Abstract
This review presents a systematic diagnostic approach to myoclonus, a clinical sign characterized by rapid, brief involuntary movements caused by muscle contraction (positive myoclonus) or inhibition (negative myoclonus/asterixis). Following Marsden's classification, myoclonus is divided into four etiological categories: physiological (e.g., hypnic jerks in healthy individuals), essential (sporadic palatal myoclonus or hereditary myoclonus with onset before age 20, autosomal dominant inheritance, and benign course), epileptic (myoclonus occurring in the context of seizure disorders), and symptomatic (secondary to neurological or systemic disease, including drug/toxin exposure, hypoxic encephalopathy, neurodegenerative disease, autoimmune conditions, and metabolic disorders). An additional anatomical-physiological classification identifies five origin sites: cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral—each with distinct clinical and electrophysiological signatures useful for lesion localization. Diagnostic workup proceeds through four stages: syndrome identification via history and clinical examination (attending to distribution, temporal pattern, and activation characteristics); supportive laboratory testing (electrolytes, glucose, renal/hepatic/thyroid function, paraneoplastic antibodies, EEG, neuroimaging); clinical neurophysiological testing (surface EMG, simultaneous EEG-EMG polygraphy, somatosensory evoked potentials, jerk-locked back-averaging) when the diagnosis remains unclear; and specialized testing for rare causes (whole-body imaging for occult malignancy, enzyme assays, genetic testing for conditions such as Unverricht-Lundborg disease, Lafora body disease, and Wilson's disease) when standard workup is unrevealing.
