Abstracts

Rationale: Trigeminal nerve stimulation (TNS) is an emerging therapy for drug resistant epilepsy. Establishing the safety of external TNS is essential to future phase II and phase III clinical trials. We report the safety and tolerability of external TNS from the initial pilot feasibility study, and the effect of external TNS on acute and long-term heart rate, systolic and diastolic blood pressure. Methods: Research committee approval was obtained for a pilot open study of external TNS in epilepsy. Informed consent was obtained before enrollment. Inclusion/exclusion criteria were age 18-65 years, > 3 complex-partial/generalized tonic-clonic seizures/month, no progressive medical conditions, and exposure to > 2 antiepileptic drugs (AED s). Subjects were enrolled in a 4-week pretreatment baseline, and were evaluated at 1, 2, 3, 6, and 12 months. AED s remained unchanged unless essential for patient safety. Stimulation settings were as follows: frequency 120 Hz, pulse duration 250 us, < 30 seconds on and < 30 seconds off for 12 - 24 hours per day. 1.25-inch disposable, silver-gel, adhesive electrodes were utilized, spaced 2 inches apart. Initially, unilateral infraorbital stimulation was utilized in subjects 1-3, but subsequent subjects have undergone bilateral supraorbital stimulation. Serial blood pressure and heart rate monitoring was performed every 5 minutes for one-hour on the first day of stimulation. Routine pulse, blood pressure, and clinical examinations were performed at each subsequent visit. Results: 13 subjects were enrolled. TNS was well tolerated. Side effects included skin irritation in five subjects, which improved by reducing stimulation to 12-16 hours/day, or with hydrocortisone 1% cream. Tingling, forehead pressure, and headache were reported, but improved with reduction of current. On day one of treatment, the mean pre-treatment heart rate (bpm) was 70.6 SD 11.2, versus 67 SD 10.3 after one hour of stimulation (n/s, p > 0.05) Pretreatment mean systolic blood pressure (mmHg) was 125.7 SD 13.4, versus 123.7 SD 15.1 after one hour of stimulation (n/s, p > 0.05 t-test). Likewise, pretreatment diastolic blood pressure (mmHg) was 70.5 SD 8.7, versus 70.2 SD 10.4 after one hour of stimulation (n/s P > 0.05). Long-term heart rate, systolic and diastolic blood pressure were not significantly changed at six months compared with the pretreatment baseline (all comparisons n/s, t-test, p > 0.05). Conclusions: External TNS was well tolerated. Skin irritation was the most common side effect. External TNS was not associated with acute or long-term effects on heart rate, systolic or diastolic blood pressure. This pilot study provides evidence of excellent acute and long-term safety of external TNS for epilepsy. This study provides the foundation for larger double-blind safety and efficacy trials.