Trigeminal nerve stimulation may not be effective for the treatment of refractory partial seizures.

Commentary Stimulatory devices offer a novel approach for the treatment of refractory partial seizures. Both peripheral and central stim-ulatory devices that provide either continuous or responsive stimulation have been studied. Currently the only approved device is the vagus nerve stimulator (VNS). Stimulatory devices may provide a safe and well-tolerated means of reducing seizures for patients with refractory seizures. Trigeminal nerve stimulation (TNS) is a neuromodula-tory device that has been studied in animal and pilot clinical trials. The original article investigating its potential antiepi-leptic properties was an animal study evaluating its effect on pentylenetetrazole-induced seizure activity in awake rats (1). Continuous unilateral stimulation of the trigeminal nerve reduced electrographic seizure severity and duration activity in a frequency-dependent fashion at frequencies >100 Hz. Bilateral trigeminal stimulation was more effective than unilateral stimulation. A proof-of-concept clinical trial investigated safety and efficacy among seven subjects using transcutaneous stimulation of the infraorbital and supraorbital branches of the trigeminal nerve (2). In this study, TNS was well tolerated, and four of seven subjects who completed ≥3 months had a ≥50% reduction in seizure frequency. Another study evaluated its effect in depression and found significant improvement in cli-nician-and individual-rated depression scales among five subjects (3). There has not previously been a randomized, blinded, controlled trial among persons with refractory epilepsy. DeGiorgio and colleagues completed a phase-2 random-ized, double-blind, multicenter trial evaluating external TNS (eTNS) among subjects with drug-resistant partial-onset epilepsy (having two or more complex partial or generalized tonic seizures per month for 2 consecutive months) (4). Subjects were randomized to either active treatment (frequency of 120 OBJECTIVE: To explore the safety and efficacy of external trigeminal nerve stimulation (eTNS) in patients with drug-resistant epilepsy (DRE) using a double-blind randomized controlled trial design, and to test the suitability of treatment and control parameters in preparation for a phase III multicenter clinical trial. METHODS: This is a double-blind random-ized active-control trial in DRE. Fifty subjects with 2 or more partial onset seizures per month (complex partial or tonic-clonic) entered a 6-week baseline period, and then were evaluated at 6, 12, and 18 weeks during the acute treatment period. Subjects were randomized to treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters. RESULTS: At entry, subjects were highly drug-resistant, averaging 8.7 seizures per month (treatment group) and 4.8 seizures per month (active controls). On average, subjects failed 3.35 antiepileptic drugs prior to enrollment, with an average duration of …