Movement Disorders in Children

Overview• Childhood movement disorders occur secondary to a wide range of genetic and

acquired disorders affecting brain development. •  Classification by type of abnormal movement

– Bradykinetic disorders – Hyperkinetic disorders

• Classification by Etiology– Primary – Secondary

• Fixed Structural lesion• Degenerative• Metabolic• Drug Induced• Infectious

• Important point– Any disorder that affects the basal ganglia can cause a wide array of different movement disorders– Static brain injury may nonetheless cause a changing movement disorder, as development and brain

plasticity alter the brain’s response to injury.

Basal Ganglia• Group of deep nuclei – Caudate nucleus – Putamen– Globus pallidus– Substantia nigra

• dopamine-rich pars compacta• pars reticularis

• Inputs: Corpus striatum (caudate nucleus and putamen) receives input from the cerebral cortex and the thalamus

• Outputs: projects by way of the thalamus to the cerebral cortex and then to the pyramidal system

Bradykinetic vs. Hyperkinetic• Bradykinetic disorders

– Very rare in children– Parkinson disease is the most common bradykinetic disorder

• Hyperkinetic disorders– Tic Disorders– Dystonia– Sterotypies– Chorea– Athetoses– Ballismus– Tremor– Myoclonus– Dyskinesia

Tic Disorders• Tics are repeated, intermittent movements that

are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement

• Tourette syndrome : Multiple motor and vocal tics• Etiology– Primary:

• the vast majority– Secondary:

• Huntingtons, encephalitis, medication induced, carbon monoxide poisoning, neuroacantocytosis

Tics• Diagnosis:

– Typical movements– Don’t occur in sleep– Patient usually unaware of it occurring– Patient can usually suppress for a short time– But when they do, it is accompanied by a discomfort and a strong urge to do the tic (a compulsion)– Wax and wane over time– Worsen with stress

• Associated with ADHD and OCD– Make sure to ask both of patient and family history

• PANDAS• Treatment

– Reassurance• Tics tend to wax and wane; most children outgrow them

– Medications (when necessary)• Stimulants bring out tics; if the have ADHD, they can’t use stimulants• Tenex• Risperidone

Dystonia

• Involuntary sustained or intermittent muscle contractions that cause twisting and repetitive movements, abnormal postures, or both.

Dystonia

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Classification of Dystonia

• By location– Generalized dystonia affects most or all of the body.– Focal dystonia is localized to a specific part of the body.

• Blepharospasm, Cervical Dystonia, Task Specific Dystonia (eg Writers cramp)– Multifocal dystonia involves two or more unrelated body parts.– Segmental dystonia affects two or more adjacent parts of the body.– Hemidystonia involves the arm and leg on the same side of the body.

• By etiology– Primary: by definition, no other neurologic impairment– Secondary: Cerebral Palsy the most common cause in children– Psychogenic

Primary Dystonias• Genetic Dystonias

– DYT1 dystonia • dominantly inherited generalized dystonia• typically begins in childhood, affects the limbs first, and progresses• A great deal of phenotypic variability

– Dopa-responsive dystonia (Segawa’s disease)• onset during childhood and have progressive difficulty with walking. • Symptoms characteristically fluctuate and are worse late in the day

and after exercise. • Some forms are due to mutations in the DYT5 gene for GTP

cyclohydrolase 1. • Patients with this disorder have dramatic improvements in symptoms

after treatment with levodopa– Many other genes that cause dystonic syndromes have been

found

Secondary Dystonias• Fixed Injury/Structural:

– Kernicterus,, head trauma, encephalitis; tumors, stroke, congenital malformations• Degenerative:

Fahr's disease , pantothenate-kinase associate dneurodegenerative disease (Hallervorden-Spatz disease), Huntington's disease, spinocerebellar ataxias ; neuronal ceroid lipofuscinosis; Rett syndrome; Tay-Sachs disease; Sandhoff's disease; Niemann-Pick type C; metachromatic leukodystrophy; Leigh's disease; neuroacanthocytosis;;Pelizaeus-Merzbacher disease; ataxia-telangiectasia

• Chemical/Metabolic:Glutaric aciduria; mitochondrial disorders; Wilson's disease; homocystinuria; Lesch-Nyhan

disease; methylmalonic aciduria; tyrosinemia, vitamin E deficiency• Drug- or Toxin-induced:

– Neuroleptic and anti-emetic medications (e.g., haloperidol, thorazine, olanzapine, risperidone, quetiapine, compazine, prochlorperazine, metoclopramide, etc.); calcium channel blockers; stimulants , anticonvulsants (e.g., carbamazepine, phenytoin, ); thallium; manganese; carbon monoxide; ethylene glycol; cyanide; methanol; wasp sting

• Paroxysmal:– Paroxysmal kinesogenic choreoathetosis; familial periodic paralysis; complex migraine; alternating

hemiplegia; paroxysmal torticollis of infancy• Psychogenic• Disorders That Mimic Dystonia:

– Tonic seizures, syringomyelia; Arnold-Chiari malformation type II; posterior fossa mass; cervical spine malformation, Sandifer's syndrome; spasmus nutans; tics; self-stimulation; spasticity; myotonia; hyperexplexia; disorders

Work up of Dystonia

• Take careful history of medication, drug and supplement use

• Consider Genetic testing (especially DYT1)• Consider empiric trial of levodopa• Consider metabolic testing: amino acids,

organic acis, Wilsons testing, lysosomal storage diseases

• Consider MRI

Treatment of Dystonia• Botulinum toxin

– Particularly for focal dystonias

• Medications– Anticholinergic agents: trihexyphenidyl and benztropine.

– GABAergic agents : benzodiazepines, baclofen– Dopaminergic agents: tetrabenazine– Levodopa for Dopa-responsive dystonia (DRD)

• Deep brain stimulation (DBS)• Physical and other therapies

Sterotypies

• Repetitive, simple movements that can be voluntarily suppressed.

• Examples include repetitive chewing, rocking, twirling, or touching movements

• Most common in children with autism or mental retardation; can occur in otherwise normal children.

Rett Syndrome

Chorea, athetosis and ballismus

• Chorea– an irregular, rapid, uncontrolled, involuntary, excessive

movement that seems to flow randomly from one part of the body to another.

– The affected child often appears fidgety or restless and can’t sit still

• Athetosis– A slower writhing and twisting movement.

• Ballism (ballismus)– chorea that affects proximal joints such as shoulder or hip,

leading to large amplitude flailing movements of the limbs

Etiology of Chorea• Fixed injury/Structural

– Cerebral Palsy (Kernicterus), Tumor, Trauma, Stroke

• Degenerative– Huntingtons, Neuroacanthocytosis, Ataxia-telangiectasia; Fahr's disease; pantothenate kinase 2 deficiency

("Hallervorden-Spatz disease"); Rett syndrome; Niemann-Pick disease type C , Pelizaeus-Merzbacher disease; GM1 gangliosidosis, metachromatic leukodystrophy; Wilson's disease ,etc

• Drug Induced/Toxins:– Neuroleptics, antiparkinson drugs, tricyclics , amphetamines, anticonvulsants, anticholinergics

• Metabolic:– Hyperthyroid, hypoparathyroid, pregnancy, hyper and hypo natremia, hypomagnesemia, hypoclaciemia,

nutrional deficiencies (beriberi, pellagra, B12 deficiency)– Acyl-CoA dehydrogenase deficiency; Lesch-Nyhan disease;; methylmalonic aciduria; vitamin E deficiency;

propionic acidemia;

• Infectious– Sydenhams chorea

• Immunological– SLE, HSP

• Migraine• Psychogenic

Kernicterus

Sydenham chorea • Sydenham chorea is a movement disorder characterized by chorea, emotional lability, and

hypotonia. It is one of the major clinical manifestations of acute rheumatic fever (ARF). • Symptoms of SC usually begin one to eight months after the onset of ARF. The symptoms typically

improve gradually, with a mean duration of 12 to 15 weeks (• At least 30 percent of individuals have clinical carditis in association with SC. • Diagnosis

– The diagnosis of SC is made clinically, based on characteristic neurological findings and a careful cardiac examination. If carditis is present, this confirms the diagnosis.

– The antistreptolysin O (ASLO) titer is of limited use in patients with SC, because titers generally peak before the onset of SC symptoms and children without rheumatic fever or SC often have low positive titers of ASLO.

– The antideoxyribonuclease (anti-DNAse) B titer is more useful for supporting the diagnosis of SC because it tends to remain elevated longer.

– If not clinicually definite, other causes of chorea should be excluded, including systemic lupus erythematosus, Huntington’s disease, and Wilson’s disease.

• Treatment– Most patients with SC recover fully without treatment, with symptoms lasting from a few weeks to one year or more. – For those with significant impairment of motor function and the possibility of self injury consider corticosteroids (prednisone 1 mg/kg

daily for two weeks and then tapered over two to three weeks) – Valproic acid if needed to treat chorea

• Up to 30 percent of individuals with SC experience a recurrence, usually within a few years of the initial episode. The risk is probably reduced, by chronic treatment with prophylactic antibiotics.

Sydenham Chorea

Athetosis

• http://www.youtube.com/watch?v=gNKKZAfMr8M

Work up

• Take careful history of medication, drug and supplement use

• If acute onset: throat culture and streptococcal blood antigen test (ASLO, anti-DNAse), electrolytes, magnesium, calcium, thyroid function, CBC

• Consider amino and organic acid studies, ammonia, antinuclear antigen (ANA), antiphospholipid antibodies (APLA), work up for Wilsons disease (start with ceruloplasmin), evaluation of CBC for acanthocytes.

• Consider MRI

Treatment of Chorea• May be difficult to treat. • Taper or discontinue any medications that can cause or worsen

chorea• In adults, the mainstay of treatment in adults is neuroleptics,

including haloperidol and pimozide. • In children the incidence of side effects in children is high. • Therefore, treatment is usually

– Benzodiazepine, particularly clonazepam, diazepam, or clobazam– Valproate, especially in Sydenham's chorea.

• Sydenham's chorea – There is considerable debate about whether children with Sydenham's

chorea due to streptococcal infection should be given long-term antibiotics. There is not yet scientific evidence to support this, although short-term treatment is certainly needed in order to prevent complications such as rheumatic fever.

Tremor

• A rhythmic back-and-forth or oscillating involuntary movement about a joint.

Classification of Tremor• Classification by type of tremor

– Rest Tremor• Parkinsons, Wilson Disease, Severe essential tremor

– Action Tremor• Postural• Kinetic• Intention: Cerebellar Tremor• Task Specific• Isomeric

• Classification by Etiology– Physiologic tremor– Essential tremor– Associated w/ Peripheral Neuropathy: Charcot MarieTooth– Psychogenic

Etiology of Tremor• Primary Tremors:

– Enhanced physiologic tremor – Essential Tremor

• Static (fixed) injury:Stroke (particularly in the midbrain or cerebellum); multiple sclerosis

• Degenerative:– Juvenile parkinsonism; Wilson's disease; Huntington's disease; Tay-Sachs disease

• Chemical/metabolic:– Hyperthyroidism; hyper-adrenaline state (including anxiety or

pheochromocytoma); hypomagnesemia; hypocalcemia; hypoglycemia; hepatic encephalopathy

• Drug-induced– Valproate; lithium; thyroid hormone; albuterol, tricyclic antidepressants;

stimulants, neuroleptics; cyclosporine; mercury; thallium; nicotine; lead; manganese; arsenic; cyanide; ethanol

• Psychogenic tremor• Other causes of tremor:

– Peripheral neuropathy, cerebellar disease or malformation,spasmus nutans

Essential Tremor

• Tremor should be the only neurologic manifestation

• Usually benign, but may progress to a disabling movement disorder.

• Hereditary ET can begin in infancy– hereditary chin tremor and shuddering attacks.

Work up of Tremor• Any medications that may worsen tremor should be

avoided, if possible. • Check electrolytes, including glucose, calcium and

magnesium, thyroid function, copper in the urine (for Wilson's disease), and possibly the amount of adrenaline metabolites (for pheochromocytoma).

• Consider MRI if the tremor had sudden onset, • Consider EEG if there is suspicion for seizures.• If parkinsonian features are present, consider a trial of L-

DOPA • If there is a family history of tremor, it may be helpful to of

alcohol ( in the affected family member). This suggests essential tremor.

Treatment of Tremor

• Often, mild tremor does not require treatment.

• Medications: – Propranolol– Primidone– benzodiazepines (i.e., clonazepam, diazepam,

lorazepam).

Myoclonus

• Sudden, brief, jerky, shock-like involuntary movements.

• May be triggered by attempts at voluntary movement, sensory stimulation or startle

• Myoclonus is not suppressible and is often activated by volitional movement.

• Negative myoclonus is a sudden involuntary relaxation of a muscle, rather than a contraction.

• Myoclonus is often associated with epilepsy.

Classification and Etiology of Myoclonus

• Physiological: e.g., sleep myoclonus, benign myoclonus of infancy• Essential Myoclonus: familial essential myoclonus, essential myoclonus-dystonia,

stimulus-sensitive myoclonus• Epileptic: e.g., juvenile myoclonic epilepsy, progressive myoclonic epilepsies,

epilepsia partialis continua, Rasmussen's encephalitis, early infantile myoclonic encephalopathy, infantile spasms, Lennox-Gastaut syndrome, benign familiar myoclonic epilepsy, Angelman syndrome

• Symptomatic– Fixed injury: e.g., carbon-monoxide poisoning, hypoxic injury or near-drowning, heatstroke,

trauma, stroke, electrocution– Storage/Degenerative diseases: e.g., sialidoses, lipidosis, storage diseases, Wilson's disease,

Rett syndrome, mitochondrial disorders, spinocerebellar ataxias– Infections/Para-infectious: e.g., Creutzfeldt-Jacob disease, steptococcus, viral encephalitis– Endocrine: e.g., hyperthyroidism, hyponatremia, hypoglycemia– Structural: e.g., tumors that irritate brain in direct manner or release chemicals into the blood– Drug-induced/Toxins: e.g., anti-seizure medications, antidepressants, stimulants, liver-toxic

medications, respiratory depressants, corticosteroids, acyclovir, L-dopa– Associated with systemic illness: e.g., dialysis, renal failure, liver failure, pulmonary disease,

carbon dioxide intoxication