Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics

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.

Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

“…Th1-like cytokines, such as IL-2, IL-12, and interferon (IFN)-γ, are often increased in active disease states [8][9][10][11], whereas Th2-like cytokines, including IL-4 and IL-10, may be increased during remission [15][16][17][18]. Nevertheless, concomitant increases in the expression of Th1-and Th2-like cytokines may be present during an acute attack [5,19]. Recently, we observed that TNF-β NcoI polymorphism is significantly associated with MS, i.e., the TNFB2/B2 genotype is associated with MS and with increased TNF-α levels [20].…”

“…Increased levels of IO&NS biomarkers are observed in the brain, cerebrospinal fluid (CSF), and blood of MS patients [4,5]. For example, increased levels of the proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), are observed in the plasma or CSF of patients with MS [6][7][8][9][10][11].…”

The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders

“…Interestingly, serum IgM levels to these anchorage molecules were significantly higher in patients afforded a diagnosis of chronic fatigue syndrome than they were in patients with major depression disorder suggesting increased levels of ROS and RNS [267]. Numerous authors have reported a range of other antibodies towards different lipid species whose origin is largely difficult to determine, although it is highly likely that reported antiganglioside antibodies were directed against gangliosides shed from disrupted lipid rafts [7].…”

“…Oxidative and nitrosative stress (O&NS) and chronic systemic inflammation are interrelated factors implicated in the pathophysiology of Alzheimer's disease [1,2], Parkinson's disease [3,4], multiple sclerosis [5,6], chronic fatigue syndrome [7,8], schizophrenia [9,10] and major depression [11,12].…”

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

“…Many such patients are afforded the exclusionary, non-specific, diagnosis of chronic fatigue syndrome (CFS), according to a plethora of different selection criteria [3], if rudimentary testing does not reveal the cause of their symptoms. Sophisticated tests, however, often reveal profound immunological abnormalities in such patients and evidence of active pathogen activity [4,5]. A study of 375 patients with apparently idiopathic disabling fatigue revealed pathological stimulation of lymphocytes together with abnormally elevated and distributed pattern of CD4 + , CD8 + , and CD19 + leucocytes in 53 % of patients and depleted levels of IgG 3 in 59 % of the study population.…”