Update on Paediatric Neurology · Cerebral palsy – most common cause of secondary dystonia ......

UpdateonPaediatricNeurologyPrac%calPaediatrics,June2017

DrDanielELumsdenConsultantinPaediatricNeurologyComplexMotorDisordersService

EvelinaChildren’sHospital

Outline:u Neurologicalexamina2onu MovementdisordersExamplesande2ologyManagementStatusDystonicusu EpilepsyWhentoreferseizures/epilepsyu Autoimmuneencephali2s

Neurologicalexamina2on•  Observa2on

– Playinwai2ngarea– Walkingintoclinic– Facialfeatures– Posture– Movements– Speechandcogni2on– Visualbehaviour– Abnormalmovements,events

Neurologicalexamina2on

•  FunandGames(screening)– Standingup(chairorfloor)– Armsout– Eyesclosed– Standingononeleg– Hopping,skipping– Walkingon2ptoes,heels,tandemwalking– Climbontocouch

Neurologicalexamina2on•  Targetedformalexamina2on

–  Tone(trunkandlimbs)–  Power(fullan2gravity=3/5)–  Reflexes–  Cranialnerves(vision,eyemovements,facialasymmetry,swallowingdiffculty,cough)

–  Sensa2on– Measurements

•  Weight,height,headcircumference–  Extras

•  Heart,abdomen,spine,hipsetc


Movementdisorders

Movement/MotorDisordersinChildrenandYoungPeople

Hyperkine=c•  Tremor•  Myoclonus•  Chorea/Ballismus•  Athetosis•  Dystonia•  Tics•  Stereotypies

Hypertonic•  Spas2city•  Dystonia•  Rigidity

SangerTD,ChenDetal:DefiniAonandclassificaAonofhyperkineAcmovementsinchildhood;MovDisord.2010Aug

SangerTD,DelgadoLetal:ClassificaAonanddefiniAonofdisorderscausinghypertoniainchildhood;Paediatrics2003Jan

Nega=vesignsu weakness

u Reducedselec2vemotorcontrolu Ataxia

u Apraxia

SangerTD,ChenDetal:DefiniAonsandclassificaAonofnegaAvemotorsignsinchildhood;Paediatrics2006


Movementdisordercanbeinterpretedasseizuresandshouldbecarefullydifferen2ated!

Spasticity “Versus” Dystonia

•  Spasticity: •  Velocity dependent increase in tone •  Component of the UMN complex •  Implies dysfunction of the Corticospinal tract/Descending

motor pathways and loss inhibition at spinal cord level

•  Dystonia: •  Disorder of involuntary sustained or intermittent muscle

contractions causing abnormal movements or postures •  Traditionally “basal ganglia” disorder – now appreciated

to be due to dysfunction across (potentially) broader motor network

•  CST function not involved.

Spas2city=Somethingyou“feel”

Dystonia=Somethingyou“see”

34childrenwithCP:87%hadspas=city78%haddystonia

2009


Spas=city:• Velocitydependantincreaseoftone• Briskjerks• Sustainedankleclonus• weakness

Dystonia

Dystonia:involuntarycon=nuousorintermiGentmusclespasmscausingrepeatedtwis=ngmovementsorposturesorboth.Tonenotvelocitydependant,jerksnormalorcanbeabsent“Nottofast–nottooslow,nottosmall-nottoobig,nottoostrong–nottooweak”

Myoclonus

myoclonus:arrhythmic,short,shock-likemovementscausedbysuddenmusclespasmorrelaxa2on


Chorea

Tremor

Tremor: rhytmic movements around a joint

Myoclonus Chorea Athetosis Dystonia

Spectrum?

Do these grey areas matter?


•  Structuralbraindamage–  Cerebralpalsies–  Childhoodstrokes–  Encephali2s–infec2ve/autoimmune–  Tumours–  Acquiredbraininjury(trauma2c,

hypoxic)

•  Metabolicanddegenera2vedisorders

•  Other–  Infec2on,vascularmalforma2ons,–  Gene2c:Recsyndrome,DYT1,

DYT11,TITF1,othergene2cmovementdisorders

–  Toxic:medica2on,CO

•  Alldeservedetailedinves2ga2ons

•  Brainscans,bloodandurinetests,gene2ctests

Inves2ga2onsformovementdisorders–tailoredtosuspectedae2ology

Avoid Triggering Factors

Treat Triggers

Treat Dystonia

Good pressure/skin care Good sleep hygiene Nutrition/varied diet Vaccination Emotional/Psychological support

Choice of medication Depends upon: Background meds Urgency of treatment Other aspects of Motor Disorder etc

Analgesia Laxatives Relieve urinary retention Orthopaedic input Antibiotics

Spas2cityØ BaclofenØ BenzodiazepinesØ TizanidineØ DantroleneØ Botulinumtoxin


Medica=onforspas=cityanddystonia

DystoniaØ BaclofenØ TrihexyphenidylØ BenzodiazepinesØ L-dopaØ TetrabenazineØ TizanidineØ ClonidineØ ChloralhydrateØ GabapentinØ CarbamazepineØ DantroleneØ Botulinumtoxin

Intrathecalbaclofenpump

DeepBrainS2mula2on

Intrathecalbaclofenpump

Alwaysthinkaboutgoalsfortreatment!

Selec2vedorsalrhizotomy


Statusdystonicus


Statusdystonicus:casevigneGe9yboywithquadriplegicCP,ex-prem,PEG1dayHxpffever38.5Distressed,unsecled,increasedmovementsIncreasedrespiratorysecre2ons?Chestinfec2on:CRP9,WBC11,ChestX-Ray–possibleperi-bronchialchangesinrightlowerlobe,urineclearUrea7.4,normalelectrolytesandcrea2nineStartedtreatmentwithco-amoxiclavDay3–con2nuestospikefeverupto39.5at2mes,unsecledChestX-Rayreviewed–noconvincingsignsofchestinfec2oninflammatorymarkerslowmumsays–sleepsverylicle,howmuch?NotdocumentedCK60000urea8.5normalelectrolytescrea2nine–uppernormalrange


Statusdystonicus:defini=onLifethreateningmovementdisorderemergencyIncreasinglyfrequentorcon2nuoussevereepisodesofgeneralizeddystonicspasms(contrac2ons)Statusdystonicus:Ø Tonic–mainlysustainedcontracturesandposturesØ Phasic–rapidandrepe22vedystoniccontrac2ons

Consideredrare–only100reportedcases,butlikelyunderreportedandunderrecognisedUpto60%betweenages5and16yearsCerebralpalsy–mostcommoncauseofsecondarydystoniainchildren Allenetal2013

Lumsden et al 2013

Adapted from Allen et al 2013


StatusDystonicus:ManagementPlan

q Considerifincreaseds2ffness,movements,irritability,poorsleep,feverq CheckCK,electrolytes,urea,crea2nine,liver,Ca,Mg,P,BGq Lookforcontribu2ngfactorsandtreat–infec2on,pain(o22s,fracture,gut),ITBorDBSmalfunc2on.q Talktoyourpaediatricneurologyteam

ü Maintainfeedingifpossibleü Ensuregoodhydra2onenteral/IV–monitorurineoutput,fluidchart,renalfunc2ontests,BGasrequired,CK,urinedips2ckforblood(myoglobinuria)ü Sleepcharttoclearlydocumentperiodsofsleepü Extremespasms,discomfortpar2cularlyifairwaycompromise–IVlorazepam/PRdiazepamorbuccalmidazolamastemporizingmeasureü “sleepabolishesdystonia”chloralhydrate30-50mg/kgasrequiredupto4-6hourlyclonidinefirstdose1mcg/kgandrepeat4-6-8hourlyeverynextdosecanbeincreasedby1mcg/kguptp25mcgifresponseunsa2sfactorydosesupto2mcg/kg/hourIVorenteral.MonitorBPandHR.ü Considermidazolaminfusionbuttolerancedevelopsquickly.


EpilepsyWhentorefer?


Casestudy4/12boy

•  Term delivery, IUGR, thrombocytopenia resolved •  New onset of focal seizures: eyes deviation and flickering +/- upper

limb jerks •  Seizures stopped after phenytoin load •  Normal CT, baseline bloods and LP

•  Refer to neurology? Y N •  Clinic or on call service?


ü Infantsü Abnormalimagingü Focalonsetseizuresü Con2nuingseizuresfollowingtrialsof2AEDs(refractoryepilepsy)ü Possibleneuro-degenera2onü Uncertain2esrediagnosisü Ongoing?Non-epilep2cevents

NeurologyreferralKnowyourserviceandpathway!


Casestudy:18/12girl

Ex prem 29/40 Neonatal sepsis, early seizures Developmental delay Evolving motor disorder – tone mostly increased in left UL, brisk DTR Meds: valproate + phenobarbiton Mum reports episodes of stiffness with glazed look Valproate increased trihexyphenidyl started – some improvement EEG normal


18/12girl,exprem-homevideoMedica=on:Navalproate,phenobarbiton,trihexyphenidyl

•  Wasitepilep2c?infant toddler Older child

Normal movements ‘Shuddering attacks’ Rigors Sleep myoclonus Gratification disorder Gastro-oesophageal reflux Movement disorder (eg paroxysmal tonic upgaze) Cardiac arrhythmia

Behavioural Breath holding Night terrors Gratification disorder Stereotypies Day-dreaming Learning Diffs

Migraine Syncope Cardiac Benign paroxysmal vertigo Movement disorder Fabricated illness

Tic disorder Cardiac Vaso-vagal syncope Movement disorder Pseudo-seizures/non epileptic attacks

PaediatricEpilepsyTraining

•  Standardisedcourses•  Availableinallregions•  PET1•  PET2•  PET3

www.bpna.org.uk/pet

Encephali=sAutoimmuneencephali=s

Case:5yearoldgirl

•  Intermicentslurredspeech3daysaqerminorheadinjury

•  NormalbrainMRI•  Withinnextfewdays:progressiveepisodesofconfusionandbehaviouralchange

•  Choreaoftheleqhand

Case:5yoldgirl•  Fewfocalseizures•  Speechproblemsworsentonospeech•  choreaonehandpersists•  EEGencephalopathic•  CSF–normalcells,sugarandprotein

•  Viralserologyandculturesnega2ve

•  Rx:an2bio2cs,an2virals,phenytoin

Case:5yoldgirl

•  NMDAreceptoran2bodyposi2ve

•  Highdosesteroids

•  Fullrecoveryat12monthsFU

Auto-immuneencephali2des•  Treatablecauseofencephali2s•  Neuropsychiatricfeaturesverycommon:behaviouralchange63%confusion50%hallucina2ons25%Seizures83%andmovementdisorder38%Hacohenetal2013•  Auto-an2bodiestocellsurfacean2gens,crucialfor

neurotransmission•  VGKC,GAD,NMDAreceptoran2bodies...•  >400casesclinicallyrelevantelevated2tresinUKoverlast3

years•  Increasinglydiagnosedinchildrens2llunderdiagnosed•  Paraneoplas2c–muchmorefrequentinadults

NMDAencephali2s•  Shorthistory–days/weeks•  Seizures/oddepisodes•  Behaviouralchange,encephalopathy•  Involuntarymovements

•  EEGabnormal,lymphocytesinCSF,+/-imagingabnormali2es•  NMDAreceptoran2bodyposi2ve•  N-methyl-D-aspartateglutamatevoltage-dependentchannels•  Associa2onwithovarianteratomaandotherneoplasia

(20-50%adults)

VGKCencephali2s•  Canpresentaslimbicencephali2s,butother

presenta2onspossible•  Subacutepersonalitychange,memoryproblems,

seizureswithinfirstfewdays;temporallobeepilepsy•  MRIchanges–highsignalmedialtemporallobeoqen

withcontrastenhancement•  Associa2onwithmalignancy(adults;recentUKstudy–39childrenVGKCAb+,none

hadneoplasm;presentedatBPNAconference2014)•  oqenmonophasicillness•  An2body2tresfallwithtreatment

Auto-immuneencephali2searlytreatment

•  Byrneetal,2014:NMDARencephali2s,literaturereview,43cases88%treatedwithin15dayshadfullrecovery36%treatedaqer15dayshadfullrecoveryTreatment:steroids,IVIG,plasmaexchange,rituximab

Autoimmuneencephali2s–diagnos2ccriteriaZulianietal2012

Criteria • Acute or subacute (<12 weeks) onset of symptoms • Evidence of CNS inflammation (at least one of): CSF (lymphocytic pleocytosis, CSF specific oligoclonal bands or elevated IgG index) MRI inflammatory changes Inflammatory neuropathology on biopsy • Exclusion of other causes (infective, trauma, toxic, metabolic, tumors, demyelinating or history of previous CNS disease

Supportive features •  History of other autoimmune disorder •  Preceding infectious illness or viral-disease-like prodromes

DrDanielELumsdenPrac%calPaediatrics,June2017


Statusepilep=cus


Statusepilep=cus:casestudy7yboyPreviouslyfitandwell,grandmotherwastreatedforseizuresasachildFewhoursHxofnauseaandnotfeelingwellGTCseizure,fever40Conambulancearrival,rectaldiazepamgivenTakentoA&Elorazepam–phenytoin–phenobarbitone-midazolaminfusionI/V,CTsuspicionofsinusvenousthrombosis(dismissedlater),retrivedtoPICUPICU:AbnormalposturingandlowGCSonacemptstowakeupIni2alnormalMRI,onday5–widespreadwhitemacerchangesassociatedwithcri2calcondi2on.nega2veinfec2onscreenincludingLP(CRP,WBCini2allymildlyraised)Ini2allyhighCK,liverenzymes,mildrenalandcoagula2onabnormalityNega2vemetabolicandgene2cinves2ga2onsReviewofpresenta2on:40minCSEbeforearrivaltoA&E,80mintotaldura2onpH6.9,PCO2>20(unrecordable)onini2alBGSequelae:wheelchairbound,quadriplegia,anarthria,PEG,seizures,intelectualimpairment.


Statusepilep=cus

ChinRF,NevilleBG,PeckhamC,etal:Incidence,cause,andshort-termoutcomeofconvulsivestatusepilepAcusinchildhood:ProspecAvepopulaAon-basedstudy.Lancet368:222-229,2006

Themostcommonpaediatricneurologicemergencyincidence18-23per100000childrenperyear

32%prolongedfebrileseizures17%Acutesymptoma2c(mostCNSinfec2onoracutemetabolicdecompensa2on)12%idiopathic(withdiagnosisofidiopathicepilepsy)7%unclasified


Statusepilep=cus:defini=onsILAE2014:Statusepilep2cus:Seizurelas2ngmorethan30minutesorseizureswithoutfullrecoverybetweenthemlas2ngformorethan30minutesRefractorystatusepilep2cus:seizureorseizureswithoutfullrecoverybetweenthem,whichfailedtreatmentwithbenzodiazepinsand1AEDProlongedseizure:las2ngmorethan5minutes.

Neurocri=calCareSocietyguideline2012:Statusepilep2cus:seizureorseizureswithoutfullrecoverylas2ng>5minDefinitecontrolshouldbeestablishedwithin60minofonset


Convulsivestatusepilep=cus:inves=ga=onsofe=ology

Abendetal2014

• Bloodglucose,bloodgas,Na,K,Ca,Mg,P,renalfunc2on,liverfunc2on,FBC,CRP,coagula2on,bloodculture,AEDlevels,toxicology• Virology-respiratorypanel,throatandrectalswabforenterovirus,serumforHSVPCRandsavesample.• CT,ifnormal–MRI• LPincludingPCRforHSV,VZV,enterovirussavesampleforfurthertestincludingNMDARan2bodies.• Ammonia,lactate,considerothermetabolicinves2ga2ons• An2thyroidan2bodies.


Convulsivestatusepilep=cus:mortalityandmorbidity

Novoroletal:Outcomeofconvulsivestatusepilep%cus:areview.ArchDisChild.2007Nov;92(11)

2.7-5.2%mortalityinchildren5-8%admicedtoICU0-2%inunprovokedoffebrileCSE

13%adults38%elderly

• <10%or<15%childrenwillhaveneurologicaldeficit• Causeappearstobemaindeterminantofmortalityandmorbidity• Somestudiessugges2ngneurologicaldeficitrelatedtolongerdura2onofCSE• Animalmodels:wealthofdataindica2ngthatlongerseizuresareharmfulandresultinworseoutcomes.


Statusepilep=cus

Median2metoadministersecondan2convulsanttoaseizingchild:24minutesLewenaetal200923%receivedbenzodiazepinedosesoutsideofguidelinesTobiasetal2008

NatRevNeurol.2015Jun;11(6):310.doi:10.1038/nrneurol.2015.93.Epub2015May26.Epilepsy:Childrenwithstatusepilep=cuscanfaceconsiderabledelaysbeforereceivingeffec=vean=seizuretreatment.


Statusepilep=cus:APLS


Statusepilep=cus:Neurocri=calcareguideline

UnlesstheSEe2ologyhasbeeniden2fiedanddefini2velycorrected,allchildrenshouldalsoreceivean“urgent”categoryan2convulsantinaddi2ontoabenzodiazepineIntuba2onby10minifairwayandgasexchangecompromised

Statusepilep=cus:neonatesphenobarbitalphenytoinmidazolam?leve2racetampirydoxine


Statusepilep=cus:leve=racetam

• Broadspectruman2convulsant• IncreasingevidenceofsafetyandefficacyinSE• Observa2onalstudiesinchildrenreportedsafetyandefficacyinSEandacutesymptoma2cseizuresat20-60mg/kg• Nohepa2cmetabolism• Lowerriskofseda2onorcardiorespiratorydepression• Clearancedependantonrenalfunc2on–needsdosereduc2onformaintenance• Mostcommonloadingdose30mg/kg

Abendetal2014

Clonidine

Ø DystoniatreatmentØ Spinalandsupraspinalα2adrenergicreceptoragonistØ ReducesaspartateandglutamatereleaseinpresynapticterminalsanitinocioceptivepropertiesØ InitiallyusedfortreatmentofarterialhypertensionØ Sideeffects:somnolence,bradycardia,lowBPØ Sameoral/transdermalandIVdailydose

Clonidine-ourexperience

•  1 mcg /kg test dose - monitor BP •  3 – 8 doses or continuous IV infusion •  Max dose used in our group: 3-4 mcg/kg/hour enteral and 48 mcg/kg/day (2mcg/kg/hour) IV •  Side effects at high doses (in combination with

chloral hydrate): • 

Chloralhydrate

Ø Seda2veandhypno2cthroughenhancingGABAreceptorsØ IngredientofMickeyFinnØ Metabolizestotri-chloro-ethanolØ Dose:30-50mg/kgor100mg/kg/24hin3-4doses,max4g/24hØ Sideeffects:deepseda2on,respiratorydepression,lowbloodpressure,liverfailure,tolerance,dependency,withdrawalsymptoms

JamesBondsays,"that's...chloralhydrate"inthemovie"TheLivingDaylights"beforecollapsingfromit'seffects

Case2:15y

References:•  Abendetal:Statusepilep2cusandrefractorystatusepilep2cusmanagement.SeminPediatr

Neurol21:263-274.2014•  LewenaS,PenningtonV,AcworthJ,etal:Emergencymanagementofpediatricconvulsive

statusepilep2cus:Amul2centerstudyof542pa2ents.PediatrEmergCare25:83-87,2009•  TobiasJD,BerkenboschJW:Managementofstatusepilep2cusininfantsandchildrenpriorto

pediatricICUadmission:Devia2onsfromthecurrentguidelines.SouthMedJ101:268-272,2008

ITB–whatisit?


• Baclofen-GABA(b)agonist–laminaeI-IVofspinalcord,inhibi2onofneurotransmicersrelease• Ini2allydiscoveredasan2-epilep2c

• Poorlycrossesblood-brainbarrier

• Intrathecaldeliverymuchmoreefficient

• Differentmodesofdelivery:con2nuousinfusion,variableinfusion,boluses

Effec=ve,but:Ø RiskofoverdoseincludingrespiratorydepressionØ Riskofwithdrawalincludingrhabdomyolysis

DBS:Vocabulary

Pallidal Deep Brain Stimulation (DBS)

Burke Fahn Marsden Dystonia Rating Scale (BFMDRS) –videobasedscoremotorscore(eyes,mouth,speech/swallowing,neck,upperlimbs,trunk,lowerlimbs)0-120

disabilityscore(speech,wri=ng,feeding,ea=ng,hygiene,dressing,walking0-30

Dystonia

Verygoodresultsinprimary(gene2c)dystonia.Meaningfulbutmodestresultsinsecondarydystoniae.g.CP

Update on Paediatric Neurology · Cerebral palsy – most common cause of secondary dystonia ......

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