Vagus nerve infection hypothesis

The Vagus Nerve Infection Hypothesis (VNIH) proposes that the symptoms of Chronic Fatigue Syndrome are caused by an infection in or around the vagus nerve.

In 2013, Michael VanElzakker, then a postdoctoral researcher at Harvard Medical School, published the hypothesis.

The vagus nerve, also called the tenth cranial nerve, starts in the brain and runs down the trunk of the body, with branches that innervate all of the major organs. It is responsible for the sickness response, an involuntary response characterized by fatigue, fever, myalgia, depression, and other symptoms that are often observed in patients with CFS.

Theory
As explained by Dr. Michael VanElzakker: "The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia [structures containing a number of nerve cell bodies] or paraganglia [non-nerve cells that surround nerves] are themselves infected with any virus or bacteria.... [The] glial cells [cells that support and protect neurons] can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen." The neuroimmune cells whose job is to protect the nerve, such as mast casts and glial cells, can sense an infectious agent and become activated, in turn signaling the vagus nerve to tell the brain there is an infection present, causing a systemic reaction.

VanElzakker believes that any infectious agent with an affinity for nerve tissues can cause a vagus nerve infection, including HHV-6, Epstein-Barr virus, Varicella zoster virus, Chickenpox, certain kinds of enteroviruses and even Borrelia, the bacterium that causes Lyme disease. He thinks this could explain why no single infective agent has been isolated as the cause of CFS, even though all of these agents have been associated with disease.

To test his hypothesis, VanElzakker suggests that vagus nerve biopsy samples should be sought from CFS patients who have died prematurely from other causes. In addition, he is using a combined MRI and PET scan with radiolabeled antibodies to look for "increased cellular activity in the brain stem in a place called the nucleus of the solitary tract, which is where about 80 percent of these sensory vagus nerve fibers have their cell bodies...The idea is that if we can see extra signal there, there’s more activity there in Chronic Fatigue Syndrome patients than there is in healthy people, that would be evidence that there’s an exaggerated signal coming from the vagus nerve into the brain."

Treatment
Potential treatments include:
 * antiviral treatments - potential problems with antivirals are that these drugs would need to be a broad spectrum antiviral because a specific virus may not be identified and that antiviral drugs tend not to be effective on the vagal paraganglia. Dr. Jose Montoya and Dr. Martin Lerner, have published studies suggesting that IV valganciclovir therapy may be effective for the subset of CFS patients suspected of having elevated IgG for EBV. Lerner, also included patients with elevated IgG for CMV. Both Montoya and Lerner have shown that longer treatment terms (>6 months) have achieved greater success than short-term antiviral therapy.


 * glial cell inhibitors - such as lbudilast, an anti-inflammatory drug used mainly in Japan for asthma, stroke, and treatment of neuropathic pain as an adjunct with opiods


 * vagus nerve stimulation - involves delivering electrical impulses to the vagus nerve via a medical devise. Use is currently reserved as an adjunctive treatment for certain types of intractable epilepsy and treatment-resistant depression, but it is being researched as a viable treatment for many other conditions, including ME, CFS, and fibromyalgia


 * Ampligen - a drug that stimulates the production of natural interferon

Notable studies

 * 2016: Autonomic correlations with MRI are abnormal in the brainstem vasomotor centre in Chronic Fatigue Syndrome
 * 2013, Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis.

Learn more

 * 2016, CFS Remission blog - ''Vagus Nerve Infection Hypothesis and the Driscoll Theory'
 * 2015, The Low Histamine Chef podcast - Chronic Fatigue from Vagus Nerve Infection a Psychoneuroimmunological Hypothesis transcript of podcast
 * 2015, The Low Histamine Chef blog- The vagus nerve inflammation connection
 * 2014, Michael VanElzakker Ph.d Talks – About the Vagus Nerve Infection Hypothesis and Chronic Fatigue Syndrome (ME/CFS), by Cort Johnson]
 * 2013, HHV-6 Foundation Website - Article about [[Michael VanElzakker] and his theory]
 * 2013, One Theory To Explain Them All? The Vagus Nerve Infection Hypothesis for Chronic Fatigue Syndrome, by Cort Johnson]