Abstract
Background‘Encephalomyelitis disseminata’ (multiple sclerosis) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization. This review aims to compare the phenomenological and neuroimmune characteristics of MS with those of ME/CFS.DiscussionThere are remarkable phenomenological and neuroimmune overlaps between both disorders. Patients with ME/CFS and MS both experience severe levels of disabling fatigue and a worsening of symptoms following exercise and resort to energy conservation strategies in an attempt to meet the energy demands of day-to-day living. Debilitating autonomic symptoms, diminished cardiac responses to exercise, orthostatic intolerance and postural hypotension are experienced by patients with both illnesses. Both disorders show a relapsing-remitting or progressive course, while infections and psychosocial stress play a large part in worsening of fatigue symptoms. Activated immunoinflammatory, oxidative and nitrosative (O+NS) pathways and autoimmunity occur in both illnesses. The consequences of O+NS damage to self-epitopes is evidenced by the almost bewildering and almost identical array of autoantibodies formed against damaged epitopes seen in both illnesses. Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels.SummaryThis review shows that there are neuroimmune similarities between MS and ME/CFS. This further substantiates the view that ME/CFS is a neuroimmune illness and that patients with MS are immunologically primed to develop symptoms of ME/CFS.
Highlights
Background: ‘Encephalomyelitis disseminata’ and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization
Defective functionality of T regulatory (Treg) cells is evidenced in both illnesses and clonal exhaustion of T cells is found in patients with Multiple sclerosis (MS) and ME/CFS
While MS is characterized by increased in vivo expression of CD69, a decreased ex vivo CD69 expression is found in ME/CFS
Summary
Phenomenological similarities between MS and ME/CFS Many patients with MS have symptoms that are characteristic for ME/CFS. Other indicators include elevated antibody titers towards phospholipids, gangliosides and serotonin; anti-lamine SS DNA as well as anti-68/48 kDa and microtubule-associated proteone [215,216,217] In addition to these increased antibody levels that are observed in MS, patients with ME/CFS show various other markers of autoimmunity. T lymphocytes from relapsing-remitting MS patients demonstrate an impaired response to antigen stimulation following treatment with rituximab [230] This finding supports the hypothesis that B cell activity is needed to maintain disease activity in MS [230,231]. ME/CFS patients display a significant increase in intracellular lactate levels following exercise compared to controls [263,267] They display a significantly lower ATP resynthesis rate during recovery from exercise than normal controls stemming from impaired oxidative phosphorylation [263]. Author details 1Tir Na Nog, Pembrey, Llanelli, UK. 2Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand. 3Department of Psychiatry, Deakin University, Geelong, Australia
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