The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups

Abstract

Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are used interchangeably, the diagnostic criteria define two distinct clinical entities. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after a minor exertion, are distinctive symptoms of ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic fatigue (syndrome), other disorders and deconditioning. The introduction of the label, but more importantly the diagnostic criteria for CFS have generated much confusion, mostly because chronic fatigue is a subjective and ambiguous notion. CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and unrefreshing sleep. Most of the research into ME and/or CFS in the last decades was based upon the multivalent CFS criteria, which define a heterogeneous patient group. Due to the fact that fatigue and other symptoms are non-discriminative, subjective experiences, research has been hampered. Various authors have questioned the physiological nature of the symptoms and qualified ME/CFS as somatization. However, various typical symptoms can be assessed objectively using standardized methods. Despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively, e.g., immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction. However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms, as much as possible that well-defined clinical and biological subgroups of ME and CFS patients are investigated in more detail, and that patients are monitored before, during and after interventions with objective measures and biomarkers.

Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn

“…The heterogeneity of the CFS patient group [23] due to its vague definition, is one of the important reasons why research into CFS [5] has not been very effective, yielding positive findings, no significant differences and contradictive results in CFS [9,24]. So, research into patients with “ME/CFS” [9], an even more heterogonous patient population than CFS [5], most likely will not yield any significant findings and discriminative abnormalities, which will “confirm” the incorrect perception [9] that ME [2,3,4], CFS [5], “ME/CFS” (SEID) [9] are “functional somatic syndromes” [25].…”

An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods

“…To establish the presence and severity of symptoms and to assess the health status of patients impartially objective test measures are indispensable [51]. Subjective measures solely based on questionnaires, e.g.…”

“…repeated exercise tests [41,42], cognitive tests [43,44], tilt table tests [45,46], muscle power (endurance) tests [47,48], for diagnosing patients [49] and determining the effect of interventions [50], to find correlations between symptoms/subjective measures and objective test outcomes, and to define symptomatic subgroups of the ME and CFS patient population [51].…”

Dangerous exercise. The detrimental effects of exertion and orthostatic stress in Myalgic Encephalomyelitis and chronic fatigue syndrome

“…Although ME and CFS are often declared to be synonyms [4], the diagnostic criteria define two distinct clinical entities. ME is primarily defined by muscle weakness (and myalgia) after a minor exertion lasting for days and characteristic neurological features, while CFS is primarily defined by (unexplained, incapacitating) chronic fatigue [4].…”

“…ME is primarily defined by muscle weakness (and myalgia) after a minor exertion lasting for days and characteristic neurological features, while CFS is primarily defined by (unexplained, incapacitating) chronic fatigue [4]. Although ME and CFS are to be considered to be two distinct, partially overlapping, diagnostic labels [4], the Institute of Medicine [5] confirmed that post-exertional "malaise", defined as a prolonged aggravation of typical symptoms (e.g. "brain fog"/ cognitive deficits and muscle and joint pain) is the hallmark feature of "ME/CFS".…”