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ME/CFS/SEID: It goes by many aliases, but its blood-chemistry signature is a giveaway

It's the disease that dare not speak its name without tripping over one of its other names. Call it what you will - chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME) or its latest, Institute of Medicine-sanctioned designation, systemic exertion intolerance disease (SEID). It's very real, affecting between 1 million and 4 million people in the United States alone, according to Stanford infectious-disease sleuth Jose Montoya, MD, who has closely followed more than 200 SEID patients for several years and done extensive testing on these patients in an effort to find out what's causing their condition.

Different authorities have quoted different numbers regarding those with SEID. The name-calling and number-assigning squishiness stems from the fact that beyond its chief defining symptom - overwhelming, unremitting exhaustion lasting for six months or longer - it's tough to pin down. Additional symptoms can range from joint and muscle pain, incapacitating headaches or food intolerance to sore throat, lymph-node enlargement, gastrointestinal problems, abnormal blood-pressure or hypersensitivity to light, noise or other sensations.

Research into the hows and whys of SEID has been plagued by the inability to establish any characteristic biochemical or neuroanatomical underpinnings of the disorder. Although many viral suspects have been interrogated, no accused microbial culprit has been indicted. To this day, there are no valid laboratory tests for diagnosing SEID.

But a burst of insight into SEID's physiological substrate came only months ago when Stanford neuroradiologist Mike Zeineh, MD, PhD, working with patients from Montoya's registry, found that they shared a pattern of white-matter loss in specific parts of the brain. The discovery drew a great deal of attention in the press as well as the CFS community. (See our news release about that study for details.)

Now a high-profile, multi-institution team including Montoya has published a study in Science Advances showing yet another physiological basis for a diagnosis of SEID: a characteristic pattern, or "signature," consisting of elevated levels of various circulating immune-signaling substances in the blood.

Previous attempts to establish such a signature have fallen flat. In retrospect, that may be because, in those analyses, the researchers lumped together short-term and long-term patients (SEID can last for decades).

But in the new study, the investigators separated short-term (less than three years) from long-term (more than three years) patients, and observed distinct differences between the short-termers' blood chemistry and that of healthy subjects. These differences - elevations of several different pro- and anti-inflammatory proteins, suggesting some kind of battle royale raging in the immune system - were absent in those who'd been sick longer. Apparently the body's defense system fights a free-for-all against some shadowy SEID-triggering entity and then, after a few years, gives up. (Or was the immune system, for some still-inexplicable reason, just chasing its own shadow to begin with?)

In any case, this finding further establishes the physiological reality underlying the subjective complaints voiced by SEID patients and may point to ways of diagnosing the condition early - and, perhaps, to therapeutic interventions as well.

It also says something about statistical pitfalls. After all, the "average" human has one breast and one testicle.

Previously: Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed, Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation and Patients' reaction to ME/CFS coverage in Stanford Medicine magazine
Photo by Internet Archive Book Images

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