What antiepileptics (Anti-Epileptic Drugs) are beneficial in treating post-hypoxic myoclonic seizures?

From the Guidelines

For post-hypoxic myoclonic seizures, the most beneficial antiepileptic medications include valproic acid, levetiracetam, and clonazepam, as they have been shown to be effective in suppressing epileptiform activity and improving outcomes 1. The choice of antiepileptic medication should be based on the individual patient's needs and medical history.

• Valproic acid is typically started at 20-30 mg/kg/day in divided doses, with therapeutic levels between 50-100 μg/mL.
• Levetiracetam is often initiated at 1000-1500 mg twice daily, which can be titrated up to 3000 mg daily if needed.
• Clonazepam may be used at 0.5-2 mg three times daily, particularly for acute management. These medications work through different mechanisms: valproic acid enhances GABA inhibition and blocks sodium channels, levetiracetam binds to synaptic vesicle protein SV2A to reduce neurotransmitter release, and clonazepam potentiates GABA-mediated inhibition. Treatment should begin promptly after myoclonic seizures are identified, as early control may improve neurological outcomes 1. Combination therapy is often required for refractory cases. Continuous EEG monitoring is recommended during treatment to assess response. These medications are particularly effective because they target the widespread neuronal hyperexcitability that occurs following cerebral hypoxia, helping to stabilize neural networks and prevent further seizure activity. It is essential to note that prophylactic anticonvulsant drugs after cardiac arrest in adults have been insufficiently studied, and routine seizure prophylaxis in post-cardiac arrest patients is not recommended due to the risk of adverse effects and the poor response to anti-epileptic agents among patients with clinical and electrographic seizures 1. However, treatment of recurrent seizures and status epilepticus constitutes “standard of care” in other patient populations, and ongoing seizures have the potential to worsen brain injury 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 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 beneficial in treating myoclonic seizures, as evidenced by a statistically significant reduction in myoclonic seizure days per week in patients with juvenile myoclonic epilepsy (JME) 2. However, the label does not specifically address post-hypoxic myoclonic seizures. Therefore, no conclusion can be drawn about the effectiveness of levetiracetam in treating post-hypoxic myoclonic seizures.

From the Research

Antiepileptic Drugs for Post-Hypoxic Myoclonic Seizures

• Valproate is commonly used as the first choice, alone or in combination with some benzodiazepines or levetiracetam, for treating myoclonic seizures 3, 4, 5.
• Levetiracetam is also widely used, and is suggested as first-line treatment for cortical myoclonus 6.
• Some benzodiazepines, such as clonazepam, are used to treat myoclonic seizures, including cortical-subcortical myoclonus and subcortical-nonsegmental myoclonus 3, 4, 6, 5.
• Brivaracetam has been shown to be superior to levetiracetam in a rat model of post-hypoxic myoclonus, with more potent anti-seizure and anti-myoclonic activity 7.
• Topiramate and zonisamide may be used as adjunctive therapy, but there is still insufficient evidence for their use as monotherapy 3, 4.

Important Considerations

• Avoidance of medications that may aggravate myoclonic seizures, such as carbamazepine and phenytoin, is crucial 3, 4.
• Treatment of myoclonic seizures is often based on clinical experience, with limited evidence from randomized clinical trials 3, 4, 5.
• A better understanding of the pathophysiologic mechanisms of myoclonic seizures and myoclonic epilepsies could lead to improved treatment options and quality of life for patients 3, 4, 5.