Current challenges in the pathophysiology, diagnosis, and treatment of paroxysmal movement disorders

Abstract

Introduction: Paroxysmal movement disorders mostly comprise paroxysmal dyskinesia and episodic ataxia, and can be the consequence of a genetic disorder or symptomatic of an acquired disease.

Areas covered: In this review, the authors focused on certain hot-topic issues in the field: the respective contribution of the cerebellum and striatum to the generation of paroxysmal dyskinesia, the importance of striatal cAMP turnover in the pathogenesis of paroxysmal dyskinesia, the treatable causes of paroxysmal movement disorders not to be missed, with a special emphasis on the treatment strategy to bypass the glucose transport defect in paroxysmal movement disorders due to GLUT1 deficiency, and functional paroxysmal movement disorders.

Expert opinion: Treatment of genetic causes of paroxysmal movement disorders is evolving towards precision medicine with targeted gene-specific therapy. Alteration of the cerebellar output and modulation of the striatal cAMP turnover offer new perspectives for experimental therapeutics, at least for paroxysmal movement disorders due to selected causes. Further characterization of cell-specific molecular pathways or network dysfunctions that are critically involved in the pathogenesis of paroxysmal movement disorders will likely result in the identification of new biomarkers and testing of innovative-targeted therapeutics.

Keywords: ADCY5; ATP1A3; PRRT2; SLC2A1; cAMP; cerebellum; episodic ataxia; ketogenic diet; paroxysmal dyskinesia; triheptanoin.