Pediatrics

Paroxysmal dyskinesia

OVERVIEW: What every practitioner needs to know

Are you sure your patient has paroxysmal dyskinesia? What are the typical findings for this disease?

Paroxysmal dyskinesias are a class of episodic hyperkinetic movement disorders. These movements can include chorea, athetosis or dystonia, and can occur in combination.

Chorea is rapid, random, continuous, irregular, nonstereotyped and involuntary movements that are bilateral and generalized. The movements may vary from moment to moment. Chorea usually worsens during attempted voluntary movements.

Athetosis, in comparison, is a slow writhing movement that predominantly involves the distal extremities. It is often accompanied by hyperextension and flexion of the digits.

Dystonia is simultaneous sustained contraction of agonist and antagonist muscle groups about a joint resulting in a distorted posture. A balanced contracture produces a fixed posture, whereas an unbalanced contracture results in a twisting movement ending in a fixed, extreme posture.

Paroxysmal dyskinesias are categorized by triggers of the abnormal movement typically coming out of a background of normal movement and behavior:

Paroysmal kinesigenic dyskinesia (PKD):

Occur at the initiation of movement, typically after rest.

Dystonia is most common, but chorea is often seen as well.

Startle can also induce an attack.

The attack can be generalized, but can affect only one extremity.

The dyskinesia is short lived (most < 1 minute).

Frequency can vary widely, but may occur multiple times a day (up to 100 times).

There is no alteration in awareness associated with the dyskinesia.

An aura (abnormal sensation) is often reported prior to onset of dyskinesia.

Paroxysmal nonkinesigenic dyskinesia (PNKD):

Can occur at random, but typically induced by fatigue, stress or caffeine.

A combination of dystonia and chorea is present in most.

The attacks are less frequent than the kinesigenic form; 3 per day to 2 per year.

Attacks are longer in duration (minutes to 3-4 hours) than kinesigenic form.

An aura is often reported prior to onset of dyskinesia.

Paroxysmal exercise-induced dyskinesia (PED):

Occurs after prolonged exertion.

Dystonia is the commonest dyskinesia seen, with the foot being most affected. However, exercise of any body part can induce dystonia in that part.

The attacks are infrequent (no more than once a day) and can last up to 30 minutes.

The dyskinesia stops soon after ceasing exertion.

Nearly half of children with PKD have a history of infantile seizures, with myoclonus being a common seizure type. An association with seizures is not seen in children with PNKD.

What other disease/condition shares some of these symptoms?

Differential diagnosis for paroxysmal dyskinesias:

Seizures

Pseudoseizures

Action dystonia

Tics

DOPA-responsive dystonia

Secondary causes of paroxysmal dyskinesias:

Vascular

Moyamoya

Structural

Periventricular leukomalacia

Trauma

Metabolic

Hypothyroidism

Hypoparathyroidism

Pseudohypoparathyroidism

Kernicterus

Fahr disease (basal ganglia calcifications)

Hypoglycemia

Hypernatremia

Neuro-degenerative

Wilson disease

Mitochondrial encephalopathy

Huntington disease

Inflammatory

Multiple sclerosis/demyelinating disease

Celiac disease

Neoplasm

Medication

Methylphenidate

Antipsychotics

Phenytoin

What caused this disease to develop at this time?

  • Paroxysmal kinesigenic dyskinesia typically starts in childhood, before age 20 years.

  • Paroxysmal nonkinesigenic dyskinesia starts at approximately 8 years of age, and may not present until early adulthood.

  • Paroxysmal exercise-induced dyskinesia starts at approximately age 5 years, but may not present until adulthood.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

  • A complete metabolic panel is recommended to check for electrolyte imbalances.

  • Thyroid studies.

  • Spinal fluid should be obtained if multiple sclerosis is considered.

  • EEG should be obtained, particularly if there is concern for altered awareness during epsiodes.

Would imaging studies be helpful? If so, which ones?

  • Magnetic resonance imaging (MRI) of the brain is recommended.

If you are able to confirm that the patient has paroxysmal dyskinesia, what treatment should be initiated?

For paroxysmal kinesigenic dyskinesia, low dose anticonvulsants are effective. Carbamazepine 1-2 mg/kg/day is the first line therapy. Other anticonvulsants shown to have efficacy in PKD include phenytoin, oxcarbazepine and topiramate. The absence of any response to these agents should lead one to reconsider the diagnosis of PKD.

For PKND identification and avoidance of triggers is critical. Anticonvulsants are less effective in PKND as compared to PKD. Benzodiazepines, such as clonzaepam 2-4 mg/day) have some utility. There are case reports where gabapentin and levetiracetam were effective.

For PED, avoidance of prolonged exercise decreases attack frequency. Anticonvulsants and benzodiazepines have not been effective. Gabapentin and levodopa have been reported effective in adults.

What are the adverse effects associated with each treatment option?

Carbamazepine: sedation, ataxia, nystagmus, hyponatremia, bone marrow suppression, Stevens Johnson syndrome.

Clonazepam: sedation, ataxia, respiratory depression.

What are the possible outcomes of paroxysmal dyskinesia?

Paroxysmal kinesigenic dyskinesia has a favorable outcome, and symptoms typically wane in adulthood.

Paroxysmal nonkinesigenic dyskinesia has a favorable outcome and attacks decrease in frequency with age.

What causes this disease and how frequent is it?

  • Paroxysmal kinesigenic dyskinesia:

    • Can be inherited or sporadic.

    • Familial forms are usually inherited in an autosomal dominant manner.

    • Penetrance is between 80 - 90%.

    • Males and females are equally affected in those with a family history; females are more affected in sporadic cases.

    • Linkage analysis has identified loci for PKD on chromosome 16 near the centromere. The specific gene mutation, however, has yet to be identified.

  • Paroxysmal nonkinesigenic dyskinesia:

    • Inherited in an autosomal dominant manner.

    • Penetrance is >90%.

    • Males are affected more than females.

    • Associated with mutations in the myofibrillogenesis regulator 1 gene (MR-1) on chromosome 2.

      • If the MR-1 mutation is present, disease onset is usually noted at an earlier age, with one-third presenting in infancy.

  • Paroxysmal exercise-induced dyskinesia:

    • Rare.

    • Inherited in an autosomal dominant manner.

    • An association with the GLUT1 transporter was suggested in children with PED and epilepsy.

    • Variant of PED with spasticity (spastic paraplegia) has been mapped to chromosome 1p in the vicinity of a potassium channel gene.

How do these pathogens/genes/exposures cause the disease?

The function of MR-1 is not understood.

What complications might you expect from the disease or treatment of the disease?

None

Are additional laboratory studies available; even some that are not widely available?

How can paroxysmal dyskinesia be prevented?

Paroxysmal kinesigenic and non-kinesigenic dyskinesias are inherited in an autosomal dominant manner. Genetic counselling is recommended for prenatal planning.

What is the evidence?

Selected references:

Mink, JW. "Paroxysmal dyskinesias". Curr Opin Pediatr.. vol. 19. 2007. pp. 652-6.

(A concise review, focusing on genetic findings in paroxysmal dyskinesias and their implications.)

Bhatia, KP. "Paroxysmal dyskinesias". Mov Disord.. vol. 26. 2011. pp. 1157-65.

(Reviews genetics and pathophysiology.)

Sohn, YH, Lee, PH. "Paroxysmal choreodystonic disorders". Handb Clin Neurol.. vol. 100. 2011. pp. 367-73.

Strzelczyk, A, Burk, K, Oertel, WH. "Treatment of paroxysmal dyskinesias". Expert Opin Pharmacother. vol. 12. 2011. pp. 63-72.

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