Welcome to the Clinical Center Grand Rounds, a weekly series of educational lectures for physicians and health care professionals broadcast from the Clinical Center at the National Institutes of Health in Bethesda, MD. The NIH Clinical Center is the world's largest hospital totally dedicated to investigational research and leads the global effort in training today's investigators and discovering tomorrow's cures. Learn more by visiting us online at http://clinicalcenter.nih.gov OUR SPEAKER TODAY IS DR. MARK HALLET WHO IS AN NIH DISTINGUISHED INVESTIGATOR AND THE CHIEF OF THE HUMAN MOTOR CONTROL SECTION AT THE NATIONAL INSTITUTE NEUROLOGICAL DISORDERS AND STROKE AND AN INTERNATIONAL RECOGNIZED EXPERT IN MOVEMENT DISORDERS. DR. HALLET COMPLETED HIS BOTH HIS DEGREES FROM HARVARD UNIVERSITY. COMPLETED HIS MEDICAL RESIDENCY AT BRIGHAM AND RESIDENCY AT MASSACHUSETTS GENERAL HOSPITAL AND FELLOWSHIPS IN NEUROPHYSIOLOGY AT BOTHLET NIH AND THE DEPARTMENT OF NEUROLOGY AT THE INSTITUTE OF PSYCHIATRY IN LONDON, ENGLAND. BEFORE RETURNING TO THE NIH IN 1984, DR. HALLET WAS CHIEF OF THE PHYSIOLOGICAL LABORATORY AT BOSTON AND ASSOCIATE PROFESSOR AT HARVARD MEDICAL SCHOOL, AT NINDS HE SERVED AT THE CLINICAL NEUROSCIENCES PROGRAM AT THE DIVISION OF INTRAMURAL RESEARCH FROM 1987 UNTIL JULY 2000. DR. HALLET IS PAST PRESIDENT OF INTERNATIONAL FEDERATION OF CLINICAL NEUROPHYSIOLOGY AND THE INAUGURAL PRESIDENT OF THE NEWLY FOUNDED FUNCTIONAL NEUROLOGICAL DISORDER SOCIETY. HE HAS SERVED AS THE PAST PRESIDENT OF THE NEUROLOGICAL DISORDER SOCIETY AND EDITOR IN CHIEF OF CLINICAL NEUROPHYSIOLOGY. HE'S RECEIVED MANY AWARDS FOR ACADEMIC ACHIEVEMENT INCLUDING THE HERBERT H. JASPER AWARD FROM THE AMERICAN LYNNICAL NEW O PHYSIOLOGY SOCIETY AND A WORLD FEDERATION MEDAL FOR CONTRIBUTIONS TO NEUROSCIENCE RECENTLY IN OCTOBER 2019. HIS ONGOING RESEARCH FOCUSES ON THE PRINCIPLES OF MOTOR CONTROL AND THE PATHOPHYSIOLOGY OF MOVEMENT DISORDERS WITH A MAJOR FOCUS ON FUNCTIONAL MOVEMENT DISORDERS. WE NOW WELCOME DR. HALLET TO THE VIRTUAL PODIUM TO SPEAK ON FUNCTIONAL MOVEMENT DISORDERS PROGRESS. >> THANK YOU. THANK YOU VERY MUCH. I'M SORRY, YOU NEED TO--SHARING MY POWER POINT NOW, I THINK, IS THAT RIGHT? >> YES. >> ALL RIGHT. SO YOU CAN SEE THIS ALL RIGHT NOW? ALL RIGHT. VERY GOOD. SO, THANK YOU VERY MUCH FOR THAT NICE INTRODUCTION. AND I'M HAPPY TO TALK ABOUT 1 OF MY FAVORITE TOPICS, FUNCTIONAL MOVEMENT DISORDERS AND I'M GOING TO TALK ABOUT PROGRESS IN THE LAST FEW YEARS. THE REASON FOR THAT IS THAT I GAVE A LECTURE AT GRAND ROUNDS IN 2016, THE JOHN LAWS DECKER MEMORIAL LECTURE ON THIS SAME TOPIC IN 2016 AND I WILL FOCUS PARTICULARLY ON THE PROGRESS SINCE THAT TIME. I HAVE NOTHING RELEVANT TO DISCLOSE, THERE ARE NO DRUGS THAT I'M GOING TO BE DEALING WITH, AND THEN WE GET TO THE LEARNING OBJECTIVES OF THE LECTURE AND THEY ARE TO UNDERSTAND THE NATURE OF A FUNCTIONAL NEUROLOGICAL DISORDERS, TO APPRECIATE HOW TO DIAGNOSE FUNCTIONAL MOVEMENT DISORDERS SPECIFICALLY AND TO LEARN HOW TO APPROACH THE TREATMENT OF PATIENTS WITH FUNCTIONAL MOVEMENT DISORDERS I'M GOING TO BEGIN BY SHOWING YOU THIS PATIENT SEBT TO US FOR THE CONSIDERATION OF DEEP BRAIN STIMULATION FOR ESSENTIAL TRIEWMOR. SHE HAS BEEN BOTHERED BY TREMOR FOR ABOUT 20 YEARS. NO MEDICATION HELPED HER AND IF ARE THAT REASON AND THE FACAS ACCOUNT THAT IT WAS BOTHERSOME TO HER, THERE WAS A CONSIDERATION OF DEEP BRAIN STIMULATION SURGERY. SO WHAT I WILL SHOW YOU IN THIS VIDEOTAPE IS PART OF HER PHYSICAL EXAM NATION. SNOW NOW I WOULD LIKE TO YOU TAP WITH ME USING YOUR LEFT HAND. THERE YOU GO, RIGHT WITH ME. AND NOW YOU JUST KEEP TAPPING ON YOUR OWN. >> ALL RIGHT, SO WE CAN ASK THE QUESTION WHAT WAS THE MATTER WITH THIS PATIENT? AND OF COURSE, THAT'S VERY IMPORTANT TO MAKE A PROPER DIAGNOSIS BEFORE DECIDING ON THE THERAPY. HER NEUROLOGIC EXAM NATION EXCEPT FOR THE TREMOR YOU SAW WAS FULLY NORMAL. ALL LABBATORY TESTING WAS NORMAL INCLUDING NEUROIMAGING. THE TREMOR BEHAVED LIKE VOLUNTARY TREMOR AND WHAT WE MEAN BY VOLUNTARY TREMOR IS THAT VOLUNTEERS UP TARY TREMOR IS AN OS LATTERY MOVEMENT MADE BY A PERSON WITHOUT A TREMOR AND THAT'S WHAT WE REFER TO AS VOLUNTARY TREMOR AND IT DID NOT--SO IT BEHAVED LIKE THAT AND NOT LIKE ESSENTIAL TREMOR OR ANY OTHER KNOWN PATHOLOGICAL TREMOR. SHE WAS CAMABLE OF NORMAL FUNCTION AND THE TREMOR WAS INVOLUNTEERS UNSUPPORTED TAR NEUROECTODERMAL NATURE. COMPLETELY INVOLUNTARY TO HER, SO THE ANSWER OBVIOUSLY IS THAT SHE HAS A FUNCTIONAL MOVEMENT DISORDER WHICH HAD BEEN CALLED IN THE PAST PSYCHOGENIC MOVEMENT DISORDER. NOW FUNCTIONAL MOVEMENT DISORDERS ARE A TYPE OF FUNCTIONAL NEUROLOGICAL DISORDERS SO IT'S A SUBCLASS OF NEUROLOGICAL DISORDERS AND IT'S ANY MOVEMENT DISORDER CAUSED BY A BRAIN NETWORK DYSFUNCTION WHICH DOES NOT EXCLUDE THE POSSIBILITY OF NORMAL FUNCTION, SOMETIMES DUE IN PART TO PSYCHOLOGICAL CAUSE ON AND NOT EXPLAINED BY OTHER NEUROLOGIC PATHOLOGY THAT MAY OR MAY NOT BE PRESENT. SYMPTOMS MAY BE INCONSISTENT OR INCOMPATIBLE WITH OTHER KNOWN NEUROLOGICAL DISORDERS, HUMAN ANATOMY OR PHYSIOLOGY. AND THE NOTION OF FUNCTIONAL IS THAT IT'S A DISORDER OF A BRAIN NETWORK FUNCTION AND THAT'S WHERE THIS TERM COMES FROM. NOW FROM A--IN TERMS OF THE--SORRY, TO GO BACK 1 SLIDE HERE, IN TERMS OF THE CLASS OF DISORDERS, IT FALLS WITHIN THE DSM 5 CATEGORY OF SOMATICKICISM TONL AND RELATED DISORDERS AND THERE'S A LIST OF THEM HERE BUT THE PARTICULAR 1 IS 1 VERSION DISORDER, ALSO KNOWN IN DSM5 AS FUNCTIONAL NEUROLOGICAL SYMPTOM DISORDER SO A VERY SIMILAR TERM THERE. IN TERMS OF CONVERSION DISORDER, THAT PARTICULAR TERM IS A FREUDIAN 1, IT COMES FROM SIGMUD FREUD, IT WAS PRESUMABLY RESULTS IN A PSYCHOLOGICAL DISORDER AND THE PSYCHOLOGICAL DISORDER IS CONVERTED INTO THE SYMPTOM AS A WAY OF DEALING WITH THE DISORDER. AND THIS PARTICULAR CONVERSION IS WHAT'S CALLED THE PRIMARY GAIN OF CONVERSION, SECONDARY GAINS ARE THE BENEFITS OF BEING SICK. IT TURNS OUT THAT FUNCTIONAL DISORDERS, FUNCTIONAL NEUROLOGICAL DISORDERS ARE VERY COMMON AND THIS IS A VERY NICE EXAMPLE OF LOOKING AT WHAT TYPE OF PATIENT'S COME INTO NEUROLOGY CLINICS. THIS IS A REVIEW OF CLOSE TO 4000 NEW PATIENTS SEEN IN CLINICS IN THE UNITED KINGDOM BUT THIS IS THE LIST OF DIFFERENT TYPES OF DISORDERS THAT CAME IN AND BECAUSE THERE ARE A LOT OF THEM HERE, I'M JUST GOING TO BLOW UP THE TOP OF THE TABLE AND THE MOST COMMON DISORDER THAT NEUROLOGYSTS SEE IS HEADACHE, ACCOUNTING FOR 19% OF THE NEW PATIENTS BUT THE NEXT CATEGORIES OF DIAGNOSIS IS PSYCHOLOGICAL OR FUNCTIONAL ACCOUNTING FOR 16% OF THE DIAGNOSIS, MORE THAN EPILEPSY, AT 14%, PERIPHERAL NERVE DISORDERS AT 11% AND SO ON DOWN THE LINE. IN TERMS OF MORE EPIDEMIOLOGICAL INFORMATION, THE INCIDENTS OF FUNCTIONAL NEUROLOGICAL DISORDER SYSTEM ESTIMATED TO BE ABOUT 4-12 PER HUNDRED THOUSAND PEOPLE IN THE UNITED STATES. AND FUNCTIONAL MOVEMENT DISORDERS SPECIFICALLY 4-5 PER HUNDRED THOUSAND. PREVALENCE BEING ABOUT 50 PER HUNDRED THOUSAND. IN THIS ARTICLE THAT I SHOWED YOU BEFORE, WITH THE DATA ANALYZED SLIGHTLY DIFFERENTLY, 5.4% HAD A PRIMARY DIAGNOSIS OF FUNCTIONAL NEUROLOGICAL DISORDER AND IT WAS PART OF THE DIAGNOSIS IN 30%. SO ABOUT A THIRD OF THE CASES, THE ISSUES HERE OF FUNCTIONAL DISORDERS BECAME RELEVANT. ANOTHER IMPORTANT POINT IS THAT WOMEN ARE 60-75% OF THE PATIENT POPULATION AND THIS IS TRUE IN ALMOST ALL THE STUDIES THAT HAVE BEEN DONE AND WE WILL COME BACK TO THAT POINT A LITTLE BIT LATER BECAUSE THAT NEEDS TO BE EXPLAINED. IN TERMS OF THE IMPACT ON DISABILITY AND QUALITY OF LIFE, FUNCTIONAL NEUROLOGICAL DISORDERS AND IN PARTICULAR FUNCTIONAL MOVEMENT DISORDERS HAVE SIMILAR TYPES OF DISABILITY AND QUALITY OF LIFE AS PATIENTS WITH PARKINSON'S DISEASE. THIS IS A STUDY IN 2007, A LARGE GROUP OF PEASHTS WITH FUNCTIONAL MOVEMENT DISORDYS WITH PATIENTS WITH PARKINSON'S DISEASE, PHYSICAL DISABILITY, PHYSICAL LELGT AND WORSE LEVELS OF MENTAL HEALTH. RECENTLY, THERE HAS BEEN SOME ATTENTION EVEN TO MORTALITY OF PATIENT WHO IS HAVE FUNCTIONAL DISORDERS, THIS IS A PAPER ABOUT FUNCTIONAL SEIZURES WHICH STILL ARE OFTEN CALLED PSYCHOGENIC NONEPILEPTIC SEIZURES. THIS IS A VERY BIG STUDY LOOKING AT 5508 PATIENTS WITH VIDEO EEG, 674 OF THEM HAD FUNCTIONAL SEIZURES, 3000 + HAD EPILEPSY AND BOTH WERE SEEN IN 175 CASES. THE MORTALITY RATIO COMPARED TO INDIVIDUALS WITHOUT SEIZURES WAS 2.5 AND IT WAS VIRTUALLY THE SAME IN PATIENTS WITH EPILEPSY AND FUNCTIONAL SEIZURES. AT 20% OF THE DEATHS WERE DUE TO SUICIDE IN THOSE LESS THAN 50 YEARS OF AGE. SO THIS IS NOT A BENIGN CONDITION. THERE'S GREAT DISABILITY, PROBLEMS WITH QUALITY OF LIFE AND EVEN INCREASED MORTALITY IN THESE PATIENTS. NOW WHAT DO WE UNDERSTAND ABOUT THE ETIOLOGY? WHERE DO THESE COME FROM? AND THE WAY OF THINKING ABOUT THESE IS A MULTIFACTORIAL CAUSE THAT CAN BE THOUGHT OF IN TERMS OF A BIOPSYCHOSOCIAL MODEL. THE BIOCYCLE SOCIAL MODEL INCLUDES BIOLOGICAL FACTORS, SUCH AS AGE, GENDER, GENETICS, EPIGENETICS AND SO ON, PSYCHOLOGICAL FACTORS SUCH AS MENTAL HEALTH, EMOTIONAL HEALTH, BELIEFS AND EXPECTATIONS AND SOCIOLOGICAL LOGICAL FACTORS SUCH AS INTERPERSONAL RELATIONSHIPS, SOCIAL SUPPORT DYNAMICS, SOCIOECONOMICS AND STRESSES OF VARIOUS KINDS, INCLUDING EARLY LIFE AND CONTEMPORARY STRESS. AND I'M GOING TO REVIEW SOME OF THE INFORMATION THAT HAS BEEN LEARNED IN THE LAST FEW YEARS. FIRST TO POINT OUT THAT THE THESE BIOSOCIAL MODELS CAN INTERACT, THIS IS AN EXAMPLE BUT IT WILL BE RELEVANT FOR US. EARLY CHILDHOOD TRAUMA CAN LEAD TO CHANGES IN THE DEVELOPING BRAIN SUCH AS A SMALLER SIZE OF THE AMYGDALA AND ALSO EPIGENETIC CHANGES OF SPECIFIC GENOTYPES THAT WILL LEAD TO LESS RESILIENCE TO STRESS LATER IN LIFE, PROPENSITY TO ANXIETY AND DEPRESSION AS WELL AS THE DEVELOPMENT OF A FUNCTIONAL NEUROLOGICAL DISORDER. NOW THE FIRST THING I'M GOING TO MENTION TO YOU IS THAT WE HAVE RECENTLY BEEN ABLE TO IDENTIFY THE FIRST POLYMORPHISM THAT IS RELEVANT TO PATIENTS WITH FUNCTIONAL MOVEMENT DISORDERS AND THIS IS IN A PAPER HAS HAD JUST APPEARED. THS IS NOW PRIOR TO PRINT IN THE JOURNAL OF NEUROLOGY AND PSYCHIATRY AND STUDIED BY A MEMBER OF OUR GROUP CALLED [INDISCERNIBLE], THIS IS A TRANSCRIPT O FAN 2 GENE AND WE SHOW IT RELATES TO CHILDHOOD TRAUMA IN RELATION TO FUNCTIONAL MOVEMENT DISORDYS. SO THE 68 PATIENTS WE STUDIED WITH FUNCTIONAL MOVEMENT DISORDERS THEY WERE PREDOMINANTLY FEMALE AS IS CHARACTERISTIC OF THE DISORDER AS I POINTED OUT EARLIER, PRIMARILY CAUCASIAN WITH A MEAN AGE OF 46.7 YEARS, 53% REPORTED EXPOSURE TO CHILDHOOD TRAUMA. APPROXIMATE HERE ARE THE RESULTS THAT WE HAVE. THIS IS GOING TO DEAL WITH THE G703 T POLYMORPHISM IN THIS JEERN --GENE AND WE'RE LOOKING AT GG-HOMOZYGOTES AND THOSE THAT CARRY THE T-ALLELE EITHER TGOR TT. THIS GRAPH HERE LOOKS AT THE AGE OF ONSET OF THE PATIENTS AND THOSE THAT HAVE THE T-ALLELE HAVE AN EARLIER AGE OF ONSET THAN THOSE THAT ARE GG HOMOZYGOTES. ADDITIONALLY, IF 1 RELATES THE SYMPTOM SEVERITY. THOSE T-CARRIERS, THE MORE CHILDHOOD TRAUMA THAT THEY HAVE EXPERIENCED THE GREATER IS THE SEVERITY OF THEIR DISORDER. THIS IS NOT TRUE OF THE GG-CARRIERS. THIS IS RELATIVELY FLAT GRAPH IN THIS RELATIONSHIP. AND THE THIRD FINDING IS THAT THE T-CARRIERS EXHIBITED DECREASED RESTING STATE FUNCTIONAL CONNECTIVITY IN FUNCTIONAL MRI STUDY BETWEEN THE REORGANIZATION OF THE INSTITUTE AMYGDALA AND THE RIGHT MIDDLE FRONTAL GYRUS. SO, FROM THE RIGHT AMIG DUALA DUAL ATHESE 3 AREAS HAVE DECREASED CONNECTIVITY JUST IN THOSE CARRIERS OF THE T-ALLELE. SO THE IMPLICATION HERE IS THAT THIS POLYMORPHISM IS ASSOCIATED WITH AN EARLIER AGE OF ONSET, SIGNIFICANT INTERACTION WITH CHILDHOOD TRAUMA IN PREDICTING WORSE SYMPTOM SEVERITY. NOW WHAT DOES THIS GENE DO? IT ENCODES A NEURON SPECIFIC ENZYME CATALYZING THE RATE LIMITING STEP IN SEROTONIN SYNTHESIS, AND SEROTONIN TURNS OUT NOW TO BE RELEVANT IN PATIENTS WITH DIFFERENT SOMATIC DISORDERS, THERE'S A VERY INTERESTING PAPER WRITTEN AND PUBLISHED HERE IN 2019 AND THE ANNALS OF NEUROLOGY SHOWING THAT A SNPOT AADC GENE WHICH ENCODES AN ENZYME IMPLICATED IN THE SYNTHESIS OF SEROTONIN HAS BEEN ASSOCIATE WIDE GREATER FREQUENCY OF SOPHISTICATED MAT O FORM SYMPTOMS IN PATIENTS WITH TEMP ROW MANDIBULAR DISORDERS. SO OVERALL STRATEGY HERE WE HAVE THE FIRST ELEMENT IN THE BIOLOGY IN TERMS OF GENETICS RELEVANT TO THIS ENTITY. NOW IN RELATION TO CHILDHOOD TRAUMA, WHICH I'VE ALREADY NOW MENTIONED A COUPLE OF TIMES, THIS HAS BEEN LOOKED AT IN A NUMBER OF STUDIES, THIS IS A META-ANALYSIS THAT APPEARED IN 2018 THAT INCLUDES A NUMBER OF STUDIES INCLUDING OURS FROM THE NIH, EXPW IN THIS GRAPH HERE ANYTHING TO THE RIGHT INDICATES MORE IN THE PATIENT'S WHO HAVE FUNCTIONAL NEUROLOGICAL--AND HERE IS CHILDHOOD EMOTIONAL NEGLECT, CHILDHOOD SEXUAL ABUSE, CHILDHOOD PHYSICAL ABUSE, ALL MORE IN THE PATIENTS THIS IS ALSO TRUE IN ADULT LIFE. ADULT EMOTIONAL ABUSE, SEXUAL ABUSE AND PHYSICAL ABUSE. SO THIS DOES APPEAR TO BE A RELEVANT SOCIOLOGICAL LOGICAL FACTOR IN THIS THIS ENTITY. NOW I MENTIONED I WAS GOING TO GO BACK TO THIS ISSUE OF SEXUAL PREPONDERANCE OF WOMEN MORE THAN MEN. AND WE WERE WONDERING WHETHER THE ISSUE OF CHILDHOOD TRAUMA WAS RELEVANT IN THIS REGARD, SO THIS IS THE STUDY OF THE NIH PATIENTS PLUS PATIENTS FROM KATHRYN LAFAVOR AT THE UNIVERSITY OF LOUISVILLE THAT WAS PUBLISHED LAST YEAR. NOW IN TERMS OF LOOKING AT A HISTORY OF SEXUAL ABUSE PARTICULARLY, LOOKING AT WOMEN AND MEN, THE FREQUENCY WAS 48% IN WOMEN COMPARED TO NORMAL NONAFFECTED CONTROLS OF 16%. AND IN MEN, IT WAS 9.3% COMPARED TO NONAFFECTED CONTROLS OF 7.14%. SO, A MUCH GREATER INCREASE IN WOMEN COMPARED TO MEN OF SEXUAL TRAUMA AND MORE WITH RESPECT TO CONTROLS FOR WOMEN BUT NOT THAT MUCH FOR MEN. AND THEN THE SECOND QUESTION IS IF THERE IS SEXUAL TRAUMA, WHAT IS THE PROBE DEVELOPMENT CATALOG OF EXCUSE MING DOWN WITH THE FUNCTIONAL MOVEMENT DISORDER AND IN WOMEN, THE ODDS RATIO OF THAT WAS 4.82 COMPARED TO MEN WITH AN ODDS RATIO OF 1.33. SO NOT ONLY IS THERE MORE FREQUENT SEXUAL ABUSE IN WOMEN, BUT THE CHANCES OF DEVELOPING A FUNCTIONAL MOVEMENT DISORDER AFTER SEXUAL TRAUMA IS MORE IN WOMEN THAN IN MEN. SO THIS IS AT LEAST 1 OF THE ASPECTS THAT LEADS TO GREATER FUNCTIONAL MOVEMENT DISORDERS IN WOMEN COMPARED TO MEN. IN TERMS OF PSYCHOLOGICAL FACTORS, THERE IS IN OUR OWN POPULATION HERE AT THIS TIME, WE WERE CALLING IT PSYCHOGENIC MOVEMENT DISORDERS, THIS WAS ALMOST 10 YEARS AGO, WE COMPARED TO HEALTHY VOLUNTEERS IN PATIENTS WITH FOCAL HAND DYSTONIA, WHICH IS ANOTHER LARGE GROUP IN OUR LABORATORY, IN TERMS OF MAJOR DEPRESSION OR MAJOR GENERALIZED ANXIETY DISORDER, THERE ISN'T AN INCREASE IN THE--IN OUR PATIENTS, BUT IN TERMS OF MILDER DEPRESSION AND ANXIETY, THIS IS IN FACT INCREASED IN OUR PATIENTS WITH FUNCTIONAL MOVEMENT DISORDERS COMPARED BOTH TO HEALTHY VOLUNTEERS AND TO PATIENTS WITH FOCAL HAND DYSTONIA. ONE LAST BIT OF BACKGROUND IN THIS REGARD GOING BACK NOW TO THE BIOLOGICAL ASPECTS, WE HAVE DONE A VOXALL BASED MORPH ORDER OF MICRONSETRY STUDY OF FUNCTIONAL MRI AND FUNCTIONAL MOVEMENT DISORDER CASES. THIS WAS PUBLISHED A COUPLE YEARS AGO. AND WHAT THIS SHOW SYSTEM THAT THERE IS AN INCREASE IN GRAY MATTER IN THE LEFT AMYGDALA, LEFT PUTAMEN, LEFT KAWDATE AND BILATERAL THAT --THALAMI, NOW THIS IS NOT PICKED UP ON A STRUCTURAL MRI, SO IT'S NOT PICKED UP IN A USUAL BASES BUT ON AVERAGE THERE IS IN FACT ABNORMAL FINDINGS IN THIS STRUCTURAL MRI ITSELF. SO AS YOU CAN SEE HERE, THERE ARE A VARIETY OF ABNORMALITIES IN THE BASIC BIOLOGY, PSYCHEICOLOGY AND SOCIOLOGY OF PATIENTS AND BECAUSE OF THEIR INTERACTIONS THERE ARE THESE MULTIFACTORIAL FACTORS THAT LEAD TO FUNCTIONAL MOVEMENT DISORDERS AND FUNCTIONAL NEUROLOGICAL DISORDERS IN GENERAL. SO I'M NOW GOING TO SHIFT TO GENERAL PRINCIPLES OF DIAGNOSIS. AND, IN THE DEFINITION ITSELF,--AND INCONSISTENCY HERE MEANS INCONSISTENCY IN TIME THAT IT IS PRESENT AT 1 TIME AND NOT ANOTHER OR IT COULD BE VARIABLE IN INTENSITY AT 1 TIME OR ANOTHER. INCONGRUENSEL REFERS TO INCONGRUENCE WITH OTHER--WITH ANY OTHER NEUROLOGICAL DISORDER OR HUMAN ANATOMY AND PHYSIOLOGY. IT JUST DOESN'T MAKE ANY SENSE. ANOTHER GENERAL PRINCIPLE IS THAT IT'S THESE DISORDERS TEND TO BE P A ROXYSMALL, THEY ALSO TEND TO BE DISTRACTIBLE, THAT MEANS IF SOMEONE'S ATTENTION IT PULLED ARK WAY FROM THE DISORDER IT MAY WELL IMPROVE, ON THE OTHER HAND IT CAN BE SUGGESTIBLE, IF 1 FOCUSES ATTENTIONOT DISORDER THEN IT TENDING TO INCREASE. NOW OF COURSE, NOTHING HERE IS ABSOLUTELY A DIAGNOSTIC FEATURE, EVERYTHING HAS TO BE TAKEN WITH A GRAIN OF SALT, THERE ARE OFTEN EXCEPTIONS BUT THESE ARE VERY GOOD GUIDELINES FOR MAKING THE DIAGNOSIS. OTHERWISE, AND I WILL POINT THIS OUT ON SUBSEQUENT SLIDES THERE ARE IMPORTANT POSITIVE FEATURES THAT LEAD TO THE DIAGNOSIS OF INDIVIDUAL TYPES OF FUNCTIONAL MOVEMENT DISORDERS. AND I'M GOING TO FOCUS HERE AS IS THE FOCUS THAT WE HAVE THESE DAYS ON TOZ 55 FEATURES MAKING THE DIAGNOSIS OF A FUNCTIONAL DISORDER IS NOT A RULE OUT, - IT IS A RULE IN AND ON THE POSITIVE FEATURES IT WILL MAKE THE DIAGNOSIS. SO WITH FUNCTIONAL TREMORS THE MOVEMENTS TEND TO BE COMPLEX RATHER THAN SIMPLE IN A PARTICULAR PLANE, VARIABILITY AND I MENTIONED VARIABILITY AS A GENERAL RULE BUT HERE THE VARIABILITY IS A FREQUENCY, DIRECTION AND AMPLITUDE OF THE TREMOR. IF YOU HAVE THE SAME FREQUENCY ON BOTH SIDES OF THE BODY, THIS ALSO IS AN ELEMENT OF FUNCTIONAL TREMORS, TREMORS LIKE PARKINSON'S TREMOR FOR EXAMPLE ARE NEVER THE SAME ON BOTH SIDES, AND THEN THERE IS ENTRAINMENT OR ALTERATION WITH RHYTHMIC TAPPING OF ANOTHER BODY PART, AND I SHOWED YOU THAT IN THE FIRST PATIENT THAT WE SAW IN THIS LECTURE. WE WERE GETTING HER TO ENTRAIN THE TREMOR BY RHYTHMIC TAPPING OF ANOTHER BODY PART. BUT I WANT TO YOU NOTE THAT CLINICAL NEUROLOGICAL PHYSICAL TESTING IN THESE PATIENT CANS MAKE THE FINDINGS MORE OBJECTIVE IF ANY OF THESE ARE UNCERTAIN ON CLINICAL PRESENTATION. SO NOW I WILL SHOW YOU A PATIENT OF A CLINICAL TREMOR, THIS 1 OF A DIFFERENT TYPE THAN THE OTHER 1. YOU CAN SEE THAT THIS IS A VERY COMPLEX TYPE OF TREMOR, IT IS P A RXYSMALL IN 98URE AND ANOTHER FEATURE IS THAT IT EXHAUSTS HER. SHE SIGHS LIKE YOU JUST SAW THERE, THAT SIGHING IS SOMETIMES CALLED THE HUFFING AND PUFFING SIGN AND IS SOMETHING THAT HAPPENS ALSO IN THESE PEASHTS. THEY GET EXHAUSTED OFTEN BY THE INVOLUNTARY MOVEMENTS. SO THE NEXT FEATURE I WANT TO TALK ABOUT IS THE FUNCTIONAL MYOCLONEUS, WE LOOK FOR FEATURES FOR ORGANIC MYOCLONUS, AND 1 OF THESE IMPORTANT REGARD IS LONG OR VARIABLE LATENCY FOR STIMULUS INDUCED JERKS. OFTEN YOU CAN INDUCE MYOCLONUS WITH A TAP TO THE TENDON OR A TAP TO THE FINGERS AND IF THE LATENCY IS LONG OR VARIABLE THAT WOULD BE CONSIST WENT FUNCTIONAL MYOCLONUS, ANOTHER INTERESTING FEATURE ARE THE ANTICIPATORY JUNKS THAT COULD BE STOPPED BY TENDON HAMMER JUST SORT SHORT OF CONTACT. IF YOU STOP THE TENDON HAMMER JUST SHORT OF CONTACT, CAN YOU HAVE A PARTICIPATORY JERK THAT SHOWS IT'S NOT ACTUALLY SOMATOSENSORY MY O CLONUS. SO SOME OF THE PATIENTS HAVE BEEN--CRITICAL NEUROPHYSIOLOGY HERE CAN BE PARTICULARLY USEFUL IN PART TO DEMONSTRATE LONG LATENCY AND VARIABILITY WHICH IS SOMETHING THAT YOU MIGHT BE ABLE TO PICK UP CLINICALLY BUT YOU CAN CERTAINLY PICK IT UP WITH CLINICAL NEUROPHYSIOLOGY. AND THERE'S ALSO A FINDING THAT 1 CANNOT DO CLINICALLY, THAT'S TO LOOK AT THE EEG ACTIVITY PRIOR TO THE MYOCLONUS AND THERE'S AN EEG POTENTIAL CALLED THE BEREITSCHAFTSPOTENTIAL OR THE READINESS POTENTIAL AS IT CAN BE ANOTHER FACTOR THAT DEMONSTRATES IT IS FUNCTIONAL. LET ME SHOW YOU SOME VIDEOTAPES THIS A PATIENT THAT HAS THE APPEARANCE OF AN EXAGGERATED STARTLE AND IF THERE IS A SUDDEN SOUND OR A SUDDEN SHE WILL HAVE THIS MOVEMENT AND IT WILL ALSO HAPPEN SPONTANEOUSLY AS IT IS HAPPENING HERE AND EVEN IF SHE KNOWS THE SOUND IS COMING WHICH WE WILL DEMONSTRATE IN A MOMENT, SO IT IS NOT REALLY TOTALLY SURPRISING. IT WILL STILL INDUCE A FUNCTIONAL MYOCLONIC MOVEMENT. IT'S COMING IN JUST A SECOND HERE. SO SHE KNOWS IT WAS COMING BUT IT STILL OCCURS. SO THIS IS A VERY TAPEICAL, THIS IS AN EXAMPLE OF THE ANTICIPATORY JERKS. SHE HAD SOMATOSENSORY INDUCED MYOCLONUS, I COULD INDUCE IT BY STOPPING SHORT, USUALLY THAT JUST CS ONCE BUT THIS PARTICULAR PATIENT IT OCCURRED MULTIPLE TIMES AS YOU SAW. IT'S ALSO VERY UNUSUAL TO HAVE MY O CLONEUS IN THE LEFT ARM INDUCED BY STIMULI ALL OVER THE BODY AND THIS IS SOMETHING THAT THE CASE OF HER, THIS IS VERY UNUSUAL AND AGAIN A MANIFESTATION OF A FUNCTIONAL MYOCLONUS. >> OKAY, SO THE NEXT ENTITY I WILL TALK ABOUT IS FUNCTIONAL DYSTONIA, FUNCTIONAL DYSTONIA DOES REMAIN DIFFICULT FOR US AND FOR MOST CASES WE RELY ON GENERAL PRINCIPLES. HOWEVER, THERE ARE SOME PATTERNS OF DYSTONIA WHICH ARE COMMONLY FUNCTIONAL. ONE OF THEM IS A FIXED DYSTONIA, ANOTHER IS PULLING OF THE MOUTH, POST-TRAUMATIC DYSTONIA IS ANOTHER 1 AND THEN, DYSTONIA ASSOCIATED WITH COMPLEX REGIONAL PAIN SYNDROME CAN OFTEN BE FUNCTIONAL AS WELL. AND LET ME JUST SHOW YOU AGAIN SOME OF WHAT THIS LOOKS LIKE VISUALLY. SO HERE IS SOME EXAMPLES OF POST-TRAUMATIC DYSTONIA. THERE COULD BE ABNORMAL FIXED POSTURES OF THE FOOT, OF THE HAND, OF THE SHOULDER COMING POST TRAUMA. AND MANY OF THESE ARE A FUNCTIONAL IN NATURE. NOW THE NEXT VIDEO THAT I'M GLG -GOING TO SHOW YOU IS A PATIENT WITH THE PULLING OF THE MOUTH. THIS IS INTERMITTENT THAT YOU WILL SEE BUT AGAIN THIS, IS QUITE CHARACTERISTIC OF A FUNCTIONAL DISORDER. >> WELL IT'S BEEN WORKING EXPW ALSO YESTERDAY, I WENT UP ON THE EFEXOR SO I'M THINKING THAT THESE GAPS IN MY SEIZURES WHICH I'M STARTING TO GET NOW, HAVE MORE TO DO WITH THE AFFECTS OF IT THAN THE [INDISCERNIBLE]. >> OKAY, OKAY. >> OR MAYBE IT'S BOTH TOGETHER. I HAVE NO WAY OF KNOWING. >> SURE. AND WHEN THESE HAPPEN, WHAT KIND OF THINGS-- >> ALL RIGHT, SO, YOU SAW THE INTERMITTENT PULLING OF THE MOUTH IN DIFFERENT DIRECTIONS THERE, THAT PARTICULAR MANIFESTATION IS ONLY FUNCTIONAL, IT HAS NOT BEEN SEEN IN ANY OTHER TYPE OF DYSTONIA. NOW WE'LL TALK ABOUT FUNCTIONAL PARKINSONISM, IN THESE PATIENTS. THERE IS EXTREME SLOWNESS THAT DOESN'T HAVE THE CHARACTERISTICS OF BRADY KIN EASIA IN PARKINSON'S DISEASE ITSELF. THERE COULD BE A TREMOR AT REST THAT DOES NOT IMPROVEMENT WITH MOVEMENT WHEREAS PARKINSON'S USUALLY DOES, THERE CAN BE THE-TRUE RIGIDITY, GEGENHALTEN IS RATHER TRUE THAN RIGIDITY. YOU HAVE THE SENSE THAT SOMEONE IS FIGHTING YOU RATHER THAN A CONSISTENT AMOUNT OF INCREASED RESISTANCE AND OF COURSE IN THE LABORATORY, 1 CAN DO A DAT SCAN WHICH IS A TEST FOR THE DOPAMINE TRANSFORTER THAT WILL ALWAYS BE POSITIVE IN PATIENTS WITH NORMAL PARKINSON'S DISEASE. INTERESTINGLY, THERE SEEMS TO BE A HIGH CO-CURRENCE WITH FUNCTIONAL PARKINSON'SISM WITH REGULAR PUCKERINSON'S DISEASE, THE EXPLANATION FOR THAT IS NOT COMPLETELY CLEAR. SO HERE'S A PATIENT WHO HAD RELATIVELY NORMAL LOOKING MOVEMENTS OR AS I WAS TALKING WITH HER, BUT THEN ASKING HER TO TAP HER FINGERS TOGETHER PRODUCED THIS EXTREME SLOWNESS THAT YOU CAN SEE HERE THAT IS VERY SURPRISING AND FOCUSING HER ATTENTION ON THE PARTICULAR ENTITY BRINGS OUT THE ABNORMALITY, ALSO YOU CAN SEE THAT INDUCED A CERTAIN AMOUNT OF FATIGUE IN HER BECAUSE THIS PARTICULAR TASK EXHAUSTED HERE. FUNCTIONAL GAIT DISORDERS ARE ALSO IMON. THEY CAN BE BIZARRE IN NATURE AND 1 VERY IMPORTANT CLUE IS THAT THE PEASHTS BALANCE IS DEMONSTRATED TO BE MUCH BETTER THAN CLAIMED. SO HERE'S AN EXAMPLE OF A PASHT WITH A VERY COMMON TYPE OF DISORDER. THIS IS THE BUCKLING KNEE PROBLEM, THE CLAIM HERE IS THAT THEIR BALANCE IS BAD BUT IN FACT, YOU CAN'T DO THIS WITH BAD BALANCE, YOUR BALANCE HAS TO BE GOOD IN ORDER TO DO THIS. ALL RIGHT, SO, THOSE ARE THE WAYS THAT 1 WITH MAKE THE DIAGNOSIS ON A POSITIVE FEATURES AND NOW WHAT I WOULD LIKE TO DO IS FOCUS A BIT ON THE PATHOPHYSIOLOGY. SO WE TALKED ABOUT ETIOLOGY BEFORE. THOSE ARE THE ROOT CAUSES OF A PARTICULAR DISEASE BUT THEN 1 NEEDS TO UNDERSTAND THE PATHOPHYSIOLOGY TO GET TO THE PHENOTYPE AND THAT'S WHAT WE'RE GOING TO BE LOOKING AT NEXT. SO I WANT TO DISCUSSION THE BRAIN'S INTENTION. THE BRAIN'S INTENTION IS WHAT PRODUCES A MOVEMENT. AND THERE ARE SENSORY INFLUENCES THAT COME FROM THE POSTERIOR HALF OF THE BRAIN, THERE ARE PLANNING FEATURES AND DECIDING FEATURES THAT COME FROM THE FRONTAL LOBE. THERE ARE BELIEFS THAT ARE PROBABLY LARGELY FRONTAL LOBE, ALTHOUGH THEIR INSTANTATION IN THE BRAIN IS NOT COMPLETELY CLEAR. REWARD MECHANISMS WITH DOPAMINE CAN GIVE RISE TO INTENTIONS, EMOTIONS FROM THE LIMBIC SYSTEM, AND MOVE FROM THE HYPOTHALAMUS AND THERE COULD BE NOISE IN THE BRAIN AND THESE LEAD TO AN INTENTION. NOW INTENTION SAYS LEAD TO MOVEMENT AND MOVEMENT IS PRODUCED IN THE PRIMARY MOTOR CORTEX AND THAT PRODUCES A MOVEMENT. AND IN ADDITION TO THEIR BEING THE BRAINS INTENTION PRODUCING THE MOVEMENT IT ALSO SENDS THE FEED FORWARD SIGNAL TO THE REST OF THE BRAIN SAYING THAT A MOVEMENT IS GOING TO BE CREATED AND THERE'S ALSO FEEDBACK FROM THE MOVEMENT THAT IS OCCURRING. AND THEN THERE BECOMES A NETWORK WHICH MATCHES FEED FORWARD AND FEEDBACK AND IF THE BRAIN HAS INTENDED AND WILLS SOMETHING AND IT ACTUALLY HAPPENS, THEN THERE IS THE SENSE OR THE QUALIA IN THE BRAIN OF "YOU WILLED IT AND I AM THE AGENT OF THE MOVEMENT" AND WILLING AND AGENCY ARE WHAT MAKES SOMETHING FEEL VOLUNTARY. IF YOU ARE THE AGENT OF THE MOVEMENT, THEN YOU ARE THE 1 THAT CREATED IT. AND IT AM CANS FROM THE FACT THAT YOU WILLED IT AND THAT IT ACTUALLY HAPPENED. NOW WHAT I WOULD LIKE TO NOW MENTION IS THAT THERE ARE SOME ABNORMALITIES HERE. THERE IS AN ABNORMAL BELIEF IN THE PATIENTS, IT'S CERTAIN BUT IT DOES AND IT'S VERY DIFFICULT TO GET PATIENTS OUT OF THE NOTION THAT THEY DO HAVE A SICKNESS OF SOME KIND. AND WHEN THE FUNCTIONAL NEUROLOGICAL DISORDERS MANIFEST, IT ACTUALLY SUPPORTS THAT INCORRECT BELIEF, SO YOU SET UP A POSITIVE FEEDBACK LOOP NOW ANOTHER ABNORMALITY IS AN EMOTIONAL PROCESSING AND THESE ARE DATA COMING FROM OUR LAB RATORSKPE BAKUGAN OUR PAPER LED BY VALERIE VU, THIS IS NOW AN OLD 1 ABOUT 10 YEARS AGO, WE SHOWED PATIENTS EMOTIONAL FACES EITHER FEARFUL OR HAPPY OR NEUTRAL, AND WE ASK THEM THOUGH TO SAY WHAT THE SEX OF THE PATIENT WAS, MALE OR FEMALE. BUT THE EMOTION THEMSELVES PRODUCES REACTION IN THE BRAIN AND IN THE AMYGDALA AND IN THIS CASE THE RIGHT AMYGDALA THERE WAS OVERACTIVITY IN THE PATIENTS COMPARED TO HEALTHY VOLUNTEERS. THEN WE ALSO IDENTIFIED THAT THE AGENCY PROCESS IS MALFUNCTIONING IN PATIENTS WITH FUNCTIONAL MOVEMENT DISORDERS. AND IN THIS STUDY, AGAIN, ABOUT 10 YEARS AGO, LED BY VALERIE VUN, THERE IS A IN THIS STUDY, WE DID A COMPARISON WITH PATIENTS WITH FUNCTIONAL TREMOR WHO ALSO VOLUNTARILY MIMICKED THEIR TREMOR. SO WE LOOKED AT THE FUNCTIONAL MRI, WITH THE TREMOR BEING VOLUNTARY AND INVOLUNTARY AND LOOKED FOR THE DIFFERENCE. AND THERE WAS AN AREA OF HYPOACTIVITY IN THE RIGHT TEMPORAL PARIETAL JUNCTION. THE RIGHT TPJ, THE RIGHT TEMPORAL PARIETAL JUNCTION IS A CRITICAL PLACE IN THE AGENCY NETWORK. SO GOING BACK TO THIS DIAGRAM OF THE BRAIN'S INTENTION, WE CAN SEE THAT THERE ARE ABNORMAL BELIEFS, PATIENTS HAVE THE SENSE OF THE--THE FACT THAT THEY ARE SICK AND THERE IS AN OVERACTIVITY OF THE LIMBIC SYSTEM, OVERACTIVITY OF THE EMOTIONAL SET UP IN THESE INDIVIDUALS. THERE MAY BE ABNORMALITIES IN OTHERS BUT WE HAVE IDENTIFIED THOSE AT LEAST IN THE THE HOMENT THAT FEED INTO THE BRAIN'S INTENTION. NOW GOING BACK TO THIS DECEMBER THEN, THE BRAIN'S INTENTION IS ABNORMALITIES NORNLAL. IT BECOMES ABNORMAL BECAUSE OF THE ABNORMAL FACTORS THAT ARE COMING INTO IT, AND BECAUSE THE INTENTION IS ABNORMAL THE FEET FORWARD SIGNAL WILL BE ABNORMAL AND NOT ONLY IS THE FEET FORWARD SIGNAL ABNORMAL BUT WE KNOW THAT THE QUALITY OF AGENCY BECOMING ABNORMAL BECAUSE THE INDIVIDUALS FEEL THAT THE MOVEMENTS ARE INVOLUNTARY THE MOVEMENTS ARE NOT VOLUNTARY TO THEM AND SO THIS NETWORK OF AGENCY WHICH INCLUDES THE RIGHT TEMP ROUGH ATOM PARIETAL JUNCTION IS ABNORMAL AND IT COULD BE ABNORMAL IN PART BECAUSE THE FEET FORWARD SIGNAL COMING TO IT IS ABNORMAL OR THERE COULD BE OTHER ELEMENTS OF ABNORMALITY WITHIN THE RIGHT TEMPORAL PARIETAL JUNCTION NETWORK ITSELF. SO WE HAVE A SENSE NOT ONLY OF THE ETIOLOGY OF THE PATHOPHYSIOLOGY OF HOW THESE DISORDERS COME ABOUT NOW THE LAST TOPIC THEY WILL DISCUSS IS THAT OF TREATMENT. BECAUSE AGAIN IN TERMS OF THE ISSUE OF PROGRESS THERE'S BEEN A GREAT DEAL OF PROGRESS IN THE TREATMENT CONSIDERATIONS IN THE LAST FEW YEARS AT THE TIME THAT I SPOKE 4 YEARS AGO, WE DIDN'T REALLY HAVE MUCH TO OFFER, THE PATIENTS, THINGS WERE BEING TRIED BUT WE DIDN'T KNOW HOW MUCH ANYTHING WORKED AND NOW WE HAVE SOME INTERESTING INFORMATION. SO THE FIRST ISSUE IS HOW TO TELL THE PATIENT WHAT'S WRONG AND THE SENSE THATEM PEOPLE HAD BEEN DEVELOPING WITH MORE AND MORE EXPERIENCE IN THE LAST FEW YEARS IS THAT THE DIAGNOSIS SHOULD BE DELIVERED AS ANY OTHER DIAGNOSIS. YOU HAVE A FUNCTIONAL NEUROLOGICAL DISORDER, YOU HAVE A FUNCTIONAL MOVEMENT DISORDER, QUITE SIMILAR TO YOU HAVE MULTIPLE SCLEROSIS, YOU HAVE--NOT UNUSUAL AND IN FACT IT'S VERY COMMON, MORE COMMON THAN MANY OF THE OTHER DIAGNOSIS. THIS HAS ALSO BECOME CLEAR THAT IT WAS HELPFUL TO SHOW THE PATIENT HOW THE DIAGNOSIS WAS MADE. I SHOWED YOU SOME OF THE TRICKS AND THE OBSERVATION OF THE POSITIVE FINDINGS AND IF YOU SHOW THE PATIENT THOSE AND TELL THEM THIS IS THE WAY WE MAKE THE DIAGNOSIS THEYER MORE KEEN TO BELIEVE IT. AND OF COURSE 1 OF THE OTHER THINGS THAT 1 CAN SAY IS THAT THE BRAIN ITSELF IS FINE, IT'S A SOFTWARE PROBLEM, NOT A HARDWARE PROBLEM, SOMETHING LIKE THAT, THAT IS OFTEN RECOGNIZED BY THE PATIENT. WE--AS THE TERM IMPLYING FUNCTIONAL THIS IS A FUNCTION, NETWORK DYSFUNCTION THAT THE BRAIN IS CAPABLE OF NORMAL FUNCTIONING, YOU JUST HAVE TO GET IT TO FUNCTION PROPERLY. SO I THINK THIS IS THE WAY TO TELL THE PATIENT WHAT'S WRONG AND THEN THERE MAY BE THE NEED FOR MULTIDISCIPLINARY TREATMENT AND THAT CAN BE PHARMACOLOGICAL IT CAN BE PSYCHOLOGICAL WITH THINGS LIKE COGNITIVE BEHAVIORIAL THERAPY, WITH THE HELP OF A PSYCHIATRIST IS VERY PREQUENTLY NEEDED IN THIS SITUATION. PHYSICAL THERAPY CAN BE HELP EMPLOY AND SOCIAL WORK OF COURSE CAN BE HELPFUL AS WELL AND QUITE IMPORTANT FOR SOME PATIENTS. SO LET ME SHOW YOU A COUPLE OF RECENT STUDIES THAT HAVE BEEN DONE THAT DOCUMENT THE FACT THAT SOME OF THESE TYPES OF THERAPY CAN BE VALUABLE. SO HERE'S A STUDY THAT WAS PUBLISHED JUST LAST YEAR, IN FUNCTIONAL TREMOR, USING COGNITIVE BEHAVIORIAL THERAPY COGNITIVE BEHAVIORIAL THERAPY WAS DELIVERED TO HALF THE PATIENTS IN IN PARTICULAR STUDY FOR 12 WEEKS AND THE PATIENTS WERE FOLLOWED. THIS WAS AN OPEN LABEL STUDY SO ALL THE PATIENTS WERE ACTUALLY TREATED, SO HERE IS A SCALE OF THE MOVEMENT DISORDER MEASUREMENT, PSYCHOGENIC MOVEMENT DISORDER RATING SCALE SCORE BEFORE THE INTERVENTION AND THIS WAS THE LEVEL HERE MEAN OF ABOUT 30 AND AFTER THE CBT, THIS IS RIGHT AFTER THE CBT, CAN YOU SEE IT'S MARKEDLY IMPROVED SO THEREYA A BIG CHANGE OF ABOUT 20-POINTS IN THIS SCORE. SEVENTY-THREE% OF THE PATIENTS WENT INTO FULL REMISSION. THIRTEEN% HAD A PARTIAL RESPONSE AND ANOTHER 13% HAD NO RESPONSE, COGNITIVE BEHAVIORIAL THERAPY TURNS OUT TO BE VERY USEFUL IN IT PARTICULAR SITUATION AS YOU CAN SEE AND HERE IS SOME EVIDENCE FOR THAT. THERE'S BEEN A NUMBER OF STUDIES OF PHYSICAL THERAPY AND THE PHYSICAL THERAPY HERE IS GENERALLY PSYCHOLOGICALLY SUPPORTED PHYSICAL THERAPY. BUT THIS HAS BEEN SHOWN IN A NUMBER OF STUDIES TO BE QUITE USEFUL THIS IS THE LARGEST STUDY THAT'S BEEN DONE. THIS IS A RANDOMIZED STUDY OF 60 PATIENTS, RANDOMIZED THROUGH INTERVENTION OR TREATMENT AS USUAL. NOW THE PHYSICAL THERAPY HERE WAS DELIVERED OVER 5 DAYS, THERE WAS JUST 5 DAYS OF TREATMENT AND THEN THE MEASURES WERE DONE AT 6 MONTHS. ACTUALLY DONE AT BASE LINE 1 MONTH AND 6 MONTHS THIS IS THE BASE LINE AND 6 MONTH FOLLOW UP DATA. THESE ARE ALL THE DIFFERENT MEASURES AND I'M JUST GOING TO SHOW YOU THE CRITICAL FEATURES HERE, THERE WAS A SUBSTANTIAL IMPROVEMENT IN PHYSICAL FUNCTION, THE WALKING TIME FOR 10-METERS AND THE FUNCTIONAL MOBILITY SCALE. AND HERE'S ANOTHER FIGURE AND TABLE FROM THAT PAPER. THIS IS LOOKING AT THE GLOBAL IMPRESSION SCALE AT 6 MONTHS AND MUCH IMPROVED 35% IN THE INTERVENTION GROUP, 0 IN THE CONTROL GROUP, 38% IMPROVED, 18% IN CONTROLS, NO CHANGE IN 24, 50, AND THE CONTROL GROUP WORSE 3 PERCENT, WORSE 21. CALL THE EQ 5 D5 L LOOKING AT A NUMBER OF FEATURES OF QUALITY OF LIFE AND YOU CAN SEE THAT THERE'S A BIG BOUNCE OF THOSE THAT HAD THE INTERVENTION AND IT STAYED UP FOR 6 MONTHS SO PHYSICAL THERAPY SEEMS TO WORK VERY WELL IN THESE PATIENTS NOW WHY DOES PHYSICAL THERAPY WORK SO WELL AND SO RAPIDLY I SHOWED YOU THAT COGNITIVE BEHAVIORIAL THERAPY, REQUIRED 12 INTERVENTIONS OR 12 WEEKS IN ORDER TO BE USEFUL AND HERE PHYSICAL THERAPY WORKED EXTREMELY WELL WITH 5 SESSIONS IN 1 WEEK AND HAD A BENEFIT THAT LASTED AT LEAST 6 MONTHS, AND THERE ARE I THINK 2 WAYS OF THINKING, 2 REASONS FOR THINKING ABOUT THIS. THE BALANCE, STRENGTH AND ACCORD NATION OF THESE PATIENTS IS ACTUALLY GOOD AS I POINTED OUT TO YOU BEFORE, THE DEFINITION OF THESE PATIENTS IS THAT THEY ARE CAPABLE OF NORMAL FUNCTION IT'S JUST THAT THEY'RE NOT DOING IT AND BECAUSE THEY'RE CAPABLE OF NORMAL FUNCTION THEY CAN ACTUALLY SWITCH VERY RAPIDLY. THE OTHER FEATURE AND I THINK THAT THIS IS THIS MAY WELL BE AN IMPORTANT CLUE ALTHOUGH IT HASN'T BEEN PROVEN THAT THE ERRONEOUS BELIEF MAY WELL BE PLAYING A ROLE. IF 1 CAN SWITCH THAT BELIEF THEN THE FUNCTIONAL CHANGE MAY HAPPEN QUICKLY. IF YOU CAN TAKE SOMEONE OUT OF THE SICK ROLE AND IF THEY BELIEVE THAT THEY ARE THAT THEY CAN DO IT THEN THEY MIGHT WELL BE ABLE TO DO IT RATHER RAPIDLY IF ANY EVENT PHYSICAL THERAPY WHEN,A LIED WELL WITH WORK VERY QUICKLY AND IT'S ALSO COMAN STRAIGHTED THAT COGNITIVE BEHAVIORIAL THERAPY WILL BE GOOD AS WELL. SO NOW WE COME TO CONCLUSION HERE. FUNCTIONAL MOVEMENT DISORDERS AND OTHER CONVERSION DISORDERS ARE COMMON, REAL AND DISABLING. DIAGNOSIS CAN BE MADE ON POSITIVE FEATURES AND CLINICAL NEUROPHYSIOLOGICAL TESTING CAN BE HELPFUL IN THE PATIENTS. TREATMENT HAS BEEN DIFFICULT IN THE PAST, I THINK WITH THE NEW INFORMATION WE ARE DOING BETTER CLEARLY, ABOUT YOU IT WILL OFTEN REQUIRE A MULTIDISCIPLINARY TEAM. WE THINK THAT THE NEUROLOGYSTS SHOULD STILL STAY IN CHARGE, BUT PSYCHIATRY, PHYSICAL THERAPY, REHABILITATION SPECIALISTS, SOCIAL WORKERS, OCCUPATIONAL THERAPY, ALL WORKING TOGETHER SEEM TO HAVE BETTER OUTCOME AND THERE ARE A NUMBER OF PLACES NOW THROUGHOUT THE WORLD WHERE THESE MULTIDISCIPLINARY TEAMS ARE DEVELOPING. I SHOWED YOU HOW THERE ARE DIFFERENT FACTORS THAT ARE RELEVANT IN DIFFERENT PATIENTS AND SO, THERE MAY WELL BE DIFFERENT TREATMENTS, DIFFERENT THAT--DIFFERENT MEMBERS OF THE MULTIDISCIPLINARY TEAM NEED TO HELP MAKE THE PATIENTS BETTER. AND JUST A COUPLE POINTS HERE AT THE END, WE'VE BEEN WORKING IN THIS AREA FOR THE PAST 15 YEARS OR SO ON FUNCTIONAL MOVEMENT DISORDERS AND I'VE HAD THE PLEASURE AND GREAT BENEFIT OF WORKING WITH A GREAT GROUP OF FELLOWS THAT HAVE MANAGED OUR FUNCTIONAL MOVEMENT DISORDE PROJECT OVER THE YEARS, I SHOWED YOU EARLY WORK FROM VALERIE VOON, KATHRYN LAFAVOR TOOK OVER THE PROJECT, CARIIN, E, MAURER, AND THE RECENT INFORMATION HAS COME FROM VERA SPAGNOLA O, AND SEPIDEH, AND NOW IN CHARGE OF OUR WORK AND I'M LOOKING FORWARD TO HER CONTRIBUTIONS WHICH WILL MATCH THE GREAT CONTRIBUTIONS OF THESE EARLIER MEMBERS. THE LAST PART I WOULD LIKE TO MENTION, YOU HAD HEARD THAT I'M THE FIRST PRESIDENT OF THIS NEW SOCIETY CALLED THE FUNCTIONAL NEUROLOGICAL DISORDER SOCIETY IN IS A GREAT ADVENTURE. IT IS PROBABLY AS FAR AS WE CAN TELL THE FIRST MULTIDISCIPLINARY SOCIETY FOR A SOMATIC SYMPTOM DISORDER IN ANY FIELD OF MEDICINE. WE ARE IN--IT IS OPEN TO ANY HEALTHCARE WORKER THAT DEALS WITH THESE SITUATIONS, THIS IS PSYCHOLOGISTS, PSYCHIATRISTS, PHYSICAL THERAPISTS AND SO ON, AND FOR ANYONE INTERESTED WE WOULD BE VERY HAPPY TO HAVE THEM JOIN OUR NEW SOCIETY. SO WITH THAT, INFORMATION, I HOPEFULLY HAVE HELPED YOU UNDERSTAND WHAT OUR PROGRESS IS IN FUNCTIONAL MOVEMENT DISORDERS AND FUNCTIONAL NAWROLOGICAL DISORDERS, AND I WILL BE HAPPY TO DEAL WITH ANY QUESTIONS YOU MIGHT HAVE. >> THANK YOU VERY MUCH, MARK, FOR A VERY STIMULATING PRESENTATION, WILE WE'RE WAITING IF ARE ANY QUESTIONS TO BE SUBMITTED I DO HAVE MY QUESTION TO YOU WITH RESPECT TO THE ISSUE OF THE UNDERLYING TRAUMA HERE, SO, DO YOU THINK THAT IN ESSENCE THIS IS SORT OF A DELAYED ONSET POST-TRAUMATIC STRESS DISORDER? RIGHT SOY POST-TRAUMATIC STRESS SYNDROME IS A DIFFERENT DISORDER, THEY HAVE DIFFERENT CHARACTERISTICS. I THINK WHAT WE ARE SEEING HERE IS A DIFFERENT MANIFESTATION, NOW THERE CAN BE SIMILAR TYPES OF PREEXISTING FACTORS, AS I POINTED OUT EARLY LIFE TRAUMA, REALLY LEADS TO DECREASED RESILIENCE OF THE BRAIN. THERE IS A DECREASE OF THABILITY OF THE BRAIN TO MANAGE STRESS OF VARIOUS KINDS AND SO WITH OTHER TYPES OF THESE DIFFERENT FACTORS 1 GOES DOWN A PARTICULAR PATH OR A DIFFERENT PATH AND THE FEATURES EVER THESE PATIENTS REALLY DIFFER FROM THOSE PATIENTS WITH POST-TRAUMATIC STRESS SYNDROME. AND I SHOULD ALSO SAY, WHILE THERE'S A DIFFERENT TYPE OF CO MORBIDITY TO THOSE THAT HAVE SEVERE DEPRESSION AND ANXIETY, THESE PATIENTS DO HAVE HOWEVER A LOT OF DEPRESSION AND ANXIETY AS WELL THAT IS CHARACTERIZING THEM. >> OKAY, MY SECOND QUESTION REALLY RELATES TO COMPLEX REGIONAL PAIN SYNDROME, YOU ALLUDED TO THAT BUT I'M JUST WONDERING IS COMPLEX REGIONAL PAIN SYNDROME THE EQUIVALENT ON THE SENSORY SIDE OF WHAT YOU'RE DESCRIBING ON THE MOTOR SIDE? >> RIGHT. SO COMPLEX REGIONAL PAIN SYNDROME IS A VERY COMPLEX ENTITY JUST BY--EVEN JUST BY ITS NAME. AND I THINK THAT THERE ARE MIXED VIEWS OF WHAT ITS NATURE IS AND THERE ARE PROBABLY DIFFERENT TYPES OF PATIENTS THAT HAVE THIS PARTICULARRENTITY. THERE ARE CERTAINLY MANY PATIENTS THAT WE SEE WHO HAVE COMPLEX REGIONAL PAIN SYNDROME WHERE THE DISORDER APPEARS TO BE A FUNCTIONAL SENSORY DISORDER. AND I THINK THAT THE PATHOPHYSIOLOGY OF THIS CIRCUMSTANCE IS THAT IF SOMEONE HAS A FUNCTIONAL SENSORY DISORDER AND IN THE SETTING LIKE THAT, WHERE IT HURTS TO MAKE A MOVEMENT, PATIENTS MAY STOP MAKING MOVEMENTS OF A PARTICULAR BODY PART AND IF HAVE YOU A BODY PART THAT IS NOT MOVING, THEN THERE CAN BE SECONDARY AUTONOMIC CHANGES IN THAT BODY PART. AND SO 1 CAN GIVE RISE TO THE FINDINGS HERE. SO PATIENTS THAT HAVE COMPLEX REGIONAL PAIN SYNDROME BY ITSELF, MANY OF THEM HAVE A FUNCTIONAL DISORDER AND THOSE THAT HAVE COMPLEX REGIONAL PAIN SYNDROME AND DYSTONIA IS A SUBCLASS OF THOSE PATIENTS AND THAT SUBGROUP APPEARS TO BE PARTICULARLY PRONE TO HAVING A FUNCTIONAL DISORDER. >> GREAT WE HAVE NO FURTHER QUESTIONS FROM THE AUDIENCE SO WE WRAP UP TODAY'S GRAND ROUNDS SESSION AND THANK YOU AGAIN FOR A STIMULATING