Description of the state-of-the-art

Research on ME/CFS in Europe is characterised by the absence of a collaborative approach between research centres, whereas at the national level research and health services provision are usually concentrated in few centres of competence. Research efforts in the field have been restricted to some disease-specific calls from funding agencies (mainly in the UK). Consequently, they have been very fragmented, with sub-priorities (e.g. viral, immunological and environmental) determined by organisational affiliations and funding programmes. Therefore a major and concerted effort is crucial in order to align biobanks and bioinformatics platforms and to attain conformity in biomarker sets. Tissue samples are scarce. New frontiers of biomedical research are hindered by the absence of validated animal models. Imaging data consists mainly of MRI and unspecific findings (e.g., Evans index abnormalities). Only a small number of PET studies for neuro-inflammation have been completed.

Clinical practice involves unspecific ailments, alternative pathways, and competing nosological

Severe comorbidities usually overshadow ME/CFS symptomatology, and there is still no consensus among research groups and health care systems on diagnosis based on clinical criteria. The Fukuda criteria (CDC-1994) and the Reeves empirical criteria differ in their diagnostic power by a factor of 10. The Canadian Consensus Criteria and the later International Consensus Criteria (ICC) for ME for clinical diagnosis require more specific symptoms. These requirements reflect some current research findings.

A large number of diverse causative factors

 e.g. viral infection, immune activation, exposure to toxins, chemicals, and pesticides, low intensity radiation and EM fields - have been suggested as aetiological factors (multifactorial disease). Altered gene expression profiles in ME and CFS patient populations have been reported. Pathways of disease development involve metabolic dysregulation as a chronic pathological state. Mitochondrial dysfunction also has been proposed for ME/CFS. Similarity to the pathways observed in ageing with mitochondrial (SOD, GPx) and cellular enzyme (catalase) concentration and/or decrease in activity could explain the similarity with ageing processes
Objective clinical signs related to symptoms are found only in severely affected cases. The elaboration of the quantitative International Consensus Symptom Scale is ongoing, and the older Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale remains in use. The ICC recommends that identified ME patients should be distinguished from those identified by the Reeves and NICE criteria as having CFS. However, a clear stratification approach has not yet been described. Major sources of ME/CFS cases are those identified by general practitioners (GPs)/family doctors, and neurologists. Smaller numbers are identified by occupational medicine specialists and disability assessors. Paediatric cases are often referred to child psychiatrists. ME/CFS still lacks validated molecular diagnostic criteria