Advances in Epilepsy
Although antiepileptic drug therapy is satisfactory for the majority of people with epilepsy, approximately 25% of patients continue to have seizures and require alternative or adjunctive therapies, such as novel antiepileptic drugs, epilepsy surgery, the vagus nerve stimulator, or the ketogenic or modified Atkins diet. In November, National Epilepsy Month, 2 new therapeutic options in epilepsy care were approved by the FDA: a new drug, eslicarbazepine acetate, and a new device, the NeuroPace RNS System® (NeuroPace; Mountain View, California).
Eslicarbazepine acetate, marketed as Aptiom® by Sunovion, Inc., is a "third-generation" antiepileptic drug, sharing a dibenzazepine nucleus with carbamazepine and oxcarbazepine. Eslicarbazepine acetate is a prodrug that metabolizes primarily to its S enantiomer, eslicarbazepine. Unlike carbamazepine, it lacks autoinduction and does not produce an epoxide metabolite.
Pooled data from 1049 patients in 3 phase 3 double-blind, randomized, placebo-controlled studies demonstrated a median relative reduction in seizure frequency of 35% (800 mg/day) and 39% (1200 mg/day) vs placebo (15%). Although head-to-head trials have not been performed, adverse events appear improved over both carbamazepine and oxcarbazepine, with rare events of hyponatremia and rash. However, eslicarbazepine is a weak cytochrome P450 3A4 inducer and may render hormonal contraception ineffective. One practical advantage of eslicarbazepine acetate over both carbamazepine and oxcarbazepine is its long half-life of 20-24 hours, facilitating once-daily administration.
The RNS System is the first closed-loop responsive brain stimulation system approved for the treatment of epilepsy. Eligible patients must be adults with frequent and disabling partial-onset seizures refractory to 2 or more antiepileptic medications who have had diagnostic testing identifying no more than 2 epileptogenic foci.
Typically, the NeuroPace RNS System would be appropriate for patients referred for epilepsy surgery who prove not to be good surgical candidates because of more than 1 epileptic focus or presence of a focus in unresectable eloquent cortex. The distinctive feature of the RNS System is its ability to detect epileptic activity at the beginning of a seizure and deliver an electrical impulse that aborts the incipient seizure.
The FDA approval was based primarily on a prospective, randomized, double-blind, sham stimulation study that demonstrated a 37.9% seizure reduction compared with a 17.3% reduction in the sham treatment group. The device was well tolerated, without mood or cognitive effects.
Vagus Nerve Stimulation for Children With Epilepsy
The vagus nerve stimulator has a long history in clinical practice, with its first implant in 1988 and clinical approval for patients older than 12 years with refractory partial seizures in 1997. This year, an updated AAN guideline concluded that the vagus nerve stimulator "may be considered" for the treatment of seizures of children with epilepsy, including Lennox-Gastaut syndrome.
Neurostimulation on the Horizon
Two other neurostimulation strategies have been applied to the treatment of epilepsy. Deep-brain stimulation of the anterior nucleus of the thalamus produced a median seizure reduction of 40.5% compared with 14.5% in a randomized, placebo-controlled, multicenter study. Deep-brain stimulation for epilepsy has been approved in Europe but not the United States. A randomized, double-blind trial of external trigeminal nerve stimulation demonstrated a nonsignificant seizure reduction of 16.1% vs 10.5% in controls. These results were disappointing, but further research on this technique is ongoing.