[Update from Sept. 2018 here!] In a recent paper, Dr. Willy Eriksen proposes a complete explanation for the development, diversity, and persistence of myalgic encephalomyelitis, aka chronic fatigue syndrome (ME/CFS). He also suggests a possible cure. Seeing that this potentially groundbreaking research was attracting little attention, I contacted Dr. Eriksen and interviewed him via email. This post contains a summary of his hypothesis, which I’ve tried to present in everyday language.

Other posts contain 1) the interview, which contains considerable new information about his hypothesis, and 2) my understanding of how Eriksen’s model fits with other research—and with my experience.

Eriksen holds an MD and PhD and is a research professor at the Norwegian Institute of Public Health. So he presumably has the specialized knowledge to assess ME/CFS research and propose alternatives. (I’m an anthropologist, so I don’t.) While this is his first publication on this disease, his article cites 146 references, and he notes, “I have read, literally speaking, thousands of scientific abstracts, articles, and reports on ME/CFS.”

Ultra-short summary

I’ve read his full article (“The spread of EBV to ectopic lymphoid aggregates may be the final common pathway in the pathogenesis of ME/CFS”), which languishes behind a paywall. Fortunately, the abstract is freely available, but written for specialists. Here’s my ultra-short synopsis of his hypothesis:

Clumps of immune cells form in one or more key spots along the nervous system. Epstein-Barr virus (EBV) infects the clump(s), and this causes inflammation in the area. This inflammation provokes a reaction in the nervous system, which directly and indirectly accounts for the symptoms of ME/CFS. Extracting a patient’s immune cells, priming them to fight EBV, and returning them to his or her body might cure the disease.

Longer summary, with more details

First, some disease, injury, or toxic chemical leads to the clumping of immune cells (an “ectopic lymphoid aggregate”) in one or more places along the nervous system. Eriksen suggests that the dorsal root ganglia, which are located between the vertebrae, are a likely location, because these connect the peripheral nerves (in fingertips, for example) to the spine and thus the central nervous system. (A nice summary is here.) It is well-established that these clumps sometimes form in people, but their role in ME/CFS has not been shown—or discussed much.

Second, the Epstein-Barr virus (EBV) infects one of the immune cells that has clumped along the nervous system, and the virus spreads to other cells in the clump. It’s known that EBV infects such cells.

Over time, new clumps might form in different parts of the nervous system and become infected, and older clumps might get cleared of their EBV infections.

Third, the EBV infection causes the usual response: inflammation in the infected area.

Fourth, this inflammation provokes particular reactions in the nervous system, starting with “glial cell activation,” and this affects other parts of the body. So some symptoms are common to all people with ME/CFS because these changes ramify throughout the central nervous system or otherwise circulate throughout the body. Indeed, glial cell activation can put messenger molecules (cytokines) into the bloodstream, and these might cause the problems with metabolism that researchers have found in other kinds of cells.

Other symptoms are more variable because the clumps of infected immune cells are sitting by different nerves. For example, a person with an infection by the lower spine would suffer differently from someone with an infection along the upper spine.

For more information about glial cells, see this basic page, the Wikipedia entry, or some of the many videos on YouTube.

Fifth, battling this infection for an extended time leads to “immune cell exhaustion.” Thus the disease becomes relatively stable—in other words, chronic.

But that’s not the whole hypothesis. Unlike some other researchers—Robert Naviaux, for example—Eriksen also explains post-exertional malaise (PEM). He proposes that ultimately PEM results from physical stress—too much movement, stretching, or pressure—on the peripheral nerves, such as the ones running along our arms and legs. This intensifies the reactions in the nervous system (aka glial cell activation) that drive ME/CFS.

In the interview he clarifies that other forces, such as psychological stress or toxic chemicals, can make it easier for physical activity to trigger PEM. So it might seem to the person with ME/CFS that the psychological stress is the sole cause of PEM, when really it just reduces the threshold for physical activity to cause it—from walking to sitting up, for example.

Finally, Eriksen proposes a possible cure: “infusions of autologous EBV-specific T-lymphocytes.” Here’s what that means: T-cells—a kind of immune cell—will be taken from the blood of each ME/CFS patient and exposed to EBV in a lab. This will train the T-cells to attack EBV. Then the T-cells will be fed back into the patient intravenously, and, if all goes according to the hypothesis, some will eventually circulate to where the infected cells lying near the nervous system are causing ME/CFS. The T-cells will eradicate the virus there and thus cure the disease. (Yay!) This type of treatment has worked against other forms of disease caused by EBV.

For more information …

Of course, Eriksen’s paper has much more information – and precision! – than this discussion. The interview (highly recommended!) and my blog post evaluating this hypothesis also add some details. But the technically inclined reader who yearns for more (including other researchers, I hope) should either find a library that receives the journal Medical Hypotheses or ask a question here.