>> GOOD AFTERNOON AND WELCOME TO
TODAY'S CLINICAL CENTER GRAND
ROUNDS THE HOPKINS CME ACTIVITY
CODE FOR GRAND ROUNDS IS 57871.
PLEASE TEXT THIS TO THE NUMBEROT
SLIDE TO RECEIVE CREDIT FOR
TODAY'S LECTURE.
WE KINDLY ASK YOU TO PROVIDE
SURVEY VIA LINK.
IT WILL BE USED TO PROVIDE US
IMPORTANT INFORMATION ABOUT THIS
PRESENTATION AND SUBMIT ANY
SUGGESTIONS FOR FUTURE GRAND
ROUND TOPICS.
FOLLOWING THE SPEAKER, QUESTIONS
WILL BE TAKEN FROM THE
MICROPHONES IN THE AISLES,
ADDITIONALLY, YOU CAN ALSO
SUBMIT QUESTIONS BY CLICKING THE
LIVE FEEDBACK BUTTON ON THE
WEBSITE.
QUESTIONS WILL BE ANSWERED AS
TIME PERMITSA THE CONCLUSION OF
THE PRESENTATION.
OUR SPEAKER TODAY IS D
R. SARA INATI, WITH THE
NATIONAL INSTITUTE OF
NEWOLOGICAL DISORDERS AND
STROKE.
DR. INATI COMPLOATED HER USHED
GRAD STUDIES AT HARVARD
UNIVERSITY AND EARNED HER DEGREE
FROM DARTMOUTH MEDICAL SCHOOL.
SHE COMPLETED HER INTERNSHIP AT
THE LENOIR OX MEDICAL HOSPITAL,
TRAINING AT THE COLUMBIA MEDICAL
INSTITUTE, AND FELLOWSHIP AT THE
EPILEPSY AND COMPREHENSIVE
EPILEPSY CENTER.
IN 2010 DR. INATI JOINED THE NIH
WITH THE NINDS CONSULT SERVICE
AND JOINED THE EEG SECTION THE
FOLLOWING YEAR WHERE SHE SERVED
AS CHIEF FROM 2012-2021.
IN 2021 SHE WAS EMPLOYED AS HEAD
OF NEUROPHYSIOLOGY EPILEPSY
UNIT.
HER INTERESTS INCLUDES SURGICAL
EPILEPSY, TUMOR RELATED EPILEPS
EXPE CHARACTERIZATION OF
EPILEPSY RELATED TO RARE GENETIC
DISORDERS AND WITH HER TEAM SHE
EXPLORES DEEP PHENOTYPES OF
PATIENTS AT THE CLINICAL CENTER
INCLUDING NEWS O PHYSIOLOGIC
EEG, MEG AS WELL AS STRUCTURAL
AND FUNCTIONAL NEURAL IMAGING.
SHE SEEKS TO IMPROVE THE ABILITY
TO IMPROVE SEIZE OUR FON, CI AND
BETTER UNDERSTAND HOW SEIZURE
ACTIVITY SPREAD THROUGHOUT THE
BRAIN TO IMPROVE THE EFFICACY OF
TARGET MEDICATIONS TO INDIVIDUAL
PATIENTS WITH FOCUS BASED
EPILEPSY.
--I JUST GAVE YOU A NEW NAME.
I'LL TAKE CREDIT FOR THAT.
DR. INATI, IS A PASSIONATE
EDUCATOR AND MENTOR SERVING AS
PROGRAM DIRECTOR FOR THE
EPILEPSY FELLOWSHIP PROGRAM
WHICH SHE ESTABLISH INDEED 2015
AND ASSISTANT PROGRAM DIRECTOR
FOR THE CLINICAL NEUROPHYSIOLOGY
FELLOWSHIP, THE PROGRAM HERE AT
NE H.
A PROLIFIC INVESTIGATOR WITH
OVER 60 PEER REVIEW
INVESTIGATORS, DR. INATI IS
BOARD CERTIFIED WITH
QUALIFICATIONS IN EPILEPSY AND
CLINICAL NEUROPHYSIOLOGY AND A
MEMBER OF THE AMERICAN CLINICAL
NEUROPHYSIOLOGY SOCIETY, THE
AMERICAN EPILEPSY SOCIETY, AND
THE AMERICAN ACADEMY OF
NEUROLOGY.
THE TITLE OF TODAY'S
PRESENTATION IS MAPPING EPILEPSY
IN THE HUMAN BRAIN.
NOW PLEASE JOIN ME IN WELCOMING
TODAY'S GRAND ROUND SPEAKERS
DR. EPILEPSY.
[LAUGHTER]
>> IT'S GOING TO STICK NOW.
>> [LAUGHTER]
>> [ APPLAUSE ]
>> ALL RIGHT.
I THINK THE COMPUTER'S ACTUALLY
WORKING, THIS IS ALL VERY
EXCITING.
THANK YOU SO MUCH FOR THAT KIND
INTRODUCTION AND THANK YOU FOR
THE INVITATION TO SPEAK HERE
TODAY EMPLOY I'M EXCITED TO TALK
TO YOU ABOUT MAPPING EPILEPSY IN
THE HUMAN BRAIN AND TO GET MY
NEW NICKNAME OUT OF ALL THIS.
AND YES, EVERYBODY THAT'S
PICTURED HERE HAS BEEN KNOWN TO
HAVE EPILEPSY.
I HAVE NOTHING TO DISCLOSE, NO
UNAPPROVED OR OFF LABEL DRUGS
WILL BE DISCUSS AND I'M HOPING
BY THE END OF THIS, YOU ALL CAN
IDENTIFY APPROACHES FOR SEIZURES
APPROACHES AND IN PATIENTS
UNDERGOING SURGERY EVALUATION
AND UNDERSTAND IN A BROAD SENSE
HOW PATHOLOGICAL ACTIVITY
SPREADS IN THE BRAIN IN FOCAL
EPILEPSY.
SO TO START OFF, EPILEPSY IS
COMN, AT THE INTRAMURAL PROGRAM,
WE STUDY RARE DISEASES BUT
EPILEPS SE1 OF THE MOST COMMON
DISEASE, ALMOST 3.5 MILLION
PEOPLE IN THE U.S. AND OVER
50 MILLION PEOPLE HAVE ACTIVE
EPILEPSY IN 2021 AND 1 IN 26
PEOPLE WILL DEVELOP EPILEPSY IN
THEIR LIVES.
THAT MEANS IN THIS ROOM HAVE HAD
OR WILL HAVE EPILEPSY.
AND THE INTERESTING THING ABOUT
THAT IS ALTHOUGH THERE'S A TON
OF STIGMA ATTACHED TO EPILEPSY,
MOAF OF WILL NEVER KNOW WHO THEY
ARE, RIGHT?
BECAUSE MOST PEOPLE WILL APPEAR
NORMAL IN BETWEEN THEIR
SEIZURES.
I PUT THIS MAP UP BECAUSE WE'RE
STUDYING THE PSYCHOSIS AND THIS
IS 1 REASON WHY THE PREVALENCE
OF EPILEPSY DIFFERS ACROSS THE
WORLD AND A LOT OF THIS IS IN
DEVELOPING COUNTRIES, SO IT'S A
SIGNIFICANT PUBLIC HEALTH
BURDEN.
I PUT THIS HERE ON THE SIDE TO
SHOW YOU THAT EPILEPSY DOES
CONSIDER ACROSS THE ENIRE AGE
RANGE, FROM THE VERY YOUNG TO
THE VERY OLD AND A LOT OF
EPILEPSY PRESENTS VERY EARLY AND
THESE ARE USUALLY INFANTS
ANDNYONATINGS WITH DISORDERS OF
VARIOUS SORTS AND IN OLD AGE IT
HAPPENS A LOT AND THIS IS DUE TO
ANY INSULT IN THE BRAIN BEING
ABLE TO LEAD TO EPILEPSY IN THE
BREAN IN CERTAIN PEOPLE.
BECAUSE OF THAT, THIS IS RED,
LIVES WITH DISABILITY AND LIVES
LOST.
I SAY THIS BECAUSE PEOPLE WITH
EPILEPSY DO SUFFER DISABILITY
OVER THE COURSE OF THEIR
LIFETIME.
IT STARTS EARLY BUT ALSO WE HAVE
A LOT OF PEOPLE WHERE SEIZURES
DEVELOP IN THEIR LATE TEENS AND
20S.
AND THAT'S TRAJECTORY WHEN THIS
HAPPENS TO THESE PEOPLE.
THEY LIVE WITH DISABILITY AND
THEY LIVE WITH THE FEAR OF
INCREASED MORETALLITY.
THAT CAN BE DUE TO BRAIN TUMORS,
OTHER SYNDROMES BUT EVEN
EPILEPSY ITSELF CAN LEAD TO
DEATH EITHER THROUGH ACCIDENTS
AND INJURIES, SUICIDE IS
INCREASED IN THESE PATIENTS AND
THE OTHER UNEXPLAINED DEATH IN
EPILEPSY AND PATIENTS IN
REFRACTORY EPILEPSY THIS CAN
OCCUR UP TO 1 PERCENT A YEAR
WHICH SOUNDS PRETTY RARE UNTIL
YOU GET DIAGNOSED AT THE AGE OF
20, THE RISK IS PRETTY HIGH IF
YOU ARE PROJECTING YOU ARE GOING
TO LIVE ANOTHER 20 OR 30 YEARS.
SO I THINK YOU START TO GET A
SENSE OF THIS, BUT THE EPILEPSYS
ARE EXTREMELY HETEROGENEOUS SO
WE'RE NOT TALKING ABOUT 1
DISORDER HERE, BUT A FAMILY OF
DISORDERS WITH A COMMON PATHWAY,
I LIKE THIS BECAUSE IT REFLECTS
THAT, IT HAPPENS IN NEOINATES IN
MITTED, AND WHAT HAPPENS IN
ADULTS ON THE OUTSIDE, I'M AN
ADULT NEUROLOGIST SO I'M DEALING
WITH THAT PERIMETER THERE, SO
YOU CAN SEE THAT THIS IS THE
RANGE FROM SEVERE TO BENIGN.
WE HAVE A LOT OF PEOPLE WITH
RELATIVELY BENIGN SEIZURES,
THESE ARE THE 1S THAT PEOPLE
TYPICALLY GROW OUT OF OR HAVE
WELL CONTROLLED MEDICINE.
AND SOME OF OUR PATIENTS RADIOLE
LOAMACYY DO SUFFER FROM
SIGNIFICANT COMPLICATIONS FROM
THEIR EPILEPSY.
IT CAN BE CAUSED BOO I A MILLION
DIFFERENT CAUSES.
TRAUMA, STROKE, TUMORS,
INFECTIONS, CONGENITAL LESIONS,
BIRTH, HIPOXIC ESCHEMIC INJURY,
BUT IN THE VAST MAIORITY OF
PATIENTS WE DON'T HAVE AN ANSWER
FOR THAT QUESTION.
WE STILL DON'T KNOW WHY THEY'RE
HAVING SEIZURES AND THIS IS A
SOURCE OF TURNOVERRED EFFORTS
AND RESEARCH AND OVERTIME WE
THINK WE LABELED A LOT OF THESE
AS GENETIC DISORDERS BUT WE'RE
NOT REALLY FINDING THAT IN OUR
INITIAL STUDIES SO THIS IS STILL
PART OF A POLYMORPHIC AND I
THINK IT'S UNDER SIGNIFICANT
INVESTIGATION.
TO GIVE YOU BASIC DEFINITIONS,
EPILEPSY IS NOT SUBTLE IN MOST
PATIENTS, IT'S BEEN RECOGNIZED
FOR ALMOST AS LONG AS WE ARE
TEXT BACK TO THE ANCIENT GREEKS,
ROMANS, THERE'S A LOT OF ART
WORK PORTRAYING THESE DRAMATIC
SEIZURES.
SO WHAT IS AN EPILES SEIZURE?
IT'S A TRANSIENT OCCURRENCE OF
SIGNS SYMPTOMS OF TO SYNCHRONOUS
NEURONAL ACTIVITY IN THE BRAIN,
SO THAT IS COMPLICATED BUT THIS
IS TO GET RID OF ANYTHING THAT'S
CAUSED BY OTHER FUNCTIONS THAT
ARE NOT ELECTRICAL IN ETIOLOGY
AND I THINK IT'S REALLY
IMPORTANT THAT WE RECOGNIZE THAT
THESE SIGNS OR SYMPTOMS ARE
REALLY DIFFERENT ACROSS ALL OF
OUR PATIENTS AND THEY REALLY DO
REPRESENT THIS HIJACKING OF
NORMAL BRAIN FUNCTION BY THIS
PATHOLOGICAL ACTIVITY.
SO I THINK THIS IS THE FIRST
WAVE I WILL TALK ABOUT IN WHICH
EPILEPTIC ACTIVITY AND NORMAL
FUNCTIONAL BRAIN ACTIVITY ARE
REALLY TIED TOGETHER.
EPILEPSY ITSELF ALTHOUGH DEFINED
BY THIS TENDENCY TO SO THERE'S
OTHER AND THE EXPERIENCE OF OUR
PATIENTS WITH EPILEPSY.
WE CALL SOME OF THESE EPILEPSY
AND CO-MORBIDITIES IN THE SENSE
IT'S NOT RELATED TO THE
SEIZURES.
SO THIS IS INTERECTOMYOSINNAL,
THESE ARE THINGS THEY EXPERIENCE
IN BETWEEN SEIZURES AND IT SEEMS
TO BE RELATED TO WHAT BRAIN
SYSTEM IS INVOLVED IN THAT
PATIENT'S EPILEPSY.
SO FOR EXAMPLE, OUR MOOF THE
COMMON TIME IS TEMPORAL LOBE
EPILEPSY AND MANY OF THEM WILL
HAVE CONCOGNITIVE PROBLEMS
PARTICULARLY WITH MEMORY AND
LANGUAGE, A LOT OF THEM SINCE IT
INVOLVES THE EMILY CIBOL SYSTEM
WILL HAVE PROBLEMS WITH
DEPRESSION OR ANXIOUS AND MANY
OF OUR PATIENTS HAVE HEADACHES
AND SLEEP DISORDERS AS WELL, AND
ALL OF THESE COMBINE TO CREATE
THE EXPERIENCE OUR PATIENTS HAVE
LIVING WITH EPILEPSY.
I THINK I CAN'T GIVE A TALK TO A
GENERAL AUDIENCE WITHOUT AT
LEAST MENTIONING STIGMA AND
EPILEPSY BECAUSE THIS 1 OF THE
MOST INTENSE AND DISTRESSING
FEATURES OF THE ILLNESS FOR A
LOT OF OUR PATIENTS AND YOU CAN
IMAGINE ALL OF YOU SITTING HERE,
IF YOU DON'T HAVE EPILEPSY, IF
YOU WERE TO JUST SUDDENLY HAVE A
SEIZURE TODAY OR TOMORROW, JUST
IMAGINE FOR A MEMORY CLONE THAT
HE WENT WOULD MEAN TO YOU AND
YOUR FAMILY, WHAT WOULD THAT
MEAN FOR YOUR JOB, WHAT WOULD
THAT MEAN FOR YOUR SCHOOL, A LOT
OF TIMES IF YOU HAVE A SEIZURE,
YOU CAN'T DRIVE FOR 3-12 MONTHS
SO THIS IS AN EXTREMELY
TROUBLING EVENT FOR PEOPLE.
NOT TO MENTION WE HAD PEOPLE ON
VERY IMPRESSIVE TELECONFERENCES,
VIDEOS WHO ALL OF A SUDDEN WILL
HAVE A SEIZURE IN THE MIDDLE OF
THOSE AND YOU CAN IMAGINE THIS
IS REALLY PROBLEMATIC FOR THEM
IN THEIR PROFESSIONAL CAREERS
EMPLOY BECAUSE IT'S REALLY SCARY
AND IT SCARES PEOPLE THAT SEE
IT.
I PUT THIS UP BECAUSE I FOUND
THIS IN EPILEPS EXPE ME IN THE
WELCOME COLLECTION WHICH IS A
SERIES ONLINE AND THIS IS AN
ARTIST AND SOMEBODY WHO IS
WRITING ABOUT THEIR LIVED
EXPERIENCE WITH EPILEPS EXPE
THIS IS THE ART WORK THEY CAME
UP TO DRIEB.
SO PART OF THIS IS RELATED TO
THEIR INTERACTIONS WITH THE
MEDICAL SYSTEM.
A LOT OF OUR PATIENTS HAVE
RECURRENT SEIZURES AND IF
THEY'RE NOT CONTROLLED THIS
INVOLVES TO WAKING UP PEOPLE
STANDING UP AND STARING AT THEM,
THIS INVOLVES GETTING CARTED OFF
TO EMERGENCY ROOMS OVER AND OVER
AGAIN, SIGNIFICANT COST,
EMBARRASSMENT BUT ALSO THE
MEDICAL SYSTEM CAN BE A BIT
UNKIND TO THESE PATIENTS.
A LOT OF TIMES THEY COME IN THAT
ARE CONFUSED, COMBATIVE, A LOT
OF OUR PATIENTS HAVE HAD
INTERACTIONS WITH POLICE BECAUSE
THEY'RE BEHAVING UNPREDICTABLY.
A LOT OF TIME EMERGENCIES ARE
NOT PARTICULARLY SYMPATHETIC TO
THESE PATIENTS BECAUSE THEY CAN
BE BEHAVIORIALLY DIFFICULT TO
DEAL WITH, THEY HAVE MEMORY
PROBLEMS, CAN'T COME UP WITH
MEDICINES, CAN'T EXPLAIN WHAT'S
GOING ON AND THEY GET EVALUATED
OVER AND OVER AGAIN THIS, IS HER
IMAGES PROJECTING THAT, YOU FEEL
A LITTLE BIT LIKE A ROBOT OR AN
AUTOTOM TON LIKE WE LIKE TO DO
WITH OUR EEGS, THE PROBLEMS WITH
OUR JOBS, MANY OF OUR PATIENTS
HAVE LOST THEIR JOBS WHEN
THEY'VE HAD A SEIZURE ON THEIR
JOBS, IF PEOPLE FIND OUT THEY
WON'T HIRE THEM FOR JOBS AND IN
FACT IF YOU LOOK AT THE ASYLUMS
WE USED TO HAVE IT WAS ASIGNIFY
LEMS FOR THE EPILEPSICS AND THE
INSANE.
SO THAT TELLS YOU A LOT ABOUT
THEIR EXPERIENCE.
A LOT OF THEM TRY AND SUPPRESS
THE KNOWLEDGE THEY HAVE EPILEPSY
FOR FEAR THIS WILL IMPACT THEIR
ABILITY TO HAVE--TO MARRY, HAVE
CHILDREN, AFFECT CHILDREN GOING
FORWARD.
SO THAT'S MY LITTLE PIECE ABOUT
WHAT IT'S LIKE TO LIVE WITH
EPILEPSY.
I'M HAPPY TO TALK WITH ANYBODY
ABOUT WHAT THAT IS.
THE THING I DIDN'T MENTION THERE
IS THE IMPACT ON THEIR FAMILIES,
A LOST THEIR FAMILIES END UP
DRIVING PEOPLE THESE PLACES AND
ARE ALMOST A LOT MORE
TRAUMATIZED THAN THE PATIENTS
BECAUSE THE PATIENTS FOR GET THE
SEIZURES BUT THE FAMILIES HAVE
TO LIVE THROUGH THEM EMPLOY SO
THIS IS A DISORDER THAT AFFECTS
THE FAMILIES SO AS AN
EPIATOLOGYIST WHAT CAN I DO TO
HELP THEM.
THE MAIN STAY IS MEDICATIONS.
WE'VE HAD THIS AMAZING EXPLOSION
IN THE NUMBER OF SEIZURE
MEDICATIONS OVER THE LAST 10 OR
20 YEARS.
WE USED TO HAVE BASICALLY
BROMID, BORAX, AND PHENOBARB
TOLL-LIKE RECEPTOR, AND NOW WE
HAVE A HUGE NUMBER OF MEDICINE
AND THEY HAVE A WHOLE BUNCH OF
MECHANISMS OF ACTION WHICH ARE
SUPER INTERESTING AND WE COULD
TALK ABOUT FOR AN ENTIRE DAY OR
COURSE, MOSTLY AFFECTING, TRYING
TO INCREASE GABBA INHIBITION OR
DECREASE GLUTEA MITTERGIC
EXCITATION.
SADLY, I SAY THE POSITIVE SIDE
IS THESE ARE MUCH BETTER
TOLERATED THAN OLD MEDICINES,
OUR PATIENTS TEND TO HAVE FEWER
SIDE EFFECTS ON THEM.
HOWEVER, NONE OF THEM WORK ANY
BETTER THAN ANY OTHER MEDICINE
IN TREATING THE SEIZURES
THEMSELVES, SO THIS IS SAD AND
IT ACTUALLY DIDN'T AFFECT THE
TRAJECTORY OF THE ILLNESS,
EITHER.
SO IT'S KIND OF LIKE TAKING AN
ADVIL, IT WILL SETTLE THINGS BUT
IT WON'T CHANGE THE UNDERLYING
PREDISPOSITION TO HAVE SEIZURES.
SO SEIZURE CONTROL MEDICATIONS,
YOUR FIRST DRUG, HALF OF OUR
PATIENTS WILL BECOME SEIZURE
FREE.
BY THE TIME YOU'RE TRYING A
THIRD, FOURTH, FIFTH, SIXTH,
SEVENTH DRUG, THE CHANCE THAT
YOU WILL BE SEIZURE FREE ARE
INCREDIBLY SMALL.
ABOUT A THIRD OF OUR PATIENTS
WILL HAVE DRUG RESISTANT
EPILEPSY OR SEIZURES THAT WILL
CONTINUE BASICALLY NO MATTER
WHICH MEDICINE WE TRY TO TREAT
THEM WITH WHICH LEADS ME TO THE
THING I'VE ENDED UP THINK BEING
A LOT WHICH IS SURMLY.
SO WHAT OTHER COPDS EXIST FOR
THIS ONE-THIRD OF PATES WHERE
REALLY THE MEDICINES AREN'T
GOING TO DO THE JOB AND YOU KNOW
THIS AFTER A YEAR OR 2.
SO IF YOU AGGRESSIVELY TRY THESE
MEDICINE, YOU KNOW PRETTY
QUICKLY IN THESE PATIENTS, YOU
ARE NOT A PATIENT WHERE IT'S
GOING TO WORK.
SO NOBODY WANTS TO THINK ABOUT
BRAIN SURGERY, IT'S NOT
SOMETHING PEOPLE ARE EXCITED
ABOUT YOU BUT OFTEN THE TROUBLE
PEOPLE ARE HAVING IN THEIR LIVES
LEADS THEM TO CONSIDER THIS AS
AN OPTION.
BY FAR THE BIGGEST SURGERY DONE
OVER TIME IS A TEMPORAL
RESECTION OF THE TEMPORAL LOBE,
PLUS THE MEDIAL STRUCTURE CALLED
THE HIPPOCAMPUS.
I THINK MANY OF YOU HAVE HEARD
OF THE HIPPOCAMPUS AS BEING
INCREDIBLE LOAMACYY IMPORTANT
FOR MEMORY, SO CAN YOU IMAGINE
THERE ARE PROBLEMS ASSOCIATE
WIDE RESECTION OF A HYPOCAMPUS.
SO THERE HAVE BEEN EFFORTS TO
MINIMIZE THE COGNITIVE SIDE
EEIVETS OF THESE SURGERIES,
INCLUDING SELECTIVE RESECTIONS,
WE NOW HAVE LASER OBLATIONS
WHERE YOU PUT AN LASER IN, IT'S
ALMOST AN OUTPATIENT PROCEDURE
AND THEY CAN ABLATE THE
HIPPOCAMPUS WITHOUT AFFECTING
THENY O CORTEX AND THERE'S BEEN
AN EXPLOSION IN THE
NEUROMODDULATION OPTIONS, SO
THESE ARE AREAS OF ONGOING WORK
THAT WE'RE REALLY EXCITED ABOUT,
DEFINITELY CAUSING SIDE EFFECTS
BUT THE EFFICACY HAS NEVER
REALLY MATCHED THE EFFICACY OF A
STANDARD ANTERIOR TEMPORAL
LOBECTOMY.
SO THIS IS JUST FOR EPILEPSY
RESECTIVE SURGERIES WHICH IS
STILL THE MOST EFFECTIVE OPTION
WE CAN OFFER OUR PATIENTS.
IF YOU LOOK AT ALL PATIENTS, AND
THIS IS OVER YEARS ON THE
BOTTOMACIS HERE, CAN YOU SEE
THAT THAT A MEAN OF 80-90%
SEIZURE REDUCTION.
SO THESE SURGERIES TEND TO BE
QUITE EFFECTIVE.
SO IF YOU LOCK AT THE 25th
PERCENTILE, THEY DO
EXCEPTIONALLY WELL, HOWEVER WE
HAVE THIS GROUP IN THE TENTH
PERCENTILE THAT DOES MUCH, MUCH
LESS WELL AND ALL COMERS ARE NOT
THE SAME.
PEOPLE WITH TEMPORAL LOBE
EPILEPSY WHICH IS THE BLACK AND
BLUE LINE UP HERE AT 10 YEARS
OUT TEND TO BE OVER 50% ARE
ACTUALLY SEIZURE FREE AFTER
THESE SURGERIES BUT WHEN YOU GET
OUTSIDE THE TEMPORAL LOBE, THE
OUTCOMES ARE HARDER.
SO THIS GREEN LINE IS A TEMPORAL
LOBE EPILEPSY WITH A LESION, AND
TEMPORAL LOBE WITH EPILEPSY
WITHOUT A LESION, CAN YOU SEE WE
HAVE A LOT OF WORK TO DO.
SO THIS IS REALLY WHY THE TITLE
COMES FROM WITH MAPPING EPILEPSY
IN THE HUMAN BRAIN AND SO WHY DO
WE THINK THESE PEOPLE ARE NOT
GETTING THE EFFECT THAT WE'RE
LOOKING FOR, SO 1 IN INCOMPLETE
RESECTION, BUT THIS CAN BE BY
ACCIDENT OR ON PURPOSE, IF
THEY'RE COMING FROM THE ELOQUENT
PART OF THE BRAIN, YOU WE WENT
WANT TO GIVE SOMEBODY A HORRIBLE
DEVELOPMENTAL ENDOCRINOLOGY SILT
SO WE CAN ON PURPOSE NOT RESECT
SOAZ PLACES AND THEY HAVE A
LOWER CHANCE OF BECOMING SEIZURE
FREE.
SOMETIMES WE'RE STILL JUST
GETTING IT WRONG AND THIS IS
WHERE I THINK THAT ALL OF THESE
FANCY NEW TECHNOLOGIES THAT WE
HAVE CAN REALLY HAVE AN IMPACT
ON YOUR CHAIR OF PATIENTS AND
THE LESS IS DIFFUSE FROM
MULTIFOCAL DISEASE, SO SOME
PEOPLE HAVE A NEURODEGENERATIVE
DISORDER OR MULTIFOCAL OR
INFLAMMATORY DISORDER AND TAKING
OUT 1 PLACE MAY NOT TAKE CARE OF
THE WHOLE PROBLEM, THAT'S A
TOPIC FOR THE DIFFERENT DAY.
SO I WILL FOCUS ON THE
INACCURATE LOCALIZATION FOR THE
REST OF THIS.
SO EPILEPSY SURGERY HAS ALWAYS
CLOSELY MIRRORED MAPPING EPILEPS
EXPE MAPPING NORMAL BRAIN
FUNCHES AND I JUST WANT TO TAKE
A MOMENT TO POINT OUT HERE,
JASPER PUBLISHED THE FIRST EEG
IN THE U.S. AND THE BIG IMPACT
HE HAD WAS THAT HE FELT LIKE YOU
COULD ACTUALLY REGIONALIZE WHERE
SEIZURES WERE COMING FROM USING
THIS CRAZY EEG TECHNOLOGY AND
THIS IS THEIR 2 CHANNEL EEG BACK
IN THE DAY.
THIS IS THE FIRST 1 THAT WAS
PUBLISHED AND HE ACTUALLY
EVENTUALLY MET UP WITH PENFIELD
WHO WAS IN MONTREAL AND I HAVE
THIS EEG THAT MAY TELL US WHERE
THE SEIZURES MIGHT BE COMING
FROM.
IT'S A REVOLUTIONARY THING.
I LOVE THE PICTURE, SO I'M THE
EPILEAPTOLOGYIST IN ALL THIS, SO
HERE'S THE DOCTORS AND JASPER'S
BACK HERE DOING OUR SQUIGGLING
LINES SO NOTHING'S CHANGED BUT
TOGETHER THEY PUT OUT THIS BOOK
WHICH I THINK ALL OF YOU AND IF
YOU WENT TO MEDICAL SCHOOL OR
BASIC NEUROSCIENCE CLASSES WE
ALL KNOW THE HOMOCULUS, SO THIS
IS SOMETHING WE LEARNED THROUGH
EPILEPSY SURGERY.
ANOTHER THING YOU MAY HAVE HEARD
ABOUT IS HM OTHERS ANOTHER CASE
OF EPILEPSY SURGERY, TEACHING US
MORE THAN WE WANTED TO KNOW FOR
HIM AT LEAST ABOUT BRAIN
FUNCTION AND MEMORY.
SO WE CONTINUE TO LEARN ABOUT
LANGUAGE ABOUT MOTOR FUNCTION, A
LOT OF THE BRAIN MACHINE
INTERFACE WORK IS COMING OUT OF
OUR PATIENTS WITH EPILEPTSY IS
MOVING INTO OTHER PATIENT
POPULATIONS, SO, THAT'S MY PITCH
FOR EPILEPSY AND NORMAL BRAIN
FUNCTION, THAT IS NOT WHAT I'M
DOING AT ALL.
I AM REALLY INTERESTED IN
UNDERSTANDING EPILEPSY THROUGH
ALL THESE TOOLS AND SO OUR IDEA
OF WHAT EPILEPSY IS, AND HOW IT
FUNCTIONS IN THE BRAIN SO THIS
CONCEPT OF HIJACKING NORMAL
BRAIN FUNCTION HAS BEEN AROUND
FOR A LONG TIME BUT IT HAS
CHANGED.
SO 1950S WE'RE BACK WITH THE
PICTURE I WAS SHOWING YOU OF
JASPER AND PENFIELD DOING INTRA
OPERATIVE RECORDINGS, SO THESE
WOULD BE RELATIVELY BRIEF, SO
MAYBE OVER MINUES TO HOURS AND
YOU WOULD LOOK AT THESE
ACTIVITIES, THE SPIKING AND USE
THAT TO MAP OUT FUNCTION.
SO THEN [INDISCERNIBLE]--THERE'S
A FAMOUS PICTURE I ALMOST PUT IN
HERE, BUT THEY PIONEERED THE USE
OF ELECTRODES, THAT THEY WOULD
ALWAYS PUT SIDE WAYS, THEY
ACTUALLY HAD ANGIOGRAPHYS SO
THEY COULD TELL WHERE THE BLOOD
VESSELS WERE TO AVOID THEM AND
THIS IS WHERE THE
[INDISCERNIBLE] ATLAS CAME FROM
FOR ANY OF YOU.
THEY WOULD PUT THESE DEPTH
ELECTRODES IN AND KEEP THEM IN
LONG ENOUGH TO RECORD SEIZURES,
SO THEY REALLY FOCUSED ON
SEEDSURES AND DEPTH ELECTRODE
RECORDINGS TO SEE HOW SEIZURES
WORKED IN THE BRAIN AND WHAT
AREAINGS THEY WANT TO RESECT TO
MAKE THE SEIZURES BETTER.
BY THE WAY THIS BASICALLY IS
TILL DONE ESSENTIALLY THE SAME
WAY WITH FANCIER TECHNOLOGY BUT
TO THIS DAY.
THE NEXT BIG CHANGES WERE
SEVERAL DECADES LATER WHERE
PARTICULARLY IN THE UNITED
STATES FOR SOME REASON IN
EUROPE, KIND OF CONTINUED THIS
IS NEVER CHANGED.
THE UNITED STATES WENT ALL IN ON
SUBDURANNAL RECORDINGS, SO THE
OTHER THING THAT HAPPENED AROUND
THAT TIME WAS BRAIN IMAGING SO
THE ADVENT OF MRI CHANGED HOW WE
THINK ABOUT SEIZURE FOCUS
LOCALIZATION.
BEFORE WE WERE REALLY RELYING
ENTIRELY ON ELECTROPHYSIOLOGY
BUT NOW WE HAVE BRAIN NRI THAT
JUST SAYS, THERE'S THE PROBLEM,
RIGHT, SO THAT ALLOWED US TO
LEARN A LOT ABOUT EPILEPSY AND
SO THIS WAS PUT TOGETHER BY
LEUTERS AT CLEVELAND CLINIC AND
HE TALKED ABOUT THESE STRECTURAL
LESION, AND THERE WAS A SUBSET
WROAN AND IT WAS A STATIC
DIAGRAM AND THE MORE THEY
OVERLAPPED THE BETTER OUR
SITUATION WAS IN TERMS OF
KNOWING WHAT TO DO TO TRY AND
FIX THE PERSON'S SEIZURES.
OVER TIME THIS IS REALLY EVOLVED
TO A MORE KIND OF DYNAMIC VIEW
OF THINGS WHICH WE LOOSELY REFER
TO AS NETWORKS BUT THAT TERM IS
NONSPECIFIC AND SO TAKING INTO
ACCOUNT BOTH SPACE AND TIME AND
SO I'M GOING TO GIVE YOU AN
EXAMPLE OF WHAT THAT LOOKS LIKE
BY THE WAY WE THINK ABOUT
SCHEMEIOLOGY, IT'S SIGNS AND
SYMPTOMS ANYONE HAS DURING
SEIZURES AND WHEN I STARTED OFF
I WAS EXCITED ABOUT THESE
BASICALLY LOCALIZATIONIST MAPS.
WHERE YOU WOULD BE LIKE A
SEIZURE COMING FROM HERE OR
OLFACTORY OR ICHTALL FEAR, LIKE
A SYMPTOM CAME FROM A SPECIFIC
PLACE, OKAY IN WHAT'S HAPPENED
OVER TIME IS WE REALIZE WE WERE
IGNORING THE RULE OF WHITE
MATTER IN ALL OF THIS SO I THINK
BOTH DTI IMAGING, A LOT OF
ANIMAL WORK FROM FUNCTIONAL MRI
HAS SHOWED US THERE ARE THESE
DISTRIBUTED AND DISTANTLY
LOCATED BRAIN NETWORKS THAT WORK
TOGETHER AND WE NOW THINK THAT
IS ALSO HUGH IT GENERATES THE
SIGNS AND SYMPTOMS THAT WOE SEE
DURING SEIZURES, SO I WILL GIVE
YOU A COUPLE EXAMPLES, SO
AUTONOMICKISM SYMPTOMS, WE WOULD
SAY AMYGDALA BECAUSE IT WAS
MEDIAL LOBE, TEMPORAL LOBE, EPS
LE, BUT NOW WHEN WE THINK ABOUT
IT, WE CAN SEE IT RELEASE
SIGNALS FROM ALL THESE DEFINITE
REGIONS IN THE BRAIN ARE HIGHLY
CONNECTED AND ACTIVATION OF 1
LEADS TO ACTIVATION OF THE REST
AND WE END UP WITH VERY SIMILAR
APPEARING SYMPTOMS.
FRONTAL LOBE EPILEPSY I THINK I
SHOWED YOU EARLIER, WE'RE STILL
NOT GOOD AT DEALING WITH.
IF YOU LOOK AT THE FRONTAL AND
STRUCTURAL CONNECTIVITY OF THE
FRONTAL LOBE, IT'S SMALL WONDER
WE HAVE TROUBLE DEALING WITH
THIS WITH THE RECORRINGS BY
THEMSELVES BECAUSE IF YOU LOOK
THESE ARE BROADLY DRIEWBT
NETWORKS SO IF I SEE SOMETHING
IN THIS DORSAL LATERAL
PREFRONTAL CORTEX, JUST BASED ON
SYMPTOMS IT COULD JUST AS EASILY
BE COMING FROM THE PARIETAL PART
OF THE CORTEX.
SO THIS IS SOMETHING WE GAIN
APPRECIATION FOR AND POSSIBLY
MOVING THIS BACK TO THE EEG
ELECTRODES WHERE YOU SAMPLE VERY
FAR APART PLACES IN THE BRAIN.
MY LAST EXAMPLE IS THE ROLE OF
THE INSULA, WHICH WAS NOT WELL
APPRECIATED PARTICULARLY BY
TRUSTEESS THAT WERE ONLY USING
SUBDURANNAL ELECTRODES SINCE
THOSE DIDN'T SAMPLE THE INSULA
AT ALL.
AND WE KNOW IT'S ANOTHER GREAT
MIMICKER THAT CAN LOOK LIKE
SEIZURES COMING FROM ANY PART OF
THE BRAIN.
SO WHY DID INTRA CRANIAL EEG NOT
SOLVE THIS PROBLEM?
WELL 1 IS WHAT I WAS TELLING YOU
WHICH IS THE ACTIVITY SPREADS
REALLY FAR AND REALLY FAST.
ANOTHER IS THAT EVEN WHEN WE
THINK WE'RE COVERING THIS
MASSIVE PART OF THE BRAIN, THIS
IS AN EXAMPLE OF 4 BY 8 GRID,
PEOPLE HAVE USED EVEN 8 BY 8
GRIDS THAT COVER WHOLE
HEMISPHERES ON THE SURFACE OF
THE BRAIN, THEY PUT THOSE
CERTAINLY--CERTAINLY LECT RODES
ON THE BRAIN SURFACE FOR THE
PATIENT IT ALLOWS YOU TO BLOW
THE BRAIN UP, SO THE BLAINE IS
ALL FOLDED BUT IF YOU THINK OF
PUTTING A STRAW IN AND INFLATING
IT SO IT LOOKS LIKE A BALL, THIS
IS WHERE THOSE ELECTRODES ARE,
SO FOR ME THAT KIND OF
HIGHLIGHTED EXACTLY HOW SPARSE
OUR SAMPLING IS EVEN WHEN IT
LOOKS LIKE WE LIKE COVERED THE
BRAIN WITH ELECTROCOVERRAGE.
SO THERE'S A PAPER THAT CAME OUT
QUANTIFYING THIS AND IF YOU LOOK
AT FOR EXAMPLE, TEMPORAL LOBE
IMPLANT, THIS IS THE COVERAGE OF
THE REGION BY PERCENTAGE, SO
WHEN YOU HAVE STRIPS AND GRIDS
YOU CAN COVER MAYBE
OPTIMISTICALLY, ALMOST 5% OF THE
BRAIN MAXIMUM, EVEN IN THAT
TEMPORAL LOBE, RIGHT?
AND DEPTH ELECTRODES DO NOT FIX
THIS PROBLEM.
THE SPATIAL SAMPLING IS STILL
QUITE LOW.
WHAT I WOULD LIKE TO SAY IS THAT
I THINK PARTICULARLY WHEN WE
TALK ABOUT THESE BROADLY
DRIEWBTED BRAIN NETWORKS, INTRA
CRANIAL EEKB SIN BY ITSELF I
THINK CANNOT BE THE ANSWER.
SO THAT IS WHAT LED ME BACK IN
2014, I STARTED THIS, BUT WE
STARTED COLLECTING DATA IN 2015
TO HAVE A STANDARDIZED
MULTIMODAL NONINVASIVE IMAGING
COHORT THAT ALL OF OUR PATIENTS
UNDERGO THE SAME SET OF STUDIES
WITH THE IDEA THAT WE COULD AT
LEAST HAVE A STANDARDIZED DAILY
BASIS THEA SET WE COULD COLLECT
OVERTIME AND GO BACK AND TRY TO
SAY HOW CAN THESE OTHER
MODALITIES HELP US MAKE BETTER
HYPOTHESIS SO THAT WE CAN PUT
THESE CERTAINLY--CERTAINLY LECT
RODES IN THE MOST PLACES THAT
WILL BE THE MOST INFORMAIVE IT
FOR US.
THIS IS WHAT I HAD BEFORE IS
JUST THE STANDARD SET UP THAT
MOST EPILEPSY CENTERS HAVE FOR
TESTING THAT YOU DO ON A PATIENT
UPDATER GOING PRESURGICAL
EVALUATION, TO THAT WE HAVE
ADDED 7 T IMAGING AND ALSO GET
DIFFUSER IMAGING, ASL, CEREBRAL
BLOOD FLOW ESTIMATES, WE DO OUR
MAPPING FOR FMRI LANGUAGE, BUT
WE ALSO GET RESTING STATE FMRI
AND THEN IN PATIENTS WHERE IT'S
RELEVANT WHERE THEY WILL GET
INTRA CRANIAL RECORDINGS IN
CLOSE COLLABORATION WITH THE
NEUROLOGY BRANCH AND DR. ZAGULL.
SO THE WAY WE HAVE INDIVIDUAL
PATIENT HYPOTHESIS, RIGHT?
AND WE TEST THEM WITH OUR
RESECTION, SO, IF THE PATIENT
BECOMES SEIZURE FREE, WE ASSUME
THE SEIZURES WERE COMING FROM
SOMEWHERE IN THE AREA OF
RESECTION, IF THE PATIENT
DOESN'T BECOME SEIZURE FREE, WE
ASSUME THE PROBLEM WAS NOT IN
THAT REGION.
SO I WILL TELL YOU ABOUT A
COUPLE PROGECS WOO EVALUATION
PROCESS DONE TRYING TO MAP
EPILEPSY.
IN OUR PATIENT COHORT USING THAT
EPILEPSY IMAGING PROTOCOL, SO
I'M GOING STOCK EXCHANGE START
OFF BY TALKING ABOUT THE
STRUCTURAL ABNORMALITIES.
SO 1 OF THE THINGS THAT WHEN I
STARTED I KNEW COULD MAKE AN
IMMEDIATE DIFFERENCE FOR OUR
PATIENTS, WAS TRYING TO FIND
LESIONS THAT WEREN'T IMMEDIATELY
OBVIOUS WHEN WE LOOK THROUGH THE
IMAGE, SO IF YOU LOOK OVERALL AT
TEMPORAL AND EXTRA TEMPORAL LOBE
EPILEPSY, IN LESIONIONAL
PATIENTS, THEY WERE ACHIEVING
APPROXIMATELY 68% SEIZURE
FREEDOM.
IN NONLESIONAL PATIENTS WE HAD
40%, RIGHT?
BECAUSE THESE PEOPLE HAVE
MULTIFOCAL DISEASE OR DIDN'T
FIND THE LESION AND DIDN'T
THEREFORE HAVE THE RIGHT ANSWER.
SO HERE'S AN EXAMPLE OF AN
EPILEPTIC LESION THAT I DON'T
THINK YOU NEED THE RED ARROW
FOR, CAN YOU SEE THAT, THE
PATIENTS GET SEIZURES IN THESE
CABER NOAMAS, THIS IS NOT A
MYSTERY.
THE PATH OF LESION FOR
CAVERNOMA, THEY EXIST ON A
SPECTRUM, THEIR BRAIN
MALFORMATIONS THAT HAPPEN DURING
BRAIN DEVELOPMENT, SOME OF THEM
ARE REALLY, REALLY OBVIOUS, I
THINK YOU CAN SEE HERE THE
BRIGHT LESIONOT FLAIR IMAGE WITH
THE TAIL GOING BACK TOWARDS THE
VENTRICLE, IT LOOKS THICK AND
BLURRY AND YOU CAN SEE IT ON
THESE IMAGES.
I PUT THE ARROW THERE IN CASE
YOU COULDN'T SEE IT.
AND THEN THERE ARE MORE SUBTLE
TYPES OF FOCAL CORDICLE
DISPLASSIAS THAT PEOPLE MISS AND
SO, IF YOU LOOK AT THIS PATIENT,
THIS PATIENT WAS SEEN IN
MULTIPLE DEFINITE CENTERS, ALL
IS CONSIDERED NONLESIONAL
PATIENT AND I'M NOT SURE IF IT
WAS JUST THAT WE HAD A BETTER
HYPOTHESIS OR THAT IMAGES WERE
GETTING BETTER OVER TIME BUT WE
WERE ABLE TO IDENTIFY LESION AND
WHAT YOU CAN SEE IS THAT IT'S
SIMILAR TO THIS LESION UP HERE
BUT IT'S JUST MORE SUBTLE BUT
THERE'S A LITTLE BIT OF LEARNING
AND SIGNAL CHANGES AND HYPER
INTENSITY BUT THIS IS A THING
THAT A PARTICULAR PERIOD OF
RADIOLOGISTS AND IT'S REALLY
EASY TO MISS THESE, AND YOU CAN
SEE THERE'S 1 WHERE THERE ISN'T
SO, SO THAT'S AN IMPORTANT
CONSIDERATION, ALSO.
HERE'S HISTOLOGIC LOAMACYY WHAT
WE KNOW IS HAPPENING, THIS IS A
NORMAL HAPPY 6 LAYEREDNY O
CORTEX, WHAT HAPPENS OVER HERE
IS IN THE MOST SEVERE FORM IS
YOU HAVE LOSS OF THAT 6 LAYERED
STRUCTURES, YOU HAVE DISLAM
NATION, UNDER IT YOU HAVE LOCAL
INFLAMMATION SO THERE ARE A LOT
OF HISTOLOGIC CHANGES THAT WE
KNOW ABOUT THAT ARE VERY WELL
DESCRIBED THAT WE CAN DETECT.
SO MY LAY MAN'S SUMMARY IS
HERE'S THE WHERE'S WALDO
PROBLEM.
IF SOMEBODY SAYS, OH, LOOK,
WALDO, YES, I SEE HIM BUT I
CAN'T FIND HIM OVER HERE.
SO OUR JOB IS CAN WE USE ALL
THIS NEW MACHINE LEARNING,
IMAGING, ALL THESE THINGS TO
BASICALLY POINT OUT EYE TO A
PLACE WHERE WE WOULD HAVE SEEN
IT IF WE HAD ALREADY LOOKED.
SO THERE ARE OTHER PEOPLE THAT
HAVE OBVIOUSLY DONE THIS ALSO,
WE CAME UP WITH THE NORMATIVE
MODELING THIS YEAR.
IT'S A LOT MORE ROBUST, REQUIRES
LESS TRAINING, WE DEFINITELY
BENEFITED FROM RESOURCESSA THE
NIH CLINICAL CENTER, INCLUDING
OUR COLLEAGUES AND SOME OF THE
PEOPLE IN THE OTHER IMAGING
CORES HERE, SO THIS WAS
DEFINITELY A GROUP EFFORT AND
NOT JUST FROM ME AS THE
EPILEAPTOLOGYIST BUT WHAT YOU
CAN SEE AT THE END OF THIS IS
THAT WE END UP WITH SIMILARITY
MAPS AND WE CAN ACTUALLY POINT
OUR EYE, THIS IS THE SAME
PATIENT, THIS IS THEIR LESION
LOCATION AND IT ACTUALLY SAYS,
HEY, JUST LOOK HERE WHICH TURNS
OUT TO BE VERY USEFUL IN OUR
PATIENTS, SO THIS THE OTHER MORE
OBVIOUS PATIENT I SHOWED YOU.
ONE THING WE LEARNED ABOUT THIS
IS THAT THERE'S AREAS OF THE
BRAIN THAT REALLY LOOK A LOT
LIKE FOCAL DISPLASSIA, O THIS
HAS HELPED US AVOID
FALSE-POSITIVES IN THOSE AREAS
WHEN WE LOOK AT IMAGES.
HERE'S ANOTHER PATIENT WHERE
THIS ABNORMALITY, WHEN YOU LOOK
BACK IT WAS MISSED ON MULTIPLE
PREVIOUS EVALUATIONS BUT OF
COURSE, NOW THAT I POINTED TO,
YOU'RE LIKE, OH YEAH, THERE IT
IS.
SO THIS HAS BEEN A HELPFUL TOOL
FOR US, WE ARE TRYING TO FIGURE
OUT THE ROLE OF 7 T IMAGING IS
IN HELPING FIND THESE
DYSPLASIAS, WE GET A BEAUTIFUL
POINT AT THIS PART WITH THE
DETAIL BUT AGAIN IT'S THE
WHERE'S WALDO PROBLEM, WHERE
THIS LOOKS ABNORMAL TO ME MAYBE
BECAUSE I LOOK AT THESE IMAGE IT
IS MORE ON THE 3 T MRI, THIS IS
THE SAMEOT 7 T MRI, BUT COMPARE
IT IT'S HARDER IF ARE ME TO TELL
WHAT'S NORMAL AND ABNORMAL SO I
THINK THIS IS AN ONGOING PROJECT
IN TERMS OF HOW THE 7 T IMAGES
FIT INTO THIS WHOLE STRUCTURAL
IMAGING PICTURE.
BUT I THINK WE'RE ALL VERY
EXCITED ABOUT THE POSSIBILITIES
OF IT AND SO THAT'S DEFINITELY A
FUTURE DIRECTION GOING FORWARD.
ALL RIGHT, SO I WILL TAKE A
BRIEF MOMENT TO TALK ABOUT
FUNCTIONAL ABNORMALITIES, I
THINK THESE CAN TELL US A LOT
ABOUT LOCAL PATHOLOGY IN THE
AREA OF THE EPILEPTOGENIC REGION
BUT THEY CAN ALSO BE USED TO
FIND EPILEPTIC REGION AND THIS
IS COMMONLY DONE.
WE KNOW THAT THERE ARE HUGE
CHANGES THAT HAPPEN AROUND THE
TIME OF THE SEIZURE VERY
ELEGANTLY HERE AS MY RED STAR
THING.
SO WHEN YOU LOOK AROUND THE TIME
OF A SEIZURE, THERE'S DEFINITELY
HUGE LOCAL CHANGES IN THE
TISSUE.
SO THERE'S HYPER ACTIVATION OF
NEURONS, THERE'S VASE O
DILATION, INCREASED CEREBRAL
BLOOD FLOW, INFLATION, BLOOD
BRAIN BARRIER BREAK DOWN,
THERE'S A WHOLE LOT WHEN THESE
COME TOGETHER AND A HUGE
SYNCHRONOUS FIRING EVENT.
WE KNOW THIS THROUGH ROUTINE
CLINICAL PRACTICE USING IMCANCER
CENTERING SO THIS LOOKS AT
PROFUSION AND YOU CAN SEE THAT
IN BETWEEN SEIZURES AND THIS
PATIENT, THAT'S AN EXAMPLE,
THERE'S HYPOPROFUSION, SO
THERE'S THIS INTER-ICTAL,
PERIOD, AND WHEN YOU DO THE
SUBTRAPGZ IMAGES YOU CAN
LOCALIZE THE AREA OF SEIZURES
ASK IT REQUIRES SOMEBODY SITTING
AND PATIENTS WE WAIT DAYS OR
WEEKS TO SEE A SEIZURE SO WE
REALLY, THE USE OF
THIS--ALTHOUGH IT'S AMAZING THIS
IS LIMITED TO CENTERS WITH A
VERY WELL TRAINED STAFF, WHO CAN
GET THIS INJECTION IN AND IN
PATIENTS WHO HAVING FREQUENT
SEIZURES.
PET IMAGES WE ALSO DO
INTERICTALLY, WE SEE
HYPOMETABOLISM, SO WE USE FTG
PET, AND ACTUALLY IN WORK HERE
WITH BILL AND BOB AND PETER,
THERE'S BEEN A WHOLE BUVEN OF
PET LIGANDS THAT HAVE BEEN USED
THAT FOUND INTERESTING MARKERS
OF INFLAMMATION AND OTHER
MARKERS, HOWEVER, THE STANDARD
CLINICAL USE IS FTG PET AND
USUALLY THIS IS HOPE O METABOLIC
IN BETWEEN SEIZURES AND HYPER
METABOLIC AROUND THE TIME OF
SEIZURES.
ANYWAYS, SO OUR HYPOTHESIS WAS
CAN WE USE ASL WHICH IS AN MRI
ABOUT 6 MINUTE SEQUENCE,
NONINVASIVE TO AT LEAST
LATERALIZE EPILEPSY BETWEEN
SEIZURES ISSUES SO WHY DO WE DO
THAT WHEN WE KNEW IT WOULD WORK
WAY BETTER, WELL IT'S NOT REALLY
EASY TO IMAGE PEOPLE RIGHT
AROUND THE TIME OF SEIZURES,
TURNS OUT MOST OF THE TIME WHEN
WE KNOW THAT'S' HAPPENING MOST
OF THEM HAVE ELECTRODES ON THEIR
HEAD, THOAR MEAOF THELY NOT MRI
COMPATIBLE, SO IT'S DIFFICULT TO
GET THE IMAGES SO WE WANTED TO
KNOW IF WE COULD FIND A SIGNAL
INTERICTLY.
AND WE FOUND THIS IN TEMPORAL
LOBE EPILEPSY.
WHEN WE LOOK AT PATIENTS WITH
MEDIALIZE.
THE PROBLEM IS ALREADY KNEW THE
ANSWER, RIGHT?
BECAUSE THEY ALREADY HAD MEDIAL
TEMPORAL SCLEROSIS, SO WE FOUND
OUT IN TERMS OF PATHOPHYSIOLOGY
THAT YES, THERE IS INTERICTAL
HYPOPROFUSION ON THE SIDE OF THE
LESION BUT IN OUR NONLESIONAL
PATIENTS WHICH ARE THESE GREEN
PATIENTS, IT WAS ACTUALLY
COMPLETELY CEMET RICK.
IF YOU LOOK AT THE RAW SCORES ON
EACH SIDE ISSUES THE DARKER
COLOR ON THE SIDE, THE THIS IS
THE TEMPORAL LOBE, YOU CAN SEE A
HUGE DIFFERENT IN OUR PATIENTS
WITH THE SCLEROSIS, SHOWING
THERE ARE BLOOD FLOW CHANGES BUT
WHEN YOU LOOK AT OUR NONLESIONAL
PATIENTS, YOU CAN SEE THEY'RE
NEARLY IDENTICAL FROM SIDE TO
SIDE.
SO AGAIN, HYPOPROFUSE COMPARED
TO HEALTHY VOLUNTEERS BUT NOT
SOMETHING THAT WILL HELP US IN
AN INDIVIDUAL PATIENT TO TELL
WHICH SIDE THE SEIZURES ARE
COMING FROM IN THESE NONLESIONAL
PATIENTS.
SO WE'RE STILL LOOKING AT THAT,
WE THINK THERE'S SOME INITIAL
SUGGESTION THAT MAY BE AN
FCDs, THERE'S ALSO PROFUSION
CHAIVENLGS INTERICTALLY BUT
THAT'S ONGOING WORK WE'RE DOING
AND THEN I WILL SPEND THE REST
OF THE TIME I HAVE HERE, TALKING
TO YOU ABOUT SOME OF THE
NEUROPHYSIOLOGY WORK THAT WE'VE
BEEN TRYING TO DO AND TRYING TO
UNDERSTAND INTERICTAL EPILEPTIC
FORM ACTIVITY AND TO MAP IT IN
THE BRAIN WHICH MAKES SENSE
WHICH I WAS ACTUALLY AN EEG
PERSON BY TRAINING.
SO THERE'S A LOT OF WAYS THAT WE
HAVE IN HUMANS OF MAPPING
INTERICTAL ACTIVITY.
I LIKE THIS BECAUSE IT HAS
SPATIAL RESOLUTION COMPARED TO
TEMPORAL RESOLUTION, MANY OF YOU
WHO HAVE DONE NEURAL IMAGING
UNDERSTAND THAT ECOG, MEG AND
EEG ALL HAVE REALLY GOOD
TEMPORAL RESOLUTION, BUT THEY
DIFFER A LOT IN TERMS OF THEIR
SPATIAL RESOLUTION.
SO, THEORETICALLY ECOG HAS
BETTER SPATIAL RESOLUTION BUT
LESS COVERAGE WHEREAS EEG AND
MEG HAVE LESS SPATIAL RESOLUTION
BIEW WHOLE BRAIN COVERAGE SO
THERE'S A DEFINITE TRADE-OFF
THERE IN CASE YOU CAN ASK
SOMETHING THAT WAS USING EEG,
FMRI HAS THE BEST SPATIAL
RESOLUTION BUT THE TEMPORAL
RESOLUTION AND NOT THAT GOOD AND
PET IS A LITTLE WORSE ALSO,
OBVIOUSLY STRUCTURAL MRI HAS NO
TEMPORAL RESOLUTION.
SO WHAT DOES THIS LOOK LIKE?
I WANT TO GIVE YOU AN IMAGE SO
THAT YOU CAN SEE KIND OF WHAT IT
LOOKS LIKE ON EEG, SO THIS IS
SCALP EEG, WE HAVE STANDARDIZED
ELECTRODE PLACEMENTS.
THIS IS STANDARD MEDICAL STUDENT
KNOWLEDGE RIGHT, AND SO, IN
BETWEEN SEIZURES WHEN THE
PATIENT IS AT LEAST TO ALL
INTENTS AND PURPOSES,
SYMPTOMATIC WILL SEE THESE
MARKERS OF CORTICAL IRRITABILITY
APPEARS THROUGHOUT THE RECORD.
DURING THE SEIZURE, WE WILL SEE
THIS WHICH IS AN ACTUAL SEIZURE
ON EEG SO HAVE YOU THIS
INCREASING RHYTHMIC ACTIVITY IN
THE BRAIN SO THIS IS WHAT THAT
LOOKS LIKE IN A SCALP EEG.
WHAT DOES THAT LIKE LIKE ON
INTRA CRANIAL EEG.
I THINK YOU WILL SEE IT LOOKS
NOT THAT DIFFERENT ISSUES RIGHT?
SO ON INTRA CRANIAL EEG
RECORDINGS, THIS IS FOR DEPTHS
AND SUBDURANNAL ELECTRODES AND
YOU SEE IT'S VERY SIMILAR TO
WHAT WE SEE ON SCALP, EEG,
ALTHOUGH EACH OF THOSE IS ONLY
LOOKING AT THE VERY LOCAL AREA
AROUND ITS LOCATION, SIMILARLY,
SEIZURES DON'T LOOK THAT
DIFFERENT, EITHER.
WE KNOW THAT TO SEE IT ON SCALP
EEG, WE NEED ABOUT SOMEWHERE
BETWEEN 6 AND 20 SQUARE
CENTIMETERS OF OF THE INTRA
CRANIAL ELECTRODES TO EVEN TURN
UP ON THE SCALP SO WE DO HAVE
THAT BETTER SPATIAL RESOLUTION,
BUT YOU CAN SEE THE ACTIVITY
ITSELF REALLY DOESN'T LOOK THAT
DIFFERENT.
AND MEG WHICH I WILL TALK ABOUT
THE END OF THIS, WE GEAP HAVE
WHOLE BRAIN COVERAGE LIKE WE DO
WITH THE SCALP EEG AND AGAIN,
YOU SEE MOSTLY INTERICTAL
ACTIVITY BECAUSE OUR PATIENTS
USUALLY TOLERATE MEGS LASTING
ABOUT AN HOUR OR SO BUT NOT MUCH
LONGER SO WE VERY RARELY RECORD
SEIZURES.
AND IN OUR MEG, AGAIN WE HAVE
WAY MORE SENSORS BUT AGAIN YOU
SEE THE SPIKE IN WAVE ACTIVITY.
SO NO MATTER WHICH WAY WE RECORD
IT, THE ACTIVITY LOAMACY BEINGS
SIMILAR AND GOING BACK TO THAT
LIEWTERS MODEL OF THINKING ABOUT
THIS, WHY DON'T WE JUST USE
INTERICTAL ACTIVITY ALL THE
TIME?
SO USUALLY INTERICTAL ACTIVITY,
INVOLVES THE SAME AREA AS WHERE
THE SEIZURES START BUT OFTEN
TIMES INVOLVES A MUCH BROADER
REGION AND THEY CAN ALSO BE
MULTIPLE POPULATIONS SOME OF
WHICH NEVER GO ON TOEN GENERATE
SEIZURES, SO THE IRRITATED ZONE,
AND CAN BE CONSIDERED A
RELATIVELY LESS SPECIFIC MARKER
OF THE SEIZURES ARE COMING FROM
AND THAT'S WHY WE STILL BOTHER
TO TRY TO RECORD SEIZURES.
SO WHY IS IT A NONSPECIFIC
MARKER?
SO 1 REASON THAT IT'S
NONSPECIFIC IS BECAUSE WE CAN
HAVE MULTIPLE POPULATIONS OF
DISCHARGES.
THE OTHER REASON THAT IT'S A
NONSPECIFIC MARKER IS BECAUSE
THIS EPILET ACTIVITY PROPAGATES,
RIGHT?
SO IT PRES FROM WHEREVER THE
SOURCE IS TO OTHER AREAS OF THE
BRAIN.
THE PROBLEM THAT WE HAVE WHEN
STUDYING PEOPLE IS THAT WE DON'T
KNOW WHAT AREA IT IS THAT WAS
STARTING OFF THIS ACTIVITY,
RIGHT IN SO WE LOOK BACK TO
ANIMAL MODELS AND WHEN YOU LOOK
AT AN ANIMAL MODEL WHERE THEY
KNOW THEY SET OFF THE SEIZURE,
RIGHT IN THAT WHAT THEY SEE IS
THAT THIS ACTIVITY DOES INFACT
SPREAD, AND IT SPREADS IF THEY
STARTED THE SEIZURE HERE, IT
SPREADS RADIALLY, SO LONG THE
CORTICALE SURFACE WHICH ISN'T
SURPRISING, THAT'S KIND OF THE
MENTAL MODEL MOST OF US HAVE BUT
GOING BACK TO THIS NETWORK IDEA,
IT ALSO SPREADS ALONG WHITE
MATTER PATHWAYS, AND THOSE CAN
BE VERY DISTANT, RIGHT?
SO WE CAN GET THESE
DISCONTIGUOUS AND TIMES OF
ACTIVATION DURING INTERICTAL
ACTIVITY AND SEIZURE ACTIVITY.
SO THEY BOTH FOLLOW SIMILAR
SPREAD PATTERNS, HERE'S MY
BEAUTIFUL CIRCLE DIAGRAM THAT
KEEPS IT SIMPLE FOR MYSELF, SO
IF THERE'S A SEIZURE FOCUS IT
CAN TRAVEL ALONG THIS GRAY
MATTER SURFACE, IT CAN TRAVEL TO
WHITE MATTER AND THE THING THE
MOUSE MODEL DOESN'T ADDRESS IS
WE STILL DON'T UNDERSTAND THE
ROLE OF THE SUBCORTICALE
STRUCTURES EITHER WHICH ARE
INTERESTING AND BECOMING
INCREASINGLY OF INTEREST AS WE
TALK ABOUT NEUROMODDULATION.
ALL RIGHT, SO AGAIN I MENTION
THIS BUT I WANT TO BRING IT UP
AGAIN, SO IF WE THINK OF THE
SEIZURE ACTIVITY AS SPREADING
LOCALLY AND DISTANTLY OVER WHITE
MATTER PATHWAYS, CAN YOU SEE
THIS IS WHERE THE SPARSE SPATIAL
SAMPLING, BECOMES PROBLEMATIC
FOR US AND WHERE THIS INITIAL
HYPOTHESIS IS SUPER IMPORTANT.
THE OTHER THING WE'RE THINKING
ABOUT AS WE THOUGHT ABOUT WHY
WE'RE SEEING THE SPIKE IN
ACTIVITY ALL OVER THE PLACE IS
HOW CAN THIS HAPPEN SO FAST AND
WHY CAN'T WE TELL THE
DIFFERENCE?
AND SOMETHING THAT'S IMPORTANT
TO RECOGNIZE IS EEG ACTIVITY WE
SEE, REALLY DOESN'T REPRESENT
ACTION POETIC TEBTIALS WHICH ARE
THE ACTUAL FIRING AND ACTIVE
PART WHEN IT REALLY REPRESENT
SYSTEM RECEIPT OF SIGNATURES NOX
FAMILY ACTIVATOR, SO, EVERY
NEURON, SO THE ACTION POTENTIAL
WOULD COME DOWN FROM HERE,
RIGHT, BUT THEY'RE ALL RECEIVING
SIGNALS FROM EVERYWHERE IN THE
BRAIN, ALL THE TIME.
RIGHT IN AND THIS IS HOW IT
INTEGRATES AND THEN FIRES IF YOU
REMEMBER THAT, SO THIS IS THE
INTEGRATION IS HAPPENING WITH
THESE POST SYNAPTIC POTENTIALS
WHERE YOU HAVE INHIBITORY AND
POST EXCITALLORY POTENTIALS THAT
SPREAD LOCALLY AND DISTANTLY AND
EACH NEURON GETS TONS OF THESE
AND SO WHEN THEY GET SYNCHRONOUS
ENOUGH, THEN WE SEE IT
NEUROPHYSIOLOGICALLY,
INTERACTIVITY.
SO, IN KEEPING WITH THAT, A
NUMBER OF GROUPS HAVE NOW BEEN
THINKING ABOUT MAPPING
INTERECTOMYOSINNAL DISCHARGES
USING THE IDEA THAT IT'S RECEIPT
OF SIGNAL, NOT GENERATED SIGNAL.
AND SO IN [INDISCERNIBLE] LAB
HERE, WE WORK CLOSELY WITH THEM
BUT THEY DEVELOPED THIS MODEL
WHERE YOU COULD TELL THE SOURCE
OF BOTH INTERICTAL ANDICTAL
ACTIVITY BY LOOK BEING AT TIME
DELAYS ACROSS SENSORS SO THIS
CAME FROM EARTHQUAKE DETENTION
IF THEY HAVE THEIR SENSORS
STATICALLY PLACED AROUND THE
COUNTRY, WHICHEVER SEES IT FIRST
IS THE CLOSEST BUT NOT
NECESSARILY WHERE THE EARTHQUAKE
STARTED SO WE CAN USE A SIMILAR
APPROACH TO LOCALIZE, OKAY, EVEN
THOUGH WE ONLY HAVE ELECTRODES
HERE AND HERE, WE CAN PUT ALL
THE INFORMATION TOGETHER ACROSS
THESE PATES TO REALIZE THE
SEIZURES ARE COMING FROM THIS
LOCATION EMPLOY THIS IS A WAY OF
DEALING WITH THE SPARSE SPATIAL
SAMPLING PROBLEM WE HAVE WITH
OUR INTRA CRANIAL EEGs AND WE
DID THIS WITH THEICTAL ACTIVITY
AND FOUND OUT YOU HAD SIMILAR
CASES IN BOTH REGIONS.
THE PROBLEM IS THIS IS A LOCAL
THING.
THEY CAN LOOK AT A REGION RIGHT
AROUND THE PLACE WHERE THEY'RE
SAMPLING BUT THEY CAN'T ACCOUNT
FOR PLACES WHERE WE'RE NOT
LOOKING.
SO ANOTHER GROUP TRIED TO DO
THIS WITH DTI AND WHITE MATTER
PATHWAYS AND SAID IF WE HAVE
THESE 3 AREAS AND THEY'RE
CONNEBBED ALONG WHITE MATTER
PATHWAYS CAN WE USE THIS FOR
WHITE MATTER FIBERS, SO THIS HAS
FUNDAMENTAL FLAWS IN IT, BECAUSE
I DON'T THINK THIS IS COMING
FROM THE JUNCTION OF WHITE
MATTER TRACKS IN THE MIDDLE OF
THE BRAIN BUT IT WAS 1 OF THE
FIRST TIMES HISEEN SOMEBODY TRY
AND INCORPORATE WHITE MATTER
INTO THIS LEADING AND LAGGING
THING.
SO SOMETHING WE DID IN OUR LAB
IS CAN WE USE OUR MULTIMODAL
DATABASE HERE AND TRY TO
INCORPORATE WHITE MATTER AND
GRAY MATTER PROPAGATION AND SO
THE WAY THAT THIS IS
TRADITIONALLY BEEN DONE AND THE
WAY I WAS TAUGHT TO DO IT AND
CLINICALLY WHEN WE'RE LOOKING
VISUALLY AT EEG, WHEN YOU SEE 3
ELET RODES HAVING SPIKES, YOU,A
SIEWM THE FIRST 1 IS THE SOURCE
OF THE ACTIVITY, PRETTY LOGICAL,
RIGHT, KIND OF LIKE THE ERGT
QUAKE THING WHERE THE FIRST 1
SHOULD BE CLOSER TO THE SOURCE
THAN THE FARTHER AWAY 1INGS BUT
WHAT WE FOUND IS LIEUSING
LITERALLURE FROM EVOKED
POTENTIALS AND INTRA CRANIAL
RECORDINGS AS WELL AS OTHER
LITERATURE, GRAY MATTER
CONDUCTION VELOCITIES ARE IN THE
RANGE AND WHITE MATTER
CONDUCTION IS MUCH, MUCH FASTER,
OKAY IN AND SO WHAT WE SAID IS,
OKAY, WELL, IF THE SOURCE IS
HERE, AND WE KNOW THERE ARE TIME
DELAYS AND WE KNOW OUR DISTANCES
ALONG THE CORTICALE SURFACE WE
SHOULD BE ABLE TO EXPLAIN ALL
THIS TIMES, RIGHT IN SO IF YOU
USE THAT LEADING ELECT ROAD
THEORY AND THIS IS AN EXAMPLE OF
PATIENTS THAT WERE INVOLVED IN
THE DISCHARGE, WHAT WE FOUND IF
YOU ASSUME THE SOURCES AT THIS
FIRST ELECTRODE, YOU COULD
EXPLAIN PROPAGATION TO 1 OF THE
OTHER EELECTRODE RODES WITH THE
TIMES WE OBSERVED.
THIS IS KIND OF THE HERTZ UNIT
MODEL.
WE SAID LET'S ASSUME THE SOURCE
COULD BE ANYWHERE AND WE'RE
RECEIVING SIGNAL, BUT WE WANT IT
TO SAY INSTEAD OF JUST RECEIVING
SIGNAL THROUGH THIS CORTICALE
TRAVELING WAY OF PROPAGATION,
LET'S SAY WHITE MATTER
PROPAGATION CAN ALSO HAPPEN, SO
SOUNDS LOGICAL SO FAR, RIGHT IN
SO WHEN WE DID THAT JUST LOOKING
FOR TRAVELING WAVE PROPAGATION,
YOU CAN HARDLY SEE IT BURIED IN
THE [INDISCERNIBLE] HERE, BUT
THIS IS THE SOURCE THAT BEST
EXPLAINED TIMING OF EACH OF
THESE 3 ELECTRODES, BUT WE
COULDN'T EXPLAIN WHERE WE WERE
SEEING A SPIKE IN THE FOURTH
ELECTRODE, BECAUSE IT WAS TOO
FAR AWAY.
LET'S SAY IT'S WHITE MATTER,
WHAT ANSWER DO WE GET WITH THESE
VELOCITIES AND ANSWERS WITH THE
D FI AND WE FOUND AGAIN WE
COULDN'T EXPLAIN THE LAST SPIKE
THAT WAS INVOLVED.
SO WHAT WE FOUND AND THIS IS
TRUE ACROSS ALL OF OUR PATIENTS
IS IF YOU ALLOW FOR WHITE MATTER
CONDUCTION AND/OR TRAVELING WAVE
CONDUCTION AND THIS ISN'T REALLY
A SURPRISE BUT HADN'T REALLY
BEEN DONE, YOU CAN FIND THAT
WILL EXPLAIN THE TIMING OF BY
FAR THE MOST SEQUENCES SO WHAT
WE THINK IS THIS GOES WITH WHAT
THE ANIMAL WORK SHOWED US IS
THAT WE SHOULD BE EXPECTING TO
SEE GRAY MATTER AND WHITE MATTER
PROPAGATION AND THAT SHOULD HELP
TO EXPLAIN, ALSO MAYBE EXPLAIN
WHY WE MISSED SOME OF THESE
LOCALIZATIONS.
SO IF WE'RE ASSUMING THE
LOCALIZATIONS ARE COMING FROM
WHERE WE PUT ELECTRODES, THAT'S
PROBABLY NOT A GOOD ASSUMPTION,
RIGHT?
AND THEN ALSO THE SURPRISING
THING THAT WE FOUND FROM THIS,
SO THIS IS THE COMBINED GRAY
MATTER AND WHITE MATTER ANSWER.
AND WE ALWAYS THOUGHT THAT THE
LEADING EELECTRODE RODE WILL BE
THE BEST ESTIMATE AND THAT'S
BECAUSE EVEN LOGICALLY WE WERE
TRAVELING ONLY WAVE
PROVEIGATION, SO IT TURNS OUT IF
YOU HAVE THESE COMBINED GRAY
MATTER AND WHITE MATTER
PATHWAYS, ACTUALLY THE WHEAT
MATTER IS SO MUCH FASTER THAT
THOSE SPIKES CAN TURN UP MUCH
EARLIER THAN THE 1S THAT ARE
MOVING KIND OF MORE SLOWLY AND
LOCALLY.
SO THIS IS ACTUALLY I THINK 1 OF
THE REASONS WHY WE SOMETIMES
HAVE MISS LOCALIZATION,
BASICALLY RELATED TO POOR
SAMPLING OF OUR ELECTRODES, WHEN
WE HAD DISTANT SOURCES LIKE
THIS, WE FOUND A LOT OF TIMES
THERE WERE 0 ELECTRODES IN THE
AREA WHERE THAT SOURCE WAS SO I
CAN'T PROVE THAT THESE ARE TRUE
BECAUSE WE ACTUALLY DIDN'T LOOK
THERE, AND IT TURNS OUT THIS
PATIENT HAD A RESECTION OF THEIR
ANTERIOR TEMPORAL REGION THAT
INCLUDE ALL THE SPIKING
CERTAINLY--CERTAINLY LECT RODES
AND DIDN'T BECOME SEIZURE FREE,
SO CAN YOU IMAGINE THAT THIS
WOULD HAVE A DIRECT IMPACT ON
OUR APPROACH.
SO WE SAID LET'S GO BACK TO OUR
RECORDINGS IN THESE PATES AND
SEE IF WE CAN SEE WHAT WE EXPECT
WHICH IS AND PROPAGATION AND
WHITE MATTER PROPAGATION, WHEN I
LOOK AT THIS, I ALREADY SHOWED
YOU THIS WHEN YOU LOOK AT IT,
THEY LOOK REALLY SIMILAR, WE
HAVE A WAY OF LOCALIZING THEM
WITH A DISCIPLINARY POLE MODEL
WHERE YOU EXPECT THE SOURCE IS
THE ACTUAL SOURCE, SOMEWHERE
BETWEEN THE AREAS OF NEGATIVE
AND POSITIVE APPLICATION.
SO THE CURRENT GOLD STANDARD IN
THIS PATIENT, I PUT IN THIS
VIDEO AND LET'S SEE IF IT WORKS
BUT WHAT I WANTED YOU TO SEE IS
WHEN WE DID A DRIEWBTED SOURCE
MODEL, SO WHEN MEG, IT'S
DIFFERENT THAN IN EEG, AND
DIFFERENT THAN INTRA CRANIAL EEG
AND YOU KNOW EXACTLY WHAT PART
OF CORTEX YOU ARE SAMPLING, ON
MEG, YOU HAVE THE OUTSIDE AND
YOU ARE USING MATHEMATICAL
MODELS TO INFER WHAT BRAIN
ACTIVITY IS GENERATING THAT
LOCATION, I THINK WE'RE ABOUT TO
GET TO THE SPIKE, SO DON'T
BLINK.
SO IT'S VERY QUIET AND THIS
SHOWS YOU HOW BIG AN OUTLIER
THIS SPIKING ACTIVITY IS, BUT
HERE IT IS, OKAY?
SO YOU CAN SEE THAT THE
DISCIPLINARY POLE MODEL WAS NOT
WRONG BUT IT WASN'T ENTIRELY
CORRECT, EITHER BECAUSE THIS
HIEWNL AREA OF BRAIN IS GETTING
INVOLVED IN THIS DISCHARGE AND
THIS IS WHAT WE TEND TO SEE, AND
YOU CAN SEE HOW THIS DOES GO
ALONG WITH THE TRAVELING WAVE WE
ARE TALKING ABOUT SO HAVE YOU
THIS BIG AREA OF ACTIVATION
THAT'S GROWING BUT IT'S A HUGE
AREA WHICH IS WHY WE THINK IT'S
NONSPECIFIC BUT IF YOU LOOK, THE
THING IEMG NOT SHOWING YOU FROM
THE MOVE SETHIS IS WHAT'S
HAPPENING IN THE
INTERHEMISPHERIC PART OF BRAIN.
SO THIS IS JUST AS BIG AN AREA
OF ACTIVATION HAPPENING SOME
PLACE WE WEREN'T EVEN LOOKING SO
IT'S TRUE THAT THIS ACTIVITY IS
NONSPECIFIC.
THIS PATIENT ACTUALLY GOT THIS
RESECTION AND BECAME SEIZURE
FREE AFTERWARDS SO IN FACT THE
DIPOLE WAS CORRECT BUT MAYBE NOT
A COMPLETE REPRESENTATION OF THE
ACTIVITY THAT'S HAPPENING.
SO 1 OF THE THINGS THAT WE'VE
BEEN DOING CAN THIS IS WORK
THAT'S HAPPENING IN MY LAB RIGHT
NOW WITH [INDISCERNIBLE], WE ARE
TRYING TO SEE CAN WE SEE THIS
GRAY MATTER AND WHITE MATTER
PROPAGATION, SO WHAT WE DID IS
WE SOURCE LOCAL EYATION TO GET
THESE DISTRIBUTED SOURCES AND
THEN JUST LOOKED OVER THE WHEEL
TIME COURSE OF THE SPIKE, IF YOU
ADD UP THE ACTIVITIES TO LOOK AT
THE AREA UNDER THE CURVE AND
PICK THE AREAS WITH THE BIGGEST
AREA UNDER THE CURVE SO WE'RE
NOT LOOKING AT LEADING OR
LAGGING OR ANYTHING ELSE, JUST
SAID WHERE'S THE MOST ACTIVATION
HAPPENING IN THIS GENERAL TIME
REGION AND YOU CAN SEE THIS IS A
DIFFERENT PATIENT.
CAN YOU SEE THE AREA UNDER THE
CURVE ALMOST FOLLOWS THE SAME
PATTERN WHERE THERE'S A BIG AREA
IN THE CURVE AND IT FALLS OFF,
THIS THRESHOLD SO THIS ACTIVITY
KEEPS GOING FOR QUITE A BIT.
THIS IS WHAT THEY LOOK LEAK.
YOU CAN SEE THIS IS THE AREA
WITH THE LARGEST--THIS IS THE
SENSOR WITH THE LARGEST AREA
UNDER THE CURVE BUT THESE OTHER
1S ALSO ARE FOLLOWING AND YOU
CAN KIND OF SEE THIS TIME DELAY
THAT WE'RE EXPECTING TO SEE.
WHEN WE TAKE THE AREA OF THE
CURVE AND GO OUTWARD FROM THE
VIRTUAL SENSOR WITH THE MAXIMUM
AREA IN THE CURVE, CAN YOU SEE
THE AREA IN THE CURVE IS FALLING
OFF, WHICH MATCHES WHAT YOU SEE,
WHERE THE END OF THE CURVE IS
GOING BACK TO THE YELLOW THINGS
AND WE SEE THIS PROPERIGATION IN
OUR MEG RECORRINGS WHICH IS
PRETTY COOL BECAUSE I DON'T
THINK ANYBODY'S TRIED TO TIE
THESE 2 THINS TOGETHER, THE
OTHER THING WE SAW THAT THE
PRIMARY CLUSTERS OVERLAP THE
RESECTION IN OUR ANGLE 1 PATIENT
WHO IS ARE SEIZURE FREE PATIENTS
IN ALMOST ALL OF OUR PATIENTS WE
LOOKED AT AND MOST OF THEM HAVE
THIS CORRELATION AT LEAST IN
THEIR PRIMARY OR LARGEST
CLUSTER.
AND THEN WHAT ABOUT THAT WHITE
MATTER PROPAGATION, SO I SHOWED
NUCLEOTIDES THE PATIENT WE SAW A
HUGE AREA OF ACTIVATION
LATERALLY AND HUGE AREA OF
ACTIVATION DISCONTIGUOUSLY
IMMEDIATELY, SO DOES THIS MAKE
SENSE THIS, IS WORK THAT'S JUST
HAPPENING RIGHT NOW.
AND WHAT YOU CAN SEE, IS THAT WE
ACTUALLY USE THIS THRESHOLD TO
SEE AT WHAT POINT THESE AREAS
BECAME ACTIVATED, IF YOU USE
THAT THRESHOLD TIME, WHAT YOU
CAN SEE ACROSS CLUSTERS IS THAT
THERE--THAT YOU'RE SEEING THE
GRAY MATTER TRACHING CAN
PROPAGATION LATER AND LATER WITH
ACTIVATION WITH EACH CLUSTER AND
YOU ARE ALSO SEEING SUBSEQUENT
CLUSTERS ACTIVATE AT LATER TIME
PERIODS RIGHT?
SO THIS SUGJEFFS THEY ARE MOST
LIKELY COMING FROM THE EARLIER
CLUSTER AND SPREADING ACROSS AND
WE SUSPECT IT'S CONTIGER
DATABASE USOUS, SO AGAIN, KIND
OF FOLLOWING WITH THE EPITHELIAL
RACRANIAL ACTIVITY, IF YOU LOOK
AT THE TIMING AND THE DISTANCES,
WE ACTUALLY SAW THAT SEVERAL OF
THESE AREAS IN THE PRIMARY
EARLIEST CLUSTER COULD EXPLAIN
BY DISTANCE AND TIMING
PROPAGATION TO THIS LARGER
CLUSTER.
SO WE THINK WE'RE SEEING
SOMETHING REALLY SIMILAR IN THE
MEG DATA WHICH IS KIND OF
SUPPORTING OUR THOUGHTS FROM THE
INTRA CRANIAL DATA.
OBVIOUSLY THERE'S MORE WORK TO
DO HERE AND I THINK IT'S
INTERESTING TO COMPARE WHAT
WE'RE SEEING IN THE MEG AND
INTRA CRANIAL DATA BUT I'M
HOPING THAT SOME DAY THAT WILL
HELP US TO PUT
CERTAINLY--CERTAINLY LET RODES
IN THESE AREAS OF PARTICULAR
INTEREST AND SO THAT WE WILL NO
LONGER BE HAVING THIS POTENTIAL
SOURCE WITH NO ELECTRODE THERE.
SO AS YOU CAN SEE HOW THAT WOULD
DIRECTLY LEAD TO MORE UTILITY IN
OUR INTRA CRANEICALRIA CORDINGS.
I WILL SAY THE MAIN PROBLEM WE
HAVE IS THAT IF WE'RE CORRECT
AND IF WE ACTUALLY IMPLANT THESE
AREAS THAT ARE SEPARATE, YOU
COULD IMAGINE WE WILL HAVE
ACTIVITY THAT'S SPREADING REALLY
FAST BETWEEN THEM AND SO THEN WE
WILL HAVE TO USE ALL THE FUN
TOOLS FOR THE PEOPLE WHO USE
EPITHELIAL RACRANIAL EEG CAN
GIVE US BECAUSE I THINK IT'S
GOING TO BE DIFFICULT TO
DISTINGUISH WHERE IT'S COMING
FROM AND WHERE IT'S GOING TO.
SO I THINK WE HAVE A LOT OF WORK
LEFT TO DO BUT I THINK THIS IS A
REALLY EXCITING AREA AND I'M
HOPING AND LOOK FORWARD TO
CONTINUING THIS AND I WANT TO
ACKNOWLEDGE ALL MY PEOPLE IN THE
GROUP AND COLLEAGUES WHO WE
WORKED WITH AND EVERYBODY IN THE
BRANCHES AND THE PATIENTS,
FAMILIES, MECH CORFACILLITY, MRI
CORE FACILITY AND ALL THE NURSES
WHO HELP TO TAKE WEAR OF THESE
PATIENT WHO IS CAN BE VERY
CHALLENGING, SO THANK YOU AND
HAPPY TO ANSWER ANY QUESTIONS.
[ APPLAUSE ]
>> IF ANYBODY HAS ANY QUESTIONS
YOU MAY APPROACH THE MICROPHONES
BUT 1 QUESTION I WANT TO START
OFF WITH BECAUSE I THINK IT'S
BECOMING MORE AND MORE PART OF
OUR CONVERSATIONS IS ESPECIALLY
WITH YOUR WORK INVOLVING
MULTIMODALITY, PHENOTYPING HOW
AI CAN COME INTO PLAY TO HELP
WITH THIS LOCALIZATION?
IT SEEMS LOAMACYIC IT WOULD BE
RIPE FOR THAT.
I DON'T UNDERSTAND IT BUT YOU
KNOW.
>> I THINK WE WERE TALKING ABOUT
AI IN SOME OF THESE THINGS SO AI
IS DEFINITELY PLAYING A ROLE
ALREADY, I THINK AI RIGHT NOW IS
REALLY GOOD AT TELLING PATIENTS
WHO ARE NOT GOING TO DO WELL AT
SURGERY.
BUT OUR FCU DETECTION WAS A
MACHINE LEARNING ALGORITHM
ALREADY, RIGHT, SO IMAGING AI IS
DEFINITELY ALREADY PLAYING A
ROLE AND THEN THE INTRA CRANIAL
EEG, A LOT OF PEOPLE ARE ALSO
DOING AI APPROACHES WITH IT BUT
MY WHOLE STILL HYPOTHESIS IS IF
WE DON'T PUT THE ELECTRODES IN
THE RIGHT PLACE IT'S GOING TO BE
HARD FOR AI TO FIND THE ANSWER
BECAUSE WE DON'T KNOW THE
ANSWER.
SO YOU HAVE TO TRAIN ON
SOMETHING, SO CAN YOU TRAIN ON
ANIMAL MODELS BUT APPROXIMATE
YOU DON'T NOT ANSWER IT BECOMES
REALLY HARD.
BUT WE'RE TRYING TO IMLESM AI
FOR A LOT OF REALLY MEG
APPROACHES AND USING INTRA
CRANIALLY EEG AND AI IS HERE AND
WILL CONTINUE TO BE HERE.
>> YOU MENTIONED AT THE
BEGINNING, YOU CAN CAN OFTEN SEE
WITHIN A YEAR IF A PATIENT IS
NOT GOING RESPOND TO FOLLOWING
AND QUALITY OF LIFE, SO?
>> YEAH, SO THIS IS I TOPIC NEAR
AND DAILY BASISSER TO MY HEART.
THE AVERAGE TIME I BELIEVE LAST
TIME I LOOKED FOR PEOPLE TO GET
REFER FOR EPILEPSY SURGERY IS
STILL BETWEEN THE TENT AND 20
YEARS SO IT'S A HUGE EFFORT THAT
WE'RE ALL MAKING TO EDUCATE
PEOPLE TO SAY, YOU DON'T NEED TO
WAIT 10 OR 20 YEARS.
PEOPLE SAY OH WELL THERE'S
ANOTHER MEDICINE THEY HAVEN'T
TRIED YET, BUT THERE CHANCE IS
SO LOW, RIGHT?
SO I THINK PEOPLE ARE GETTING
BETTER AT DOING THE TRIALS OF 2
MEDICINE AND THEN REFERRING
PEOPLE WHO HAVE CLEAR LESIONS
THAT THEY THINK ARE SAFE, OKAY?
SO I THINK THE NONLESIONAL
PATIENTS.
THEY'RE STILL RELUCTANT TO
REFER, WE A LOT OF PATIENTS THAT
TOLD US THEY'RE HUNDRED PERCENT
NOT A SURGICAL CANDIDATE IF
ANYBODY TRIES TO DO SURGERY,
THEY WILL BE A VEGETABLE,
THERE'S A LOT OF FEAR OF
NEUROSURGERY OUT THERE, SO THIS
IS SOMETHING WE'RE STILL
OVERCOMING TO A LARGE EXTEND AND
WE'RE HOPING THAT LECTURES LIKE
THIS AND OTHER LECTURES OUT IN
THE COMMUNITY WILL HELP PEOPLE
BE AWARE OF WHAT THEIR OPTIONS
ARE AND I THINK NEURAL
MODULATION IS PLAYING A HUGE
ROLE IN THIS, TOO, BECAUSE A LOT
OF PEOPLE FEEL SAFER WITH THE
IDEA OF A DEVICE THAN THEY DO
WITH THE IDEA OF A SURGEON
REMOVING SOME PART OF THEIR
BRAIN SO I THINK THAT'S KIND OF
OPENING PEOPLE'S EYES TO MAYBE
THE POSSIBILITIES AND THE HOPE
IS THAT ONCE THEY GET TO A LARGE
EPILEPSY SURGERY IS IT, WHERE
THEY CAN GET A COMPLETE
EVALUATION THEN WE CAN MAKE
DECISIONS ABOUT WHETHER THAT'S
ACTUALLY THE MOST APPROPRIATE
THING.
BUT MY MESSAGE TO EVERYBODY OUT
THERE IS IF YOU HAVE TRIED 2
MEDICINE AT FULL DOSES AND IT'S
NOT WORKING, YOU ARE BASICALLY
BECOMING A SURGICAL CANDIDATE.
SO WE TRY TO KEEP IT VERY
SIMPLE.
NANY OTHER QUESTIONS HERE, WE
HAVE A QUESTION FROM OUR
VIDEOCAST AUDIENCE: WHAT IS THE
ROLE OF AMPLATTORY MONITORING IN
EPILEPSY RESEARCH AND DIAGNOSIS?
>> YES, SO WE DON'T DO
AMBULATORY MONITORING HERE SO
ALL I KNOW IS TALKING TO MY
COLLEAGUES AND FELLOWSHIP WHICH
IS A LITTLE WHILE AGO BUT I
THINK IT'S AMAZING FOR THE RIGHT
QUESTIONS.
SO NOBODY UPONS TO SIT AND HERE
WHEN THEY'RE ESSENTIAL HEALTHY
AND WAIT FOR US TO MONITOR THEM
AND THEY FEEL GOOD AND THEY'RE
TRAP INDEED A HOSPITAL ROOM.
SO FIELD FUNCTIONS KNOW WHAT
YOU'RE SEIZURES ARE LIKE, AND
I'M WONDERING ARE YOU HAVING
SEIZURES YOU'RE NOT AWARE OF,
THEN AMPLATTORY MONITORING IS
GREAT.
WE HAVE THIS WITH LEFT TEMPORAL
LOBE PATIENTS WHERE A LOT OF
TIMES THEY ARE UNAWARE OF THEIR
SEIZURES AND IF THEY LIVE BY
THEMSELVES, THEY'RE HAVING TONS
OF SEIZURES AND DON'T KNOW IT OR
MAYBE THEY DON'T HAVE ANY AT
ALL.
SO IT'S LIKE A YES NO QUESTION.
IT'S LESS GOOD IF YOU'RE TRYING
TO DECIDE WHERE YOU WOULD LIKE
TO DO A SURGERY IN WHICH CASE WE
REALLY WANT THE VIDEO AND MORE
CONTROLLED SCENARIO, BUT I THINK
AMBULATORY EEG IS,A MAZING AND
IT'S A REALLY GOOD TOOL WHEN
USED IN APPROPRIATE SITUATIONS.
>> DR. INATI, THANK YOU VERY
MUCH FOR SHARINGIOURE WORK AND
YOUR INSIGHTS ANDY WOO LOOK
FORWARD TO HEARING ABOUT YOUR
WORK IN THE FUTURE.
THANK YOU FOR COMING OUT TODAY
AND WE'LL SEE YOU ALL NEXT WEEK.
[ APPLAUSE ]
>> THANK YOU SO MUCH.