What is the treatment for myoclonus?

Treatment of Myoclonus

Levetiracetam is the first-line treatment for myoclonus, particularly for cortical myoclonus, with valproate and clonazepam as alternative or adjunctive options. 1

Classification and Diagnosis

• Myoclonus presents as a sudden brief jerk caused by involuntary muscle activity, typically 10-50 ms in duration 2
• It is essential to determine the anatomical source of myoclonus (cortical, subcortical, brainstem, or spinal) as this guides treatment selection 1
• EEG should be performed in the presence of myoclonic jerks to detect any associated epileptiform activity and distinguish epileptic from non-epileptic myoclonus 3
• Myoclonus can be classified as physiological, essential, epileptic, or symptomatic (most common) 4

First-Line Pharmacological Treatment

• For cortical myoclonus:

  • Levetiracetam is a first-line agent, FDA-approved specifically for myoclonic seizures in patients 12 years and older 5, 1
  • Standard dosing begins at 1000 mg/day (500 mg twice daily) with increases of 1000 mg/day every 2 weeks to a recommended dose of 3000 mg/day 5
  • Levetiracetam is particularly effective for myoclonic jerks and has fewer adverse effects than other options 6

• For subcortical and brainstem myoclonus:

  • Clonazepam is the first-line agent, though levetiracetam and valproic acid can also be effective 1
  • Benzodiazepines are particularly useful for acute management of myoclonus 3

• For spinal myoclonus:

  • Clonazepam is the first-line agent 1
  • Spinal myoclonus typically does not respond well to anti-epileptic drugs 1

Alternative and Adjunctive Treatments

• Valproic acid is an effective antimyoclonic agent and can be used as first-line or adjunctive therapy 6, 7

  • Low doses (500-1000 mg/day) may be effective for myoclonus, particularly in juvenile myoclonic epilepsy 8

• Combination therapy is often necessary for severe myoclonus 7

  • Common effective combinations include:
    • Valproate + clonazepam + levetiracetam
    • Valproate + clonazepam + primidone
    • Levetiracetam + clonazepam 7

• For refractory cases, additional options include:

  • L-5-Hydroxytryptophan
  • Sodium oxybate
  • Piracetam (often in combination with other agents) 1, 7

Special Considerations

• Avoid phenytoin and carbamazepine as they may paradoxically worsen myoclonus 1

• For post-anoxic myoclonus (following cardiac arrest):

  • Propofol is effective for suppressing myoclonus and should be considered as a first-line agent 6
  • Status myoclonus within 72 hours after return of spontaneous circulation is associated with poor neurological outcome 3
  • EEG should be used to distinguish between epileptic and non-epileptic post-anoxic myoclonus 6

• For focal spinal myoclonus, botulinum toxin injections may be beneficial 1

• For functional (psychogenic) myoclonus:

  • Multimodal treatment including psychotropic medications and physical/occupational therapy 1
  • Collaboration between neurologists and psychiatrists is essential 1

Monitoring and Follow-up

• Assess treatment efficacy based on reduction in frequency and severity of myoclonic jerks 6

• Monitor for common adverse effects:

  • Levetiracetam: somnolence (12%), dizziness (9%), and psychiatric effects like irritability and mood changes 5
  • Valproate: gastrointestinal disturbances, tremor, weight gain, and potential hepatotoxicity 8
  • Clonazepam: sedation, cognitive impairment, and risk of tolerance/dependence 7

• Consider EEG monitoring to evaluate treatment response, especially in patients with epileptic myoclonus 6

Treatment Algorithm

1. Identify the anatomical source of myoclonus (cortical, subcortical, brainstem, or spinal)
2. Rule out reversible causes (medications, metabolic disorders)
3. For cortical myoclonus: Start with levetiracetam 500 mg twice daily, titrate up to 3000 mg/day as needed 5, 1
4. If inadequate response, add valproate or clonazepam 7
5. For severe, refractory myoclonus: Consider combination therapy with multiple agents 7
6. For post-anoxic myoclonus: Consider propofol for acute management 6
7. For spinal myoclonus: Start with clonazepam; consider botulinum toxin for focal cases 1