By David Tuller, DrPH
For decades, investigators have argued over the causes of the illness or cluster of illnesses variously called myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), ME/CFS, CFS/ME and other names. In the absence of an adequate explanation for the debilitating symptoms, a flawed approach to intervention based on the perceived need for psychological and behavioral rehabilitation has been relentlessly promoted by a committed band of professional campaigners at high levels in UK medicine and academia; their favored treatments are cognitive behavior therapy (CBT) and graded exercise therapy (GET).
These CBT/GET ideological brigades grounded their interventions in an interesting but unproven hypothesis. In their view, a cognitive disturbance in the form of purported â€œunhelpfulâ€ beliefs–specifically, beliefs of having a serious organic disorder–was a major factor in perpetuating the devastating symptoms. Disrupting the hegemony of these ideological brigadiers and their followers has beenâ€”and continues to beâ€”a necessary step toward progress in seeking legitimate and evidence-based treatments.
However, assessing risk factors for ME/CFS itself presents major difficulties. People often seek medical attention long after getting sick; obtaining an ME/CFS diagnosis can take years. Reliable and authoritative data from patientsâ€™ pre-sickness days are often not available. Doctors and researchers then have to rely on patient recall, which is subject to significant bias.
Thatâ€™s why prospective researchâ€”like a study from investigators at DePaul University and Northwestern University, both in Chicagoâ€”is so important. It is well-known that a significant minority of young adults who contract infectious mononucleosis go on to develop ME/CFS. For the Chicago study, the investigators enrolled Northwestern University students between 2014 and 2018 and tracked the group for cases of mononucleosis. They collected questionnaire data and blood samples at multiple time-points to assess differences between those who developed ME/CFS after mononucleosis and those who didnâ€™t.
The study used the DePaul Symptom Questionnaire to assess whether participants met any of three separate case definitionsâ€”the 1994 Fukuda definition, in which the core symptoms of post-exertional malaise (PEM) is not required, along with the 2003 Canadian Consensus Criteria and 2015 Institute of Medicine definition, both of which do require PEM. Participants who met more than one of the three definitions were characterized as having severe ME/CFS. (The logic behind this decision was not provided.)
DePaul University psychology professor Leonard Jason is one of the lead investigators. On Christmas, the journal Clinical Infectious Diseases published some key results. (Jason and colleagues have also adapted the study to track cases of Covid-19 and any subsequent prolonged symptoms. Earlier this year, I wrote about this redeployment of the research for STAT.)
After reviewing their data on risk factors for developing ME/CFS after a bout of mononucleosis, Jason and his colleagues reached this firm conclusion: â€œAt baseline, those who developed ME/CFS had more physical symptoms and immune irregularities, but not more psychological symptoms, than those who recovered.â€
Of particular note, those who ended up with an ME/CFS diagnosis did not differ at baseline for depression, anxiety, stress and coping from those who did not end up with an ME/CFS diagnosis. Moreover, their baseline scores on the DePaul Symptom Questionnaire were higher and levels of some cytokines were significantly different.
In other words: The study provided no evidence that â€œunhelpful cognitionsâ€ have anything to do with generating the symptoms characteristic of ME/CFS. That means interventions based on such reasoningâ€”like CBT and GETâ€”would not be indicated.
In the study, of 4501 participants with baseline data, 238 developed infectious mononucleosis. Of those 238, 55 (23%) met at least one case definition for ME/CFS six months later and 157 (66%) had no remaining symptoms. Of the 55 participants identified as having ME/CFS under any of the three definitions, 20 patientsâ€”or 8% of the sample with mononucleosis–met more than one definition and were categorized as having severe ME/CFS.
Interestingly, the lower percentage is more in line with previous research on the prevalence of an ME/CFS-like illness after mononucleosis, so perhaps the investigatorsâ€™ strategy for defining severe disease weeded out some of those without the full spectrum of core symptoms. Some of the participants who remained symptomatic at six months were perhaps experiencing a natural but prolonged recovery from post-viral fatigue rather than an actual case of ME/CFS. It would be useful to learn the results at 12 months.