Paroxysmal Dyskinesias

https://doi.org/10.1016/j.spen.2017.12.007Get rights and content

Paroxysmal dyskinesias (PD) are hyperkinetic movement disorders where patients usually retain consciousness. Paroxysmal dyskinesias can be kinesigenic (PKD), nonkinesigenic (PNKD), and exercise induced (PED). These are usually differentiated from each other based on their phenotypic and genotypic characteristics. Genetic causes of PD are continuing to be discovered. Genes found to be involved in the pathogenesis of PD include MR-1, PRRT2, SLC2A1, and KCNMA1. The differential diagnosis is broad as PDs can mimic psychogenic events, seizure, or other movement disorders. This review also includes secondary causes of PDs, which can range from infections, metabolic, structural malformations to malignancies. Treatment is usually based on the correct identification of type of PD. PKD responds well to antiepileptic medications, whereas PNKD and PED respond to avoidance of triggers and exercise, respectively. In this article, we review the classification, clinical features, genetics, differential diagnosis, and management of PD.

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

References (101)

  • C. Castiglioni et al.

    Pyruvate dehydrogenase deficiency presenting as isolated paroxysmal exercise induced dystonia successfully reversed with thiamine supplementation. Case report and mini-review

    Eur J Paediatr Neurol

    (2015)
  • K.P. Thomas et al.

    Paroxysmal kinesigenic dyskinesias and pseudohypo-parathyroidism type Ib

    Pediatr Neurol

    (2010)
  • C.A. Morres et al.

    Movement disorders as a manifestation of nonketotic hyperglycemia

    J Emerg Med

    (1989)
  • L. Tschopp et al.

    Neuroacanthocytosis and carbamazepine responsive paroxysmal dyskinesias

    Parkinsonism Relat Disord

    (2008)
  • C.H. Ko et al.

    Ictal (99m)Tc ECD SPECT in paroxysmal kinesigenic choreoathetosis

    Pediatr Neurol

    (2001)
  • T.D. Sanger et al.

    Movement Disorders

    Swaiman′s Pediatric Neurology: Principles and Practice

    (2012)
  • A.R. Gardiner et al.

    The clinical and genetic heterogeneity of paroxysmal dyskinesias

    Brain

    (2015)
  • L.M. Reback

    S. Familial paroxysmal choreoathetosis

    Arch Neurol

    (1940)
  • A. Kertesz

    Paroxysmal kinesigenic choreoathetosis. An entity within the paroxysmal choreoathetosis syndrome. Description of 10 cases, including 1 autopsied

    Neurology

    (1967)
  • R.N. Richards et al.

    Paroxysmal dystonic choreoathetosis. A family study and review of the literature

    Neurology

    (1968)
  • J.W. Lance

    Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes

    Ann Neurol

    (1977)
  • M. Demirkiran et al.

    Paroxysmal dyskinesias: clinical features and classification

    Ann Neurol

    (1995)
  • J. Blakeley et al.

    Secondary paroxysmal dyskinesias

    Mov Disord

    (2002)
  • I. Unterberger et al.

    Diagnosis and treatment of paroxysmal dyskinesias revisited

    Ther Adv Neurol Disord

    (2008)
  • M.K. Bruno et al.

    Genotype-phenotype correlation of paroxysmal nonkinesigenic dyskinesia

    Neurology

    (2007)
  • A. Albanese et al.

    Phenomenology and classification of dystonia: a consensus update

    Mov Disord

    (2013)
  • U. Müller et al.

    Clinical and molecular genetics of primary dystonias

    Neurogenetics

    (1998)
  • C. Marras et al.

    Fixing the broken system of genetic locus symbols: Parkinson disease and dystonia as examples

    Neurology

    (2012)
  • C.H. Camargo et al.

    The genetics of the dystonias-a review based on the new classification of the dystonias

    Arq Neuro-Psiquiatr

    (2014)
  • S.-S. Hao et al.

    Neuropathophysiology of paroxysmal, systemic, and other related movement disorders

    Eur Rev Med Pharmacol Sci

    (2015)
  • M.K. Bruno et al.

    Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria

    Neurology

    (2004)
  • E. Byrne et al.

    Familial dystonic choreoathetosis with myokymia; a sleep responsive disorder

    J Neurol Neurosurg Psychiatry

    (1991)
  • Byrne E ea. Familial dystonic choreoathetosis with myokymia; a sleep responsive disorder. - PubMed - NCBI....
  • K.P. Bhatia

    Familial (idiopathic) paroxysmal dyskinesias: an update

    Semin Neurol

    (2001)
  • S. Fahn

    The early history of paroxysmal dyskinesias

    Adv Neurol

    (2002)
  • R. Fekete

    Paroxysmal nonkinesigenic dyskinesia with tremor

    Case Rep Neurol Med

    (2013)
  • S. Zittel et al.

    Fatal paroxysmal non-kinesigenic dyskinesia

    Eur J Neurol

    (2015)
  • Ha A JJPd. Paroxysmal dyskinesias. 2016;...
  • T. Sato et al.

    A child with paroxysmal exertion-induced dyskinesia

    No To Hattatsu

    (2012)
  • M. Bozi et al.

    Paroxysmal exercise-induced dystonia as a presenting feature of young-onset Parkinson’s disease

    Mov Disord

    (2003)
  • K.P. Bhatia et al.

    Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesia

    Mov Disord

    (2012)
  • A.R. Gardiner et al.

    PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine

    Neurology

    (2012)
  • R. Erro et al.

    Paroxysmal dyskinesias revisited: a review of 500 genetically proven cases and a new classification

    Mov Disord

    (2014)
  • A. Labate et al.

    Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype wtih mental retardation, episodic ataxia, and absences

    Epilepsia

    (2012)
  • H.Y. Lee et al.

    The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway

    Hum Mol Genet

    (2004)
  • E. Stefanova et al.

    Clinical characteristics of paroxysmal nonkinesigenic dyskinesia in Serbian family with Myofibrillogenesis regulator 1 gene mutation

    Mov Disord

    (2006)
  • D.C. De Vivo et al.

    Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay

    N Engl J Med

    (1991)
  • Reference GH. SLC2A1 gene. 2017;...
  • R. Pons et al.

    The spectrum of movement disorders in Glut-1 deficiency

    Mov Disord

    (2010)
  • D. Wang et al.

    Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects

    Ann Neurol

    (2005)
  • Cited by (19)

    • Principles and Practice of Movement Disorders

      2021, Principles and Practice of Movement Disorders
    • Lacosamide for children with paroxysmal kinesigenic dyskinesia

      2020, Brain and Development
      Citation Excerpt :

      Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterized by short, repetitive episodes of involuntary movements typically triggered by sudden voluntary movements, including chorea, dystonia, athetosis, and ballism, either alone or in combination [1,2].

    View all citing articles on Scopus
    View full text