Myoclonus remains a challenging movement phenotype to characterize, evaluate, and treat. A systematic assessment of the temporal sequence, phenomenology, and distribution of movements can assist in the rational approach to diagnosis and management.
Cortical forms of myoclonus are increasingly recognized as primarily cerebellar disorders. A syndrome of orthostatic myoclonus has been recognized by electrophysiology in patients with neurodegenerative disorders, mainly in Alzheimer disease, accounting for impairments in gait and balance previously mischaracterized as normal pressure hydrocephalus or orthostatic tremor. Tyrosine hydroxylase deficiency and Silver-Russell syndrome (uniparental disomy of chromosome 7) have been established as two novel causes of the myoclonus-dystonia syndrome. Mutations in the glycine receptor (GlyR) α1-subunit gene (GLRA1) explain the major expression of hyperekplexia, an inherited excessive startle disorder, butnewly identified mutations in GlyR β-subunit (GLRB) and glycine transporter 2 (GlyT2) genes (SLC6A5) account for “minor” forms of this disorder manifested as excessive startle and hypnic jerks. The entity previously known as palatal myoclonus has been reclassified as palatal tremor in recognition of its clinical and electromyographic features and no longer enters the differential diagnosis of myoclonic disorders. Increasing documentation of psychogenic features in patients previously characterized as having propriospinal myoclonus has cast doubts on the existence of this distinctive disorder.
Myoclonus can be a prominent manifestation of a wide range of disorders. Electrophysiologic testing aids in distinguishing myoclonus from other mimics and classifying them according to cortical, subcortical, or spinal origin, which assists the choice of treatment. Despite the lack of randomized clinical trials, levetiracetam appears most effective in patients with cortical myoclonus, whereas clonazepam remains the only first-line therapeutic option in subcortical and spinal myoclonus.
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Address correspondence to Dr Alberto J. Espay, Department of Neurology, University of Cincinnati, 260 Stetson St, Suite 2300, Cincinnati, OH 45267, firstname.lastname@example.org.
Relationship Disclosure: Dr Espay receives grant support from Cleveland Medical Devices Inc/Great Lakes NeuroTechnologies, the Davis Phinney Foundation, and the Michael J. Fox Foundation, and received a K23 Career Development Award from the National Institute of Mental Health. Dr Chen has received personal compensation for activities with Allergan, Inc; EMD Serono, Inc; Medtronic, Inc; Merz Pharmaceuticals LLC; the Movement Disorders Society; University of California, Los Angeles; and the University of Pittsburgh. Dr Chen has provided expert testimony and affidavit in welding-related litigations. Dr Chen receives research support from the Canadian Institutes of Health Research, the Dystonia Medical Research Foundation, Medtronic, Inc, and the Michael J. Fox Foundation.
Unlabeled Use of Products/Investigational Use Disclosure: Drs Espay and Chen discuss the use of medications currently recommended for the treatment of myoclonus, none of which have been US Food and Drug Administration–approved.
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