Abstracts

RATIONALE: Levetiracetam (LEV) is a new antiepileptic drug (AED) shown to be effective as add-on therapy and may offer sustained seizure control in adult pts. with partial onset seizures. We report experience with single-agent LEV in 6 pts. with benign or malignant brain neoplasms and refractory partial seizures.
METHODS: Six pts. (4 male, 2 female; ages 50-63) were seen for management of neoplasms and associated seizure disorder; 3 had meningiomas, 2 had glioblastoma multiforme (GBM) and one had metastatic lung adenocarcinoma with multiple brain metastases and leptomeningeal tumor spread. Two meningioma pts. had total tumor resection, one had subtotal resection. The glioblastoma pts. had subtotal tumor resection followed by radiation and chemotherapy. The patient with lung cancer was treated with whole brain radiation and systemic and intrathecal chemotherapy. All pts. had sustained and repetitive simple partial, complex partial, and/or secondarily generalized seizures. The majority of pts. had 4 to 5 simple partial seizures daily and were treated with a variety of medications including phenytoin (PH), lamotrigine, carbamazepine, gabapentin, tiagabine, sodium divalproex (VPA), intravenous valproate, oxcarbazepine, and phenobarbital (PB). One patient with a subtotal resection of meningioma had good control of seizures on PH and PB but had debilitating cognitive side effects.
RESULTS: LEV was begun at 500 mgs twice daily and maintained from a total dose of 1500-2000 mgs daily. Five pts. had complete and sustained control of seizures within 7 days of onset of LEV therapy. In all but one case, concomitant medication was discontinued with continued complete control of seizures. In the patient with cognitive side effects from PB, seizure control was maintained and the patient had return of normal cognition. One patient was maintained on VPA and LEV, but with reduction of VPA, energy improved substantially and control of seizures was maintained. This patient previously had two 1 hour or longer episodes of simple partial status which did not recur on LEV. He now has a rare, very brief focal motor seizure.
CONCLUSIONS: LEV was effective in reducing and eliminating partial onset seizures in all of our brain tumor pts. with intractable partial seizures with improvement in cognition and without concern of P450 interactions with concomitant chemotherapy. Although the mechanism of LEV is uncertain, given the necrosis associated with neoplasms, particularly malignant neoplasms, one reported possible mechanism for LEV (selective interference with abnormal neuronal activity by inhibiting cortical spread of hippocampal spike and verse discharges) may be important. LEV may represent an effective alternative to refractory seizures in pts. with brain neoplasms, and may offer important advantages in pharmacology and toxicity profile over other available agents.