2OverviewChildhood movement disorders occur secondary to a wide range of genetic and acquired disorders affecting brain development. Classification by type of abnormal movementBradykinetic disordersHyperkinetic disordersClassification by EtiologyPrimarySecondaryFixed Structural lesionDegenerativeMetabolicDrug InducedInfectiousImportant pointAny disorder that affects the basal ganglia can cause a wide array of different movement disordersStatic brain injury may nonetheless cause a changing movement disorder, as development and brain plasticity alter the brain’s response to injury.
3Basal Ganglia Group of deep nuclei Caudate nucleusPutamenGlobus pallidusSubstantia nigradopamine-rich pars compactapars reticularisInputs: Corpus striatum (caudate nucleus and putamen) receives input from the cerebral cortex and the thalamusOutputs: projects by way of the thalamus to the cerebral cortex and then to the pyramidal system
7Bradykinetic vs. Hyperkinetic Bradykinetic disordersVery rare in childrenParkinson disease is the most common bradykinetic disorderHyperkinetic disordersTic DisordersDystoniaSterotypiesChoreaAthetosesBallismusTremorMyoclonusDyskinesia
8Tic DisordersTics are repeated, intermittent movements that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movementTourette syndrome : Multiple motor and vocal ticsEtiologyPrimary:the vast majoritySecondary:Huntingtons, encephalitis, medication induced, carbon monoxide poisoning, neuroacantocytosis
9Tics Diagnosis: Associated with ADHD and OCD PANDAS Treatment Typical movementsDon’t occur in sleepPatient usually unaware of it occurringPatient can usually suppress for a short timeBut when they do, it is accompanied by a discomfort and a strong urge to do the tic (a compulsion)Wax and wane over timeWorsen with stressAssociated with ADHD and OCDMake sure to ask both of patient and family historyPANDASTreatmentReassuranceTics tend to wax and wane; most children outgrow themMedications (when necessary)Stimulants bring out tics; if the have ADHD, they can’t use stimulantsTenexRisperidone
10DystoniaInvoluntary sustained or intermittent muscle contractions that cause twisting and repetitive movements, abnormal postures, or both.
15Classification of Dystonia By locationGeneralized 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 etiologyPrimary: by definition, no other neurologic impairmentSecondary: Cerebral Palsy the most common cause in childrenPsychogenic
16Primary Dystonias Genetic Dystonias DYT1 dystonia dominantly inherited generalized dystoniatypically begins in childhood, affects the limbs first, and progressesA great deal of phenotypic variabilityDopa-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 levodopaMany other genes that cause dystonic syndromes have been found
19Work up of DystoniaTake careful history of medication, drug and supplement useConsider Genetic testing (especially DYT1)Consider empiric trial of levodopaConsider metabolic testing: amino acids, organic acis, Wilsons testing, lysosomal storage diseasesConsider MRI
20Treatment of Dystonia Botulinum toxin Medications Particularly for focal dystoniasMedicationsAnticholinergic agents: trihexyphenidyl and benztropine.GABAergic agents : benzodiazepines, baclofenDopaminergic agents: tetrabenazineLevodopa for Dopa-responsive dystonia (DRD)Deep brain stimulation (DBS)Physical and other therapies
21SterotypiesRepetitive, simple movements that can be voluntarily suppressed.Examples include repetitive chewing, rocking, twirling, or touching movementsMost common in children with autism or mental retardation; can occur in otherwise normal children.
23Chorea, athetosis and ballismus 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 stillAthetosisA 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
26Sydenham choreaSydenham 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.DiagnosisThe 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.TreatmentMost 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 choreaUp 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.
29Work 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, CBCConsider 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
30Treatment of Chorea May be difficult to treat. Taper or discontinue any medications that can cause or worsen choreaIn 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 usuallyBenzodiazepine, particularly clonazepam, diazepam, or clobazamValproate, especially in Sydenham's chorea.Sydenham's choreaThere 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.
31TremorA rhythmic back-and-forth or oscillating involuntary movement about a joint.
32Classification of Tremor Classification by type of tremorRest TremorParkinsons, Wilson Disease, Severe essential tremorAction TremorPosturalKineticIntention: Cerebellar TremorTask SpecificIsomericClassification by EtiologyPhysiologic tremorEssential tremorAssociated w/ Peripheral Neuropathy: Charcot MarieToothPsychogenic
33Etiology of Tremor Primary Tremors: Enhanced physiologic tremorEssential TremorStatic (fixed) injury: Stroke (particularly in the midbrain or cerebellum); multiple sclerosisDegenerative:Juvenile parkinsonism; Wilson's disease; Huntington's disease; Tay-Sachs diseaseChemical/metabolic:Hyperthyroidism; hyper-adrenaline state (including anxiety or pheochromocytoma); hypomagnesemia; hypocalcemia; hypoglycemia; hepatic encephalopathyDrug-inducedValproate; lithium; thyroid hormone; albuterol, tricyclic antidepressants; stimulants, neuroleptics; cyclosporine; mercury; thallium; nicotine; lead; manganese; arsenic; cyanide; ethanolPsychogenic tremorOther causes of tremor:Peripheral neuropathy, cerebellar disease or malformation,spasmus nutans
34Essential Tremor Tremor should be the only neurologic manifestation Usually benign, but may progress to a disabling movement disorder.Hereditary ET can begin in infancyhereditary chin tremor and shuddering attacks.
35Work up of TremorAny 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-DOPAIf there is a family history of tremor, it may be helpful to of alcohol ( in the affected family member). This suggests essential tremor.
36Treatment of Tremor Often, mild tremor does not require treatment. Medications:PropranololPrimidonebenzodiazepines (i.e., clonazepam, diazepam, lorazepam).
37Myoclonus Sudden, brief, jerky, shock-like involuntary movements. May be triggered by attempts at voluntary movement, sensory stimulation or startleMyoclonus 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.
38Classification and Etiology of Myoclonus Physiological: e.g., sleep myoclonus, benign myoclonus of infancyEssential Myoclonus: familial essential myoclonus, essential myoclonus-dystonia, stimulus-sensitive myoclonusEpileptic: 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 syndromeSymptomaticFixed injury: e.g., carbon-monoxide poisoning, hypoxic injury or near-drowning, heatstroke, trauma, stroke, electrocutionStorage/Degenerative diseases: e.g., sialidoses, lipidosis, storage diseases, Wilson's disease, Rett syndrome, mitochondrial disorders, spinocerebellar ataxiasInfections/Para-infectious: e.g., Creutzfeldt-Jacob disease, steptococcus, viral encephalitisEndocrine: e.g., hyperthyroidism, hyponatremia, hypoglycemiaStructural: e.g., tumors that irritate brain in direct manner or release chemicals into the bloodDrug-induced/Toxins: e.g., anti-seizure medications, antidepressants, stimulants, liver-toxic medications, respiratory depressants, corticosteroids, acyclovir, L-dopaAssociated with systemic illness: e.g., dialysis, renal failure, liver failure, pulmonary disease, carbon dioxide intoxication