Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder of unknown physiopathology with multisystemic repercussions, framed in ICD-11 under the heading of neurology (8E49). There is no specific test to support its clinical diagnosis. Our objective is to review the evidence in neuroimaging and dysautonomia evaluation in order to support the neurological involvement and to find biomarkers serving to identify and/or monitor the pathology. The symptoms typically appear acutely, although they can develop progressively over years; an essential trait for diagnosis is “central” fatigue together with physical and/or mental exhaustion after a small effort. Neuroimaging reveals various morphological, connectivity, metabolic, and functional alterations of low specificity, which can serve to complement the neurological study of the patient. The COMPASS-31 questionnaire is a useful tool to triage patients under suspect of dysautonomia, at which point they may be redirected for deeper evaluation. Recently, alterations in heart rate variability, the Valsalva maneuver, and the tilt table test, together with the presence of serum autoantibodies against adrenergic, cholinergic, and serotonin receptors were shown in a subgroup of patients. This approach provides a way to identify patient phenotypes. Broader studies are needed to establish the level of sensitivity and specificity necessary for their validation. Neuroimaging contributes scarcely to the diagnosis, and this depends on the identification of specific changes. On the other hand, dysautonomia studies, carried out in specialized units, are highly promising in order to support the diagnosis and to identify potential biomarkers. ME/CFS orients towards a functional pathology that mainly involves the autonomic nervous system, although not exclusively.

Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome With Partial Least Squares Discriminant Analysis: Relevance of Blood Extracellular Vesicles

“…In 2015 the Institute of Medicine (IOM) in the US (37) informed that ME/CFS is a medical illness and should not be considered a psychiatric condition. In support of IOM conclusions that ME/CFS has a biological basis numerous studies show neurologic (38), immune (39), and metabolic (40) disturbances in these patients. Still, ME/CFS biomarker validation remains an important challenge with many research groups identifying putative diagnostic markers which could help move forward our understanding of the affected pathways in the disease.…”

“…As described in a previous study (12), study participants were women with an average age of 46.8 (age range [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] for the disease cohort and 45.2 (age range 18-52) years for the matched HC group. Median ages were 48 years and 47 for the ME/CFS and HC group, respectively.…”

Müdigkeit, Fatigue und Erschöpfung: Alles das Gleiche oder Ausprägungen eines Kontinuums? – Ein Diskussionsanstoß

“…(2019) [ 11 ] n = 172 SOFI ( α = 0,86–0,93) COPSOQ-II ( α = 0,85) Fatigue ist assoziiert mit extremer Müdigkeit oder Schläfrigkeit und ist meist ein Zustand, der sich im Laufe der Zeit zu einer chronischen körperlichen und mentalen Beeinträchtigung ausweiten kann Frone and Blais (2019) [ 15 ] n = 1375 3D-WFI ( α = 0,97–0,99) Fatigue wird durch extreme Müdigkeit und eingeschränkte Funktionsfähigkeit beschrieben, die während und am Ende des (Arbeits‑)Tages subjektiv erlebt wird, und von Schläfrigkeit abgegrenzt werden muss Gandasegui et al. (2021) [ 16 ] – – Fatigue wird definiert als Gefühl der Müdigkeit, die nicht mir körperlicher Aktivität zusammenhängt, sich unverhältnismäßig verschlimmern kann und sich nicht durch Ruhe bessert Guest et al. (2021) [ 19 ] n = 386 OFER-15 ( α > 0,84) Anhaltende Fatigue entsteht, wenn Betroffene sich geringfügig von starker Müdigkeit erholen.…”

“…In den uns hier vorliegenden Arbeiten wird Fatigue charakterisiert durch einen Energiemangel mit extremem Ausmaß. Dies hängt jedoch nicht mit körperlicher Aktivität zusammen und kann sich zudem unproportional verschlimmern [ 16 , 32 , 55 ]. In Abgrenzung zur Müdigkeit nimmt die körperliche und mentale Einschränkung bei Fatigue trotz angemessener Erholung und Entspannung nicht ab [ 10 , 21 , 44 , 48 ].…”

Stress, Asthenia, and Cognitive Disorders

“…Asthenia syndrome developed evolutionarily as a type of protective mechanism, signaling depletion of energy resources and the need for this to be corrected. It is therefore a characteristic feature of asthenic syndrome that it disappears after rest, as soon as the energy defi cit which operated as the initiating element in pathological fatigue is compensated [2]. Asthenia has a variety of causes, including stress, various infectious diseases, acute and chronic somatic and neurological pathologiesi.e., anything whose occurrence increases the "expenditure" of energy or requires signifi cant energy outlay for recovery will be accompanied by the development of this state.…”