It is not unusual for patients who say they are sick to have normal results on standard laboratory testing. The physician often concludes that there is no “real” illness and that the patients’ symptoms likely stem from a psychological disorder. An alternative conclusion, often honored in the breach, is that the standard laboratory tests are measuring the wrong things.
Chronic fatigue syndrome (CFS)―also called myalgic encephalomyelitis/chronic fatigue syndrome―is such an illness. Often, the condition begins suddenly, following an “infectious-like” illness. For years, patients do not return to full health. The illness waxes and wanes, and at its worst leads patients to be bedridden or unable to leave their homes. A report from the National Academies estimates that CFS affects up to 2.5 million people in the United States and generates direct and indirect expenses of $17–24 billion annually (1). The most widely used case definition (2) consists only of symptoms. This, along with typically normal results on standard laboratory tests, has raised the question of whether there are any “real” objective, biological abnormalities in CFS. In PNAS, Montoya et al. (3) report the latest evidence that there are such abnormalities.
Indeed, research over the past 30 y has discovered pathology involving the central nervous system (CNS) and autonomic nervous system (ANS), energy metabolism (with associated oxidative and nitrosative stress), and the immune system, as described in a detailed review (4). This Commentary will briefly summarize the evidence, providing citations only to work published since this review. I will then place the report by Montoya et al. (3) in context, and speculate about the pathophysiology of the illness.
Studies of the Nervous System
