Paroxysmal Dyskinesias
Introduction
Paroxysmal dyskinesias (PD) are rare hyperkinetic movement disorders which include chorea, dystonia, athetosis, and ballism, isolated or in combination. Patients are asymptomatic between episodes. They may or not be induced by movement, called kinesigenic (duration seconds to minutes) or nonkinesigenic (minutes to hours).1
The first documented case consistent with PD was described in 1892 in a 23-year-old Japanese man.2 The clinical syndrome was not fully described until 1940 by Mount and Reback.3 They wrote about a young male with episodes of dystonia and chorea caused by coffee and alcohol. It was at the time termed “familial paroxysmal choreoathetosis.”3 In 1967, Kertesz4 described a group of patients with episodes that were very brief in duration and precipitated by sudden movement naming this “paroxysmal kinesigenic choreoathetosis.”4 In 1968, Richards and Barnett5 suggested the term “paroxysmal dystonic choreoathetosis of Mount and Reback” since the postural and tone changes accompanied the choreoathetoid movements described in the Canadian family in their study.5 In 1977, Lance6 described a family with attacks that were provoked by prolonged exercise, which became classified as “paroxysmal exercise-induced dystonia.”6 In described cases of PD, there is significant overlapping of manifestations in regard to type of movements, duration, and precipitating factors. They may present as dystonias, chorea, athetosis, or ballism either individually or in varied combinations.
The most widely used classification for PDs was created by Demirkiran and Jankovic.7 Etiology and pathogenesis of PDs are still under investigation and not fully understood. Most cases are thought to be idiopathic. However, many secondary causes have been reported.8 Owing to the familial nature of this neurological disorder, the role of genetics is currently under extensive research.
Section snippets
Classification
As indicated above, in 1995 Demirkiran and Jankovic developed a widely used classification of PDs based on phenotype, precipitant factors, duration, and etiology.7 The proposed classification divided paroxysmal dyskinesias into 4 categories based on clinical features: Paroxysmal kinesigenic dyskinesias (PKD), paroxysmal nonkinesigenic dyskinesias (PNKD), paroxysmal exercise-induced dykinesias (PED), and paroxysmal hypnogenic dyskinesias (PHD). Each clinical feature is further subdivided by
Genetics
It has been reported that 40%-70% of PD cases are familial. Many genes that have been described are associated with PDs (Fig. 1).
Secondary Causes
In a study by Blakeley and Jankovic,8 92 patients with PDs were evaluated. Vascular causes were common in older patients, whereas trauma was more common in younger individuals. Other causes included kernicterus, multiple sclerosis, cytomegalovirus encephalitis, meningovascular syphilis, and migraines.
Acquired immunodeficiency syndrome (AIDS) and subacute sclerosing panencephalitis (SSPE) have also been described.57 Many metabolic disorders such as Wilson’s disease, Maple syrup urine disease,
Disorders That Mimic Paroxysmal Dyskinesias
Mimics of PDs include dopa-responsive dystonia, seizures, and tics.30 Dopa-responsive dystonia is a type of dystonia presenting in childhood with diurnal fluctuation and excellent response to low doses of oral dopamine.86 Kim et al87 looked at proton magnetic resonance spectroscopy (MRS) in 5 patients with idiopathic PKD and noticed that 2 patients had significant decrease in choline and myoinositol in their unilateral basal ganglia and 1 patient just had decreased myoinositol in unilateral
Diagnostic Work-up
A detailed history, family history, and video documentation of events are paramount in the differential diagnosis of PDs. Frontal lobe epilepsy should be ruled out. Interictal EEG may be useful in ruling out seizures whereas video EEG monitoring may provide better characterization of the phenomenon. Brain MRI should be obtained in the absence of a family history, especially in older patients to rule out secondary causes. Blood work will rule out metabolic causes such as
Treatment
Proper treatment relies on adequate identification of the type of PD and primary vs secondary causes. PKD have shown good response to antiepileptic drugs (AEDs) typically at lower doses than usually used to treat epileptic seizures. The most commonly used AEDs are carbamazepine/oxcarbazepine and phenytoin.93 In individual case studies or reviews, other AEDs have shown some success including phenobarbital, leviteracetam, gabapentin, valproate, lamotrigine, and topiramate.94 Patients with PKDs do
Conclusion
PD are a rare form of hyperkinetic movement disorders with preserved consciousness. They are usually divided into groups of kinesigenic, nonkinesigenic, and exercise induced based on phenotype. In genetic cases, mutations in PRRT2 are commonly implicated in patients with PKD, whereas MR-1 mutation is more often found in PNKD. Despite several genes recently found, we are just beginning to understand genotype/phenotype relationship and the complex genetics of patients with PD. Whole genome and
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