Front. Physiol. | doi: 10.3389/fphys.2014.00109
Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): The
essence of objective assessment, accurate diagnosis, and acknowledging
biological and clinical subgroups.
Frank N. Twisk1*
1ME-de-patiënten Foundation, Netherlands
Although Myalgic Encephalomyelitis and Chronic Fatigue Syndrome are
used interchangeably, the diagnostic criteria define two distinct
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 Myalgic Encephalomyelitis (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 Chronic Fatigue Syndrome (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
Various authors have questioned the physiological nature of the
symptoms and qualified ME/CFS as somatisation. However, various
typical symptoms can be assessed objectively using standardized
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
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.