Background     Myoclonus is an abnormal movement described as a sudden, brief, shock-like, involuntary movement caused by active muscle contraction (positive myoclonus) or inhibition of ongoing muscle contraction (negative myoclonus).  Myoclonus can have a distribution that is focal, multifocal, or generalized.  This Fast Fact discusses its causes, evaluation, and therapy in patients with serious illness.

Characteristics of myoclonus    Hiccups are an example of normal, physiological positive myoclonus, while asterixis is an example of negative myoclonus seen with metabolic encephalopathy. In nocturnal myoclonus or periodic leg movement disorder, there is activity in the flexor muscles of the legs and feet during light sleep. It can be seen in the setting of chronic nervous system diseases or in elderly patients with no other abnormalities. The brief, shock-like movements of myoclonus may be difficult to distinguish from other involuntary movements such as cramps, spasms, fasciculations, and dystonia.  Fasciculations are brief involuntary muscle twitches that, unlike myoclonus, often do not result in movement across a joint. Dystonia is characterized as slow, repetitive, patterned, sustained movements (an example is writer’s cramp).  An acute dystonic reaction is often caused by dopamine blocking medications including certain antipsychotics (haloperidol), antiemetics (metoclopramide), and calcium-channel blockers. Myoclonus may be more common when patients are going in and out of sleep.

Causes of myoclonus are too numerous to comprehensively name in this Fast Fact.  Near the end of life, metabolic abnormalities and medication-induced myoclonus predominate. Collaboration with a neurologist and/or pharmacist may be needed in diagnostic dilemmas.  In certain cases, electroencephalography (EEG), thyroid tests, comprehensive metabolic panel, infectious work-ups, and/or brain imaging may be ordered to help identify the cause of myoclonus. 

• Metabolic causes include liver failure, renal failure, hyponatremia, and hypoglycemia.
• CNS damage from tumors, stroke, encephalitis, encephalopathies (viral, metabolic, genetic, or neurodegenerative), seizure disorders, anoxic brain injury, and disorders affecting the spinal cord and peripheral nerves.
• Medications and toxins associated with myoclonus include opioids, anticonvulsants (gabapentin, phenytoin, valproate, lamotrigine, and phenobarbital), tricyclic antidepressants, selective serotonin reuptake inhibitors, contrast dye, anesthetics, antibiotics (penicillins, cephalosporins, imipenem, and quinolones), cannabinoids, and anti-neoplastic agents like ifosfamide.  When myoclonus is due to a medication, it is usually accompanied by encephalopathy, more multifocal or generalized in nature, and provoked by a stimulus or voluntary movement.

General treatment strategies    Myoclonus can disrupt sleep, make coordinated movements difficult, and be bothersome to patients with serious illness and their families. Treatment consists of correction of the underlying cause if medically appropriate and consistent with goals of care. If the offending agent is a non-essential medication, discontinue it.  For opioid-induced myoclonus, rotation to a different opioid may be advised since opioid-induced myoclonus often results from a buildup of toxic metabolites. Hence, the myoclonus can be a precursor to more concerning neuroexcitatory effects from opioids like allodynia, hyperalgesia, and even seizures.  Meperidine and codeine are most associated with myoclonus, but morphine, oxycodone, hydrocodone, and hydromorphone have also been associated. Fentanyl and methadone may be less likely to cause myoclonus.

Pharmacologic treatment is often challenging due to the transitory nature of myoclonus. It is typically reserved for persistent myoclonus that is causing significant distress to the patient or family. There is a lack of good research data to guide pharmacologic management of myoclonus, so medication selection is often based on anecdote and experience. Benzodiazepines are the primary symptomatic treatment at end-of-life for myoclonus. Their use must be weighed by their tendency to worsen cognition and coordination.  Clonazepam and lorazepam are the most used benzodiazepines for myoclonus.  A continuous infusion of midazolam has also been described in the literature.  Sedation is likely when using benzodiazepines. If sedation is to be avoided, anticonvulsants such as levetiracetam (1,000-3,000 mg/day) and valproic acid (1200-2000 mg/day) may be helpful.  The muscle relaxant dantrolene in doses of 50-100 mg/day has been reported as effective as has intrathecal baclofen in a few case reports.

References 

1. Caviness, J.  Treatment of myoclonus.  Neurotherapeutics. 2014; 11:188-200.
2. Daroff R, Fenichel G., et al.  Bradley’s Neurology in Clinical Practice. 6th ed. Philadelpha, PA: Elsevier Saunders; 2012.
3. Fahn S. Overview, history, and classification of myoclonus. Adv Neurol. 2002; 89:13-17.
4. Restrepo D, Kochav J, Goodheart AE, et al.  The importance of identifying myoclonus in the setting of mental status abnormalities: differential diagnosis and treatment. Pim Care Companion CNS Disord 2016; 18(5).
5. Gordon MF. Toxin and drug-induced myoclonus. Adv Neurol. 2002; 89:49-76.
6. Mihelucci R, Pasini E, Riguzzi P, et al.  Myoclonus and seizures in progressive myoclonus epilepsies: pharmacology and therapeutic trials. Epileptic Disorders 2016; 18(s2):S145-S153.
7. Mercadante S. Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain. 1998; 74:5-9.
8. Rivest J. Myoclonus (Rev). Can J Neurol Sci. 2003; 30(Suppl 1):S53-58.
9. Whitlock JA Jr, Dumigan RW. Treatment of postanoxic action myoclonus with intrathecal baclofen: a case report. Phys Med and Rehab 2018;10(8):870.

Version History:  This Fast Fact was originally edited by David E Weissman MD and published in May 2004; 2nd Edition in April 2009; 3rd Edition in June 2015 by Sam Maiser MD; 4th Edition in March 2025.
Conflicts of Interest: None to report.