Vagus Nerve Stimulation for Treatment of Partial Seizures: 3. Long‐Term Follow‐Up on First 67 Patients Exiting a Controlled Study

Abstract

Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinical studies, in pilot studies in humans, and in the acute phase of a multicenter, double-blinded, randomized study. After completion of a 14-week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected to continue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizure frequency during the 3-month treatment blocks was compared with a 12-week baseline. For both groups, all periods of high VNS demonstrated a significant decrease in seizure frequency (p < 0.01 level) as compared with baseline. For the 16-18-month period of VNS, data were available for 26 of the 31 patients randomized to high VNS. This group achieved a 52.0% mean seizure frequency percentage reduction as compared with baseline. For those converted from low to high VNS, data were available for 24 of the 36 patients at the 16-18-month time period. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safety/side effect profile was reported during long-term follow-up. The previously reported side effects of hoarseness/voice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow-up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy.

Vagal nerve stimulation for the treatment of medically refractory epilepsy: a review of the current literature

“…1,2,4,5,[8][9][10][11]15,[24][25][26][27][28] Five of the remaining studies used the mean or median frequency reduction from baseline. 3,14,17,22,23 The mean seizure reduction in these investigations was 42.8% (range 28%-66%). Four studies additionally included data on the percentage of patients achieving freedom from seizures, typically quoted at the 1-year time frame.…”

“…With extended follow-up durations from 1 to 6 years, the 7 publications identified here provide strong evidence for the use of VNS in multiple epilepsy syndromes over extended periods of treatment. With large, prospectively collected data sets, the investigations of George et al 14 and Salinsky et al 25 have served to confirm the utility of high-stimulation VNS for increased seizure control. BenMenachem et al 4 expanded the prospective application of VNS to patients with generalized seizures and LennoxGastaut syndrome.…”

“…George and colleagues 14 prospectively followed 67 of the patients initially randomized in the E03 study for an additional 16-18 months. The population included 31 patients initially receiving high stimulation and 36 receiving low stimulation.…”

Beneficial effects on sleep of vagus nerve stimulation in children with therapy resistant epilepsy

“…This may be due to the small number of patients and the fact that increased SWS is only one of several contributing factors to improved QOL together with decreased epileptiform activity, seizure frequency and severity. Parker et al 5 and George et al 30 reported that the effects of VNS are positively correlated to the length of the treatment period. In this view 9 months may still be a too short observation time to find effects on sleep architecture in addition to effects on epileptiform activity.…”

Vagus Nerve Stimulation in the Treatment of Refractory Epilepsy

“…Beginning parameter settings of 30-Hz signal frequency, 500-s pulse width, 30 s on-time, and 5 minutes off-time have been found to be effective in double-blind, controlled studies, although these parameters may vary considerably in practice. 20,21 Incremental increases in output current of 0.25 to 0.5 mA every 2 to 4 weeks allow for gradual acclimation, and may ultimately increase a patient's tolerance for higher output current if required for optimal seizure control.…”