What is the best approach to manage frequent breakthrough focal seizures in a patient with a history of oligodendroglioma (a type of brain tumor) status post (s/p) craniotomy resection?

Management of Breakthrough Focal Seizures in Post-Craniotomy Oligodendroglioma

For a patient with oligodendroglioma status post craniotomy who is experiencing frequent breakthrough focal seizures, you should optimize their current antiepileptic drug (AED) regimen by either increasing the dose or adding a second-generation non-enzyme-inducing AED, with levetiracetam or lamotrigine as preferred first-line agents. 1

Immediate Management Approach

Assess Current AED Therapy

• Verify the patient is on an appropriate AED at therapeutic doses. Third-generation agents such as levetiracetam, lamotrigine, or pregabalin are strongly preferred over first-generation drugs (phenytoin, carbamazepine, phenobarbital) which induce hepatic metabolism and interfere with chemotherapy agents. 1
• Levetiracetam has become the drug of first choice at most neuro-oncology centers due to its efficacy, favorable side-effect profile, and lack of drug interactions with chemotherapy. 1
• Check serum drug levels if applicable to assess compliance and therapeutic dosing. 1

Optimization Strategy

• If the patient is on subtherapeutic doses of their current AED, increase to therapeutic levels first. 1
• If already on therapeutic monotherapy with persistent breakthrough seizures, add a second non-enzyme-inducing AED rather than switching agents abruptly. 1
• Lamotrigine is an effective alternative but requires several weeks of gradual titration to reach therapeutic levels. 1
• Lacosamide may be considered as add-on therapy for patients whose seizures are not controlled by monotherapy. 1

Critical Reassessment Required

Rule Out Tumor Progression

• Worsening of a pre-existing seizure disorder in brain tumor patients often heralds tumor progression. Order repeat brain MRI immediately to assess for recurrent tumor growth. 1
• If near gross total resection was achieved initially and the patient has been seizure-free, but now has breakthrough seizures, this is particularly concerning for recurrence. 1

Evaluate for Other Precipitants

• Review medication compliance and potential drug interactions. 1
• Assess for metabolic derangements, infection, or other systemic factors that could lower seizure threshold. 1
• Consider EEG if seizure semiology has changed or if subclinical seizure activity is suspected. 1

Long-Term Management Considerations

Duration of AED Therapy

• Brain tumor patients who have suffered epileptic seizures should receive secondary prophylaxis until local control has been achieved. 1
• If near gross total resection is achieved with subsequent tumor regression from radiation or chemotherapy, tapering and stopping AEDs can be considered, but only after a period of seizure freedom and confirmed tumor control. 1
• After tumor resection, the indication for anti-seizure therapy should be revisited at each follow-up, but in this case with breakthrough seizures, continuation and optimization is clearly indicated. 1

Specific Drug Recommendations

Preferred Agents (in order)

1. Levetiracetam: Most commonly used, well-tolerated, no drug interactions, can be titrated relatively quickly. 1, 2
2. Lamotrigine: Good antiseizure activity but requires slow titration over several weeks. 1
3. Lacosamide: Effective as add-on therapy for refractory cases. 1

Agents to Avoid

• Do not use enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) as they interfere with chemotherapy metabolism and have worse side-effect profiles. 1
• Valproic acid, while effective, carries risks of thrombocytopenia and hepatotoxicity, particularly in patients on chemotherapy. 1

Common Pitfalls to Avoid

• Do not assume breakthrough seizures are simply medication failure without imaging to exclude tumor progression. This is the most critical error to avoid. 1
• Do not switch to or continue first-generation AEDs (phenytoin, carbamazepine, phenobarbital) due to drug interactions and side effects. 1
• Do not abruptly discontinue AEDs in a patient with established seizure disorder, even if considering a medication change. 1
• Psychiatric side effects, particularly with levetiracetam, should be monitored but do not preclude its use in most patients. 1

Patient and Caregiver Education

• Instruct patients and caregivers on how to respond to seizures and whom to contact in case of recurrent seizures. 1
• Discuss driving restrictions according to local regulations, considering both epilepsy and other aspects of neurological function. 1
• Emphasize medication compliance and the importance of not missing doses. 1