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.