PediatricStrokeandVascularServiceCMECourse.September7th,2017ERICGRABOWSKIFERDINANDO BUONANNO

PATRICIAL. MUSOLINOMASSACHUSETTS GENERAL HOSP ITAL HARVARD MEDICAL SCHOOL

Drs.Grabowski,Buonanno andMusolinohavenofinancialdisclosures

PediatricStrokeandVascularService

PediatricStrokeTeamatMGHRapid,coordinatedresponsetothemanagementofpediatricstrokecases.

Long-termfollow-upcareforthesepatients.

Resourcesforfamiliesandpatients§www.massgeneral.org/children/services/treatmentprograms.aspx?id=1628

WhyaPediatricStrokeServiceisImportanttoPediatriciansIncreasedrecognitionofafrequentlyunsuspected,orevenmisdiagnosed,conditioninpediatrics.

Efficacyofanti-thrombotictherapyintheolderchild.

Majorroleforthrombophiliaintheolderchild,vs. atherosclerosis,diabetes,hypotension,andlipidsinolderpatients.

Amultidisciplinaryteamapproachprovidestheneededexpertiseandtoolstodiagnoseandmanagepediatricstrokeeffectively.

Apediatricstrokespecialistcanappreciatethedistinctnessofstrokeinthenewborn,vs. theolderchild,vs. thechildwithsicklecelldisease.

AcutePediatricStroke-statisticsPrevalence:11-24/100,000(comparabletostrokeincidenceinyoungadults)

Incidence:3/100,000/yr,vs. 65/100,000/yr inadults

AtMGH,consistentwiththeabove,25pediatricand800+adultstrokeswereevaluatedandmanagedin2016.

InternationalPediatricStrokeStudyCenters60Centers,5151ChildrenEnrolled(9/2016)

CerebrovasculardiseaseinchildrendiffersfromthatinadultsMoredifficulttodiagnoseRiskfactorsaredifferentLesserdegreesofresidualdysfunctioninsomeRehabilitationpotentialandchallengesaredifferentMultidisciplinarycareisalwaysneeded

DifferentStrokeManifestationsAdultsandolderchildren

§ acutefocaldeficitinarterialterritory

Neonates§ Seizures;apnea;autonomicinstability§ Hypotonia;abnormalreflexes§ Lethargy;encephalopathy§ Earlyhandedness(<18mos);developmentaldelay(CP)§ None(untilage2-3months,orserendipitousfindinguponCNSimaginginlaterlife)

CategoriesofRiskFactorsPlasma-phasebasedriskfactors

Structuralfactors

Familyhistoryandhereditaryconditions

Co-morbidconditions(andtriggers)

Maternal,LaborandDelivery,forperinatalstroke

Sickle-celldisease

ImpactofThrombophiliaonAISorCSVTinChildrenEvaluationofallstudiesofpediatricstrokeand/orCSVTfrom1970to2009(185publications)

22ofthesesatisfiedcriteriaforinclusioninameta-analysistoestimateoddsratiosandconfidenceintervals

1526childrenwithAIS,238withCSVTvs.2799Controls

MGHwasoneof28centersworldwidewhichcontributedtothestudy

Kenet etal,2010

Riskfactor Pts/controls OddsratioProteinCdef 844/1207 11.0(5.1-23.6)

APA/LA 930/1194 7.0(3.7-13.1)

Lipoprotein(a) 616/578 6.5(4.5-9.6)

FVG1691A1014/2581 3.7(2.8-4.9)

FIIG20210A1059/2278 2.6(1.7-4.1)

MTHFRTT 777/1715 1.6(1.2-2.1)

≥2genetictraits701/1265 18.8(6.5-54.1)

ImpactofThrombophiliaonAISorCSVTinChildren

Kenet etal,2010

ImpactofThrombophiliaonthrombo-embolisminChildren(moregenerally)

Evaluationofallstudiesofpediatricthrombo-embolismfrom1970to2007(50publications)

35ofthesesatisfiedcriteriaforinclusioninameta-analysistoestimateoddsratiosandconfidenceintervals

2653childrenwiththrombo-embolicevents(PE,DVT,AIS,CSVT)vs.1979controls

MGHwasoneof23centersworldwidewhichcontributedtothestudy

Youngetal,2008

PediatricStroke-NeonatalandInfantPerinataldepression

§ HIE,ECMO,Sepsis,meningitis§ CongenitalHeartDisease

Dehydration,hypernatremia

Coagulopathy§ Prothrombotic (DIC,APLA,polycythemia)§ Bleedingdiatheses(vW disease,hemophilia,NAIT,severeliverdisease)

Metabolic(organicacidemias,mitochondrialdisorders)

Maternal(pre-eclampsia,diabetes,PROM,cocaine)

Placental(chorioammionitis,abruption,thrombosis)

PerinatalStrokeandPlacenta

CourtesyofNeuroplacentology StudyGroup

PediatricStroke-OlderChild(1-13y.o.)Congenitalheartdisease,mitralvalveprolapse,ECMO

PFOwithrighttoleftshunt

Coagulopathy

Infectious§ rheumaticheartdisease,endocarditis,meningitis,mastoiditis

Canceranditstreatment(lymphoreticular,ProML,ALL,gliomas,s/pXRT,chemo)

Autoimmunediseases(esp.SLE,PAN,Takayasu)

Metabolic(MELAS,Kearns-Sayre,Fabry’s,homocystinuria)

Vasculopathies(HHT,Ehlers-Danlos,NF,Down’s,moya-moya)

Pediatricstroke-AdolescenceSameasforages1-13,plus:§FMD§Dissections§Trauma(EDH,SDH,SAH,IPH,IVH)§OCPs,pregnancy§Cocaine,otherdrugs

Stroke- DiagnosticworkupDiagnosticevaluation§ HeadUS(maymisssuperficialandischemiclesions)§ CTheadtoruleouthemorrhageifthrombolytictherapyisbeingconsidered§ RapidMRI,MRAandMRVtoestablishtypeofstrokeandvesselanatomy§ CTAtoidentifydissectionsandprimaryvascularanomalies

MetabolicandHematologicalEvaluation

Geneticsasindicated

CARASIL-Cerebralautosomalrecessivearteriopathy withleukoencephalopathyandstroke(HTRA)

CADASIL-Cerebralautosomaldominant

arteriopathy withleukoencephalopathyand

stroke(NOTCH3)Loeys-DietzSyndrome(TGFBR1-TGFBR2-SMAD3-TGFB2)Hereditaryangiopathy withnephropathy,aneurysmsandmusclecramps(COL4A1,COL4A2)Marfans Syndrome(FBN1)

MonogeneticVascularDiseasesaremorefrequentinpediatricstroke

Fabry disease(GLA)Rendu-Osler-WeberSyndrome(HHT-ENG)Hereditaryendotheliopathy withretinopathy,nephropathyandstroke(TREX1)

Arteriopathy (ACTA2)Arteriopathy (MYLK)

Aicardi–Goutieressyndrome(SAMHD1)

ADA2(CECR1)MoyaMoya(RNF213)

Stroke- AcuteManagementClinicaldiagnosis,acutestabilization

§ (e.g.O2;BP;controlseizures),andtriage

Diagnosticimaging

Studiesforthrombophilia

Anticoagulation/Clottingfactorreplacement

Follow-up

CorrectionofHypoxemia.Treatanemia

Euthermia,Euglycemia

HypothermiashouldnotbeusedoutsideclinicaltrialorconcomitantHIE

Normotension.Treatdehydration

MonitorandcontrolICPtokeepadequateCPP

ContinuousEEGmonitoring§ Intheabsenceofclinicalorelectrographicseizures,NOAEDsisindicated

Stroke- AcuteManagement

Case 1: Arterial Ischemic Stroke in a neonate

Initialpresentationandimaging:MRI3.3Kgboybornat403/7gestation

Uncomplicatedvaginaldelivery

Apgars:6and9

EveningofDOL1:tonicclonicactivityLlimbs,oralsmacking,Leyeblinking

FurtherworkupEchocardiogram:§diffusethickening,shaggyandirregular,ofseptalleafletoftricuspidvalve,c/wvegetationorthrombus

§ rightatrialdilatation

Basicmetabolic,cultures,hypercoag studiesallnegative

Managementandfollow-upimagingTreatedwithphosphenytoin andphenobarbital;LMWH

DGwasanticoagulatedinviewofthickeningoftheseptalleafletofhistricuspidvalve,combinedwithapatentforamenovale.

Hedidnothaveanyplasma-phasebasedriskfactors

Follow-upFLAIRsequenceatage7months

ArterialIschemicStrokeinNewbornsUsuallyduetoperinatal/maternalfactors,anddonotrequireanticoagulation.Butanechocardiogramshouldbeperformedtoexcludethrombusinaventricleoronavalve,aswellasright-to-leftshunting.

Asmanyas30%,however,maybeassociatedwithaplasma-phasebasedriskfactor.Studiesareunderwaytoconfirmthatthissubgroupdoesneedanticoagulationinordertopreventrecurrence.

ArterialIschemicStrokeinNewbornsRecurrentthromboemboliceventsarenotcommon:3.3%of215neonateswithAIS.Thisreflectsthedominanceofperinatalandmaternalfactors.

However,perinatalthromboticevents,nonetheless,areassociatedwiththepresenceofplasmaphaseriskfactorsinthesettingofunderlyingsystemicdisease

Infact,prothrombotic riskfactorsareactuallyveryfrequent:127/215,or61%ofneonatesintheKurnik study,and15/50,or30%ofperinatalAIS’satMGH

Kurnik etal,Stroke34:2887-93,2003;Grabowski,BuonannoandMusolino,Blood2010

Prothrombotic riskfactorsarefrequentandimportantTheidentificationofsuchriskfactorsisthusveryimportant:§ Closureforparentsasking“Whyourchild?”§ Maypredictincreasedriskofthromboembolisminlaterlife:canthen

mitigaterisks§ MaypredictsignificantrecurrenceriskinCSVT

Kenet etal,Blood106:1629,2006; Nowak-Gottl etal,2009;Youngetal,2010Grabowski,BuonannoandMusolino,2010

DifferencesontreatmentofAISaroundtheglobe

AnticoagulationGuidelinesAlthoughnewbornswithstrokeusuallydonotrequireanticoagulanttherapy,thistherapyshouldbeusedinthefollowingsituations:

§ Presenceofathrombusinaheartchamberand/oronaheartvalve,and/orinthemajorarterialtree(e.g.,aorticarch),especiallyinthepresenceofaPFO,VSD,orASD.

§ CSVTorcorticalvenousthrombosiswithvenousinfarctionorriskofterritorytobelostwithvenousinfarction.

§ Radiologically-confirmedprogressionofstroke,orstrokerecurrence(bothrare).

Neonatalstroke-prognosisSurvival

§ 60-80%afterhemorrhage,§ 85-95%afterischemicinfarct

Neurologicresiduain75%§ Paresis,focaldisorders(hemianopsia,language,etc.),movementdisorder§ Behavioralandcognitivedeficitsarenotinfrequent(11%behavioral,21%language,69%reductionof≥1IQindexmeasure.

Seizuresremitinmostofchildren.However,between38%and46%ofneonateswithAISwilldevelopepilepsy.

§ Riskfactorsfordevelopmentofepilepsyincludedseizureatpresentationandinfantilespasms

Case 2: Sino-venous thrombosis in a child

Case 2 : CSVO -clinical summary6yo RHF,healthy,noprodromes;negFH

3dhx ofHA,N,V,progressivelethargy

DOA:RUEtwitching,urinaryincontinence

Exam:meningismus,T:100.2

Laboratory:§ PT14.6(nl 11.1-13.1)§ D-dimer>1000ng/ml(nl <500)§ α-2-AP140%(nl:80-130)§ Otherhypercoagulationstudiesnormal

InitialMRV

FollowupMRVafterendovascularthromborhexis

Case 3: Sino-venous thrombosis in a neonate

Initialpresentationandimaging:CThead

§Fulltermboy

§Vacuumassisteddelivery

§BW3.72Kg(25th %ile);headcircumf.36.5cm(10th)

§Intubatedatdeliveryb/orespiratorydistress

NeonatalCSVT:CTV-sag§CTVenogram

§PartialcompressionposteriorthirdSSS

§MRIandMRV,whenavailable,mayreplaceCTandCTV

SinusThrombosisinNeonatesThereisa15-20%incidenceofprogression,basedonexperienceatMGHPediatricsandDenverChildren’sHospital.

Riskfactorsinclude:§ involvementofadominanttransversesinusand/orthetorcula;presenceofaseizure

§ intracranialhemorrhageinatermNBintheabsenceoftrauma,§ vacuumextraction,§ orableedingdiathesis,§ positivefamilyhistoryforahypercoagulabilitydisorder

AnticoagulationinneonatesandchildrenwithCSVTAsymptomaticchild(noneurologicchanges,noheadandneckedema):§ Thereisnoconsensusatthistimeconcerningtheuseof

anticoagulanttherapy.§ Intheabsenceofintracranialhemorrhage,wepreferto

anticoagulate (optimallywithlowMWheparin)inviewofasignificantincidenceofprogressiontoheadandneckedema.

Symptomaticchild (noneurologicchanges,noheadandneckedema):§Consensusexiststousestandardunfractionatedheparin,butthereisnodatatosupportornotsupporttheearlyuseoffull-doseanticoagulanttherapy,especiallyinthesettingofapre-existingintracranialhemorrhage.

AnticoagulationinneonatesandchildrenwithCSVT

HeparinDosingLowmolecularweightheparin(enoxaparin)◦ Age>1yr 1mg/KgbidSC◦ Age3mo -1year 1.2mg/KgbidSC◦ Newborn– 3months 1.5mg/KgbidSC

Unfractionatedheparin(newbornto3months)◦ Standarddose 28U/Kg/hr◦ Lowdose 10U/Kg/hr

CSVT- longtermoutcomesDevelopmentaldelay 28-58%

Learningdisabilities ~5%

Cerebralpalsy 6-28%

Epilepsy 6-20%

Case 4: Arterial ischemic stroke in a 14 y.o. with Down’s syndrome

InitialPresentationandMRI14y.o.girlwithDown’ssyndrome

OnOCPsformenstrualregulation

4dayhistoryofRweakness(F/A/L),slurredspeech,attimesaphemic

VesselImaging:MRA,CTA

Conventionalcatheterangiogram

Disordersassociatedwithmoya-moya pattern§Sicklecelldisease

§Post-XRT(usuallyofopticglioma,craniopharyngioma,hypothalamicorbasalgangliaglioma)

§Neurofirbomatosis (NF-1)

§Tuberoussclerosis

§Down’ssyndrome

§Sturge-Webersyndrome

§TB,pyogenicmeningitis,leptospirosis

§Marfan’s;pseudoxanthomaelasticum;connectivetissuedisorders;FMD

§Aorticcoarctation

§Apert’s syndrome;Fanconi’s anemia

§Polyarteritis nodosa

§Glycogenstoragedisorders

Moya-MoyaBimodaldistribution<10,or>30y.o.§Youngerpatients->ischemicinfarcts§Olderpatients->hemorrhages(incl.‘rysmal)

Notassociatedwithspecificstroketype§RecurrentTIAs,esp.afterhyperventilation§TIAsaccruinginfarcts§ Infarctfromoutset

RiskFactors§LeftMCA:M1stenosis,withriskoffuturemoya-moya changesintrisomy21

§ElevatedLipoprotein(a):24mg/dL (nl <3)

§Familyhistory:mothersufferedanacuteMIinher50s

ApoaproteinboundtoLDLKringle andproteasedomainshomologoustoplasminogen

HeterogeneityofLp(a)[180-650kDa]duetonumberofKringle 4repeatsinApoa

Lipoprotein(a)

6.5- fold increased risk

Lipoprotein(a)Alowdensitylipoproteinwithahighdegreeofsequenceidentitywithplasminogen

Elevationsconfera6.5-foldincreasedriskofstrokeandCSVT(Kenet etal.,Stroke 2010) and3.2-foldofthromboembolisminchildhood(vonDepka etal,Blood,2002)

Antifibrinolytic(thereforepro-thrombotic)viacompetitionwithplasminogenforbindingsitesonaspecificendothelialcellreceptor

Bindsandinactivatestissuefactorpathwayinhibitor

Carriescholesteroltothevesselwall

Lipoprotein(a)inDown’sSyndromeItisunknownwhetherlipoprotein(a)iselevatedinTrisomy21§However,thereissomeevidencethatlipidsandlipoproteinsaregenerallyelevatedinthisgeneticcondition

PediatricstroketreatmentModifystrokeriskfactorsandtreatunderlyingconditions§SCD,CCAD,hypercoag states,moya-moya,Fabry’s,etc§Fesupplementation

Properdiet;exercise;tobaccoanddrugavoidance

AlternativestoOCPs◦ Norethindrone◦ Norgestrel (MirenaIUD)

t-PAforPediatricAcuteIschemicStroke?Norandomizedcontrolledtrials.

Importanttoestablishtimeofonset,whichcanbedifficultintheyoungchild

Requirementoftimelyimaging

Riskofcatheter-associatedthrombosisduringintra-arterialadministration(issues:useofheparin,catheterasforeignsurface,contrastmediumhyperosmolality)

ThrombolysisinPediatricStroke(TIPS)Five-yearmulti-centerinternationaltrial§ Safetyanddose-findingstudyofintravenous(IV)tPA inchildrenwithacuteAIS§ Determinethemaximalsafedoseofintravenous(IV)tPA§ Threedoses(0.75.0.9,1.0mg/kg)forchildrenage2-17years§Within4.5hoursfromonsetofacuteAIS.

Terminatedbecauseoflackofpatientaccrual,

Butdidleadto“consensus”dosesoft-PAtouseforthoseuncommoncasesinwhicht-PAisindicated

Amlie-Lefond C, et al. 2009 Lancet Neurology 2009

IPSScaseseriesoftPA use2003-2007(n=18)§ NostandardizedpediatrictPA guidelines,sotreatment‘realworld’§ basedonindividualcentres’ protocol/practicee.g.adulttPA protocol§ N=18children(9intra-arterial-tPA,9intravenous-tPA),16/18Ant.Circ.§ 2.2%ofchildrenwithAIS(vs.Janjua healthrecordlinkagestudy:1.6%)§ Treatmentfrequently‘offprotocol’e.g.IVMean3.3hrs post-onset

Outcome at Discharge IA or IV tPAN=18

No tPAN=656

Neurologically Normal 11% (2) 21%Neurological Deficit 78% (14) 74%Death 11% (2*) 3%Post-tPA ICH 22% (4) (all asymptomatic) NAOther Femoral A. thrombosis

+ foot amputation

*1 brain herniation, 1 brainstem infarct

IPSSOfflabel-compassionateuseoftPA

AspirinTherapyLow-dosecanbeaseffectiveas“full”dose,ifabsorbedproperly

Theremayalsobean“optimal”dosewhichblocksplateletthromboxanewhilepreservingatleastsomeendothelialcellprostacyclinproduction(i.e.,20to40mgQDinanadult)

Facedwithaspirin“failure,”onemayswitchtoclopidogrel

AspirinResistanceMaybeacauseofrecurrentischemicvasculareventsinpatients

takingaspirin.

Actuallyreferstomanydifferentphenomena:§ inabilityofaspirintoprotectpatientsfromvascularevents

(clinical);§ inabilityofaspirintoaffectanyoneofseveralmeasuresof

platelet(biochemical)§ inabilityofGItracttoabsorbASA

PlateletThrombi

Platelet-FibrinThrombusFormationInFlowingWholeBloodE.F.Grabowski2015

Platelets:greenFibrin:red

Case 5: Stroke in a child with Sickle Cell Disease

InitialPresentationandImaging:-TOFMRA11y/oAfricanAmericanboywithSickleCellDisease

PlayingbasketballallafternoonwhenhedevelopedsuddenonsetofLweakness(F/A/L),slurredspeech

UponarrivaltoMGHED,MRI,MRAwereobtained

Sicklecell- acuteandchronicinfarctions

SickleCellDiseaseAffects0.16%ofBlacks

25%havecerebrovasculardiseaseonneuroimaging,withorwithoutsymptoms§Cerebralinfarction 75%§ ICH20%§ SAH1-2%§Cerebralsino-venousocclusion§ FatembolismfromHbS-relatedboneinfarcts

q

RelativeIncidenceofSSStrokevs.AISinPediatrics§ArterialIschemicStroke

~0.05%byage18yrs (1/2000)

§HemoglobinSSStroke

16%byage18yrs (1/6)inSSdisease

SickleCellDisease:InfarctionIn70-80%,strokeoccursinunder-15y.o.

In60%,recurrent,usuallywithin3years

Occursinpatientswith§morefrequentcrises,andattimeofcrisis§ cardiomegaly§ concurrentinfection

andisaccompaniedby§ seizuresand§ alteredmentalstatus(but“cerebral,”oranalgesicdruguse?)

SickleErythrocytesandCerebralArteryOcclusion

SickleCellDisease:StrokeManagementO2andassure/establishairway

Controlofseizureactivity

Redcellpheresis toHgbS <30%

AvoidHct of>30owingtohyper-viscosityandconsequentimpairedO2delivery:SSRBCsareinherentlylessdeformableandgiverisetonearlythesameviscosityasAAblood,eventhoughSSHCTisnormallyonly20-24.

Anticoagulationiscontroversial;underinvestigation,butnotcurrentstandardofcare

StrokePreventioninSickleCellDisease(STOP)- TCDIfnormalPSV(<170cm/sec):annualscreening(orsemiannualif2-10y.o.)IfPSV>200cm/sec,repeatstudyinonemonth,andrepeatin3-6monthsStrokePreventionTrialinSickleCellAnemia(STOP):chronictransfusiontoHgbS <30%inchildrenwithpersistentlyabnormalTCDresultsOutcome:Incidenceofstrokedecreasedby90%

HydroxyureatrialsinSickleCellDiseaseSWITCH

90%secondarystrokeprevention

Stoppedbecauseofsafetyandfutilityconcerns§ Wareetal,StrokewithTransfusionsChangingtoHydroxyureaClinicalTrial(SWITCH).Blood2012;119:32925;§ Alvarezetal,AmJHematol,2013;88(11):932

TWITCH(TCDWithTransfusionsSwitchingtoHydroxyurea)

100%primarystrokepreventioninchildrenwithelevatedTCDvelocities

Inmaintenance,hydroxyureaequivalenttotransfusiontherapy§ Wareetal.HydroxyureaversuschronictransfusionformaintenanceoftranscranialDopplerflowvelocitiesinchildrenwithsicklecellanemia- TCDwithtransfusionschangingtohydroxyurea(TWITCH):amulticenter,open-label,phase3,non-inferioritytrial.Lancet2016;387:661

NovelNeuroprotectantsinAcuteIschemicStroke3K3A-APC§ GeneticallyengineeredactivatedproteinC,usedincombinationwitht-PA§ Clinicaltrialforsafety(Rhapsody,May2015-May2017)

Pre-Implantationfactor(PIF)§ Promotesembryotrophic andneuroprotectivedecidual genes

PlacentaleXpanded (PLX)cells§ ProtectPC12cells- anestablishedmodelofvariousnervecellsincludingdopaminergicneurons- fromdeathafteroxygenandglucosedeprivation

Case 6: Compelling risk factors for stroke

Primary Stroke Prevention

Nostroke,butcompellingriskfactorsina13y.o.boyDiagnosis:At-high-risk-for-Stroke

FH:mothersufferedanischemicstrokeatage42;hadmigraines,ANAof1:21,000,andfoundtohaveproteinSdeficiency.

Patienthad:§Migraines§ ANAof1:1280§ ProteinSof41%§ Lipoprotein(a)of65mg/dl(normal<30mg/dl)§ PFOwithright-to-leftshunting.

ManagementWarfarinand81mgASAx8months,untilPFOclosure

81mgASAsubsequently

Niaspantocorrecttheelevatedlipoprotein(a)§ Interestingly,hisheadachesdisappearedafterPFOclosure.

ConclusionsMortalityduetountreatedpediatricstrokeisapproximately9-10%

Thereissignificantneurologicalandneurocognitivemorbidityinthesurvivors,includingseizures,hemiparesis,andneurocognitiveissues

Neonatesoverallhaveabetterprognosisthanolderchildren

ConclusionsNeonateswithearlypresentationhavebetterprognosisthanthosewithdelayedpresentation,especiallyintermsofmotordeficits

ThosewithAIStendtohavemoredeficitsthanthosewithCVST

Thereisasignificantcorrelationbetweenthepresenceofmotordeficitsandbothepilepsyandneurocognitivedeficits

ConclusionsPost-strokeevaluationmustinclude:§Physicaltherapy§Occupationaltherapy§Speechandlanguagepathology§Neuropsychologicalevaluation§Vocationaltraining§Psychology/socialwork§Psychiatry(ifindicated)

SummaryStrokeinchildhood,whilenotcommon,isalso

a)notrare,and

b)frequentlyunsuspectedatpresentation.

Thecausesandpatternsofpediatricstrokediffermarkedlyfromthoseofadultstroke.

Acoordinatedmulti-disciplinarypediatricstroketeamisnecessarytoprovideeffectiveandtimelyevaluationandmanagement.

TeamMembersatMGHNeurology:P.Musolino,K.Krishnamoorthy,andF.Buonanno

PediatricHematology/Oncology:E.Grabowski

PediatricNeuroradiology:P.Caruso

Neurosurgery:W.ButlerandC.Duhaime

CoagulationLab:E.VanCott

Neuropsychology:A.Morgan

PediatricPMR:D.Nimec,S.Quinn

Follow-upClinic:E.Grabowski,F.Buonanno,P.Musolino

ThefullteamatMGHwww.massgeneral.org/children/services/treatmentprograms.aspx?id=1628

HowtoreachusForACUTE cerebro-vascularreferrals:§ call617-726-2000§ andpage21333,the“pediatricneurologyresidentoncall.”

§ thispersonthenactivatesthepediatricstroketeam

ForOUTPATIENT evaluationsandfollow-up:§ call617-726-2737

Thankyou….

Thankyou...questions?

NeurogenesisduringEmbryoniclifeà SVZ

Arias-Carrión InternationalArchivesofMedicine2008NatureNeuroscience14,1382–1389(2011)

PostnatalNeurogenesisà PerivascularNiche

AdaptedfromZacchigna etal.NeuralStemCells- NewPerspectivesbyLucaBonfanti.Chapter8.2013

ACUTESTROKEin2-18yearoldpatientPediNeuro FellowConsultPaged

Likely IschemicStroke LSW <6hs

PediNeuro FellowactivatesPediStrokeGroupPage

Examine patient and obtain history (if at home page Adult Acute Stroke Fellow and ask to start evaluation)

PICUResourceNurse•NotifyPICUfellow•Preparebedforpossibleadmission•AlertsRapidResponseTeam

EDorFloorRN•CheckFSBS•Place18-20gaIVsx2•SendLabs;Heme,Chem-7,Coags•PrepareptforCTorrapidMRI- CheckBP- O2tokeepSpO2>94%•WeightptorestimateusingBroselow traumatapeStrictNPO•AvoidplacingNGT/foley•VSq15”

EDPharmacist•Respondtopt’sbedside•CommunicatewithCRConcallnurse(pager)•Reviewptweight• CalculatestPA dosagewithTIPStrialpharmacist•DispensetPA fromTIPStrialtoMD•Dispenseothermeds(D50W,labetolol,nicardipine)

PediNeuro andPICUFellow•Gatherparent/guardiancontactinfo•PerformsPediatricNIHSS•VerifiesLSWandcontraindications•AssuresCT/CTA/MRIandlabordersareplacedbyEDresident•ReviewsMRIsafetyquestionswithparent/guardian•UpdatesPedi-StrokeandConsultAttending

EDResident•Orderslabs,MRIbrainpediatricstrokeprotocolandCT/CTAheadandneckstrokeprotocol•Helpscoordinatesedation(ifneeded)withpediatricanesthesia

CRCNurse•AssistsEDnurseandTIPStrialpharmacist•Startsexamsandblooddrawsperprotocol•FacilitatestransitiontoPICUnurse

PediStrokeAttending•DeterminesImagingprotocolneeded•PerformsPediatricNIHSS•DetermineseligibilityforRxinterventions

Discusswithparentstherapeuticoptionsandrisks

NosignificantchangesfrominitialNIHSSManageSBPandDBPtokeep<90%ile

IfCT/MRIokPediStrokeAttendingconsideranticoagulation,IVtPA orendovascularRx

TransportpttoEDCT/MRIscanner