DerekOtt,M.D.,M.S.AssociateClinicalProfessor

UCLADavidGeffenSchoolofMedicineDivisionofChild&AdolescentPsychiatryDirector,PediatricNeuropsychiatryClinic

Whatisbehavior?� Chronic/learned/conditionedresponse� Adaptationtonewenvironmentorcircumstance�  Symptomsofapsychiatricissue� Medicationsideeffects�  Symptomsofmedicalissues

� UltimatelyBehaviorIScommunication

Whatisbehavior?�  Chronic/learned/conditionedresponse

�  Chronicself-injuriousbehavior(SIB)assensoryseeking/soothing�  Adaptationtonewenvironmentorcircumstance

�  NewonsetSIBasacopingmechanism�  Symptomsofapsychiatricissue

�  NewonsetSIBasanxietydisorder/OCD�  Medicationsideeffects

�  NewonsetSIBrelatedtoconfusion,cognitiveissues,etc.�  Symptomsofmedicalissues

�  NewonsetSIBrelatedtogastrointestinal/painissues

�  UltimatelyBehavioriscommunication

Maladap2vebehaviorinau2sm� Asmanyas40%ofindividualswithdevelopmentaldisabilitymayexperienceaperiodofdisturbedbehavior/functionatsomepointintheirlives

� Suddenchangeinbehavior/functioningshouldpromptmedicalorclinicalevaluationtoidentifiedanytreatablemedicalcauses

� Needtounderstandpriorbaselinebehavior� Needtocoordinatewithotherproviderssuchasneurologist,internist,pediatrician,behaviorist,therapist,etc.

Maladap2vebehaviors-common(orReasonforPsychiatricReferral)

� Aggression� Moodlability/irritability� Lowfrustrationtolerance/tantrums/propertydestruction� Noncompliance/oppositionalbehavior� Impulsive/Hyperactivity� Sleepdisturbance� Regressioninfunctioning� Elopement

Maladap2vebehaviors-lessfrequent�  Primarilypresentinindividualswhoarenonverbalorhavemoresevereintellectualdisability

�  Stereotypies�  Repetitiveorritualisticmovements,postureorutterance

�  Selfinjuriousbehavior(SIB)�  Veryintense/repetitive

�  Fecalsmearing�  Pica

�  Swallowingofnonfooditems�  Rumination

�  Regurgitationoffoodfollowingconsumption.

E2ologyofbehaviorinau2sm�  Chronicbehaviors

�  Stereotypies/SIB�  Adaptivedysfunction�  Psychiatricdisorders

�  Medicationissues�  Medicalissues

�  Pain�  G.I.�  Neurologic�  Sleep

✳ Oftenmultiplecauses/triggers

Stereotypicalbehavior� Primarilypresentinindividualswhoarenonverbalorhavemoresevereintellectualdisability

�  Stereotypies�  Repetitiveorritualisticmovements,postureorutterance�  Typicallychronicbutcanchangeovertime�  Frequency,intensity,circumstances,etc.

�  Selfinjuriousbehavior(SIB)�  Consideredstereotypicalbehavioraswell�  Canvaryfrommild/lowfrequency(“habitual”)toveryintense/repetitive

Stereotypicalbehavior/SIB� Needtodeterminewhatisbaselinestereotypicalbehavior�  Chronicvsnew/acute� Distinguishfromtics,dyskinesia(abnormalmovements),dystonia(musclestiffness),otherabnormalmovements

�  Someofthesecouldbemedicationsideeffects�  Antipsychotics-risperidone,Abilify,etc.�  Antinausea/G.I.drugs-Reglan

�  Indicativeofmedicalissues�  Gastrointestinal-reflux,constipation,gastritis,etc.�  Pain-dental,ear,etc.�  PANDAS/PANS

Adap2vedysfunc2on� Mismatchbetweenneeds,abilities,goalsofindividualandenvironment/circumstances/expectations� Home�  Residence�  School� Dayprogram

�  Changeinparents/careproviders�  Changeinhealth-illness/pregnancy/death�  Changeinenvironment�  Changeinpeople-staff,students,residents�  Changeinschedule-home,school,dayprogram,residence

“Diagnos2covershadowing”�  =tendencytoassesscomorbidpsychopathologyinpersonswithintellectualdisabilitylessaccuratelythanpersonswithout(Rice,Leviton+Szyszko(1982))

� Assumethatcognitivedeficitsnegativelyimpactclinicianjudgmentsaboutpsychopathology

� Mayimpact�  Severity-howseverethesymptomsare?�  Category/diagnosis-whatdiagnosisthepersonhas�  Treatment-howthedisordershouldbetreated

�  Jopp,Keys,diagnosticovershadowingreviewedandreconsidered,AmJMR,2001

DevelopmentalDisability+Psychopathology

� PsychopathologyinpersonswithIDis3-4xhighervsgenpop

� 35-40%ofchildren/adolescentswithID-diagnosablepsychiatricdisorder

� 30-42%vs7%-IsleofWightstudyRutter,etal.,IsleofWightstudies1964-1974,PsychMed,1976

Medicalcausesofchallengingbehaviors�  Medicationissues

�  Druginteractions�  Sideeffects�  GenericsvsBrand

�  Medicalissues�  Cardiac-bradycardia�  GIrefluxpicaconstipation�  Pain-dentalear�  Hormonal�  Sleep-apnea�  Neurologic-HA,seizures

�  Oftenmultiplecauses

Medica2onEffects� Druginteractions� SideEffects� GenericsvsBranded

� Multiplemedications� Confoundedby

� Multipleproviders� Current+historicalinformationoftenlimited� Medicationnoncompliance

Medica2on–Druginterac2ons� Anticonvulsants

�  Somecaninducemetabolismviaimpactonliverenzymefunction�  Carbamazepine/Tegretol,valproicacid/Depakote,phenobarbital

�  Asaconsequence,theeffectivedoseofotherdrugisdecreased�  Thusmayrequirehigherdosesinthepresenceoftheseanticonvulsants

� Antidepressants�  Inhibitmetabolismviaimpactonliverenzymes(cytochromes)

�  Fluoxetine/Prozac,paroxetine/Paxil�  Asaconsequencetheeffectivedoseofanotherdrugcanbeincreased

�  Risperidoneinthepresenceofeitherdrugcouldbeeffectivelyincreasedtwofold

Medica2onSideEffects-an2convulsants�  Phenobarbital

� Notcommonlyused�  Attention,otheraspectsofcognition,hyperactivity,depression

�  Topiramate/Topomax� Memoryissues,wordfindingdifficulties

�  Gabapentin/Neurontin�  Typicallyverywelltoleratedespeciallyinadults�  Psychosisespeciallyinyoungerindividuals

�  Leviteracetam/Keppra� Widelyusedbecauseoflackofdruginteractions� Well-establishedmoodsymptoms-20%�  Irritability,agitation,aggressionanddepression� MaybenefitfromtreatmentwithvitaminB12(50-100mg)

Medica2onSideEffects-benzodiazepines� Drowsiness� Confusion/mentalclouding� Memoryproblems

�  especiallyifolder+long-termuse� Disinhibition?

� Appearasifintoxicated� Morelikelyinindividualswithdevelopmentalissues?

Medica2onSideEffects-benzodiazepines� Longacting/half-life-Clonazepam(Klonopin)

� Accumulate>drowsiness&mentalclouding+confusion

� Short-acting/halflife-Alprazolam(Xanax)�  Interdosereboundsymptoms

� Worseningofanxietypriortoscheduleddoses>higherdoses>dependence/tolerance

� Riskofseizuresinthepresenceofabruptdiscontinuation

Medica2onSideEffects-an2psycho2cs� Risperidone/Risperdal,aripiprazole/Abilify

� Parkinsonism/akathisia(restlessness)�  Confusedwithworseningagitation�  Canleadtocounterproductiveincreaseindose

� Alertness/mentalperformance�  Somehavemorenegativecognitiveimpact-haloperidol

� Precipitousreductionindosage�  >agitation,behavioraldeterioration�  >worseningabnormalinvoluntarymovements(transientwithdrawaldyskinesias)

AtypicalAn2psycho2c-SideEffects� Weightgain

�  Canbesubstantial20-40pounds�  Createsnewissues

� ↑Glucoselevels� Newonsetdiabetes

� ↑Lipidlevels� ↑Prolactinlevels

�  Gynecomastia(breastgrowth)

GenericvsBrandedMedica2ons�  Branded+genericmedicationsdoindeedcontaintheexactsameactiveingredientorDRUG�  GenericsareBIOEQUILIVENT

�  Branded+genericmedicationsmaydifferin2significantways�  AsestablishedbytheFDA,genericproductsareconsideredbioequivalentif

theycontain80-125%doseoftheactivecompound�  Genericmedicationsusuallycontainlessratherthanmore

�  Brandstypicallyvarybyonly3-5%ofthedose�  Packing,fillers,colorsmaydiffersignificantly

�  Thesedifferencesmayimpactefficacyandsideeffects�  Canimpactdrugbreakdown,absorption,bloodlevelrise,etc.�  Therefore,notallgenericsareconsideredtohavethesame

BIOAVAILABILITY

GenericvsBrandedMedica2onsConcertaProblem

�  BRAND�  OriginallymanufacturedbyOrthoMcNeilJanssen�  Veryspecificreleasemechanism(OROS)responsiblefortheextendedrelease

�  Specificallydesignedandpatentedbarrelshapedcapsule�  GENERICS

�  WhenConcertawentgenericin2014,severalgenericalternativesemergedincludingWatson(purchasedbyActavis)andseveralothers

�  Theseareverydifferentintermsofsize,shape,designandultimatelyrelease.

�  ManyoftheseareNOTOROSdesign

GenericvsBrandedMedica2onsConcertaProblem�  Concertaproblems� OriginallymanufacturedbyOrthoMcNeilJanssen+subsequentlybyWatson/Actavis

�  VersionsbyMalinckrodt+Kudco

GenericvsBrandedMedica2onsConcertaProblem

�  Concerta/methylphenidateERwasdesignedtoreleasethedrugoveraperiodof10-12hours

�  AnalysisbytheFDArevealedthatMallinckrodtandKudcoproductstheydeliveredthedrugataslowerrateof7-12hours

�  Asaresult,theFDAchangethetherapeuticequivalenceratingfortheseproductsfromABtoBX�  TheseproductsarestillapprovedandcanbeprescribedthatarenolongerrecommendedasautomaticsubstitutionthatthepharmacyforConcerta

�  FDArequestedthatthesemanufacturersconfirmthebioequivalenceoftheirproductsorvoluntarilywithdrawthemfromthemarket

�  http://www.fda.gov/Drugs/DrugSafety/ucm422568.htm

Medicalcausesofchallengingbehaviors�  Medication

�  Druginteractions�  Sideeffects�  GenericsvsBrand

� Medicalissues� General� Gastrointestinal� Pain� Hormonal� Sleep� Neurological

�  Oftenmultiplecauses

MedicalEvalua2onofPersonswithMRreferredforPsychiatricAssessment(Ryan,Sunada,1997)

�  InterdisciplinaryteamevaluationclinicspecificallyforthosewithIDandbehavioralchallenges

� Consecutivesampleof1135adults�  aveage32.9yrs�  ID(moderatetosevere)�  50%nonverbal�  46%nonpsychiatricmeds

� Evaluatedby2-stepprocess(physicalexam+screeninglabsfollowedbyselectivetesting)

MedicalEvalua2onofPersonswithMRreferredforPsychiatricAssessment(Ryan,Sunada,1997)

Condition % of cases Epilepsy (untreated or undiagnosed) 45.8 Hypothyroidism 12.7 Tourette’s syndrome 11.5 Gastroesophageal reflux 9.7 Severe closed head trauma 8.8 Chronic pain 8.7 Cerebral palsy (complicated) 6.5 Open brain injury 6.3 Abnormal (spike-wave) EEG 5.4 Arthritis (autoimmune) 5.0 Hypertension, symptomatic 4.7 Scoliosis (untreated) 4.1 Peptic ulcer disease 4.0

MedicalEvalua2onofPersonswithMRreferredforPsychiatricAssessment(Ryan,Sunada,1997)�  Results

�  75%had>1undiagnosed/untreatedmedicalproblems�  AlmostallhadNOdiagnosisotherthanIDbeforethestudy�  Mostcommonpsychiatricdiagnosis-anxiety,depression

�  Comments�  Commonconditionspresentatypically�  Conditionsconsidered“uncommon”mayoccurmorefrequently�  Greaternumberoftestsmaybenecessarybecausehistoryoftennotavailableorhelpful�  Workupconsideredcompletewhenpersonisimprovingorhasaspecificterminaldiagnosis

andiscomfortable

http://www.ddhealthinfo.org/

Generalpain/discomfort(highac2vity,rocking,head-banging,orotherbehavior)�  Arthritis�  Bonefracture�  Cervicalbodysubluxation

�  Cardiacdisease

�  Constipation�  Intestinalobstruction�  Gastroesophagealreflux(w/orw/oesophagitis)�  Hernia�  Rectalfissure

�  Dentalpathology

�  Dehydration�  Electrolyteorglucoseabnormality

�  Pneumonia

�  Headacheormigraine�  Hydrocephalus�  Ocularandvisionproblems�  Seizures�  Changeofconsciousness

�  Sepsis�  Occultinfection(sinusitis,otitismedia,dental,

urinarytractinfection,vaginitis,prostatitis)

�  Medicationtoxicity

�  Traumaincludingabuseorneglect�  Psychiatricdisordersincludingdepression

Hands/FingersinMouth�  Sinusproblem� Eustachiantube� Middleearproblem� Dentalpathology� Gastroesophagealreflux� Asthma� Nausea

� Cardiacproblems�  Seizures�  Syncopeororthostasis� Vertigo� Atlanto-axialdislocation

SuddenSiWng

Medicalcausesofbehavior-Allergies� Environmental/hayfever,foodallergies,atopicdermatitis,allergicasthma� Canoccurforthefirsttimewhensettingorenvironmentischanged

�  Changeinweather/seasons� Potentiallyundiagnosedinnonverbalindividualsasmanysymptomsmaynotbeapparentandcouldimpactbehavior�  Symptoms(runnynose,itchiness,redeyes,shortnessofbreath,swelling,etc.)&associateddiscomfortcanimpactbehavior

� Uncomfortability>irritability,anxiety,agitation,SIB� Associatedmedicationsalsohavesideeffects

�  Antihistamines-sedation+moodchanges(especiallyZyrtec)

Medicalcausesofbehavior-Allergies� Correlationofallergies/asthmawithbehavioralissuesandASDhasnotbeenexaminedindepth

� Medicalcomorbiditieslikeallergiesinthegeneralpopulationareoftenrelatedtoincreasedirritabilityandpoorfunctionaloutcomesinchildren(Jyonouchi,2010)

� Asthma&AllergiesinChildrenwithAutismSpectrumDisorders:ResultsfromtheCHARGEStudy(Lyall,etal.,2015)� OverallallergyinchildrenwithASDwasassociatedwithhigherstereotypyscoresasmeasuredbytheAberrantBehavioralChecklist(ABC)

Medicalcausesofbehavior-allergies� Caseexample�  45-year-oldnonverbalmalewithprofoundintellectualdisability+autismwhowouldrepeatedlyforciblyinserthishandsinhismouth/throatandalsohadsevereSIB(banginghisheadwithhishands)

� Discoveredthathehadsevereenvironmentalallergieswhichcausedairritation/itchingofhispalette(roofofhismouth)whichwasthetriggerfortheinsertionofhishandsinhismouth

� AntihistaminehydroxyzineandotherrelevantinterventionshasproducedsomebenefitincludingtheeliminationofthisbehaviorbutcontinuestohaveSIB

Medicalcausesofbehavior-cardiac� Caseexample�  60-year-oldverbalmalewithmildID,autism,possiblemooddisorderincludingbipolarwithsuddenonsetofdroppingtothefloorincludinginpublic

� Viewedbystaffasnoncompliancepossibleassociatedwithanxiety� Ultimatelydiagnosedwithbradycardia(slowheartrate)whichrequiredplacementofapacemaker.

�  Followingthis,nofurtherdroppingbehaviorornoncomplianceandanxietywasoverallreduced

Medicalcausesofbehavior-pain� Manymedical/dentalissuescangoundiagnosedinindividualswithdevelopmentaldisabilitiesandleadtothedevelopmentofpain

� Painmaybeexperiencedverydifferentlyinindividualswithdevelopmentaldisabilities� Diminishedorhigherpainthresholdmany� Heightenedsensitivityinsomeindividualsperhapsrelatedtosensoryissues

� Awarenessbutlackofunderstandingandstillimpactbehavior/functioning� Discomfort,anxiety,irritability,agitation,aggression,SIB,insomnia

Medicalcausesofbehavior-pain� Dentalissues

� Dentalvisits/cleaningsareoftenverylimited/infrequentornotpossibleinsomeindividuals

�  Asaresultvariousissuescandevelop(i.e.impactedteeth,infection,gumissues,etc.)whichcancausediscomfort/painandassociatedbehavioralmanifestations

�  Loseteeth+bracescanalsobeproblematic�  Sinus/ear/nasalissues

�  Canbeacuteorchronicandsignificantlyimpactbehavior� Bothcouldpotentiallycontributetodiscomfortandassociatedirritability,SIB(headbanging,slapping)and/oraggressiontowardsothers

Medicalcausesofbehavior-gastrointes2nal

�  StudiessuggestthatchildrenwithASDareatincreasedriskforgastrointestinalproblems(Ibrahimetal,2009)

�  FrequentG.I.complaintsincludingconstipation,reflux,foodallergies/sensitivities

� GastrointestinalSymptomsinAutismSpectrumDisorder:AMetaAnalysis,McElhanon,etal,2015

�  Analysisof15peer-reviewedstudies(1980-2012)�  ChildrenwithASDexperiencedsignificantlymoreG.I.symptoms� Diarrhea(OR,3.63/95%CI1.82-7.23),constipation(OR3.86/2.23-6.71),abdominalpain(OR2.45/1.19-5.07).

Medicalcausesofbehavior-gastrointes2nal�  StudiessuggestthatchildrenwithASDareatincreasedriskforgastrointestinalproblems(Ibrahimetal,2009)andmaybemoredifficulttoevaluate(Buieet.al.,2015)

�  FurthersuggestedthatcertainbehavioralproblemsinchildrenwithASDmaybeindicativeofachild’sresponsetooranattempttocommunicatethepainordiscomfortofthisunderlyingG.I.issue(Horvath,etal.1999,Williamsatall2010,Bauman,2010)

�  Specificsuggestedbehaviorsincludesleepdisturbance,stereotypicalrepetitivebehaviors,selfinjuriousbehaviors(SIB),aggression,oppositionality,irritability,tantrums,andothermooddisturbances

Medicalcausesofbehavior-gastrointes2nal�  Briefreport:Associationbetweenbehavioralfeatures&gastrointestinalproblemsamongchildrenwithautismspectrumdisorder,Maener,etal,2011

�  Cross-sectionalstudyofchildrenwithASD35/487(7.2percent)haddocumentedhistoryofG.I.issues�  Constipation,abdominalpain,diarrhea,encopresis,gastroesophagealrefluxdisease(GERD),gastritis,abdominalbloating,disaccharideacedeficiencies,inflammationofGItract,abnormalitiesofentericnervoussystem,functionalabdominalpain,irritablebowelsyndrome(IBS),flatulence,celiacdisease

�  Constipation,encopresis,GERD-mostcommondocumented�  Significantassociation-Unusualsleeping(p<0.01)oreatinghabits(p<.02),oppositionalbehavior(P<0.04)

�  Associationbutnotsignificant-Mooddisturbance(P<.08),tantrums(p<0.05)�  Noassociation-stereotypic/repetitivebehaviors+SIB

�  UnusualsleepingoreatinghabitsandoppositionalbehaviorweresignificantlyassociatedwithGIproblems

Medicalcausesofbehavior-gastrointes2nal�  Pica

�  Persistenteatingofnon-nutritive,nonfoodsubstancesoveraperiodof1month(DSMV)

�  Paper,soap,cloth,hair,string,wool,soil,chalk,paint,gum,metal,pebbles,ice,coins

� Occursinthecontextofintellectualdisability,autism,schizophreniaorothermedicalconditionincludingpregnancy

�  Caseexample�  39-year-oldmalewithahistoryofsevereintellectualdisabilityandchildhoodTBIwithachronichistoryofpica

� WouldoftenswallowballoonsorrubbergloveswhichcouldcauseG.I.irritationincludingconstipation

�  Constipation/holdingofstooling�  Perhapsrelatedtosensory/painissuesindividualsmaynotbeawareoftheassociateddiscomfortandimpactonbehavior

Medicalcausesofbehavior-hormonal� Mostmenstruatingwomenexperiencesomepremenstrualsymptoms� Approximately20-40%considerthemsevereenoughtoseekmedicalhelp

� Premenstrualdysphoricdisorder�  includesmoodlability,irritability,dysphoriaandanxietysymptomsthatoccursrepeatedlyduringthepremenstrualphaseofthecycleandremitaroundtheonsetofmensesorshortlythereafter

�  Alsoincludesphysicalandbehavioralsymptoms�  12monthprevalence=1.8-5.8%ofmenstruatingwomen

Medicalcausesofbehavior-hormonal� Prevalenceofpremenstrualsyndromeandautism:aprospectiveobservatorratedstudy,Obaydi+Puri2008

�  Comparedwomenwithautism+learningdisability(26)withagroupwithlearningdisabilityonly(36)

�  24/26(92%)metcriteriaforlatelutealphasedysphoricdisordervs11%ofcontrols(p<.000001)

�  Increasedsymptoms-affectivelability,angerorirritability,clumsiness,anxietyortension,depressedmood,impairmentofworkperformance,socialactivitiesrelationship,socialwithdrawal,isolationanddecreasedinterestinusualactivities,decreasedconcentration,tempertantrums,physicalaggression,selfharm,stereotypiesorrepetitivemovements,destructivebehavior,hypersomnia,insomnia,changeinappetiteorspecificfoodcraving,headache

Medicalcausesofbehavior-hormonal� Caseexample�  23-year-oldlargelynonverbalfemalewithautism,priordiagnosisofADHDandbipolardisorderbeginninginlateteens

� Developedcyclicalmoodchangesinadditiontohormonalchangesinmood

� Respondedwelltomoodstabilizers/antipsychoticsaswellastheadditionoftransdermalbirthcontrol

� Withthiscombinationcyclicalandhormonalmoodchangesarelargelyundercontrol

Medicalcausesofbehavior-sleepdisorders�  Sleepwakecycleinindividualswithautismappearstobeabnormal�  Sleepproblems

�  CommoninchildrenwithASD-45-86%Liu,Hubbard,Fabes&Adam,2006,Maskeyetal.,2008

�  Morechronic–remission8.3%vs52.4%Silversenetal.,2012�  ConsideredasacoexistingsymptomofASDnotsignificantlyinfluencedbyrace,gender,ageorIQMayes&Calhoun2009

�  Impactontheindividualandthefamily/careprovidersisprofound�  Significantstresstofamilies�  Shortsleepdurationassociatedwithhigherratesofstereotypicalbehavior33aswellassocialdeficits32

�  Mayworsendaytimebehaviorsincludinginattention/hyperactivity28

Medicalcausesofbehavior-insomnia�  Insomnia=Difficultyinitiatingormaintainingsleep�  Types-Prolongedsleeplatency(timetofallasleep),bedtimeresistance,decreasedsleepefficiency,decreasedsleepduration+continuityandincreasedawakenings

�  Sleeponsetinsomniaismoreprevalentthansleepmaintenanceinsomnia17,34� Manypossiblecontributingfactors

�  Aberrationsofneurotransmittersystemsthatarerelatedtosleep+regularsleepwakecycle(e.g.melatonin)

�  Psychiatricdisorders-anxiety/depression,ADHD,obsessive/repetitivebehavior�  Medicalissuesthatdisruptsleepcontinuity-epilepsy,G.I.disorders,pain,constipation,breathingissues/asthma

�  Neurologicissues-sleepapnea,periodiclimbmovement,restlesslegsyndrome�  Difficultyestablishingaproperbedtimebehaviorandroutine�  Sensoryissues

Medicalcausesofbehavior-sleepapnea�  Sleepdisorderedbreathingincludesdisordersrelatedtoairwayobstruction/obstructivesleepapnea

� Commoninthegeneralpediatricpopulationincludingthosewithautism� Contributingfactors-allergies,tonsillitis,hypotonia,medicationrelatedsedation

� Contributestodaytimesleepinesswhichcanimpactbehavior,mood,attention,etc.

Medicalcausesofbehavior-headaches�  Prevalence

�  37-51%duringelementaryschoolyears,57-82%-highschool�  Frequent/severeheadachesincludingmigraine-17%ofchildren+adolescence

� Migraineheadaches=moderate/severerecurrentheadaches�  otherssymptomsincludingnausea,vomiting,sensitivities(light,sound,smell),visual/visiondisturbances,frequenttriggers

�  Familyhistory�  Hormonal+othertriggers

�  Inthosewithlanguage/communicationdifficultiesheadachesmaybehardtodiagnosebutcancausesignificantimpactonpain

�  Empiricaltreatment?

Medicalcausesofbehavior-neurological�  PrevalenceofepilepsyinASDranges11-39%� Moreseverecognitivedysfunctionassociatedwithhigherriskofseizures�  EEGabnormalitiescanbefoundin8-31%ofthosewithoutepilepsy� Morecommonlyassociatedwithregression–seeninabout30%ofASD,usually18-24mos�  Inthissubset,upto80%inonestudyhadepileptiformactivityonEEGduringsleep(ESESorCSWS)

� OnsetofESEScommonlyassociatedwithonsetofseizures,mostfrequentlyabsence

Medicalcausesofbehavior-neurological�  Epilepsy=Recurrentseizures

�  Complexpartialseizures/temporallobeepilepsy�  Absenceseizures/petitemal�  Frontallobeseizures

� Mixedseizuretypes/syndromes�  LennoxGastautSyndrome

�  Continuousspikewavesinslowwavesleep(CSWS)�  LandauKleffnerSyndrome

Medicalcausesofbehavior-neurological� Epilepsy=Recurrentseizures�  Frequentseizuresespeciallyatnightcanimpactcognition/development� Whenveryfrequentcancontributetothedevelopmentofachronicconfusedstate(encephalopathy).

� Theadditionofrequiredmedicationcanfurthercontributetothisconfusedstate

� Thelocationofbeingabnormalelectricalactivitycanberelevanttofunctioningofthebraininthatareaincludingbehavior.

Medicalcausesofbehavior-neurological� CSWS–Continuousspikewavesinslowwavesleep

�  Presentwithregression–lossoflanguageandtemporospatialskills,hyperactivity,aggression

� Mayhavemotordeficits–ataxia,apraxia,dyspraxia� Mostlyexpressiveaphasia(receptiveusuallyspared)�  Seizuresarepresentingsymptominupto80%�  Ageofonsetvariable,mean4-8years

�  Youngeronset,worseprognosis

Medicalcausesofbehavior-neurological-LandauKleffnerSyndrome�  Onset-3-8yearswithpeak4-5years�  Acquiredaphasia

� Normaldevelopmentuntil4-6yrs�  Languagearrest>jargonizedspeech

�  Othersymptoms� Hyperactive/impulsive,autisticlike

�  Seizures�  Presentand70-80%�  EEG-Bilateralindependenttemp/parietalspike/waveorfocaltemporal

�  Differential-Autism

Medicalcausesofbehavior-neurological-PANDAS� PediatricAutoimmuneNeuropsychiatricDisordersAssociatedwithStreptococcalInfections�  Specifically,groupAbeta-hemolyticStreptococcus(GABHS)

�  Firstdescribedin1998withacaseseriesof50casesbySusanSwedoattheNIH.�  SwedoSE,LeonardHL,GarveyM,etal.PANDAS:ClinicalDescriptionoftheFirst50Cases.AmericanJournalof

Psychiatry1998;155:264-271.

�  AntibodiesgeneratedagainstGABHScross-reactwithself-antigensexpressedinthebasalgangliaand/orotherbrainstructures(molecularmimicry).

PANDASCriteria1.   TicdisorderorObsessiveCompulsiveDisorder

meetingDSMcriteria2.  Onsetpriortopuberty(usually3-12)3.   Abruptonsetofsymptomsorepisodiccourse(severe)4.   Temporalassociationofsymptomexacerbationand

streptococcalinfections(onset+oneexacerbation,oratleasttwoexacerbationsconfirmedbycultureorrepeatedrisinganti-streptolysinO/antiDNAseBtiters)

5.  Presenceofneurologicalabnormalitiesduringperiodsofsymptomsexacerbation(e.g.-choreiformmovements(butnotchorea),tremor,cognitivedeficits,motorichyperactivity)

Medicalcausesofbehavior-neurological-PANDASs  AdditionalresearchrevealedassociationbetweenPANDASinthepresenceofcomorbidADHD,separationanxiety,vocalandmotortics,frequenturination,handwritingdeterioration,anddeclineinschoolperformance.

s  ChildrenwithPANDASweremoreliketopresentwithdramaticonsetofsymptoms,completeremission,temporalassociationofsymptomswithGASinfectionandclumsiness.

Medicalcausesofbehavior-neurological-PANS

�  PediatricAcuteonsetNeuropsychiatricSyndrome�  ConsensusconferenceMay2013�  JournalofAcademyofChild&AdolescentPsychopharmacology

�  PANDAS“morphed”asresearchidentifiedpotentialinfectioustriggersbeyondGroupAstreptococcusaswellasnoninfectiousormetabolicfactors

�  CliniciansconfrontedwiththedifficultydiagnosingyouthwhomeetallbutonecriteriaofthePANDASsubtype,evidenceofGASinfectionbeforesymptomonset.�  IncreasingevidencesuggestingabsenceofsignificantroleforGASinfection

�  Proposedabroadertermthatencompassesacuteonsetneuropsychiatricsymptomswithoutaspecificenvironmentalorimmunerelatedtrigger(Swedoetal.,2012)

Medicalcausesofbehavior-neurological-PANS

� CliniciansconfrontedwiththedifficultydiagnosingyouthwhomeetallbutonecriteriaofthePANDASsubtype,evidenceofGASinfectionbeforesymptomonset.

�  IncreasingevidencesuggestingabsenceofsignificantroleforGASinfection

� Proposedabroadertermthatencompassesacuteonsetneuropsychiatricsymptomswithoutaspecificenvironmentalorimmunerelatedtrigger(Swedoetal.,2012)

Medicalcausesofbehavior-neurological-PANS

� PANSCriteria� Abrupt,dramaticonsetofOCDORseverelyrestrictedfoodintake+�  2ormoreconcurrentneuropsychiatricsymptomsalsowithacuteonset

�  Sensorysymptoms� Handwritingdeterioration�  Separationanxiety�  Emotionallability

Medicalcausesofbehavior-neurological-PANS

� Otherfeatures� Anxiety� Emotionallylability,depression,orboth�  Irritability,aggressionorsevereoppositionalbehaviororcombination� Behavioralregression� Deteriorationinschoolperformance�  Sensorymotorabnormalities�  Somaticsignsorsymptomsincludingsleepdisturbance,enuresisorurinaryfrequency

Medicalcausesofbehavior-neurological-PANS

� Laboratorytests–PANS� ASOtiterelevationsbeganoneweekafterinfectionandpeakafter2-3weeks

� Anti-DNAseBtiterelevationsafter4-8weeks� Useofbothreducesthepossibilityofobtainingfalsenegatives

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