

4723
02:07:07,335 --> 02:07:09,431
but I think some of this is also

4724
02:07:09,431 --> 02:07:09,824
about

4725
02:07:09,824 --> 02:07:11,864
the difficulty of studying sleep

4726
02:07:11,864 --> 02:07:13,362
this this very intimate

4727
02:07:13,362 --> 02:07:14,796
biological process in

4728
02:07:14,796 --> 02:07:16,114
individuals with some

4729
02:07:16,114 --> 02:07:17,432
of these conditions.

4730
02:07:17,432 --> 02:07:19,019
We've already heard pieces of

4731
02:07:19,019 --> 02:07:20,697
that in some of the talks that

4732
02:07:20,697 --> 02:07:21,536
were that were

4733
02:07:21,536 --> 02:07:22,770
presented this morning.

4734
02:07:22,770 --> 02:07:24,064
And I'm going to expound a

4735
02:07:24,064 --> 02:07:25,606
little bit on that in my talk.

4736
02:07:26,274 --> 02:07:27,736
So this is a framework that I

4737
02:07:27,736 --> 02:07:28,643
like to think in,

4738
02:07:28,643 --> 02:07:29,966
in terms of challenges for

4739
02:07:29,966 --> 02:07:31,646
studying sleep in this scenario,

4740
02:07:31,646 --> 02:07:33,097
if we take neurodevelopmental

4741
02:07:33,097 --> 02:07:34,630
disorders and break it down to

4742
02:07:34,630 --> 02:07:35,550
studying sleep in

4743
02:07:35,550 --> 02:07:36,462
circadian rhythms,

4744
02:07:36,462 --> 02:07:37,973
what are the assessments that

4745
02:07:37,973 --> 02:07:38,286
we're

4746
02:07:38,286 --> 02:07:39,354
really talking about?

4747
02:07:39,354 --> 02:07:39,700
And I,

4748
02:07:39,700 --> 02:07:41,591
and I'll use the word assessment

4749
02:07:41,591 --> 02:07:42,123
for this

4750
02:07:42,123 --> 02:07:43,562
talk to really talk about

4751
02:07:43,562 --> 02:07:44,852
research sign research

4752
02:07:44,852 --> 02:07:46,728
methodologies for probing these

4753
02:07:46,728 --> 02:07:47,295
processes.

4754
02:07:47,695 --> 02:07:49,422
We can think of sleep as both

4755
02:07:49,422 --> 02:07:51,321
the behavior, something that we

4756
02:07:51,321 --> 02:07:51,566
do,

4757
02:07:51,566 --> 02:07:53,351
something that we perceive and

4758
02:07:53,351 --> 02:07:55,136
has quality components to it.

4759
02:07:55,370 --> 02:07:56,962
And you've heard little bits

4760
02:07:56,962 --> 02:07:58,301
today already about the

4761
02:07:58,301 --> 02:07:59,407
neurophysiological

4762
02:07:59,407 --> 02:07:59,754
media,

4763
02:07:59,754 --> 02:08:01,475
the psychobiology of sleep in

4764
02:08:01,475 --> 02:08:02,010
terms of

4765
02:08:02,010 --> 02:08:03,549
its regulation at the brain

4766
02:08:03,549 --> 02:08:05,146
level and in the periphery.

4767
02:08:05,380 --> 02:08:06,699
So first we have to think about

4768
02:08:06,699 --> 02:08:07,835
what it is we are actually

4769
02:08:07,835 --> 02:08:08,316
measuring.

4770
02:08:08,850 --> 02:08:10,291
Once we come to that answer,

4771
02:08:10,291 --> 02:08:11,926
we see that we have a number of

4772
02:08:11,926 --> 02:08:12,453
different

4773
02:08:12,453 --> 02:08:13,246
ways in which we

4774
02:08:13,246 --> 02:08:14,088
can probe sleep.

4775
02:08:14,355 --> 02:08:15,656
They range from self

4776
02:08:15,656 --> 02:08:16,891
or part or recall.

4777
02:08:16,891 --> 02:08:18,303
These are things that might be

4778
02:08:18,303 --> 02:08:19,749
done at the bedside as well as

4779
02:08:19,749 --> 02:08:20,328
in research

4780
02:08:20,328 --> 02:08:20,695
studies.

4781
02:08:21,129 --> 02:08:22,934
They can scale from one question

4782
02:08:22,934 --> 02:08:24,232
to multiple questions.

4783
02:08:24,232 --> 02:08:25,266
Daily Diaries.

4784
02:08:25,500 --> 02:08:26,892
We talk about actigraphy as a

4785
02:08:26,892 --> 02:08:28,176
way to look at sleep, wake

4786
02:08:28,176 --> 02:08:28,669
behavior.

4787
02:08:28,870 --> 02:08:29,827
And then of course,

4788
02:08:29,827 --> 02:08:31,439
we have the physiological tool,

4789
02:08:31,439 --> 02:08:32,890
some of which you've heard of

4790
02:08:32,890 --> 02:08:34,474
already, EEG being different in

4791
02:08:34,474 --> 02:08:35,343
neurodevelopment

4792
02:08:35,343 --> 02:08:36,916
disorders and of course the EEG

4793
02:08:36,916 --> 02:08:37,779
milieu of sleep.

4794
02:08:38,312 --> 02:08:39,965
But we also have the periphery,

4795
02:08:39,965 --> 02:08:41,487
melatonin, biomarkers of the

4796
02:08:41,487 --> 02:08:42,683
circadian rhythms and

4797
02:08:42,683 --> 02:08:43,418
other aspects.

4798
02:08:43,618 --> 02:08:44,952
So measurement of sleeping

4799
02:08:44,952 --> 02:08:46,209
circadian rhythms is not

4800
02:08:46,209 --> 02:08:47,622
monolithic as as Demetrius

4801
02:08:47,622 --> 02:08:48,548
mentioned earlier,

4802
02:08:48,548 --> 02:08:50,183
it really is a complex state to

4803
02:08:50,183 --> 02:08:50,658
measure.

4804
02:08:51,659 --> 02:08:53,035
Understanding the domain of

4805
02:08:53,035 --> 02:08:54,440
measurement, then we have a

4806
02:08:54,440 --> 02:08:55,430
number of options.

4807
02:08:55,763 --> 02:08:57,594
We have gold standards that that

4808
02:08:57,594 --> 02:08:59,356
emerge from the sleep research

4809
02:08:59,356 --> 02:08:59,767
field.

4810
02:08:59,767 --> 02:09:01,116
And then we have all the way up

4811
02:09:01,116 --> 02:09:02,449
to novel technologies of folks

4812
02:09:02,449 --> 02:09:03,204
trying to get at

4813
02:09:03,204 --> 02:09:04,505
the problem in different ways.

4814
02:09:04,705 --> 02:09:05,902
We can do this at home,

4815
02:09:05,902 --> 02:09:07,401
in the laboratory and in the

4816
02:09:07,401 --> 02:09:07,775
field.

4817
02:09:08,176 --> 02:09:10,017
And then we have this incredible

4818
02:09:10,017 --> 02:09:11,910
complexity that comes to bear on

4819
02:09:11,910 --> 02:09:12,146
the

4820
02:09:12,146 --> 02:09:13,269
question development

4821
02:09:13,269 --> 02:09:14,449
across the lifespan.

4822
02:09:14,449 --> 02:09:16,059
I'm going to focus mostly on

4823
02:09:16,059 --> 02:09:17,880
applications to youth, children

4824
02:09:17,880 --> 02:09:18,820
to adolescents,

4825
02:09:18,820 --> 02:09:20,311
but these lessons apply to

4826
02:09:20,311 --> 02:09:22,137
adults and to little infants as

4827
02:09:22,137 --> 02:09:22,490
well.

4828
02:09:22,890 --> 02:09:24,558
Then of course environmental

4829
02:09:24,558 --> 02:09:26,271
factors, social media of the

4830
02:09:26,271 --> 02:09:26,761
family,

4831
02:09:26,761 --> 02:09:28,478
medical complexity, cognitive

4832
02:09:28,478 --> 02:09:30,412
ability, sensory differences and

4833
02:09:30,412 --> 02:09:31,499
sensitivities and

4834
02:09:31,499 --> 02:09:33,329
Co occurring conditions all add

4835
02:09:33,329 --> 02:09:34,545
to the complexity of

4836
02:09:34,545 --> 02:09:35,336
measurement.

4837
02:09:36,604 --> 02:09:38,515
So I like to think of assessment

4838
02:09:38,515 --> 02:09:40,409
of sleep is really this lost in

4839
02:09:40,409 --> 02:09:41,142
translation

4840
02:09:41,142 --> 02:09:42,043
component here,

4841
02:09:42,043 --> 02:09:43,891
where the tools of traditional

4842
02:09:43,891 --> 02:09:44,445
sleep in

4843
02:09:44,445 --> 02:09:45,998
circadian science might be

4844
02:09:45,998 --> 02:09:47,702
useful in some scenarios and

4845
02:09:47,702 --> 02:09:49,283
might not be as useful in

4846
02:09:49,283 --> 02:09:49,684
others.

4847
02:09:50,485 --> 02:09:51,944
And so how do we go about

4848
02:09:51,944 --> 02:09:53,788
choosing which measurements and

4849
02:09:53,788 --> 02:09:55,156
assessments we want to

4850
02:09:55,156 --> 02:09:55,790
use in PDD?

4851
02:09:56,324 --> 02:09:56,662
Again,

4852
02:09:56,662 --> 02:09:58,281
I'm going to focus mostly on

4853
02:09:58,281 --> 02:09:58,860
tools and

4854
02:09:58,860 --> 02:10:00,233
approaches for scientific

4855
02:10:00,233 --> 02:10:01,585
research and mechanistic

4856
02:10:01,585 --> 02:10:02,430
methodologies,

4857
02:10:02,430 --> 02:10:04,104
but I think similar principles

4858
02:10:04,104 --> 02:10:05,833
apply to clinical assessments.

4859
02:10:05,833 --> 02:10:07,585
We've already heard little bits

4860
02:10:07,585 --> 02:10:09,377
about sort of the difficulty of

4861
02:10:09,377 --> 02:10:10,071
traditional

4862
02:10:10,071 --> 02:10:11,702
polystynography, for example,

4863
02:10:11,702 --> 02:10:13,374
in certain neurodevelopmental

4864
02:10:13,374 --> 02:10:14,008
disorders.

4865
02:10:14,909 --> 02:10:16,159
I'd like to start with this

4866
02:10:16,159 --> 02:10:17,397
paper, which is relatively

4867
02:10:17,397 --> 02:10:17,778
recent.

4868
02:10:17,778 --> 02:10:19,436
This is from Matt Jones's group

4869
02:10:19,436 --> 02:10:21,130
at the University of Bristol in

4870
02:10:21,130 --> 02:10:21,949
the UK looking

4871
02:10:21,949 --> 02:10:22,912
at sleep spindles,

4872
02:10:22,912 --> 02:10:24,613
and you heard a talk about that

4873
02:10:24,613 --> 02:10:25,052
earlier

4874
02:10:25,052 --> 02:10:25,887
in this context.

4875
02:10:25,887 --> 02:10:28,389
22 Q 11.2 deletion syndrome.

4876
02:10:28,856 --> 02:10:30,680
This was I think a really

4877
02:10:30,680 --> 02:10:32,914
amazing study because they did

4878
02:10:32,914 --> 02:10:34,328
have an incredibly

4879
02:10:34,328 --> 02:10:36,437
exhaustive examination of the

4880
02:10:36,437 --> 02:10:38,293
sleep EEG in less than 50

4881
02:10:38,293 --> 02:10:40,001
participants in A22Q11

4882
02:10:40,001 --> 02:10:40,434
group.

4883
02:10:40,434 --> 02:10:41,872
And I highlight that because the

4884
02:10:41,872 --> 02:10:43,344
sample size is still quite small

4885
02:10:43,344 --> 02:10:43,804
given the

4886
02:10:43,804 --> 02:10:45,208
heterogeneity and presentations

4887
02:10:45,208 --> 02:10:46,370
that we know are in their

4888
02:10:46,370 --> 02:10:46,974
development.

4889
02:10:47,575 --> 02:10:48,576
And what were they able to see?

4890
02:10:48,576 --> 02:10:48,866
Well,

4891
02:10:48,866 --> 02:10:50,778
they they were able to show this

4892
02:10:50,778 --> 02:10:52,133
incredible topography of

4893
02:10:52,133 --> 02:10:53,974
differences across the scalp for

4894
02:10:53,974 --> 02:10:55,183
spindle features and

4895
02:10:55,183 --> 02:10:56,618
slow wave features in the

4896
02:10:56,618 --> 02:10:57,652
coupling thereof.

4897
02:10:58,419 --> 02:11:00,856
This incredibly rich mechanistic

4898
02:11:00,856 --> 02:11:03,113
approach, but also one that's

4899
02:11:03,113 --> 02:11:04,358
not scalable to

4900
02:11:04,358 --> 02:11:06,352
routine measurement in the

4901
02:11:06,352 --> 02:11:08,553
clinic or even in a research

4902
02:11:08,553 --> 02:11:09,497
laboratory.

4903
02:11:10,731 --> 02:11:12,667
The talk on on sleep spindles we

4904
02:11:12,667 --> 02:11:14,520
heard earlier talked about the

4905
02:11:14,520 --> 02:11:15,570
need to to scale

4906
02:11:15,570 --> 02:11:17,321
this up to larger studies and

4907
02:11:17,321 --> 02:11:18,739
bringing a high density

4908
02:11:18,739 --> 02:11:20,341
polysomnographic array to

4909
02:11:20,341 --> 02:11:21,533
those larger studies

4910
02:11:21,533 --> 02:11:22,843
is really hard to do.

4911
02:11:23,444 --> 02:11:24,527
Even traditional

4912
02:11:24,527 --> 02:11:26,249
polysomnography, the gold

4913
02:11:26,249 --> 02:11:28,316
standard of sleep research as

4914
02:11:28,316 --> 02:11:30,432
well as Sleep Medicine might be

4915
02:11:30,432 --> 02:11:31,252
burdensome,

4916
02:11:31,252 --> 02:11:32,863
more intolerable to some

4917
02:11:32,863 --> 02:11:33,956
individuals with

4918
02:11:33,956 --> 02:11:35,985
neurodevelopmental conditions

4919
02:11:35,985 --> 02:11:36,824
due to both

4920
02:11:36,824 --> 02:11:38,989
the intrusional component of the

4921
02:11:38,989 --> 02:11:40,932
wires and the sense of being

4922
02:11:40,932 --> 02:11:41,696
monitored.

4923
02:11:41,929 --> 02:11:43,853
The requirement to potentially

4924
02:11:43,853 --> 02:11:45,885
sleep in an unknown environment

4925
02:11:45,885 --> 02:11:46,867
such as a lab,

4926
02:11:46,867 --> 02:11:48,398
or even just the sensory

4927
02:11:48,398 --> 02:11:50,087
complexity of having these

4928
02:11:50,087 --> 02:11:51,906
sensors on your head and on

4929
02:11:51,906 --> 02:11:52,540
your body.

4930
02:11:52,873 --> 02:11:54,770
And that goes for both low

4931
02:11:54,770 --> 02:11:57,178
resolution EEG montages and PSG,

4932
02:11:57,178 --> 02:11:59,443
as well as state of the science

4933
02:11:59,443 --> 02:12:01,415
high density EEG montages.

4934
02:12:01,816 --> 02:12:02,297
So wow,

4935
02:12:02,297 --> 02:12:04,129
these tools are incredibly

4936
02:12:04,129 --> 02:12:05,186
meaningful for

4937
02:12:05,186 --> 02:12:06,854
parsing sleep Physiology.

4938
02:12:07,588 --> 02:12:09,041
They are both difficult,

4939
02:12:09,041 --> 02:12:10,836
burdensome, and in some cases

4940
02:12:10,836 --> 02:12:11,826
intolerable for

4941
02:12:11,826 --> 02:12:12,526
individuals.

4942
02:12:12,827 --> 02:12:13,995
So where does that leave us?

4943
02:12:14,695 --> 02:12:14,944
Well,

4944
02:12:14,944 --> 02:12:16,319
if we want to look at sleep

4945
02:12:16,319 --> 02:12:16,931
Physiology,

4946
02:12:16,931 --> 02:12:17,807
we actually have a

4947
02:12:17,807 --> 02:12:18,733
number of options.

4948
02:12:18,733 --> 02:12:20,184
On the left here we have that

4949
02:12:20,184 --> 02:12:21,535
traditional polysomnogram.

4950
02:12:22,169 --> 02:12:24,090
Then we can move out of the lab

4951
02:12:24,090 --> 02:12:26,073
into ambulatory polysonography.

4952
02:12:26,507 --> 02:12:28,397
And one step beyond that,

4953
02:12:28,397 --> 02:12:30,569
home sleep apnea testing and

4954
02:12:30,569 --> 02:12:31,345
other non

4955
02:12:31,345 --> 02:12:33,758
full PSG paradigms are beginning

4956
02:12:33,758 --> 02:12:35,416
to be explored again,

4957
02:12:35,416 --> 02:12:37,752
more so in adults than in kids.

4958
02:12:37,752 --> 02:12:39,063
Although comments were made

4959
02:12:39,063 --> 02:12:40,648
earlier about Ignacio Tapios and

4960
02:12:40,648 --> 02:12:41,589
Christiello's work

4961
02:12:41,589 --> 02:12:43,057
trying to look at this in kids.

4962
02:12:44,058 --> 02:12:46,260
On the right side of the graph

4963
02:12:46,260 --> 02:12:48,582
we have what I call these novel

4964
02:12:48,582 --> 02:12:49,930
new technologies.

4965
02:12:50,231 --> 02:12:51,854
In the intermediate we have a

4966
02:12:51,854 --> 02:12:53,701
slew of different EEG wearables.

4967
02:12:53,701 --> 02:12:54,735
These are all headbands.

4968
02:12:54,735 --> 02:12:56,070
I just highlighted 3 of them.

4969
02:12:56,504 --> 02:12:57,951
As Demetrius commented,

4970
02:12:57,951 --> 02:12:59,889
the the state of this field is

4971
02:12:59,889 --> 02:13:00,341
really

4972
02:13:00,341 --> 02:13:01,676
changing dynamically.

4973
02:13:01,676 --> 02:13:02,921
There's new instruments coming

4974
02:13:02,921 --> 02:13:03,544
out every day.

4975
02:13:03,778 --> 02:13:05,347
Here are three of of what I

4976
02:13:05,347 --> 02:13:07,022
think are are among the most

4977
02:13:07,022 --> 02:13:07,381
used.

4978
02:13:07,381 --> 02:13:08,748
The Dream Headband, the

4979
02:13:08,748 --> 02:13:10,561
Hypnodyne Z Max, and the Muse,

4980
02:13:10,561 --> 02:13:12,253
all of which are headbands.

4981
02:13:12,253 --> 02:13:13,777
All of which requires something

4982
02:13:13,777 --> 02:13:15,336
sort of relatively constricting

4983
02:13:15,336 --> 02:13:15,990
on the head.

4984
02:13:16,524 --> 02:13:18,013
And then in the far right is a,

4985
02:13:18,013 --> 02:13:19,446
is a instrument that's that's

4986
02:13:19,446 --> 02:13:19,694
just

4987
02:13:19,694 --> 02:13:21,169
emerging that actually takes it

4988
02:13:21,169 --> 02:13:22,582
one step further, gets rid of

4989
02:13:22,582 --> 02:13:23,264
the headband,

4990
02:13:23,264 --> 02:13:24,618
but still you have a sensory

4991
02:13:24,618 --> 02:13:25,633
sticker on the head.

4992
02:13:25,633 --> 02:13:27,243
And some individuals, you know,

4993
02:13:27,243 --> 02:13:28,950
can respond to that in different

4994
02:13:28,950 --> 02:13:29,270
ways.

4995
02:13:29,704 --> 02:13:31,349
So we've gone from full scale

4996
02:13:31,349 --> 02:13:32,918
polysonography where we can

4997
02:13:32,918 --> 02:13:33,674
measure both

4998
02:13:33,674 --> 02:13:35,424
brain and peripheral signals to

4999
02:13:35,424 --> 02:13:37,151
some of these instruments that

5000
02:13:37,151 --> 02:13:38,245
maybe only measure

5001
02:13:38,245 --> 02:13:39,321
one or two channels

5002
02:13:39,321 --> 02:13:40,114
all together.

5003
02:13:41,549 --> 02:13:43,109
It might be great for looking at

5004
02:13:43,109 --> 02:13:44,555
things like sleep spindles or

5005
02:13:44,555 --> 02:13:45,353
slow waves that

5006
02:13:45,353 --> 02:13:46,744
are a function of the brain,

5007
02:13:46,744 --> 02:13:47,788
but ignore pulse ox.

5008
02:13:47,788 --> 02:13:48,872
We're not going to be able to

5009
02:13:48,872 --> 02:13:49,657
look at sleep apnea.

5010
02:13:49,657 --> 02:13:51,350
We're not going to be able to

5011
02:13:51,350 --> 02:13:53,160
look at restless leg syndrome,

5012
02:13:53,160 --> 02:13:54,965
periodic leg movements or other

5013
02:13:54,965 --> 02:13:56,130
peripheral signals.

5014
02:13:56,464 --> 02:13:58,739
So just switching to these, you

5015
02:13:58,739 --> 02:14:00,501
know, modern wearables,

5016
02:14:00,501 --> 02:14:02,536
it gets us one step further.

5017
02:14:02,536 --> 02:14:04,226
We can do those large scale

5018
02:14:04,226 --> 02:14:06,081
studies where we can scale up

5019
02:14:06,081 --> 02:14:07,041
who is able to

5020
02:14:07,041 --> 02:14:08,932
participate in maybe crossover

5021
02:14:08,932 --> 02:14:10,933
some of the sensory barriers or

5022
02:14:10,933 --> 02:14:11,579
the other

5023
02:14:11,579 --> 02:14:13,275
limitations of environment,

5024
02:14:13,275 --> 02:14:15,349
but it hinders us in other ways.

5025
02:14:16,617 --> 02:14:18,145
And so I want to think, you

5026
02:14:18,145 --> 02:14:19,999
know, just one comment about the

5027
02:14:19,999 --> 02:14:20,521
clinical

5028
02:14:20,521 --> 02:14:22,207
applicability of some of this,

5029
02:14:22,207 --> 02:14:23,930
you know, this is that work by

5030
02:14:23,930 --> 02:14:24,792
Chris that was

5031
02:14:24,792 --> 02:14:26,309
mentioned earlier about the

5032
02:14:26,309 --> 02:14:28,088
feasibility of home sleep apnea

5033
02:14:28,088 --> 02:14:29,063
testing and Down

5034
02:14:29,063 --> 02:14:29,563
syndrome.

5035
02:14:30,030 --> 02:14:31,992
You know, we need to be thinking

5036
02:14:31,992 --> 02:14:32,666
about, OK,

5037
02:14:32,666 --> 02:14:34,467
even for an evaluation in the

5038
02:14:34,467 --> 02:14:35,336
sleep clinic,

5039
02:14:35,336 --> 02:14:36,860
how are we adopting these

5040
02:14:36,860 --> 02:14:38,663
procedures that are the bread

5041
02:14:38,663 --> 02:14:39,907
and butter of sleep

5042
02:14:39,907 --> 02:14:41,612
assessments in adults and in

5043
02:14:41,612 --> 02:14:43,537
kids without neurodevelopmental

5044
02:14:43,537 --> 02:14:44,779
conditions to these

5045
02:14:44,779 --> 02:14:45,946
unique populations?

5046
02:14:46,180 --> 02:14:48,006
And the solutions might be

5047
02:14:48,006 --> 02:14:50,085
different for different ND DS

5048
02:14:50,085 --> 02:14:51,519
that have different

5049
02:14:51,519 --> 02:14:53,353
collections of, of sensory

5050
02:14:53,353 --> 02:14:55,085
experiences, tolerances,

5051
02:14:55,085 --> 02:14:56,457
cognitive ability,

5052
02:14:56,457 --> 02:14:58,582
and the necessity for parental

5053
02:14:58,582 --> 02:15:00,113
environment caregiver

5054
02:15:00,113 --> 02:15:01,061
involvement.

5055
02:15:03,330 --> 02:15:04,972
So I want to switch gears and

5056
02:15:04,972 --> 02:15:06,777
talk a little bit about another

5057
02:15:06,777 --> 02:15:07,067
Ave.

5058
02:15:07,067 --> 02:15:07,735
of assessment.

5059
02:15:07,735 --> 02:15:08,505
That's again,

5060
02:15:08,505 --> 02:15:10,455
sort of the traditional measures

5061
02:15:10,455 --> 02:15:10,638
of

5062
02:15:10,638 --> 02:15:12,170
behavioral Sleep Medicine,

5063
02:15:12,170 --> 02:15:13,407
which is actigraphy.

5064
02:15:13,707 --> 02:15:15,843
We can learn a tremendous amount

5065
02:15:15,843 --> 02:15:17,754
about sleep from octographic

5066
02:15:17,754 --> 02:15:18,846
estimated sleep

5067
02:15:18,846 --> 02:15:20,614
and, and, and wake rhythms.

5068
02:15:21,048 --> 02:15:22,874
These tools are used in the lab

5069
02:15:22,874 --> 02:15:24,819
as well as the clinic every day.

5070
02:15:24,819 --> 02:15:25,866
And on the far left,

5071
02:15:25,866 --> 02:15:27,371
we have what I call the gold

5072
02:15:27,371 --> 02:15:27,855
standard

5073
02:15:27,855 --> 02:15:29,323
traditional sleep octographs.

5074
02:15:29,723 --> 02:15:31,426
The one here is the AMI micro

5075
02:15:31,426 --> 02:15:32,660
micro motion logger.

5076
02:15:32,660 --> 02:15:34,601
Phillips was in many individuals

5077
02:15:34,601 --> 02:15:36,351
labs up until a couple years

5078
02:15:36,351 --> 02:15:36,664
ago.

5079
02:15:37,231 --> 02:15:38,199
We take one step to

5080
02:15:38,199 --> 02:15:39,166
the right of that.

5081
02:15:39,166 --> 02:15:40,591
We have instruments that are

5082
02:15:40,591 --> 02:15:42,251
widely used in research, but not

5083
02:15:42,251 --> 02:15:43,237
in sleep research,

5084
02:15:43,237 --> 02:15:44,872
the actigraph being one of them.

5085
02:15:44,872 --> 02:15:45,696
That's that's,

5086
02:15:45,696 --> 02:15:47,566
that's only now developing sort

5087
02:15:47,566 --> 02:15:48,108
of their

5088
02:15:48,108 --> 02:15:49,543
tools for sleep and wake.

5089
02:15:50,244 --> 02:15:51,286
One step further,

5090
02:15:51,286 --> 02:15:53,048
we have these open source or

5091
02:15:53,048 --> 02:15:53,614
wearable

5092
02:15:53,614 --> 02:15:55,422
octagraphs that are bare bones

5093
02:15:55,422 --> 02:15:57,342
accelerometers or even a Garmin

5094
02:15:57,342 --> 02:15:57,651
type

5095
02:15:57,651 --> 02:15:59,354
device or Fitbit type device

5096
02:15:59,354 --> 02:16:01,157
that aren't even designed for

5097
02:16:01,157 --> 02:16:02,089
research grade

5098
02:16:02,089 --> 02:16:03,602
accelerometry but give us

5099
02:16:03,602 --> 02:16:04,692
interesting data.

5100
02:16:05,392 --> 02:16:07,153
And then in the far right of

5101
02:16:07,153 --> 02:16:09,206
this we have the novel wearables

5102
02:16:09,206 --> 02:16:10,297
and veneerables,

5103
02:16:10,297 --> 02:16:12,313
things that are in the room that

5104
02:16:12,313 --> 02:16:14,114
might help us differentially

5105
02:16:14,114 --> 02:16:15,336
capture aspects of

5106
02:16:15,336 --> 02:16:15,703
sleep.

5107
02:16:16,136 --> 02:16:18,045
All of this is an open box for

5108
02:16:18,045 --> 02:16:18,873
exploration,

5109
02:16:18,873 --> 02:16:20,818
particularly when we talk about

5110
02:16:20,818 --> 02:16:21,850
individuals with

5111
02:16:21,850 --> 02:16:23,077
neurodevelopmental

5112
02:16:23,077 --> 02:16:23,711
disorders.

5113
02:16:25,045 --> 02:16:26,295
I want to spend a couple of

5114
02:16:26,295 --> 02:16:27,476
minutes talking about the

5115
02:16:27,476 --> 02:16:28,516
difficulties of doing

5116
02:16:28,516 --> 02:16:29,640
traditional lactography,

5117
02:16:29,640 --> 02:16:30,951
which is the gold standard,

5118
02:16:30,951 --> 02:16:32,158
highly stable estimate of

5119
02:16:32,158 --> 02:16:33,220
sleeping wakefulness.

5120
02:16:33,220 --> 02:16:34,455
It's been around for decades.

5121
02:16:34,455 --> 02:16:36,032
It's highly predictive of

5122
02:16:36,032 --> 02:16:37,392
sleeping wake against

5123
02:16:37,392 --> 02:16:38,492
polystomography,

5124
02:16:38,492 --> 02:16:40,227
but it comes with some cons.

5125
02:16:40,628 --> 02:16:42,388
It is costly relative to some of

5126
02:16:42,388 --> 02:16:44,022
those novel wearables that we

5127
02:16:44,022 --> 02:16:44,698
have today.

5128
02:16:45,266 --> 02:16:46,447
The ergonomics, again,

5129
02:16:46,447 --> 02:16:48,152
some individuals can't tolerate

5130
02:16:48,152 --> 02:16:48,702
wearing a

5131
02:16:48,702 --> 02:16:49,485
watch for both

5132
02:16:49,485 --> 02:16:51,129
neurodevelopmental reasons as

5133
02:16:51,129 --> 02:16:52,642
well as a neuropsychiatric

5134
02:16:52,642 --> 02:16:53,340
conditions.

5135
02:16:53,340 --> 02:16:54,898
Individuals will will not

5136
02:16:54,898 --> 02:16:56,644
tolerate wearing the watch.

5137
02:16:56,644 --> 02:16:57,711
It needs to stay on.

5138
02:16:57,711 --> 02:16:58,253
Once it's off,

5139
02:16:58,253 --> 02:16:59,129
we don't have any more

5140
02:16:59,129 --> 02:16:59,647
measurement.

5141
02:17:00,447 --> 02:17:01,678
Traditional sleep wake

5142
02:17:01,678 --> 02:17:03,390
actigraphy is highly dependent

5143
02:17:03,390 --> 02:17:04,418
on sleep Diaries,

5144
02:17:04,418 --> 02:17:06,231
either by the individual or by a

5145
02:17:06,231 --> 02:17:06,854
caregiver,

5146
02:17:06,854 --> 02:17:08,540
and then the scoring decisions

5147
02:17:08,540 --> 02:17:09,979
that get made using those

5148
02:17:09,979 --> 02:17:10,958
Diaries to get a

5149
02:17:10,958 --> 02:17:11,926
reliable estimate.

5150
02:17:12,426 --> 02:17:14,600
When we say actigraphy is well

5151
02:17:14,600 --> 02:17:15,869
validated against

5152
02:17:15,869 --> 02:17:17,064
polysonography,

5153
02:17:17,064 --> 02:17:19,248
we assume all of these factors

5154
02:17:19,248 --> 02:17:21,420
are in order, the Diaries are

5155
02:17:21,420 --> 02:17:21,869
good,

5156
02:17:21,869 --> 02:17:23,834
and scoring rules are using

5157
02:17:23,834 --> 02:17:25,873
validated methods to do so.

5158
02:17:26,206 --> 02:17:27,713
If you break any one of those

5159
02:17:27,713 --> 02:17:29,144
things, the validity of the

5160
02:17:29,144 --> 02:17:30,311
instrument goes down.

5161
02:17:30,978 --> 02:17:31,665
Moreover,

5162
02:17:31,665 --> 02:17:33,786
actigraphy is an incredibly

5163
02:17:33,786 --> 02:17:34,415
limited

5164
02:17:34,415 --> 02:17:35,316
assessment.

5165
02:17:35,316 --> 02:17:36,617
It gives us activity.

5166
02:17:36,617 --> 02:17:37,701
From the activity,

5167
02:17:37,701 --> 02:17:39,386
we estimate sleep and wake.

5168
02:17:39,386 --> 02:17:41,043
We maybe have light in some

5169
02:17:41,043 --> 02:17:42,369
devices, we have body

5170
02:17:42,369 --> 02:17:43,190
temperature,

5171
02:17:43,190 --> 02:17:45,113
but we're relatively limited in

5172
02:17:45,113 --> 02:17:47,022
some of these other peripheral

5173
02:17:47,022 --> 02:17:47,595
signals.

5174
02:17:48,128 --> 02:17:49,029
So what do we get?

5175
02:17:49,029 --> 02:17:50,658
We get a beautiful octogram that

5176
02:17:50,658 --> 02:17:52,269
tells us a lot about sleep wake

5177
02:17:52,269 --> 02:17:53,100
rhythms when we

5178
02:17:53,100 --> 02:17:54,268
score it appropriately.

5179
02:17:54,268 --> 02:17:55,902
This is a child with ADHD from

5180
02:17:55,902 --> 02:17:56,937
one of my studies.

5181
02:17:56,937 --> 02:17:58,498
You can see a little bit of

5182
02:17:58,498 --> 02:18:00,174
irregularity in their sleep.

5183
02:18:01,609 --> 02:18:03,811
I want to highlight a discussion

5184
02:18:03,811 --> 02:18:06,060
that's going on and this is Lisa

5185
02:18:06,060 --> 02:18:07,114
Meltzer's work

5186
02:18:07,114 --> 02:18:09,247
to really evaluate the rules we

5187
02:18:09,247 --> 02:18:10,933
use for evaluating sleep

5188
02:18:10,933 --> 02:18:12,620
actigraphy in pediatric

5189
02:18:12,620 --> 02:18:13,187
samples.

5190
02:18:13,420 --> 02:18:15,497
It is not as simple as finding

5191
02:18:15,497 --> 02:18:17,703
sleep the way we find it on the

5192
02:18:17,703 --> 02:18:18,058
EEG.

5193
02:18:18,058 --> 02:18:19,388
We have assumptions that get

5194
02:18:19,388 --> 02:18:20,527
made from the activity.

5195
02:18:21,095 --> 02:18:23,182
One of the traditional rules

5196
02:18:23,182 --> 02:18:25,388
that are used is that we look

5197
02:18:25,388 --> 02:18:26,834
for unconsolidated

5198
02:18:26,834 --> 02:18:29,136
sleep to define the sleep out.

5199
02:18:29,136 --> 02:18:31,129
We could be looking for three

5200
02:18:31,129 --> 02:18:32,573
minutes, 10 minutes,

5201
02:18:32,573 --> 02:18:34,769
15 minutes of of low activity on

5202
02:18:34,769 --> 02:18:36,884
the actigraph rhythm to define

5203
02:18:36,884 --> 02:18:37,378
sleep.

5204
02:18:37,745 --> 02:18:38,056
Well,

5205
02:18:38,056 --> 02:18:40,098
there were consequences to these

5206
02:18:40,098 --> 02:18:40,481
rules

5207
02:18:40,481 --> 02:18:42,468
and I think they come to bear on

5208
02:18:42,468 --> 02:18:44,518
understanding neurodevelopmental

5209
02:18:44,518 --> 02:18:46,437
conditions where sleep is not a

5210
02:18:46,437 --> 02:18:48,355
stable phenomenon necessarily.

5211
02:18:48,989 --> 02:18:50,745
This is an example octogram from

5212
02:18:50,745 --> 02:18:52,205
a child with a psychiatric

5213
02:18:52,205 --> 02:18:53,160
condition that's

5214
02:18:53,160 --> 02:18:54,428
recorded in our center.

5215
02:18:54,828 --> 02:18:56,250
And I think, you know,

5216
02:18:56,250 --> 02:18:58,237
if you're looking at in in red

5217
02:18:58,237 --> 02:18:58,899
are areas

5218
02:18:58,899 --> 02:19:00,904
where our traditional algorithm

5219
02:19:00,904 --> 02:19:02,884
see sleep and you see this red

5220
02:19:02,884 --> 02:19:04,138
throughout the day

5221
02:19:04,138 --> 02:19:05,409
because the child is

5222
02:19:05,409 --> 02:19:06,807
relatively sedentary.

5223
02:19:07,708 --> 02:19:09,223
So if you were to just squint

5224
02:19:09,223 --> 02:19:10,477
and say where is sleep,

5225
02:19:10,477 --> 02:19:11,596
you would I think find

5226
02:19:11,596 --> 02:19:12,613
it reasonably well.

5227
02:19:12,846 --> 02:19:14,648
But how do we put that into an

5228
02:19:14,648 --> 02:19:16,150
algorithm's perspective?

5229
02:19:16,150 --> 02:19:17,994
Where do we begin the night and

5230
02:19:17,994 --> 02:19:18,886
end the night,

5231
02:19:18,886 --> 02:19:20,665
particularly for an individual

5232
02:19:20,665 --> 02:19:22,427
whose cognitive abilities and

5233
02:19:22,427 --> 02:19:23,157
psychiatric

5234
02:19:23,157 --> 02:19:25,002
comorbidities might be blocking

5235
02:19:25,002 --> 02:19:26,708
their ability to do accurate

5236
02:19:26,708 --> 02:19:27,561
recall on the

5237
02:19:27,561 --> 02:19:28,670
sleep diary, how do

5238
02:19:28,670 --> 02:19:29,897
we define the night?

5239
02:19:30,764 --> 02:19:32,031
And so our group has been

5240
02:19:32,031 --> 02:19:33,500
interested in this recently.

5241
02:19:33,500 --> 02:19:34,797
We've been re evaluating

5242
02:19:34,797 --> 02:19:35,769
the rules we use.

5243
02:19:35,769 --> 02:19:37,495
And this is just an example of

5244
02:19:37,495 --> 02:19:39,106
how we can alter the rules.

5245
02:19:39,740 --> 02:19:41,742
So if we go from three minutes

5246
02:19:41,742 --> 02:19:43,579
to set to onset sleep and 5

5247
02:19:43,579 --> 02:19:45,212
minutes to offset sleep

5248
02:19:45,212 --> 02:19:47,363
versus looking for 15 minutes of

5249
02:19:47,363 --> 02:19:49,301
consolidated sleep on either

5250
02:19:49,301 --> 02:19:49,717
side,

5251
02:19:49,717 --> 02:19:51,522
we actually can reduce the

5252
02:19:51,522 --> 02:19:53,664
amount of ambiguities by about

5253
02:19:53,664 --> 02:19:54,021
50%.

5254
02:19:54,021 --> 02:19:54,901
But in doing that,

5255
02:19:54,901 --> 02:19:56,456
we are also shrinking the sleep

5256
02:19:56,456 --> 02:19:56,857
periods

5257
02:19:56,857 --> 02:19:58,192
that we're scoring, right.

5258
02:19:58,192 --> 02:19:59,806
We're moving the sleep estimate

5259
02:19:59,806 --> 02:20:01,400
and that might be meaning that

5260
02:20:01,400 --> 02:20:02,463
might be meaningful

5261
02:20:02,463 --> 02:20:04,131
when we have to care about sleep

5262
02:20:04,131 --> 02:20:05,675
and make recommendations on a

5263
02:20:05,675 --> 02:20:06,633
one to one level.

5264
02:20:06,834 --> 02:20:08,228
The variance will hold the same

5265
02:20:08,228 --> 02:20:09,201
when we look at group

5266
02:20:09,201 --> 02:20:09,803
differences.

5267
02:20:10,204 --> 02:20:11,302
But how does this translate

5268
02:20:11,302 --> 02:20:12,134
clinically into your

5269
02:20:12,134 --> 02:20:13,173
recommendations for your

5270
02:20:13,173 --> 02:20:13,707
patients?

5271
02:20:13,707 --> 02:20:15,150
We have to think very carefully

5272
02:20:15,150 --> 02:20:15,709
about this.

5273
02:20:15,709 --> 02:20:16,822
Where do we decide

5274
02:20:16,822 --> 02:20:18,245
sleep begins and ends?

5275
02:20:18,245 --> 02:20:20,450
Even at traditional active graph

5276
02:20:20,450 --> 02:20:22,423
level, the scoring is highly

5277
02:20:22,423 --> 02:20:23,550
time consuming.

5278
02:20:23,550 --> 02:20:25,756
It relies on those Diaries that

5279
02:20:25,756 --> 02:20:27,950
I mentioned and whether or not

5280
02:20:27,950 --> 02:20:28,388
those

5281
02:20:28,388 --> 02:20:29,927
Diaries are filled out

5282
02:20:29,927 --> 02:20:31,325
every single night.

5283
02:20:31,325 --> 02:20:31,991
Are they filled out

5284
02:20:31,991 --> 02:20:32,693
by the participant?

5285
02:20:32,693 --> 02:20:33,594
By the caregiver?

5286
02:20:33,594 --> 02:20:35,926
How much can we ask, when do we

5287
02:20:35,926 --> 02:20:37,731
ask, and who do we ask?

5288
02:20:38,098 --> 02:20:40,014
And how do we judge the data

5289
02:20:40,014 --> 02:20:41,898
quality of those Diaries in

5290
02:20:41,898 --> 02:20:43,504
order to make accurate

5291
02:20:43,504 --> 02:20:45,405
scoring of our actigraphy?

5292
02:20:45,405 --> 02:20:47,472
All of this is usually a human

5293
02:20:47,472 --> 02:20:49,676
process and I want to make a a,

5294
02:20:49,676 --> 02:20:51,457
a a a plea that one of the

5295
02:20:51,457 --> 02:20:53,554
things that I think might help

5296
02:20:53,554 --> 02:20:54,882
us translate these

5297
02:20:54,882 --> 02:20:56,728
methods to places where the

5298
02:20:56,728 --> 02:20:58,820
sleep scoring of actigraphy is

5299
02:20:58,820 --> 02:21:00,354
not as cut and dry in

5300
02:21:00,354 --> 02:21:02,542
neurodevelopmental disorders are

5301
02:21:02,542 --> 02:21:04,525
these data-driven solutions?

5302
02:21:04,525 --> 02:21:06,175
And here are just two of them

5303
02:21:06,175 --> 02:21:07,811
that I think are taking some

5304
02:21:07,811 --> 02:21:08,395
traction,

5305
02:21:08,395 --> 02:21:09,630
GGIR and active sleep.

5306
02:21:09,630 --> 02:21:10,184
These are two

5307
02:21:10,184 --> 02:21:11,165
different R pipelines.

5308
02:21:11,465 --> 02:21:13,116
I did not write them, others

5309
02:21:13,116 --> 02:21:14,744
did, but they are solving a

5310
02:21:14,744 --> 02:21:15,769
similar problem.

5311
02:21:16,336 --> 02:21:18,541
How can we take device agnostic

5312
02:21:18,541 --> 02:21:20,796
data, feed them through unified

5313
02:21:20,796 --> 02:21:21,742
pipelines to

5314
02:21:21,742 --> 02:21:23,455
produce reproducible and

5315
02:21:23,455 --> 02:21:24,812
scalable analysis?

5316
02:21:25,913 --> 02:21:27,381
There's a lot of power to that.

5317
02:21:27,648 --> 02:21:29,261
The problem is they're not well

5318
02:21:29,261 --> 02:21:30,250
validated in kids,

5319
02:21:30,250 --> 02:21:31,759
they're not well validated in

5320
02:21:31,759 --> 02:21:33,320
neurodevelopmental disorders,

5321
02:21:33,320 --> 02:21:34,864
and they require working with,

5322
02:21:34,864 --> 02:21:36,343
you know, software coding to

5323
02:21:36,343 --> 02:21:36,924
make work.

5324
02:21:36,924 --> 02:21:38,427
They're not quite as plug and

5325
02:21:38,427 --> 02:21:39,827
play or clinically useful.

5326
02:21:41,128 --> 02:21:42,381
So what if we leave

5327
02:21:42,381 --> 02:21:43,897
actigraphy altogether?

5328
02:21:44,565 --> 02:21:46,153
There's been an incredible

5329
02:21:46,153 --> 02:21:48,023
proliferation of wearables and

5330
02:21:48,023 --> 02:21:49,269
narrables for sleep

5331
02:21:49,269 --> 02:21:49,970
measurement.

5332
02:21:49,970 --> 02:21:51,004
We have the Nanate over here.

5333
02:21:51,004 --> 02:21:52,673
It's a video stenography device.

5334
02:21:52,673 --> 02:21:53,525
On the left we

5335
02:21:53,525 --> 02:21:54,741
have mattress pads.

5336
02:21:54,741 --> 02:21:56,409
We have things that are ambient

5337
02:21:56,409 --> 02:21:57,626
in the room, measuring

5338
02:21:57,626 --> 02:21:58,345
temperature,

5339
02:21:58,345 --> 02:21:59,213
measuring sound,

5340
02:21:59,213 --> 02:22:00,948
measuring humidity in the room.

5341
02:22:00,948 --> 02:22:02,719
There's been some incredible

5342
02:22:02,719 --> 02:22:04,398
work using temperature and

5343
02:22:04,398 --> 02:22:05,819
humidity and sound to

5344
02:22:05,819 --> 02:22:07,344
look at sleep disordered

5345
02:22:07,344 --> 02:22:09,122
breathing as sort of the X,

5346
02:22:09,122 --> 02:22:10,626
the exhalation component

5347
02:22:10,626 --> 02:22:11,692
of the disorder.

5348
02:22:12,259 --> 02:22:14,205
And then we have our rings and

5349
02:22:14,205 --> 02:22:16,332
our wearable wrist monitors like

5350
02:22:16,332 --> 02:22:16,864
Fitbit.

5351
02:22:17,097 --> 02:22:18,815
These are highly innovative,

5352
02:22:18,815 --> 02:22:20,534
passive of data collection,

5353
02:22:20,534 --> 02:22:22,348
often no intervention from the

5354
02:22:22,348 --> 02:22:23,844
researcher, no diary, no

5355
02:22:23,844 --> 02:22:24,404
scoring.

5356
02:22:24,671 --> 02:22:26,232
And they often get us many other

5357
02:22:26,232 --> 02:22:27,841
things, cardiovascular function,

5358
02:22:27,841 --> 02:22:28,962
heart rate variability,

5359
02:22:28,962 --> 02:22:30,561
temperature, light, sound and so

5360
02:22:30,561 --> 02:22:30,911
forth.

5361
02:22:31,745 --> 02:22:32,652
But once again,

5362
02:22:32,652 --> 02:22:34,514
we're often dealing with black

5363
02:22:34,514 --> 02:22:34,948
boxes,

5364
02:22:34,948 --> 02:22:36,159
changing algorithms,

5365
02:22:36,159 --> 02:22:37,551
subscription services,

5366
02:22:37,551 --> 02:22:39,112
unclear ownership of data,

5367
02:22:39,112 --> 02:22:40,407
and very few of these

5368
02:22:40,407 --> 02:22:41,455
instruments have

5369
02:22:41,455 --> 02:22:43,380
been tested in kids or adults or

5370
02:22:43,380 --> 02:22:45,047
kids with nerve development

5371
02:22:45,047 --> 02:22:45,726
disorders.

5372
02:22:46,026 --> 02:22:47,989
So everything has a caveat and

5373
02:22:47,989 --> 02:22:50,128
that has really pushed the field

5374
02:22:50,128 --> 02:22:51,064
to I think be

5375
02:22:51,064 --> 02:22:53,014
much more proactive in saying,

5376
02:22:53,014 --> 02:22:54,940
OK, you can go out and use an

5377
02:22:54,940 --> 02:22:56,003
instrument that

5378
02:22:56,003 --> 02:22:57,713
appears attractive to your

5379
02:22:57,713 --> 02:22:59,799
context, but let's do some work

5380
02:22:59,799 --> 02:23:00,674
to validate.

5381
02:23:01,174 --> 02:23:03,179
And Luca Mangini and others have

5382
02:23:03,179 --> 02:23:05,245
recently put out this framework,

5383
02:23:05,245 --> 02:23:06,812
which I think is really a

5384
02:23:06,812 --> 02:23:08,789
beautiful step by step approach

5385
02:23:08,789 --> 02:23:10,384
to how we evaluate these

5386
02:23:10,384 --> 02:23:12,323
trackers that we might purchase

5387
02:23:12,323 --> 02:23:14,303
and how do we determine what is

5388
02:23:14,303 --> 02:23:15,389
and is not ready

5389
02:23:15,389 --> 02:23:16,189
for research.

5390
02:23:17,424 --> 02:23:19,363
That's been summarized in this

5391
02:23:19,363 --> 02:23:21,211
lovely paper in Sleep Health

5392
02:23:21,211 --> 02:23:22,596
last year by Ju Ong,

5393
02:23:22,596 --> 02:23:24,271
where they took actually a

5394
02:23:24,271 --> 02:23:26,378
number of different tractors and

5395
02:23:26,378 --> 02:23:27,234
came to some

5396
02:23:27,234 --> 02:23:28,268
recommendations.

5397
02:23:28,769 --> 02:23:30,315
One being that, yeah,

5398
02:23:30,315 --> 02:23:32,661
we actually can get some pretty

5399
02:23:32,661 --> 02:23:33,040
good

5400
02:23:33,040 --> 02:23:34,868
Physiology from these EEG

5401
02:23:34,868 --> 02:23:37,180
wearables where we require that

5402
02:23:37,180 --> 02:23:38,745
degree of stability.

5403
02:23:39,746 --> 02:23:40,890
On the other hand,

5404
02:23:40,890 --> 02:23:42,657
we can go to these consumer

5405
02:23:42,657 --> 02:23:43,050
grade

5406
02:23:43,050 --> 02:23:44,636
trackers and we can get a

5407
02:23:44,636 --> 02:23:46,581
reasonable balance of accuracy

5408
02:23:46,581 --> 02:23:47,554
and tolerance,

5409
02:23:47,554 --> 02:23:49,274
but maybe only for healthy

5410
02:23:49,274 --> 02:23:51,258
sleepers and their and their.

5411
02:23:51,258 --> 02:23:52,465
And this is all a quote from

5412
02:23:52,465 --> 02:23:53,655
their conclusions because I

5413
02:23:53,655 --> 02:23:54,361
think it really

5414
02:23:54,361 --> 02:23:54,828
sums it up.

5415
02:23:54,828 --> 02:23:55,959
Lovely healthy sleepers,

5416
02:23:55,959 --> 02:23:57,169
individuals without sleep

5417
02:23:57,169 --> 02:23:57,798
problems and

5418
02:23:57,798 --> 02:23:59,180
certainly individuals without

5419
02:23:59,180 --> 02:24:00,211
neurodevelopmental or

5420
02:24:00,211 --> 02:24:00,801
psychiatric

5421
02:24:00,801 --> 02:24:01,301
conditions.

5422
02:24:01,835 --> 02:24:03,524
And then they issue the low cost

5423
02:24:03,524 --> 02:24:04,738
trackers all together,

5424
02:24:04,738 --> 02:24:06,274
the very cheap accelerometers

5425
02:24:06,274 --> 02:24:07,787
that you can buy because the

5426
02:24:07,787 --> 02:24:08,976
algorithms are really

5427
02:24:08,976 --> 02:24:09,710
not there yet.

5428
02:24:10,110 --> 02:24:10,837
So there's a lot

5429
02:24:10,837 --> 02:24:11,745
of work to be done.

5430
02:24:12,179 --> 02:24:14,183
I've only talked about a couple

5431
02:24:14,183 --> 02:24:16,229
of these of these opportunities

5432
02:24:16,229 --> 02:24:17,351
for measurement,

5433
02:24:17,351 --> 02:24:19,358
but even if you're not going to

5434
02:24:19,358 --> 02:24:20,889
put an instrument on an

5435
02:24:20,889 --> 02:24:21,688
individual,

5436
02:24:21,688 --> 02:24:23,488
I want to make a case that a

5437
02:24:23,488 --> 02:24:25,454
simple self reporter recall is

5438
02:24:25,454 --> 02:24:26,960
equally informative of

5439
02:24:26,960 --> 02:24:27,728
some things.

5440
02:24:28,128 --> 02:24:29,957
You know, during the ADHD talk

5441
02:24:29,957 --> 02:24:31,885
earlier, we heard that a kid or

5442
02:24:31,885 --> 02:24:33,066
an adult with ADHD

5443
02:24:33,066 --> 02:24:34,968
needs to be evaluated for sleep.

5444
02:24:35,569 --> 02:24:37,153
That simple evaluation

5445
02:24:37,153 --> 02:24:38,305
can shed light.

5446
02:24:38,605 --> 02:24:40,037
And this was some work that we

5447
02:24:40,037 --> 02:24:41,304
did in autism in the Rhode

5448
02:24:41,304 --> 02:24:42,376
Island Consortium for

5449
02:24:42,376 --> 02:24:42,709
Autism.

5450
02:24:43,310 --> 02:24:44,711
We need to wrap it up.

5451
02:24:44,711 --> 02:24:45,445
I'm going to close

5452
02:24:45,445 --> 02:24:46,179
in just a second.

5453
02:24:46,780 --> 02:24:47,881
OK, I'm going to close

5454
02:24:47,881 --> 02:24:48,782
in just a second.

5455
02:24:48,782 --> 02:24:50,644
But just to make the point that

5456
02:24:50,644 --> 02:24:52,493
asking about sleep matters and

5457
02:24:52,493 --> 02:24:52,986
you can

5458
02:24:52,986 --> 02:24:54,421
distinguish A diagnosis.

5459
02:24:54,821 --> 02:24:55,689
So take homes.

5460
02:24:56,089 --> 02:24:56,952
These are all things

5461
02:24:56,952 --> 02:24:57,858
that everyone knows.

5462
02:24:57,858 --> 02:24:59,292
I apologize for going over time.

5463
02:24:59,292 --> 02:25:01,087
I added a couple of of slides as

5464
02:25:01,087 --> 02:25:01,928
we were going.

5465
02:25:02,229 --> 02:25:03,470
But basically ask critical

5466
02:25:03,470 --> 02:25:04,891
questions of what you want to

5467
02:25:04,891 --> 02:25:05,332
measure,

5468
02:25:05,332 --> 02:25:06,776
who you're measuring it in and

5469
02:25:06,776 --> 02:25:07,862
what the needs of your

5470
02:25:07,862 --> 02:25:08,702
measurement are.

5471
02:25:09,036 --> 02:25:10,285
Reach out and thank

5472
02:25:10,285 --> 02:25:11,271
you very much.

5473
02:25:12,939 --> 02:25:13,874
Thank you, Jared.

5474
02:25:14,775 --> 02:25:16,367
If you have questions for Jared,

5475
02:25:16,367 --> 02:25:17,811
you can put them in the Q&A.

5476
02:25:17,811 --> 02:25:20,010
We can perhaps get to them at

5477
02:25:20,010 --> 02:25:21,982
the end of the day today.

5478
02:25:21,982 --> 02:25:23,796
We have some time for a panel

5479
02:25:23,796 --> 02:25:24,985
discussion in Q&A.

5480
02:25:25,619 --> 02:25:27,252
Our next speaker today

5481
02:25:27,252 --> 02:25:28,588
is Annette Estes.

5482
02:25:28,588 --> 02:25:30,008
She's an adjunct Assistant

5483
02:25:30,008 --> 02:25:31,400
Research Professor in the

5484
02:25:31,400 --> 02:25:32,793
Department of Psychology

5485
02:25:32,793 --> 02:25:34,528
at the University of Washington.

5486
02:25:34,995 --> 02:25:36,129
She's director of the

5487
02:25:36,129 --> 02:25:37,264
Autism Center there.

5488
02:25:37,564 --> 02:25:39,700
She is especially interested in

5489
02:25:39,700 --> 02:25:41,461
the role of the family in

5490
02:25:41,461 --> 02:25:42,869
supporting positive

5491
02:25:42,869 --> 02:25:44,660
outcomes for children with

5492
02:25:44,660 --> 02:25:46,767
disabilities and improving the

5493
02:25:46,767 --> 02:25:48,241
lives of people with

5494
02:25:48,241 --> 02:25:48,508
ASD.

5495
02:25:49,076 --> 02:25:51,029
She will describe the use of

5496
02:25:51,029 --> 02:25:53,250
cohort studies that can improve

5497
02:25:53,250 --> 02:25:53,680
early

5498
02:25:53,680 --> 02:25:55,782
recognition of infants at risk

5499
02:25:55,782 --> 02:25:57,856
for autism and identify brain

5500
02:25:57,856 --> 02:25:59,286
mechanisms that may

5501
02:25:59,286 --> 02:26:01,389
need lead to new strategies to

5502
02:26:01,389 --> 02:26:03,404
prevent or ameliorate autism

5503
02:26:03,404 --> 02:26:04,124
symptoms.

5504
02:26:05,492 --> 02:26:06,893
Annette, thank you.

5505
02:26:07,828 --> 02:26:08,704
Just to clarify,

5506
02:26:08,704 --> 02:26:09,999
I'm actually a research

5507
02:26:09,999 --> 02:26:10,730
professor in

5508
02:26:10,730 --> 02:26:12,278
speech and hearing sciences,

5509
02:26:12,278 --> 02:26:14,094
but I am a psychologist, so, you

5510
02:26:14,094 --> 02:26:14,434
know,

5511
02:26:14,434 --> 02:26:15,597
these things are very

5512
02:26:15,597 --> 02:26:16,870
complicated sometimes.

5513
02:26:17,337 --> 02:26:17,938
Thank you.

5514
02:26:18,538 --> 02:26:19,906
I'm sorry for the mistake.

5515
02:26:20,607 --> 02:26:21,308
That's fine.

5516
02:26:21,775 --> 02:26:22,142
Great.

5517
02:26:22,142 --> 02:26:23,276
So we can move on.

5518
02:26:23,710 --> 02:26:25,416
I'm gonna be talking about sleep

5519
02:26:25,416 --> 02:26:26,560
and the developmental

5520
02:26:26,560 --> 02:26:27,814
progression of autism.

5521
02:26:28,715 --> 02:26:30,357
And I wanted to start by saying

5522
02:26:30,357 --> 02:26:32,052
I have no conflicts to declare,

5523
02:26:32,052 --> 02:26:33,704
but we did receive funding from

5524
02:26:33,704 --> 02:26:35,121
the National Institutes of

5525
02:26:35,121 --> 02:26:36,156
Health and Simon's

5526
02:26:36,156 --> 02:26:36,892
Foundation for

5527
02:26:36,892 --> 02:26:37,891
some of this work.

5528
02:26:38,325 --> 02:26:40,718
And thank you to the families

5529
02:26:40,718 --> 02:26:42,574
for all their all with

5530
02:26:42,574 --> 02:26:44,598
everything that they've

5531
02:26:44,598 --> 02:26:45,730
given to these

5532
02:26:45,730 --> 02:26:47,267
research projects.

5533
02:26:47,834 --> 02:26:49,703
So next slide, what we have,

5534
02:26:49,703 --> 02:26:51,759
what I want to go over is that

5535
02:26:51,759 --> 02:26:52,239
autism

5536
02:26:52,239 --> 02:26:53,707
spectrum disorders and

5537
02:26:53,707 --> 02:26:55,642
neurodevelopmental disorder,

5538
02:26:55,642 --> 02:26:57,732
but it's based on behavior that

5539
02:26:57,732 --> 02:26:58,945
starts before H3.

5540
02:26:59,846 --> 02:27:02,259
We all might have heard that the

5541
02:27:02,259 --> 02:27:04,572
US prevalence recently changed

5542
02:27:04,572 --> 02:27:05,652
to one in 31.

5543
02:27:06,019 --> 02:27:07,880
It's more common in boys than

5544
02:27:07,880 --> 02:27:09,662
girls, but found across all

5545
02:27:09,662 --> 02:27:10,190
racial,

5546
02:27:10,190 --> 02:27:11,193
ethnic and socio

5547
02:27:11,193 --> 02:27:12,259
economic groups.

5548
02:27:12,526 --> 02:27:13,593
Next slide, please.

5549
02:27:15,395 --> 02:27:17,076
It's a diagnostic term that

5550
02:27:17,076 --> 02:27:18,864
describes a group of complex

5551
02:27:18,864 --> 02:27:19,566
disorders.

5552
02:27:20,467 --> 02:27:22,705
The commonality is 2 domains of

5553
02:27:22,705 --> 02:27:24,191
functioning, social,

5554
02:27:24,191 --> 02:27:25,305
communication,

5555
02:27:25,305 --> 02:27:27,410
and restricted and repetitive

5556
02:27:27,410 --> 02:27:28,964
behaviors and sensory

5557
02:27:28,964 --> 02:27:31,111
alterations are are found in

5558
02:27:31,111 --> 02:27:32,353
autism and that's

5559
02:27:32,353 --> 02:27:33,813
how we diagnose it.

5560
02:27:33,813 --> 02:27:35,182
OK, next slide.

5561
02:27:36,716 --> 02:27:39,109
The development of autism is a

5562
02:27:39,109 --> 02:27:41,421
complex thing to talk about,

5563
02:27:41,421 --> 02:27:43,981
but it arises over the course of

5564
02:27:43,981 --> 02:27:46,276
early development due to the

5565
02:27:46,276 --> 02:27:47,260
interaction

5566
02:27:47,260 --> 02:27:49,155
between several factors,

5567
02:27:49,155 --> 02:27:50,497
largely genetic.

5568
02:27:50,497 --> 02:27:52,433
So the the vast majority of the

5569
02:27:52,433 --> 02:27:54,419
variability in autism is due to

5570
02:27:54,419 --> 02:27:54,868
genes.

5571
02:27:56,102 --> 02:27:57,719
There's a little bit of

5572
02:27:57,719 --> 02:27:59,230
influence by prenatal

5573
02:27:59,230 --> 02:28:00,740
environment as well.

5574
02:28:01,508 --> 02:28:03,914
These things lead to alterations

5575
02:28:03,914 --> 02:28:06,075
in brain structure and brain

5576
02:28:06,075 --> 02:28:06,846
function,

5577
02:28:06,846 --> 02:28:09,107
which then lead to very subtle

5578
02:28:09,107 --> 02:28:11,518
early behavioral deficits that,

5579
02:28:11,518 --> 02:28:13,341
in a kind of ***********

5580
02:28:13,341 --> 02:28:15,088
developmental process,

5581
02:28:15,088 --> 02:28:17,060
lead to what later becomes

5582
02:28:17,060 --> 02:28:19,259
diagnosable autism symptoms.

5583
02:28:19,492 --> 02:28:20,427
Next slide, please.

5584
02:28:22,229 --> 02:28:24,172
So we ask ourselves in some of

5585
02:28:24,172 --> 02:28:26,167
our research, when does autism

5586
02:28:26,167 --> 02:28:26,633
start?

5587
02:28:26,633 --> 02:28:28,826
We know it's possible in many of

5588
02:28:28,826 --> 02:28:30,581
our research protocols to

5589
02:28:30,581 --> 02:28:31,705
diagnose autism

5590
02:28:31,705 --> 02:28:33,373
between 12 and 36 months.

5591
02:28:33,773 --> 02:28:36,232
There's sort of the variety of

5592
02:28:36,232 --> 02:28:37,544
of onset times.

5593
02:28:37,978 --> 02:28:40,437
The average in the US is closer

5594
02:28:40,437 --> 02:28:42,182
to five years of age.

5595
02:28:43,049 --> 02:28:43,918
But if you look,

5596
02:28:43,918 --> 02:28:45,316
there are some very early

5597
02:28:45,316 --> 02:28:45,819
emerging

5598
02:28:45,819 --> 02:28:47,333
features that are able to be

5599
02:28:47,333 --> 02:28:49,056
recognized in the first year of

5600
02:28:49,056 --> 02:28:49,389
life.

5601
02:28:50,090 --> 02:28:51,424
Next slide, please.

5602
02:28:52,092 --> 02:28:53,650
So one of the questions that we

5603
02:28:53,650 --> 02:28:55,190
have is when do sleep problems

5604
02:28:55,190 --> 02:28:56,062
in autism start?

5605
02:28:57,464 --> 02:28:59,399
We wonder about whether sleep

5606
02:28:59,399 --> 02:29:01,579
problems are an emerging feature

5607
02:29:01,579 --> 02:29:02,669
of autism along

5608
02:29:02,669 --> 02:29:04,616
with some of these other core

5609
02:29:04,616 --> 02:29:06,465
alterations that we see and

5610
02:29:06,465 --> 02:29:08,108
whether they contribute

5611
02:29:08,108 --> 02:29:09,990
to the developmental cascade

5612
02:29:09,990 --> 02:29:12,060
that precedes autism onset and

5613
02:29:12,060 --> 02:29:12,612
sort of

5614
02:29:12,612 --> 02:29:14,295
contribute to the ongoing

5615
02:29:14,295 --> 02:29:16,516
development of autism over time.

5616
02:29:17,284 --> 02:29:18,551
Next slide please.

5617
02:29:20,787 --> 02:29:22,571
So most autistic children have

5618
02:29:22,571 --> 02:29:23,523
sleep problems.

5619
02:29:24,257 --> 02:29:26,293
Many estimates are over 80%.

5620
02:29:27,093 --> 02:29:28,746
We all know that sleep can

5621
02:29:28,746 --> 02:29:30,305
adversely affect health,

5622
02:29:30,305 --> 02:29:31,798
cognitive development,

5623
02:29:31,798 --> 02:29:32,381
behavior,

5624
02:29:32,381 --> 02:29:34,504
functioning and increased family

5625
02:29:34,504 --> 02:29:35,035
stress.

5626
02:29:35,568 --> 02:29:37,178
But another thing to consider is

5627
02:29:37,178 --> 02:29:38,780
that sleep disruptions might be

5628
02:29:38,780 --> 02:29:39,039
more

5629
02:29:39,039 --> 02:29:40,609
consequential at critical times

5630
02:29:40,609 --> 02:29:41,775
for brain development.

5631
02:29:41,775 --> 02:29:44,161
So the work of Marcos Frank

5632
02:29:44,161 --> 02:29:46,687
showing the visual system of

5633
02:29:46,687 --> 02:29:48,581
cats being very much

5634
02:29:48,581 --> 02:29:50,250
affected by sleep.

5635
02:29:50,250 --> 02:29:52,333
And so we know that early brain

5636
02:29:52,333 --> 02:29:54,535
development in the first several

5637
02:29:54,535 --> 02:29:55,155
years of

5638
02:29:55,155 --> 02:29:57,257
life is is rapid, super dynamic.

5639
02:29:57,257 --> 02:30:00,021
Same thing at adolescence and

5640
02:30:00,021 --> 02:30:02,595
perhaps also in older age.

5641
02:30:03,029 --> 02:30:04,331
OK, continue please.

5642
02:30:05,899 --> 02:30:06,533
Next one.

5643
02:30:06,533 --> 02:30:06,933
Yes.

5644
02:30:07,300 --> 02:30:09,542
So in autism insomnia is the

5645
02:30:09,542 --> 02:30:11,839
most frequent sleep disorder

5646
02:30:11,839 --> 02:30:12,906
that we see.

5647
02:30:12,906 --> 02:30:15,107
So problems initiating sleep,

5648
02:30:15,107 --> 02:30:17,599
maintaining sleep, waking up too

5649
02:30:17,599 --> 02:30:18,144
early.

5650
02:30:19,179 --> 02:30:21,137
Less frequent but also notable

5651
02:30:21,137 --> 02:30:23,147
in autism are circadian rhythm

5652
02:30:23,147 --> 02:30:23,616
sleep,

5653
02:30:23,616 --> 02:30:24,598
wake disorders,

5654
02:30:24,598 --> 02:30:26,751
sleep related movement disorders

5655
02:30:26,751 --> 02:30:27,020
and

5656
02:30:27,020 --> 02:30:27,862
sleep related

5657
02:30:27,862 --> 02:30:29,222
breathing disorders.

5658
02:30:29,989 --> 02:30:32,072
I think one thing we don't know

5659
02:30:32,072 --> 02:30:34,137
is whether these less frequent

5660
02:30:34,137 --> 02:30:34,894
challenges

5661
02:30:34,894 --> 02:30:36,910
that we've noted in autism are

5662
02:30:36,910 --> 02:30:38,904
over and above what you would

5663
02:30:38,904 --> 02:30:39,866
expect in the

5664
02:30:39,866 --> 02:30:41,850
general population or whether

5665
02:30:41,850 --> 02:30:43,903
they are increased in autism.

5666
02:30:43,903 --> 02:30:45,705
So that's a question to address.

5667
02:30:46,106 --> 02:30:46,873
Next slide, please.

5668
02:30:49,075 --> 02:30:52,174
So we'd love this graph from

5669
02:30:52,174 --> 02:30:55,715
this National Sleep Foundation.

5670
02:30:56,015 --> 02:30:58,365
It illustrates the very large

5671
02:30:58,365 --> 02:31:00,931
changes that occur over time in

5672
02:31:00,931 --> 02:31:02,255
sleep duration,

5673
02:31:02,255 --> 02:31:04,775
with the highest sleep duration

5674
02:31:04,775 --> 02:31:07,194
in newborns and then reducing

5675
02:31:07,194 --> 02:31:08,027
over time

5676
02:31:08,027 --> 02:31:09,462
through older age.

5677
02:31:10,663 --> 02:31:13,166
Sleep timing also changes.

5678
02:31:13,166 --> 02:31:14,907
Babies develop circadian rhythm

5679
02:31:14,907 --> 02:31:16,571
over the first six months and

5680
02:31:16,571 --> 02:31:17,604
then increasingly

5681
02:31:17,604 --> 02:31:19,238
consolidate sleep to occur in

5682
02:31:19,238 --> 02:31:20,140
the night time.

5683
02:31:20,740 --> 02:31:22,776
Sleep architecture also changes.

5684
02:31:22,776 --> 02:31:23,815
So babies having

5685
02:31:23,815 --> 02:31:25,245
more active or R.E.M.

5686
02:31:25,245 --> 02:31:27,084
like sleep and then shifting to

5687
02:31:27,084 --> 02:31:28,448
more deep or in R.E.M.

5688
02:31:28,448 --> 02:31:29,549
sleep over time.

5689
02:31:29,749 --> 02:31:30,417
Next slide.

5690
02:31:33,086 --> 02:31:34,623
So one of the questions that

5691
02:31:34,623 --> 02:31:36,415
we're gonna address here is what

5692
02:31:36,415 --> 02:31:37,424
the developmental

5693
02:31:37,424 --> 02:31:39,147
timing and progression of sleep

5694
02:31:39,147 --> 02:31:40,427
problems is in autism.

5695
02:31:40,427 --> 02:31:41,661
That's something that

5696
02:31:41,661 --> 02:31:42,896
we're interested in.

5697
02:31:42,896 --> 02:31:44,820
We need to know a lot more about

5698
02:31:44,820 --> 02:31:46,478
that and what the impact of

5699
02:31:46,478 --> 02:31:47,767
sleep problems is on

5700
02:31:47,767 --> 02:31:48,851
behavior and brain

5701
02:31:48,851 --> 02:31:50,236
development in autism.

5702
02:31:51,137 --> 02:31:52,205
So next slide please.

5703
02:31:54,174 --> 02:31:55,918
One of the ways that we can

5704
02:31:55,918 --> 02:31:57,895
address this question in early

5705
02:31:57,895 --> 02:31:59,279
development is using

5706
02:31:59,279 --> 02:32:01,047
infant sibling study design.

5707
02:32:01,815 --> 02:32:02,969
And what that is,

5708
02:32:02,969 --> 02:32:05,061
is where we recruit and follow

5709
02:32:05,061 --> 02:32:05,618
infants

5710
02:32:05,618 --> 02:32:06,553
who have older

5711
02:32:06,553 --> 02:32:07,821
autistic siblings.

5712
02:32:08,154 --> 02:32:10,588
We sort of label this group as

5713
02:32:10,588 --> 02:32:12,859
high likelihood for autism.

5714
02:32:13,226 --> 02:32:15,406
The reason that we have that

5715
02:32:15,406 --> 02:32:17,872
label is that autism recurrence

5716
02:32:17,872 --> 02:32:19,065
is over 20% in

5717
02:32:19,065 --> 02:32:20,766
infants who have older

5718
02:32:20,766 --> 02:32:22,235
autistic siblings.

5719
02:32:22,702 --> 02:32:24,253
These infants also have other

5720
02:32:24,253 --> 02:32:25,680
learning and developmental

5721
02:32:25,680 --> 02:32:26,339
challenges.

5722
02:32:26,339 --> 02:32:28,293
About 30% of infant siblings

5723
02:32:28,293 --> 02:32:30,500
will have some kind of learning

5724
02:32:30,500 --> 02:32:31,711
or developmental

5725
02:32:31,711 --> 02:32:33,683
challenge even if they don't

5726
02:32:33,683 --> 02:32:35,515
have an autism diagnosis.

5727
02:32:35,949 --> 02:32:38,058
So this is a very important

5728
02:32:38,058 --> 02:32:40,525
population to study and it also

5729
02:32:40,525 --> 02:32:42,355
clinically and it also

5730
02:32:42,355 --> 02:32:44,475
allows us to study the very

5731
02:32:44,475 --> 02:32:46,889
earliest development of autism

5732
02:32:46,889 --> 02:32:47,694
and other

5733
02:32:47,694 --> 02:32:49,573
developmental challenges

5734
02:32:49,573 --> 02:32:51,570
associated with autism by

5735
02:32:51,570 --> 02:32:53,566
assessing and monitoring

5736
02:32:53,566 --> 02:32:55,365
infants even before the

5737
02:32:55,365 --> 02:32:57,930
behaviors associated with autism

5738
02:32:57,930 --> 02:32:58,571
emerge.

5739
02:32:59,205 --> 02:33:00,507
So next slide, please.

5740
02:33:02,575 --> 02:33:04,363
One of the groups that is

5741
02:33:04,363 --> 02:33:06,331
studying this is the infant

5742
02:33:06,331 --> 02:33:08,081
brain imaging study and

5743
02:33:08,081 --> 02:33:10,376
this is a consortium that's been

5744
02:33:10,376 --> 02:33:12,721
ongoing for over 20 years now at

5745
02:33:12,721 --> 02:33:13,820
the University

5746
02:33:13,820 --> 02:33:15,111
of North Carolina,

5747
02:33:15,111 --> 02:33:17,463
Washington University Children's

5748
02:33:17,463 --> 02:33:18,124
Hospital

5749
02:33:18,124 --> 02:33:20,304
of Philadelphia and University

5750
02:33:20,304 --> 02:33:21,394
of Washington.

5751
02:33:21,394 --> 02:33:23,779
And we have a data coordinating

5752
02:33:23,779 --> 02:33:25,164
center at McGill.

5753
02:33:26,032 --> 02:33:27,100
Next slide please.

5754
02:33:28,935 --> 02:33:29,527
And the,

5755
02:33:29,527 --> 02:33:31,654
the study design in the Ibis

5756
02:33:31,654 --> 02:33:32,338
study is

5757
02:33:32,338 --> 02:33:34,682
assessing infants who have older

5758
02:33:34,682 --> 02:33:36,854
siblings and also infants who

5759
02:33:36,854 --> 02:33:37,977
have no family

5760
02:33:37,977 --> 02:33:40,326
history of autism at 6/12/24 and

5761
02:33:40,326 --> 02:33:41,648
36 months of age.

5762
02:33:42,549 --> 02:33:44,800
At each of the time points

5763
02:33:44,800 --> 02:33:46,619
infants undergo MRI,

5764
02:33:46,619 --> 02:33:49,132
sleeping MRI to measure brain

5765
02:33:49,132 --> 02:33:51,535
structure, connectivity and

5766
02:33:51,535 --> 02:33:52,425
function.

5767
02:33:52,725 --> 02:33:54,830
Also we conduct developmental

5768
02:33:54,830 --> 02:33:57,125
assessments to measure behavior

5769
02:33:57,125 --> 02:33:58,531
over time and then

5770
02:33:58,531 --> 02:34:00,729
clinical assessment for autism

5771
02:34:00,729 --> 02:34:02,268
at 24 and 36 months.

5772
02:34:02,969 --> 02:34:03,903
OK, next slide.

5773
02:34:05,204 --> 02:34:07,782
So our first cohort of infants,

5774
02:34:07,782 --> 02:34:10,443
we collected 450 infants and we

5775
02:34:10,443 --> 02:34:12,918
categorize them into 3 outcome

5776
02:34:12,918 --> 02:34:15,453
groups based on their 24 month

5777
02:34:15,453 --> 02:34:16,382
diagnosis.

5778
02:34:16,950 --> 02:34:18,800
So we had high likelihood

5779
02:34:18,800 --> 02:34:21,138
infants with the older siblings

5780
02:34:21,138 --> 02:34:22,722
who are autistic who

5781
02:34:22,722 --> 02:34:24,812
also had an autism diagnosis

5782
02:34:24,812 --> 02:34:27,126
themselves at 24 or 36 months.

5783
02:34:27,627 --> 02:34:29,283
Then we had a group of infants

5784
02:34:29,283 --> 02:34:30,634
who are high likelihood,

5785
02:34:30,634 --> 02:34:32,098
negative or non autistic.

5786
02:34:33,499 --> 02:34:35,300
Then there's the low likelihood

5787
02:34:35,300 --> 02:34:37,197
group who had older siblings who

5788
02:34:37,197 --> 02:34:38,204
are not autistic

5789
02:34:38,204 --> 02:34:39,939
and no first degree relatance.

5790
02:34:40,573 --> 02:34:41,774
Next slide, please.

5791
02:34:43,610 --> 02:34:44,822
So what about sleep

5792
02:34:44,822 --> 02:34:45,778
in this group?

5793
02:34:46,546 --> 02:34:47,477
Well, sadly,

5794
02:34:47,477 --> 02:34:49,946
no sleep measures were included

5795
02:34:49,946 --> 02:34:50,583
in this

5796
02:34:50,583 --> 02:34:52,680
original Ibis study design,

5797
02:34:52,680 --> 02:34:54,441
but I was concurrently

5798
02:34:54,441 --> 02:34:55,321
conducting

5799
02:34:55,321 --> 02:34:57,418
randomized clinical trials,

5800
02:34:57,418 --> 02:34:58,939
a very early autism

5801
02:34:58,939 --> 02:35:00,059
intervention.

5802
02:35:00,526 --> 02:35:03,217
And as we were concluding one of

5803
02:35:03,217 --> 02:35:04,731
our final trials,

5804
02:35:04,731 --> 02:35:07,254
I asked parents and clinicians

5805
02:35:07,254 --> 02:35:09,751
what we needed to study, what

5806
02:35:09,751 --> 02:35:10,870
did we miss?

5807
02:35:10,870 --> 02:35:12,023
And overwhelmingly,

5808
02:35:12,023 --> 02:35:13,539
they talked about sleep.

5809
02:35:14,073 --> 02:35:16,087
So one of the biggest challenges

5810
02:35:16,087 --> 02:35:17,823
that is not being addressed

5811
02:35:17,823 --> 02:35:19,045
right now in early

5812
02:35:19,045 --> 02:35:20,968
autism intervention is helping

5813
02:35:20,968 --> 02:35:22,315
families with sleep.

5814
02:35:22,982 --> 02:35:24,947
And that got me thinking, well,

5815
02:35:24,947 --> 02:35:26,964
what's going on in our siblings

5816
02:35:26,964 --> 02:35:27,420
in the

5817
02:35:27,420 --> 02:35:28,054
IVA study?

5818
02:35:28,488 --> 02:35:30,790
And next slide, please.

5819
02:35:31,691 --> 02:35:33,342
So what we found out I was

5820
02:35:33,342 --> 02:35:34,899
working with a wonderful

5821
02:35:34,899 --> 02:35:36,262
postdoctoral fellow,

5822
02:35:36,262 --> 02:35:38,037
Kate Mcduffie is that we did

5823
02:35:38,037 --> 02:35:39,432
have a questionnaire,

5824
02:35:39,432 --> 02:35:40,636
the infant behavior

5825
02:35:40,636 --> 02:35:42,377
questionnaire that measures

5826
02:35:42,377 --> 02:35:44,504
infant temperament and there are

5827
02:35:44,504 --> 02:35:46,493
five items that ask about sleep

5828
02:35:46,493 --> 02:35:48,080
onset, latency and night

5829
02:35:48,080 --> 02:35:48,675
wakings.

5830
02:35:48,675 --> 02:35:50,543
And so we took those five items.

5831
02:35:50,977 --> 02:35:52,145
Next slide please.

5832
02:35:53,913 --> 02:35:56,318
And luckily in this multi site

5833
02:35:56,318 --> 02:35:58,612
study, a subset of the IABUS

5834
02:35:58,612 --> 02:36:00,086
infants also were

5835
02:36:00,086 --> 02:36:02,571
given some questionnaire called

5836
02:36:02,571 --> 02:36:04,370
the brief infant sleep

5837
02:36:04,370 --> 02:36:06,659
questionnaire that has been

5838
02:36:06,659 --> 02:36:08,989
validated and we were able to

5839
02:36:08,989 --> 02:36:11,528
show a high concurrence between

5840
02:36:11,528 --> 02:36:13,166
scores on this ISOP

5841
02:36:13,166 --> 02:36:15,521
or infant sleep onset problem

5842
02:36:15,521 --> 02:36:17,470
score and the BIZ cube.

5843
02:36:17,904 --> 02:36:20,264
So next slide and we asked the

5844
02:36:20,264 --> 02:36:22,511
question of whether this new

5845
02:36:22,511 --> 02:36:24,277
ISOP score at six and

5846
02:36:24,277 --> 02:36:26,405
12 months of age-related to

5847
02:36:26,405 --> 02:36:28,848
diagnosis at 24 months of age.

5848
02:36:29,415 --> 02:36:31,289
And you can see here that in the

5849
02:36:31,289 --> 02:36:32,285
high likelihood,

5850
02:36:32,285 --> 02:36:33,908
non autism and green and low

5851
02:36:33,908 --> 02:36:35,681
likelihood groups there really

5852
02:36:35,681 --> 02:36:36,923
wasn't a statistical

5853
02:36:36,923 --> 02:36:37,523
difference.

5854
02:36:37,790 --> 02:36:38,725
Next slide please.

5855
02:36:40,693 --> 02:36:42,928
But the three groups did differ

5856
02:36:42,928 --> 02:36:45,282
overall statistically and that's

5857
02:36:45,282 --> 02:36:46,532
because the high

5858
02:36:46,532 --> 02:36:48,488
likelihood autism group had

5859
02:36:48,488 --> 02:36:50,554
higher parent reported sleep

5860
02:36:50,554 --> 02:36:52,472
onset problems at six and

5861
02:36:52,472 --> 02:36:53,172
12 months.

5862
02:36:53,773 --> 02:36:55,481
And it's important to think

5863
02:36:55,481 --> 02:36:57,224
about this because it's a a

5864
02:36:57,224 --> 02:36:58,644
natural experiment in

5865
02:36:58,644 --> 02:37:00,335
which the families who were

5866
02:37:00,335 --> 02:37:02,121
reporting did not know which

5867
02:37:02,121 --> 02:37:03,716
kids were going to go on

5868
02:37:03,716 --> 02:37:05,651
to develop autism at 24 months.

5869
02:37:05,985 --> 02:37:07,982
Adding a measure of that

5870
02:37:07,982 --> 02:37:10,697
prospective measure kind of adds

5871
02:37:10,697 --> 02:37:12,225
a little validity

5872
02:37:12,225 --> 02:37:14,569
that we often don't get with

5873
02:37:14,569 --> 02:37:16,496
retrospective reports.

5874
02:37:17,430 --> 02:37:18,865
OK, next slide, please.

5875
02:37:20,099 --> 02:37:22,456
Next we ask whether sleep during

5876
02:37:22,456 --> 02:37:24,711
infancy predicted brain volume

5877
02:37:24,711 --> 02:37:26,139
at 6 to 24 months.

5878
02:37:26,539 --> 02:37:28,498
So we use linear mixed models

5879
02:37:28,498 --> 02:37:30,424
looking at six brain regions

5880
02:37:30,424 --> 02:37:32,145
subcortical the caudate,

5881
02:37:32,145 --> 02:37:34,313
amygdala, hippocampus, thalamus,

5882
02:37:34,313 --> 02:37:36,549
glowus, pallidus and putainment.

5883
02:37:36,849 --> 02:37:38,236
We controlled for age,

5884
02:37:38,236 --> 02:37:40,174
sex and total brain volume and

5885
02:37:40,174 --> 02:37:40,820
scan site

5886
02:37:40,820 --> 02:37:41,957
because as I said,

5887
02:37:41,957 --> 02:37:43,790
we had four different sites.

5888
02:37:44,423 --> 02:37:46,125
So next slide please.

5889
02:37:47,660 --> 02:37:49,675
And what we found is the sleep

5890
02:37:49,675 --> 02:37:51,870
infant sleep onset problem score

5891
02:37:51,870 --> 02:37:52,899
only predicted

5892
02:37:52,899 --> 02:37:54,177
hippocampal volume,

5893
02:37:54,177 --> 02:37:56,384
not any of the other subcortical

5894
02:37:56,384 --> 02:37:56,936
nuclei.

5895
02:37:57,904 --> 02:38:00,016
And this was only for infants

5896
02:38:00,016 --> 02:38:02,275
who went on to develop autism.

5897
02:38:02,275 --> 02:38:04,708
So if you look at this graphic

5898
02:38:04,708 --> 02:38:06,412
representation here,

5899
02:38:06,412 --> 02:38:08,760
you can see in green the high

5900
02:38:08,760 --> 02:38:11,236
likelihood autism group and in

5901
02:38:11,236 --> 02:38:13,052
pink and blue the low

5902
02:38:13,052 --> 02:38:15,504
likelihood and high likelihood

5903
02:38:15,504 --> 02:38:17,056
non autism groups.

5904
02:38:17,590 --> 02:38:19,660
And this was a significant

5905
02:38:19,660 --> 02:38:22,018
interaction where worse sleep

5906
02:38:22,018 --> 02:38:23,563
onset problems was

5907
02:38:23,563 --> 02:38:26,112
related to higher actually rates

5908
02:38:26,112 --> 02:38:28,245
of increase of hippocampal

5909
02:38:28,245 --> 02:38:28,901
volume.

5910
02:38:31,003 --> 02:38:31,940
And so yeah,

5911
02:38:31,940 --> 02:38:34,426
I think longer sleep onset at 6

5912
02:38:34,426 --> 02:38:34,907
to 12

5913
02:38:34,907 --> 02:38:37,133
months associated with autism

5914
02:38:37,133 --> 02:38:39,325
diagnosis at 24 months and a

5915
02:38:39,325 --> 02:38:41,047
different hippocampal

5916
02:38:41,047 --> 02:38:42,415
growth trajectory.

5917
02:38:42,748 --> 02:38:43,649
Next slide, please.

5918
02:38:46,252 --> 02:38:48,950
So the next step was to look at

5919
02:38:48,950 --> 02:38:51,811
the same group of kids at school

5920
02:38:51,811 --> 02:38:52,258
age.

5921
02:38:52,258 --> 02:38:54,023
So we're doing longitudinal

5922
02:38:54,023 --> 02:38:56,094
follow up with these infants or

5923
02:38:56,094 --> 02:38:57,029
with formerly

5924
02:38:57,029 --> 02:38:57,552
infants,

5925
02:38:57,552 --> 02:38:59,362
infants that are siblings I

5926
02:38:59,362 --> 02:39:00,166
should say,

5927
02:39:00,166 --> 02:39:02,058
now that they're older and we

5928
02:39:02,058 --> 02:39:03,800
added measures of sleep at

5929
02:39:03,800 --> 02:39:04,604
school age.

5930
02:39:05,171 --> 02:39:08,147
So next slide please and ask the

5931
02:39:08,147 --> 02:39:10,902
question whether or how we're

5932
02:39:10,902 --> 02:39:12,612
hoping to ask the

5933
02:39:12,612 --> 02:39:14,841
question how to do sleep

5934
02:39:14,841 --> 02:39:17,874
problems progress from 24 months

5935
02:39:17,874 --> 02:39:19,485
of age to school

5936
02:39:19,485 --> 02:39:22,589
age and we're doing that through

5937
02:39:22,589 --> 02:39:23,656
actimetry.

5938
02:39:23,656 --> 02:39:25,954
So direct assessment, 10 days in

5939
02:39:25,954 --> 02:39:28,154
the home, online sleep Diaries

5940
02:39:28,154 --> 02:39:29,328
and also a home

5941
02:39:29,328 --> 02:39:31,394
environment sensor looking at

5942
02:39:31,394 --> 02:39:33,653
temperature, light and sound in

5943
02:39:33,653 --> 02:39:34,600
the bedroom,

5944
02:39:34,600 --> 02:39:36,669
parent report questionnaires.

5945
02:39:36,669 --> 02:39:37,806
And then of course,

5946
02:39:37,806 --> 02:39:39,341
we're leveraging the Ibis

5947
02:39:39,341 --> 02:39:40,139
longitudinal

5948
02:39:40,139 --> 02:39:41,540
brain and behavior data.

5949
02:39:42,742 --> 02:39:45,827
We just finished assessing this

5950
02:39:45,827 --> 02:39:48,514
cohort of school age kids.

5951
02:39:48,514 --> 02:39:49,515
Next slide, please.

5952
02:39:51,617 --> 02:39:54,240
And so this is sort of a cartoon

5953
02:39:54,240 --> 02:39:56,918
if you will of the patterns that

5954
02:39:56,918 --> 02:39:58,257
we're seeing in

5955
02:39:58,257 --> 02:40:00,624
this initial look at our data

5956
02:40:00,624 --> 02:40:03,285
and what we found on the left in

5957
02:40:03,285 --> 02:40:05,031
the children's sleep

5958
02:40:05,031 --> 02:40:06,754
habits questionnaire,

5959
02:40:06,754 --> 02:40:09,362
the parent report measure was a

5960
02:40:09,362 --> 02:40:10,036
pattern

5961
02:40:10,036 --> 02:40:11,404
that we expected.

5962
02:40:11,404 --> 02:40:13,179
This is our we hypothesized that

5963
02:40:13,179 --> 02:40:14,822
we'd see the lowest levels of

5964
02:40:14,822 --> 02:40:15,841
sleep problems in

5965
02:40:15,841 --> 02:40:17,227
the low likelihood group,

5966
02:40:17,227 --> 02:40:18,826
an intermediate level in the

5967
02:40:18,826 --> 02:40:19,111
high

5968
02:40:19,111 --> 02:40:20,728
likelihood non autism and the

5969
02:40:20,728 --> 02:40:22,497
highest level of sleep problems

5970
02:40:22,497 --> 02:40:23,182
in the high

5971
02:40:23,182 --> 02:40:24,116
likelihood group.

5972
02:40:24,817 --> 02:40:26,673
This could be indicating an

5973
02:40:26,673 --> 02:40:28,579
endophenotypic pattern that

5974
02:40:28,579 --> 02:40:29,355
relates to

5975
02:40:29,355 --> 02:40:30,638
the sort of genetic

5976
02:40:30,638 --> 02:40:32,124
liability for autism.

5977
02:40:33,426 --> 02:40:36,234
It also could be influenced by

5978
02:40:36,234 --> 02:40:38,640
the environmental kind of

5979
02:40:38,640 --> 02:40:39,699
similar or

5980
02:40:39,699 --> 02:40:42,710
challenges that come with having

5981
02:40:42,710 --> 02:40:44,403
an older sibling.

5982
02:40:44,403 --> 02:40:46,811
But when you see that increased

5983
02:40:46,811 --> 02:40:48,674
autism score there you,

5984
02:40:48,674 --> 02:40:50,990
you really think about it that

5985
02:40:50,990 --> 02:40:53,370
the disorder of autism is, you

5986
02:40:53,370 --> 02:40:53,846
know,

5987
02:40:53,846 --> 02:40:56,337
predictably related to increased

5988
02:40:56,337 --> 02:40:57,583
sleep problems.

5989
02:40:58,084 --> 02:40:59,871
Now the curious thing that I

5990
02:40:59,871 --> 02:41:01,759
would love to hear more about

5991
02:41:01,759 --> 02:41:03,255
from all these experts

5992
02:41:03,255 --> 02:41:04,712
in the room is that our

5993
02:41:04,712 --> 02:41:06,646
actimetry data, this objective

5994
02:41:06,646 --> 02:41:08,194
measure of sleep for 10

5995
02:41:08,194 --> 02:41:10,186
days in the home is not showing

5996
02:41:10,186 --> 02:41:11,664
our expected patterns.

5997
02:41:11,664 --> 02:41:14,391
This is just a a glimpse at the

5998
02:41:14,391 --> 02:41:16,502
total sleep time score.

5999
02:41:16,502 --> 02:41:18,607
This is similar though for sleep

6000
02:41:18,607 --> 02:41:20,499
efficiency and other kind of

6001
02:41:20,499 --> 02:41:21,107
measures

6002
02:41:21,107 --> 02:41:23,072
that come from actimetry where

6003
02:41:23,072 --> 02:41:24,742
there's not statistically

6004
02:41:24,742 --> 02:41:26,412
significant differences.

6005
02:41:26,412 --> 02:41:27,909
And if there is small

6006
02:41:27,909 --> 02:41:30,163
differences, it's that the high

6007
02:41:30,163 --> 02:41:31,617
likelihood negative

6008
02:41:31,617 --> 02:41:33,605
kids are having kind of more

6009
02:41:33,605 --> 02:41:35,200
problems than the high

6010
02:41:35,200 --> 02:41:37,156
likelihood positive or low

6011
02:41:37,156 --> 02:41:37,923
likelihood.

6012
02:41:38,457 --> 02:41:40,736
So this is really interesting

6013
02:41:40,736 --> 02:41:43,060
and we're thinking that about

6014
02:41:43,060 --> 02:41:44,663
some of the reasons

6015
02:41:44,663 --> 02:41:46,832
that this could be the case.

6016
02:41:46,832 --> 02:41:47,769
So first of all,

6017
02:41:47,769 --> 02:41:49,329
it could be that the sleep

6018
02:41:49,329 --> 02:41:50,169
problems that

6019
02:41:50,169 --> 02:41:51,792
parents are reporting in the

6020
02:41:51,792 --> 02:41:53,686
high likelihood autism group are

6021
02:41:53,686 --> 02:41:54,573
being treated.

6022
02:41:54,907 --> 02:41:57,697
So we're looking right now at

6023
02:41:57,697 --> 02:42:00,679
the very complicated messy of,

6024
02:42:00,679 --> 02:42:03,091
but seem to be analyzable

6025
02:42:03,091 --> 02:42:05,985
medication data that we have.

6026
02:42:05,985 --> 02:42:07,528
And there are a lot of

6027
02:42:07,528 --> 02:42:09,600
medications and we've heard a

6028
02:42:09,600 --> 02:42:11,457
lot about them today that

6029
02:42:11,457 --> 02:42:13,587
can influence sleep either for

6030
02:42:13,587 --> 02:42:14,794
for good or ill.

6031
02:42:15,194 --> 02:42:17,586
And so that could be one of the

6032
02:42:17,586 --> 02:42:18,898
things going on.

6033
02:42:19,732 --> 02:42:21,567
Another thing that I'm

6034
02:42:21,567 --> 02:42:23,777
interested in is this high

6035
02:42:23,777 --> 02:42:26,072
likelihood negative group,

6036
02:42:26,072 --> 02:42:28,503
we could have increased sleep

6037
02:42:28,503 --> 02:42:30,982
challenges as well because we

6038
02:42:30,982 --> 02:42:32,778
know that this group

6039
02:42:32,778 --> 02:42:35,364
is more likely to have ADHD and

6040
02:42:35,364 --> 02:42:38,087
anxiety, two things that we know

6041
02:42:38,087 --> 02:42:39,618
are disruptive of

6042
02:42:39,618 --> 02:42:40,086
sleep.

6043
02:42:40,086 --> 02:42:42,201
So something that we're going to

6044
02:42:42,201 --> 02:42:43,656
be looking more into.

6045
02:42:44,490 --> 02:42:45,424
OK, next slide.

6046
02:42:46,659 --> 02:42:47,542
So to wrap up,

6047
02:42:47,542 --> 02:42:49,223
sleep alterations might be

6048
02:42:49,223 --> 02:42:50,129
present prior

6049
02:42:50,129 --> 02:42:51,831
to the diagnosis of autism.

6050
02:42:53,032 --> 02:42:54,945
We know they're related to brain

6051
02:42:54,945 --> 02:42:56,662
and behavioral developmental

6052
02:42:56,662 --> 02:42:57,336
changes in

6053
02:42:57,336 --> 02:42:58,602
autism and that inter

6054
02:42:58,602 --> 02:43:00,203
relationship between sleep

6055
02:43:00,203 --> 02:43:01,373
behavior and brain

6056
02:43:01,373 --> 02:43:02,443
development may be

6057
02:43:02,443 --> 02:43:03,809
particularly relevant.

6058
02:43:04,810 --> 02:43:06,102
So next slide,

6059
02:43:06,102 --> 02:43:08,946
what we don't know is what are

6060
02:43:08,946 --> 02:43:09,515
these

6061
02:43:09,515 --> 02:43:11,951
longitudinal relationships?

6062
02:43:12,551 --> 02:43:14,461
Do sleep problems in the first

6063
02:43:14,461 --> 02:43:16,543
two years of life predict school

6064
02:43:16,543 --> 02:43:17,389
age sleep or

6065
02:43:17,389 --> 02:43:18,824
behavioral functioning?

6066
02:43:19,492 --> 02:43:21,040
Are sleep problems associated

6067
02:43:21,040 --> 02:43:22,786
with altered brain developmental

6068
02:43:22,786 --> 02:43:23,496
trajectories

6069
02:43:23,496 --> 02:43:24,230
in school age?

6070
02:43:24,630 --> 02:43:26,589
And that's to say nothing of

6071
02:43:26,589 --> 02:43:28,726
longitudinal relationships and

6072
02:43:28,726 --> 02:43:30,436
outcomes in adolescents

6073
02:43:30,436 --> 02:43:31,604
and older adults.

6074
02:43:31,604 --> 02:43:33,567
We have a real great need for

6075
02:43:33,567 --> 02:43:35,162
longitudinal studies to

6076
02:43:35,162 --> 02:43:36,342
understand this.

6077
02:43:37,076 --> 02:43:37,877
And finally,

6078
02:43:37,877 --> 02:43:39,793
all of this is in service of

6079
02:43:39,793 --> 02:43:40,546
developing

6080
02:43:40,546 --> 02:43:42,214
and testing approaches to

6081
02:43:42,214 --> 02:43:43,949
improve sleep and autism,

6082
02:43:43,949 --> 02:43:45,055
so we have to get

6083
02:43:45,055 --> 02:43:46,485
back to that as well.

6084
02:43:47,586 --> 02:43:48,487
Thank you very much.

6085
02:43:50,890 --> 02:43:51,690
Thank you, Annette.

6086
02:43:51,690 --> 02:43:53,592
You've kept us right on time.

6087
02:43:53,592 --> 02:43:55,121
If you have questions again,

6088
02:43:55,121 --> 02:43:56,595
you can put them in the Q&

6089
02:43:56,595 --> 02:43:58,175
A and we'll try to get to them,

6090
02:43:58,175 --> 02:43:59,792
some of those at the end of the

6091
02:43:59,792 --> 02:44:00,366
day today.

6092
02:44:00,933 --> 02:44:02,474
Our next speaker

6093
02:44:02,474 --> 02:44:04,303
is Natasha Morris.

6094
02:44:04,303 --> 02:44:06,101
She's a child and adolescent

6095
02:44:06,101 --> 02:44:07,803
psychiatrist and associate

6096
02:44:07,803 --> 02:44:09,375
professor at Washington

6097
02:44:09,375 --> 02:44:11,463
University School of Medicine in

6098
02:44:11,463 --> 02:44:12,311
Saint Louis.

6099
02:44:12,945 --> 02:44:14,504
Our clinical practice is

6100
02:44:14,504 --> 02:44:16,293
centered on early childhood

6101
02:44:16,293 --> 02:44:17,816
evaluations for autism

6102
02:44:17,816 --> 02:44:18,984
spectrum disorder,

6103
02:44:18,984 --> 02:44:21,053
as well as school consultations

6104
02:44:21,053 --> 02:44:21,320
for

6105
02:44:21,320 --> 02:44:22,876
students with autism and

6106
02:44:22,876 --> 02:44:24,334
associated psychiatric

6107
02:44:24,334 --> 02:44:25,925
conditions for research

6108
02:44:25,925 --> 02:44:26,592
interests.

6109
02:44:26,592 --> 02:44:28,430
Simply new approaches for

6110
02:44:28,430 --> 02:44:30,563
assessing autism phenotypes,

6111
02:44:30,563 --> 02:44:32,898
neurocircuitry and risk factors.

6112
02:44:33,132 --> 02:44:35,169
And our talk today will describe

6113
02:44:35,169 --> 02:44:37,269
progress in some of these areas.

6114
02:44:37,937 --> 02:44:41,207
So, Natasha, all right.

6115
02:44:41,207 --> 02:44:42,890
So here are disclosures or here

6116
02:44:42,890 --> 02:44:43,976
are my disclosures.

6117
02:44:43,976 --> 02:44:46,027
A lot of these relate to the

6118
02:44:46,027 --> 02:44:47,967
infant brain imaging study

6119
02:44:47,967 --> 02:44:49,982
funding from the NMANIACHD

6120
02:44:49,982 --> 02:44:50,616
and NIMH.

6121
02:44:51,150 --> 02:44:53,019
And I will talk about some of

6122
02:44:53,019 --> 02:44:54,799
these cohort results mostly

6123
02:44:54,799 --> 02:44:55,854
related to Down

6124
02:44:55,854 --> 02:44:56,422
syndrome.

6125
02:44:57,990 --> 02:45:00,085
So in terms of the relevance of

6126
02:45:00,085 --> 02:45:01,950
cohort studies of sleep and

6127
02:45:01,950 --> 02:45:03,262
neurodevelopmental

6128
02:45:03,262 --> 02:45:03,946
disorders,

6129
02:45:03,946 --> 02:45:05,931
cohort studies are a form of

6130
02:45:05,931 --> 02:45:07,960
observational analytic studies

6131
02:45:07,960 --> 02:45:09,552
that provide a temporal

6132
02:45:09,552 --> 02:45:10,936
framework to assess

6133
02:45:10,936 --> 02:45:11,937
causal factors.

6134
02:45:12,805 --> 02:45:14,432
And they do that through, you

6135
02:45:14,432 --> 02:45:16,162
know, some of that, again, you

6136
02:45:16,162 --> 02:45:16,508
know,

6137
02:45:16,508 --> 02:45:18,079
looking at things over time,

6138
02:45:18,079 --> 02:45:19,144
they're, you know,

6139
02:45:19,144 --> 02:45:20,265
part of the speed of

6140
02:45:20,265 --> 02:45:22,114
observational studies, you know,

6141
02:45:22,114 --> 02:45:23,210
some of which can be

6142
02:45:23,210 --> 02:45:24,416
more cross-sectional.

6143
02:45:24,416 --> 02:45:26,405
And for most of the descriptions

6144
02:45:26,405 --> 02:45:27,586
today, I'm really,

6145
02:45:27,586 --> 02:45:29,388
really tried to focus on ones

6146
02:45:29,388 --> 02:45:30,846
that had a longitudinal

6147
02:45:30,846 --> 02:45:32,558
component in terms of what

6148
02:45:32,558 --> 02:45:34,287
this can allow when thinking

6149
02:45:34,287 --> 02:45:35,235
about sleep and

6150
02:45:35,235 --> 02:45:37,129
neurodevelopmental disorders.

6151
02:45:37,396 --> 02:45:39,435
It can help to figure out what

6152
02:45:39,435 --> 02:45:41,582
the nature of sleep problems is

6153
02:45:41,582 --> 02:45:42,968
and issues with the

6154
02:45:42,968 --> 02:45:44,461
timing, the emergence,

6155
02:45:44,461 --> 02:45:46,344
as Doctor Estes just talked

6156
02:45:46,344 --> 02:45:46,972
about in

6157
02:45:46,972 --> 02:45:47,796
Persistence,

6158
02:45:47,796 --> 02:45:49,835
taking a look at contributory

6159
02:45:49,835 --> 02:45:50,609
factors to

6160
02:45:50,609 --> 02:45:52,650
these sleep conditions as well

6161
02:45:52,650 --> 02:45:54,595
as the impacts on health and

6162
02:45:54,595 --> 02:45:55,914
general functions,

6163
02:45:55,914 --> 02:45:57,486
and also looking at the

6164
02:45:57,486 --> 02:45:59,168
effectiveness of certain

6165
02:45:59,168 --> 02:46:00,219
interventions.

6166
02:46:01,153 --> 02:46:02,476
And when used in a

6167
02:46:02,476 --> 02:46:04,796
developmentally informed way to

6168
02:46:04,796 --> 02:46:06,592
examine the development

6169
02:46:06,592 --> 02:46:08,804
of sleep problems over time in

6170
02:46:08,804 --> 02:46:11,163
different developmental stages.

6171
02:46:11,897 --> 02:46:13,822
It can also allow for potential

6172
02:46:13,822 --> 02:46:15,724
insights into mechanisms which

6173
02:46:15,724 --> 02:46:16,802
can then in term

6174
02:46:16,802 --> 02:46:18,305
and form assessments and

6175
02:46:18,305 --> 02:46:20,372
treatments over the life course.

6176
02:46:23,342 --> 02:46:25,094
I will focus today on cohort

6177
02:46:25,094 --> 02:46:26,702
studies of sleep and Down

6178
02:46:26,702 --> 02:46:27,346
syndrome,

6179
02:46:27,346 --> 02:46:29,096
which is an area that I have

6180
02:46:29,096 --> 02:46:31,073
been able to become involved in

6181
02:46:31,073 --> 02:46:32,284
as part of working

6182
02:46:32,284 --> 02:46:34,095
with the infant brain imaging

6183
02:46:34,095 --> 02:46:35,944
study and following an infant

6184
02:46:35,944 --> 02:46:37,156
cohort of children

6185
02:46:37,156 --> 02:46:38,841
with Down syndrome and Down

6186
02:46:38,841 --> 02:46:40,319
syndrome is as has been

6187
02:46:40,319 --> 02:46:41,026
discussed,

6188
02:46:41,026 --> 02:46:42,451
is a multi system neuro

6189
02:46:42,451 --> 02:46:43,629
genetic condition.

6190
02:46:43,629 --> 02:46:45,320
This this recent review article

6191
02:46:45,320 --> 02:46:46,465
shows it quite well.

6192
02:46:46,899 --> 02:46:48,716
Multiple medical comorbidities

6193
02:46:48,716 --> 02:46:50,212
are associated with Down

6194
02:46:50,212 --> 02:46:50,836
syndrome.

6195
02:46:51,070 --> 02:46:52,773
It is the most common genetic

6196
02:46:52,773 --> 02:46:54,033
cause of intellectual

6197
02:46:54,033 --> 02:46:55,474
developmental disorder,

6198
02:46:55,474 --> 02:46:56,901
which is one of its most

6199
02:46:56,901 --> 02:46:58,210
penetrant phenotypes.

6200
02:46:58,944 --> 02:47:01,043
But when thinking about sleep in

6201
02:47:01,043 --> 02:47:02,815
this particular condition,

6202
02:47:02,815 --> 02:47:04,780
there's just also the issue of

6203
02:47:04,780 --> 02:47:06,583
realizing that there's many

6204
02:47:06,583 --> 02:47:08,120
comorbidities and that

6205
02:47:08,120 --> 02:47:09,290
these can all have

6206
02:47:09,290 --> 02:47:10,656
reinforcing impacts.

6207
02:47:11,390 --> 02:47:13,248
Sleep problems are common and

6208
02:47:13,248 --> 02:47:14,701
persistent as has been

6209
02:47:14,701 --> 02:47:15,427
discussed,

6210
02:47:15,427 --> 02:47:16,896
and when looking at the

6211
02:47:16,896 --> 02:47:18,919
literature on cohort studies in

6212
02:47:18,919 --> 02:47:19,898
Down syndrome,

6213
02:47:19,898 --> 02:47:21,768
many of the studies have been

6214
02:47:21,768 --> 02:47:22,735
retrospective,

6215
02:47:22,735 --> 02:47:23,999
involving clinically

6216
02:47:23,999 --> 02:47:25,137
referred samples.

6217
02:47:25,738 --> 02:47:28,022
This has been very helpful for

6218
02:47:28,022 --> 02:47:30,277
looking again at associations

6219
02:47:30,277 --> 02:47:31,677
with Co occurring

6220
02:47:31,677 --> 02:47:34,051
conditions as well as following

6221
02:47:34,051 --> 02:47:36,476
when at different points in the

6222
02:47:36,476 --> 02:47:37,649
life stage the

6223
02:47:37,649 --> 02:47:38,929
sleep problems in

6224
02:47:38,929 --> 02:47:40,586
Down syndrome emerge.

6225
02:47:41,820 --> 02:47:43,417
There are also prospective

6226
02:47:43,417 --> 02:47:45,171
studies which generally have

6227
02:47:45,171 --> 02:47:46,425
looked at treatment

6228
02:47:46,425 --> 02:47:48,207
response and the beginning of

6229
02:47:48,207 --> 02:47:50,023
predictive modeling to try to

6230
02:47:50,023 --> 02:47:51,463
understand what's what

6231
02:47:51,463 --> 02:47:53,382
predicts who will go on to have

6232
02:47:53,382 --> 02:47:55,345
sleep problems like obstructive

6233
02:47:55,345 --> 02:47:56,168
sleep apnea,

6234
02:47:56,168 --> 02:47:56,721
you know,

6235
02:47:56,721 --> 02:47:58,611
and what might be factors that

6236
02:47:58,611 --> 02:47:59,304
could help

6237
02:47:59,304 --> 02:48:00,724
determine which type of

6238
02:48:00,724 --> 02:48:02,183
treatment would be most

6239
02:48:02,183 --> 02:48:03,008
appropriate.

6240
02:48:04,209 --> 02:48:05,641
And one other thing is that a

6241
02:48:05,641 --> 02:48:07,257
lot of the work has been done in

6242
02:48:07,257 --> 02:48:07,813
childhood.

6243
02:48:07,813 --> 02:48:09,630
There is work in adults work in

6244
02:48:09,630 --> 02:48:11,546
infancy is pretty rare when when

6245
02:48:11,546 --> 02:48:12,384
good piece of

6246
02:48:12,384 --> 02:48:14,242
news when thinking about some of

6247
02:48:14,242 --> 02:48:16,083
the literature on Down syndrome

6248
02:48:16,083 --> 02:48:16,855
in the field

6249
02:48:16,855 --> 02:48:17,558
I deal with,

6250
02:48:17,558 --> 02:48:19,478
which is often brain development

6251
02:48:19,478 --> 02:48:19,958
is that

6252
02:48:19,958 --> 02:48:21,846
there does seem to be a range of

6253
02:48:21,846 --> 02:48:23,262
sample sizes, you know,

6254
02:48:23,262 --> 02:48:25,017
and it does seem like this has

6255
02:48:25,017 --> 02:48:26,929
been helped, you know, depending

6256
02:48:26,929 --> 02:48:27,766
on, you know,

6257
02:48:27,766 --> 02:48:29,219
sometimes access to large

6258
02:48:29,219 --> 02:48:30,832
databases or large clinical

6259
02:48:30,832 --> 02:48:31,370
centers.

6260
02:48:33,539 --> 02:48:35,053
So in terms of, you know,

6261
02:48:35,053 --> 02:48:36,855
just key findings of what has

6262
02:48:36,855 --> 02:48:37,476
have been

6263
02:48:37,476 --> 02:48:39,184
learned across some of these

6264
02:48:39,184 --> 02:48:41,122
cohort studies I had mentioned,

6265
02:48:41,122 --> 02:48:41,747
you know,

6266
02:48:41,747 --> 02:48:43,385
that one one thing to think

6267
02:48:43,385 --> 02:48:45,128
about is the nature of sleep

6268
02:48:45,128 --> 02:48:45,751
problems.

6269
02:48:46,585 --> 02:48:48,001
And as has been discussed,

6270
02:48:48,001 --> 02:48:49,619
there is a high prevalence of

6271
02:48:49,619 --> 02:48:50,289
obstructive

6272
02:48:50,289 --> 02:48:51,857
sleep apnea at multiple ages.

6273
02:48:52,424 --> 02:48:52,936
You know,

6274
02:48:52,936 --> 02:48:54,751
we heard how it is identifiable

6275
02:48:54,751 --> 02:48:54,927
in

6276
02:48:54,927 --> 02:48:55,394
infants.

6277
02:48:55,727 --> 02:48:56,273
Currently,

6278
02:48:56,273 --> 02:48:57,949
pediatric guidelines recommend

6279
02:48:57,949 --> 02:48:58,564
testing or

6280
02:48:58,564 --> 02:49:00,139
assessment for that at age 4,

6281
02:49:00,139 --> 02:49:01,866
but it does look to be starting

6282
02:49:01,866 --> 02:49:02,367
earlier.

6283
02:49:03,035 --> 02:49:04,341
But again, as mentioned,

6284
02:49:04,341 --> 02:49:05,902
infant studies are much less

6285
02:49:05,902 --> 02:49:06,572
common than

6286
02:49:06,572 --> 02:49:07,668
studies in childhood

6287
02:49:07,668 --> 02:49:08,874
or even in adulthood.

6288
02:49:09,908 --> 02:49:12,141
Increasing work has been done to

6289
02:49:12,141 --> 02:49:13,745
show that parasomnias,

6290
02:49:13,745 --> 02:49:14,639
insomnias and

6291
02:49:14,639 --> 02:49:16,014
daytime sleepiness.

6292
02:49:16,381 --> 02:49:18,125
So non respiratory issues

6293
02:49:18,125 --> 02:49:20,257
associated with sleep problems

6294
02:49:20,257 --> 02:49:21,820
are also very common,

6295
02:49:21,820 --> 02:49:24,042
as well as emerging evidence for

6296
02:49:24,042 --> 02:49:25,963
a movement disorder related

6297
02:49:25,963 --> 02:49:26,959
issues during

6298
02:49:26,959 --> 02:49:28,485
sleep such as periodic

6299
02:49:28,485 --> 02:49:29,595
limb movements.

6300
02:49:30,529 --> 02:49:32,296
And the sleep problems are also

6301
02:49:32,296 --> 02:49:33,265
very persistent.

6302
02:49:33,265 --> 02:49:34,590
And this is even true when

6303
02:49:34,590 --> 02:49:36,068
getting surgical treatments.

6304
02:49:36,969 --> 02:49:38,596
But also just in, in general,

6305
02:49:38,596 --> 02:49:40,326
they, they do, they do tend to

6306
02:49:40,326 --> 02:49:40,672
last.

6307
02:49:40,672 --> 02:49:42,330
I'm in looking at cohort

6308
02:49:42,330 --> 02:49:44,377
studies, observation of sleep

6309
02:49:44,377 --> 02:49:45,577
trouble or sleep

6310
02:49:45,577 --> 02:49:47,721
problems or using a milder non,

6311
02:49:47,721 --> 02:49:49,923
non surgical treatments in some

6312
02:49:49,923 --> 02:49:50,349
cases

6313
02:49:50,349 --> 02:49:51,311
often seems to

6314
02:49:51,311 --> 02:49:52,618
have mixed effect.

6315
02:49:53,752 --> 02:49:55,562
And then in terms of factors in

6316
02:49:55,562 --> 02:49:56,788
predictive modeling,

6317
02:49:56,788 --> 02:49:58,524
there is evidence that obesity

6318
02:49:58,524 --> 02:50:00,178
and as well as Tonsiller and

6319
02:50:00,178 --> 02:50:01,360
adenoid hypertrophy

6320
02:50:01,360 --> 02:50:03,045
are factors that increase the

6321
02:50:03,045 --> 02:50:04,963
risk of obstructive sleep apnea.

6322
02:50:05,631 --> 02:50:07,627
Other issues include early

6323
02:50:07,627 --> 02:50:09,981
feeding problems or periods of

6324
02:50:09,981 --> 02:50:11,236
long NICU stay,

6325
02:50:11,236 --> 02:50:13,372
you know, during early life.

6326
02:50:14,139 --> 02:50:15,493
And there have been the

6327
02:50:15,493 --> 02:50:17,295
beginnings of some models that

6328
02:50:17,295 --> 02:50:18,377
take a variety of

6329
02:50:18,377 --> 02:50:19,796
clinical and demographic

6330
02:50:19,796 --> 02:50:21,542
features that have identified

6331
02:50:21,542 --> 02:50:23,048
good negative predictive

6332
02:50:23,048 --> 02:50:24,820
value in terms of children who

6333
02:50:24,820 --> 02:50:26,754
you know were are unlikely to go

6334
02:50:26,754 --> 02:50:27,419
on to have

6335
02:50:27,419 --> 02:50:29,092
obstructive sleep apnea with

6336
02:50:29,092 --> 02:50:29,988
Down syndrome.

6337
02:50:30,422 --> 02:50:31,775
But models have been less

6338
02:50:31,775 --> 02:50:33,432
effective looking for positive

6339
02:50:33,432 --> 02:50:34,426
predictive value.

6340
02:50:36,194 --> 02:50:37,690
Other areas that have been

6341
02:50:37,690 --> 02:50:39,216
assessed with these cohort

6342
02:50:39,216 --> 02:50:40,566
studies are related to

6343
02:50:40,566 --> 02:50:41,611
practice patterns,

6344
02:50:41,611 --> 02:50:43,161
treatment effects and then

6345
02:50:43,161 --> 02:50:43,936
relationship

6346
02:50:43,936 --> 02:50:45,070
to function overall.

6347
02:50:46,104 --> 02:50:48,270
And so guidelines that have been

6348
02:50:48,270 --> 02:50:50,490
developed in the past decade and

6349
02:50:50,490 --> 02:50:50,976
1/2 or

6350
02:50:50,976 --> 02:50:52,938
so appear to have benefit and

6351
02:50:52,938 --> 02:50:54,949
children getting assessed and

6352
02:50:54,949 --> 02:50:55,781
referred to

6353
02:50:55,781 --> 02:50:57,182
treatment more often.

6354
02:50:57,983 --> 02:50:59,613
Although treatment effects as

6355
02:50:59,613 --> 02:51:01,278
have been mentioned have been

6356
02:51:01,278 --> 02:51:02,254
mixed, you know,

6357
02:51:02,254 --> 02:51:03,941
even those surgical treatments

6358
02:51:03,941 --> 02:51:05,290
are very commonly done.

6359
02:51:05,290 --> 02:51:07,370
The resolution of OHOSA symptoms

6360
02:51:07,370 --> 02:51:09,061
tends to be only partial,

6361
02:51:09,061 --> 02:51:10,475
although in many cases

6362
02:51:10,475 --> 02:51:11,697
it's been helpful.

6363
02:51:12,564 --> 02:51:14,234
There are newer treatments that

6364
02:51:14,234 --> 02:51:15,717
have been tried in terms of

6365
02:51:15,717 --> 02:51:17,035
hypoglossal stimulation

6366
02:51:17,035 --> 02:51:18,552
to increase tone and in that

6367
02:51:18,552 --> 02:51:20,100
upper airway and evidence in

6368
02:51:20,100 --> 02:51:21,206
adolescence through

6369
02:51:21,206 --> 02:51:22,868
adults as well as the beginning

6370
02:51:22,868 --> 02:51:24,209
of evidence in children.

6371
02:51:25,110 --> 02:51:26,629
And as I mentioned earlier,

6372
02:51:26,629 --> 02:51:28,246
while there are a variety of

6373
02:51:28,246 --> 02:51:28,880
treatments

6374
02:51:28,880 --> 02:51:30,525
that have been discussed that

6375
02:51:30,525 --> 02:51:32,328
have been tried and such as non

6376
02:51:32,328 --> 02:51:32,851
invasive

6377
02:51:32,851 --> 02:51:34,151
ventilation support and

6378
02:51:34,151 --> 02:51:35,994
medication, these often times do

6379
02:51:35,994 --> 02:51:37,089
not appear to have

6380
02:51:37,089 --> 02:51:37,887
the, you know,

6381
02:51:37,887 --> 02:51:39,757
even the relative consistency of

6382
02:51:39,757 --> 02:51:40,225
effects

6383
02:51:40,225 --> 02:51:41,811
that has been seen with more

6384
02:51:41,811 --> 02:51:43,430
surgical treatments and even

6385
02:51:43,430 --> 02:51:44,529
those are somewhat

6386
02:51:44,529 --> 02:51:44,863
mixed.

6387
02:51:45,063 --> 02:51:46,845
So there's a need to improve

6388
02:51:46,845 --> 02:51:48,470
treatments, you know, and

6389
02:51:48,470 --> 02:51:49,835
treatment targeting.

6390
02:51:50,469 --> 02:51:51,633
And then in terms of

6391
02:51:51,633 --> 02:51:53,205
relationships to function,

6392
02:51:53,205 --> 02:51:55,049
there has been a lot of work and

6393
02:51:55,049 --> 02:51:56,652
already discussed that, you

6394
02:51:56,652 --> 02:51:57,009
know,

6395
02:51:57,009 --> 02:51:58,339
aspects of cognition or

6396
02:51:58,339 --> 02:51:59,611
psychiatric symptoms.

6397
02:51:59,911 --> 02:52:01,580
These things are likely to be

6398
02:52:01,580 --> 02:52:03,248
affected when sleep is poor.

6399
02:52:03,582 --> 02:52:05,020
Although cohort studies in

6400
02:52:05,020 --> 02:52:06,657
general have not always found

6401
02:52:06,657 --> 02:52:07,786
these effects to be

6402
02:52:07,786 --> 02:52:08,946
consistent, you know,

6403
02:52:08,946 --> 02:52:10,589
which suggests that more work

6404
02:52:10,589 --> 02:52:11,156
should be

6405
02:52:11,156 --> 02:52:12,867
or needs to be done in terms of

6406
02:52:12,867 --> 02:52:14,333
measuring these things and

6407
02:52:14,333 --> 02:52:15,460
parsing some of the

6408
02:52:15,460 --> 02:52:16,595
sleep conditions that

6409
02:52:16,595 --> 02:52:17,729
are being looked at.

6410
02:52:18,563 --> 02:52:20,466
You know, more more precisely in

6411
02:52:20,466 --> 02:52:21,833
terms of, for example,

6412
02:52:21,833 --> 02:52:23,672
respiratory and non respiratory

6413
02:52:23,672 --> 02:52:24,503
sleep issues.

6414
02:52:27,105 --> 02:52:28,607
So just as a big broad, you

6415
02:52:28,607 --> 02:52:30,256
know, summary of kind of what

6416
02:52:30,256 --> 02:52:31,109
what the field

6417
02:52:31,109 --> 02:52:32,818
you know has has shown in terms

6418
02:52:32,818 --> 02:52:34,576
of looking at cohorts over time

6419
02:52:34,576 --> 02:52:34,746
of

6420
02:52:34,746 --> 02:52:36,448
individuals with Down syndrome.

6421
02:52:37,416 --> 02:52:39,302
There really has been, you know,

6422
02:52:39,302 --> 02:52:40,995
a lot of characterization of

6423
02:52:40,995 --> 02:52:41,720
respiratory

6424
02:52:41,720 --> 02:52:43,138
sleep problems primarily

6425
02:52:43,138 --> 02:52:44,898
relative to obstructive sleep

6426
02:52:44,898 --> 02:52:45,323
apnea,

6427
02:52:45,323 --> 02:52:46,984
with more work needing to be

6428
02:52:46,984 --> 02:52:48,623
done in the non respiratory

6429
02:52:48,623 --> 02:52:49,594
sleep problems.

6430
02:52:50,262 --> 02:52:52,054
You know, things like daytime

6431
02:52:52,054 --> 02:52:53,598
sleepiness, for example,

6432
02:52:53,598 --> 02:52:55,564
or parasomnias or insomnias that

6433
02:52:55,564 --> 02:52:57,205
also are thought to affect

6434
02:52:57,205 --> 02:52:57,836
function.

6435
02:52:58,904 --> 02:53:00,621
The representation across the

6436
02:53:00,621 --> 02:53:02,380
lifespan seems to be skewed a

6437
02:53:02,380 --> 02:53:03,108
lot towards

6438
02:53:03,108 --> 02:53:04,358
childhood and beyond,

6439
02:53:04,358 --> 02:53:06,144
less so in early development.

6440
02:53:06,144 --> 02:53:07,546
And as was discussed in the last

6441
02:53:07,546 --> 02:53:08,246
talk, you know,

6442
02:53:08,246 --> 02:53:09,609
there can be work to be done in

6443
02:53:09,609 --> 02:53:11,016
these areas when thinking about

6444
02:53:11,016 --> 02:53:12,284
neurodevelopmental conditions.

6445
02:53:13,251 --> 02:53:15,359
And some work needing to be done

6446
02:53:15,359 --> 02:53:16,774
on the consistency of

6447
02:53:16,774 --> 02:53:18,323
relationships of sleep

6448
02:53:18,323 --> 02:53:20,169
problems to outcomes and the

6449
02:53:20,169 --> 02:53:22,050
need to have treatments that

6450
02:53:22,050 --> 02:53:23,662
allow better resolution

6451
02:53:23,662 --> 02:53:25,783
of symptoms and ongoing interest

6452
02:53:25,783 --> 02:53:27,616
in evaluating the impact of

6453
02:53:27,616 --> 02:53:28,567
treatments on

6454
02:53:28,567 --> 02:53:29,868
health and function.

6455
02:53:30,268 --> 02:53:31,744
And that seemed to be an area

6456
02:53:31,744 --> 02:53:33,405
that was not particularly or not

6457
02:53:33,405 --> 02:53:34,339
as well addressed

6458
02:53:34,339 --> 02:53:35,474
as some of the others.

6459
02:53:37,676 --> 02:53:39,617
So in terms of additional work

6460
02:53:39,617 --> 02:53:41,728
that can be done on using cohort

6461
02:53:41,728 --> 02:53:42,981
studies, you know,

6462
02:53:42,981 --> 02:53:44,802
for for infant infancy, as I

6463
02:53:44,802 --> 02:53:46,925
mentioned, you heard a bit about

6464
02:53:46,925 --> 02:53:48,053
the infant brain

6465
02:53:48,053 --> 02:53:48,954
imaging study.

6466
02:53:48,954 --> 02:53:49,755
So I will be

6467
02:53:49,755 --> 02:53:51,156
somewhat brief here.

6468
02:53:51,356 --> 02:53:52,724
Multi site study.

6469
02:53:53,425 --> 02:53:55,072
We focus on developmental

6470
02:53:55,072 --> 02:53:55,994
neuroimaging.

6471
02:53:55,994 --> 02:53:57,651
We've been funded for over a

6472
02:53:57,651 --> 02:53:59,223
decade originally starting

6473
02:53:59,223 --> 02:54:00,432
looking at children

6474
02:54:00,432 --> 02:54:02,222
who have an increased familial

6475
02:54:02,222 --> 02:54:03,535
likelihood of autism,

6476
02:54:03,535 --> 02:54:05,440
but we've also done work in Down

6477
02:54:05,440 --> 02:54:07,405
syndrome and fragile X syndrome.

6478
02:54:08,273 --> 02:54:10,033
And this timeline of the Infant

6479
02:54:10,033 --> 02:54:11,600
Brain Imaging Study Network

6480
02:54:11,600 --> 02:54:12,644
shows the variety

6481
02:54:12,644 --> 02:54:14,243
of cohorts that we have been

6482
02:54:14,243 --> 02:54:15,213
able to explore,

6483
02:54:15,213 --> 02:54:16,919
which does in the future allow

6484
02:54:16,919 --> 02:54:18,774
for some opportunities for cross

6485
02:54:18,774 --> 02:54:19,818
cohort comparison

6486
02:54:19,818 --> 02:54:21,112
with neurodevelopmental

6487
02:54:21,112 --> 02:54:21,787
conditions.

6488
02:54:22,854 --> 02:54:23,734
More recently,

6489
02:54:23,734 --> 02:54:25,735
we have taken up more work with

6490
02:54:25,735 --> 02:54:26,057
Down

6491
02:54:26,057 --> 02:54:27,791
syndrome, which is the, the,

6492
02:54:27,791 --> 02:54:29,821
the reason I've been focusing on

6493
02:54:29,821 --> 02:54:30,328
that on

6494
02:54:30,328 --> 02:54:30,929
that here.

6495
02:54:32,964 --> 02:54:35,127
However, at the same time, our,

6496
02:54:35,127 --> 02:54:37,267
our work, you know, looking at

6497
02:54:37,267 --> 02:54:38,336
the, you know,

6498
02:54:38,336 --> 02:54:38,963
children,

6499
02:54:38,963 --> 02:54:41,249
you have increased likelihood of

6500
02:54:41,249 --> 02:54:41,606
Down

6501
02:54:41,606 --> 02:54:43,836
syndrome has been helpful in our

6502
02:54:43,836 --> 02:54:45,901
ability to begin to establish

6503
02:54:45,901 --> 02:54:47,112
relationships of

6504
02:54:47,112 --> 02:54:49,264
behavioral differences in terms

6505
02:54:49,264 --> 02:54:51,416
of sleep issues and the brain.

6506
02:54:51,750 --> 02:54:53,201
And so I just wanted to briefly

6507
02:54:53,201 --> 02:54:54,684
allude to some of the work that

6508
02:54:54,684 --> 02:54:55,353
doctor Estes,

6509
02:54:55,353 --> 02:54:56,454
you know, had mentioned.

6510
02:54:57,088 --> 02:54:59,543
This basically showed that with

6511
02:54:59,543 --> 02:55:01,824
parent report information on

6512
02:55:01,824 --> 02:55:02,394
sleep,

6513
02:55:02,394 --> 02:55:04,837
our team was able to show under

6514
02:55:04,837 --> 02:55:07,104
her leadership that children

6515
02:55:07,104 --> 02:55:07,833
that the

6516
02:55:07,833 --> 02:55:10,347
children who went on to have ASD

6517
02:55:10,347 --> 02:55:12,840
did show strong associations of

6518
02:55:12,840 --> 02:55:13,805
their sleep

6519
02:55:13,805 --> 02:55:14,817
problems with

6520
02:55:14,817 --> 02:55:16,374
hippocampal volume.

6521
02:55:16,675 --> 02:55:18,220
This was also true with other

6522
02:55:18,220 --> 02:55:19,857
groups, but especially true in

6523
02:55:19,857 --> 02:55:20,512
that group,

6524
02:55:20,512 --> 02:55:21,895
and it was specific to the

6525
02:55:21,895 --> 02:55:23,471
hippocampus relative to other

6526
02:55:23,471 --> 02:55:24,449
brain structures.

6527
02:55:25,884 --> 02:55:27,894
Currently what we are are are

6528
02:55:27,894 --> 02:55:30,016
have been able to do and again

6529
02:55:30,016 --> 02:55:31,289
acknowledging Dr.

6530
02:55:31,289 --> 02:55:33,823
Estes with this work is to look

6531
02:55:33,823 --> 02:55:35,910
at our current new infant

6532
02:55:35,910 --> 02:55:37,829
samples and to look at

6533
02:55:37,829 --> 02:55:40,211
a cohort of infants with Down

6534
02:55:40,211 --> 02:55:42,894
syndrome as well as a new cohort

6535
02:55:42,894 --> 02:55:44,236
of infants that

6536
02:55:44,236 --> 02:55:46,850
increase familial likelihood for

6537
02:55:46,850 --> 02:55:49,439
ASD at six and 12 months of age

6538
02:55:49,439 --> 02:55:50,609
are too early

6539
02:55:50,609 --> 02:55:52,377
time points the study.

6540
02:55:52,377 --> 02:55:54,832
The study is continuing to have

6541
02:55:54,832 --> 02:55:57,182
data collected through the 24

6542
02:55:57,182 --> 02:55:58,316
month outcome

6543
02:55:58,316 --> 02:56:00,703
and to begin to ask what kinds

6544
02:56:00,703 --> 02:56:02,897
of sleep characteristics by

6545
02:56:02,897 --> 02:56:04,522
parent report do we

6546
02:56:04,522 --> 02:56:06,831
see in these two cohorts when

6547
02:56:06,831 --> 02:56:09,060
followed across these ages.

6548
02:56:09,060 --> 02:56:11,333
And so this table here shows our

6549
02:56:11,333 --> 02:56:13,594
current sample sizes about, you

6550
02:56:13,594 --> 02:56:14,032
know,

6551
02:56:14,032 --> 02:56:16,028
close to 60 kids in the Down

6552
02:56:16,028 --> 02:56:17,168
syndrome Group,

6553
02:56:17,168 --> 02:56:19,279
A large group of children with

6554
02:56:19,279 --> 02:56:21,502
increased family likelihood for

6555
02:56:21,502 --> 02:56:23,008
autism and you know,

6556
02:56:23,008 --> 02:56:23,308
173.

6557
02:56:23,942 --> 02:56:25,481
And then also a group of

6558
02:56:25,481 --> 02:56:27,115
children without a family

6559
02:56:27,115 --> 02:56:28,880
history of autism are most

6560
02:56:28,880 --> 02:56:30,578
likely to be our typically

6561
02:56:30,578 --> 02:56:31,950
developing controls.

6562
02:56:35,020 --> 02:56:36,439
And parent reported sleep

6563
02:56:36,439 --> 02:56:38,291
concerns were obtained using the

6564
02:56:38,291 --> 02:56:39,391
Brief Infant Sleep

6565
02:56:39,391 --> 02:56:40,191
Questionnaire.

6566
02:56:40,992 --> 02:56:43,243
And we began by taking a look

6567
02:56:43,243 --> 02:56:44,329
at, you know,

6568
02:56:44,329 --> 02:56:46,500
what was the level of parent

6569
02:56:46,500 --> 02:56:49,037
reported sleep problems reported

6570
02:56:49,037 --> 02:56:50,068
in these two

6571
02:56:50,068 --> 02:56:52,456
groups and comparing across the

6572
02:56:52,456 --> 02:56:54,893
the Down syndrome group as well

6573
02:56:54,893 --> 02:56:56,308
as the group that

6574
02:56:56,308 --> 02:56:57,699
has that increased

6575
02:56:57,699 --> 02:56:59,899
neurodevelopmental liability

6576
02:56:59,899 --> 02:57:02,414
related to increased likelihood

6577
02:57:02,414 --> 02:57:03,248
for autism.

6578
02:57:04,149 --> 02:57:05,264
And at six months,

6579
02:57:05,264 --> 02:57:07,046
parents of infants with Down

6580
02:57:07,046 --> 02:57:07,619
syndrome

6581
02:57:07,619 --> 02:57:09,608
reported fewer concerns than the

6582
02:57:09,608 --> 02:57:11,067
high likelihood and low

6583
02:57:11,067 --> 02:57:12,590
likelihood groups here.

6584
02:57:12,590 --> 02:57:13,184
So again,

6585
02:57:13,184 --> 02:57:15,356
that group with increased chance

6586
02:57:15,356 --> 02:57:15,560
of

6587
02:57:15,560 --> 02:57:16,517
autism and then

6588
02:57:16,517 --> 02:57:17,729
our control group.

6589
02:57:18,330 --> 02:57:20,333
So an interesting finding there,

6590
02:57:20,333 --> 02:57:22,323
especially given how many sleep

6591
02:57:22,323 --> 02:57:22,901
problems

6592
02:57:22,901 --> 02:57:24,910
there are in Down syndrome later

6593
02:57:24,910 --> 02:57:26,604
in the in the life course.

6594
02:57:28,273 --> 02:57:28,863
However,

6595
02:57:28,863 --> 02:57:30,987
in infants with longitudinal

6596
02:57:30,987 --> 02:57:31,443
data,

6597
02:57:31,443 --> 02:57:33,713
what we did find when comparing

6598
02:57:33,713 --> 02:57:35,954
6 and 12 month scores was that

6599
02:57:35,954 --> 02:57:37,449
the group with Down

6600
02:57:37,449 --> 02:57:39,711
syndrome showed the greatest or

6601
02:57:39,711 --> 02:57:42,096
should increased parent reported

6602
02:57:42,096 --> 02:57:43,288
sleep concerns.

6603
02:57:43,655 --> 02:57:45,288
And so that can be seen by the

6604
02:57:45,288 --> 02:57:46,846
increased size in the darker

6605
02:57:46,846 --> 02:57:47,792
Gray bars in the

6606
02:57:47,792 --> 02:57:49,478
beginning of a little black bar

6607
02:57:49,478 --> 02:57:51,206
showing up in the Down syndrome

6608
02:57:51,206 --> 02:57:51,763
group and

6609
02:57:51,763 --> 02:57:52,620
compared between

6610
02:57:52,620 --> 02:57:53,531
6 and 12 months.

6611
02:57:54,366 --> 02:57:56,416
So suggesting here that some

6612
02:57:56,416 --> 02:57:58,584
advancement of development is

6613
02:57:58,584 --> 02:58:00,005
beginning to have,

6614
02:58:00,005 --> 02:58:00,669
you know,

6615
02:58:00,669 --> 02:58:03,020
some some change in the ease of

6616
02:58:03,020 --> 02:58:03,475
sleep

6617
02:58:03,475 --> 02:58:04,617
that parents are

6618
02:58:04,617 --> 02:58:06,044
able to pick up on.

6619
02:58:09,347 --> 02:58:11,752
And looking at the the bisque

6620
02:58:11,752 --> 02:58:14,223
questions on day sleep, night

6621
02:58:14,223 --> 02:58:14,819
sleep,

6622
02:58:14,819 --> 02:58:16,326
night wakefulness,

6623
02:58:16,326 --> 02:58:18,654
night wakefulness and sleep

6624
02:58:18,654 --> 02:58:19,257
onset.

6625
02:58:19,657 --> 02:58:21,763
And we were able to compare the

6626
02:58:21,763 --> 02:58:23,909
change in sleep characteristics

6627
02:58:23,909 --> 02:58:25,363
from 6 to 12 months.

6628
02:58:26,297 --> 02:58:28,071
And looking at the groups,

6629
02:58:28,071 --> 02:58:30,239
we could see that both the Down

6630
02:58:30,239 --> 02:58:30,869
syndrome

6631
02:58:30,869 --> 02:58:32,568
and children at increased

6632
02:58:32,568 --> 02:58:34,506
likelihood of autism did not

6633
02:58:34,506 --> 02:58:36,374
increase in night sleep as

6634
02:58:36,374 --> 02:58:37,375
much as the low

6635
02:58:37,375 --> 02:58:38,576
likelihood group.

6636
02:58:39,210 --> 02:58:41,377
So this would be an expected

6637
02:58:41,377 --> 02:58:43,756
part of development that seems

6638
02:58:43,756 --> 02:58:44,549
to be not

6639
02:58:44,549 --> 02:58:46,870
proceeding at the same pace as

6640
02:58:46,870 --> 02:58:48,186
it is, you know,

6641
02:58:48,186 --> 02:58:49,959
for the for the control

6642
02:58:49,959 --> 02:58:52,399
children, the Down syndrome and

6643
02:58:52,399 --> 02:58:53,658
high likelihood

6644
02:58:53,658 --> 02:58:56,130
groups also increased relatively

6645
02:58:56,130 --> 02:58:57,829
in night wakefulness.

6646
02:58:58,396 --> 02:58:58,978
So again,

6647
02:58:58,978 --> 02:59:00,836
in terms of what's happening

6648
02:59:00,836 --> 02:59:01,566
during the

6649
02:59:01,566 --> 02:59:03,450
typical development or in the

6650
02:59:03,450 --> 02:59:05,270
typically developing group,

6651
02:59:05,270 --> 02:59:06,871
this is also a different.

6652
02:59:07,906 --> 02:59:10,095
And the Down syndrome group also

6653
02:59:10,095 --> 02:59:12,051
showed increased sleep onset

6654
02:59:12,051 --> 02:59:13,378
latency versus the

6655
02:59:13,378 --> 02:59:14,779
low likelihood group.

6656
02:59:15,146 --> 02:59:17,188
So something between 6 and 12

6657
02:59:17,188 --> 02:59:19,492
months is beginning to change in

6658
02:59:19,492 --> 02:59:20,285
the in the

6659
02:59:20,285 --> 02:59:22,463
children with Down syndrome and

6660
02:59:22,463 --> 02:59:24,561
is looking in many cases even

6661
02:59:24,561 --> 02:59:24,923
more

6662
02:59:24,923 --> 02:59:27,032
significant than what is being

6663
02:59:27,032 --> 02:59:28,987
seen in the high likelihood

6664
02:59:28,987 --> 02:59:29,494
group,

6665
02:59:29,494 --> 02:59:31,755
at least when looking grossly at

6666
02:59:31,755 --> 02:59:33,098
these percentages.

6667
02:59:34,466 --> 02:59:36,436
So what we do see then is signs

6668
02:59:36,436 --> 02:59:38,470
of emergence of sleep problems.

6669
02:59:38,470 --> 02:59:39,947
And this is something, you know,

6670
02:59:39,947 --> 02:59:41,272
again that the Down syndrome

6671
02:59:41,272 --> 02:59:41,840
group stood

6672
02:59:41,840 --> 02:59:43,074
out in in certain respects.

6673
02:59:43,908 --> 02:59:45,591
And this suggests that when

6674
02:59:45,591 --> 02:59:47,571
thinking about the relationship

6675
02:59:47,571 --> 02:59:48,146
of sleep

6676
02:59:48,146 --> 02:59:50,029
differences and and mechanisms

6677
02:59:50,029 --> 02:59:51,955
of biology that can contribute

6678
02:59:51,955 --> 02:59:52,917
to these sleep

6679
02:59:52,917 --> 02:59:53,673
differences,

6680
02:59:53,673 --> 02:59:55,351
there may be some specific

6681
02:59:55,351 --> 02:59:56,254
profiles that

6682
02:59:56,254 --> 02:59:58,127
could be compared between Down

6683
02:59:58,127 --> 03:00:00,177
syndrome and the high likelihood

6684
03:00:00,177 --> 03:00:00,625
group,

6685
03:00:00,625 --> 03:00:02,497
which could again provide some

6686
03:00:02,497 --> 03:00:04,346
helpful information about the

6687
03:00:04,346 --> 03:00:05,430
differences than

6688
03:00:05,430 --> 03:00:06,479
brain development

6689
03:00:06,479 --> 03:00:07,899
that are contributing.

6690
03:00:08,833 --> 03:00:10,386
There is parental awareness of

6691
03:00:10,386 --> 03:00:11,972
these sleep problems that does

6692
03:00:11,972 --> 03:00:12,871
appear to change

6693
03:00:12,871 --> 03:00:13,338
with age,

6694
03:00:13,338 --> 03:00:14,672
although correlation with

6695
03:00:14,672 --> 03:00:15,206
objective

6696
03:00:15,206 --> 03:00:16,508
metrics would be helpful.

6697
03:00:17,008 --> 03:00:18,696
And there's the implication then

6698
03:00:18,696 --> 03:00:20,155
that earlier sleep targeted

6699
03:00:20,155 --> 03:00:20,912
interventions

6700
03:00:20,912 --> 03:00:22,464
could be helpful for outcomes

6701
03:00:22,464 --> 03:00:23,748
and in this population.

6702
03:00:25,316 --> 03:00:27,275
So I will, you know, so that is

6703
03:00:27,275 --> 03:00:29,020
a, you know, using a parent

6704
03:00:29,020 --> 03:00:30,054
report measure,

6705
03:00:30,054 --> 03:00:31,882
a very interesting, you know,

6706
03:00:31,882 --> 03:00:33,458
way to get at, you know,

6707
03:00:33,458 --> 03:00:35,361
the issues with sleep that are

6708
03:00:35,361 --> 03:00:37,328
being reported in this cohort.

6709
03:00:38,196 --> 03:00:40,586
But through the include project

6710
03:00:40,586 --> 03:00:43,112
and NIH wide research initiative

6711
03:00:43,112 --> 03:00:43,902
to expand

6712
03:00:43,902 --> 03:00:45,922
research in Down syndrome,

6713
03:00:45,922 --> 03:00:48,390
our Ibis network team will also

6714
03:00:48,390 --> 03:00:49,107
have the

6715
03:00:49,107 --> 03:00:51,372
opportunity to participate in

6716
03:00:51,372 --> 03:00:52,544
another study,

6717
03:00:52,544 --> 03:00:55,049
which will allow a more lifespan

6718
03:00:55,049 --> 03:00:56,381
cohort approach.

6719
03:00:57,148 --> 03:00:58,472
And so as part of include,

6720
03:00:58,472 --> 03:01:00,151
there's a goal to investigate Co

6721
03:01:00,151 --> 03:01:01,790
occurring conditions that affect

6722
03:01:01,790 --> 03:01:03,368
individuals with Down syndrome

6723
03:01:03,368 --> 03:01:03,788
and the

6724
03:01:03,788 --> 03:01:05,067
general population and to

6725
03:01:05,067 --> 03:01:06,216
increase the number of

6726
03:01:06,216 --> 03:01:07,625
investigators and trainees

6727
03:01:07,625 --> 03:01:09,115
studying Down syndrome and to

6728
03:01:09,115 --> 03:01:10,584
engage a wide range of those

6729
03:01:10,584 --> 03:01:11,529
with DS and their

6730
03:01:11,529 --> 03:01:11,996
families.

6731
03:01:12,463 --> 03:01:14,844
And this this cohort project is

6732
03:01:14,844 --> 03:01:16,534
1 one way to do that.

6733
03:01:17,569 --> 03:01:19,704
And so this this research effort

6734
03:01:19,704 --> 03:01:21,272
is known as the include

6735
03:01:21,272 --> 03:01:22,840
collaboration for Down

6736
03:01:22,840 --> 03:01:24,008
syndrome progress.

6737
03:01:24,976 --> 03:01:26,329
And the goal is to study the

6738
03:01:26,329 --> 03:01:27,908
Natural History of Down syndrome

6739
03:01:27,908 --> 03:01:28,746
in a deeper way.

6740
03:01:28,746 --> 03:01:31,008
That's been done before with a

6741
03:01:31,008 --> 03:01:33,315
multi site cohort through data

6742
03:01:33,315 --> 03:01:34,852
collection and this

6743
03:01:34,852 --> 03:01:36,073
lifespan cohort,

6744
03:01:36,073 --> 03:01:38,590
which will involve 5 study sites

6745
03:01:38,590 --> 03:01:40,875
evaluating children, children,

6746
03:01:40,875 --> 03:01:43,161
adults and infants, you know,

6747
03:01:43,161 --> 03:01:45,096
all across different ages.

6748
03:01:45,430 --> 03:01:46,927
We'll be able to examine Co

6749
03:01:46,927 --> 03:01:48,512
occurring medical conditions

6750
03:01:48,512 --> 03:01:49,701
that will also allow

6751
03:01:49,701 --> 03:01:51,318
us to understand the range of

6752
03:01:51,318 --> 03:01:53,033
individual differences in Down

6753
03:01:53,033 --> 03:01:53,605
syndrome.

6754
03:01:54,372 --> 03:01:56,289
A lot of data will be collected

6755
03:01:56,289 --> 03:01:57,941
that allow identifying the

6756
03:01:57,941 --> 03:01:58,576
impact of

6757
03:01:58,576 --> 03:02:00,491
experience as an environment on

6758
03:02:00,491 --> 03:02:02,523
development and the hope will be

6759
03:02:02,523 --> 03:02:02,714
to

6760
03:02:02,714 --> 03:02:04,651
provide a foundation for future

6761
03:02:04,651 --> 03:02:06,150
therapeutic approaches.

6762
03:02:06,684 --> 03:02:07,974
And at the same time,

6763
03:02:07,974 --> 03:02:09,988
this program will also strive to

6764
03:02:09,988 --> 03:02:10,555
keep the

6765
03:02:10,555 --> 03:02:12,530
community engaged in creating an

6766
03:02:12,530 --> 03:02:14,259
inclusive research program.

6767
03:02:15,059 --> 03:02:16,431
So I'll show the structure of

6768
03:02:16,431 --> 03:02:17,928
the study and then briefly talk

6769
03:02:17,928 --> 03:02:18,796
about some of the

6770
03:02:18,796 --> 03:02:19,637
sleep metrics that

6771
03:02:19,637 --> 03:02:20,665
we will be obtaining.

6772
03:02:21,232 --> 03:02:23,653
These five boxes here describe

6773
03:02:23,653 --> 03:02:26,214
the different projects that are

6774
03:02:26,214 --> 03:02:27,205
involved in

6775
03:02:27,205 --> 03:02:29,254
the in the include cohort

6776
03:02:29,254 --> 03:02:30,975
development program.

6777
03:02:30,975 --> 03:02:32,910
So the Infant Down syndrome baby

6778
03:02:32,910 --> 03:02:34,763
Brain study is an extension of

6779
03:02:34,763 --> 03:02:35,813
the Ibis network

6780
03:02:35,813 --> 03:02:37,585
that will continue to look at

6781
03:02:37,585 --> 03:02:39,470
infants at six, 1224 months of

6782
03:02:39,470 --> 03:02:39,784
age.

6783
03:02:40,451 --> 03:02:42,081
But we have several other

6784
03:02:42,081 --> 03:02:43,254
groups, you know,

6785
03:02:43,254 --> 03:02:45,230
collaborating from institutions

6786
03:02:45,230 --> 03:02:46,988
around the country that are

6787
03:02:46,988 --> 03:02:48,226
looking at quality

6788
03:02:48,226 --> 03:02:49,907
of life factors, you know,

6789
03:02:49,907 --> 03:02:51,633
related to quality of life

6790
03:02:51,633 --> 03:02:52,363
factors in

6791
03:02:52,363 --> 03:02:54,033
health and youth and young

6792
03:02:54,033 --> 03:02:55,767
adults with Down syndrome,

6793
03:02:55,767 --> 03:02:57,535
aspects of metabolic health.

6794
03:02:57,902 --> 03:02:59,270
Yes, one minute left.

6795
03:02:59,771 --> 03:03:00,705
OK, thank you.

6796
03:03:01,572 --> 03:03:02,446
Metabolic health,

6797
03:03:02,446 --> 03:03:03,474
lifestyle and risk.

6798
03:03:03,875 --> 03:03:05,599
A Latin American project and a

6799
03:03:05,599 --> 03:03:06,978
study looking at omics.

6800
03:03:07,812 --> 03:03:09,392
These groups will do a common

6801
03:03:09,392 --> 03:03:10,782
protocol of measures that

6802
03:03:10,782 --> 03:03:12,116
persisted or that cover

6803
03:03:12,116 --> 03:03:12,923
various domains

6804
03:03:12,923 --> 03:03:14,052
across the lifespan.

6805
03:03:14,952 --> 03:03:16,633
And we will have work with the

6806
03:03:16,633 --> 03:03:18,089
data Coordinating center,

6807
03:03:18,089 --> 03:03:19,730
clinical Coordinating center,

6808
03:03:19,730 --> 03:03:20,692
a biorepository,

6809
03:03:20,692 --> 03:03:22,427
and a community Advisory Board.

6810
03:03:23,294 --> 03:03:25,153
These are the common protocol

6811
03:03:25,153 --> 03:03:27,249
domains that we are collecting a

6812
03:03:27,249 --> 03:03:28,166
vast array of

6813
03:03:28,166 --> 03:03:29,956
neuropsychological data that

6814
03:03:29,956 --> 03:03:31,527
will focus on cognition,

6815
03:03:31,527 --> 03:03:32,770
adaptive function,

6816
03:03:32,770 --> 03:03:33,927
attention, memory,

6817
03:03:33,927 --> 03:03:35,910
medical data that will include

6818
03:03:35,910 --> 03:03:36,240
deep

6819
03:03:36,240 --> 03:03:38,197
medical history and extraction

6820
03:03:38,197 --> 03:03:39,110
from the EHR,

6821
03:03:39,110 --> 03:03:40,892
biospecimens that will allow

6822
03:03:40,892 --> 03:03:42,778
Monti omics, neuroimaging and

6823
03:03:42,778 --> 03:03:43,948
physical activity

6824
03:03:43,948 --> 03:03:45,550
measures with actigraphy.

6825
03:03:46,017 --> 03:03:46,788
For sleep,

6826
03:03:46,788 --> 03:03:48,928
we will be doing two or two

6827
03:03:48,928 --> 03:03:49,721
different

6828
03:03:49,721 --> 03:03:51,133
kinds of home sleep

6829
03:03:51,133 --> 03:03:52,323
study measures.

6830
03:03:53,024 --> 03:03:54,540
There will be a portable

6831
03:03:54,540 --> 03:03:55,993
polysonography system,

6832
03:03:55,993 --> 03:03:57,949
the Knox A 1S that will be done

6833
03:03:57,949 --> 03:03:59,887
at several ages as well as the

6834
03:03:59,887 --> 03:04:00,598
watch pad,

6835
03:04:00,598 --> 03:04:02,371
a device used for diagnosing

6836
03:04:02,371 --> 03:04:03,701
sleep apnea at home.

6837
03:04:04,102 --> 03:04:05,686
We'll also have actigraphy as

6838
03:04:05,686 --> 03:04:07,135
mentioned as another sleep

6839
03:04:07,135 --> 03:04:08,473
measure and sleep diary

6840
03:04:08,473 --> 03:04:09,456
and activity logs,

6841
03:04:09,456 --> 03:04:11,026
sleep quality questionnaires

6842
03:04:11,026 --> 03:04:11,642
which have

6843
03:04:11,642 --> 03:04:13,285
been helpful for us before and

6844
03:04:13,285 --> 03:04:14,469
medical record record

6845
03:04:14,469 --> 03:04:15,146
extraction.

6846
03:04:15,513 --> 03:04:16,881
And overall these,

6847
03:04:16,881 --> 03:04:19,148
the population will be around

6848
03:04:19,148 --> 03:04:19,617
2000.

6849
03:04:20,218 --> 03:04:21,353
So there will be well,

6850
03:04:21,353 --> 03:04:22,675
while some of these sleep

6851
03:04:22,675 --> 03:04:23,521
studies will be

6852
03:04:23,521 --> 03:04:24,563
done as sub samples,

6853
03:04:24,563 --> 03:04:26,169
there will be opportunities to

6854
03:04:26,169 --> 03:04:26,491
track

6855
03:04:26,491 --> 03:04:27,886
sleep problems at different

6856
03:04:27,886 --> 03:04:29,127
stages of the lifespan.

6857
03:04:29,394 --> 03:04:30,620
And the project will have

6858
03:04:30,620 --> 03:04:31,896
longitudinal assessments.

6859
03:04:31,896 --> 03:04:33,536
So we'll be able to look at the

6860
03:04:33,536 --> 03:04:35,274
association of sleep issues with

6861
03:04:35,274 --> 03:04:35,600
both,

6862
03:04:35,600 --> 03:04:36,083
you know,

6863
03:04:36,083 --> 03:04:37,802
contributory medical factors or

6864
03:04:37,802 --> 03:04:38,748
associated medical

6865
03:04:38,748 --> 03:04:39,904
factors and outcomes.

6866
03:04:40,772 --> 03:04:41,826
We'll have very deep

6867
03:04:41,826 --> 03:04:43,434
characterization in early life

6868
03:04:43,434 --> 03:04:45,042
with our infant cohort and be

6869
03:04:45,042 --> 03:04:46,362
able to study early brain

6870
03:04:46,362 --> 03:04:48,039
development is related to sleep

6871
03:04:48,039 --> 03:04:48,579
outcomes.

6872
03:04:49,414 --> 03:04:50,409
So in conclusion,

6873
03:04:50,409 --> 03:04:52,049
cohort studies of sleep and

6874
03:04:52,049 --> 03:04:53,321
neurodevelopment token

6875
03:04:53,321 --> 03:04:55,209
conditions can clarify a variety

6876
03:04:55,209 --> 03:04:56,154
of features and

6877
03:04:56,154 --> 03:04:57,364
contributory factors,

6878
03:04:57,364 --> 03:04:58,670
impact and elements of

6879
03:04:58,670 --> 03:04:59,323
treatment.

6880
03:04:59,323 --> 03:05:00,825
They can influence practice.

6881
03:05:01,459 --> 03:05:03,285
Developmentally informed cohorts

6882
03:05:03,285 --> 03:05:05,096
and lifespan cohorts can really

6883
03:05:05,096 --> 03:05:05,797
enhance our

6884
03:05:05,797 --> 03:05:07,346
ability to study these more

6885
03:05:07,346 --> 03:05:08,923
thoroughly, especially when

6886
03:05:08,923 --> 03:05:10,501
using multimodal measures.

6887
03:05:11,302 --> 03:05:12,888
And multidisciplinary cohort

6888
03:05:12,888 --> 03:05:14,739
studies as well can be important

6889
03:05:14,739 --> 03:05:15,606
in quantifying

6890
03:05:15,606 --> 03:05:16,719
factors and outcomes

6891
03:05:16,719 --> 03:05:17,608
across domains.

6892
03:05:17,975 --> 03:05:19,585
And we're very excited to be

6893
03:05:19,585 --> 03:05:21,342
able to use a variety of sleep

6894
03:05:21,342 --> 03:05:22,747
measures to study this.

6895
03:05:23,648 --> 03:05:24,818
And for acknowledgements,

6896
03:05:24,818 --> 03:05:26,118
I'd like to thank again our

6897
03:05:26,118 --> 03:05:26,551
funders.

6898
03:05:26,851 --> 03:05:28,669
P is of the infant brain imaging

6899
03:05:28,669 --> 03:05:30,531
study, especially a Doctor Estes

6900
03:05:30,531 --> 03:05:31,055
who is a

6901
03:05:31,055 --> 03:05:32,712
champion sleep moving forward

6902
03:05:32,712 --> 03:05:33,998
and our include cohort

6903
03:05:33,998 --> 03:05:35,226
development program.

6904
03:05:35,226 --> 03:05:36,670
The P is of the sites,

6905
03:05:36,670 --> 03:05:38,758
the infrastructure and also the

6906
03:05:38,758 --> 03:05:39,230
remote

6907
03:05:39,230 --> 03:05:40,465
studies work group.

6908
03:05:40,832 --> 03:05:41,884
Doctor Tapia who's been

6909
03:05:41,884 --> 03:05:43,143
mentioned several times has

6910
03:05:43,143 --> 03:05:44,402
helped advise on the sleep

6911
03:05:44,402 --> 03:05:45,303
measures being used.

6912
03:05:45,303 --> 03:05:45,770
Thank you.

6913
03:05:48,005 --> 03:05:48,806
Thank you, Natasha.

6914
03:05:48,806 --> 03:05:50,772
We're going to move on to the

6915
03:05:50,772 --> 03:05:52,655
last speaker in the session

6916
03:05:52,655 --> 03:05:53,144
today,

6917
03:05:53,144 --> 03:05:54,745
and that's Kristen Lyle.

6918
03:05:55,179 --> 03:05:57,331
He's an associate professor and

6919
03:05:57,331 --> 03:05:59,177
chair of the Department of

6920
03:05:59,177 --> 03:06:00,384
Epidemiology and

6921
03:06:00,384 --> 03:06:02,019
Biostatistics at Drexel.

6922
03:06:02,286 --> 03:06:03,773
She has experience in

6923
03:06:03,773 --> 03:06:05,721
environmental, nutritional,

6924
03:06:05,721 --> 03:06:07,525
perinatal, reproductive,

6925
03:06:07,525 --> 03:06:09,527
and psychiatric epidemiology.

6926
03:06:10,127 --> 03:06:11,911
Her current research examines

6927
03:06:11,911 --> 03:06:13,423
environmental factors in

6928
03:06:13,423 --> 03:06:14,432
relationship to

6929
03:06:14,432 --> 03:06:16,139
neurodevelopmental outcomes,

6930
03:06:16,139 --> 03:06:17,969
has a strong focus on autism.

6931
03:06:18,503 --> 03:06:20,378
Your talk today will describe

6932
03:06:20,378 --> 03:06:22,356
how you can use data from ECHO

6933
03:06:22,356 --> 03:06:23,741
and other cohorts to

6934
03:06:23,741 --> 03:06:25,632
characterize the influence of

6935
03:06:25,632 --> 03:06:26,611
these factors.

6936
03:06:27,345 --> 03:06:29,160
Thank you for the opportunity to

6937
03:06:29,160 --> 03:06:30,616
come despite my technical

6938
03:06:30,616 --> 03:06:31,315
challenges.

6939
03:06:32,316 --> 03:06:33,939
So I'm going to in some ways

6940
03:06:33,939 --> 03:06:35,478
kind of build on the prior

6941
03:06:35,478 --> 03:06:36,721
speaker and thinking

6942
03:06:36,721 --> 03:06:38,125
about cohort studies and

6943
03:06:38,125 --> 03:06:39,675
specifically with the lens

6944
03:06:39,675 --> 03:06:41,225
towards looking at autism

6945
03:06:41,225 --> 03:06:43,027
and environmental risk factors.

6946
03:06:43,027 --> 03:06:45,114
So if you go into the next slide

6947
03:06:45,114 --> 03:06:45,897
and just a,

6948
03:06:45,897 --> 03:06:47,652
a brief outline in terms of

6949
03:06:47,652 --> 03:06:49,575
thinking about the context of

6950
03:06:49,575 --> 03:06:50,902
autism etiology and

6951
03:06:50,902 --> 03:06:52,912
and sort of the role of cohorts

6952
03:06:52,912 --> 03:06:54,907
and advancing or understanding

6953
03:06:54,907 --> 03:06:55,506
of that.

6954
03:06:57,375 --> 03:06:58,983
I think it's helpful if in

6955
03:06:58,983 --> 03:07:00,557
thinking about consortium

6956
03:07:00,557 --> 03:07:02,446
efforts to also kind of think

6957
03:07:02,446 --> 03:07:04,458
about the steps along the way to

6958
03:07:04,458 --> 03:07:05,149
get there.

6959
03:07:05,816 --> 03:07:07,779
But I am going to be focusing my

6960
03:07:07,779 --> 03:07:09,230
talk mainly on the ECHO

6961
03:07:09,230 --> 03:07:09,987
consortium,

6962
03:07:09,987 --> 03:07:11,879
which I'll I'll define as we go

6963
03:07:11,879 --> 03:07:13,820
forward and thinking about some

6964
03:07:13,820 --> 03:07:14,258
future

6965
03:07:14,258 --> 03:07:15,092
opportunities.

6966
03:07:16,060 --> 03:07:18,162
So if we advance to the next

6967
03:07:18,162 --> 03:07:20,264
slide, you know, autism is,

6968
03:07:20,264 --> 03:07:22,568
is a condition which I think is

6969
03:07:22,568 --> 03:07:24,481
has been reviewed in this

6970
03:07:24,481 --> 03:07:25,169
session.

6971
03:07:26,270 --> 03:07:28,215
So won't spend too much time on,

6972
03:07:28,215 --> 03:07:29,674
on diagnostic criteria.

6973
03:07:29,674 --> 03:07:31,840
But given the heightened focus

6974
03:07:31,840 --> 03:07:34,078
on autism and continued focus,

6975
03:07:34,078 --> 03:07:36,250
I think it's important to also

6976
03:07:36,250 --> 03:07:37,915
review if you advance.

6977
03:07:38,215 --> 03:07:39,314
There's some slide

6978
03:07:39,314 --> 03:07:40,351
animations here.

6979
03:07:40,685 --> 03:07:42,255
The what we know and what we

6980
03:07:42,255 --> 03:07:44,095
don't know about the etiology of

6981
03:07:44,095 --> 03:07:44,555
autism.

6982
03:07:44,555 --> 03:07:46,549
So in terms of what is known,

6983
03:07:46,549 --> 03:07:48,528
we do know that autism has a

6984
03:07:48,528 --> 03:07:49,093
complex

6985
03:07:49,093 --> 03:07:49,694
etiology.

6986
03:07:49,694 --> 03:07:51,940
There's no one single 'cause it

6987
03:07:51,940 --> 03:07:54,245
is complex and multiple factors

6988
03:07:54,245 --> 03:07:54,765
likely

6989
03:07:54,765 --> 03:07:55,533
contribute.

6990
03:07:56,467 --> 03:07:57,068
In addition,

6991
03:07:57,068 --> 03:07:58,401
there are likely different

6992
03:07:58,401 --> 03:07:59,170
causal sets in

6993
03:07:59,170 --> 03:08:00,271
different case groups.

6994
03:08:01,105 --> 03:08:02,506
So that's on the known side.

6995
03:08:02,506 --> 03:08:03,829
On the unknown side,

6996
03:08:03,829 --> 03:08:05,937
I would say the etiology is not

6997
03:08:05,937 --> 03:08:06,277
well

6998
03:08:06,277 --> 03:08:08,318
defined for all cases and we're

6999
03:08:08,318 --> 03:08:10,003
still learning more about

7000
03:08:10,003 --> 03:08:11,148
different causal

7001
03:08:11,148 --> 03:08:11,849
mechanisms.

7002
03:08:11,849 --> 03:08:13,579
We know there's a strong role of

7003
03:08:13,579 --> 03:08:15,347
genetics as well as evidence for

7004
03:08:15,347 --> 03:08:16,120
environmental

7005
03:08:16,120 --> 03:08:16,556
factors,

7006
03:08:16,556 --> 03:08:18,287
but we have a long way to go in

7007
03:08:18,287 --> 03:08:18,789
terms of

7008
03:08:18,789 --> 03:08:20,136
better understanding that

7009
03:08:20,136 --> 03:08:21,733
background susceptibility and

7010
03:08:21,733 --> 03:08:22,560
thinking about

7011
03:08:22,560 --> 03:08:23,260
interactions.

7012
03:08:24,395 --> 03:08:25,405
In addition,

7013
03:08:25,405 --> 03:08:27,932
and when we're thinking about

7014
03:08:27,932 --> 03:08:30,198
environmental risk factors,

7015
03:08:30,198 --> 03:08:32,010
there is evidence for

7016
03:08:32,010 --> 03:08:33,304
susceptibility

7017
03:08:33,304 --> 03:08:35,139
windows and very early

7018
03:08:35,139 --> 03:08:37,514
development and, and even in

7019
03:08:37,514 --> 03:08:40,144
utero as as a critical window.

7020
03:08:40,444 --> 03:08:42,446
But we're in terms of specific

7021
03:08:42,446 --> 03:08:43,648
risk factors and,

7022
03:08:43,648 --> 03:08:45,316
and when they exert their

7023
03:08:45,316 --> 03:08:46,584
strongest effects,

7024
03:08:46,584 --> 03:08:48,386
we we don't have that fully

7025
03:08:48,386 --> 03:08:50,588
understood for all risk factors.

7026
03:08:51,689 --> 03:08:53,760
There's also evidence shared

7027
03:08:53,760 --> 03:08:55,644
pathways for for multiple

7028
03:08:55,644 --> 03:08:57,828
different neurodevelopmental

7029
03:08:57,828 --> 03:08:58,568
disorders,

7030
03:08:58,568 --> 03:09:00,993
but less known about specificity

7031
03:09:00,993 --> 03:09:01,599
of risk

7032
03:09:01,599 --> 03:09:03,740
factors to different disorder

7033
03:09:03,740 --> 03:09:05,930
pathways and contributions to

7034
03:09:05,930 --> 03:09:07,138
variability and

7035
03:09:07,138 --> 03:09:08,005
functioning.

7036
03:09:08,773 --> 03:09:10,552
So if we go on to the next slide

7037
03:09:10,552 --> 03:09:12,258
and I'm not going to spend too

7038
03:09:12,258 --> 03:09:13,110
much time here

7039
03:09:13,110 --> 03:09:13,666
given our,

7040
03:09:13,666 --> 03:09:15,376
our prior speaker did a really

7041
03:09:15,376 --> 03:09:15,946
wonderful

7042
03:09:15,946 --> 03:09:17,550
job of of kind of summarizing

7043
03:09:17,550 --> 03:09:19,248
the benefits of cohort studies

7044
03:09:19,248 --> 03:09:19,984
and thinking

7045
03:09:19,984 --> 03:09:21,699
about the opportunities to have

7046
03:09:21,699 --> 03:09:22,887
that longitudinal and

7047
03:09:22,887 --> 03:09:24,188
prospective follow up.

7048
03:09:25,389 --> 03:09:26,631
So if you advance,

7049
03:09:26,631 --> 03:09:28,753
there are also some challenges

7050
03:09:28,753 --> 03:09:29,460
of course

7051
03:09:29,460 --> 03:09:31,518
with the cohort design and and

7052
03:09:31,518 --> 03:09:33,347
the overall relatively low

7053
03:09:33,347 --> 03:09:34,331
prevalence of

7054
03:09:34,331 --> 03:09:36,261
autism despite an increasing

7055
03:09:36,261 --> 03:09:38,444
prevalence for a general cohort

7056
03:09:38,444 --> 03:09:39,570
approach and of

7057
03:09:39,570 --> 03:09:41,507
course the sort of practical

7058
03:09:41,507 --> 03:09:43,374
implications here as well.

7059
03:09:43,374 --> 03:09:45,412
So if we advance to the next

7060
03:09:45,412 --> 03:09:47,493
slide, before I get got into

7061
03:09:47,493 --> 03:09:48,979
talking about ECHO,

7062
03:09:48,979 --> 03:09:51,313
I also wanted to touch base on a

7063
03:09:51,313 --> 03:09:53,471
couple of cohort studies that

7064
03:09:53,471 --> 03:09:54,885
I've been involved

7065
03:09:54,885 --> 03:09:56,924
in that I do think have have

7066
03:09:56,924 --> 03:09:59,316
helped advance understanding and

7067
03:09:59,316 --> 03:09:59,690
also

7068
03:09:59,690 --> 03:10:01,940
contributed in some ways to the

7069
03:10:01,940 --> 03:10:04,237
the path of of why studies like

7070
03:10:04,237 --> 03:10:05,496
ECHO are needed.

7071
03:10:05,496 --> 03:10:07,520
So very similar to the Ibis

7072
03:10:07,520 --> 03:10:09,738
cohort that our prior speaker

7073
03:10:09,738 --> 03:10:11,268
went through early,

7074
03:10:11,268 --> 03:10:13,435
which stands for Early Autism

7075
03:10:13,435 --> 03:10:15,808
risk longitudinal investigation

7076
03:10:15,808 --> 03:10:16,574
is a high

7077
03:10:16,574 --> 03:10:18,969
likelihood autism cohort design,

7078
03:10:18,969 --> 03:10:21,346
which really capitalizes on the

7079
03:10:21,346 --> 03:10:22,113
fact that

7080
03:10:22,113 --> 03:10:24,505
we know that younger siblings of

7081
03:10:24,505 --> 03:10:26,946
children with autism have a much

7082
03:10:26,946 --> 03:10:28,319
higher likelihood

7083
03:10:28,319 --> 03:10:30,688
of developing autism themselves.

7084
03:10:31,388 --> 03:10:33,292
So by enrolling pregnant women

7085
03:10:33,292 --> 03:10:35,178
who already have at least one

7086
03:10:35,178 --> 03:10:35,893
child with

7087
03:10:35,893 --> 03:10:37,494
autism and following that

7088
03:10:37,494 --> 03:10:39,389
younger sibling through their

7089
03:10:39,389 --> 03:10:40,631
early development,

7090
03:10:40,631 --> 03:10:42,671
it really enables this efficient

7091
03:10:42,671 --> 03:10:43,974
design to be able to

7092
03:10:43,974 --> 03:10:45,603
prospectively study risk

7093
03:10:45,603 --> 03:10:46,103
factors.

7094
03:10:47,872 --> 03:10:48,680
And so yeah,

7095
03:10:48,680 --> 03:10:50,820
of course there's a a wealth of

7096
03:10:50,820 --> 03:10:51,442
exposure

7097
03:10:51,442 --> 03:10:53,177
data that can be collected

7098
03:10:53,177 --> 03:10:55,284
prospectively under this design

7099
03:10:55,284 --> 03:10:56,847
enabling bio specimens

7100
03:10:56,847 --> 03:10:58,660
to be collected and what we

7101
03:10:58,660 --> 03:11:00,715
suspect to be critical windows

7102
03:11:00,715 --> 03:11:02,153
and also paired with

7103
03:11:02,153 --> 03:11:04,312
really rigorous clinical outcome

7104
03:11:04,312 --> 03:11:05,189
assessments.

7105
03:11:06,090 --> 03:11:08,151
The challenge of course with a

7106
03:11:08,151 --> 03:11:09,593
design like this is,

7107
03:11:09,593 --> 03:11:11,768
is some small sample sizes in in

7108
03:11:11,768 --> 03:11:13,642
trying to and especially if

7109
03:11:13,642 --> 03:11:15,099
we're trying to look

7110
03:11:15,099 --> 03:11:16,901
at rarer exposures as well.

7111
03:11:17,868 --> 03:11:20,432
If we advance to the next slide

7112
03:11:20,432 --> 03:11:22,977
in comparison population based

7113
03:11:22,977 --> 03:11:23,741
cohorts,

7114
03:11:23,741 --> 03:11:26,224
so thinking about capitalizing

7115
03:11:26,224 --> 03:11:28,845
on large cohorts that have been

7116
03:11:28,845 --> 03:11:30,114
drawn from the

7117
03:11:30,114 --> 03:11:31,649
general population.

7118
03:11:32,750 --> 03:11:35,050
Some work I've done includes

7119
03:11:35,050 --> 03:11:37,648
using the nurses health studies

7120
03:11:37,648 --> 03:11:39,156
and and there are

7121
03:11:39,156 --> 03:11:41,325
different cohorts of these.

7122
03:11:41,325 --> 03:11:43,450
So nurses Health Study 2 was

7123
03:11:43,450 --> 03:11:45,933
initiated in 1989 following sort

7124
03:11:45,933 --> 03:11:46,864
of a mailed

7125
03:11:46,864 --> 03:11:48,628
questionnaire structure

7126
03:11:48,628 --> 03:11:50,603
including over 100,000 US

7127
03:11:50,603 --> 03:11:51,235
nurses.

7128
03:11:51,769 --> 03:11:53,606
There have been sleep sub

7129
03:11:53,606 --> 03:11:56,002
studies within the Nurses Health

7130
03:11:56,002 --> 03:11:57,575
Study two which have

7131
03:11:57,575 --> 03:11:59,931
included sleep diary data and in

7132
03:11:59,931 --> 03:12:02,186
addition we conducted A nested

7133
03:12:02,186 --> 03:12:03,614
case control study

7134
03:12:03,614 --> 03:12:05,892
of autism within the context of

7135
03:12:05,892 --> 03:12:07,924
Nurses 2 and there's a more

7136
03:12:07,924 --> 03:12:09,053
detailed study

7137
03:12:09,053 --> 03:12:10,571
following children of

7138
03:12:10,571 --> 03:12:12,089
this cohort as well.

7139
03:12:13,190 --> 03:12:15,216
Currently we're collecting some

7140
03:12:15,216 --> 03:12:17,024
quantitative trait data and

7141
03:12:17,024 --> 03:12:17,962
Nurses Health

7142
03:12:17,962 --> 03:12:19,872
Study 3 related to autism and

7143
03:12:19,872 --> 03:12:21,688
there's maternal health sub

7144
03:12:21,688 --> 03:12:23,100
studies which really

7145
03:12:23,100 --> 03:12:25,016
focus on pregnancy and a wide

7146
03:12:25,016 --> 03:12:26,337
range of exposures.

7147
03:12:26,337 --> 03:12:27,897
And I think, you know,

7148
03:12:27,897 --> 03:12:30,148
thinking about what are the key

7149
03:12:30,148 --> 03:12:30,875
strengths

7150
03:12:30,875 --> 03:12:32,793
of this study population is

7151
03:12:32,793 --> 03:12:34,712
really rich maternal data,

7152
03:12:34,712 --> 03:12:36,976
including information on dietary

7153
03:12:36,976 --> 03:12:39,141
factors, reproductive factors,

7154
03:12:39,141 --> 03:12:40,584
medical conditions,

7155
03:12:40,584 --> 03:12:42,052
pregnancy conditions.

7156
03:12:42,653 --> 03:12:44,780
What's more limited when we're

7157
03:12:44,780 --> 03:12:46,951
outside the context of some of

7158
03:12:46,951 --> 03:12:48,325
these sub studies,

7159
03:12:48,325 --> 03:12:49,295
it is detailed

7160
03:12:49,295 --> 03:12:51,095
information on the child.

7161
03:12:52,129 --> 03:12:54,346
So if we go on to the next

7162
03:12:54,346 --> 03:12:56,961
slide, this then kind of leads

7163
03:12:56,961 --> 03:12:58,269
us to thinking

7164
03:12:58,269 --> 03:13:00,371
about consortium efforts.

7165
03:13:01,205 --> 03:13:03,540
So I've been really excited to

7166
03:13:03,540 --> 03:13:06,110
be involved in the ECHO program.

7167
03:13:06,377 --> 03:13:08,342
So ECHO stands for environmental

7168
03:13:08,342 --> 03:13:09,983
influences on child health

7169
03:13:09,983 --> 03:13:10,614
outcomes.

7170
03:13:11,815 --> 03:13:13,702
The sample includes

7171
03:13:13,702 --> 03:13:15,886
over 50,000 children.

7172
03:13:16,387 --> 03:13:18,675
ECHO was first initiated in 2016

7173
03:13:18,675 --> 03:13:20,942
with 69 pediatric and pregnancy

7174
03:13:20,942 --> 03:13:21,892
cohorts that

7175
03:13:21,892 --> 03:13:24,109
already existed in this country

7176
03:13:24,109 --> 03:13:26,447
and were already collecting data

7177
03:13:26,447 --> 03:13:27,398
on their own

7178
03:13:27,398 --> 03:13:29,614
study populations and then came

7179
03:13:29,614 --> 03:13:31,807
together to pool and harmonize

7180
03:13:31,807 --> 03:13:32,903
existing data,

7181
03:13:32,903 --> 03:13:35,069
but then also collect new data

7182
03:13:35,069 --> 03:13:36,874
under a common protocol.

7183
03:13:37,808 --> 03:13:39,994
ECHO is now in its second seven

7184
03:13:39,994 --> 03:13:40,911
-year cycle,

7185
03:13:40,911 --> 03:13:42,562
which includes a set of

7186
03:13:42,562 --> 03:13:44,715
continuing pediatric cohorts.

7187
03:13:44,715 --> 03:13:46,717
So really having a very unique

7188
03:13:46,717 --> 03:13:48,768
opportunity to follow children

7189
03:13:48,768 --> 03:13:49,520
from birth

7190
03:13:49,520 --> 03:13:51,468
into adulthood as well as new

7191
03:13:51,468 --> 03:13:53,459
pregnancy cohorts and a novel

7192
03:13:53,459 --> 03:13:54,558
interconception

7193
03:13:54,558 --> 03:13:55,225
follow up.

7194
03:13:55,926 --> 03:13:57,775
And the goals of ECHO are really

7195
03:13:57,775 --> 03:13:58,964
to better understand

7196
03:13:58,964 --> 03:13:59,797
environmental

7197
03:13:59,797 --> 03:14:01,466
contributions to child health

7198
03:14:01,466 --> 03:14:03,345
across 5 primary outcomes and to

7199
03:14:03,345 --> 03:14:04,401
find solutions to

7200
03:14:04,401 --> 03:14:05,569
advance child health.

7201
03:14:06,103 --> 03:14:07,913
So those outcomes include pre

7202
03:14:07,913 --> 03:14:09,761
peri and post Natal outcomes,

7203
03:14:09,761 --> 03:14:10,908
obesity, Airways,

7204
03:14:10,908 --> 03:14:12,073
positive health and

7205
03:14:12,073 --> 03:14:13,177
neurodevelopment.

7206
03:14:13,844 --> 03:14:15,685
And as an autism researcher,

7207
03:14:15,685 --> 03:14:17,708
I can say this presents really

7208
03:14:17,708 --> 03:14:18,315
exciting

7209
03:14:18,315 --> 03:14:20,409
opportunities for autism when we

7210
03:14:20,409 --> 03:14:22,149
pool data across all these

7211
03:14:22,149 --> 03:14:23,354
different cohorts

7212
03:14:23,354 --> 03:14:25,393
to be able to have sample sizes

7213
03:14:25,393 --> 03:14:27,283
to address some really novel

7214
03:14:27,283 --> 03:14:28,025
questions.

7215
03:14:28,926 --> 03:14:31,174
There is also a public use data

7216
03:14:31,174 --> 03:14:33,548
set available within ECHO and in

7217
03:14:33,548 --> 03:14:34,365
my updated

7218
03:14:34,365 --> 03:14:36,469
slides I had added some other

7219
03:14:36,469 --> 03:14:38,690
figures, but I'll just kind of

7220
03:14:38,690 --> 03:14:40,170
talk through those.

7221
03:14:40,170 --> 03:14:43,629
So there are, you know, over 50,

7222
03:14:43,629 --> 03:14:45,142
000 children.

7223
03:14:45,509 --> 03:14:46,279
In addition,

7224
03:14:46,279 --> 03:14:47,990
we have mother data on the

7225
03:14:47,990 --> 03:14:48,846
mothers and,

7226
03:14:48,846 --> 03:14:50,714
and some father data as well.

7227
03:14:51,382 --> 03:14:53,614
There's also a clinical trials

7228
03:14:53,614 --> 03:14:56,050
arm, a public use data set and a

7229
03:14:56,050 --> 03:14:56,887
scientific

7230
03:14:56,887 --> 03:14:59,275
dissemination webinar series and

7231
03:14:59,275 --> 03:15:01,643
various different efforts to to

7232
03:15:01,643 --> 03:15:02,559
communicate

7233
03:15:02,559 --> 03:15:03,727
science as well.

7234
03:15:05,195 --> 03:15:06,835
So when we think about using

7235
03:15:06,835 --> 03:15:08,065
ECHO data, you know,

7236
03:15:08,065 --> 03:15:09,653
there's challenges with any

7237
03:15:09,653 --> 03:15:11,515
longitudinal study in, in terms

7238
03:15:11,515 --> 03:15:12,536
of missing data.

7239
03:15:12,936 --> 03:15:14,019
With extant data,

7240
03:15:14,019 --> 03:15:16,047
we have to consider things like

7241
03:15:16,047 --> 03:15:16,440
cross

7242
03:15:16,440 --> 03:15:17,431
site variability

7243
03:15:17,431 --> 03:15:18,609
and harmonization.

7244
03:15:19,510 --> 03:15:20,734
But I think these are all

7245
03:15:20,734 --> 03:15:22,331
addressable problems and we have

7246
03:15:22,331 --> 03:15:23,280
methods to account

7247
03:15:23,280 --> 03:15:24,815
for them in different ways that

7248
03:15:24,815 --> 03:15:26,350
we can consider these factors.

7249
03:15:26,784 --> 03:15:28,874
So if we advance to the next

7250
03:15:28,874 --> 03:15:31,188
slide in terms of autism data,

7251
03:15:31,188 --> 03:15:33,197
so we have parent report of

7252
03:15:33,197 --> 03:15:35,553
clinician diagnosis and then we

7253
03:15:35,553 --> 03:15:36,693
can also think

7254
03:15:36,693 --> 03:15:39,089
about the the existing data that

7255
03:15:39,089 --> 03:15:41,538
cohorts came in to ECHO with and

7256
03:15:41,538 --> 03:15:42,533
some cohorts

7257
03:15:42,533 --> 03:15:43,854
including detailed

7258
03:15:43,854 --> 03:15:45,469
clinical assessments.

7259
03:15:46,870 --> 03:15:48,695
Along those lines ECHO as a

7260
03:15:48,695 --> 03:15:50,281
compilation of multiple

7261
03:15:50,281 --> 03:15:52,142
different cohorts includes

7262
03:15:52,142 --> 03:15:53,410
different different

7263
03:15:53,410 --> 03:15:54,344
cohort types.

7264
03:15:54,344 --> 03:15:56,082
So that early study the high

7265
03:15:56,082 --> 03:15:57,448
likelihood of autism.

7266
03:15:57,448 --> 03:15:59,546
There were also a couple Ibis

7267
03:15:59,546 --> 03:16:01,763
and BSRC sites included in the

7268
03:16:01,763 --> 03:16:03,020
initial cycle of

7269
03:16:03,020 --> 03:16:03,387
ECHO.

7270
03:16:04,021 --> 03:16:06,059
So there is also the opportunity

7271
03:16:06,059 --> 03:16:08,079
to do some of those interesting

7272
03:16:08,079 --> 03:16:08,926
cross cohort

7273
03:16:08,926 --> 03:16:09,993
type comparisons.

7274
03:16:09,993 --> 03:16:11,209
We have preterm,

7275
03:16:11,209 --> 03:16:13,707
both birth cohorts as well and a

7276
03:16:13,707 --> 03:16:14,098
case

7277
03:16:14,098 --> 03:16:16,221
control study in addition to

7278
03:16:16,221 --> 03:16:18,246
parent report of clinician

7279
03:16:18,246 --> 03:16:19,103
diagnosis.

7280
03:16:19,503 --> 03:16:21,105
There are screening data

7281
03:16:21,105 --> 03:16:23,284
collected via the NCHAT and then

7282
03:16:23,284 --> 03:16:24,374
sort of broader

7283
03:16:24,374 --> 03:16:26,376
measures and dimensional trait

7284
03:16:26,376 --> 03:16:28,312
measures, including the SRS,

7285
03:16:28,312 --> 03:16:30,433
the Child Behavior Checklist and

7286
03:16:30,433 --> 03:16:32,265
NH Toolbox, as well as some

7287
03:16:32,265 --> 03:16:33,350
other measures,

7288
03:16:33,350 --> 03:16:35,486
which I'll talk a bit more about

7289
03:16:35,486 --> 03:16:37,688
on the next slide if we advance.

7290
03:16:41,024 --> 03:16:42,995
So one of the things that is

7291
03:16:42,995 --> 03:16:45,299
most exciting about ECHO is this

7292
03:16:45,299 --> 03:16:46,163
really this

7293
03:16:46,163 --> 03:16:47,708
breadth of data across

7294
03:16:47,708 --> 03:16:49,426
longitudinal time window

7295
03:16:49,426 --> 03:16:51,502
spanning early childhood and

7296
03:16:51,502 --> 03:16:52,700
middle childhood,

7297
03:16:52,700 --> 03:16:54,803
adolescence and now even into

7298
03:16:54,803 --> 03:16:55,239
early

7299
03:16:55,239 --> 03:16:55,939
adulthood.

7300
03:16:57,541 --> 03:16:59,764
There are data across medical,

7301
03:16:59,764 --> 03:17:02,187
social, psychosocial, lifestyle,

7302
03:17:02,187 --> 03:17:03,247
neighborhood,

7303
03:17:03,247 --> 03:17:05,215
all these different areas.

7304
03:17:05,215 --> 03:17:06,076
In addition,

7305
03:17:06,076 --> 03:17:07,626
there are biospecimen

7306
03:17:07,626 --> 03:17:08,585
collections,

7307
03:17:08,585 --> 03:17:10,838
so offering the ability to it to

7308
03:17:10,838 --> 03:17:12,993
look at genetic and epigenetic

7309
03:17:12,993 --> 03:17:14,358
factors to conduct

7310
03:17:14,358 --> 03:17:16,338
novel environmental chemical

7311
03:17:16,338 --> 03:17:18,290
assays and then think about

7312
03:17:18,290 --> 03:17:19,663
examining multiple

7313
03:17:19,663 --> 03:17:21,792
different types of outcomes in

7314
03:17:21,792 --> 03:17:24,134
addition to different diagnosis.

7315
03:17:25,302 --> 03:17:27,575
And one of the things that that

7316
03:17:27,575 --> 03:17:29,824
I'm particularly excited about

7317
03:17:29,824 --> 03:17:30,874
under Cycle 2

7318
03:17:30,874 --> 03:17:32,858
is continuing to follow our

7319
03:17:32,858 --> 03:17:35,032
cohort sites specifically for

7320
03:17:35,032 --> 03:17:36,680
these autism familial

7321
03:17:36,680 --> 03:17:38,756
cohorts into adolescence and

7322
03:17:38,756 --> 03:17:40,017
young adulthood.

7323
03:17:40,884 --> 03:17:42,674
And the table is just showing

7324
03:17:42,674 --> 03:17:44,500
sort of a snapshot of some of

7325
03:17:44,500 --> 03:17:45,822
the neurodevelopment

7326
03:17:45,822 --> 03:17:47,667
specific measures and ECHO and

7327
03:17:47,667 --> 03:17:49,370
these capture developmental

7328
03:17:49,370 --> 03:17:50,127
milestones,

7329
03:17:50,127 --> 03:17:51,972
temperament, social cognition,

7330
03:17:51,972 --> 03:17:53,240
emotional behavioral

7331
03:17:53,240 --> 03:17:54,064
functioning,

7332
03:17:54,064 --> 03:17:55,919
general cognition and perceive

7333
03:17:55,919 --> 03:17:57,824
stress if we go on to the next

7334
03:17:57,824 --> 03:17:58,268
slide.

7335
03:18:00,571 --> 03:18:03,150
So I have to address the caveat

7336
03:18:03,150 --> 03:18:05,358
here that I am not a sleep

7337
03:18:05,358 --> 03:18:07,311
researcher and my work

7338
03:18:07,311 --> 03:18:08,993
primarily focuses on

7339
03:18:08,993 --> 03:18:11,348
environmental risk factors.

7340
03:18:11,348 --> 03:18:13,447
And so I just wanted to touch

7341
03:18:13,447 --> 03:18:15,755
base and OfferUp some summaries

7342
03:18:15,755 --> 03:18:16,053
of,

7343
03:18:16,053 --> 03:18:18,169
of work that my team has been

7344
03:18:18,169 --> 03:18:19,556
doing within Echo,

7345
03:18:19,556 --> 03:18:21,807
which I think can also then be,

7346
03:18:21,807 --> 03:18:24,185
you know, considered in addition

7347
03:18:24,185 --> 03:18:24,928
to sleep.

7348
03:18:24,928 --> 03:18:25,195
And,

7349
03:18:25,195 --> 03:18:27,248
and there are opportunities to

7350
03:18:27,248 --> 03:18:27,864
consider

7351
03:18:27,864 --> 03:18:29,566
how various different risk

7352
03:18:29,566 --> 03:18:31,368
factors may impact sleep or

7353
03:18:31,368 --> 03:18:32,903
interact with sleep to

7354
03:18:32,903 --> 03:18:34,690
influence various different

7355
03:18:34,690 --> 03:18:36,873
outcomes across the life course.

7356
03:18:37,941 --> 03:18:38,923
So within ECHO,

7357
03:18:38,923 --> 03:18:40,873
we've been using a lot of the

7358
03:18:40,873 --> 03:18:41,411
outcome

7359
03:18:41,411 --> 03:18:42,710
data in some sort of

7360
03:18:42,710 --> 03:18:44,496
psychometric assessments to

7361
03:18:44,496 --> 03:18:46,216
think about measuring the

7362
03:18:46,216 --> 03:18:48,113
autism phenotype and, and how

7363
03:18:48,113 --> 03:18:49,851
can we, and can we validly

7364
03:18:49,851 --> 03:18:51,188
measure things in a

7365
03:18:51,188 --> 03:18:51,822
brief way.

7366
03:18:52,689 --> 03:18:54,458
We've also been looking at

7367
03:18:54,458 --> 03:18:56,193
demographic correlates of

7368
03:18:56,193 --> 03:18:57,928
diagnosis versus treats.

7369
03:18:59,196 --> 03:19:00,430
There's really novel

7370
03:19:00,430 --> 03:19:02,330
opportunities to study dietary

7371
03:19:02,330 --> 03:19:02,899
factors.

7372
03:19:02,899 --> 03:19:04,587
And so we've done some work

7373
03:19:04,587 --> 03:19:05,926
demonstrating inverse

7374
03:19:05,926 --> 03:19:07,838
associations between prenatal

7375
03:19:07,838 --> 03:19:09,713
fish intake and autism as well

7376
03:19:09,713 --> 03:19:11,755
as autism related traits as well

7377
03:19:11,755 --> 03:19:12,776
as sort of this

7378
03:19:12,776 --> 03:19:14,432
middle panel is looking at

7379
03:19:14,432 --> 03:19:15,579
mixture analysis,

7380
03:19:15,579 --> 03:19:17,582
but as applied to nutrients that

7381
03:19:17,582 --> 03:19:19,564
we know are really important in

7382
03:19:19,564 --> 03:19:20,651
neurodevelopment

7383
03:19:20,651 --> 03:19:22,216
and suggesting an inverse

7384
03:19:22,216 --> 03:19:24,199
association with broader autism

7385
03:19:24,199 --> 03:19:25,222
related traits.

7386
03:19:26,423 --> 03:19:28,465
And then also kind of doing some

7387
03:19:28,465 --> 03:19:30,355
work comparing across outcome

7388
03:19:30,355 --> 03:19:31,528
types, types and,

7389
03:19:31,528 --> 03:19:33,187
and looking at things like

7390
03:19:33,187 --> 03:19:35,082
maternal metabolic conditions

7391
03:19:35,082 --> 03:19:35,866
and showing

7392
03:19:35,866 --> 03:19:37,773
associations not only with the

7393
03:19:37,773 --> 03:19:39,595
diagnosis, but also with the

7394
03:19:39,595 --> 03:19:40,570
broader traits

7395
03:19:40,570 --> 03:19:42,426
suggesting sort of a shift in

7396
03:19:42,426 --> 03:19:44,391
the distribution of the traits

7397
03:19:44,391 --> 03:19:45,242
with certain

7398
03:19:45,242 --> 03:19:47,085
risk factors and ongoing work

7399
03:19:47,085 --> 03:19:48,703
planning on on looking at

7400
03:19:48,703 --> 03:19:50,580
interactions across factors.

7401
03:19:51,381 --> 03:19:53,637
So if we go to the next slide,

7402
03:19:53,637 --> 03:19:56,033
so there's a wealth of of sleep

7403
03:19:56,033 --> 03:19:56,420
data

7404
03:19:56,420 --> 03:19:58,447
being collected and already

7405
03:19:58,447 --> 03:20:00,283
collected in ECHO on the

7406
03:20:00,283 --> 03:20:02,426
prenatal and maternal side,

7407
03:20:02,426 --> 03:20:04,531
there are measures capturing

7408
03:20:04,531 --> 03:20:06,371
maternal sleep health in

7409
03:20:06,371 --> 03:20:08,365
pregnancy including sleep

7410
03:20:08,365 --> 03:20:10,621
disturbances and sleep related

7411
03:20:10,621 --> 03:20:13,103
impairment via promise measures.

7412
03:20:13,537 --> 03:20:15,417
There is also measured physical

7413
03:20:15,417 --> 03:20:16,782
activity and sleep via

7414
03:20:16,782 --> 03:20:18,208
accelerometer data and

7415
03:20:18,208 --> 03:20:19,076
sleep Diaries.

7416
03:20:20,811 --> 03:20:23,178
And in in terms of the child,

7417
03:20:23,178 --> 03:20:25,360
there are sort of parallel

7418
03:20:25,360 --> 03:20:26,116
measures

7419
03:20:26,116 --> 03:20:28,585
looking at sleep health across.

7420
03:20:29,252 --> 03:20:31,817
The age bands in children and

7421
03:20:31,817 --> 03:20:34,160
adolescents and even early

7422
03:20:34,160 --> 03:20:36,593
adulthood and infant sleep

7423
03:20:36,593 --> 03:20:39,338
ecology questionnaires and both

7424
03:20:39,338 --> 03:20:42,237
parent and and child report data

7425
03:20:42,237 --> 03:20:43,233
available.

7426
03:20:43,233 --> 03:20:45,016
So right now the participant

7427
03:20:45,016 --> 03:20:46,836
numbers across these various

7428
03:20:46,836 --> 03:20:48,071
different measures

7429
03:20:48,071 --> 03:20:50,071
sort of range from about 900 to

7430
03:20:50,071 --> 03:20:50,974
over 17, 000.

7431
03:20:51,575 --> 03:20:53,563
And with cycle 2 are the current

7432
03:20:53,563 --> 03:20:55,214
funding cycle of ECHO data

7433
03:20:55,214 --> 03:20:56,546
collections ongoing?

7434
03:20:56,546 --> 03:20:57,638
These numbers are only

7435
03:20:57,638 --> 03:20:58,582
going to increase.

7436
03:20:59,616 --> 03:21:00,470
So if we advance

7437
03:21:00,470 --> 03:21:01,485
to the next slide.

7438
03:21:03,954 --> 03:21:05,566
So what's been done in terms of

7439
03:21:05,566 --> 03:21:07,170
sleep and neurodevelopment and

7440
03:21:07,170 --> 03:21:07,491
ECHO.

7441
03:21:08,325 --> 03:21:10,406
So Sheffrey ET all examined

7442
03:21:10,406 --> 03:21:12,796
considerations of of trying to

7443
03:21:12,796 --> 03:21:14,634
incorporate sleep health

7444
03:21:14,634 --> 03:21:16,974
measures into autism screening

7445
03:21:16,974 --> 03:21:18,769
to look at the utility

7446
03:21:18,769 --> 03:21:21,211
of of whether screening could be

7447
03:21:21,211 --> 03:21:23,316
improved by capturing sleep

7448
03:21:23,316 --> 03:21:24,875
disturbances within

7449
03:21:24,875 --> 03:21:25,409
autism.

7450
03:21:25,409 --> 03:21:27,479
And while they did not find

7451
03:21:27,479 --> 03:21:29,749
improvement in screening with

7452
03:21:29,749 --> 03:21:31,314
incorporation of of

7453
03:21:31,314 --> 03:21:33,633
parent reported sleep problems

7454
03:21:33,633 --> 03:21:35,719
in this study, there were,

7455
03:21:35,719 --> 03:21:38,104
consistent with prior research,

7456
03:21:38,104 --> 03:21:40,311
high rates of sleep problems

7457
03:21:40,311 --> 03:21:41,258
found in in

7458
03:21:41,258 --> 03:21:43,226
ECHO children with autism.

7459
03:21:44,628 --> 03:21:45,587
In addition,

7460
03:21:45,587 --> 03:21:48,218
a a couple of papers have looked

7461
03:21:48,218 --> 03:21:48,465
at

7462
03:21:48,465 --> 03:21:50,538
children's sleep health in

7463
03:21:50,538 --> 03:21:52,975
relationship to other outcomes

7464
03:21:52,975 --> 03:21:55,005
and and other behaviors.

7465
03:21:55,005 --> 03:21:57,583
And so a paper examined looking

7466
03:21:57,583 --> 03:21:59,546
at children's executive

7467
03:21:59,546 --> 03:22:00,911
functioning and

7468
03:22:00,911 --> 03:22:03,330
sleep as well as other health

7469
03:22:03,330 --> 03:22:04,915
related behaviors.

7470
03:22:05,615 --> 03:22:07,961
That paper did not see an any

7471
03:22:07,961 --> 03:22:10,372
significant associations with

7472
03:22:10,372 --> 03:22:10,954
sleep,

7473
03:22:10,954 --> 03:22:12,893
but more in In addition,

7474
03:22:12,893 --> 03:22:15,546
another paper is looked at sleep

7475
03:22:15,546 --> 03:22:16,126
health

7476
03:22:16,126 --> 03:22:18,381
in relationship to offspring

7477
03:22:18,381 --> 03:22:21,013
ADHD symptomatology and did find

7478
03:22:21,013 --> 03:22:22,165
a significant

7479
03:22:22,165 --> 03:22:24,581
association between poor sleep

7480
03:22:24,581 --> 03:22:27,134
and pregnancy and ADHD symptoms

7481
03:22:27,134 --> 03:22:28,205
according to

7482
03:22:28,205 --> 03:22:29,554
the CBCL or child

7483
03:22:29,554 --> 03:22:31,141
behavior checklist.

7484
03:22:32,142 --> 03:22:34,197
So if we go into the next slide,

7485
03:22:34,197 --> 03:22:35,545
I think you know it,

7486
03:22:35,545 --> 03:22:37,385
we were actually just talking

7487
03:22:37,385 --> 03:22:38,485
about this in the

7488
03:22:38,485 --> 03:22:40,484
neurodevelopment working group

7489
03:22:40,484 --> 03:22:40,684
in

7490
03:22:40,684 --> 03:22:41,384
ECHO today.

7491
03:22:42,085 --> 03:22:44,333
There's really an opportunity to

7492
03:22:44,333 --> 03:22:46,089
utilize this sleep data.

7493
03:22:46,089 --> 03:22:48,012
Very few studies have have

7494
03:22:48,012 --> 03:22:50,196
looked at this yet and within

7495
03:22:50,196 --> 03:22:52,229
ECHO in terms of sleep and

7496
03:22:52,229 --> 03:22:52,729
autism.

7497
03:22:52,729 --> 03:22:54,641
And so there's an opportunity to

7498
03:22:54,641 --> 03:22:55,298
expand on,

7499
03:22:55,298 --> 03:22:57,198
on those existing studies and to

7500
03:22:57,198 --> 03:22:58,777
think also about using the

7501
03:22:58,777 --> 03:22:59,870
longitudinal data

7502
03:22:59,870 --> 03:23:01,467
that are available in novel

7503
03:23:01,467 --> 03:23:03,220
ways, which I know is a theme

7504
03:23:03,220 --> 03:23:04,307
that has has come

7505
03:23:04,307 --> 03:23:05,809
up in prior talks as well.

7506
03:23:07,310 --> 03:23:09,010
There's the ability to,

7507
03:23:09,010 --> 03:23:11,448
to start pairing these different

7508
03:23:11,448 --> 03:23:13,812
environmental factors with sleep

7509
03:23:13,812 --> 03:23:15,997
data and, and examine how how

7510
03:23:15,997 --> 03:23:17,654
multiple factors are,

7511
03:23:17,654 --> 03:23:19,353
are influencing various

7512
03:23:19,353 --> 03:23:21,612
different outcomes and to also

7513
03:23:21,612 --> 03:23:23,193
think about sleep as

7514
03:23:23,193 --> 03:23:23,343
a,

7515
03:23:23,343 --> 03:23:25,033
a moderator of certain

7516
03:23:25,033 --> 03:23:26,263
associations as

7517
03:23:26,263 --> 03:23:26,630
well.

7518
03:23:27,764 --> 03:23:30,358
And then sort of more broadly,

7519
03:23:30,358 --> 03:23:33,114
I think the wealth of data that

7520
03:23:33,114 --> 03:23:33,470
are

7521
03:23:33,470 --> 03:23:35,522
collected and ECHO offer

7522
03:23:35,522 --> 03:23:37,959
opportunities to think about

7523
03:23:37,959 --> 03:23:40,310
comparing across different

7524
03:23:40,310 --> 03:23:41,511
outcome types.

7525
03:23:42,712 --> 03:23:44,961
And that may be my last slide,

7526
03:23:44,961 --> 03:23:47,269
but just to to kind of broadly

7527
03:23:47,269 --> 03:23:47,884
comment

7528
03:23:47,884 --> 03:23:50,215
about lessons learned from ECHO

7529
03:23:50,215 --> 03:23:52,138
data harmonization and an

7530
03:23:52,138 --> 03:23:53,523
individual cohort

7531
03:23:53,523 --> 03:23:55,408
site variability can be a

7532
03:23:55,408 --> 03:23:57,403
challenge and, but we have

7533
03:23:57,403 --> 03:23:59,629
methods to kind of carefully

7534
03:23:59,629 --> 03:24:00,611
consider and,

7535
03:24:00,611 --> 03:24:02,858
and address that and within a

7536
03:24:02,858 --> 03:24:03,633
course in

7537
03:24:03,633 --> 03:24:05,168
consortium framework.

7538
03:24:05,168 --> 03:24:06,130
And ultimately,

7539
03:24:06,130 --> 03:24:08,042
I think these consortium data

7540
03:24:08,042 --> 03:24:08,438
offer

7541
03:24:08,438 --> 03:24:10,275
really novel opportunities to

7542
03:24:10,275 --> 03:24:12,344
address questions that are often

7543
03:24:12,344 --> 03:24:13,443
not possible for

7544
03:24:13,443 --> 03:24:14,972
outcomes like autism and

7545
03:24:14,972 --> 03:24:16,246
individual studies.

7546
03:24:17,914 --> 03:24:19,035
And, you know,

7547
03:24:19,035 --> 03:24:21,580
to think about trajectories and

7548
03:24:21,580 --> 03:24:22,319
multiple

7549
03:24:22,319 --> 03:24:24,815
help domains and exposures from

7550
03:24:24,815 --> 03:24:26,022
a broad range.

7551
03:24:27,057 --> 03:24:29,065
And just to acknowledge my

7552
03:24:29,065 --> 03:24:31,512
funding as well as no conflicts

7553
03:24:31,512 --> 03:24:32,696
of interest to

7554
03:24:32,696 --> 03:24:33,229
report.

7555
03:24:34,030 --> 03:24:36,637
So hopefully I I helped get us

7556
03:24:36,637 --> 03:24:38,201
back on time and,

7557
03:24:38,201 --> 03:24:40,531
and apologies again for the

7558
03:24:40,531 --> 03:24:43,181
initial technical problems you

7559
03:24:43,181 --> 03:24:44,240
did, Chris,

7560
03:24:44,240 --> 03:24:46,760
Kristen and great performance

7561
03:24:46,760 --> 03:24:48,845
under pressure as well.

7562
03:24:50,180 --> 03:24:51,715
I want to thank all of the

7563
03:24:51,715 --> 03:24:53,249
speakers in this session.

7564
03:24:53,249 --> 03:24:55,051
And I suspect you know what

7565
03:24:55,051 --> 03:24:57,166
we've heard will kind of enable

7566
03:24:57,166 --> 03:24:58,121
a really rich

7567
03:24:58,121 --> 03:24:59,226
discussion at the

7568
03:24:59,226 --> 03:25:00,657
end of the day today.

7569
03:25:01,591 --> 03:25:03,081
But I'm going to close this

7570
03:25:03,081 --> 03:25:04,713
session and go on to the next

7571
03:25:04,713 --> 03:25:05,895
since we are running

7572
03:25:05,895 --> 03:25:07,297
just a few minutes behind.

7573
03:25:10,100 --> 03:25:10,967
Thanks so much, Cindy.

7574
03:25:10,967 --> 03:25:12,561
So the next session is on

7575
03:25:12,561 --> 03:25:14,445
perspectives from parents and

7576
03:25:14,445 --> 03:25:15,939
caregivers and patient

7577
03:25:15,939 --> 03:25:16,573
advocates.

7578
03:25:17,340 --> 03:25:19,590
And Lucia Pesotto Pesciotto,

7579
03:25:19,590 --> 03:25:21,277
one of my Co chairs,

7580
03:25:21,277 --> 03:25:23,380
is moderating that session.

7581
03:25:23,380 --> 03:25:26,361
So Lucia, welcome everybody,

7582
03:25:26,361 --> 03:25:28,385
and it's an honor.

7583
03:25:28,985 --> 03:25:29,686
Can you hear me?

7584
03:25:30,186 --> 03:25:31,087
Yes, thank you.

7585
03:25:31,087 --> 03:25:31,372
Yes,

7586
03:25:31,372 --> 03:25:33,639
it's an honor to chair the last

7587
03:25:33,639 --> 03:25:34,224
session

7588
03:25:34,224 --> 03:25:34,991
of the day.

7589
03:25:35,258 --> 03:25:36,593
My name is Lucia Pesciotto.

7590
03:25:36,593 --> 03:25:37,966
I'm an associate professor at

7591
03:25:37,966 --> 03:25:39,467
the Department of Translational

7592
03:25:39,467 --> 03:25:40,096
Medicine and

7593
03:25:40,096 --> 03:25:41,424
Physiology and the Sleep and

7594
03:25:41,424 --> 03:25:42,877
Performance Research Center at

7595
03:25:42,877 --> 03:25:43,700
Washington State

7596
03:25:43,700 --> 03:25:44,234
University.

7597
03:25:45,068 --> 03:25:46,869
This session is focusing on the

7598
03:25:46,869 --> 03:25:48,438
perspectives from parents,

7599
03:25:48,438 --> 03:25:49,245
caregiving and

7600
03:25:49,245 --> 03:25:50,340
patient advocates.

7601
03:25:50,740 --> 03:25:52,317
Our first speaker is Doctor

7602
03:25:52,317 --> 03:25:53,309
Kathleen Nadeau.

7603
03:25:53,977 --> 03:25:55,645
She's a clinical psychologist

7604
03:25:55,645 --> 03:25:57,466
and the founder and director of

7605
03:25:57,466 --> 03:25:58,348
the Chesapeake

7606
03:25:58,348 --> 03:25:59,682
Center in Bethesda, MD,

7607
03:25:59,682 --> 03:26:01,227
one of the largest private

7608
03:26:01,227 --> 03:26:02,118
clinics in the

7609
03:26:02,118 --> 03:26:03,847
United States that specializes

7610
03:26:03,847 --> 03:26:05,270
in ADHD, autism spectrum

7611
03:26:05,270 --> 03:26:05,922
disorders,

7612
03:26:05,922 --> 03:26:07,272
and auto neurodelemental

7613
03:26:07,272 --> 03:26:07,891
disorders.

7614
03:26:09,125 --> 03:26:10,864
Doctor Nadeau has written over a

7615
03:26:10,864 --> 03:26:12,585
dozen books related to ADHD and

7616
03:26:12,585 --> 03:26:13,363
has long been

7617
03:26:13,363 --> 03:26:14,421
considered a thought

7618
03:26:14,421 --> 03:26:15,532
leader in the field.

7619
03:26:15,865 --> 03:26:16,442
It's a pleasure

7620
03:26:16,442 --> 03:26:17,133
to have you here.

7621
03:26:17,133 --> 03:26:19,234
Welcome Doctor Nadeau,

7622
03:26:19,234 --> 03:26:21,985
and to just introduce myself

7623
03:26:21,985 --> 03:26:22,672
again,

7624
03:26:22,672 --> 03:26:25,510
I have been an ADHD specialist

7625
03:26:25,510 --> 03:26:28,311
for more than the lifespan of

7626
03:26:28,311 --> 03:26:30,146
most of the people

7627
03:26:30,146 --> 03:26:33,102
that have been presenting here,

7628
03:26:33,102 --> 03:26:35,646
and I have a very personal

7629
03:26:35,646 --> 03:26:36,820
interest in

7630
03:26:36,820 --> 03:26:38,488
the topic of ADHD.

7631
03:26:38,488 --> 03:26:39,055
In fact,

7632
03:26:39,055 --> 03:26:41,382
I would wager that I am the only

7633
03:26:41,382 --> 03:26:41,891
person

7634
03:26:41,891 --> 03:26:44,015
giving a lecture today who has

7635
03:26:44,015 --> 03:26:46,261
the neurodevelopmental disorder

7636
03:26:46,261 --> 03:26:47,130
about which

7637
03:26:47,130 --> 03:26:48,031
I'm speaking.

7638
03:26:48,832 --> 03:26:51,513
I come from a family where I

7639
03:26:51,513 --> 03:26:54,555
have daughters, granddaughters,

7640
03:26:54,555 --> 03:26:55,438
sisters,

7641
03:26:55,438 --> 03:26:56,308
brothers,

7642
03:26:56,308 --> 03:26:59,085
all sorts of other relatives

7643
03:26:59,085 --> 03:27:00,076
with ADHD

7644
03:27:00,076 --> 03:27:02,839
and sleep in and of itself is

7645
03:27:02,839 --> 03:27:05,467
just a hugely important and

7646
03:27:05,467 --> 03:27:07,317
largely overlooked

7647
03:27:07,317 --> 03:27:07,884
topic.

7648
03:27:08,284 --> 03:27:10,390
I would wager even within my

7649
03:27:10,390 --> 03:27:12,541
clinic, and we have gathered

7650
03:27:12,541 --> 03:27:13,923
together probably

7651
03:27:13,923 --> 03:27:15,732
the largest private ADHD

7652
03:27:15,732 --> 03:27:17,596
speciality clinic in the

7653
03:27:17,596 --> 03:27:18,294
country.

7654
03:27:18,294 --> 03:27:19,848
We have almost 40

7655
03:27:19,848 --> 03:27:22,132
providers at this point.

7656
03:27:22,132 --> 03:27:24,816
And yet, even within our center,

7657
03:27:24,816 --> 03:27:27,569
I think we are not paying nearly

7658
03:27:27,569 --> 03:27:28,171
enough

7659
03:27:28,171 --> 03:27:29,672
attention to ADHD.

7660
03:27:29,672 --> 03:27:31,508
And interestingly,

7661
03:27:31,508 --> 03:27:33,710
we have continuing Ed

7662
03:27:33,710 --> 03:27:35,178
presentations

7663
03:27:35,178 --> 03:27:36,012
monthly.

7664
03:27:36,012 --> 03:27:38,250
I consulted a group of sleep

7665
03:27:38,250 --> 03:27:40,856
specialists in the Maryland area

7666
03:27:40,856 --> 03:27:42,485
and not one of them

7667
03:27:42,485 --> 03:27:44,074
was prepared to talk

7668
03:27:44,074 --> 03:27:45,822
about ADHD and sleep.

7669
03:27:46,055 --> 03:27:48,410
And yet ADHD is such a common

7670
03:27:48,410 --> 03:27:50,410
neurodevelopmental order

7671
03:27:50,410 --> 03:27:51,494
disorder and

7672
03:27:51,494 --> 03:27:53,830
sleep is such a common issue.

7673
03:27:54,030 --> 03:27:56,864
So it's a greatly neglected area

7674
03:27:56,864 --> 03:27:59,757
and I'm just delighted that I've

7675
03:27:59,757 --> 03:28:01,204
been invited to

7676
03:28:01,204 --> 03:28:02,405
talk about it.

7677
03:28:02,705 --> 03:28:04,668
So there are lots of differences

7678
03:28:04,668 --> 03:28:06,308
that need to be taken into

7679
03:28:06,308 --> 03:28:06,876
account.

7680
03:28:06,876 --> 03:28:09,136
And I'm very frustrated when I

7681
03:28:09,136 --> 03:28:11,453
hear, you know, use good sleep

7682
03:28:11,453 --> 03:28:12,148
hygiene.

7683
03:28:12,448 --> 03:28:14,651
What I would say about good

7684
03:28:14,651 --> 03:28:17,144
sleep hygiene and ADHD is it's

7685
03:28:17,144 --> 03:28:19,055
necessary but far from

7686
03:28:19,055 --> 03:28:21,576
sufficient to understand what's

7687
03:28:21,576 --> 03:28:24,067
going on in the ADHD brain and

7688
03:28:24,067 --> 03:28:25,562
how to help those

7689
03:28:25,562 --> 03:28:28,131
of us with ADHD to sleep better.

7690
03:28:28,331 --> 03:28:30,348
There's structural differences

7691
03:28:30,348 --> 03:28:32,419
in the ADHD brain that impacts

7692
03:28:32,419 --> 03:28:32,902
sleep.

7693
03:28:33,303 --> 03:28:35,517
We have a smaller pineal gland

7694
03:28:35,517 --> 03:28:37,263
which effects melatonin

7695
03:28:37,263 --> 03:28:38,174
production.

7696
03:28:38,775 --> 03:28:40,176
Prefrontal cortex, of

7697
03:28:40,176 --> 03:28:41,578
course, is impacted.

7698
03:28:41,578 --> 03:28:43,806
We're all familiar with that,

7699
03:28:43,806 --> 03:28:45,702
leading to the executive

7700
03:28:45,702 --> 03:28:46,649
functioning

7701
03:28:46,649 --> 03:28:49,152
issues that hugely impact sleep.

7702
03:28:49,152 --> 03:28:51,348
If we're very disorganized,

7703
03:28:51,348 --> 03:28:53,056
if we're time blind,

7704
03:28:53,056 --> 03:28:55,570
it's going to be very difficult

7705
03:28:55,570 --> 03:28:58,137
for us, more difficult than for

7706
03:28:58,137 --> 03:28:59,462
other people to

7707
03:28:59,462 --> 03:29:01,531
follow good sleep hygiene.

7708
03:29:02,131 --> 03:29:03,275
There are neurochemical

7709
03:29:03,275 --> 03:29:04,567
differences in our brain.

7710
03:29:04,567 --> 03:29:07,604
We have baseline lower dopamine.

7711
03:29:07,604 --> 03:29:09,202
We have lower melatonin

7712
03:29:09,202 --> 03:29:11,118
production, which of course

7713
03:29:11,118 --> 03:29:12,609
effects sleep onset.

7714
03:29:13,142 --> 03:29:14,496
And interestingly,

7715
03:29:14,496 --> 03:29:16,963
and I don't hear a lot of people

7716
03:29:16,963 --> 03:29:17,580
talking

7717
03:29:17,580 --> 03:29:18,416
about this,

7718
03:29:18,416 --> 03:29:20,135
we have neural network

7719
03:29:20,135 --> 03:29:21,150
differences.

7720
03:29:22,819 --> 03:29:25,309
Curiously, in the ADHD brain,

7721
03:29:25,309 --> 03:29:27,865
the default mode network does

7722
03:29:27,865 --> 03:29:28,658
not turn

7723
03:29:28,658 --> 03:29:30,104
off when the task

7724
03:29:30,104 --> 03:29:32,061
mode network turns on.

7725
03:29:32,495 --> 03:29:35,698
And we call that mind wandering.

7726
03:29:36,466 --> 03:29:38,549
I call it listening to multiple

7727
03:29:38,549 --> 03:29:40,757
channels in my brain at the same

7728
03:29:40,757 --> 03:29:41,170
time.

7729
03:29:41,170 --> 03:29:42,785
And you can imagine how that

7730
03:29:42,785 --> 03:29:44,617
impacts settling down and going

7731
03:29:44,617 --> 03:29:45,208
to sleep.

7732
03:29:46,175 --> 03:29:48,225
And our sleep architecture in

7733
03:29:48,225 --> 03:29:49,779
general is different.

7734
03:29:49,779 --> 03:29:51,247
It's fragmented.

7735
03:29:51,447 --> 03:29:53,960
There's reduced deep sleep

7736
03:29:53,960 --> 03:29:56,720
phases in the ADHD being and

7737
03:29:56,720 --> 03:29:58,888
diminished REM sleep.

7738
03:29:59,222 --> 03:30:00,209
And interestingly,

7739
03:30:00,209 --> 03:30:01,784
I'll talk a little bit about

7740
03:30:01,784 --> 03:30:02,458
this later,

7741
03:30:02,458 --> 03:30:03,262
I think this is

7742
03:30:03,262 --> 03:30:04,227
hugely important.

7743
03:30:04,460 --> 03:30:06,791
But we now know that the

7744
03:30:06,791 --> 03:30:09,899
glymphatic system of the brain,

7745
03:30:09,899 --> 03:30:12,906
which was just discovered a few

7746
03:30:12,906 --> 03:30:15,585
years ago, is the pulsating

7747
03:30:15,585 --> 03:30:17,173
system by which

7748
03:30:17,173 --> 03:30:20,173
cerebrospinal fluid goes in and

7749
03:30:20,173 --> 03:30:22,011
out of our brains,

7750
03:30:22,011 --> 03:30:23,932
cleansing our brains

7751
03:30:23,932 --> 03:30:25,949
of toxins, proteins.

7752
03:30:26,316 --> 03:30:28,568
And if we have less deep sleep,

7753
03:30:28,568 --> 03:30:30,802
then we have less cleansing of

7754
03:30:30,802 --> 03:30:31,621
the brain.

7755
03:30:31,621 --> 03:30:33,561
And I really think that

7756
03:30:33,561 --> 03:30:35,889
extremely important area of

7757
03:30:35,889 --> 03:30:37,527
research should be

7758
03:30:37,527 --> 03:30:39,545
linking that to the also

7759
03:30:39,545 --> 03:30:41,860
recently documented greater

7760
03:30:41,860 --> 03:30:43,833
likelihood of dementia

7761
03:30:43,833 --> 03:30:45,435
in those with ADHD.

7762
03:30:45,635 --> 03:30:46,405
So these,

7763
03:30:46,405 --> 03:30:48,692
there's so many incredibly

7764
03:30:48,692 --> 03:30:49,572
important

7765
03:30:49,572 --> 03:30:51,941
things for us to talk about.

7766
03:30:51,941 --> 03:30:54,570
Their long term consequences for

7767
03:30:54,570 --> 03:30:57,172
us with ADHD because of chronic

7768
03:30:57,172 --> 03:30:58,514
sleep problems,

7769
03:30:58,514 --> 03:31:00,827
they're much higher rates of

7770
03:31:00,827 --> 03:31:03,553
obesity and metabolic disorders.

7771
03:31:03,953 --> 03:31:06,005
Of course we all are familiar

7772
03:31:06,005 --> 03:31:08,318
with poor academic and poor work

7773
03:31:08,318 --> 03:31:09,258
performance,

7774
03:31:09,258 --> 03:31:10,756
executive functioning

7775
03:31:10,756 --> 03:31:12,719
difficulties, dysfunctional

7776
03:31:12,719 --> 03:31:14,464
family interactions and

7777
03:31:14,464 --> 03:31:16,586
relationships impacted by many

7778
03:31:16,586 --> 03:31:18,901
people in the same family having

7779
03:31:18,901 --> 03:31:19,769
chronically

7780
03:31:19,769 --> 03:31:21,501
inadequate sleep and non

7781
03:31:21,501 --> 03:31:22,872
restorative sleep.

7782
03:31:23,539 --> 03:31:26,747
And research that just came out

7783
03:31:26,747 --> 03:31:29,284
of the UKA few weeks ago

7784
03:31:29,284 --> 03:31:31,714
documenting that those

7785
03:31:31,714 --> 03:31:34,618
with ADHD on average have an

7786
03:31:34,618 --> 03:31:37,389
almost decade long shorter

7787
03:31:37,389 --> 03:31:38,454
lifespan.

7788
03:31:38,755 --> 03:31:40,056
Huge consequence.

7789
03:31:40,056 --> 03:31:41,870
And I think the chronic sleep

7790
03:31:41,870 --> 03:31:43,721
problems we experience have a

7791
03:31:43,721 --> 03:31:45,061
lot to do with that.

7792
03:31:47,730 --> 03:31:48,331
So what?

7793
03:31:48,331 --> 03:31:50,081
What are the primary sleep

7794
03:31:50,081 --> 03:31:52,168
problems associated with ADHD?

7795
03:31:52,702 --> 03:31:54,971
Certainly sleep deprivation.

7796
03:31:54,971 --> 03:31:56,572
I mean, it's ubiquitous.

7797
03:31:56,572 --> 03:31:58,551
It's ubiquitous in kids and

7798
03:31:58,551 --> 03:32:00,309
adolescents and adults.

7799
03:32:00,610 --> 03:32:03,012
We don't get enough sleep.

7800
03:32:03,346 --> 03:32:05,418
And that has to do with the

7801
03:32:05,418 --> 03:32:07,608
delayed sleep phase syndrome

7802
03:32:07,608 --> 03:32:09,485
that many of you may be

7803
03:32:09,485 --> 03:32:10,477
familiar with

7804
03:32:10,477 --> 03:32:12,155
associated with ADHD.

7805
03:32:12,688 --> 03:32:14,443
I sort of refer to

7806
03:32:14,443 --> 03:32:16,392
it as ADHD jet lag.

7807
03:32:16,392 --> 03:32:18,277
Our bodies may be on the East

7808
03:32:18,277 --> 03:32:20,136
Coast, our brains are on the

7809
03:32:20,136 --> 03:32:21,397
West Coast and not

7810
03:32:21,397 --> 03:32:23,066
nearly ready to go to bed.

7811
03:32:23,766 --> 03:32:26,529
Very common disordered sleep,

7812
03:32:26,529 --> 03:32:29,672
breathing in kids and in adults.

7813
03:32:29,906 --> 03:32:31,474
There are movement disorders.

7814
03:32:31,474 --> 03:32:34,421
We've talked about restless leg

7815
03:32:34,421 --> 03:32:37,051
syndrome and other movement

7816
03:32:37,051 --> 03:32:38,414
disorders and

7817
03:32:38,414 --> 03:32:41,150
disrupted sleep architecture.

7818
03:32:41,150 --> 03:32:43,768
So lots of things are going on

7819
03:32:43,768 --> 03:32:46,353
in the ADHD brain that get in

7820
03:32:46,353 --> 03:32:47,957
the way and think

7821
03:32:47,957 --> 03:32:49,960
specific to ADHD in the

7822
03:32:49,960 --> 03:32:52,623
environment that affects sleep

7823
03:32:52,623 --> 03:32:54,664
have to do with family

7824
03:32:54,664 --> 03:32:55,698
environment.

7825
03:32:55,698 --> 03:32:57,652
If you have kids with ADHD,

7826
03:32:57,652 --> 03:33:00,031
you almost certainly have adults

7827
03:33:00,031 --> 03:33:00,403
with

7828
03:33:00,403 --> 03:33:02,353
ADHD in the family and that

7829
03:33:02,353 --> 03:33:04,567
means that this recommendation

7830
03:33:04,567 --> 03:33:05,675
for good sleep

7831
03:33:05,675 --> 03:33:06,275
hygiene.

7832
03:33:07,076 --> 03:33:08,220
It sounds good,

7833
03:33:08,220 --> 03:33:10,331
but how in the world do you

7834
03:33:10,331 --> 03:33:11,347
achieve that

7835
03:33:11,347 --> 03:33:13,549
If you have a child with ADHD

7836
03:33:13,549 --> 03:33:15,573
and a parent with ADHD and

7837
03:33:15,573 --> 03:33:16,586
there's time

7838
03:33:16,586 --> 03:33:17,941
blindness, there's

7839
03:33:17,941 --> 03:33:19,222
disorganization.

7840
03:33:19,222 --> 03:33:20,927
How in the world do I get my

7841
03:33:20,927 --> 03:33:22,851
kids to bed at night and how do

7842
03:33:22,851 --> 03:33:24,093
I get myself to bed

7843
03:33:24,093 --> 03:33:24,627
at night?

7844
03:33:25,027 --> 03:33:27,435
There are all kinds of lifestyle

7845
03:33:27,435 --> 03:33:28,865
factors including.

7846
03:33:29,098 --> 03:33:31,440
Haven't heard a lot of talk

7847
03:33:31,440 --> 03:33:33,436
about digital devices,

7848
03:33:33,436 --> 03:33:35,518
but I think our national

7849
03:33:35,518 --> 03:33:38,344
international addicted addiction

7850
03:33:38,344 --> 03:33:40,376
to our digital devices

7851
03:33:40,376 --> 03:33:42,706
is even more ubiquitous and

7852
03:33:42,706 --> 03:33:45,267
powerful when ADHD comes into

7853
03:33:45,267 --> 03:33:46,415
the picture.

7854
03:33:47,183 --> 03:33:49,526
I know of so many teenagers that

7855
03:33:49,526 --> 03:33:51,848
leave their alerts on all night

7856
03:33:51,848 --> 03:33:52,822
long so that

7857
03:33:52,822 --> 03:33:54,579
they're constantly being

7858
03:33:54,579 --> 03:33:56,893
reawakened because they want to

7859
03:33:56,893 --> 03:33:58,461
be sure that they're

7860
03:33:58,461 --> 03:34:00,378
in the mix if one of their

7861
03:34:00,378 --> 03:34:02,501
friends text them during the

7862
03:34:02,501 --> 03:34:03,032
night.

7863
03:34:04,433 --> 03:34:07,679
And all kinds of time management

7864
03:34:07,679 --> 03:34:11,003
issues that impact our inability

7865
03:34:11,003 --> 03:34:12,041
to really

7866
03:34:12,041 --> 03:34:14,689
follow good sleep hygiene,

7867
03:34:14,689 --> 03:34:17,947
restless leg syndrome and ADHD.

7868
03:34:17,947 --> 03:34:20,818
It's the prevalence is between

7869
03:34:20,818 --> 03:34:23,019
10 and 40% among kids,

7870
03:34:23,019 --> 03:34:25,870
slightly lower 20 to 33% among

7871
03:34:25,870 --> 03:34:28,974
adults, but basically in general

7872
03:34:28,974 --> 03:34:30,526
twice the risk.

7873
03:34:31,394 --> 03:34:34,333
And there is a lot of emerging

7874
03:34:34,333 --> 03:34:37,034
research that talks about a

7875
03:34:37,034 --> 03:34:39,135
common physiological

7876
03:34:39,135 --> 03:34:41,879
pathway between restless leg

7877
03:34:41,879 --> 03:34:44,977
syndrome and ADHD that involves

7878
03:34:44,977 --> 03:34:46,976
sleep fragmentation

7879
03:34:46,976 --> 03:34:48,532
and dopaminergic

7880
03:34:48,532 --> 03:34:50,379
system impairment.

7881
03:34:52,448 --> 03:34:54,001
There's also a greater

7882
03:34:54,001 --> 03:34:56,085
likelihood of having periodic

7883
03:34:56,085 --> 03:34:57,954
limb movement disorder if

7884
03:34:57,954 --> 03:34:58,955
you have ADHD.

7885
03:34:59,422 --> 03:35:01,085
And interestingly,

7886
03:35:01,085 --> 03:35:03,751
fairly recent research shows

7887
03:35:03,751 --> 03:35:04,227
that

7888
03:35:04,227 --> 03:35:07,074
periodic limb movement disorder

7889
03:35:07,074 --> 03:35:09,699
is much more likely in those

7890
03:35:09,699 --> 03:35:11,667
with great symptoms.

7891
03:35:11,667 --> 03:35:13,236
Severity in ADHD, more

7892
03:35:13,236 --> 03:35:15,051
pronounced anxiety, worse

7893
03:35:15,051 --> 03:35:17,373
executive functioning deficits.

7894
03:35:18,574 --> 03:35:20,970
If you look at the circadian

7895
03:35:20,970 --> 03:35:23,589
rhythm, we talked about this a

7896
03:35:23,589 --> 03:35:25,248
little bit earlier

7897
03:35:25,248 --> 03:35:27,384
about delayed sleep phase

7898
03:35:27,384 --> 03:35:29,217
syndrome, the natural

7899
03:35:29,217 --> 03:35:31,487
progression is for people

7900
03:35:31,487 --> 03:35:33,884
with ADHD to become more and

7901
03:35:33,884 --> 03:35:36,682
more alert and able to focus and

7902
03:35:36,682 --> 03:35:37,994
function until

7903
03:35:37,994 --> 03:35:40,196
about 2:00 in the morning.

7904
03:35:40,496 --> 03:35:42,633
I've had so many adult clients

7905
03:35:42,633 --> 03:35:44,755
say that if the world left me

7906
03:35:44,755 --> 03:35:45,268
alone,

7907
03:35:45,268 --> 03:35:47,523
I would probably get much better

7908
03:35:47,523 --> 03:35:49,611
sleep and I would go to sleep

7909
03:35:49,611 --> 03:35:50,906
about 3:00 in the

7910
03:35:50,906 --> 03:35:52,249
morning and I would

7911
03:35:52,249 --> 03:35:53,309
sleep till 10.

7912
03:35:53,609 --> 03:35:55,594
And some people who are self

7913
03:35:55,594 --> 03:35:57,908
-employed actually arrange to be

7914
03:35:57,908 --> 03:35:59,282
able to conform to

7915
03:35:59,282 --> 03:36:01,350
their natural sleep schedule.

7916
03:36:01,550 --> 03:36:03,176
But as we all know,

7917
03:36:03,176 --> 03:36:04,887
we're raising kids.

7918
03:36:04,887 --> 03:36:06,265
They have to get to school,

7919
03:36:06,265 --> 03:36:07,490
we have to get to work.

7920
03:36:07,490 --> 03:36:10,506
And so we're sort of enforcing

7921
03:36:10,506 --> 03:36:13,384
chronic sleep deprivation on

7922
03:36:13,384 --> 03:36:15,131
those with ADHD.

7923
03:36:16,299 --> 03:36:18,123
The sleep issues differ

7924
03:36:18,123 --> 03:36:19,869
depending on the age.

7925
03:36:20,269 --> 03:36:22,534
We heard a little bit about

7926
03:36:22,534 --> 03:36:25,022
this, but bedtime resistance,

7927
03:36:25,022 --> 03:36:26,309
hyperactivity,

7928
03:36:26,309 --> 03:36:29,015
and difficulty with sleep on set

7929
03:36:29,015 --> 03:36:31,794
are very common in children with

7930
03:36:31,794 --> 03:36:32,315
ADHD.

7931
03:36:32,615 --> 03:36:33,307
For boys,

7932
03:36:33,307 --> 03:36:35,836
just motoric restlessness during

7933
03:36:35,836 --> 03:36:36,152
the

7934
03:36:36,152 --> 03:36:37,753
night is very common.

7935
03:36:37,753 --> 03:36:38,739
For girls,

7936
03:36:38,739 --> 03:36:41,786
anxiety is another contributor

7937
03:36:41,786 --> 03:36:42,091
to

7938
03:36:42,091 --> 03:36:44,627
difficulty falling asleep.

7939
03:36:44,627 --> 03:36:44,918
See,

7940
03:36:44,918 --> 03:36:47,238
that's something characteristic

7941
03:36:47,238 --> 03:36:47,463
of

7942
03:36:47,463 --> 03:36:49,702
females throughout the lifespan

7943
03:36:49,702 --> 03:36:51,767
and sadly it starts in early

7944
03:36:51,767 --> 03:36:53,169
childhood for many

7945
03:36:53,169 --> 03:36:53,569
girls.

7946
03:36:54,303 --> 03:36:55,849
Then with adolescents,

7947
03:36:55,849 --> 03:36:57,656
all adolescents as you're

7948
03:36:57,656 --> 03:36:58,307
probably

7949
03:36:58,307 --> 03:36:59,289
familiar with,

7950
03:36:59,289 --> 03:37:01,311
have a natural delayed sleep

7951
03:37:01,311 --> 03:37:01,744
phase

7952
03:37:01,744 --> 03:37:02,378
syndrome.

7953
03:37:02,378 --> 03:37:05,954
So it's only compounded when you

7954
03:37:05,954 --> 03:37:07,183
have ADHD.

7955
03:37:07,516 --> 03:37:08,538
On top of that,

7956
03:37:08,538 --> 03:37:10,292
there's a lot more stress

7957
03:37:10,292 --> 03:37:10,853
related

7958
03:37:10,853 --> 03:37:11,471
insomnia,

7959
03:37:11,471 --> 03:37:13,512
not necessarily the anxiety I

7960
03:37:13,512 --> 03:37:14,357
was talking

7961
03:37:14,357 --> 03:37:15,390
about in girls,

7962
03:37:15,390 --> 03:37:17,526
but just the stress that many,

7963
03:37:17,526 --> 03:37:19,716
if not most teenagers experience

7964
03:37:19,716 --> 03:37:21,603
with multiple demands being

7965
03:37:21,603 --> 03:37:22,932
placed on them and

7966
03:37:22,932 --> 03:37:24,903
not knowing how to juggle and

7967
03:37:24,903 --> 03:37:26,913
manage all of the things that

7968
03:37:26,913 --> 03:37:28,437
are impacting them in

7969
03:37:28,437 --> 03:37:29,171
their life.

7970
03:37:29,372 --> 03:37:31,277
So they struggle with daytime

7971
03:37:31,277 --> 03:37:33,236
sleepiness, falling asleep in

7972
03:37:33,236 --> 03:37:33,709
class.

7973
03:37:34,410 --> 03:37:36,449
And there's an impact that

7974
03:37:36,449 --> 03:37:39,009
fragmented sleep really disrupts

7975
03:37:39,009 --> 03:37:40,449
brain development

7976
03:37:40,449 --> 03:37:41,884
during adolescence.

7977
03:37:42,685 --> 03:37:44,076
By adulthood,

7978
03:37:44,076 --> 03:37:47,589
it's estimated that 50 to 70% of

7979
03:37:47,589 --> 03:37:48,357
adults

7980
03:37:48,357 --> 03:37:50,447
with ADHD experience

7981
03:37:50,447 --> 03:37:52,328
chronic insomnia.

7982
03:37:52,828 --> 03:37:54,391
The delayed sleep phase

7983
03:37:54,391 --> 03:37:56,565
syndrome, of course, continues.

7984
03:37:57,032 --> 03:37:59,365
And because there is a

7985
03:37:59,365 --> 03:38:02,602
connection between impulsivity

7986
03:38:02,602 --> 03:38:05,408
and overeating and weight

7987
03:38:05,408 --> 03:38:05,940
gain,

7988
03:38:05,940 --> 03:38:09,332
obstructive sleep apnea becomes

7989
03:38:09,332 --> 03:38:09,879
more

7990
03:38:09,879 --> 03:38:12,314
common as we get older.

7991
03:38:16,152 --> 03:38:18,310
So when we're talking about

7992
03:38:18,310 --> 03:38:19,989
basic sleep hygiene,

7993
03:38:19,989 --> 03:38:21,985
what I always say is it's

7994
03:38:21,985 --> 03:38:23,875
necessary, but it's not

7995
03:38:23,875 --> 03:38:24,860
sufficient.

7996
03:38:24,860 --> 03:38:27,012
We have to take all of these

7997
03:38:27,012 --> 03:38:29,165
other factors into account.

7998
03:38:31,133 --> 03:38:35,304
So what does help with a DHDI?

7999
03:38:35,304 --> 03:38:36,678
Call it we're

8000
03:38:36,678 --> 03:38:39,108
treating ADHD jet lag.

8001
03:38:39,508 --> 03:38:41,534
I have experienced this myself

8002
03:38:41,534 --> 03:38:42,411
all my life.

8003
03:38:42,411 --> 03:38:44,483
My parents used to joke that I

8004
03:38:44,483 --> 03:38:46,348
never wanted to go to bed.

8005
03:38:46,348 --> 03:38:48,016
They thought I just didn't want

8006
03:38:48,016 --> 03:38:49,719
to miss anything that was going

8007
03:38:49,719 --> 03:38:50,653
on because older

8008
03:38:50,653 --> 03:38:51,740
siblings and parents

8009
03:38:51,740 --> 03:38:52,555
were still up.

8010
03:38:53,055 --> 03:38:54,520
My mother used to joke,

8011
03:38:54,520 --> 03:38:55,858
when you are my age,

8012
03:38:55,858 --> 03:38:57,695
you'll be dying to go to bed,

8013
03:38:57,695 --> 03:38:59,774
but you won't be able to because

8014
03:38:59,774 --> 03:39:00,229
you'll

8015
03:39:00,229 --> 03:39:01,664
be the adult in charge.

8016
03:39:01,664 --> 03:39:04,533
And that never happened.

8017
03:39:05,267 --> 03:39:07,590
In fact, even today I really,

8018
03:39:07,590 --> 03:39:10,052
really struggled to get myself

8019
03:39:10,052 --> 03:39:10,873
to bed at

8020
03:39:10,873 --> 03:39:12,308
a reasonable hour.

8021
03:39:13,008 --> 03:39:13,976
Why is that?

8022
03:39:14,176 --> 03:39:15,286
Because our brains

8023
03:39:15,286 --> 03:39:16,212
are waking up.

8024
03:39:16,512 --> 03:39:19,028
And the other thing that needs

8025
03:39:19,028 --> 03:39:21,774
to be taken into account is that

8026
03:39:21,774 --> 03:39:22,718
late night

8027
03:39:22,718 --> 03:39:25,156
hours are the only hours when

8028
03:39:25,156 --> 03:39:27,900
the buzzing, booming world isn't

8029
03:39:27,900 --> 03:39:29,358
interrupting us,

8030
03:39:29,358 --> 03:39:30,623
distracting us,

8031
03:39:30,623 --> 03:39:33,136
and we can finally focus much

8032
03:39:33,136 --> 03:39:33,829
better.

8033
03:39:33,829 --> 03:39:36,526
So it's really a very rewarding

8034
03:39:36,526 --> 03:39:38,926
time of day to be awake and

8035
03:39:38,926 --> 03:39:40,703
we're paying for it

8036
03:39:40,703 --> 03:39:42,152
with with chronic

8037
03:39:42,152 --> 03:39:43,772
sleep deprivation.

8038
03:39:44,106 --> 03:39:46,809
So how do we treat ADHD jet lag?

8039
03:39:47,276 --> 03:39:48,674
Pretty much the same

8040
03:39:48,674 --> 03:39:50,212
way we treat jet lag.

8041
03:39:50,713 --> 03:39:52,766
Melatonin supplementation

8042
03:39:52,766 --> 03:39:53,916
really helps.

8043
03:39:54,483 --> 03:39:55,440
Morning light

8044
03:39:55,440 --> 03:39:56,986
therapy helps a lot.

8045
03:39:56,986 --> 03:39:59,292
There are artificial dawn lights

8046
03:39:59,292 --> 03:40:01,500
that I recommend to clients so

8047
03:40:01,500 --> 03:40:02,825
that they can set

8048
03:40:02,825 --> 03:40:05,057
especially in the winter months

8049
03:40:05,057 --> 03:40:07,119
when it's dark so much later

8050
03:40:07,119 --> 03:40:08,297
they can set an

8051
03:40:08,297 --> 03:40:09,586
artificial dawn to

8052
03:40:09,586 --> 03:40:11,233
begin to wake them up.

8053
03:40:11,767 --> 03:40:13,509
To expose themselves to very

8054
03:40:13,509 --> 03:40:15,220
bright light, the very same

8055
03:40:15,220 --> 03:40:16,805
lights that are used for

8056
03:40:16,805 --> 03:40:18,541
seasonal affective disorder.

8057
03:40:19,375 --> 03:40:22,378
I own one, my daughter owns 1.

8058
03:40:22,978 --> 03:40:25,175
Putting this super bright full

8059
03:40:25,175 --> 03:40:27,420
spectrum light on your kitchen

8060
03:40:27,420 --> 03:40:28,617
table as you're

8061
03:40:28,617 --> 03:40:30,882
having breakfast for 20 minutes

8062
03:40:30,882 --> 03:40:32,855
really wakes up our brain.

8063
03:40:33,289 --> 03:40:35,998
Exercise has a huge impact on

8064
03:40:35,998 --> 03:40:39,047
regulating our biological clocks

8065
03:40:39,047 --> 03:40:40,763
and improving the

8066
03:40:40,763 --> 03:40:43,008
quality of our sleep and

8067
03:40:43,008 --> 03:40:45,534
magnesium supplementation.

8068
03:40:45,534 --> 03:40:47,969
There's more research suggesting

8069
03:40:47,969 --> 03:40:50,461
that magnesium may help regulate

8070
03:40:50,461 --> 03:40:51,240
sleep and

8071
03:40:51,240 --> 03:40:52,741
also reduce anxiety.

8072
03:40:53,008 --> 03:40:55,193
I don't see these kinds of

8073
03:40:55,193 --> 03:40:57,546
recommendations being made,

8074
03:40:57,546 --> 03:40:59,730
but we really are treating

8075
03:40:59,730 --> 03:41:02,251
chronic jet lag, if you will.

8076
03:41:03,352 --> 03:41:05,255
Then there's all the issue about

8077
03:41:05,255 --> 03:41:06,906
how do we deal with digital

8078
03:41:06,906 --> 03:41:07,456
devices.

8079
03:41:08,524 --> 03:41:11,125
I set my phone so that the light

8080
03:41:11,125 --> 03:41:13,700
being emitted by my phone after

8081
03:41:13,700 --> 03:41:14,863
9:00 at night

8082
03:41:14,863 --> 03:41:17,394
is in the red range rather than

8083
03:41:17,394 --> 03:41:18,701
the blue range.

8084
03:41:19,902 --> 03:41:20,836
But Even so,

8085
03:41:20,836 --> 03:41:22,993
we're still stimulating our

8086
03:41:22,993 --> 03:41:23,872
brains and

8087
03:41:23,872 --> 03:41:26,186
we're dealing with really sort

8088
03:41:26,186 --> 03:41:27,920
of an almost addictive

8089
03:41:27,920 --> 03:41:29,812
propensity with an ADHD

8090
03:41:29,812 --> 03:41:31,024
brain that we're

8091
03:41:31,024 --> 03:41:32,615
seeking stimulation.

8092
03:41:32,982 --> 03:41:35,077
And digital devices and

8093
03:41:35,077 --> 03:41:37,954
algorithms on various platforms

8094
03:41:37,954 --> 03:41:40,089
are designed to addict

8095
03:41:40,089 --> 03:41:41,343
us to one more

8096
03:41:41,343 --> 03:41:43,225
time, one more time.

8097
03:41:43,692 --> 03:41:45,525
And So what I find sadly,

8098
03:41:45,525 --> 03:41:47,478
is that we're training our

8099
03:41:47,478 --> 03:41:48,530
children from

8100
03:41:48,530 --> 03:41:50,794
the earliest age that the iPad

8101
03:41:50,794 --> 03:41:52,503
has become the digital

8102
03:41:52,503 --> 03:41:53,435
babysitter.

8103
03:41:53,435 --> 03:41:55,491
We're training them that the

8104
03:41:55,491 --> 03:41:57,106
world is in this box,

8105
03:41:57,106 --> 03:41:59,471
is on the screen and not outside

8106
03:41:59,471 --> 03:42:00,876
in the real world.

8107
03:42:02,978 --> 03:42:05,946
So we're particularly vulnerable

8108
03:42:05,946 --> 03:42:08,791
to digital stimulation because

8109
03:42:08,791 --> 03:42:10,119
it's designed

8110
03:42:10,119 --> 03:42:12,174
for reward seeking it,

8111
03:42:12,174 --> 03:42:15,257
it really can become dangerously

8112
03:42:15,257 --> 03:42:16,191
addictive.

8113
03:42:17,926 --> 03:42:20,129
Anxiety is another huge impact

8114
03:42:20,129 --> 03:42:22,306
that I haven't heard a lot of

8115
03:42:22,306 --> 03:42:23,432
people talking

8116
03:42:23,432 --> 03:42:23,877
about,

8117
03:42:23,877 --> 03:42:26,236
but there are lots of ways that

8118
03:42:26,236 --> 03:42:26,769
we can

8119
03:42:26,769 --> 03:42:28,075
address anxiety to

8120
03:42:28,075 --> 03:42:29,672
help us get to sleep.

8121
03:42:30,139 --> 03:42:31,899
There's been earlier talk about

8122
03:42:31,899 --> 03:42:33,375
weighted blanket therapy.

8123
03:42:33,742 --> 03:42:35,344
I think that can

8124
03:42:35,344 --> 03:42:37,246
be very promising.

8125
03:42:37,546 --> 03:42:39,415
There's sound therapy.

8126
03:42:39,615 --> 03:42:42,594
There are all sorts of there's a

8127
03:42:42,594 --> 03:42:45,635
wealth of information on calming

8128
03:42:45,635 --> 03:42:47,156
sounds that you

8129
03:42:47,156 --> 03:42:48,457
can listen to.

8130
03:42:49,091 --> 03:42:51,268
Tibetan bowl sounds which are

8131
03:42:51,268 --> 03:42:53,123
just almost hypnotic and

8132
03:42:53,123 --> 03:42:53,896
relaxing.

8133
03:42:54,196 --> 03:42:56,647
There's been research on pink

8134
03:42:56,647 --> 03:42:59,240
noise and brown noise as being

8135
03:42:59,240 --> 03:43:00,536
more relaxing.

8136
03:43:01,103 --> 03:43:02,838
Magnesium supplementation,

8137
03:43:02,838 --> 03:43:04,573
which I mentioned before.

8138
03:43:05,007 --> 03:43:07,897
And also there's biofeedback

8139
03:43:07,897 --> 03:43:10,744
training that can literally

8140
03:43:10,744 --> 03:43:12,748
train us to relax.

8141
03:43:13,148 --> 03:43:14,837
Progressive relaxation

8142
03:43:14,837 --> 03:43:16,218
with biofeedback.

8143
03:43:19,588 --> 03:43:21,502
So there's something that I

8144
03:43:21,502 --> 03:43:23,670
haven't heard anyone else talk

8145
03:43:23,670 --> 03:43:25,260
about that I think is

8146
03:43:25,260 --> 03:43:27,117
really critical in helping

8147
03:43:27,117 --> 03:43:29,331
people with ADHD get to sleep.

8148
03:43:29,832 --> 03:43:31,762
And this goes back to what I

8149
03:43:31,762 --> 03:43:33,592
mentioned before about the

8150
03:43:33,592 --> 03:43:35,070
default mode network

8151
03:43:35,070 --> 03:43:36,305
never turning off.

8152
03:43:36,905 --> 03:43:39,750
And so the less that's going on

8153
03:43:39,750 --> 03:43:41,677
in your environment,

8154
03:43:41,677 --> 03:43:43,966
the more the default mode

8155
03:43:43,966 --> 03:43:45,614
network kicks in.

8156
03:43:46,148 --> 03:43:49,051
And except when you have ADHD,

8157
03:43:49,051 --> 03:43:52,227
it's a real hyperactive bouncing

8158
03:43:52,227 --> 03:43:52,921
around

8159
03:43:52,921 --> 03:43:55,591
from one thought to another.

8160
03:43:55,591 --> 03:43:57,155
And so it may sound

8161
03:43:57,155 --> 03:43:59,836
counterintuitive, but what helps

8162
03:43:59,836 --> 03:44:01,930
our brains get ready for

8163
03:44:01,930 --> 03:44:04,318
sleep is to have something to

8164
03:44:04,318 --> 03:44:06,756
focus on rather than allowing

8165
03:44:06,756 --> 03:44:08,270
that default mode

8166
03:44:08,270 --> 03:44:09,740
network to take us

8167
03:44:09,740 --> 03:44:11,373
in 1000 directions.

8168
03:44:12,307 --> 03:44:14,458
And so we need to carefully

8169
03:44:14,458 --> 03:44:17,060
select something that's going to

8170
03:44:17,060 --> 03:44:18,280
engage us just

8171
03:44:18,280 --> 03:44:20,914
enough that we have something to

8172
03:44:20,914 --> 03:44:23,218
focus on, but not too much.

8173
03:44:23,218 --> 03:44:25,762
Not TikTok, not social media,

8174
03:44:25,762 --> 03:44:28,099
not online shopping in the

8175
03:44:28,099 --> 03:44:29,358
middle of the

8176
03:44:29,358 --> 03:44:29,858
night.

8177
03:44:30,592 --> 03:44:31,826
And I sort of call

8178
03:44:31,826 --> 03:44:33,128
it the Goldilocks.

8179
03:44:33,428 --> 03:44:35,130
The just right stimulation.

8180
03:44:35,130 --> 03:44:37,499
Not too much, not too little.

8181
03:44:37,833 --> 03:44:39,216
Interestingly,

8182
03:44:39,216 --> 03:44:42,263
my youngest granddaughter with

8183
03:44:42,263 --> 03:44:42,771
ADHD

8184
03:44:42,771 --> 03:44:45,842
discovered that she could go to

8185
03:44:45,842 --> 03:44:49,111
sleep very well listening to Mr.

8186
03:44:49,111 --> 03:44:50,012
Rogers.

8187
03:44:50,746 --> 03:44:52,381
She found that online.

8188
03:44:52,381 --> 03:44:53,916
And you know, Mr.

8189
03:44:53,916 --> 03:44:55,584
Rogers was from certainly

8190
03:44:55,584 --> 03:44:57,186
generations before her.

8191
03:44:57,419 --> 03:44:59,650
And his calming voice, his

8192
03:44:59,650 --> 03:45:01,623
reassurance, you know,

8193
03:45:01,623 --> 03:45:03,308
the friendly magical

8194
03:45:03,308 --> 03:45:04,993
neighborhood of Mr.

8195
03:45:04,993 --> 03:45:07,769
Rogers allowed her to peacefully

8196
03:45:07,769 --> 03:45:08,897
fall asleep.

8197
03:45:10,265 --> 03:45:10,725
Kathleen,

8198
03:45:10,725 --> 03:45:12,293
maybe we can give you the wrap

8199
03:45:12,293 --> 03:45:12,868
up because

8200
03:45:12,868 --> 03:45:13,625
we want to give

8201
03:45:13,625 --> 03:45:14,736
Carol Dean some time.

8202
03:45:15,370 --> 03:45:17,105
You bet, Lucy.

8203
03:45:17,105 --> 03:45:17,406
I see.

8204
03:45:17,673 --> 03:45:19,703
I see that Geraldine is actually

8205
03:45:19,703 --> 03:45:21,710
online, so maybe we can get her

8206
03:45:21,710 --> 03:45:22,811
to give her talk

8207
03:45:22,811 --> 03:45:24,246
when Kathleen wraps up.

8208
03:45:24,513 --> 03:45:24,980
OK.

8209
03:45:24,980 --> 03:45:25,447
Sure.

8210
03:45:25,647 --> 03:45:27,224
So I'm right ready

8211
03:45:27,224 --> 03:45:29,151
to wrap up right now.

8212
03:45:29,151 --> 03:45:29,418
OK.

8213
03:45:29,418 --> 03:45:29,751
Thank you.

8214
03:45:30,352 --> 03:45:33,848
And just that I think there's an

8215
03:45:33,848 --> 03:45:37,095
enormous need for research on

8216
03:45:37,095 --> 03:45:38,327
pragmatic,

8217
03:45:38,327 --> 03:45:41,287
structured efforts to teach

8218
03:45:41,287 --> 03:45:44,755
people to get better sleep that

8219
03:45:44,755 --> 03:45:46,768
go far beyond the

8220
03:45:46,768 --> 03:45:49,271
standard sleep hygiene.

8221
03:45:50,205 --> 03:45:51,846
I talked a little bit about how

8222
03:45:51,846 --> 03:45:53,255
to deal with the circadian

8223
03:45:53,255 --> 03:45:54,176
rhythm disorder.

8224
03:45:55,043 --> 03:45:57,338
I think it's also important to

8225
03:45:57,338 --> 03:45:59,756
treat the entire family that we

8226
03:45:59,756 --> 03:46:01,316
heard a little bit.

8227
03:46:01,316 --> 03:46:03,063
I was very interested this

8228
03:46:03,063 --> 03:46:04,913
morning with Heather Joseph

8229
03:46:04,913 --> 03:46:06,421
talking about helping

8230
03:46:06,421 --> 03:46:07,342
parents to get

8231
03:46:07,342 --> 03:46:08,657
their preschoolers.

8232
03:46:08,857 --> 03:46:11,944
But I think the entire family

8233
03:46:11,944 --> 03:46:14,876
needs to work on it if it's

8234
03:46:14,876 --> 03:46:17,266
going to be workable.

8235
03:46:17,466 --> 03:46:19,133
And we tend to just work with

8236
03:46:19,133 --> 03:46:20,890
individuals in our offices and

8237
03:46:20,890 --> 03:46:22,237
we give them all these

8238
03:46:22,237 --> 03:46:23,863
recommendations that is very

8239
03:46:23,863 --> 03:46:25,701
hard for them to follow because

8240
03:46:25,701 --> 03:46:26,708
of the executive

8241
03:46:26,708 --> 03:46:27,910
functioning disorder.

8242
03:46:28,310 --> 03:46:31,225
And I think we also really need

8243
03:46:31,225 --> 03:46:32,447
as a nation,

8244
03:46:32,447 --> 03:46:35,141
but goodness knows within the

8245
03:46:35,141 --> 03:46:37,991
ADHD impacted families to deal

8246
03:46:37,991 --> 03:46:39,321
with familial

8247
03:46:39,321 --> 03:46:40,989
digital addiction.

8248
03:46:40,989 --> 03:46:43,737
I think that living in a digital

8249
03:46:43,737 --> 03:46:46,277
world is hugely worsening our

8250
03:46:46,277 --> 03:46:48,030
ability to get ADHD

8251
03:46:48,030 --> 03:46:49,650
brains to calm down

8252
03:46:49,650 --> 03:46:51,099
and go to sleep.

8253
03:46:51,099 --> 03:46:52,641
So I thank you so

8254
03:46:52,641 --> 03:46:54,636
much for inviting me.

8255
03:46:54,636 --> 03:46:56,586
I apologize for the technical

8256
03:46:56,586 --> 03:46:58,656
difficulties and I'll sign off

8257
03:46:58,656 --> 03:46:59,207
now and

8258
03:46:59,207 --> 03:47:01,321
listen to the next presentation

8259
03:47:01,321 --> 03:47:02,344
with interest.

8260
03:47:03,512 --> 03:47:04,825
Thank you, Kathleen,

8261
03:47:04,825 --> 03:47:06,978
and thanks everybody for bearing

8262
03:47:06,978 --> 03:47:07,516
with us

8263
03:47:07,516 --> 03:47:09,451
with our technical challenges.

8264
03:47:09,451 --> 03:47:10,931
At the end of the day,

8265
03:47:10,931 --> 03:47:13,072
it is a pleasure to reintroduce

8266
03:47:13,072 --> 03:47:13,555
Gerald

8267
03:47:13,555 --> 03:47:14,222
and Bliss.

8268
03:47:14,222 --> 03:47:16,133
She's the president and Co

8269
03:47:16,133 --> 03:47:18,530
founder of Kyrshank and I'm just

8270
03:47:18,530 --> 03:47:20,028
gonna let her go on

8271
03:47:20,028 --> 03:47:22,374
with her talk in the interest of

8272
03:47:22,374 --> 03:47:24,625
time that I am Geraldine Bliss

8273
03:47:24,625 --> 03:47:25,600
and I have a

8274
03:47:25,600 --> 03:47:26,687
son with Fallon

8275
03:47:26,687 --> 03:47:28,136
McDermott syndrome.

8276
03:47:28,403 --> 03:47:30,493
It is caused by the loss of a

8277
03:47:30,493 --> 03:47:32,007
gene called Shank 3.

8278
03:47:32,808 --> 03:47:34,132
Shank 3 is a gene that's

8279
03:47:34,132 --> 03:47:35,820
expressed in the brain at post

8280
03:47:35,820 --> 03:47:36,945
synaptic densities.

8281
03:47:37,346 --> 03:47:37,934
And yeah,

8282
03:47:37,934 --> 03:47:39,945
I have to close teams and able

8283
03:47:39,945 --> 03:47:40,549
to share

8284
03:47:40,549 --> 03:47:41,650
my my, my slides.

8285
03:47:41,650 --> 03:47:42,367
So we're going to

8286
03:47:42,367 --> 03:47:43,085
skip the slides.

8287
03:47:43,385 --> 03:47:43,819
Charles.

8288
03:47:43,819 --> 03:47:45,487
Oh, you can see now, can you?

8289
03:47:45,487 --> 03:47:46,088
OK, great.

8290
03:47:46,088 --> 03:47:46,355
Thanks.

8291
03:47:46,355 --> 03:47:47,022
We all put them up.

8292
03:47:47,022 --> 03:47:47,889
Thanks so much.

8293
03:47:48,657 --> 03:47:50,205
Charles is a sweetheart,

8294
03:47:50,205 --> 03:47:52,129
but family McDermott syndrome

8295
03:47:52,129 --> 03:47:52,527
has a

8296
03:47:52,527 --> 03:47:54,474
profound effect on individuals

8297
03:47:54,474 --> 03:47:56,031
who are affected by it.

8298
03:47:56,932 --> 03:47:58,333
Let's go to the next slide.

8299
03:48:00,869 --> 03:48:01,086
OK,

8300
03:48:01,086 --> 03:48:03,380
this is Charles when he was was

8301
03:48:03,380 --> 03:48:03,972
a baby,

8302
03:48:03,972 --> 03:48:05,016
we did not know

8303
03:48:05,016 --> 03:48:06,408
anything was wrong.

8304
03:48:06,808 --> 03:48:08,701
Generally his development was

8305
03:48:08,701 --> 03:48:09,745
grossly normal.

8306
03:48:09,745 --> 03:48:11,717
As you can see in the very first

8307
03:48:11,717 --> 03:48:13,424
picture, he's at two months

8308
03:48:13,424 --> 03:48:14,182
propped up,

8309
03:48:14,182 --> 03:48:15,992
looking very robust, healthy,

8310
03:48:15,992 --> 03:48:17,552
walking at 9 1/2 months.

8311
03:48:17,786 --> 03:48:18,855
And at 12 months,

8312
03:48:18,855 --> 03:48:20,473
you can see very socially

8313
03:48:20,473 --> 03:48:21,056
engaged,

8314
03:48:21,056 --> 03:48:22,716
just everything, you know,

8315
03:48:22,716 --> 03:48:23,992
a family hopes for.

8316
03:48:23,992 --> 03:48:25,274
But I will say he was

8317
03:48:25,274 --> 03:48:26,495
a terrible sleeper.

8318
03:48:26,795 --> 03:48:28,649
He never slept for more than two

8319
03:48:28,649 --> 03:48:30,098
to four hours at a time.

8320
03:48:30,432 --> 03:48:32,107
And even at, you know,

8321
03:48:32,107 --> 03:48:33,978
10 months was really not

8322
03:48:33,978 --> 03:48:35,303
sleeping through

8323
03:48:35,303 --> 03:48:36,571
the night at all.

8324
03:48:36,571 --> 03:48:37,554
He was very, very

8325
03:48:37,554 --> 03:48:38,940
frequently, frequently.

8326
03:48:38,940 --> 03:48:40,159
So when I look back

8327
03:48:40,159 --> 03:48:41,986
retrospectively, I wonder if

8328
03:48:41,986 --> 03:48:43,879
that really wasn't our first

8329
03:48:43,879 --> 03:48:44,695
tip off, that

8330
03:48:44,695 --> 03:48:46,014
something was amiss.

8331
03:48:46,515 --> 03:48:47,670
And next,

8332
03:48:47,670 --> 03:48:51,743
this is Charles now when he's 2

8333
03:48:51,743 --> 03:48:53,188
years old.

8334
03:48:53,555 --> 03:48:55,424
And by now we had some concerns.

8335
03:48:55,424 --> 03:48:57,243
We knew that his speech was not

8336
03:48:57,243 --> 03:48:58,827
keeping up with his peers.

8337
03:48:58,827 --> 03:49:00,601
He had a handful of words,

8338
03:49:00,601 --> 03:49:02,839
but his expressive communication

8339
03:49:02,839 --> 03:49:03,398
was far

8340
03:49:03,398 --> 03:49:04,332
behind that of

8341
03:49:04,332 --> 03:49:05,734
other two year olds.

8342
03:49:06,068 --> 03:49:07,398
We were beginning to see some

8343
03:49:07,398 --> 03:49:08,896
behaviors that were a little bit

8344
03:49:08,896 --> 03:49:09,738
concerning and we

8345
03:49:09,738 --> 03:49:10,514
were suspecting a

8346
03:49:10,514 --> 03:49:11,473
diagnosis of autism.

8347
03:49:11,473 --> 03:49:13,660
And indeed, at the age of four,

8348
03:49:13,660 --> 03:49:15,777
he was diagnosed with autism.

8349
03:49:16,211 --> 03:49:17,230
During this time,

8350
03:49:17,230 --> 03:49:19,195
we saw a very frequent awakening

8351
03:49:19,195 --> 03:49:19,748
at night

8352
03:49:19,748 --> 03:49:21,679
and he was unable to put himself

8353
03:49:21,679 --> 03:49:22,584
back to sleep.

8354
03:49:23,151 --> 03:49:26,800
Next, when Charles was six years

8355
03:49:26,800 --> 03:49:29,830
old, he was diagnosed with

8356
03:49:29,830 --> 03:49:32,160
Thaneland McDermott

8357
03:49:32,160 --> 03:49:33,195
syndrome.

8358
03:49:33,195 --> 03:49:35,172
And this was because we had been

8359
03:49:35,172 --> 03:49:37,064
treating him for ADHD and he's

8360
03:49:37,064 --> 03:49:38,200
having some weird

8361
03:49:38,200 --> 03:49:39,013
side effects,

8362
03:49:39,013 --> 03:49:40,945
and we wondered if maybe there

8363
03:49:40,945 --> 03:49:41,203
was

8364
03:49:41,203 --> 03:49:42,396
something going on,

8365
03:49:42,396 --> 03:49:44,406
like a metabolic problem in the

8366
03:49:44,406 --> 03:49:46,279
geneticist who saw us referred

8367
03:49:46,279 --> 03:49:48,276
him for chromosomal microarray.

8368
03:49:48,643 --> 03:49:50,295
Charles was one of the very

8369
03:49:50,295 --> 03:49:51,947
first patients ever, ever,

8370
03:49:51,947 --> 03:49:53,911
anywhere to be diagnosed through

8371
03:49:53,911 --> 03:49:55,383
chromosomal microarray.

8372
03:49:55,383 --> 03:49:56,890
And we were surprised to find

8373
03:49:56,890 --> 03:49:58,533
out that he was missing a small

8374
03:49:58,533 --> 03:49:59,488
piece of the 22nd

8375
03:49:59,488 --> 03:50:00,506
chromosome involving

8376
03:50:00,506 --> 03:50:01,423
the Shank 3 gene.

8377
03:50:03,592 --> 03:50:05,079
We connected quickly with the

8378
03:50:05,079 --> 03:50:06,396
family McDermott Syndrome

8379
03:50:06,396 --> 03:50:07,028
Foundation,

8380
03:50:07,028 --> 03:50:08,326
and we learned that sleep

8381
03:50:08,326 --> 03:50:09,964
problems indeed were very, very

8382
03:50:09,964 --> 03:50:11,233
common in the syndrome.

8383
03:50:11,867 --> 03:50:12,979
A couple years later,

8384
03:50:12,979 --> 03:50:14,498
he had his first generalized

8385
03:50:14,498 --> 03:50:15,203
tonic clonic

8386
03:50:15,203 --> 03:50:15,604
seizure.

8387
03:50:15,604 --> 03:50:16,949
And it was really a

8388
03:50:16,949 --> 03:50:18,507
turning point for us.

8389
03:50:20,075 --> 03:50:21,694
The next month he had another

8390
03:50:21,694 --> 03:50:22,978
one, and then another,

8391
03:50:22,978 --> 03:50:24,412
and then it just exploded.

8392
03:50:24,412 --> 03:50:26,791
Charles was having dozens of

8393
03:50:26,791 --> 03:50:29,084
seizures every single day,

8394
03:50:29,084 --> 03:50:31,692
tonic seizures during sleep and

8395
03:50:31,692 --> 03:50:34,458
a tonic drop seizures during the

8396
03:50:34,458 --> 03:50:34,890
day.

8397
03:50:35,390 --> 03:50:37,635
And certainly the emergence of

8398
03:50:37,635 --> 03:50:40,015
the nighttime nocturnal seizure

8399
03:50:40,015 --> 03:50:40,629
pattern

8400
03:50:40,629 --> 03:50:42,952
really made me start wondering,

8401
03:50:42,952 --> 03:50:44,954
is it possible that he was

8402
03:50:44,954 --> 03:50:45,800
previously

8403
03:50:45,800 --> 03:50:47,810
having epileptiform sort of

8404
03:50:47,810 --> 03:50:50,164
subclinical seizure activity at

8405
03:50:50,164 --> 03:50:51,606
night that we just

8406
03:50:51,606 --> 03:50:53,108
weren't identifying?

8407
03:50:53,108 --> 03:50:54,103
Could that have been

8408
03:50:54,103 --> 03:50:55,380
contributing to his sleep

8409
03:50:55,380 --> 03:50:56,044
disturbance?

8410
03:50:56,244 --> 03:50:57,271
I don't know that that's

8411
03:50:57,271 --> 03:50:58,213
necessarily the case.

8412
03:50:58,213 --> 03:50:59,045
We don't hear,

8413
03:50:59,045 --> 03:51:00,752
I mean many individuals with

8414
03:51:00,752 --> 03:51:01,483
only 40% of

8415
03:51:01,483 --> 03:51:03,388
individuals with Phala McDermott

8416
03:51:03,388 --> 03:51:05,353
syndrome actually have seizures.

8417
03:51:05,353 --> 03:51:07,396
So I'm not sure that that would

8418
03:51:07,396 --> 03:51:09,011
explain all of the sleep

8419
03:51:09,011 --> 03:51:10,625
problems that we see in

8420
03:51:10,625 --> 03:51:11,793
our syndrome next.

8421
03:51:15,697 --> 03:51:15,890
OK,

8422
03:51:15,890 --> 03:51:17,739
Now this is when Charles was

8423
03:51:17,739 --> 03:51:18,400
diagnosed

8424
03:51:18,400 --> 03:51:19,534
with Lennox Gusto.

8425
03:51:19,534 --> 03:51:21,412
This was about six months after

8426
03:51:21,412 --> 03:51:23,147
that first generalized tonic

8427
03:51:23,147 --> 03:51:24,139
clonic seizure.

8428
03:51:24,606 --> 03:51:25,324
And Charles,

8429
03:51:25,324 --> 03:51:27,040
we had a very difficult time

8430
03:51:27,040 --> 03:51:27,776
getting his

8431
03:51:27,776 --> 03:51:29,110
seizures under control.

8432
03:51:29,110 --> 03:51:31,523
We have tried every medication

8433
03:51:31,523 --> 03:51:33,659
out there, ketogenic diet,

8434
03:51:33,659 --> 03:51:35,383
cannabidiol, VNSRNS,

8435
03:51:35,383 --> 03:51:37,219
now corpus callosotomy.

8436
03:51:37,786 --> 03:51:39,666
But sitting bedside with him in

8437
03:51:39,666 --> 03:51:41,122
the hospital, you know,

8438
03:51:41,122 --> 03:51:42,804
I expressed such frustration

8439
03:51:42,804 --> 03:51:44,706
with kind of the poor choice of

8440
03:51:44,706 --> 03:51:45,627
treatments for

8441
03:51:45,627 --> 03:51:46,905
managing epilepsy and

8442
03:51:46,905 --> 03:51:48,730
individuals with Linux gusto.

8443
03:51:48,730 --> 03:51:50,038
And I really bemoan the fact

8444
03:51:50,038 --> 03:51:51,474
that, you know, hey, we've got

8445
03:51:51,474 --> 03:51:52,000
this gene,

8446
03:51:52,000 --> 03:51:52,939
we know what it is,

8447
03:51:52,939 --> 03:51:54,313
we know what it does in the

8448
03:51:54,313 --> 03:51:54,669
brain.

8449
03:51:54,669 --> 03:51:55,595
Why can't we have

8450
03:51:55,595 --> 03:51:56,738
precision medicines?

8451
03:51:57,072 --> 03:51:58,474
And that was really a turning

8452
03:51:58,474 --> 03:51:59,757
point for me when I became

8453
03:51:59,757 --> 03:52:00,842
involved as a patient

8454
03:52:00,842 --> 03:52:02,404
advocate and when I thought, you

8455
03:52:02,404 --> 03:52:03,849
know, we really need to start

8456
03:52:03,849 --> 03:52:04,746
thinking not just

8457
03:52:04,746 --> 03:52:06,258
in terms of epilepsy or autism,

8458
03:52:06,258 --> 03:52:07,765
but in terms of the underlying

8459
03:52:07,765 --> 03:52:07,916
by

8460
03:52:07,916 --> 03:52:09,225
genetics and the underlying

8461
03:52:09,225 --> 03:52:10,485
pathology of the disease.

8462
03:52:10,485 --> 03:52:11,444
If we really want good

8463
03:52:11,444 --> 03:52:12,875
treatments, that's where we need

8464
03:52:12,875 --> 03:52:13,188
to go.

8465
03:52:13,755 --> 03:52:14,623
So next slide.

8466
03:52:16,825 --> 03:52:19,708
So today Charles is he's going

8467
03:52:19,708 --> 03:52:21,630
to be 27 next week.

8468
03:52:22,897 --> 03:52:24,690
He has transitioned all of his

8469
03:52:24,690 --> 03:52:26,287
medical providers to adult

8470
03:52:26,287 --> 03:52:26,901
medicine.

8471
03:52:27,902 --> 03:52:29,724
He has transitioned into the

8472
03:52:29,724 --> 03:52:31,806
adults Medicaid waiver program.

8473
03:52:32,507 --> 03:52:34,276
He lives at home with us.

8474
03:52:34,276 --> 03:52:35,237
And that's how we

8475
03:52:35,237 --> 03:52:36,311
want it right now.

8476
03:52:36,578 --> 03:52:38,679
But thinking about the future,

8477
03:52:38,679 --> 03:52:40,975
one day we won't be here to take

8478
03:52:40,975 --> 03:52:41,549
care of

8479
03:52:41,549 --> 03:52:42,083
Charles.

8480
03:52:42,083 --> 03:52:43,921
Or maybe our health concerns or,

8481
03:52:43,921 --> 03:52:45,682
you know, our capacity to care

8482
03:52:45,682 --> 03:52:46,621
for Charles may

8483
03:52:46,621 --> 03:52:48,330
diminish over time and we need

8484
03:52:48,330 --> 03:52:50,189
to kind of think about like what

8485
03:52:50,189 --> 03:52:51,293
the future options

8486
03:52:51,293 --> 03:52:52,193
for him will be.

8487
03:52:52,193 --> 03:52:53,973
So we have explored some group

8488
03:52:53,973 --> 03:52:55,917
homes in Texas where we live and

8489
03:52:55,917 --> 03:52:56,464
we found

8490
03:52:56,464 --> 03:52:58,239
absolutely nothing that will

8491
03:52:58,239 --> 03:52:59,634
serve his needs well.

8492
03:52:59,634 --> 03:53:00,101
Why?

8493
03:53:00,101 --> 03:53:00,797
Because, one,

8494
03:53:00,797 --> 03:53:02,444
because of the severity of his

8495
03:53:02,444 --> 03:53:02,937
epilepsy

8496
03:53:02,937 --> 03:53:04,550
and the fact that he has very,

8497
03:53:04,550 --> 03:53:05,840
very frequent seizures,

8498
03:53:05,840 --> 03:53:07,326
but also because most of the

8499
03:53:07,326 --> 03:53:08,679
group homes don't provide

8500
03:53:08,679 --> 03:53:09,978
nursing care overnight.

8501
03:53:09,978 --> 03:53:10,923
To to my knowledge,

8502
03:53:10,923 --> 03:53:12,456
there are only two group homes

8503
03:53:12,456 --> 03:53:12,814
in the

8504
03:53:12,814 --> 03:53:14,316
state of Texas that do provide

8505
03:53:14,316 --> 03:53:15,016
nursing care.

8506
03:53:15,016 --> 03:53:17,525
Overnight he has apnea during

8507
03:53:17,525 --> 03:53:20,171
the night, he desaturates even

8508
03:53:20,171 --> 03:53:22,023
when he's not having

8509
03:53:22,023 --> 03:53:24,726
apnea for reasons we don't know.

8510
03:53:25,327 --> 03:53:26,564
He has frequent waking,

8511
03:53:26,564 --> 03:53:28,221
he has difficulty falling back

8512
03:53:28,221 --> 03:53:28,663
asleep,

8513
03:53:28,663 --> 03:53:29,453
and he has some

8514
03:53:29,453 --> 03:53:30,665
behavioral challenges.

8515
03:53:30,665 --> 03:53:32,172
And I will say his behavioral

8516
03:53:32,172 --> 03:53:33,815
challenges are much better than

8517
03:53:33,815 --> 03:53:34,769
they were when he

8518
03:53:34,769 --> 03:53:35,391
was younger,

8519
03:53:35,391 --> 03:53:36,405
but he still has an

8520
03:53:36,405 --> 03:53:37,205
impulsiveness.

8521
03:53:37,605 --> 03:53:38,985
He would easily walk out of the

8522
03:53:38,985 --> 03:53:40,275
house given the opportunity.

8523
03:53:40,275 --> 03:53:41,665
He just doesn't understand that

8524
03:53:41,665 --> 03:53:43,011
certain things are dangerous.

8525
03:53:43,545 --> 03:53:44,145
Next.

8526
03:53:46,181 --> 03:53:46,314
OK,

8527
03:53:46,314 --> 03:53:47,545
so now I'm going to kind of

8528
03:53:47,545 --> 03:53:48,183
change tracks

8529
03:53:48,183 --> 03:53:48,750
a little bit.

8530
03:53:48,750 --> 03:53:50,058
I'm going to tell you a little

8531
03:53:50,058 --> 03:53:51,306
bit about what we know about

8532
03:53:51,306 --> 03:53:52,020
sleep and Phala

8533
03:53:52,020 --> 03:53:52,821
McDermott syndrome.

8534
03:53:53,054 --> 03:53:54,512
And the truth is not

8535
03:53:54,512 --> 03:53:55,824
really that much.

8536
03:53:55,824 --> 03:53:57,286
We've had a little bit of

8537
03:53:57,286 --> 03:53:58,900
research on sleep and Phala

8538
03:53:58,900 --> 03:54:00,095
McDermott syndrome,

8539
03:54:00,095 --> 03:54:00,662
not a lot.

8540
03:54:00,662 --> 03:54:01,584
So this is generally

8541
03:54:01,584 --> 03:54:02,230
what we know.

8542
03:54:02,864 --> 03:54:04,548
There was a study but done by

8543
03:54:04,548 --> 03:54:06,325
Ruth O'Hara and her colleagues

8544
03:54:06,325 --> 03:54:07,569
at Stanford and they

8545
03:54:07,569 --> 03:54:08,853
conducted an interview

8546
03:54:08,853 --> 03:54:09,671
with parents.

8547
03:54:09,671 --> 03:54:10,918
So that was kind of the first

8548
03:54:10,918 --> 03:54:11,606
problem, right?

8549
03:54:11,606 --> 03:54:11,887
It's,

8550
03:54:11,887 --> 03:54:13,730
it relies on parent report and I

8551
03:54:13,730 --> 03:54:14,075
think

8552
03:54:14,075 --> 03:54:15,814
our parents are amazing and can

8553
03:54:15,814 --> 03:54:17,595
report a lot of a lot of really

8554
03:54:17,595 --> 03:54:18,113
valuable

8555
03:54:18,113 --> 03:54:19,581
information about our kids.

8556
03:54:19,581 --> 03:54:20,977
But sleep is one of those

8557
03:54:20,977 --> 03:54:21,983
things, you know,

8558
03:54:21,983 --> 03:54:23,713
it's hard to understand what is

8559
03:54:23,713 --> 03:54:25,220
going on during the night.

8560
03:54:25,954 --> 03:54:28,139
That study showed that 90% of

8561
03:54:28,139 --> 03:54:30,625
parents reported sleep problems,

8562
03:54:30,625 --> 03:54:32,596
40% had difficulty falling

8563
03:54:32,596 --> 03:54:35,077
asleep, requiring a parent to be

8564
03:54:35,077 --> 03:54:35,930
with them,

8565
03:54:35,930 --> 03:54:38,209
60% did not fall asleep within

8566
03:54:38,209 --> 03:54:40,335
20 minutes of going to bed.

8567
03:54:40,335 --> 03:54:41,755
And I'm my guess is that for

8568
03:54:41,755 --> 03:54:42,871
most of the families,

8569
03:54:42,871 --> 03:54:43,721
it's more like an

8570
03:54:43,721 --> 03:54:44,672
hour or two hours.

8571
03:54:45,507 --> 03:54:48,026
70% are restless during sleep,

8572
03:54:48,026 --> 03:54:50,545
67% are incontinent at night,

8573
03:54:50,545 --> 03:54:52,732
59% awake for more than 15

8574
03:54:52,732 --> 03:54:54,582
minutes in the night.

8575
03:54:54,582 --> 03:54:55,309
And again,

8576
03:54:55,309 --> 03:54:57,616
I think that's that most famous

8577
03:54:57,616 --> 03:54:58,286
will say

8578
03:54:58,286 --> 03:55:00,449
my kid was up for hours during

8579
03:55:00,449 --> 03:55:02,728
the night and and only 22% have

8580
03:55:02,728 --> 03:55:04,125
had a sleep study.

8581
03:55:04,125 --> 03:55:05,588
And I think that that number's a

8582
03:55:05,588 --> 03:55:07,035
little concerning to me knowing

8583
03:55:07,035 --> 03:55:07,829
how common sleep

8584
03:55:07,829 --> 03:55:09,230
problems are in our population.

8585
03:55:09,497 --> 03:55:10,767
But it is a really hard

8586
03:55:10,767 --> 03:55:12,473
population to do sleep studies

8587
03:55:12,473 --> 03:55:12,700
in.

8588
03:55:12,700 --> 03:55:13,067
Why?

8589
03:55:13,067 --> 03:55:14,841
Because the kids have to go to

8590
03:55:14,841 --> 03:55:16,438
an unfamiliar environment,

8591
03:55:16,438 --> 03:55:18,214
most of our patients do have a

8592
03:55:18,214 --> 03:55:19,906
diagnosis of autism and they

8593
03:55:19,906 --> 03:55:21,176
have sensory issues.

8594
03:55:21,176 --> 03:55:22,608
It doesn't feel good to them to

8595
03:55:22,608 --> 03:55:24,118
have a bunch of sticky things on

8596
03:55:24,118 --> 03:55:24,779
their head or

8597
03:55:24,779 --> 03:55:26,211
stuck under their nose or stuck

8598
03:55:26,211 --> 03:55:27,182
to their their body.

8599
03:55:28,183 --> 03:55:30,061
It is tough for for families to

8600
03:55:30,061 --> 03:55:31,152
do sleep studies.

8601
03:55:31,986 --> 03:55:32,687
Next slide.

8602
03:55:34,589 --> 03:55:36,200
So a couple years ago we

8603
03:55:36,200 --> 03:55:37,977
organized what's called an

8604
03:55:37,977 --> 03:55:40,094
externally LED patient focused

8605
03:55:40,094 --> 03:55:41,729
drug development meeting.

8606
03:55:41,729 --> 03:55:42,935
This is a meeting that

8607
03:55:42,935 --> 03:55:44,032
we do with the FDA.

8608
03:55:44,365 --> 03:55:46,307
We had over 300 parents that

8609
03:55:46,307 --> 03:55:48,572
participated and provided either

8610
03:55:48,572 --> 03:55:49,704
oral or written

8611
03:55:49,704 --> 03:55:50,371
testimony.

8612
03:55:50,738 --> 03:55:53,246
And I look through the curated,

8613
03:55:53,246 --> 03:55:55,816
all the curated quotes from the

8614
03:55:55,816 --> 03:55:56,644
families.

8615
03:55:56,644 --> 03:55:59,274
We had 66 quotes from families

8616
03:55:59,274 --> 03:56:01,115
that involved sleep.

8617
03:56:01,115 --> 03:56:02,436
So you can tell that's a very

8618
03:56:02,436 --> 03:56:03,516
high priority topic for

8619
03:56:03,516 --> 03:56:03,985
families.

8620
03:56:04,619 --> 03:56:06,369
One of the themes was about the

8621
03:56:06,369 --> 03:56:07,708
intractability of sleep

8622
03:56:07,708 --> 03:56:08,289
problems.

8623
03:56:08,556 --> 03:56:10,293
We've been through the gamut of

8624
03:56:10,293 --> 03:56:11,526
all sleep medication.

8625
03:56:11,526 --> 03:56:12,967
I think we've tried six

8626
03:56:12,967 --> 03:56:14,949
different ones and none of them

8627
03:56:14,949 --> 03:56:16,164
have fully helped.

8628
03:56:16,164 --> 03:56:17,484
Now that is a story we hear

8629
03:56:17,484 --> 03:56:18,734
again and again in Family

8630
03:56:18,734 --> 03:56:19,734
McDermott Syndrome.

8631
03:56:20,535 --> 03:56:21,177
Next,

8632
03:56:21,177 --> 03:56:25,126
where we got the most comments

8633
03:56:25,126 --> 03:56:26,574
of all was

8634
03:56:26,574 --> 03:56:29,844
on the impact on families.

8635
03:56:30,311 --> 03:56:30,667
Sleep,

8636
03:56:30,667 --> 03:56:32,494
exhaustion and disturbance has

8637
03:56:32,494 --> 03:56:32,981
made it

8638
03:56:32,981 --> 03:56:34,764
very hard for us to carry on a

8639
03:56:34,764 --> 03:56:36,251
normal life as a family.

8640
03:56:36,551 --> 03:56:38,346
We lack energy and patience to

8641
03:56:38,346 --> 03:56:40,321
take on normal daily activities,

8642
03:56:40,321 --> 03:56:41,941
let alone the extra and fun

8643
03:56:41,941 --> 03:56:43,898
activities that typical families

8644
03:56:43,898 --> 03:56:45,059
get to experience.

8645
03:56:45,994 --> 03:56:47,689
This is a comment that we heard

8646
03:56:47,689 --> 03:56:49,370
again and again and again from

8647
03:56:49,370 --> 03:56:49,931
families.

8648
03:56:49,931 --> 03:56:51,673
This is one of the top things we

8649
03:56:51,673 --> 03:56:53,177
see every every week on our

8650
03:56:53,177 --> 03:56:54,068
Facebook group,

8651
03:56:54,068 --> 03:56:55,585
families talking about their

8652
03:56:55,585 --> 03:56:57,244
exhaustion, sort of the degree

8653
03:56:57,244 --> 03:56:58,239
of isolation that

8654
03:56:58,239 --> 03:56:59,107
they're feeling.

8655
03:56:59,908 --> 03:57:01,117
It is the combination of the

8656
03:57:01,117 --> 03:57:02,308
child not sleeping and when

8657
03:57:02,308 --> 03:57:03,278
their child is awake,

8658
03:57:03,278 --> 03:57:04,539
having a lot of really severe

8659
03:57:04,539 --> 03:57:05,713
and challenging behaviors.

8660
03:57:05,713 --> 03:57:07,184
The parents have to be vigilant

8661
03:57:07,184 --> 03:57:07,849
all the time.

8662
03:57:08,216 --> 03:57:09,000
And then at night,

8663
03:57:09,000 --> 03:57:10,116
they really don't have an

8664
03:57:10,116 --> 03:57:10,785
opportunity to

8665
03:57:10,785 --> 03:57:12,054
rest because of their child's

8666
03:57:12,054 --> 03:57:12,754
sleep problems.

8667
03:57:13,388 --> 03:57:14,022
Next slide.

8668
03:57:15,623 --> 03:57:15,924
OK.

8669
03:57:17,525 --> 03:57:18,147
And finally,

8670
03:57:18,147 --> 03:57:19,374
I think because of that

8671
03:57:19,374 --> 03:57:19,961
behavioral

8672
03:57:19,961 --> 03:57:21,267
concern during, you know,

8673
03:57:21,267 --> 03:57:22,363
when a child awakes,

8674
03:57:22,363 --> 03:57:23,587
families really they're,

8675
03:57:23,587 --> 03:57:25,256
they're, they're taking a lot of

8676
03:57:25,256 --> 03:57:25,934
precautions.

8677
03:57:26,901 --> 03:57:27,791
In this example,

8678
03:57:27,791 --> 03:57:29,444
you'll see the family reports

8679
03:57:29,444 --> 03:57:30,071
that their

8680
03:57:30,071 --> 03:57:31,632
child's room only contains 2

8681
03:57:31,632 --> 03:57:33,454
beds and a removable curtain rod

8682
03:57:33,454 --> 03:57:34,309
rod for safety

8683
03:57:34,309 --> 03:57:34,742
reasons.

8684
03:57:34,742 --> 03:57:35,983
And we had a death in our

8685
03:57:35,983 --> 03:57:37,501
community at several years ago

8686
03:57:37,501 --> 03:57:38,513
where a little girl

8687
03:57:38,513 --> 03:57:39,432
woke up and she was

8688
03:57:39,432 --> 03:57:40,448
playing in her room.

8689
03:57:40,648 --> 03:57:42,172
She became entangled in her

8690
03:57:42,172 --> 03:57:43,751
curtains and she strangled.

8691
03:57:43,751 --> 03:57:44,961
And she was found the next

8692
03:57:44,961 --> 03:57:46,386
morning by her parents and she

8693
03:57:46,386 --> 03:57:47,288
had, she was dead.

8694
03:57:47,855 --> 03:57:49,205
So a lot of our families are

8695
03:57:49,205 --> 03:57:50,783
very vigilant and they know from

8696
03:57:50,783 --> 03:57:51,326
the moment

8697
03:57:51,326 --> 03:57:52,792
their child wakes up their day

8698
03:57:52,792 --> 03:57:53,428
has started.

8699
03:57:54,228 --> 03:57:55,965
Either my husband or I sleep in

8700
03:57:55,965 --> 03:57:57,795
his room to ensure he is safe as

8701
03:57:57,795 --> 03:57:58,766
he is at risk of

8702
03:57:58,766 --> 03:58:00,508
elopement and because he rarely

8703
03:58:00,508 --> 03:58:01,970
sleeps through the night.

8704
03:58:01,970 --> 03:58:02,846
And that's a very

8705
03:58:02,846 --> 03:58:03,671
common problem.

8706
03:58:04,305 --> 03:58:05,306
Next slide.

8707
03:58:06,975 --> 03:58:07,342
OK.

8708
03:58:07,875 --> 03:58:10,045
So in family McDermott syndrome,

8709
03:58:10,045 --> 03:58:12,080
the core features are autism,

8710
03:58:12,080 --> 03:58:13,973
which about 75 to 85% of our

8711
03:58:13,973 --> 03:58:16,182
individuals either have a strict

8712
03:58:16,182 --> 03:58:17,218
a diagnosis of

8713
03:58:17,218 --> 03:58:18,753
strict autism or autism

8714
03:58:18,753 --> 03:58:20,021
spectrum disorder.

8715
03:58:20,655 --> 03:58:22,296
Intellectual disability of

8716
03:58:22,296 --> 03:58:24,230
varying degrees occurs in 100%

8717
03:58:24,230 --> 03:58:25,326
of our patients.

8718
03:58:25,326 --> 03:58:27,295
Some are a little or moderately

8719
03:58:27,295 --> 03:58:29,368
affected, others most tend to be

8720
03:58:29,368 --> 03:58:30,598
more on the severe

8721
03:58:30,598 --> 03:58:32,567
to profound end of the spectrum.

8722
03:58:32,934 --> 03:58:34,235
And infant hypotonia.

8723
03:58:34,636 --> 03:58:36,371
Seizures occur in about 40% of

8724
03:58:36,371 --> 03:58:38,204
our patients and sleep problems

8725
03:58:38,204 --> 03:58:38,973
occur in 90%

8726
03:58:38,973 --> 03:58:39,907
of our patients.

8727
03:58:40,775 --> 03:58:41,910
Certainly there are a lot of

8728
03:58:41,910 --> 03:58:43,110
things that could potentially

8729
03:58:43,110 --> 03:58:43,978
influence sleep that

8730
03:58:43,978 --> 03:58:44,996
occur in family McDermott

8731
03:58:44,996 --> 03:58:45,961
syndrome, for instance,

8732
03:58:45,961 --> 03:58:46,381
seizures.

8733
03:58:46,381 --> 03:58:47,546
What is the contribution of

8734
03:58:47,546 --> 03:58:48,883
seizures to sleep disturbance?

8735
03:58:49,150 --> 03:58:49,781
What about other

8736
03:58:49,781 --> 03:58:50,451
health problems?

8737
03:58:51,019 --> 03:58:52,726
Gastroesophageal reflux and

8738
03:58:52,726 --> 03:58:54,662
Constipation are really common

8739
03:58:54,662 --> 03:58:55,823
in our community.

8740
03:58:55,823 --> 03:58:56,568
And you know,

8741
03:58:56,568 --> 03:58:58,459
we certainly wonder if sometimes

8742
03:58:58,459 --> 03:59:00,240
discomfort from GI problems can

8743
03:59:00,240 --> 03:59:01,963
contribute to sleep problems,

8744
03:59:01,963 --> 03:59:02,964
especially reflux.

8745
03:59:03,331 --> 03:59:05,110
There's just a restlessness that

8746
03:59:05,110 --> 03:59:06,870
our kids have day and night and

8747
03:59:06,870 --> 03:59:07,835
maybe that alone

8748
03:59:07,835 --> 03:59:09,203
is a contributing factor.

8749
03:59:09,737 --> 03:59:11,045
And there's just, I mean,

8750
03:59:11,045 --> 03:59:12,759
one of the just difficult things

8751
03:59:12,759 --> 03:59:13,241
a lot of

8752
03:59:13,241 --> 03:59:14,767
parents describe as a lack of

8753
03:59:14,767 --> 03:59:15,977
sleepiness at bedtime.

8754
03:59:15,977 --> 03:59:17,283
It's if you're a parent and

8755
03:59:17,283 --> 03:59:18,762
you've been through the two to

8756
03:59:18,762 --> 03:59:19,847
three-year old stage,

8757
03:59:19,847 --> 03:59:20,285
you, you,

8758
03:59:20,285 --> 03:59:21,833
you know that feeling like when

8759
03:59:21,833 --> 03:59:22,083
your

8760
03:59:22,083 --> 03:59:23,428
child is so amped up after a

8761
03:59:23,428 --> 03:59:24,858
long day that they can't fall

8762
03:59:24,858 --> 03:59:25,253
asleep.

8763
03:59:25,653 --> 03:59:25,871
Well,

8764
03:59:25,871 --> 03:59:27,040
that's how it is in felony

8765
03:59:27,040 --> 03:59:27,355
Dermot

8766
03:59:27,355 --> 03:59:28,289
syndrome all the time.

8767
03:59:29,390 --> 03:59:29,548
So,

8768
03:59:29,548 --> 03:59:31,222
and then we also know there are

8769
03:59:31,222 --> 03:59:31,492
some

8770
03:59:31,492 --> 03:59:33,139
things that could be influenced

8771
03:59:33,139 --> 03:59:34,095
by sleep as well.

8772
03:59:34,095 --> 03:59:34,813
For instance,

8773
03:59:34,813 --> 03:59:36,566
Charles has much worse seizures

8774
03:59:36,566 --> 03:59:37,131
following

8775
03:59:37,131 --> 03:59:37,943
those nights of

8776
03:59:37,943 --> 03:59:39,133
especially bad sleep.

8777
03:59:39,701 --> 03:59:41,683
We certainly wonder about the

8778
03:59:41,683 --> 03:59:43,913
role that the kind of the effect

8779
03:59:43,913 --> 03:59:45,306
of sleep, you know,

8780
03:59:45,306 --> 03:59:47,289
sleep deprivation on learning

8781
03:59:47,289 --> 03:59:48,961
and memory and attention

8782
03:59:48,961 --> 03:59:50,912
certainly behavior and mood

8783
03:59:50,912 --> 03:59:51,446
as well.

8784
03:59:52,046 --> 03:59:52,647
Next.

8785
03:59:54,382 --> 03:59:55,918
OK, so like that's a problem,

8786
03:59:55,918 --> 03:59:57,555
like it's sort of there's this

8787
03:59:57,555 --> 03:59:57,719
bi

8788
03:59:57,719 --> 03:59:59,143
directional relationship it

8789
03:59:59,143 --> 04:00:00,814
seems between sleep and some of

8790
04:00:00,814 --> 04:00:01,622
the other like

8791
04:00:01,622 --> 04:00:03,220
troubling aspects of phaliumic

8792
04:00:03,220 --> 04:00:04,125
Dermot syndrome.

8793
04:00:04,125 --> 04:00:05,350
And I should say we could

8794
04:00:05,350 --> 04:00:06,648
probably insert many other

8795
04:00:06,648 --> 04:00:08,096
neurodevelopmental disorders

8796
04:00:08,096 --> 04:00:09,051
instead of phaliumic

8797
04:00:09,051 --> 04:00:09,864
Dermot syndrome.

8798
04:00:09,864 --> 04:00:11,519
I know these are really common

8799
04:00:11,519 --> 04:00:13,267
problems among all of the other

8800
04:00:13,267 --> 04:00:14,168
kind of genetic

8801
04:00:14,168 --> 04:00:15,837
conditions that are associated

8802
04:00:15,837 --> 04:00:17,171
with, you know, autism,

8803
04:00:17,171 --> 04:00:18,416
intellectual disability

8804
04:00:18,416 --> 04:00:19,173
and epilepsy.

8805
04:00:19,173 --> 04:00:21,251
And while they may not share the

8806
04:00:21,251 --> 04:00:22,744
exact same phenotypes,

8807
04:00:22,744 --> 04:00:24,412
they do have sort of this.

8808
04:00:24,412 --> 04:00:25,039
They seem to have

8809
04:00:25,039 --> 04:00:25,813
this bi directional.

8810
04:00:25,813 --> 04:00:27,730
You know, relationship between

8811
04:00:27,730 --> 04:00:29,619
sleep and, and behaviors and,

8812
04:00:29,619 --> 04:00:31,052
and other phenotypes.

8813
04:00:31,052 --> 04:00:31,720
So how are we going

8814
04:00:31,720 --> 04:00:32,353
to get past that?

8815
04:00:32,353 --> 04:00:33,752
And you think 1 is, you know,

8816
04:00:33,752 --> 04:00:35,192
we need to be able to measure

8817
04:00:35,192 --> 04:00:35,490
sleep

8818
04:00:35,490 --> 04:00:37,054
quality and quantity with better

8819
04:00:37,054 --> 04:00:37,592
precision.

8820
04:00:37,992 --> 04:00:38,627
And secondly,

8821
04:00:38,627 --> 04:00:40,078
we need to be able to collect

8822
04:00:40,078 --> 04:00:40,628
behavioral

8823
04:00:40,628 --> 04:00:41,496
data in real time.

8824
04:00:41,496 --> 04:00:42,163
And certainly I

8825
04:00:42,163 --> 04:00:42,964
again, this is 1.

8826
04:00:42,964 --> 04:00:44,526
I do trust our parents to report

8827
04:00:44,526 --> 04:00:46,021
on a lot of things and I think

8828
04:00:46,021 --> 04:00:46,968
they can report on

8829
04:00:46,968 --> 04:00:47,412
behavior,

8830
04:00:47,412 --> 04:00:48,778
but I don't think it can be

8831
04:00:48,778 --> 04:00:49,537
like, I think,

8832
04:00:49,537 --> 04:00:50,565
you know, in my mind,

8833
04:00:50,565 --> 04:00:51,871
maybe it's an app Families

8834
04:00:51,871 --> 04:00:52,473
report on a

8835
04:00:52,473 --> 04:00:53,062
daily basis,

8836
04:00:53,062 --> 04:00:54,572
not like once every six months

8837
04:00:54,572 --> 04:00:55,076
when they

8838
04:00:55,076 --> 04:00:56,000
go in or, you know,

8839
04:00:56,000 --> 04:00:57,496
some kind of a clinic visit or

8840
04:00:57,496 --> 04:00:57,945
clinical

8841
04:00:57,945 --> 04:00:58,546
trial visit.

8842
04:00:59,447 --> 04:01:00,148
Next slide.

8843
04:01:02,250 --> 04:01:02,434
OK,

8844
04:01:02,434 --> 04:01:04,136
so I created some data from

8845
04:01:04,136 --> 04:01:05,019
Facebook just

8846
04:01:05,019 --> 04:01:05,761
to see like,

8847
04:01:05,761 --> 04:01:07,596
what are people doing to help

8848
04:01:07,596 --> 04:01:08,356
their their

8849
04:01:08,356 --> 04:01:09,953
children with sleep in the

8850
04:01:09,953 --> 04:01:11,532
Phalen McDermott syndrome

8851
04:01:11,532 --> 04:01:12,226
community?

8852
04:01:12,226 --> 04:01:13,661
I'll tell you what doesn't work.

8853
04:01:14,061 --> 04:01:15,997
Sleep hygiene maybe minimally

8854
04:01:15,997 --> 04:01:18,179
helps, but it doesn't help their

8855
04:01:18,179 --> 04:01:19,133
kids overcome

8856
04:01:19,133 --> 04:01:20,681
all their sleep issues,

8857
04:01:20,681 --> 04:01:22,619
doesn't help them go back to

8858
04:01:22,619 --> 04:01:23,104
sleep,

8859
04:01:23,104 --> 04:01:25,039
doesn't prevent the nighttime

8860
04:01:25,039 --> 04:01:27,080
awakenings, sleep training and

8861
04:01:27,080 --> 04:01:28,509
ASMR YouTube videos.

8862
04:01:28,509 --> 04:01:29,427
See, families have

8863
04:01:29,427 --> 04:01:30,344
tried everything.

8864
04:01:31,379 --> 04:01:32,699
On the opposite side is are the

8865
04:01:32,699 --> 04:01:34,049
things that all the things that

8866
04:01:34,049 --> 04:01:34,615
families are

8867
04:01:34,615 --> 04:01:35,981
trying and I'm not going to read

8868
04:01:35,981 --> 04:01:36,450
that list.

8869
04:01:36,450 --> 04:01:37,223
I'll just let you

8870
04:01:37,223 --> 04:01:38,085
take a look at it.

8871
04:01:38,286 --> 04:01:39,876
A lot of families do use

8872
04:01:39,876 --> 04:01:41,705
melatonin, but they try all

8873
04:01:41,705 --> 04:01:42,857
kinds of things,

8874
04:01:42,857 --> 04:01:44,898
some of which don't necessarily

8875
04:01:44,898 --> 04:01:46,717
have evidence like THC, for

8876
04:01:46,717 --> 04:01:47,862
instance, right,

8877
04:01:47,862 --> 04:01:49,697
or evidence in, in children.

8878
04:01:50,264 --> 04:01:52,055
I think there's a real need to,

8879
04:01:52,055 --> 04:01:53,719
to start like doing clinical

8880
04:01:53,719 --> 04:01:54,135
trial,

8881
04:01:54,135 --> 04:01:55,860
like comparative effectiveness

8882
04:01:55,860 --> 04:01:57,389
research, looking at these

8883
04:01:57,389 --> 04:01:58,506
different options.

8884
04:01:58,506 --> 04:02:00,271
What I want to get away from is

8885
04:02:00,271 --> 04:02:01,961
parents like me and others in

8886
04:02:01,961 --> 04:02:02,777
our community

8887
04:02:02,777 --> 04:02:04,605
having to do north of 1 clinical

8888
04:02:04,605 --> 04:02:06,298
trials on our own children to

8889
04:02:06,298 --> 04:02:07,348
figure out what's

8890
04:02:07,348 --> 04:02:08,149
going to work.

8891
04:02:08,149 --> 04:02:10,024
We really need better guidance

8892
04:02:10,024 --> 04:02:11,683
on how to manage our sleep

8893
04:02:11,683 --> 04:02:13,087
problems and which of

8894
04:02:13,087 --> 04:02:14,134
these medications

8895
04:02:14,134 --> 04:02:15,489
are really effective.

8896
04:02:15,489 --> 04:02:16,943
And this is probably something

8897
04:02:16,943 --> 04:02:18,375
that we're, we could break it

8898
04:02:18,375 --> 04:02:19,560
down by different kinds

8899
04:02:19,560 --> 04:02:20,577
of genetic disorders,

8900
04:02:20,577 --> 04:02:22,029
different types of diagnosis,

8901
04:02:22,029 --> 04:02:23,068
have huge studies that

8902
04:02:23,068 --> 04:02:23,965
enroll these kids.

8903
04:02:23,965 --> 04:02:25,627
But then really where we're

8904
04:02:25,627 --> 04:02:27,454
trying to identify what works

8905
04:02:27,454 --> 04:02:28,336
for different

8906
04:02:28,336 --> 04:02:28,936
diagnosis.

8907
04:02:30,771 --> 04:02:31,852
And in family McDermott

8908
04:02:31,852 --> 04:02:33,052
syndrome, we do have some

8909
04:02:33,052 --> 04:02:34,108
consensus guidelines,

8910
04:02:34,108 --> 04:02:35,577
but they're not evidence based,

8911
04:02:35,577 --> 04:02:36,477
They haven't been,

8912
04:02:36,477 --> 04:02:37,975
there's been no like comparative

8913
04:02:37,975 --> 04:02:39,175
effectiveness research to

8914
04:02:39,175 --> 04:02:39,847
compare these

8915
04:02:39,847 --> 04:02:40,181
things.

8916
04:02:40,181 --> 04:02:41,884
These are just guidelines based

8917
04:02:41,884 --> 04:02:43,072
on some of our expert

8918
04:02:43,072 --> 04:02:43,751
physicians.

8919
04:02:44,752 --> 04:02:45,686
Next page.

8920
04:02:47,822 --> 04:02:47,984
OK,

8921
04:02:47,984 --> 04:02:49,703
so I was asked to prepare a few

8922
04:02:49,703 --> 04:02:50,258
questions

8923
04:02:50,258 --> 04:02:51,325
for future research.

8924
04:02:51,626 --> 04:02:53,601
The 1st is really to consider

8925
04:02:53,601 --> 04:02:55,205
doing genotype by sleep

8926
04:02:55,205 --> 04:02:56,530
phenotype studies.

8927
04:02:56,530 --> 04:02:57,964
And I wonder if you know,

8928
04:02:57,964 --> 04:02:59,612
thinking about other genetic

8929
04:02:59,612 --> 04:03:00,201
disorders

8930
04:03:00,201 --> 04:03:01,065
associated with

8931
04:03:01,065 --> 04:03:02,737
neurodevelopmental problems,

8932
04:03:02,737 --> 04:03:04,454
if potentially there's data in

8933
04:03:04,454 --> 04:03:05,915
electronic health records

8934
04:03:05,915 --> 04:03:07,375
including sleep studies.

8935
04:03:07,375 --> 04:03:08,845
And if this might help us

8936
04:03:08,845 --> 04:03:10,642
generate some hypothesis about

8937
04:03:10,642 --> 04:03:12,079
how you know about like

8938
04:03:12,079 --> 04:03:13,739
the different kinds of sleep

8939
04:03:13,739 --> 04:03:15,442
problems that may present in

8940
04:03:15,442 --> 04:03:16,050
different

8941
04:03:16,050 --> 04:03:17,752
neurodevelopmental disorders.

8942
04:03:18,819 --> 04:03:20,283
The second idea is to start

8943
04:03:20,283 --> 04:03:21,856
doing interventional trials,

8944
04:03:21,856 --> 04:03:23,484
enrolling different cohorts of

8945
04:03:23,484 --> 04:03:25,094
patients, especially patients

8946
04:03:25,094 --> 04:03:25,927
with different

8947
04:03:25,927 --> 04:03:26,955
genetic conditions,

8948
04:03:26,955 --> 04:03:28,342
and start doing pragmatic

8949
04:03:28,342 --> 04:03:29,230
clinical trials

8950
04:03:29,230 --> 04:03:30,821
of things that are already in

8951
04:03:30,821 --> 04:03:31,699
widespread use.

8952
04:03:31,699 --> 04:03:33,272
As you can see from the previous

8953
04:03:33,272 --> 04:03:34,631
slide, families are already

8954
04:03:34,631 --> 04:03:35,436
trying a lot of

8955
04:03:35,436 --> 04:03:36,103
things, right?

8956
04:03:36,103 --> 04:03:37,197
Doctors are prescribing

8957
04:03:37,197 --> 04:03:38,005
a lot of things.

8958
04:03:38,306 --> 04:03:40,573
Why can't we just take that and

8959
04:03:40,573 --> 04:03:42,970
then organize that into the more

8960
04:03:42,970 --> 04:03:43,644
systemic

8961
04:03:43,644 --> 04:03:45,976
systematic process instead of us

8962
04:03:45,976 --> 04:03:47,990
each doing our own and of 1

8963
04:03:47,990 --> 04:03:49,183
informal trial.

8964
04:03:49,951 --> 04:03:52,031
And the last recommendation from

8965
04:03:52,031 --> 04:03:53,759
my parent perspective as a

8966
04:03:53,759 --> 04:03:54,956
parent is that we

8967
04:03:54,956 --> 04:03:56,607
need in home studies with

8968
04:03:56,607 --> 04:03:58,259
digital data collection.

8969
04:03:58,259 --> 04:03:58,635
I mean,

8970
04:03:58,635 --> 04:04:00,233
sleep studies done in clinics

8971
04:04:00,233 --> 04:04:00,895
are really,

8972
04:04:00,895 --> 04:04:01,956
really difficult for

8973
04:04:01,956 --> 04:04:02,964
a lot of families.

8974
04:04:03,297 --> 04:04:05,682
And now we have some wonderful

8975
04:04:05,682 --> 04:04:07,560
devices, Cure Shank, my

8976
04:04:07,560 --> 04:04:08,703
organization,

8977
04:04:08,703 --> 04:04:11,025
we are funding a pilot of the

8978
04:04:11,025 --> 04:04:13,166
Dream Headband with Doctor

8979
04:04:13,166 --> 04:04:13,908
Milonis.

8980
04:04:14,542 --> 04:04:16,268
But we need lots and lots of

8981
04:04:16,268 --> 04:04:18,218
these kinds of projects just to

8982
04:04:18,218 --> 04:04:19,413
figure out what is

8983
04:04:19,413 --> 04:04:21,396
actually going to be feasible to

8984
04:04:21,396 --> 04:04:22,883
do in in home settings.

8985
04:04:23,250 --> 04:04:23,918
So anyway,

8986
04:04:23,918 --> 04:04:25,629
I am so grateful for this

8987
04:04:25,629 --> 04:04:26,587
meeting being

8988
04:04:26,587 --> 04:04:27,254
organized.

8989
04:04:27,254 --> 04:04:27,695
Many,

8990
04:04:27,695 --> 04:04:29,859
Many thanks to NHLBI for

8991
04:04:29,859 --> 04:04:31,392
organizing this.

8992
04:04:31,392 --> 04:04:33,044
I hope that you'll have

8993
04:04:33,044 --> 04:04:35,244
sustained interest and funding

8994
04:04:35,244 --> 04:04:36,564
research on sleep

8995
04:04:36,564 --> 04:04:38,898
disorders and neurodevelopmental

8996
04:04:38,898 --> 04:04:39,700
disorders.

8997
04:04:39,700 --> 04:04:41,311
And thank you so much to Lucia,

8998
04:04:41,311 --> 04:04:42,911
Larry and the other organizers

8999
04:04:42,911 --> 04:04:43,337
of this

9000
04:04:43,337 --> 04:04:43,738
meeting.

9001
04:04:46,374 --> 04:04:48,006
Thank you, Caroline,

9002
04:04:48,006 --> 04:04:50,211
and you were fast on time.

9003
04:04:50,711 --> 04:04:51,460
And thank you,

9004
04:04:51,460 --> 04:04:53,053
everybody for bearing with us

9005
04:04:53,053 --> 04:04:53,547
with our

9006
04:04:53,547 --> 04:04:54,749
technical difficulties.

9007
04:04:54,749 --> 04:04:56,751
We're going to move on all the

9008
04:04:56,751 --> 04:04:58,867
questions to our Q&A at the end

9009
04:04:58,867 --> 04:04:59,687
of the day.

9010
04:04:59,887 --> 04:05:01,329
So a lot of our speakers are

9011
04:05:01,329 --> 04:05:02,256
going to stay on.

9012
04:05:02,256 --> 04:05:04,553
So I'm going to transition to

9013
04:05:04,553 --> 04:05:06,576
Jared, who is going to be

9014
04:05:06,576 --> 04:05:08,195
moderating the Q&A.

9015
04:05:09,697 --> 04:05:10,664
Thanks, Lucy.

9016
04:05:10,664 --> 04:05:11,808
Thanks for everybody for their

9017
04:05:11,808 --> 04:05:12,864
patience with the technical

9018
04:05:12,864 --> 04:05:13,334
challenges.

9019
04:05:14,368 --> 04:05:14,902
Thanks, Jared.

9020
04:05:16,003 --> 04:05:17,371
Yes, and thank you everyone.

9021
04:05:17,571 --> 04:05:19,300
It's been an incredible day and

9022
04:05:19,300 --> 04:05:21,065
and you and I hope everyone can

9023
04:05:21,065 --> 04:05:21,976
see the breadth

9024
04:05:21,976 --> 04:05:22,143
of,

9025
04:05:22,143 --> 04:05:23,977
of conditions that we're talking

9026
04:05:23,977 --> 04:05:24,378
about,

9027
04:05:24,378 --> 04:05:25,820
types of sleep phenotypes,

9028
04:05:25,820 --> 04:05:27,353
types of interventions that

9029
04:05:27,353 --> 04:05:28,149
we're talking

9030
04:05:28,149 --> 04:05:28,918
about and also

9031
04:05:28,918 --> 04:05:30,017
what we don't know.

9032
04:05:30,818 --> 04:05:32,822
So there's a number of questions

9033
04:05:32,822 --> 04:05:34,675
in the chat for speakers that

9034
04:05:34,675 --> 04:05:35,890
are still with us.

9035
04:05:35,890 --> 04:05:37,234
I encourage you take a look can

9036
04:05:37,234 --> 04:05:38,563
add some responses because you

9037
04:05:38,563 --> 04:05:39,360
can actually type

9038
04:05:39,360 --> 04:05:40,786
them in if you can see them in

9039
04:05:40,786 --> 04:05:41,262
the Q& A.

9040
04:05:41,262 --> 04:05:42,830
If you can't let us know.

9041
04:05:42,830 --> 04:05:43,126
But I,

9042
04:05:43,126 --> 04:05:44,745
I want to open up to a couple of

9043
04:05:44,745 --> 04:05:45,099
themes

9044
04:05:45,099 --> 04:05:46,509
that have emerged and some of

9045
04:05:46,509 --> 04:05:47,968
the questions we've received.

9046
04:05:47,968 --> 04:05:50,371
And one of them I think is about

9047
04:05:50,371 --> 04:05:52,445
Co occurring conditions and

9048
04:05:52,445 --> 04:05:53,674
parsing sort of

9049
04:05:53,674 --> 04:05:54,953
either, you know,

9050
04:05:54,953 --> 04:05:56,884
comorbidities in terms of

9051
04:05:56,884 --> 04:05:57,812
psychiatric

9052
04:05:57,812 --> 04:05:58,612
components.

9053
04:05:58,612 --> 04:06:00,605
There's been questions about

9054
04:06:00,605 --> 04:06:01,816
anxiety in ADHD,

9055
04:06:01,816 --> 04:06:03,781
insomnia and ADHD parsing Co

9056
04:06:03,781 --> 04:06:05,886
occurring autism in ADHD and,

9057
04:06:05,886 --> 04:06:07,852
and what's driving the sleep

9058
04:06:07,852 --> 04:06:09,715
issue and, and where do we

9059
04:06:09,715 --> 04:06:11,292
mechanistically parse

9060
04:06:11,292 --> 04:06:11,692
these?

9061
04:06:11,692 --> 04:06:13,035
So I was wondering if any

9062
04:06:13,035 --> 04:06:14,620
speakers could talk about how

9063
04:06:14,620 --> 04:06:16,097
they treat either in their

9064
04:06:16,097 --> 04:06:17,157
research or in their

9065
04:06:17,157 --> 04:06:18,165
clinical practice.

9066
04:06:18,666 --> 04:06:19,217
You know,

9067
04:06:19,217 --> 04:06:20,852
how do you start doing the

9068
04:06:20,852 --> 04:06:21,669
differential

9069
04:06:21,669 --> 04:06:23,133
between some of these Co

9070
04:06:23,133 --> 04:06:24,884
occurring neurodevelopmental

9071
04:06:24,884 --> 04:06:25,573
disorders,

9072
04:06:25,573 --> 04:06:27,389
some of the comorbidities that

9073
04:06:27,389 --> 04:06:28,810
come with them and then

9074
04:06:28,810 --> 04:06:30,478
ultimately what the routes

9075
04:06:30,478 --> 04:06:31,885
to to to sleep are and,

9076
04:06:31,885 --> 04:06:33,834
and what folks thoughts on that

9077
04:06:33,834 --> 04:06:34,148
are?

9078
04:06:34,148 --> 04:06:35,539
That touches on a few different

9079
04:06:35,539 --> 04:06:36,750
questions folks submitted.

9080
04:06:46,994 --> 04:06:47,837
Do you have a way

9081
04:06:47,837 --> 04:06:48,729
you'd like us to?

9082
04:06:49,363 --> 04:06:49,563
No,

9083
04:06:49,563 --> 04:06:51,615
please call out if you have an

9084
04:06:51,615 --> 04:06:52,299
answer to

9085
04:06:52,299 --> 04:06:54,193
that very broad question on a

9086
04:06:54,193 --> 04:06:55,369
number of topics.

9087
04:06:55,636 --> 04:06:56,628
I am not a clinical

9088
04:06:56,628 --> 04:06:58,280
psychologist, so I will refrain

9089
04:06:58,280 --> 04:06:59,240
from parsing that

9090
04:06:59,240 --> 04:07:00,609
clinically, but I, I, I do

9091
04:07:00,609 --> 04:07:02,330
think, you know, it's absolutely

9092
04:07:02,330 --> 04:07:03,244
critical from a,

9093
04:07:03,244 --> 04:07:04,424
you know, I do research

9094
04:07:04,424 --> 04:07:05,246
mostly in ADHD.

9095
04:07:05,246 --> 04:07:07,217
We do a little bit of work in

9096
04:07:07,217 --> 04:07:09,157
autism and we take primarily

9097
04:07:09,157 --> 04:07:10,751
dimensional approaches

9098
04:07:10,751 --> 04:07:12,386
for exactly this reason.

9099
04:07:12,386 --> 04:07:15,346
And we see kids with ADHD and

9100
04:07:15,346 --> 04:07:17,591
anxiety all the time.

9101
04:07:17,591 --> 04:07:19,174
In terms of kids who come into

9102
04:07:19,174 --> 04:07:19,860
our studies,

9103
04:07:19,860 --> 04:07:21,559
we see a lot of overlap and ADHD

9104
04:07:21,559 --> 04:07:22,196
and autism.

9105
04:07:22,196 --> 04:07:23,265
We don't, you know,

9106
04:07:23,265 --> 04:07:25,065
so we make actually very we go,

9107
04:07:25,065 --> 04:07:26,742
we do not exclude for a lot of

9108
04:07:26,742 --> 04:07:28,399
these Co occurring conditions

9109
04:07:28,399 --> 04:07:29,370
because it it it

9110
04:07:29,370 --> 04:07:31,168
fundamentally changes the sample

9111
04:07:31,168 --> 04:07:32,778
from what we see in the real

9112
04:07:32,778 --> 04:07:33,641
world of kids,

9113
04:07:33,641 --> 04:07:34,145
you know,

9114
04:07:34,145 --> 04:07:35,582
coming in with with these

9115
04:07:35,582 --> 04:07:36,443
presentations.

9116
04:07:36,443 --> 04:07:37,980
So wondering how folks treat

9117
04:07:37,980 --> 04:07:38,913
this clinically.

9118
04:07:38,913 --> 04:07:39,613
Beth, go ahead.

9119
04:07:45,085 --> 04:07:48,081
Doctor Mallow, I

9120
04:07:48,081 --> 04:07:51,825
think you're muted.

9121
04:07:52,226 --> 04:07:52,448
Beth,

9122
04:07:52,448 --> 04:07:53,817
I don't know if you are trying

9123
04:07:53,817 --> 04:07:54,228
to talk,

9124
04:07:54,228 --> 04:07:55,122
your hand is raised,

9125
04:07:55,122 --> 04:07:56,363
but you should go ahead and

9126
04:07:56,363 --> 04:07:56,730
unmute.

9127
04:08:00,868 --> 04:08:01,936
OK, Hold on.

9128
04:08:01,936 --> 04:08:03,270
I think this is great.

9129
04:08:03,270 --> 04:08:03,537
Yeah.

9130
04:08:03,537 --> 04:08:05,324
I was trying to figure out how I

9131
04:08:05,324 --> 04:08:06,106
could unmute.

9132
04:08:06,106 --> 04:08:07,875
So can you hear me now?

9133
04:08:08,375 --> 04:08:09,543
Oh, that's wonderful.

9134
04:08:09,543 --> 04:08:09,743
Yeah.

9135
04:08:09,743 --> 04:08:10,244
Thanks, Beth.

9136
04:08:11,011 --> 04:08:11,912
Yeah, thanks.

9137
04:08:12,580 --> 04:08:14,260
Yeah, I was going to say I,

9138
04:08:14,260 --> 04:08:16,112
I tend and I'll try to put my

9139
04:08:16,112 --> 04:08:16,750
camera on

9140
04:08:16,750 --> 04:08:18,047
if it's enabled right

9141
04:08:18,047 --> 04:08:19,220
now, it's blocked.

9142
04:08:20,020 --> 04:08:24,263
I I really try to address the

9143
04:08:24,263 --> 04:08:28,777
the sleep problem as best as I

9144
04:08:28,777 --> 04:08:29,530
can.

9145
04:08:29,530 --> 04:08:29,787
The,

9146
04:08:29,787 --> 04:08:31,438
the reason I think the Co

9147
04:08:31,438 --> 04:08:32,099
occurring

9148
04:08:32,099 --> 04:08:34,002
conditions are important is #1

9149
04:08:34,002 --> 04:08:35,685
if there is a Co occurring

9150
04:08:35,685 --> 04:08:37,238
condition and you treat

9151
04:08:37,238 --> 04:08:37,428
it,

9152
04:08:37,428 --> 04:08:39,058
that can in and of itself

9153
04:08:39,058 --> 04:08:39,840
improve the

9154
04:08:39,840 --> 04:08:40,207
sleep.

9155
04:08:40,741 --> 04:08:43,178
And then it can also help you

9156
04:08:43,178 --> 04:08:45,660
with trying to figure out the

9157
04:08:45,660 --> 04:08:47,715
best medication, right?

9158
04:08:47,715 --> 04:08:49,654
So that we're not trying to over

9159
04:08:49,654 --> 04:08:50,684
medicate people,

9160
04:08:50,684 --> 04:08:52,549
we're trying to use medications

9161
04:08:52,549 --> 04:08:54,390
that we might already be using

9162
04:08:54,390 --> 04:08:55,556
for their anxiety,

9163
04:08:55,556 --> 04:08:56,201
their ADHD,

9164
04:08:56,201 --> 04:08:57,491
depression, whatever.

9165
04:08:58,192 --> 04:08:59,899
So those are the two reasons I

9166
04:08:59,899 --> 04:09:01,361
focus on the Co occurring

9167
04:09:01,361 --> 04:09:02,062
conditions.

9168
04:09:02,329 --> 04:09:04,245
With that said though,

9169
04:09:04,245 --> 04:09:06,831
my approach like I still find

9170
04:09:06,831 --> 04:09:07,901
often times

9171
04:09:07,901 --> 04:09:10,061
behavioral approaches and

9172
04:09:10,061 --> 04:09:12,708
medications work regardless of

9173
04:09:12,708 --> 04:09:14,208
the Co occurring

9174
04:09:14,208 --> 04:09:15,075
condition.

9175
04:09:15,075 --> 04:09:17,278
So I I tend to view the Co

9176
04:09:17,278 --> 04:09:19,782
occurring condition as making

9177
04:09:19,782 --> 04:09:21,682
sure that you address

9178
04:09:21,682 --> 04:09:24,413
it so that it's not contributing

9179
04:09:24,413 --> 04:09:26,887
to the actual sleep problem.

9180
04:09:26,887 --> 04:09:28,555
I hope that is helpful.

9181
04:09:29,490 --> 04:09:30,124
Absolutely.

9182
04:09:31,625 --> 04:09:31,859
Yeah.

9183
04:09:31,859 --> 04:09:32,547
And if I could,

9184
04:09:32,547 --> 04:09:34,061
if you could get our cameras on,

9185
04:09:34,061 --> 04:09:35,129
that would be awesome.

9186
04:09:35,129 --> 04:09:37,131
Oh wait, maybe it now popped up.

9187
04:09:37,531 --> 04:09:40,012
Other people might have the same

9188
04:09:40,012 --> 04:09:42,569
problem, other speakers, a neck.

9189
04:09:42,569 --> 04:09:42,970
Go ahead.

9190
04:09:46,340 --> 04:09:47,604
Yeah, well,

9191
04:09:47,604 --> 04:09:51,275
I was going to approach it from

9192
04:09:51,275 --> 04:09:51,512
a

9193
04:09:51,512 --> 04:09:54,826
research perspective and just

9194
04:09:54,826 --> 04:09:58,099
mention that the prospective

9195
04:09:58,099 --> 04:09:59,853
infant sibling

9196
04:09:59,853 --> 04:10:02,710
studies really pull for a

9197
04:10:02,710 --> 04:10:06,086
complex kind of less severely

9198
04:10:06,086 --> 04:10:08,996
affected sample of kids.

9199
04:10:08,996 --> 04:10:11,453
There are kids that don't tend

9200
04:10:11,453 --> 04:10:13,880
to have the genetic syndromes

9201
04:10:13,880 --> 04:10:15,302
and maybe aren't

9202
04:10:15,302 --> 04:10:17,785
super representative of who we

9203
04:10:17,785 --> 04:10:19,440
see in our clinics,

9204
04:10:19,440 --> 04:10:22,064
but they are harder in the sense

9205
04:10:22,064 --> 04:10:24,741
of that diagnostic question that

9206
04:10:24,741 --> 04:10:26,246
you started with.

9207
04:10:26,246 --> 04:10:28,788
Because we see kids that are a

9208
04:10:28,788 --> 04:10:31,474
lot of times on that borderline

9209
04:10:31,474 --> 04:10:32,686
between ADHD,

9210
04:10:32,686 --> 04:10:34,254
anxiety and autism.

9211
04:10:34,655 --> 04:10:36,757
And I think really polls for

9212
04:10:36,757 --> 04:10:38,674
asking some of those deep

9213
04:10:38,674 --> 04:10:40,361
questions about well,

9214
04:10:40,361 --> 04:10:42,606
what is the difference between

9215
04:10:42,606 --> 04:10:43,753
these different

9216
04:10:43,753 --> 04:10:46,200
neurodevelopmental disabilities

9217
04:10:46,200 --> 04:10:48,435
and what are the similarities.

9218
04:10:48,435 --> 04:10:50,923
And I think the thing that I

9219
04:10:50,923 --> 04:10:53,462
find really compelling about

9220
04:10:53,462 --> 04:10:55,275
sleep is that it is

9221
04:10:55,275 --> 04:10:57,683
something you can identify,

9222
04:10:57,683 --> 04:11:00,615
cross developmental disabilities

9223
04:11:00,615 --> 04:11:00,981
and

9224
04:11:00,981 --> 04:11:02,494
treat like, well,

9225
04:11:02,494 --> 04:11:05,414
Geraldine's talk just now points

9226
04:11:05,414 --> 04:11:06,053
to the

9227
04:11:06,053 --> 04:11:08,255
fact that you can't lump

9228
04:11:08,255 --> 04:11:10,090
everybody together.

9229
04:11:10,090 --> 04:11:12,026
They're not the same necessarily

9230
04:11:12,026 --> 04:11:14,009
in terms of how we want to treat

9231
04:11:14,009 --> 04:11:14,628
the sleep

9232
04:11:14,628 --> 04:11:15,195
problems.

9233
04:11:15,195 --> 04:11:17,372
But it does give us sort of a

9234
04:11:17,372 --> 04:11:19,400
way in at least, you know,

9235
04:11:19,400 --> 04:11:21,427
in terms of that phenotypic

9236
04:11:21,427 --> 04:11:23,587
diagnostic question that you

9237
04:11:23,587 --> 04:11:24,204
raised.

9238
04:11:24,204 --> 04:11:26,607
So it's a great question.

9239
04:11:27,307 --> 04:11:27,541
Yeah.

9240
04:11:27,541 --> 04:11:27,981
And I,

9241
04:11:27,981 --> 04:11:30,175
and I think it speaks also to

9242
04:11:30,175 --> 04:11:30,477
the

9243
04:11:30,477 --> 04:11:32,783
question that just popped into

9244
04:11:32,783 --> 04:11:35,075
the Q& A, which is about, you

9245
04:11:35,075 --> 04:11:35,549
know,

9246
04:11:35,549 --> 04:11:37,661
autism is this heterogeneous,

9247
04:11:37,661 --> 04:11:39,975
very broad term and what can we

9248
04:11:39,975 --> 04:11:40,721
do to get

9249
04:11:40,721 --> 04:11:41,879
it more specific

9250
04:11:41,879 --> 04:11:44,164
characteristics, especially vis

9251
04:11:44,164 --> 04:11:45,859
A vis specific genetic

9252
04:11:45,859 --> 04:11:46,660
ideologies.

9253
04:11:46,660 --> 04:11:47,944
And so, you know,

9254
04:11:47,944 --> 04:11:50,267
I know that there's work being

9255
04:11:50,267 --> 04:11:50,964
done in,

9256
04:11:50,964 --> 04:11:51,648
you know,

9257
04:11:51,648 --> 04:11:54,145
22 Q and then 17 and then 16 and

9258
04:11:54,145 --> 04:11:54,535
then

9259
04:11:54,535 --> 04:11:56,432
these specific, you know,

9260
04:11:56,432 --> 04:11:58,771
genetics first approaches that

9261
04:11:58,771 --> 04:11:59,239
might

9262
04:11:59,239 --> 04:12:00,146
suggest, OK,

9263
04:12:00,146 --> 04:12:02,469
different paths to overlapping

9264
04:12:02,469 --> 04:12:03,243
phenomena

9265
04:12:03,243 --> 04:12:05,210
through specific genes and

9266
04:12:05,210 --> 04:12:06,647
specific circuits.

9267
04:12:06,647 --> 04:12:08,028
And I think, you know,

9268
04:12:08,028 --> 04:12:09,705
that's part of there was a

9269
04:12:09,705 --> 04:12:10,350
mentioned

9270
04:12:10,350 --> 04:12:12,041
earlier about when you have

9271
04:12:12,041 --> 04:12:13,257
small samples and a

9272
04:12:13,257 --> 04:12:14,922
heterogeneous population,

9273
04:12:14,922 --> 04:12:16,676
you have a number of studies

9274
04:12:16,676 --> 04:12:18,400
that go one way and another

9275
04:12:18,400 --> 04:12:20,060
studies that go the other

9276
04:12:20,060 --> 04:12:20,294
way.

9277
04:12:20,294 --> 04:12:20,804
And so we,

9278
04:12:20,804 --> 04:12:22,216
we can solve that both with

9279
04:12:22,216 --> 04:12:22,896
sample size,

9280
04:12:22,896 --> 04:12:24,213
but we can solve that with

9281
04:12:24,213 --> 04:12:25,863
better sort of models about what

9282
04:12:25,863 --> 04:12:27,100
we're actually studying

9283
04:12:27,100 --> 04:12:28,726
and which samples we're actually

9284
04:12:28,726 --> 04:12:29,336
recruiting.

9285
04:12:29,336 --> 04:12:31,470
And I and I think tomorrow's

9286
04:12:31,470 --> 04:12:33,567
talk session is going to be

9287
04:12:33,567 --> 04:12:35,509
largely about model work

9288
04:12:35,509 --> 04:12:37,270
where we can, you know,

9289
04:12:37,270 --> 04:12:39,315
be much more pinpointed to

9290
04:12:39,315 --> 04:12:40,180
mechanism.

9291
04:12:40,180 --> 04:12:41,363
So that's to the question that

9292
04:12:41,363 --> 04:12:41,915
just came in.

9293
04:12:42,316 --> 04:12:42,879
I want to,

9294
04:12:42,879 --> 04:12:44,614
I want to pivot to a different

9295
04:12:44,614 --> 04:12:45,018
set of

9296
04:12:45,018 --> 04:12:46,492
questions because the last

9297
04:12:46,492 --> 04:12:48,239
couple speakers, I think there

9298
04:12:48,239 --> 04:12:48,589
were,

9299
04:12:48,589 --> 04:12:50,326
there were overlap in this idea

9300
04:12:50,326 --> 04:12:52,158
that sleep hygiene is not enough

9301
04:12:52,158 --> 04:12:52,960
in the advice

9302
04:12:52,960 --> 04:12:53,861
that gets given.

9303
04:12:54,728 --> 04:12:54,961
And,

9304
04:12:54,961 --> 04:12:56,633
and we know that there was a

9305
04:12:56,633 --> 04:12:57,231
number of

9306
04:12:57,231 --> 04:12:58,832
questions put in about Cbti,

9307
04:12:58,832 --> 04:13:00,707
cognitive behavioral therapy for

9308
04:13:00,707 --> 04:13:01,235
insomnia

9309
04:13:01,235 --> 04:13:03,059
is more than just the behavioral

9310
04:13:03,059 --> 04:13:04,871
health components and the sleep

9311
04:13:04,871 --> 04:13:05,339
hygiene

9312
04:13:05,339 --> 04:13:05,972
components,

9313
04:13:05,972 --> 04:13:07,566
but there's also this sleep

9314
04:13:07,566 --> 04:13:08,275
restriction

9315
04:13:08,275 --> 04:13:10,115
and homeostatic regulation piece

9316
04:13:10,115 --> 04:13:10,978
that comes in.

9317
04:13:11,245 --> 04:13:12,769
And can anyone speak a little

9318
04:13:12,769 --> 04:13:14,484
bit about how well those aspects

9319
04:13:14,484 --> 04:13:15,449
are tolerated and

9320
04:13:15,449 --> 04:13:16,909
some of the populations that

9321
04:13:16,909 --> 04:13:18,610
that you serve, particularly the

9322
04:13:18,610 --> 04:13:19,620
sleep restriction?

9323
04:13:19,620 --> 04:13:20,331
There were a couple

9324
04:13:20,331 --> 04:13:21,154
questions about that.

9325
04:13:23,123 --> 04:13:24,807
I can tell you experimentally,

9326
04:13:24,807 --> 04:13:26,660
'cause we restrict sleep in kids

9327
04:13:26,660 --> 04:13:28,405
experimentally to try and model

9328
04:13:28,405 --> 04:13:30,264
what they do in the school week.

9329
04:13:31,298 --> 04:13:32,145
And we and I, I,

9330
04:13:32,145 --> 04:13:33,500
I think it might actually

9331
04:13:33,500 --> 04:13:34,368
structure their

9332
04:13:34,368 --> 04:13:35,335
sleep in some ways.

9333
04:13:36,370 --> 04:13:37,404
But clinically, Dr.

9334
04:13:37,404 --> 04:13:38,296
Mallow,

9335
04:13:38,296 --> 04:13:41,950
I don't want to dominate the

9336
04:13:41,950 --> 04:13:43,777
conversation.

9337
04:13:43,777 --> 04:13:45,345
So if anybody else wants to.

9338
04:13:45,345 --> 04:13:46,912
Yeah, Well, I,

9339
04:13:46,912 --> 04:13:50,591
I have not found it that easy to

9340
04:13:50,591 --> 04:13:51,051
do.

9341
04:13:51,985 --> 04:13:53,611
You know, the the limit,

9342
04:13:53,611 --> 04:13:55,624
the sleep restriction in this

9343
04:13:55,624 --> 04:13:56,456
population,

9344
04:13:56,456 --> 04:13:58,155
because a lot of them are

9345
04:13:58,155 --> 04:14:00,260
already getting limited sleep.

9346
04:14:00,260 --> 04:14:01,718
The parents are not really

9347
04:14:01,718 --> 04:14:03,063
wanting to tolerate it.

9348
04:14:03,497 --> 04:14:05,365
The adults don't want to do it.

9349
04:14:05,365 --> 04:14:07,389
But what I do find is delaying

9350
04:14:07,389 --> 04:14:08,535
bedtime is huge.

9351
04:14:08,735 --> 04:14:10,034
That's probably the number one

9352
04:14:10,034 --> 04:14:11,269
thing I do behaviorally that

9353
04:14:11,269 --> 04:14:12,372
makes a huge difference.

9354
04:14:13,073 --> 04:14:14,949
Maybe it's because a lot of

9355
04:14:14,949 --> 04:14:16,666
these kids with NDDS are

9356
04:14:16,666 --> 04:14:17,311
delayed.

9357
04:14:17,311 --> 04:14:18,165
You don't have

9358
04:14:18,165 --> 04:14:19,446
delayed sleep phase.

9359
04:14:19,446 --> 04:14:20,712
But in any case,

9360
04:14:20,712 --> 04:14:23,230
I find that just moving bedtime

9361
04:14:23,230 --> 04:14:23,717
by 30

9362
04:14:23,717 --> 04:14:25,608
minutes or an hour is so

9363
04:14:25,608 --> 04:14:28,102
effective because if they're in

9364
04:14:28,102 --> 04:14:29,389
their forbidden

9365
04:14:29,389 --> 04:14:31,663
zone for sleep and they can't

9366
04:14:31,663 --> 04:14:33,899
express it to their parents,

9367
04:14:33,899 --> 04:14:35,896
they're going to fidget.

9368
04:14:35,896 --> 04:14:37,208
They're, you know, they're going

9369
04:14:37,208 --> 04:14:38,546
to stem, they're going to do all

9370
04:14:38,546 --> 04:14:39,299
these things that

9371
04:14:39,299 --> 04:14:40,425
are going to interfere with

9372
04:14:40,425 --> 04:14:41,134
sleep even more.

9373
04:14:41,468 --> 04:14:43,080
So it's always funny though,

9374
04:14:43,080 --> 04:14:44,564
in the clinic because the

9375
04:14:44,564 --> 04:14:45,038
parent,

9376
04:14:45,038 --> 04:14:46,762
the kids are always like, yay,

9377
04:14:46,762 --> 04:14:48,141
I get to stay up later.

9378
04:14:48,141 --> 04:14:49,465
And the parents are like,

9379
04:14:49,465 --> 04:14:51,152
we're never going to see doctor

9380
04:14:51,152 --> 04:14:51,478
Malow

9381
04:14:51,478 --> 04:14:52,145
again, right?

9382
04:14:52,446 --> 04:14:54,348
But it really does work.

9383
04:14:54,348 --> 04:14:56,415
I think so instead of like

9384
04:14:56,415 --> 04:14:59,006
focusing on calculating out this

9385
04:14:59,006 --> 04:15:00,787
restriction of sleep,

9386
04:15:00,787 --> 04:15:02,199
I just try to move

9387
04:15:02,199 --> 04:15:03,924
sleep a little later.

9388
04:15:03,924 --> 04:15:04,992
And that oftentimes

9389
04:15:04,992 --> 04:15:06,059
is very effective.

9390
04:15:09,696 --> 04:15:13,433
Doctor Nadeau I I would say that

9391
04:15:13,433 --> 04:15:17,127
kids are already doing lifelong

9392
04:15:17,127 --> 04:15:19,272
sleep restriction

9393
04:15:19,272 --> 04:15:20,674
experiments.

9394
04:15:21,208 --> 04:15:21,508
I mean,

9395
04:15:21,508 --> 04:15:22,870
just by virtue of the fact that

9396
04:15:22,870 --> 04:15:23,310
they have

9397
04:15:23,310 --> 04:15:24,372
to get up in the morning,

9398
04:15:24,372 --> 04:15:25,646
no matter how tired they are.

9399
04:15:26,013 --> 04:15:27,019
And The thing is,

9400
04:15:27,019 --> 04:15:28,382
they can't stay awake.

9401
04:15:28,649 --> 04:15:29,820
They they go, they

9402
04:15:29,820 --> 04:15:31,251
fall asleep in class.

9403
04:15:31,785 --> 04:15:33,907
Mean I remember when my daughter

9404
04:15:33,907 --> 04:15:36,076
was in kindergarten, they talked

9405
04:15:36,076 --> 04:15:36,957
to me about,

9406
04:15:36,957 --> 04:15:38,880
they were concerned about how

9407
04:15:38,880 --> 04:15:40,910
long her naps were because she

9408
04:15:40,910 --> 04:15:42,195
had not had enough

9409
04:15:42,195 --> 04:15:43,764
sleep and then long nap.

9410
04:15:43,764 --> 04:15:45,432
And then that exacerbates it.

9411
04:15:45,666 --> 04:15:47,953
One of the things that I've

9412
04:15:47,953 --> 04:15:50,202
found that is tremendously

9413
04:15:50,202 --> 04:15:52,105
helpful with kids and

9414
04:15:52,105 --> 04:15:54,829
adolescents is vigorous exercise

9415
04:15:54,829 --> 04:15:57,440
that seems to hugely help them

9416
04:15:57,440 --> 04:15:58,745
go to sleep at

9417
04:15:58,745 --> 04:16:01,415
night, if you can get into this.

9418
04:16:01,782 --> 04:16:02,245
In fact,

9419
04:16:02,245 --> 04:16:04,143
I've worked with kids who almost

9420
04:16:04,143 --> 04:16:04,618
treated

9421
04:16:04,618 --> 04:16:06,321
their sleep disorder and their

9422
04:16:06,321 --> 04:16:07,945
ADHD in general because they

9423
04:16:07,945 --> 04:16:08,989
were on the track

9424
04:16:08,989 --> 04:16:09,961
team or they were

9425
04:16:09,961 --> 04:16:10,991
in the swim team.

9426
04:16:10,991 --> 04:16:13,404
And we're just involved in this

9427
04:16:13,404 --> 04:16:15,954
amazing intense aerobic exercise

9428
04:16:15,954 --> 04:16:16,830
every day.

9429
04:16:17,030 --> 04:16:18,666
And then everything came roaring

9430
04:16:18,666 --> 04:16:20,235
back if they didn't get on the

9431
04:16:20,235 --> 04:16:20,967
track team in

9432
04:16:20,967 --> 04:16:22,408
college or didn't get in the

9433
04:16:22,408 --> 04:16:24,004
track team, the swimming team.

9434
04:16:24,337 --> 04:16:26,880
So the sleep restriction,

9435
04:16:26,880 --> 04:16:30,121
I've had some adults just say I

9436
04:16:30,121 --> 04:16:30,644
just

9437
04:16:30,644 --> 04:16:31,845
can't do it.

9438
04:16:31,845 --> 04:16:32,621
And, you know,

9439
04:16:32,621 --> 04:16:34,267
I'm driving in my car and I'm

9440
04:16:34,267 --> 04:16:34,948
slapping my

9441
04:16:34,948 --> 04:16:35,215
face.

9442
04:16:35,215 --> 04:16:36,116
It's dangerous.

9443
04:16:36,116 --> 04:16:37,784
I'm so sleep deprived.

9444
04:16:38,251 --> 04:16:39,100
And so I,

9445
04:16:39,100 --> 04:16:41,708
I think a lot of it is just

9446
04:16:41,708 --> 04:16:43,156
experimenting.

9447
04:16:43,156 --> 04:16:43,629
I mean,

9448
04:16:43,629 --> 04:16:45,779
there's almost no such thing as

9449
04:16:45,779 --> 04:16:46,126
ADHD

9450
04:16:46,126 --> 04:16:48,128
without coexisting conditions.

9451
04:16:48,128 --> 04:16:50,297
It just almost doesn't exist.

9452
04:16:50,297 --> 04:16:52,428
And so we're always having to

9453
04:16:52,428 --> 04:16:54,608
fine tune it with how much is

9454
04:16:54,608 --> 04:16:55,736
their anxiety.

9455
04:16:56,369 --> 04:16:58,089
And therefore there are all

9456
04:16:58,089 --> 04:17:00,039
kinds of things we can do with

9457
04:17:00,039 --> 04:17:01,274
calming sounds and

9458
04:17:01,274 --> 04:17:02,409
weighted blankets.

9459
04:17:03,710 --> 04:17:06,163
This I find that pink and brown

9460
04:17:06,163 --> 04:17:08,023
noise can be incredibly

9461
04:17:08,023 --> 04:17:09,883
impactful if it's loud

9462
04:17:09,883 --> 04:17:12,175
enough so that it just it's a

9463
04:17:12,175 --> 04:17:14,759
blanket that blocks out the rest

9464
04:17:14,759 --> 04:17:15,889
of the world.

9465
04:17:16,256 --> 04:17:17,717
So there there are lots of

9466
04:17:17,717 --> 04:17:19,552
different techniques that we can

9467
04:17:19,552 --> 04:17:20,527
use depending on

9468
04:17:20,527 --> 04:17:21,328
the particular.

9469
04:17:21,628 --> 04:17:24,214
I've had kids develop calm down

9470
04:17:24,214 --> 04:17:26,939
spaces in their closet and sleep

9471
04:17:26,939 --> 04:17:28,301
on the floor in

9472
04:17:28,301 --> 04:17:30,387
their closet because that

9473
04:17:30,387 --> 04:17:32,856
confined, unstimulating space

9474
04:17:32,856 --> 04:17:34,474
really helped them

9475
04:17:34,474 --> 04:17:35,965
with the anxiety,

9476
04:17:35,965 --> 04:17:38,245
with the hyper alertness.

9477
04:17:38,245 --> 04:17:39,875
So they're just a lot of

9478
04:17:39,875 --> 04:17:41,949
different things that needs to

9479
04:17:41,949 --> 04:17:43,884
be customized by the child,

9480
04:17:43,884 --> 04:17:44,751
by the adult.

9481
04:17:45,819 --> 04:17:45,986
Yeah.

9482
04:17:45,986 --> 04:17:47,156
And if I could pick up on

9483
04:17:47,156 --> 04:17:48,595
something you said at the very

9484
04:17:48,595 --> 04:17:49,122
beginning,

9485
04:17:49,122 --> 04:17:50,578
which is that children are sort

9486
04:17:50,578 --> 04:17:51,587
of living out a sleep

9487
04:17:51,587 --> 04:17:52,692
restriction experiment

9488
04:17:52,692 --> 04:17:54,101
typically as a function of how

9489
04:17:54,101 --> 04:17:55,228
we structure their day.

9490
04:17:55,862 --> 04:17:57,268
And, and I think, you know,

9491
04:17:57,268 --> 04:17:58,978
one of the important factors for

9492
04:17:58,978 --> 04:17:59,299
us is

9493
04:17:59,299 --> 04:18:00,853
that underlying development of

9494
04:18:00,853 --> 04:18:02,548
sleep and circadian rhythms that

9495
04:18:02,548 --> 04:18:03,236
creates that

9496
04:18:03,236 --> 04:18:04,743
Malstrom or as Mary Karskaden

9497
04:18:04,743 --> 04:18:06,406
calls the perfect storm, right?

9498
04:18:06,406 --> 04:18:06,829
I mean,

9499
04:18:06,829 --> 04:18:08,507
the change in the circadian

9500
04:18:08,507 --> 04:18:08,942
rhythm

9501
04:18:08,942 --> 04:18:10,677
pushing later combined with a

9502
04:18:10,677 --> 04:18:12,567
homeostatic system more capable

9503
04:18:12,567 --> 04:18:13,847
to stay up later and

9504
04:18:13,847 --> 04:18:15,691
then hitting the wall of how we

9505
04:18:15,691 --> 04:18:17,390
schedule these kids sleep is

9506
04:18:17,390 --> 04:18:18,785
eroded night to night.

9507
04:18:19,085 --> 04:18:20,821
Now all of that work is it

9508
04:18:20,821 --> 04:18:22,524
results from experimental

9509
04:18:22,524 --> 04:18:24,024
studies and typically

9510
04:18:24,024 --> 04:18:26,067
developing kids and and whether

9511
04:18:26,067 --> 04:18:28,017
or not we know that you know,

9512
04:18:28,017 --> 04:18:29,429
that kids with ADHD,

9513
04:18:29,429 --> 04:18:30,564
kids with autism,

9514
04:18:30,564 --> 04:18:32,551
kids with some of these other

9515
04:18:32,551 --> 04:18:33,099
genetic

9516
04:18:33,099 --> 04:18:35,156
conditions or kids with some Co

9517
04:18:35,156 --> 04:18:37,185
occurring psychiatric symptoms

9518
04:18:37,185 --> 04:18:38,605
go through that same

9519
04:18:38,605 --> 04:18:40,674
developmental trajectory at the

9520
04:18:40,674 --> 04:18:42,542
same time, in the same way.

9521
04:18:43,009 --> 04:18:43,680
We don't know the

9522
04:18:43,680 --> 04:18:44,311
answer to that.

9523
04:18:44,311 --> 04:18:44,845
We don't know.

9524
04:18:45,212 --> 04:18:47,016
And I think that that's really

9525
04:18:47,016 --> 04:18:48,935
fundamental too to think about,

9526
04:18:48,935 --> 04:18:49,182
OK,

9527
04:18:49,182 --> 04:18:50,981
how are those individuals then

9528
04:18:50,981 --> 04:18:52,390
going to respond to the

9529
04:18:52,390 --> 04:18:53,920
environmental influences

9530
04:18:53,920 --> 04:18:55,650
of light sounds, early school

9531
04:18:55,650 --> 04:18:57,353
start times, all these other

9532
04:18:57,353 --> 04:18:58,692
things that we always

9533
04:18:58,692 --> 04:18:59,326
talk about?

9534
04:18:59,726 --> 04:19:00,468
Are they going to

9535
04:19:00,468 --> 04:19:01,428
respond the same way?

9536
04:19:01,428 --> 04:19:03,535
I think that's right for for

9537
04:19:03,535 --> 04:19:04,664
investigation.

9538
04:19:05,232 --> 04:19:06,466
I couldn't agree more.

9539
04:19:07,934 --> 04:19:09,628
And so we, we're closed on time,

9540
04:19:09,628 --> 04:19:11,004
but I want to, I want to,

9541
04:19:11,004 --> 04:19:12,172
I want to have a theme.

9542
04:19:12,172 --> 04:19:13,826
There's a theme that came in I

9543
04:19:13,826 --> 04:19:15,634
thought was a wonderful question

9544
04:19:15,634 --> 04:19:16,142
of what,

9545
04:19:16,142 --> 04:19:17,691
how do we educate the public

9546
04:19:17,691 --> 04:19:19,273
about the intersections that

9547
04:19:19,273 --> 04:19:20,347
we've been talking

9548
04:19:20,347 --> 04:19:20,647
about?

9549
04:19:20,947 --> 04:19:21,391
You know,

9550
04:19:21,391 --> 04:19:22,557
I think there's an open

9551
04:19:22,557 --> 04:19:23,216
conversation

9552
04:19:23,216 --> 04:19:23,750
about sleep

9553
04:19:23,750 --> 04:19:24,818
education in general.

9554
04:19:24,818 --> 04:19:26,226
And, and Doctor Mallow, you,

9555
04:19:26,226 --> 04:19:27,721
you, you've done some of that

9556
04:19:27,721 --> 04:19:28,288
scientific

9557
04:19:28,288 --> 04:19:29,256
communications work.

9558
04:19:29,789 --> 04:19:31,902
How do we bring stakeholders in,

9559
04:19:31,902 --> 04:19:32,893
in the public,

9560
04:19:32,893 --> 04:19:34,791
in child health organizations

9561
04:19:34,791 --> 04:19:36,929
and and in in neurodevelopmental

9562
04:19:36,929 --> 04:19:38,064
organizations so

9563
04:19:38,064 --> 04:19:40,038
that this can be an integrated

9564
04:19:40,038 --> 04:19:42,196
conversation both from the sleep

9565
04:19:42,196 --> 04:19:42,736
side as

9566
04:19:42,736 --> 04:19:43,449
well as the

9567
04:19:43,449 --> 04:19:45,071
neurodevelopmental side?

9568
04:19:45,872 --> 04:19:47,007
And anyone please chime in.

9569
04:19:51,244 --> 04:19:51,745
Beth, go ahead.

9570
04:19:52,312 --> 04:19:52,874
I apologize,

9571
04:19:52,874 --> 04:19:54,273
but I'm going to have to sign

9572
04:19:54,273 --> 04:19:54,514
off.

9573
04:19:56,549 --> 04:19:56,983
I'm so sorry.

9574
04:19:56,983 --> 04:19:57,817
I'll have to sign off.

9575
04:19:57,817 --> 04:19:59,185
Yeah, I'll thanks so much.

9576
04:19:59,185 --> 04:20:01,032
I think, I think there's,

9577
04:20:01,032 --> 04:20:03,462
I think there's a couple of ways

9578
04:20:03,462 --> 04:20:03,690
to

9579
04:20:03,690 --> 04:20:04,591
approach it.

9580
04:20:04,791 --> 04:20:04,916
I,

9581
04:20:04,916 --> 04:20:06,717
I think that certainly we've

9582
04:20:06,717 --> 04:20:07,360
done some

9583
04:20:07,360 --> 04:20:09,226
practice pathways and position

9584
04:20:09,226 --> 04:20:11,130
statements and autism that are

9585
04:20:11,130 --> 04:20:12,399
then made available

9586
04:20:12,399 --> 04:20:14,100
and I think others have too.

9587
04:20:14,100 --> 04:20:14,860
I think she,

9588
04:20:14,860 --> 04:20:16,618
Buckley did one as well for

9589
04:20:16,618 --> 04:20:17,203
American

9590
04:20:17,203 --> 04:20:18,505
Academy of Neurology.

9591
04:20:18,505 --> 04:20:19,149
So that,

9592
04:20:19,149 --> 04:20:21,808
that's clearly something that is

9593
04:20:21,808 --> 04:20:22,575
important.

9594
04:20:22,909 --> 04:20:24,720
I think reaching the families is

9595
04:20:24,720 --> 04:20:25,512
critical too.

9596
04:20:25,512 --> 04:20:26,091
Like I,

9597
04:20:26,091 --> 04:20:28,634
I exhibited with the melatonin

9598
04:20:28,634 --> 04:20:29,482
blogs and

9599
04:20:29,482 --> 04:20:30,770
melatonin safety

9600
04:20:30,770 --> 04:20:32,218
posts and videos.

9601
04:20:32,652 --> 04:20:33,893
I because parents,

9602
04:20:33,893 --> 04:20:35,518
the problem is a lot of

9603
04:20:35,518 --> 04:20:36,790
pediatricians and

9604
04:20:36,790 --> 04:20:38,778
pediatric nurse practitioners

9605
04:20:38,778 --> 04:20:41,023
don't know about sleep and other

9606
04:20:41,023 --> 04:20:41,795
areas like

9607
04:20:41,795 --> 04:20:42,764
melatonin and,

9608
04:20:42,764 --> 04:20:44,754
and certain ways to approach

9609
04:20:44,754 --> 04:20:45,465
medicine.

9610
04:20:45,465 --> 04:20:46,214
So they're,

9611
04:20:46,214 --> 04:20:48,449
they're just in the dark and our

9612
04:20:48,449 --> 04:20:48,868
sleep

9613
04:20:48,868 --> 04:20:50,070
centers have major

9614
04:20:50,070 --> 04:20:51,071
access issues.

9615
04:20:51,338 --> 04:20:53,355
So anything that we can do to

9616
04:20:53,355 --> 04:20:55,341
get to the families and give

9617
04:20:55,341 --> 04:20:57,043
them reputable evidence

9618
04:20:57,043 --> 04:20:58,044
based medicine.

9619
04:20:58,244 --> 04:20:59,831
Actually, I heard the term

9620
04:20:59,831 --> 04:21:01,512
recently, instead of saying

9621
04:21:01,512 --> 04:21:02,882
evidence based, it's,

9622
04:21:02,882 --> 04:21:04,315
it may be better to say

9623
04:21:04,315 --> 04:21:05,685
treatments that work.

9624
04:21:05,685 --> 04:21:08,355
So giving them treatments that

9625
04:21:08,355 --> 04:21:11,024
work that are, are effective.

9626
04:21:11,024 --> 04:21:11,353
I mean,

9627
04:21:11,353 --> 04:21:12,464
they're hungry for this

9628
04:21:12,464 --> 04:21:13,093
information.

9629
04:21:13,426 --> 04:21:15,656
And we can also say here are

9630
04:21:15,656 --> 04:21:16,930
some, you know,

9631
04:21:16,930 --> 04:21:19,301
here are some simple resources

9632
04:21:19,301 --> 04:21:21,643
you can look at for trying to

9633
04:21:21,643 --> 04:21:22,936
figure out what

9634
04:21:22,936 --> 04:21:25,464
might be best for your child and

9635
04:21:25,464 --> 04:21:27,170
then bring it to your

9636
04:21:27,170 --> 04:21:28,308
pediatrician.

9637
04:21:28,742 --> 04:21:29,142
Don't.

9638
04:21:29,876 --> 04:21:30,807
We're not cutting

9639
04:21:30,807 --> 04:21:32,012
the pediatrician out.

9640
04:21:32,012 --> 04:21:34,339
I think we're just acknowledging

9641
04:21:34,339 --> 04:21:36,643
that parents can do some of can

9642
04:21:36,643 --> 04:21:37,684
look on their

9643
04:21:37,684 --> 04:21:37,984
own.

9644
04:21:37,984 --> 04:21:38,451
And if,

9645
04:21:38,451 --> 04:21:40,505
if they go to the Internet and

9646
04:21:40,505 --> 04:21:41,121
they see

9647
04:21:41,121 --> 04:21:43,175
reputable stuff that's from us,

9648
04:21:43,175 --> 04:21:44,874
then they can go to their

9649
04:21:44,874 --> 04:21:45,825
pediatricians

9650
04:21:45,825 --> 04:21:47,827
and have that discussion about

9651
04:21:47,827 --> 04:21:49,429
medicines or melatonin.

9652
04:21:49,429 --> 04:21:50,031
Because I,

9653
04:21:50,031 --> 04:21:52,005
I really think that empowers the

9654
04:21:52,005 --> 04:21:52,499
public.

9655
04:21:52,499 --> 04:21:53,064
And it's,

9656
04:21:53,064 --> 04:21:54,865
it's just super important in

9657
04:21:54,865 --> 04:21:55,702
terms of the

9658
04:21:55,702 --> 04:21:56,703
sleep education.

9659
04:21:57,070 --> 04:21:58,271
We've tried a lot of things.

9660
04:21:58,271 --> 04:21:59,916
I wish I could have expanded on

9661
04:21:59,916 --> 04:22:01,508
this a little bit more today.

9662
04:22:01,508 --> 04:22:02,809
I know our time was limited.

9663
04:22:03,777 --> 04:22:04,224
You know,

9664
04:22:04,224 --> 04:22:05,806
we've tried pamphlets and we've

9665
04:22:05,806 --> 04:22:06,112
tried

9666
04:22:06,112 --> 04:22:07,649
online modules and we've tried,

9667
04:22:07,649 --> 04:22:09,174
I wrote a book with Terry Katz

9668
04:22:09,174 --> 04:22:09,682
that's on

9669
04:22:09,682 --> 04:22:10,016
Amazon.

9670
04:22:10,350 --> 04:22:11,766
I mean, for some parents,

9671
04:22:11,766 --> 04:22:12,786
that's effective.

9672
04:22:12,786 --> 04:22:15,071
I, I really keep coming back to,

9673
04:22:15,071 --> 04:22:16,856
they need to be coached,

9674
04:22:16,856 --> 04:22:18,658
they need to be supported.

9675
04:22:18,658 --> 04:22:20,389
So that's why we're now doing

9676
04:22:20,389 --> 04:22:22,223
this project with the American

9677
04:22:22,223 --> 04:22:22,896
Academy of

9678
04:22:22,896 --> 04:22:24,267
Sleep Medicine to train

9679
04:22:24,267 --> 04:22:25,604
therapists, behavioral

9680
04:22:25,604 --> 04:22:27,367
therapist, speech therapist,

9681
04:22:27,367 --> 04:22:29,097
OT in communities so that the

9682
04:22:29,097 --> 04:22:30,470
parents can, you know,

9683
04:22:30,470 --> 04:22:32,338
they're trusted messengers for

9684
04:22:32,338 --> 04:22:33,273
these parents.

9685
04:22:33,273 --> 04:22:35,137
The parents love the therapist,

9686
04:22:35,137 --> 04:22:36,742
the therapist have amazing

9687
04:22:36,742 --> 04:22:37,544
empathy with

9688
04:22:37,544 --> 04:22:38,378
these parents.

9689
04:22:39,145 --> 04:22:40,174
And you know,

9690
04:22:40,174 --> 04:22:42,695
I think it also helps with that

9691
04:22:42,695 --> 04:22:43,183
whole

9692
04:22:43,183 --> 04:22:45,385
access at the sleep center.

9693
04:22:45,385 --> 04:22:47,172
So just wanted to add those

9694
04:22:47,172 --> 04:22:48,807
thoughts, those are good

9695
04:22:48,807 --> 04:22:49,489
thoughts.

9696
04:22:49,489 --> 04:22:51,072
And I will just chime in with

9697
04:22:51,072 --> 04:22:52,801
one more and that is that there

9698
04:22:52,801 --> 04:22:53,693
are some superb

9699
04:22:53,693 --> 04:22:55,004
patient advocacy groups,

9700
04:22:55,004 --> 04:22:56,696
especially kind of like in the

9701
04:22:56,696 --> 04:22:58,162
developmental and epileptic

9702
04:22:58,162 --> 04:22:59,275
encephalopathies and

9703
04:22:59,275 --> 04:23:00,333
neurodevelopmental

9704
04:23:00,333 --> 04:23:00,867
disorders.

9705
04:23:00,867 --> 04:23:02,773
These represent mostly represent

9706
04:23:02,773 --> 04:23:04,598
single gene disorders, not all

9707
04:23:04,598 --> 04:23:05,572
some represent,

9708
04:23:05,572 --> 04:23:06,110
you know,

9709
04:23:06,110 --> 04:23:08,012
but they're kind of organized a

9710
04:23:08,012 --> 04:23:08,441
little

9711
04:23:08,441 --> 04:23:09,157
differently,

9712
04:23:09,157 --> 04:23:11,060
but they're they're really good

9713
04:23:11,060 --> 04:23:11,244
at

9714
04:23:11,244 --> 04:23:13,092
sharing information and they're

9715
04:23:13,092 --> 04:23:15,044
really good at sharing, like you

9716
04:23:15,044 --> 04:23:15,715
just said,

9717
04:23:15,715 --> 04:23:17,565
not to use evidence based math,

9718
04:23:17,565 --> 04:23:19,157
but they're really good at

9719
04:23:19,157 --> 04:23:19,953
sharing data

9720
04:23:19,953 --> 04:23:21,821
that comes from research, right?

9721
04:23:21,821 --> 04:23:22,474
These are really

9722
04:23:22,474 --> 04:23:23,289
trustworthy groups.

9723
04:23:23,289 --> 04:23:24,870
So I'm hope you guys will rely

9724
04:23:24,870 --> 04:23:26,593
on us to help disseminate to our

9725
04:23:26,593 --> 04:23:27,293
communities.

9726
04:23:27,293 --> 04:23:28,782
Geraldine, just to clarify,

9727
04:23:28,782 --> 04:23:30,589
I wasn't saying we shouldn't use

9728
04:23:30,589 --> 04:23:31,097
evidence

9729
04:23:31,097 --> 04:23:31,498
based.

9730
04:23:31,498 --> 04:23:33,272
I was just saying for the

9731
04:23:33,272 --> 04:23:35,375
public, they might understand

9732
04:23:35,375 --> 04:23:36,536
treatments that

9733
04:23:36,536 --> 04:23:38,805
work better than evidence based.

9734
04:23:38,805 --> 04:23:40,392
Like it just it's less jargony,

9735
04:23:40,392 --> 04:23:41,007
that's all.

9736
04:23:41,007 --> 04:23:42,231
So it's such an important point

9737
04:23:42,231 --> 04:23:43,526
to use language where people are

9738
04:23:43,526 --> 04:23:43,810
right?

9739
04:23:43,810 --> 04:23:46,328
So they, I, I think, you know,

9740
04:23:46,328 --> 04:23:48,831
we're, we're right up against

9741
04:23:48,831 --> 04:23:49,349
time,

9742
04:23:49,349 --> 04:23:51,707
but I want to thank everyone

9743
04:23:51,707 --> 04:23:53,614
for, you know, a great

9744
04:23:53,614 --> 04:23:54,654
discussion.

9745
04:23:54,654 --> 04:23:56,807
I think there's so much work to

9746
04:23:56,807 --> 04:23:59,010
be done and and there's just an

9747
04:23:59,010 --> 04:23:59,792
incredible

9748
04:23:59,792 --> 04:24:01,450
excitement to bring this

9749
04:24:01,450 --> 04:24:03,356
community together, discuss

9750
04:24:03,356 --> 04:24:04,697
these themes in a,

9751
04:24:04,697 --> 04:24:06,733
in a number of different ways.

9752
04:24:07,300 --> 04:24:08,666
Thank you to everyone who's on

9753
04:24:08,666 --> 04:24:10,170
the call for attending tomorrow.

9754
04:24:10,170 --> 04:24:11,715
We're going into systems work

9755
04:24:11,715 --> 04:24:13,348
and then hopefully bringing it

9756
04:24:13,348 --> 04:24:14,274
all together and

9757
04:24:14,274 --> 04:24:15,763
thinking about how we can do

9758
04:24:15,763 --> 04:24:17,232
some translational dialogue

9759
04:24:17,232 --> 04:24:18,211
between very much

9760
04:24:18,211 --> 04:24:19,328
the human and patient

9761
04:24:19,328 --> 04:24:20,953
perspectives today and the the

9762
04:24:20,953 --> 04:24:22,415
basic science perspectives

9763
04:24:22,415 --> 04:24:22,916
tomorrow.

9764
04:24:22,916 --> 04:24:23,783
So thank you everyone.

9765
04:24:24,684 --> 04:24:25,418
Yeah, thanks Jordan.

9766
04:24:25,418 --> 04:24:26,883
Thanks to all the moderators,

9767
04:24:26,883 --> 04:24:28,437
the speakers and especially my

9768
04:24:28,437 --> 04:24:28,955
Co chairs

9769
04:24:28,955 --> 04:24:30,023
and the support team.

9770
04:24:30,490 --> 04:24:31,891
Look forward to talks tomorrow.

9771
04:24:32,258 --> 04:24:32,859
Thanks everybody.