Treatment of myoclonus

Abstract

Myoclonus creates significant disability for patients. This symptom or sign can have many different etiologies, presentations, and pathophysiological mechanisms. A thorough evaluation for the myoclonus etiology is critical for developing a treatment strategy. The best etiological classification scheme is a modified version from that proposed by Marsden et al. in 1982. Clinical neurophysiology, as assessed by electromyography and electroencephalography, can be used to classify the pathophysiology of the myoclonus using a neurophysiology classification scheme. If the etiology of the myoclonus cannot be reversed or treated, then symptomatic treatment of the myoclonus itself may be warranted. Unfortunately, there are few controlled studies for myoclonus treatments. The treatment strategy for the myoclonus is best derived from the neurophysiology classification scheme categories: 1) cortical, 2) cortical-subcortical, 3) subcortical-nonsegmental, 4) segmental, and 5) peripheral. A cortical physiology classification is most common. Levetiracetam is suggested as first-line treatment for cortical myoclonus, but valproic acid and clonazepam are commonly used. Cortical-subcortical myoclonus is the physiology demonstrated by myoclonic seizures, such as in primary epileptic myoclonus (e.g., juvenile myoclonic epilepsy). Valproic acid has demonstrated efficacy in such epileptic syndromes with other medications providing an adjunctive role. Clonazepam is used for subcortical-nonsegmental myoclonus, but other treatments, depending on the syndrome, have been used for this physiological type of myoclonus. Segmental myoclonus is difficult to treat, but clonazepam and botulinum toxin are used. Botulinum toxin is used for focal examples of peripheral myoclonus. Myoclonus treatment is commonly not effective and/or limited by side effects.

Fig. 1

Surface electromyography polygraphy recording from multiple left arm muscles in a patient with cortical myoclonus during muscle activation. Note the hypersynchronous and multifocal nature of the discharges that commonly occur with co-contraction of agonists and antagonists, sometimes across muscle segments. The electroencephalography back-averaging of these discharges is shown in Fig. 2

Fig. 2

Electroencephalography (EEG) back-averaging of the surface electromyography discharges that are shown in Fig. 1. The EEG transient has a right centro-parietal maximum, consistent with left arm cortical myoclonus. The EEG transient begins 24 ms before the 0 ms trigger point, consistent with corticospinal transmission of the myoclonus generation. The x-axis is 200 ms across left to right full extent. The y-axis is 100 μV bottom to top full extent

Fig. 3

Myoclonus treatment algorithm. See text for approach and details