Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome

Komaroff, Anthony L.

doi:10.1001/jama.2019.8312

Cited by 102 publications

(111 citation statements)

References 8 publications

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“…For a long time, many doctors have thought that there is nothing wrong in ME/CFS because routine testing does not reveal any abnormalities. However, over the past 35 years, thousands of studies using more advanced tests have documented underlying biological abnormalities involving many organ systems in patients with ME/CFS, as noted by Komaroff in a recent overview [22]. These abnormalities include metabolic changes, immunological abnormalities in lymphocytes-especially in T cells and poorly functioning natural killer cells-and significant elevation of many blood cytokines especially in the first three years of illness which are correlated with the severity of the illness.…”

Section: Advances In Understanding the Pathophysiology Of Me/cfsmentioning

confidence: 99%

Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies

Vink¹,

Vink-Niese

2019

Diagnostics

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome leads to severe functional impairment and work disability in a considerable number of patients. The majority of patients who manage to continue or return to work, work part-time instead of full time in a physically less demanding job. The prognosis in terms of returning to work is poor if patients have been on long-term sick leave for more than two to three years. Being older and more ill when falling ill are associated with a worse employment outcome. Cognitive behavioural therapy and graded exercise therapy do not restore the ability to work. Consequently, many patients will eventually be medically retired depending on the requirements of the retirement policy, the progress that has been made since they have fallen ill in combination with the severity of their impairments compared to the sort of work they do or are offered to do. However, there is one thing that occupational health physicians and other doctors can do to try and prevent chronic and severe incapacity in the absence of effective treatments. Patients who are given a period of enforced rest from the onset, have the best prognosis. Moreover, those who work or go back to work should not be forced to do more than they can to try and prevent relapses, long-term sick leave and medical retirement.

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Section: Advances In Understanding the Pathophysiology Of Me/cfsmentioning

confidence: 99%

Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies

Vink¹,

Vink-Niese

2019

Diagnostics

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“…Gut microflora changes and associated inflammation maybe one peripheral trigger of neuroinflammation. Several recent metabolomics studies indicate that ME patients are in a hypometabolic state, similar to what occurs in hibernation …”

mentioning

confidence: 93%

“…The NIH has tripled its research funding for ME/CFS from $5 million in 2014 to $16 million in 2018. Published data from these centres and other research groups were recently summarised by Komaroff, and these results have contributed to the shift in focus from a previous psychosomatic to a biomedical understanding of ME.…”

mentioning

confidence: 98%

“…In recent years, metabolic and immunological changes have been detected. One of the most exciting findings come from very new studies indicating that low‐grade neuroinflammation triggers many of the symptoms of this illness such as pain, cognitive problems and sleeping disorders . In 2016, Hornig et al analysed cytokines in the cerebrospinal fluid of ME patients and concluded that the results indicate a markedly disturbed immune signature in the cerebrospinal fluid that is consistent with immune activation in the central nervous system, and a pattern associated with autoimmunity .…”

mentioning

confidence: 99%

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Myalgic Encephalomyelitis (ME) in the Young. Time to Repent

Saugstad

2019

Acta Paediatrica

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“…According to recent estimates ME affects as many as 2.5 million people in the U.S. alone (1). The pathogenesis of ME remains poorly understood and no effective treatment is available for most of these patients.…”

Section: Introductionmentioning

confidence: 99%

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance

Lakshmikanth

et al. 2020

Preprint

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Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ~30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systemslevel monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.

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Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome

Abstract: This Viewpoint reviews new findings presented at a 2019 NIH conference about neuroendocrine, metabolic, immunologic, and physiologic abnormalities that contribute to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Cited by 102 publications

References 8 publications

Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies

Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. A Review and Appraisal of Diagnostic Strategies

Myalgic Encephalomyelitis (ME) in the Young. Time to Repent

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance

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