What is the best course of action for a post-operative patient experiencing continuous focal seizures despite being on antiepileptics (Anti-Epileptic Drugs, AEDs)?

Management of Continuous Focal Seizures in Post-Operative Patients on Antiepileptics

For a post-operative patient experiencing continuous focal seizures despite being on antiepileptic drugs, immediately optimize the current regimen by increasing the dose to therapeutic levels or adding levetiracetam (1000-2000 mg/day divided twice daily) as adjunctive therapy, while simultaneously obtaining urgent neuroimaging to exclude surgical complications such as hematoma, infection, or other structural changes. 1, 2

Immediate Assessment and Imaging

• New or worsening seizures in post-craniotomy patients often signal complications such as hematoma expansion, infection, or other structural changes; therefore, obtaining repeat neuroimaging (contrast-enhanced MRI or CT) is mandatory before attributing seizures solely to medication failure. 1, 2
• Evaluate for metabolic derangements including hypoglycemia, hyponatremia, hypoxia, and drug toxicity that may be contributing to breakthrough seizures. 3

Medication Optimization Strategy

First-Line Approach: Optimize Current Therapy

• If the patient is on subtherapeutic doses of their current antiepileptic drug, increase to therapeutic levels first before adding additional agents. 2
• Check serum drug levels (if applicable for the current medication) to assess compliance and therapeutic dosing. 2

Adding Adjunctive Therapy

• If already on therapeutic monotherapy with persistent breakthrough seizures, add levetiracetam as the preferred second agent rather than switching medications abruptly. 1, 2
• Levetiracetam is the drug of first choice at most neuro-oncology and neurosurgical centers due to its efficacy, favorable side-effect profile, lack of significant drug interactions with steroids and other medications commonly used in neurosurgical patients, and ability to be titrated relatively quickly. 1, 2
• Lacosamide should be considered as adjunctive therapy if monotherapy with levetiracetam fails to control seizures, as it has demonstrated effectiveness in focal seizures with a favorable side-effect profile. 1, 4

Alternative Second-Line Options

• Lamotrigine is an effective alternative but requires several weeks of gradual titration to reach therapeutic levels, making it less suitable for acute breakthrough seizure management. 2
• Combinations of levetiracetam with sodium channel blockers (lacosamide or lamotrigine) have shown favorable efficacy in clinical studies. 5

Agents to Avoid

• Do not use or switch to phenytoin, carbamazepine, or phenobarbital as these have unfavorable side-effect profiles, significant drug interactions with steroids and various cytotoxic agents, and require serum level monitoring. 1, 2
• Benzodiazepines (clobazam, clonazepam) are not appropriate for chronic seizure management in post-craniotomy patients; they are intended for acute seizure control or specific refractory epilepsy syndromes, not for long-term maintenance therapy in structural epilepsy. 1
• Valproic acid should be avoided in females of childbearing potential and requires regular monitoring for drug interactions, thrombocytopenia, and hepatotoxicity. 1, 6

Management of Status Epilepticus (If Seizures Are Continuous)

• If the patient meets criteria for status epilepticus (continuous seizure activity >5 minutes or recurrent seizures without return to baseline), first-line treatment is optimal dosing of benzodiazepines. 3, 6
• For benzodiazepine-refractory status epilepticus, administer intravenous fosphenytoin (18-20 PE/kg at maximum rate of 150 PE/min), valproate (20-30 mg/kg at 40 mg/min), or levetiracetam (30-50 mg/kg at 100 mg/min) as second-line agents with similar efficacy (approximately 45-47% seizure termination). 3, 6
• Levetiracetam has the lowest rate of life-threatening hypotension (0.7%) compared to fosphenytoin (3.2%) and valproate (1.6%). 6

Duration of Therapy and Long-Term Management

• Continue anticonvulsants until local control has been achieved and the patient remains seizure-free for an extended period (typically 1-2 years minimum). 1, 2
• For patients who achieve near-total resection during craniotomy and remain seizure-free, consider tapering anticonvulsants only after achieving both surgical success and prolonged seizure freedom. 1
• The indication for anti-seizure therapy should be revisited at each follow-up, but in cases with breakthrough seizures, continuation and optimization is clearly indicated. 2

Critical Pitfalls to Avoid

• The most critical error is assuming breakthrough seizures represent simple medication failure without obtaining neuroimaging to exclude tumor progression, hematoma, infection, or other structural complications. 1, 2
• Do not abruptly discontinue antiepileptic drugs in a patient with established seizure disorder, even when considering a medication change. 2
• Do not use prophylactic antiepileptics in patients who have never seized, as perioperative therapy with AEDs has no impact on seizure outcomes; however, patients who have already experienced seizures require secondary prophylaxis and treatment is strongly recommended. 3, 1

Monitoring for Adverse Events

• Monitor for levetiracetam-related behavioral issues, nausea, and rash. 6
• Monitor for lacosamide-related dizziness and potential cardiac conduction effects. 4
• If using valproate, monitor for thrombocytopenia, liver toxicity, and hyperammonemia. 6

Patient Safety Considerations

• Instruct patients and caregivers on how to respond to seizures and whom to contact in case of recurrent seizures. 2
• Discuss driving restrictions according to local regulations, considering both epilepsy and other aspects of neurological function. 2
• Emphasize the importance of medication compliance and not missing doses. 2