Seizure prophylaxis and melanoma brain metastases

Melanoma has a high propensity to metastasize to the brain. In patients with brain metastases (BM) survival is limited, neurologic morbidity is high, with seizure incidence reported up to 67%. Current guidelines recommend against antiepileptic drug prophylaxis (AED PPX) in patients without a history of seizure. We reviewed our experience with melanoma BM to determine the efficacy of AED PPX in the era of second generation AED and to delineate risk factors associated with development of seizures. We reviewed records of all patients treated at Memorial Sloan-Kettering Cancer Center with melanoma and BM between May 2006 and October 2008. Seizure risk was studied relative to BM characteristics at diagnosis and AED PPX. We identified 109 patients. Median age was 61 years (range 29-91); 56% had no neurologic symptoms at diagnosis. On neuroimaging, 94% (102/109) had cortical lesions, 60% (65/109) had more than one supratentorial lesion, 54% (59/109) had hemorrhage. Seizure led to diagnosis of BM in 13% (14/109); 20% (22/109) developed seizures later. On univariate analysis among patients without a seizure at diagnosis, AED-PPX was significantly associated with decreased risk of seizure (P = 0.03) with 3-month seizure rate of 0% compared to 17% without AED-PPX. Hemorrhage (P < 0.001) and multiple supratentorial metastases (P = 0.03) were associated with increased seizure risk. Melanoma patients with multiple supratentorial BM and hemorrhage may have an increased risk of seizure. AED PPX may be effective in selected patients, and should be addressed in a randomized controlled trial.