Major difficulties in patients with
epilepsy and
brain tumors include refractory
seizures, potential interactions between
anticonvulsants and chemotherapeutic agents and enhanced risks of toxicity, including cognitive deterioration. For seizure control,
levetiracetam,
valproic acid,
topiramate and
lamotrigine can each be considered as agents of first choice. We advocate starting with
levetiracetam monotherapy, based on efficacy, good tolerability and the absence of interactions. If
levetiracetam alone is not sufficiently effective, we propose adding a second
antiepileptic drug, rather than switching to monotherapy with another
anticonvulsant. Under these circumstances we advise the use of
valproic acid as an add-on over
topiramate or
lamotrigine, based on its reported clinical activity in
brain tumor patients. The combination of
levetiracetam and
valproic acid seems synergistic, and produces few or no cognitive side effects. Antitumor
therapy by neurosurgery, cranial radiation or
chemotherapy contribute substantially to reducing seizure activity. Future research on seizure management in
brain tumor patients should focus on better insight into the influence of
multidrug resistance proteins on
anticonvulsant drug transport over the blood-brain barrier, efficacy of new
anticonvulsants with no or few interactions with other drugs, synergistic combinations of
anticonvulsants in order to limit toxicity and therapeutic
drug monitoring of
anticonvulsants in current clinical practice and in new
drug studies, including the effects of concomitant administration of chemotherapeutic agents.