What are the treatment options for Myoclonus (involuntary muscle twitching)?

From the Guidelines

Myoclonus treatment should prioritize the use of levetiracetam, valproic acid, or clonazepam as first-line medications, with consideration of combination therapy and non-pharmacological approaches, as supported by the most recent guidelines and studies 1. When treating myoclonus, it is essential to address the underlying cause while controlling symptoms with medications. The most recent study from 2024 1 provides guidance on the treatment of myoclonus, particularly in the context of post-cardiac arrest care.

Key Considerations

• Myoclonus is a common clinical manifestation of hypoxic-ischemic brain injury, occurring in approximately 20% of cardiac arrest survivors 1.
• EEG monitoring is crucial in detecting nonconvulsive seizures and status epilepticus, as well as distinguishing between different types of myoclonus 1.
• The American Clinical Neurophysiology Society defines the ictal-interictal continuum, which is essential in guiding treatment decisions for patients with rhythmic or periodic patterns on EEG 1.

Treatment Approach

• First-line treatment often includes levetiracetam (Keppra) at 500-3000 mg/day, valproic acid (Depakote) at 750-3000 mg/day, or clonazepam (Klonopin) at 1.5-15 mg/day, as these medications enhance GABA inhibition or modulate neuronal excitability to reduce abnormal muscle jerking.
• For post-hypoxic myoclonus, a combination approach may be needed, potentially including piracetam at higher doses (8-24 g/day) 1.
• In cases of cortical myoclonus, zonisamide (100-400 mg/day) or perampanel (4-12 mg/day) may be beneficial.
• Treatment should be tailored to the specific type of myoclonus and its cause, with consideration of non-pharmacological approaches, including physical therapy and occupational therapy, to help patients manage daily activities affected by myoclonic jerks.

Monitoring and Adjustment

• Regular follow-up is essential to monitor medication effectiveness and adjust treatment as needed, with consideration of switching to another agent or using combination therapy if the first medication is ineffective or poorly tolerated.
• The TELSTAR trial, a randomized clinical trial published after the 2020 guidelines, found that protocolized tiered treatment targeting suppression of EEG rhythmic or periodic patterns did not differ in rates of poor neurological outcome between treatment arms, but suggested potential benefits for patients with unequivocal electrographic seizures or evolving patterns 1.

From the FDA Drug Label

The effectiveness of levetiracetam as adjunctive therapy (added to other antiepileptic drugs) in patients 12 years of age and older with juvenile myoclonic epilepsy (JME) experiencing myoclonic seizures was established in one multicenter, randomized, double-blind, placebo-controlled study, conducted at 37 sites in 14 countries Table 5 displays the results for the 113 patients with JME in this study Table 5: Responder Rate (≥50% Reduction From Baseline) In Myoclonic Seizure Days Per Week for Patients with JME Placebo(N=59)Levetiracetam(N=54)

• statistically significant versus placebo Percentage of responders23.7%60. 4%*

Levetiracetam is effective in treating myoclonus in patients with juvenile myoclonic epilepsy (JME), with a statistically significant reduction in myoclonic seizure days per week compared to placebo, as shown in the study with a responder rate of 60.4% for levetiracetam versus 23.7% for placebo 2.

From the Research

Myoclonus Treatment Options

• The treatment of myoclonus is mainly based on the pathophysiological origin of the neuronal discharges producing the jerks 3.
• Treatment is targeted to the underlying disorder, and if the diagnosis is not known, treatment could be directed empirically at cortical myoclonus as the most common physiology 4.
• For cortical myoclonus, the most effective drugs are sodium valproic acid, clonazepam, levetiracetam, and piracetam 4, 5, 3, 6, 7.

Classification-Based Treatment

• Cortical myoclonus can be treated with levetiracetam, valproic acid, and clonazepam as first-line agents 5, 7.
• Cortical-subcortical myoclonus may be treated with valproic acid as the mainstay of therapy, and lamotrigine can be used either alone or in combination with valproic acid 4, 5, 7.
• Subcortical-nonsegmental myoclonus may respond to clonazepam and deep-brain stimulation 4, 5, 7.
• Segmental and peripheral myoclonus are often resistant to treatment, but anticonvulsants and botulinum toxin injections may be of utility depending upon the case 5, 7.

Additional Treatment Considerations

• A ketogenic diet can be considered if everything else fails 4.
• Rituximab, adrenocorticotropic hormone, high-dose dexamethasone pulse, or plasmapheresis have been reported to improve opsoclonus myoclonus syndrome 4.
• Reticular reflex myoclonus can be treated with clonazepam, diazepam, and 5-hydrotryptophan 4, 3.
• Functional myoclonus requires multimodal and multidisciplinary treatment that may include psychotropic drugs and physical and occupational therapy 5.