Vagus Nerve Stimulation for Treatment of Partial Seizures: 2. Safety, Side Effects, and Tolerability

Abstract

Vagus nerve stimulation (VNS) significantly reduces the frequency of partial seizures in refractory epilepsy patients. We examined the serious adverse events, side effects, and tolerability as they relate to the surgical implant procedure and the stimulating device. We also reviewed potential drug interactions, device output complications, and impact of the therapy on overall health status. We analyzed the first 67 patients to exist the acute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Data were collected from case report forms used at each of the four visits during the 12-week baseline and at each of the four visits during the 14-week randomized phase of the trial. No significant complications were reported as a result of the implant procedure. Serious adverse events included 1 patient who experienced direct current to the vagus nerve owing to generator malfunction resulting in left vocal cord paralysis and withdrawal of the patient from the study. No clinically significant effects on vital signs, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group were hoarseness (35.5%), coughing (13.9%), and throat pain (12.9%). In the low group, only hoarseness (13.9%) and throat pain (13.9%) were associated with VNS. These effects generally wrre not considered clinically significant and occurred primarily during the stimulation pulses. No patients discontinued VNS therapy during the acute phase because of side effects associated with normal stimulation. Except for the one instance of a short circuit in the system resulting in a direct current, stimulating system complications were minor, limited to programming, unscheduled stimulation, and high lead impedance. Patients, investigators, and patient companions rated patients receiving high stimulation as more "improved" than those receiving low stimulation in regards to overall health status. Antiepileptic drug (AED) plasma concentrations were not affected by VNS. The implant procedure, stimulating system, and therapy proved safe and tolerable during the study. The high percentage (67 of 68) of patients completing the study reflects patient acceptance and tolerability of this mode of therapy.

Vagus Nerve Stimulation in the Treatment of Refractory Epilepsy

“…These symptoms are typically experienced transiently during the initial calibration period and are minimized with adjustment of stimulation parameters or diminish in severity with patient acclimation. 75,77 Of these, voice alteration is most commonly reported during periods of active stimulation, and is likely the result of adduction of the left vocal fold induced by stimulation of the left recurrent laryngeal nerve. 80,81 This mechanism may also account for the occurrence of some other common adverse events, such as neck or throat pain, dyspnea, and coughing.…”

“…76 Voice alteration is most commonly observed in conjunction with stimulation, but may occur postoperatively as a consequence of improper electrode placement, excessive intraoperative manipulation, device malfunction, or patient-inflicted traction injury. 77 Severe bradycardia and asystole have been reported during intraoperative electrode placement and device testing, but have proven responsive to epinephrine and/or atropine administration, along with brief cardiac compression. 78 Other uncommon complications in the immediate postoperative period include fluid accumulation in the generator pocket, partial left-sided facial paralysis, and Horner's syndrome.…”

“…78 Other uncommon complications in the immediate postoperative period include fluid accumulation in the generator pocket, partial left-sided facial paralysis, and Horner's syndrome. 51,56,77,79 …”

“…84 -86 VNS may cause a mild increase in gastric acid output, but does not affect ulcer formation or vital signs. 51,77 Targeted studies have reported no or minimal effects on cardiovascular parameters during periods of stimulation in patients without underlying heart disease. 87,88 Outpatient 24-hour Holter monitoring has also failed to demonstrate any clinically significant adverse effects on cardiac rhythm within recommended stimulation parameters.…”

Electrical Stimulation for the Treatment of Epilepsy

“…In the meantime, two prospective multicenter (n ϭ 17) double-blind randomized studies (EO3 and EO5) were started, with patients from centers in the United States (n ϭ 12) and Canada (n ϭ 1), as well as in Europe (n ϭ 4). [27][28][29][30][31] In these two studies, patients older than 12 years of age with partial seizures were randomized to a HIGH or LOW stimulation paradigm. The parameters in the HIGH stimulation group (output: gradual increase up to 3.5 mA, 30 Hz, 500 s, 30 s on, 5 min off) were those believed to be efficacious based on animal data and the initial human pilot studies.…”