ME/CFS: Dueling Hypotheses

Here’s a video with a simplified comparison of VanElzakker’s Vagus Nerve Infection Hypothesis and Eriksen’s “ectopic lympoid aggregates” hypothesis.

Here’s the script:

Nobody knows what causes myalgic encephalomyelitis, or chronic fatigue syndrome, but hypotheses abound. In this video I briefly compare two of them: VanElzakker’s Vagus Nerve Infection Hypothesis and Eriksen’s idea that clumps of immune cells along the nervous system are infected with Epstein-Barr Virus.

I appreciate that both of these hypotheses are fairly complete, but,  to keep this video’s length and language manageable, I simplify both scenarios.

The first question that both hypotheses answer is how ME/CFS gets started. And both blame infections. In the Vagus Nerve Infection Hypothesis, any type of infection will do: virus, bacteria, whatever. What’s important is that the vagus nerve itself gets infected. This is a giant nerve that connects all sorts of internal organs to the brain.

The Eriksen Hypothesis is a bit more complex. In this scenario, various nerves might be affected, but the pathogen has to be the Epstein-Barr Virus or possibly HHV-6. Here’s the idea: Some infection, injury, or other stressor causes a clump of immune cells to form by a nerve. Eriksen provides the example of a nerve that connects the spinal cord to some other part of the body. These clumps are “ectopic lymphoid aggregates,” which is an impressive thing to say at parties. These clumps get infected by the Epstein-Barr Virus, which triggers inflammation in the area, which affects the adjacent nerve, which leads to something called glial activation.

In fact, both of these hypotheses blame glial activation for symptoms. Glia are nerve cells that support and interact with the more-famous neurons and that release signals to the rest of the body. These signals come in the form of molecules, saying, among other things, “Hey, we’re sick!” Some of the effects of glial activation will be the same in everybody, and some of the symptoms—whether from glial activation or local inflammation—will differ depending on the location of the infection.

Both of these hypotheses explain changes in symptoms via the spread of the infection, or via the establishment of a new infection in new locations—that is, in another part of the vagus nerve in the Vagus Nerve Infection Hypothesis or in another clump of immune cells lying by a nerve in Eriksen’s hypothesis.

These two hypotheses have so much in common that you might expect the authors to suggest the same treatments, but they don’t. VanElzakker advocates glial inhibitors, naming ibudilast, minocycline, and others. Glial inhibitors wouldn’t end the underlying infection but would reduce the symptoms. VanElzakker’s position on antivirals is mixed, since he acknowledges that valganciclovir has helped some people but also states that antivirals can’t get to parts of the vagus nerve that are likely to be infected. In addition to glial inhibitors and antivirals, he discusses vagus nerve stimulation, which appears to be experimental, and vagotomy, which is ridiculously risky.

If Eriksen’s hypothesis is correct, any of VanElzakker’s treatments might be effective, but Eriksen proposes a possible cure for the underlying infection. Immune cells would be taken from the patient, trained in a lab to fight Epstein-Barr Virus, multiplied by the millions, and infused back into the patient’s bloodstream. The tsunami of Epstein-Barr-fighting T-cells would eradicate the infected clumps of immune cells responsible for triggering ME/CFS. Doctors, including a unit at Baylor University, have successfully tried this procedure on other conditions.

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