The Vagus Nerve: An explainer of the tenth cranial nerve and its clinical implications

By Tré LaRosa
NeuLine Health

Vagus nerve stimulation is a treatment that has been occasionally used to treat epilepsy, treatment-resistant depression, and even Alzheimer’s dementia. Are you familiar with this unusual treatment? Are you familiar with the vagus nerve? Though it’s not commonly known, it’s a critical part of your nervous system and has many potential clinical implications. Let’s chat about the vagus nerve and vagus nerve stimulation, but first, some background and context.

The Nervous System

Your body consists of several different systems that allow for all of the different cells, tissues, and organs to interact with one another. These systems include the musculoskeletal system, the endocrine system, and the nervous system. The nervous system is known as being your body’s command center, where through the brain, spinal cord, and nerves, the body sends and receives signals. Put simply, “the nervous system transmits signals between the brain and the rest of the body.”

The nervous system is divided into two parts:

Central nervous system, which consists of the brain and spinal cord, functions to interpret signals from and distributes signals to the peripheral nervous system.
Peripheral nervous system, which consists of all parts of the nervous system outside the central nervous system, such as the cranial nerves, spinal nerves and their roots and branches, and more, functions to extend from the spinal cord and the brain to reach the rest of the body. This allows for the central nervous system to receive and distribute signals from and to the rest of the body.

Both the central and peripheral nervous systems are then both subdivided into other component parts. For the time being, we won’t explore the different functions of these subdivisions, but we will delve into one group of them: the cranial nerves, and more specifically, the vagus nerve.

Neurological disorders, such as multiple sclerosis, epilepsy, amyotrophic lateral sclerosis (ALS), and Alzheimer’s, are so-called because they are all disorders of the nervous system.

The Cranial Nerves and the Vagus Nerve

There are twelve cranial nerves, all of which are part of the peripheral nervous system. The cranial nerves serve to either help a person see, smell, or hear (sensory), help a person control muscle movements in the head or neck (motor), or both. The cranial nerve that is the focus of this treatment and related blog is the vagus nerve.

The vagus nerve connects the brainstem to the body and it allows “the brain to monitor and receive information about several of the body’s different functions.” The vagus nerve has four key functions. From Medical News Today, these functions are:

Sensory: From the throat, heart, lungs, and abdomen.
Special sensory: Provides taste sensation behind the tongue.
Motor: Provides movement functions for the muscles in the neck responsible for swallowing and speech.
Parasympathetic: Responsible for the digestive tract, respiration, and heart rate functioning.

Further, in a review article published in the Frontiers in Psychiatry journal, the authors detail how the vagus nerve “establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain.”

The vagus nerve clearly has an inextricable and influential relationship with not only the rest of the nervous system but the rest of the body, so it isn’t surprising that the nerve has clinical implications for many neurological disorders.

Vagus Nerve Stimulation

Vagus nerve stimulation is generally described as any technique which stimulates the vagus nerve. This technique is not necessarily new; as reported in a review article on the technique by Dr. Robert Howland, there is a documented observation from the 1880s that “manual massage and compression of the carotid artery in the cervical region of the neck could suppress seizures, an effect attributable to crude stimulation of the vagus.” Then in the 1930s and 1940s, electrical studies were conducted to further investigate the clinical implications of stimulating the vagus nerve. In 1987, the FDA approved of an implanted device that stimulated the vagus nerve for epilepsy. Just under 20 years later, the FDA also approved the device for treatment-resistant depression.

So how does this treatment work and why might it be effective for certain disorders?

The American Association of Neurological Surgeons explains the therapy:

“Vagus nerve stimulation (VNS) sends regular, mild pulses of electrical energy to the brain via the vagus nerve, through a device that is similar to a pacemaker. There is no physical involvement of the brain in this surgery and patients cannot generally feel the pulses.

The AANS also cautions: “It is important to keep in mind that VNS is a treatment option limited to select individuals with epilepsy or treatment-resistant depression.” At the link above, the AANS also details how the device used in VNS is implanted, complete with images of the implantation device.

It is also important to note, as the Epilepsy Foundation also emphasizes, that VNS is only approved to treat what is called “drug-resistant” or refractory epilepsy, which is a form of epilepsy which causes seizures that do not respond to seizure medications.

Interestingly, the underlying mechanism of action for vagus nerve stimulation isn’t well-understood. In the Epilepsy Foundation’s fact sheet on the treatment, they state: “It’s not clear exactly how VNS works in the brain. It is designed to change how brain cells work by sending electrical impulses to certain areas involved in seizures.”

In the aforementioned factsheet, the Epilepsy Foundation details some basic facts about the efficacy of the treatment:

In the first 3 months of using VNS, about 1 out of 3 people find their seizures decrease by 50%.
Seizure control typically improves over time. About 45% of people have seizures decrease by 50% after 1 to 2 years of therapy. People who have had VNS for up to 10 years may see seizures decrease by 75%.
The majority of people report better quality of life when using VNS.
This device is not a cure for epilepsy and doesn’t work in everyone. Small numbers of people may become seizure free.

Other clinical implications and future research

As is true for all treatments, it’s of critical importance to understand the mechanism of action for a few reasons. First, it’s fundamentally valuable to understand why, either exactly or tangentially, a therapy has certain effects to evaluate the full safety efficacy implications of said therapy. Secondly, understanding the mechanism of action allows for therapies to be repurposed for other disorders. Though the mechanism of action is not yet defined, vagus nerve stimulation, originally used for refractory epilepsy, has been repurposed for use in treatment-resistant depression and Alzheimer’s. This is an example of how therapies can have multiple purposes across domains.

Ongoing research still must be done to understand the full implications of the vagus nerve and its stimulation, as well as how else this treatment can be used. To sum up its potential, a review article titled “A review of vagus nerve stimulation as a therapeutic intervention” published in the Journal of Inflammation Research opens their conclusion with the following two sentences: “VNS has been proven to be a useful treatment across a number of domains and has been used effectively to treat epilepsy and depression in adults. There is accumulating evidence to suggest that it can be used to help quell inflammation in a number of other autonomic or inflammatory disorders, which would make it useful for a wider range of pediatric patients as well.”

Resources:

How the FDA’s Patient-Focused Drug Development Program is Advancing Drug Development

Around ten years ago, the Food and Drug Administration (FDA) acknowledged the unmet need — and urgency — of including patient perspective in drug and device development in a systematic way.

Patient-Reported Outcomes Part 2 of 2: Clinical Trials and Their Crucial Role in Neurology

While patient-reported outcomes are becoming increasingly standard in clinical trials, their impact still needs to be fully understood. Clinical trials, like peer-reviewed journals, face scrutiny and require rigorous analysis before results can be considered confirmatory.

Patient-Reported Outcomes Part 1 of 2: A Primer

Patient-reported outcomes (PROs) are clinical trial measures that capture the patient’s own perspective on how they feel. While they are commonly used in clinical trials, they are also used in the clinic as another measure to gauge a patient’s health over time.