MOVEMENT MOVEMENT DISORDERSDISORDERS

IN CHILDRENIN CHILDRENSeptember 2010September 2010

Gogi Kumar MDChild NeurologistDayton Children’s HospitalWright State University

Movement disorders in Movement disorders in childrenchildren

Can be paroxysmal: Dystonia, tics, tremorsCan be paroxysmal: Dystonia, tics, tremors

No single diagnostic testNo single diagnostic test

Clinical description is importantClinical description is important

Often confused with seizures, malingering, Often confused with seizures, malingering, cerebral palsycerebral palsy

Treatment can be effective in a small Treatment can be effective in a small percentagepercentage

Type of abnormal Type of abnormal movementsmovements

Chorea Chorea

AthetosisAthetosis

DystoniaDystonia

MyoclonusMyoclonus

TicsTics

TremorsTremors

StereotypiesStereotypies

Movement disorders in Movement disorders in childrenchildren

The The most commonmost common types of abnormal types of abnormal movements in children movements in children

Tics Tics

Drug induced Drug induced

Dystonia related to CPDystonia related to CP

Sydenham’s choreaSydenham’s chorea

Essential or task specific tremorEssential or task specific tremor

Psychogenic tremorPsychogenic tremor

Movement disorders in Movement disorders in childrenchildren

Percentage in a series of 684 patients under 18 yrs of age

Movement disorders in children, Fernandez-Alvarez, Aicardi

Tics are different !!!Tics are different !!!

Can be reproduced voluntarilyCan be reproduced voluntarily

Patient has partial controlPatient has partial control

Do not interfere with voluntary activityDo not interfere with voluntary activity

Tics predominate in facial muscles, proximal Tics predominate in facial muscles, proximal limbslimbs

May persist in sleep May persist in sleep

ChoreaChorea

Chorea is a rapid, Chorea is a rapid, purposeless, irregular, jerky purposeless, irregular, jerky movement that seems to movement that seems to flow randomly from one part flow randomly from one part of the body to another.of the body to another.

EtiologyEtiology

Genetic choreasGenetic choreas

Huntington’s diseaseHuntington’s disease

NeuroacanthocytosisNeuroacanthocytosis

Ataxia telangiectasiaAtaxia telangiectasia

Spinocerebellar ataxiasSpinocerebellar ataxias

Paroxysmal kinosegenic choreoathetosisParoxysmal kinosegenic choreoathetosis

Etiology of choreaEtiology of chorea

Parainfectious and autoimmune disordersParainfectious and autoimmune disorders

Sydenham’s choreaSydenham’s chorea

SLESLE

Wilson’s diseaseWilson’s disease

Chorea gravidarumChorea gravidarum

Antiphospholipid antibody syndromeAntiphospholipid antibody syndrome

Post infectious or post vaccinal Post infectious or post vaccinal encephalitisencephalitis

Etiology of choreaEtiology of chorea

Athetotic Cerebral PalsyAthetotic Cerebral Palsy

Bilirubin encephalopathyBilirubin encephalopathy

Basal ganglia tumorsBasal ganglia tumors

Metabolic disorders.Metabolic disorders.

Sydenham’s ChoreaSydenham’s Chorea

Most common causeMost common cause of chorea in children of chorea in children

Typical age is 8-9yrs with female Typical age is 8-9yrs with female preponderance.preponderance.

4-8 weeks after GABHS pharyngitis.4-8 weeks after GABHS pharyngitis.

20 – 35% may have hemichorea.20 – 35% may have hemichorea.

Hypotonia, emotional lability, ADHD, tics, Hypotonia, emotional lability, ADHD, tics, OCD symptoms may accompany it.OCD symptoms may accompany it.

60-80%pts have cardiac involvement.60-80%pts have cardiac involvement.

Sydenham’s choreaSydenham’s chorea

Self limited disorder with remission within 6-9 Self limited disorder with remission within 6-9 months.months.

Recurrence is reported in 20-50% of patientsRecurrence is reported in 20-50% of patients

Inv: ASO titres, throat culture, cardiac Inv: ASO titres, throat culture, cardiac examination.examination.

Treatment: Sodium Valproate, Carbamazepine, Treatment: Sodium Valproate, Carbamazepine, Pimozide.Pimozide.

Tetrabenazine, TiaprideTetrabenazine, Tiapride

SSRIs for OCD symptoms.SSRIs for OCD symptoms.

Rheumatic fever prophylaxis.Rheumatic fever prophylaxis.

Patient with possible Sydenham’s chorea

History including FH and drug use,physical examination

Atypical history or hemichorea

Typical history

Imaging MRI

ESR,CRP,Echocardiogram,ECG

Jones criterion not met Jones criterion met

ASO/Anti Dnase B,Throat culture, Rapid antigen test,GABHS, RBC, TFT,Renal and hepatic function,ceruloplasmin,RF antinuclear antibodies

Sydenham’s chorea

Other cause

Other cause

No other cause

Oosterveer DM et al. Sydenham’s chorea: a practical overview of the current literature. Pediatr Neurol 2010;43:1-6.

Drug induced choreaDrug induced chorea Dopamine receptor blocking agentsDopamine receptor blocking agents

Dopamine agonistsDopamine agonists

SSRIsSSRIs

TCAsTCAs

OCPsOCPs

Lithium.Lithium.

Investigations and TreatmentInvestigations and Treatment

MRI to rule out basal ganglia lesion.MRI to rule out basal ganglia lesion. Rheumatological markers.Rheumatological markers. Specific Gene testing according to the Specific Gene testing according to the

presence of other features.presence of other features. Treatment:Treatment: Antidopaminergic drugs are Antidopaminergic drugs are

the mainstay of treatment.the mainstay of treatment. Risperidone olanzapine, tetrabenazine, Risperidone olanzapine, tetrabenazine,

haloperidol.haloperidol. Amantidine, Gabapentin, Amantidine, Gabapentin, Carbamazepine, Carbamazepine,

Valproic acid.Valproic acid.

PANDASPANDAS

PANDASen Thriving PANDASen Thriving

ExtinctExtinct

EndangeredEndangered

PANDASPANDAS(pediatric autoimmune neuropsychiatric disorders (pediatric autoimmune neuropsychiatric disorders

associated with streptococcal infections)associated with streptococcal infections)

Presence of obsessive-compulsive disorder Presence of obsessive-compulsive disorder or tic disorder or tic disorder

Onset between age 3 years and beginning of Onset between age 3 years and beginning of puberty puberty

Onset or exacerbation of signs are Onset or exacerbation of signs are temporally related to group A b-hemolytic temporally related to group A b-hemolytic streptococcal infection. streptococcal infection.

Abnormal results of neurological Abnormal results of neurological examination (hyperactivity/choreiform examination (hyperactivity/choreiform movements or tics during an exarcerbation) movements or tics during an exarcerbation)

Dystonia and AthetosisDystonia and Athetosis

Dystonia is a syndrome of Dystonia is a syndrome of sustained muscle sustained muscle contractions causing abnormal postures or contractions causing abnormal postures or twisting and repetitive movements.twisting and repetitive movements.

Athetotic movements are Athetotic movements are complex, complex, wormlike, irregular, non propositional and wormlike, irregular, non propositional and predominate over postural anomalies and predominate over postural anomalies and on the distal parts of limbs and face.on the distal parts of limbs and face.

Common types of Common types of DystoniaDystonia

Benign paroxysmal torticollis in infancyBenign paroxysmal torticollis in infancy Dopa responsive dystoniaDopa responsive dystonia Idiopathic torsion dystoniaIdiopathic torsion dystonia Transient idiopathic dystonia of InfancyTransient idiopathic dystonia of Infancy Secondary dystonia:Secondary dystonia:

1.Structural brain damage :Hemidystonia1.Structural brain damage :Hemidystonia

2. Metabolic dystonia: Glutaric aciduria2. Metabolic dystonia: Glutaric aciduria

Wilson’s disease, Lesch Nyan syndromeWilson’s disease, Lesch Nyan syndrome

Homocystinuria.Homocystinuria.

Idiopathic Torsion Dystonia Idiopathic Torsion Dystonia DYT1DYT1

Onset is before 15 yrs of ageOnset is before 15 yrs of age

Onset in 1 limb, foot inversion is commonOnset in 1 limb, foot inversion is common

Initially it appears in only certain postures.Initially it appears in only certain postures.

Course is progressive for 5-10 yrs and then Course is progressive for 5-10 yrs and then becomes stationary.becomes stationary.

N shaped progressionN shaped progression

Tremors, swallowing difficulties,Tremors, swallowing difficulties,

myoclonus can be present.myoclonus can be present.

Idiopathic Torsion Dystonia Idiopathic Torsion Dystonia DYT1DYT1

Investigations:Investigations:

Blood count and search for acanthocytesBlood count and search for acanthocytes

MRIMRI

Copper and ceruloplasminCopper and ceruloplasmin

Slit lamp examinationSlit lamp examination

Lysosomal enzymes Lysosomal enzymes (hexosaminidase,galactosidase)(hexosaminidase,galactosidase)

ERGERG

Organic acids in urine.Organic acids in urine.

Dopa responsive dystonia Dopa responsive dystonia (DYT5)(DYT5)

First 12 yrs of life (median age of onset 4.5 and 6 First 12 yrs of life (median age of onset 4.5 and 6 yrs)yrs)

Females to male 2.5:1Females to male 2.5:1

Fatiguability, clumsiness of gait, dystonic posture Fatiguability, clumsiness of gait, dystonic posture limited to one foot .limited to one foot .

Severity of the dystonia worse during the day and Severity of the dystonia worse during the day and improves with sleep.improves with sleep.

Postural tremor / Hyperactive reflexes present.Postural tremor / Hyperactive reflexes present.

Marked and prolonged effect of L-Dopa Marked and prolonged effect of L-Dopa (5-30mg/kg/day)(5-30mg/kg/day)

Mutations of DYT-5 gene GTP cyclohydrolase1 geneMutations of DYT-5 gene GTP cyclohydrolase1 gene

Transient idiopathic dystonia Transient idiopathic dystonia of infancyof infancy

Onset before 5 months of ageOnset before 5 months of age

Abnormal posture limited to one hand.Abnormal posture limited to one hand.

Arm is abducted and the forearm pronated Arm is abducted and the forearm pronated with flexion at the wristwith flexion at the wrist

May be permanent but can be paroxysmalMay be permanent but can be paroxysmal

Dystonia disappears when the infant Dystonia disappears when the infant performs propositive movements.performs propositive movements.

Transient idiopathic dystonia of Transient idiopathic dystonia of infancyinfancy

Treatment of DystoniaTreatment of Dystonia

A trial of low dose Levo Dopa (62.5mg-A trial of low dose Levo Dopa (62.5mg-100mg) 2-3 times daily is warranted100mg) 2-3 times daily is warranted

High doses of Benzhexol (Artane) Start with High doses of Benzhexol (Artane) Start with 4-5mg/day and increase to 80 mg/day4-5mg/day and increase to 80 mg/day

Tetrabenazine and Pimozide/HaloperidolTetrabenazine and Pimozide/Haloperidol

BaclofenBaclofen

Clonazepam and DiazepamClonazepam and Diazepam

BotoxBotox

Deep Brain stimulationDeep Brain stimulation

Tremor in childrenTremor in children

10-20% of pediatric movement disorders.10-20% of pediatric movement disorders.

Action tremor most common.Action tremor most common.

Rest tremor uncommon, bad prognosis.Rest tremor uncommon, bad prognosis.

Task specific tremor .Task specific tremor .

Can occur in conjunction with dystonia/ Can occur in conjunction with dystonia/ myoclonus.myoclonus.

BenignPhysiologicalShuddering attacks

JitterinessSpasmus nutansHereditary

Essential tremorFragile X premutationStrokes or Brain LesionsThalamus, midbrain, or cerebellumPeripheral neuropathiesMitochondrial encephalopathiesMetabolicHypoglycemiaB12 deficiencyInborn errors of metabolismEndocrineHyperthyroidismHyperadrenergic states

Drugs, ToxinsValproatePhenytoinCarbamazepineLamictalGabapentinLithiumTricyclic antidepressantsBronchodilatorsCaffeineAmphetaminesThyroxineNeurolepticsCyclosporinAmiodaroneSerotonin reuptake inhibitorsCocaineMercuryManganese

Psychogenic

Etiology of Tremors

Essential tremorEssential tremor Adapted from Bain and colleaguesAdapted from Bain and colleagues

Core criteriaCore criteria (features that must be present):(features that must be present):

Bilateral action tremor of the hands and forearms (but not Bilateral action tremor of the hands and forearms (but not rest tremor);rest tremor);

or isolated head tremor with no signs of dystoniaor isolated head tremor with no signs of dystonia

No other neurological signs, with the exception of the No other neurological signs, with the exception of the cogwheel phenomenoncogwheel phenomenon

Secondary criteria (features that are supportive, but not Secondary criteria (features that are supportive, but not necessarynecessary):):

Long duration of symptoms (over 3 years)Long duration of symptoms (over 3 years)

Positive family historyPositive family history

Responsiveness to alcoholResponsiveness to alcohol

Epidemiology of ETEpidemiology of ET

Adults: Prevalence of 0.24%- 4.8%, no Adults: Prevalence of 0.24%- 4.8%, no reliable data in children.reliable data in children.

15-30% of Adults report onset in childhood.15-30% of Adults report onset in childhood.

M:F 3:1 in pediatrics.M:F 3:1 in pediatrics.

Tremor onset at a mean age of between 3-Tremor onset at a mean age of between 3-11 yrs.11 yrs.

Differential diagnosis of ETDifferential diagnosis of ET

Wilson’s disease and hyperthyroidismWilson’s disease and hyperthyroidism should always be excluded.should always be excluded.

If tremors are associated with dystonia, If tremors are associated with dystonia, myoclonus,ataxia,seizures,weakness or it is myoclonus,ataxia,seizures,weakness or it is unilateral unilateral suspect other causes.suspect other causes.

Postural and kinetic tremor

Detailed medical history and examination

Findings suggest other than essential tremor History and physical examination

suggests essential tremor.

Targeted diagnostic testing Diagnosis of essential tremor

Treat underlying cause of tremor

Assess for disability and determine

whether treatment is needed.

Determine whether daily therapy is required

Monitor for progression

Propranolol as needed

Initiate maintenance therapy with propranolol 0.5–1 mg/kg/day inthree divided dosestitrated up to4 mg/kg/day

Poor response

Second-line agents:primidone, topiramate,gabapentin,benzodiazepines,botulinum toxinDeep brain

stimulation

Pediatr Drugs 2009; 11 (5)

Shudder attacksShudder attacks

http://video.yahoo.com/watch/2666541?fr=yvmtfhttp://video.yahoo.com/watch/2666541?fr=yvmtf

Start in the first yr of life.Start in the first yr of life.

Brief bursts 5-15 sec of rapid tremor of head Brief bursts 5-15 sec of rapid tremor of head and armand arm

No change in level of consciousnessNo change in level of consciousness

EEG normalEEG normal

Precede essential tremorPrecede essential tremor

Propranolol may be effective.Propranolol may be effective.

References

Pediatric Neurology ,Principles and Practice. Swaiman, Ashwal and Ferriero, Fourth Edition.Movement Disorders in Children. Emilo Fernandez-Alvarez and Jean AicardiFerrara J,Jankovic J .Epidemiology and Management of Essential Tremor in children,

Pediatric Drugs 2009;11(5):293-307.Keller S, Dure L. Tremor in childhood,Semin Pediatr Neurol 2009 ;16: 60-70.Cardoso F et al. Seminars on Chorea, Lancet Neurol 2006; 5: 589–602Sanger TD et al, Definition and Classification of Hyperkinetic Movements in Childhood, Movement Disorders Vol. 25, No. 11, 2010, pp. 1538–

1549 Gonzalez-Alegre P, The Inherited dystonias Semin Neurol 2007;27:151–158 E. Ferna´ndez-Alvarez. Dystonia : The Paediatric Perspective European Journal of

Neurology 2010, 17 (Suppl. 1): 46–51Martino D et al,The PANDAS subgroup of tic disorders and childhood-onset obsessive–

compulsive disorder Journal of Psychosomatic Research 67 (2009) 547–557Kirsch DB, Mink JW. Psychogenic movement disorder in children. Pediatr Neurol 2004;30:1-6.Oosterveer DM, Overweg-Plandsoen WCT, Roos RAC. Sydenham’s chorea: a practical

overview of the current lit- erature. Pediatr Neurol 2010;43:1-6. Jancovic Joseph, Treatment of Dystonia Lancet Neurol 2006; 5: 864–72

Thank You !