update on paediatric neurology · cerebral palsy – most common cause of secondary dystonia ......
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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
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
EvelinaChildren’sHospital
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”
EvelinaChildren’sHospital
Spas=city:• Velocitydependantincreaseoftone• Briskjerks• Sustainedankleclonus• weakness
Dystonia
Dystonia:involuntarycon=nuousorintermiGentmusclespasmscausingrepeatedtwis=ngmovementsorposturesorboth.Tonenotvelocitydependant,jerksnormalorcanbeabsent“Nottofast–nottooslow,nottosmall-nottoobig,nottoostrong–nottooweak”
EvelinaChildren’sHospital
• 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
EvelinaChildren’sHospital
Medica=onforspas=cityanddystonia
DystoniaØ BaclofenØ TrihexyphenidylØ BenzodiazepinesØ L-dopaØ TetrabenazineØ TizanidineØ ClonidineØ ChloralhydrateØ GabapentinØ CarbamazepineØ DantroleneØ Botulinumtoxin
Intrathecalbaclofenpump
DeepBrainS2mula2on
Intrathecalbaclofenpump
Alwaysthinkaboutgoalsfortreatment!
Selec2vedorsalrhizotomy
EvelinaChildren’sHospital
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
EvelinaChildren’sHospital
Statusdystonicus:defini=onLifethreateningmovementdisorderemergencyIncreasinglyfrequentorcon2nuoussevereepisodesofgeneralizeddystonicspasms(contrac2ons)Statusdystonicus:Ø Tonic–mainlysustainedcontracturesandposturesØ Phasic–rapidandrepe22vedystoniccontrac2ons
Consideredrare–only100reportedcases,butlikelyunderreportedandunderrecognisedUpto60%betweenages5and16yearsCerebralpalsy–mostcommoncauseofsecondarydystoniainchildren Allenetal2013
EvelinaChildren’sHospital
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.
EvelinaChildren’sHospital
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?
EvelinaChildren’sHospital
ü Infantsü Abnormalimagingü Focalonsetseizuresü Con2nuingseizuresfollowingtrialsof2AEDs(refractoryepilepsy)ü Possibleneuro-degenera2onü Uncertain2esrediagnosisü Ongoing?Non-epilep2cevents
NeurologyreferralKnowyourserviceandpathway!
EvelinaChildren’sHospital
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
EvelinaChildren’sHospital
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
Case:5yearoldgirl
• Intermicentslurredspeech3daysaqerminorheadinjury
• NormalbrainMRI• Withinnextfewdays:progressiveepisodesofconfusionandbehaviouralchange
• Choreaoftheleqhand
Case:5yoldgirl• Fewfocalseizures• Speechproblemsworsentonospeech• choreaonehandpersists• EEGencephalopathic• CSF–normalcells,sugarandprotein
• Viralserologyandculturesnega2ve
• Rx:an2bio2cs,an2virals,phenytoin
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
EvelinaChildren’sHospital
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.
EvelinaChildren’sHospital
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
EvelinaChildren’sHospital
Statusepilep=cus:defini=onsILAE2014:Statusepilep2cus:Seizurelas2ngmorethan30minutesorseizureswithoutfullrecoverybetweenthemlas2ngformorethan30minutesRefractorystatusepilep2cus:seizureorseizureswithoutfullrecoverybetweenthem,whichfailedtreatmentwithbenzodiazepinsand1AEDProlongedseizure:las2ngmorethan5minutes.
Neurocri=calCareSocietyguideline2012:Statusepilep2cus:seizureorseizureswithoutfullrecoverylas2ng>5minDefinitecontrolshouldbeestablishedwithin60minofonset
EvelinaChildren’sHospital
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.
EvelinaChildren’sHospital
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.
EvelinaChildren’sHospital
Statusepilep=cus
Median2metoadministersecondan2convulsanttoaseizingchild:24minutesLewenaetal200923%receivedbenzodiazepinedosesoutsideofguidelinesTobiasetal2008
NatRevNeurol.2015Jun;11(6):310.doi:10.1038/nrneurol.2015.93.Epub2015May26.Epilepsy:Childrenwithstatusepilep=cuscanfaceconsiderabledelaysbeforereceivingeffec=vean=seizuretreatment.
EvelinaChildren’sHospital
Statusepilep=cus:Neurocri=calcareguideline
UnlesstheSEe2ologyhasbeeniden2fiedanddefini2velycorrected,allchildrenshouldalsoreceivean“urgent”categoryan2convulsantinaddi2ontoabenzodiazepineIntuba2onby10minifairwayandgasexchangecompromised
Statusepilep=cus:neonatesphenobarbitalphenytoinmidazolam?leve2racetampirydoxine
EvelinaChildren’sHospital
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
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?
EvelinaChildren’sHospital
• 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