Management of Seizures in Brain Metastasis

Introduction to Seizure Management

The European Association of Neuro-Oncology (EANO) and Society for Neuro-Oncology (SNO) recommend against prophylactic anti-seizure medications for patients with brain metastases who have never had a seizure, as anticonvulsant prophylaxis is unlikely to be effective in increasing seizure-free survival or reducing first seizures at 6 months from diagnosis 1, 3
The American College of Neurology and other guideline societies support the notion that primary anticonvulsant prophylaxis is not indicated in brain tumor patients (Level I, Grade D evidence) 4

Approximately 10-20% of patients with brain metastases present with seizures at diagnosis, and another 10-11% develop seizures later, but prophylaxis does not prevent these events 5, 6
Secondary prophylaxis (treatment after a first seizure) is strongly recommended to prevent recurrence, according to the European Association of Neuro-Oncology (EANO) and European Society for Medical Oncology (ESMO) guidelines 4

Levetiracetam is the preferred first-line anti-seizure medication for patients with brain metastases who have had a seizure, due to its superior tolerability profile, lack of drug interactions, and equivalent efficacy to first-generation AEDs, as recommended by the Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) 1, 7, 4, 2, 3
Levetiracetam has fewer adverse drug reactions and higher retention rates compared to older agents like phenytoin and carbamazepine, with a recommended dosing of 1000-2000 mg/day divided twice daily 7, 9

If levetiracetam is not tolerated or contraindicated, lamotrigine is the next preferred option, with good anti-seizure activity and overall good tolerability, although it requires several weeks of gradual titration to reach therapeutic levels, as stated by the European Association of Neuro-Oncology (EANO) and European Society for Medical Oncology (ESMO) guidelines 4
Valproic acid may be considered as an add-on treatment for refractory seizures, but its use is associated with significantly higher risk of grade 3-4 hematologic toxicities when combined with temozolomide chemotherapy, and it should not be used in females of childbearing potential, according to the European Association of Neuro-Oncology (EANO) and European Society for Medical Oncology (ESMO) guidelines 4, 7, 3

Enzyme-inducing anti-seizure medications, such as phenytoin, carbamazepine, and phenobarbital, should be avoided in patients with brain metastases, as they can reduce plasma concentrations of chemotherapy agents and interact with corticosteroids, according to the European Association of Neuro-Oncology (EANO) and European Society for Medical Oncology (ESMO) guidelines 4, 8, 6

Anti-seizure medication should be continued until local tumor control has been achieved, and for patients undergoing surgery with near-total resection, anticonvulsants can be tapered and discontinued within weeks after surgery if no recurrent bleeding occurs, as recommended by the Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) 4, 9
New or worsening seizures should trigger repeat neuroimaging to evaluate for tumor progression, according to the European Association of Neuro-Oncology (EANO) and European Society for Medical Oncology (ESMO) guidelines 4, 5