Vagal Nerve Stimulation

Clinical Presentation

The vagus nerve is the largest cranial nerve. It extends from medulla to colon, extensively supplying sensory and autonomic innervation to various thoracic and abdominal viscera. It is involved in the cardiac, pulmonary, immune, gastrointestinal, and endocrine systems. It has extensive central connection that makes it useful for neuromodulation therapies. The sensory afferent neurons end in the spinal trigeminal nucleus. The cell bodies are in the jugular/superior ganglia. The fibers innervate the external auditory meatus, tympanic membrane, posterior cranial fossa dura, larynx, and upper esophagus. These fibers carry touch, pain, and temperature sensation. A pathology in this distribution can present as localized pain or referred pain in the head, ear, or throat. Common pathologies include tumor or infection. Chronic irritation of the nerve can also present as chronic hiccups. The sensory visceral afferent fibers terminate in nucleus tractus solitarius (NTS), which is a vertical column of gray matter structure that receives visceral afferents of the vagus nerve. The cell bodies are with the inferior vagal ganglia. The taste sensation is carried by special visceral afferents from the tongue and epiglottis, which end in the rostral tractus solitarius, while the general visceral afferents from hypopharynx, larynx, heart, lungs, alimentary tract, and aortic arch (baroreceptors and chemoreceptors) end in the caudal part of the nucleus. The NTS is involved in body homeostasis. It inhibits sympathetic activity by interacting with the vasomotor center, suppressing vasopressin release, and affecting heart rate, swallowing, respiratory rate, and peristalsis. The afferent and efferent fibers are involved in the Bainbridge reflex, arterial baroreflex, Hering–Breuer reflex, vasovagal reflex, and cough reflex. This is the basis of using a vagal nerve stimulator for chronic intractable cough. Kisspeptin (also known as metastin) is a hormone made in the hypothalamus that modulates magnocellular neurosecretory oxytocin secretion via peripheral vagal afferents and the NTS during pregnancy and lactation. The NTS integrates hormonal and visceral neural signals (e.g., cholecystokinin and tumor necrosis factor) and sends information to the pontine reticular formation and other vagal nuclei to control feeding behavior, gut motility, secretion, inflammatory responses, and mucosal defense. The NTS interacts with the parabrachial nucleus and paraventricular nucleus to regulate feeding behavior and autonomic activities. Appetite is tightly regulated by reciprocal interactions among the arcuate nucleus, amygdala, and nucleus accumbens. This explains the effectiveness of vagal nerve stimulation (VNS) in causing weight loss by suppressing the appetite. The NTS projects to monoamine nuclei (locus coeruleus and periaqueductal gray) in the brainstem to modulate pain and mood. These connections have been exploited to treat chronic pain conditions and refractory depression using VNS therapy. The vagus nerve also has antiinflammatory functions. Stimulation of the nerve leads to suppression of proinflammatory cytokines without affecting the antiinflammatory cytokines. The effect is mediated by cholinergic receptors and is called the cholinergic antiinflammatory pathway. This has been used to explain the therapeutic effects of VNS therapy on inflammatory bowel disease.

Other than trauma, tumor, or cerebrovascular accident, the isolated damage or dysfunction of the vagus nerve is rare. However, insulin-dependent diabetes has been reported to cause it.

Anatomy

The vagus nerve, the tenth cranial nerve, is the longest cranial nerve. It travels from the medulla to the colon, innervating structures in the neck, thorax, and abdomen. It is named vagus, using the Latin word for “the wanderer.” The nerve leaves the medulla in the groove between the olive and inferior cerebellar peduncle as ten rootlets. The rootlets converge towards the internal jugular foramen and join to become one nerve as they pass under the cerebellum. Roughly 80% of the fibers are sensory afferents. Functionally, the vagus nerve consists of five types of fibers: general somatic afferent, general visceral afferent, special visceral afferent, general visceral efferent, and special visceral efferent. It contains A-, B-, and C-type fibers, though the great majority of them are C-type. A-type fibers carry somatic afferent and efferent signals, B-type fibers are preganglionic, parasympathetic, and sympathetic in function, and C-type fibers are afferent from visceral structures.

The efferent fibers are mostly cholinergic but also include noncholinergic/nonadrenergic fibers, which use nitric oxide, calcitonin gene–related peptide (CGRP), and vasoactive intestinal peptide as neurotransmitters. Afferent fibers use glutamate, CGRP, and substance P. Central projections of vagal nuclei project extensively through higher centers, from the cerebrum to the locus ceruleus (LC), amygdala, thalamus, hypothalamus, reticular formation, and parabrachial nucleus. The projection of fibers from the NTS to the raphe nucleus (serotonergic center) in the pons and LC (adrenergic fibers) is considered a major pathway that mediates the antiseizure and antidepressive effects of VNS ( Table 42.1 ).

Surgical Anatomy

A basic understanding of the anatomy of the neck is important for the successful implantation of a vagal nerve stimulator. An understanding of the fascial planes in the neck is very important to a successful surgical exposure. The subcutaneous layer contains the platysma muscles and the superficial cervical plexus. The neck has three structures arranged in three planes, each with its own investing fascia. Under the subcutaneous tissue is an investing fascial layer, which splits to envelop the sternocleidomastoid (SCM) muscle and the trapezius muscle. The next fascial plane splits to envelope the strap muscles: the omohyoid, sternothyroid, and sternohyoid muscles. The deepest fascial layer is also called the prevertebral fascia. The carotid sheath is part of this prevertebral fascial layer. Deep to the carotid sheath is the phrenic nerve and sympathetic chain resting on the prevertebral muscles, as well as the thoracic duct on the left side. At the level of C5/C6, the vagus nerve has no branches, and the common carotid gives off no branches. The superior or middle thyroid veins may cross over the carotid to drain into the internal jugular vein (IJV). Sometimes the common facial vein is encountered on its way to IJV, but it normally drains into the IJV at a higher level. The ansa cervicalis, which arises from the cervical plexus, is formed by the anterior rami of the first four cervical nerves. The ansa cervicalis lies within the carotid sheath but it is anterior to the carotid artery and IJV. These nerves are much smaller than the vagus nerve, but still, it is important not to confuse them with the vagus nerve during lead placement.

The vagus nerve descends between the carotid artery and the IJV. It is loosely attached to the carotid artery. All three structures are within the carotid sheath. The superior laryngeal nerve and cardiac fibers come into the sheath high in the neck. The medial border of the SCM muscle covers the nerve. The vagal stimulation leads are placed by exposing the nerve at the level of cricoid cartilage on the left side, because right vagus stimulation more often leads to bradycardia by stimulating the sinoatrial node of the heart. The right vagus is used only if the left side is inaccessible for some reason or is already cut. The VNS lead is placed on the nerve distal to the cardiac branches.

Vagal Nerve Stimulation System

A VNS system is a neurocybernetic prosthesis system. It consists of an implantable, multiprogrammable pulse generator that delivers electrical signals to the vagus nerve, as presented in Fig. 42.1 . The electrical current is delivered on a predetermined schedule or initiated by the patient with an external magnet. The battery life of a VNS generator is 3 to 5 years, after which it is replaced with a new one surgically. The current is carried to the vagus nerve via a special lead. The lead has three coils at one end, which wraps around the vagus nerve and is connected to the generator at the other end. The coils contain the platinum ribbons for mechanical contact with the nerve fibers, as well as an anchor tether on the inferior end of the electrodes ( Fig. 42.1 )

Indications for VNS therapy :

• 1.

  Refractory debilitating seizures

  • a.

    US Food and Drug Administration (FDA)–approved cervical VNS therapy for refractory partial seizures in 1997 for adults and adolescents (age >12 years).

  • b.

    In June 2017, the FDA approved VNS therapy for seizures in patients as young as 4 years old.

  • c.

    Refractory epilepsy is defined as the failure of two or more appropriately dosed antiepileptic drugs.

  • d.

    VNS therapy is not indicated if patient’s epileptic lesions are amenable to resection. It may be considered after the epilepsy surgery has failed. Focal resection surgery is a better option, as it has a better seizure-free rate when the seizure source is a focal point. However, if resection cannot be done without causing language or memory impairment, then VNS therapy is preferred.

  • e.

    It is an adjunctive therapy and not a replacement for pharmacotherapy.

• 2.

  Drug-resistant depression

  • a.

    VNS therapy is also approved for drug-resistant depression.

  • b.

    It is approved as a long-term adjunctive therapy for patients aged 18 years and older who have failed to respond to four or more adequate antidepressant treatments.

• 3.

  Other indications

  • a.

    Obesity

  • b.

    Fibromyalgia

  • c.

    Pelvic pain

  • d.

    Neuropsychiatric conditions (posttraumatic stress disorder, obsessive compulsive disorder, panic disorder)

Indications for VNS therapy have been derived from clinical experience and are not based on any common underlying etiology. Age, sex, seizure type, etiology, or interictal epileptiform discharges do not predict response to VNS therapy. In 2013, the American Academy of Neurology updated their guidelines for VNS therapy for the treatment of epilepsy. The Academy found clinical evidence supporting the use of VNS therapy for a range of individuals with refractory epilepsy ( Table 42.2 ).

Unfortunately, no clinical feature or any test has been found to be of useful prognostic value in predicting a very favorable response to VNS therapy. This mean that the benefits can only be observed after the device has been implanted, and it may take months to a year for a patient to find theses benefits to be fully useful. However, some features have some favorable prognostic value ( Table 42.3 ).