The VNS has been approved by the food and drug administration (FDA) for:

More than 50% of patients with epilepsy have partial epilepsy. The AED success rate in patients with partial epilepsy is about 50% compared to more than 80% rate in primary generalized epilepsy [1–3]. The current definition of refractory epilepsy requires failure of adequate trials of two appropriate and tolerated AEDs at maximum possible doses, whether as monotherapy or in combination, for enough time (a follow-up period 3 times the longest inter-seizure interval or 1 year, whichever longer) [4]. However, only about 20% of these patients will be eligible for resective brain surgery. Therefore, in these patients, VNS Therapy is a viable palliative treatment option.

Patients with documented refractory partial epilepsy who are not eligible for brain surgery, e.g., having multifocal epilepsy, unclear seizure focus, overlapping eloquent cortex, or those who are opposed to are considered potential candidates for the VNS Therapy. VNS may have a limited role in patients with previous unsuccessful resective epilepsy surgery. In a recent series, 18.75% of such patients had ≥50% reduction in seizure frequency with one case of worsening seizures, but it may be an option given its potential antipsychotic and mood-stabilizing effects [5].

The lead electrodes must be placed below where the superior and inferior cervical cardiac branches separate from the vagus nerve. Stimulation of either of these two branches during the system diagnostics (lead test) may cause bradycardia and/or asystole. In most patients, the main vagus nerve is the largest of the three nerves (Figure 24.1).

A bipolar lead transmits stimulation from the generator to the left vagus nerve. The lead consists of a pin that connects to the generator on one end, and the helices that contain the stimulation electrodes and anchor tether on the other end.

Adjunctive use of left VNS Therapy in patients with refractory epilepsy was tried in five acute-phase landmark clinical studies in 45 centers (40 US, 1 Canada, 4 EU). A total of 454 patients were implanted with VNS with a total patient exposure of 901 device-years. Individual mean patient exposure was 24 months (8 days–7.4 years).

Eligible patients were implanted (baseline period 12 weeks) and the generator was activated 2 weeks later. In the two randomized, blinded, active control trials (E03 and E05), patients were randomized to: (1) HIGH group (higher frequency, pulse width, higher duty cycle) and (2) LOW group (active control) and were followed for a 14-week treatment period (E05: [6]).

The HIGH group showed significant seizure frequency reduction compared with the baseline and the LOW group (24.5% vs. 6.1%, p = 0.01). In the HIGH group, 31% experienced ≥50% seizure reduction as opposed to 13% in the LOW group (p = 0.02). The most common adverse events were voice alteration and dyspnea. The treatment was well tolerated and 97% patients (306 of 314) continued into the long-term follow-up phase of the study (Fig. 24.2).

VNS Therapy is based on:

Therefore, each parameter can be programmed in a variety of combinations to achieve optimal stimulation setting. However, based on animal studies stimulation at high frequency (≥50 Hz) + ON time ≥ OFF time may result in degenerative nerve damage. The ON time ≥ OFF time can be induced by continuous or very frequent magnet activation (> 8 h) and therefore should be avoided.