Vagus Nerve Stimulation



There is widespread consensus that recurrent epileptic seizures need treatment and the first line of treatment invariably involves use of antiepileptic drugs (AEDs). However, experience from several large studies has shown that only about two-thirds of patients can be controlled satisfactorily with AEDs either as monotherapy or combination therapy.1,2 The remaining patients have medically refractory epilepsy and should be evaluated at an epilepsy center to determine if they may be candidates for excisional epilepsy surgery. Of this group approximately 25% will be offered a resection (personal observation), still leaving a sizeable proportion of patients without effective medical control. Seizures in medically refractory patients have a major impact on quality of life (QOL), and may result in injuries or even death.3 Treatment options consist of additional trials of AEDs, ketogenic diet, or vagus nerve stimulation (VNS therapy). Deep brain stimulation remains investigational. Figure 57–1 outlines a treatment algorithm showing the diagnostic and therapeutic approach to a patient with epilepsy.

Figure 57–1.

Treatment algorithm showing the diagnostic steps and therapeutic approach to a patient with epilepsy.

In 1987, the Food and Drug Administration (FDA) approved VNS therapy for the adjunctive treatment of partial onset seizures in patients 12 years and older. It has not undergone testing in clinical trials for patients younger than 12 or patients with other seizure types; however, postmarketing experience indicates that VNS is useful in such situations.



VNS therapy stimulates the left vagus nerve that carries both myelinated and unmyelinated efferent (80%) and afferent (20%) fibers. The parasympathetic efferents are mostly unmyelinated and not much influenced by vagal nerve stimulation. The rationale for choosing the left vagus nerve is that it has fewer cardiac fibers supplying the SA node (although right side VNS implantation has been performed). However, McGregor et al have shown that right-sided VNS implantation is also safe and efficacious.4 Ascending fibers from the vagus nerve reach the nucleus of the Tractus Solitarius; from there widespread projections reach the limbic, reticular, and autonomic regions of the brain as well as other brain stem nuclei like the locus coeruleus and raphe magnocellularis that CSF influence serotonin and norepinephrine levels.5 Lesioning the LC appears to abolish the antiepileptic effect of VNS.

VNS in monkeys was shown to abort generalized convulsive seizures induced with pentylenetetrazole; this effect persisted beyond the time of actual stimulation.6,7 Studies in humans have shown reduction of interictal spike discharges and prolongation of the interspike interval.8 In addition, VNS is accompanied by a bilateral increase in blood flow to the thalamus, the hypothalamus, and the insular cortex and a bilateral decrease in blood flow to the amygdala, hippocampus, and posterior cingulate gyri. The reduction in thalamic blood flow was shown to correlate with seizure reduction.9,10 GABA receptor plasticity may also contribute to reduced epileptogenesis.11 In patients with depression, VNS increased glucose metabolism in the orbitofrontal cortex, cingulate gyrus, and insula.12



Currently, the only FDA-approved indication is for treatment of patients 12 years and older with partial onset seizures (with or without secondary generalization) that are refractory to antiepileptic medications. Off-label use, (i.e., not approved by the FDA) in younger age groups and for other seizure types and epilepsy syndromes has been reported extensively in the literature. VNS therapy has also been investigated in adult patients with treatment-resistant depression.



The VNS therapy system consists of an implanted device or generator with electrodes or leads that attach to it. The generator contains a lithium battery and microprocessor sealed inside a titanium case (Fig. 57–2). The device delivers intermittent stimulation to the vagus nerve using preprogrammed settings that are adjusted using a programming wand attached to a handheld computer (Fig. 57–3). When placed over the device, the programming wand transmits the device settings magnetically. The generator can also be programmed to deliver a preset stimulus by bringing a small handheld magnet close to the device for 2–3 seconds and then removing it. This allows the patient (or nearby caregiver) to manually activate the device when he/she experiences an aura or the onset of a seizure. In about half, the patients magnet stimulation may abort a seizure, shorten its duration, and permit quicker recover after the seizure.

Figure 57–2.

Schematic diagram of the device placement in the chest and lead around the left vagus nerve. The inset shows three spirals attached to the nerve: the cathode is proximal, anode distal and allowed to coil around the nerve; the lowermost or third loop is the anchoring tether. © Cyberonics

Figure 57–3.

Programming wand and handheld computer used for interrogating and programming the vagus nerve stimulator. © Cyberonics

Typically the surgeon makes two incisions: one just below the left clavicle subcutaneously for device placement and a second horizontal incision in the neck bringing the lead (tunneled subcutaneously) from the device. In infants with little subcutaneous fat, the device may be placed in the soft tissue of the belly. The vagus nerve is exposed as it lies in the carotid sheath. The two stimulating leads are placed around the vagus nerve with the cathode proximal and anode distal and allowed to coil around the nerve; a third loop acts as the anchoring tether. A loop of wire is generally left in the chest to provide strain relief.

The original models 100 and 101 had two-pin leads whereas the Model 102 is a single-pin lead. Newer models have an expected battery life of 7–10 years, up from 3–5 years for the Model 100. Battery life is influenced by stimulus parameters and the lead impedance. The newest Model 103, the Demipulse® generator has a smaller footprint and advanced circuitry.

The device and lead are tested in the operating room before and after implantation and a lead test is carried out. There have been occasional reports of bradycardia or cardiac asystole during lead testing that is done with a higher current of 1 mA (compared to a lower starting current of 0.25 mA used for initial programming); however, patients can safely continue using the VNS.13,14 The surgical procedure takes 2 hours or less and patients usually go home the same day or next morning. Absorbable sutures are used. Incisional pain is usually mild and patients may report a ticking sensation or cough when the device cycles on intermittently. The device may be turned on at the time of implantation or at an outpatient visit in 2 weeks.



Although there are differences in practice from one physician to another, the usual approach is generally to increase stimulus current stepwise every 3–4 weeks to a current intensity between 1and 2.5 mA (maximum allowable by the software is 3.5 mA). Next, the off-time is shortened from 5 to 3 minutes. Subsequently, one may try a signal frequency of 25 Hz or 20 Hz. If the patient has difficulty tolerating the stimulation due to coughing, choking sensation, or dysphagia, the pulse width can be shortened from the usual 500 to 250 or 130 microseconds although the latter setting may be less than fully effective. With each stimulus current increase, the magnet current is also increased, keeping it 0.25 mA above the stimulus current—this allows the patient to receive a stronger current at the time of a seizure and may have the added benefit of allowing the patient to become habituated to this higher current. After each adjustment in the office, it is prudent to ask the patient to wait 30–60 minutes to make sure they are tolerating the new settings. Response to the changes in VNS settings take 2–4 weeks to take full effect, so more frequent adjustments at shorter intervals are not likely to help.

The ratio of the ON time plus 2 seconds ramp-up and 2 seconds ramp-down time divided by the OFF time is called the Duty Cycle (Fig. 57–4). The duty cycle should be kept below 40% (maximum allowable is 50%) to avoid the excessive stimulation and possible nerve damage. The ramp-up and ramp-down times help reduce patient perception of the intermittent nature of the vagus nerve stimulation. Table 57–1 shows commonly used settings found to be efficacious.

Figure 57–4.

Diagram illustrating the various parameters, which may be adjusted for VNS therapy.


Device malfunction leading to excessive or continuous stimulation leading to vocal cord injury is exceedingly rare. In case of extreme discomfort, the patient can turn off the device by affixing the hand-held magnet to the chest overlying (with tape) until they can be evaluated in the doctor’s office. At each visit, a diagnostic check should be performed that gives additional information regarding model number, serial number, date of implantation, how long the device has been in use, number and time of magnet activations, lead impedance, and whether the battery is approaching the end of its useful life.

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Jan 2, 2019 | Posted by in NEUROLOGY | Comments Off on Vagus Nerve Stimulation
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