Dyskinesia

ALSO KNOWN AS: Hyperkinesia, levodopa-induced dyskinesia, paroxysmal dyskinesia, tardive dyskinesia

ANATOMY OR SYSTEM AFFECTED: Arms, brain, feet, hands, head, legs, mouth, neck, nerves, nervous system, psychic-emotional system

DEFINITION: Abnormal involuntary movements with different causes and clinical presentations.

CAUSES: Neurologic, vascular, genetic, or metabolic disorders; pharmacotherapy

SYMPTOMS: Abnormal involuntary movements

DURATION: Acute, chronic

TREATMENTS: Pharmacotherapy, drug treatment modification, deep brain stimulation

Causes and Symptoms

There are many types of dyskinesia, with different clinical appearances, pathogenetic mechanisms, and treatment modalities. The most common manifestations are (restlessness), athetosis (slow, writhing movements), ballism (arm or leg flinging), chorea (jerky, dancelike movements), dystonia (increased muscle tone with repetitive patterned movements and distorted posturing), (lightning-fast movements), stereotypy (repetitive, patterned, coordinated ritualistic movements), restless legs, tic, and tremor. These abnormal movements may involve the head, face, mouth, limbs, or trunk. Depending on the specific clinical type, the disease mechanism includes damage to cerebral or subcortical structures such as basal ganglia, stem, and cerebellum. In adults, multiple neurodegenerative diseases, inherited conditions, disorders (stroke), tumors, infections, malformations, and drug treatments can lead to dyskinesia. In children, abnormal involuntary movements can be caused by genetic conditions, hypoxia, and excessive in the (kernicterus).

Huntington’s disease, an autosomal dominant neurodegenerative disorder, is a common genetic cause of chorea and ballism. Cerebral palsy, overactive thyroid, pregnancy, metabolic abnormalities, and drug-induced disorders are some of the nongenetic causes of choreic motions.

Combinations of various involuntary movements occur in a group of conditions called paroxysmal dyskinesias, characterized by the sudden occurrence of dyskinetic movements (dystonia, chorea, athetosis, ballism), either spontaneous or triggered by an unexpected stimulus.

Neuroleptic-induced tardive dyskinesia and levodopa-induced dyskinesia are two of the most common drug-induced abnormal movement syndromes. Tardive dyskinesia manifests with grimacing, masticatory motions of the mouth and tongue, and choreo-athetoid movements of the and limbs. Most often it develops after months or years of treatment, especially with typical antipsychotic drugs (such as haloperidol). Nevertheless, it was observed in schizophrenic patients long before the advent of antipsychotic antagonists, which suggests that these individuals might be susceptible to involuntary movements. It is also known to occur after treatment (metoclopramide). The of tardive dyskinesia is not completely understood, but dopaminergic and oxidative stress are believed to be involved.

Dyskinesia can occur after years of levodopa, or L-dopa, therapy for Parkinson’s disease. Some movements appear at the peak blood levels of medication (peak-dose dyskinesia), others when the drug level is peaking and falling (biphasic dyskinesia) and even at low drug levels. Young age, longer disease duration, and high levodopa dosage are known for these complications. The intricate mechanism generating levodopa-induced dyskinesia involves an interplay between the loss of dopaminergic nerve terminals and long-term drug treatment with pulsatile stimulation of receptors.

Treatment and Therapy

Therapeutic approaches vary, depending on the type of movement and of dyskinesia. Recommended pharmacologic treatments include benzodiazepines (myoclonus, tremor, dystonia), tetrabenazine (chorea, stereotypy, tremor), agents (dystonia), dopaminergic drugs (restless legs), anticonvulsants (tremor, myoclonus), botulinum (tremors, tics, dystonia), antipsychotics, and brain enhancers. Deep brain stimulation and repetitive transcranial magnetic stimulation are effective procedures. Stress and activity often aggravate dyskinesia, while relaxation and sleep alleviate it. Physical therapy and self-help groups should be employed as necessary.

In drug-induced dyskinesia, prevention is crucial. Once the levodopa-induced dyskinesia occurs, modification of the treatment regimen becomes necessary. Deep brain stimulation and pharmacotherapy (dopaminergic agents, amantadine) are beneficial in certain categories of patients.

Patients treated with neuroleptics should be examined for involuntary movements before commencing therapy and subsequently maintained on the lowest effective dose. If symptoms develop, then dosage is advised. No agent is truly effective in treating tardive dyskinesia, but vitamin E, tetrabenazine, and botulinum toxin have been shown to alleviate the symptoms. Mild tardive dyskinesia may improve with benzodiazepines and cholinergic agents. Atypical antipsychotic drugs (clozapine, olanzapine, risperidone) are less prone to inducing dyskinesia and may even be beneficial in patients who develop the symptoms.

Perspective and Prospects

In the sixteenth century, Andrea Vesalius and Francisco Piccolomini distinguished subcortical nuclei from cerebral cortex and white matter, and Paracelsus introduced the concept of chorea. The nineteenth century brought the recognition of striatal lesions as causes of chorea and athetosis. Classifications and descriptions for myoclonic movements were introduced. In the late nineteenth century, Gilles de la Tourette and Jean M. Charcot presented cases of tic disorders. A relationship between subthalamic lesions and ballism was demonstrated in the first half of the twentieth century. Since then, the important role played by this nucleus in hyperkinetic disorders has become evident. In the late twentieth century, genetic mutations were identified in families with dystonia. Therapeutic strategies for levodopa-induced dyskinesia were implemented. Physicians and neuroscientists continue to make significant progress in elucidating the of and the pathogenesis of hyperkinetic movement disorders. Brain imaging, animal models, and molecular techniques are widely used. New modalities of delivering levodopa are being explored. Tardive dyskinesia remains a source of concern as a result of its drug-induced nature. The available data suggest a lower risk of dyskinesia with newer medications. However, more studies of relative risk and appropriate doses are needed.

While attempting to find pathogenesis-targeted therapies, it is imperative to achieve a good understanding of the clinical syndromes and to use comprehensive rating systems. This will allow for more effective patient management, with the goal of improving the quality of life by reducing disability and reliance on caregivers.

Bibliography

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Jankovic, Joseph. “Treatment of Hyperkinetic Movement Disorders.” Lancet Neurology 8, no. 9 (September, 2009): 844–56.

MedlinePlus. "Movement Disorders." MedlinePlus, April 19, 2013.

Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Tardive Dyskinesia: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002.

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