25.1 Preclinical Studies

Multiple animal studies beginning in the 1880s generated data to support the development of vagus nerve stimulation (VNS) and its implantation in humans. In early studies, VNS was found to desynchronize electrical activity and reduce or eliminate chemically induced interictal epileptic events in the frontal cortex of cats. ¹ , ² Zabara showed that VNS attenuated motor seizures that were induced by strychnine in dogs and that the beneficial effects of VNS outlasted the acute stimulation period. ³ Further animal studies by Zabara and others showed that VNS was associated with reduced seizure frequency. ⁴ , ⁵ Favorable safety and efficacy findings in animal models led to the development of a programmable pulse generator and electrode for VNS in humans. The exact mechanism by which VNS reduces seizure activity or alters mood in humans remains unclear; however, VNS is thought to exert antiseizure effects by modulating neurotransmitter expression, ⁶ , ⁷ increasing cerebral blood flow in the thalamus and cortex, ⁸ and desynchronizing ictal electroencephalogram (EEG) patterns. ⁹ Penry and Dean reported the first implanted VNS device for long-term seizure control in humans in 1988. ¹⁰

25.2 Surgical Indications

In 1997, the Food and Drug Administration (FDA) approved VNS as an adjunctive, nonpharmacological therapy for patients over 12 years of age with medically refractory partial onset seizures. ¹¹ For the treatment of seizures, VNS therapy is considered for patients with epilepsy who have failed two or more adequate antiepileptic drug trials. Reports of unanticipated improvements in mood in epileptic patients undergoing VNS, which were supported by subsequent clinical trials, led to FDA approval of VNS in 2005 as an adjunctive long-term therapy for chronic or recurrent major depression in patients over 18 years of age who failed at least four adequate antidepressant drug trials. ¹² , ¹³ More recently, the FDA has approved the use of VNS in patients as young as 4 years.

25.3 Device

VNS is currently carried out by the neurocybernetic prosthesis (NCP) system developed initially by the company Cyberonics (Houston, TX), which merged with a medical products group to form LivaNova (London, England). The device consists of a generator (▶Fig. 25.1), a stimulation lead (wire), and an electrode array that wraps around the vagus nerve (▶Fig. 25.2). The generator consists of a lithium battery housed in a titanium shell. The generator is most commonly inserted in the left chest wall in a subcutaneous, supramuscular compartment. A stimulation lead is inserted into the generator at the superior-lateral aspect and secured with a set of screws tightened by a hexagonal torque wrench. The silicone-insulated platinum iridium stimulation lead is 43 cm in length. Its other end is composed of an electrode array made up of three discrete helical coils, each with three loops that are placed around the vagus nerve. The bottom coil serves as an anchoring tether to lend extra support to the construct when the neck is turned. Suture tails that extend from both sides of the helix are used to aid in manipulation of the coils without damaging the platinum contacts inside the middle loop of each helix. ¹⁴

The generator also contains an antenna that receives radiofrequency signals from an external programming wand (▶Fig. 25.3). The internal antenna transfers the signals to a microprocessor that regulates the electrical output of the generator. The output may be programmed with respect to current, frequency, pulse width, stimulation on-time, and stimulation off-time. In addition, a handheld NCP magnet (▶Fig. 25.4) facilitates real-time control of the device. In response to an aura or seizure onset, caregivers or patients may pass the magnet over the chest wall in order to trigger stimulation superimposed on baseline generator output, which may limit seizure onset or progression. Newer versions of the device monitor deviations from the baseline heart rate, which may be associated with seizure. When a rapid increase in heart rate is detected beyond a preset threshold, the device delivers an extra dose of current in an attempt to limit or terminate a seizure.

25.4 Surgical Anatomy

An intimate understanding of the anatomy of the vagus nerve is useful not only for implantation of the VNS device, but also for understanding complications arising from direct stimulation or nerve injury. The 10th cranial nerve, the vagus nerve, arises from several brainstem nuclei to exert a wide variety of effects. Efferent fibers arise from the nucleus ambiguus and innervate somatic muscles of the pharynx and larynx. Additional efferent fibers arise from the dorsal motor nucleus and supply parasympathetic innervation to the heart, lungs, and gastrointestinal tract. ¹⁵ Unilateral lesions of the dorsal motor nucleus are rarely clinically significant, and include dysarthria and hoarseness; however, bilateral lesions may produce life-threatening autonomic instability. Injury to the pharyngeal branches of the vagus nerve causes dysphagia, while a lesion of the superior laryngeal nerve produces anesthesia of the upper part of the pharynx and paralysis of the cricothyroid muscle, leading to a weak voice that is easily fatigable. ¹⁶ Eighty percent of vagal fibers, however, are general somatic and special visceral afferents that project to the brain. ¹⁷ The vagus nerve carries sensory information from the mucosa of the oropharynx and upper gastrointestinal tract to the spinal nucleus of the trigeminal nucleus and from the thoracic and abdominal organs to the nucleus of the solitary tract. ¹⁴

The right vagus nerve preferentially innervates the sinoatrial node of the heart, whereas the left vagus nerve projects to the atrioventricular node. ¹⁴ Thus, the VNS electrode is usually applied on the left vagus nerve in order to avoid possible stimulation-induced bradycardia or asystole ¹⁸ ; however, there are several reports supporting the safety and efficacy of a right-sided approach as well. ¹⁹ , ²⁰ , ²¹ Furthermore, the midcervical portion of the vagus nerve is chosen for lead application because this portion of the nerve is relatively free from branches. In contrast, the upper cervical portion gives off branches to the pharynx, carotid sinus, and superior and inferior cardiac branches leading to the cardiac plexus. ¹⁴