Paroxysmal movement disorders – practical update on diagnosis and management

ABSTRACT

Introduction: Paroxysmal dyskinesias and episodic ataxias are often caused by mutations in genes related to cell membrane and synaptic function. Despite the exponential increase in publications of genetically confirmed cases, management remains largely clinical based on non-systematic evidence.

Areas covered: The authors provide a historical and clinical review of the main types of paroxysmal dyskinesias and episodic ataxias, with recommendations for diagnosis and management of patients suffering from these conditions.

Expert opinion: After secondary paroxysmal dyskinesias, the most common paroxysmal movement disorders are likely to be PRRT2-associated paroxysmal kinesigenic dyskinesias, which respond well to small doses of carbamazepine, and episodic ataxia type 2, which often responds to acetazolamide. Familial paroxysmal non-kinesigenic dyskinesias are largely caused by mutations in PNKD and have poor response to therapy but improve with age. Exercise-induced dyskinesias are genetically heterogeneous, caused by disorders of glucose transport, mitochondrial function, dopaminergic pathways or neurodegenerative conditions amongst others. GNAO1 and ADCY5 mutations can also cause paroxysmal movement disorders, often in the context of ongoing motor symptoms. Although a therapeutic trial is justified for classic cases and in limited resource settings, genetic testing may help direct initial or rescue therapy. Deep brain stimulation may be an option for severe cases.

KEYWORDS:

• Acetazolamide
• antiepileptic drugs
• episodic ataxias
• paroxysmal dyskinesias
• paroxysmal movement disorders

Article highlights

• Paroxysmal movement disorders encompass episodic ataxia and paroxysmal dyskinesia (dystonia/chorea)

• Paroxysmal movement disorders may be caused by genetic mutations affecting cell membrane or synaptic function, or secondary to several types of structural abnormalities.

• Clinical (phenotypic) diagnosis is mainly based on the type of movement abnormality and main triggers for the attacks.

• The main genes associated with paroxysmal movement disorders are PRRT2, PNKD, SLC2A1, CACNA1A, KCNA1, GCH1, PARKIN. These conditions have clinical overlap but respond to different treatments. Several other genetic causes have been described, including mitochondrial disorders, ATP1A3, GNAO1, ADCY5, among others.

• Genotype-phenotype correlations are complex and treatment can be directed by clinical or genetic diagnosis.

Declaration of interest

CM de Gusmao has received research funding from the National Ataxia Foundation, unrelated to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior – Brasil (CAPES) – Finance Code 001.