Does levetiracetam (Keppra) have a role in treating atonic seizures in a patient with a chronic infarct in the bilateral thalamus?

Levetiracetam for Atonic Seizures in Bilateral Thalamic Infarct

Levetiracetam has limited evidence for atonic seizures specifically, but given its proven efficacy in partial seizures, favorable safety profile in post-stroke patients, and lack of alternatives with stronger evidence for this rare scenario, it represents a reasonable treatment option for seizures arising from bilateral thalamic infarcts.

Evidence for Levetiracetam in Post-Stroke Seizures

• Levetiracetam demonstrates strong efficacy in post-stroke seizures, with 77.1% of patients achieving seizure freedom in a prospective study of late-onset post-stroke seizures (occurring ≥2 weeks after ischemic stroke) 1
• Most patients (54.3%) achieved seizure control at 1000 mg daily, with additional patients responding to 1500-2000 mg daily 1
• The drug exhibits favorable tolerability in elderly stroke patients, with only 11.4% discontinuing due to side effects (drowsiness with gait disturbance or aggressive behavior) 1

Mechanism and Seizure Type Considerations

Critical caveat: The evidence base primarily addresses partial (focal) seizures, not atonic seizures specifically. However, this distinction matters less than the underlying pathophysiology:

• Bilateral thalamic infarcts would most likely generate focal seizures with secondary generalization rather than primary generalized atonic seizures 2, 3
• Levetiracetam is FDA-approved and guideline-recommended for partial onset seizures with or without secondary generalization 4
• True atonic seizures typically arise from primary generalized epilepsy syndromes (e.g., Lennox-Gastaut syndrome), not focal structural lesions like thalamic infarcts 4

Recommended Treatment Approach

Initial Dosing Strategy

• Start with 1000 mg daily (500 mg twice daily), as this dose achieved seizure freedom in the majority of post-stroke patients 1
• Titrate to 1500 mg daily if inadequate response after 2 weeks 1
• Maximum studied dose in post-stroke patients was 3000 mg daily 1

Pharmacokinetic Advantages in Stroke Patients

• No hepatic metabolism - particularly important in elderly stroke patients with potential hepatic impairment 2
• No significant drug interactions - critical given polypharmacy common in stroke patients 2, 4
• Rapid achievement of steady-state concentrations allows quick assessment of efficacy 2

Alternative Considerations

If levetiracetam fails or is not tolerated:

• Valproate shows similar efficacy (68% vs 73% for levetiracetam) in refractory seizures 5, 6
• Phenytoin has been traditionally used post-stroke but carries higher cardiovascular risk 5
• For true atonic seizures (if confirmed by EEG), valproate or lamotrigine would be preferred, though this seems unlikely given the focal structural etiology 7

Monitoring Requirements

• EEG confirmation is essential to characterize seizure type accurately, as clinical atonic seizures may represent focal seizures with loss of postural tone rather than primary generalized atonic seizures 7
• Monitor for behavioral adverse effects (aggression, mood changes) which occurred in 8.6% of post-stroke patients 1
• Assess for somnolence and gait disturbance, particularly important in stroke patients with baseline mobility impairment 1

Safety Profile Specific to This Population

• Minimal cognitive impairment - advantageous in patients with potential thalamic cognitive deficits 4
• No drug-induced weight gain 4
• Well-tolerated in elderly patients with mean age 71.9 years in the post-stroke seizure study 1