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Purpose: Dexterity and bimanual coordination had not previously been compared between people with long COVID and people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Therefore, this study determined dexterity and bimanual coordination in people with long COVID (∼16-month illness duration; n = 21) and ME/CFS (∼16-year illness duration; n = 20), vs age-matched healthy controls (n = 20)., Methods: Dexterity and bimanual coordination was determined using the Purdue pegboard test., Results: The main findings of the present investigation were that people with ME/CFS and people with long COVID were generally comparable for Purdue pegboard tests (P > .556 and d < 0.36 for pairwise comparisons). It is worth noting however, that both these patient groups performed poorer in the Perdue pegboard test than healthy controls (P < .169 and d > 0.40 for pairwise comparisons)., Conclusions: These data suggest that both people with long COVID and people with ME/CFS have similarly impaired dexterity and bimanual coordination. Therefore, there is an urgent need for interventions to target dexterity and bimanual coordination in people with ME/CFS, and given the current pandemic, people with long COVID., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or postexertional symptom exacerbation. In a two-day model of PEM, submaximal exercise induced significant changes in activation of the dorsal midbrain during a high cognitive load working memory task (Washington 2020) (Baraniuk this issue). Controls had no net change. However, ME/CFS had increased activity after exercise, while GWI had significantly reduced activity indicating differential responses to exercise and pathological mechanisms. These data plus findings of the midbrain and brainstem atrophy in GWI inspired a review of the anatomy and physiology of the dorsal midbrain and isthmus nuclei in order to infer dysfunctional mechanisms that may contribute to disease pathogenesis and postexertional malaise. The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and control subjects underwent fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction., Methods: Activated midbrain nuclei were inferred by a re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network., Results: Before exercise, control and GWI subjects showed greater activation during cognition than ME/CFS in the left pedunculotegmental nucleus. Post exercise, ME/CFS subjects showed greater activation than GWI ones for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI, indicating reciprocal patterns of activation. The controls had no changes., Conclusions: Exercise caused the opposite effects with increased activation in ME/CFS but decreased activation in GWI, indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction. Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA. Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS. Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rayhan and Baraniuk.)

Background: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional impairment in ME/CFS patients. This study aimed to estimate the potential of the CPET., Methods: We reviewed studies of the two-day CPET and meta-analyzed the differences between ME/CFS patients and controls regarding four parameters: volume of oxygen consumption and level of workload at peak (VO 2peak , Workload peak ) and at ventilatory threshold (VO 2 @VT, Workload@VT)., Results: The overall mean values of all parameters were lower on the 2nd day of the CPET than the 1st in ME/CFS patients, while it increased in the controls. From the meta-analysis, the difference between patients and controls was highly significant at Workload@VT (overall mean: -10.8 at Test 1 vs. -33.0 at Test 2, p < 0.05), which may reflect present the functional impairment associated with PEM., Conclusions: Our results show the potential of the two-day CPET to serve as an objective assessment of PEM in ME/CFS patients. Further clinical trials are required to validate this tool compared to other fatigue-inducing disorders, including depression, using well-designed large-scale studies.

Purpose: Chronic fatigue syndrome (CFS) is a debilitating disease characterized by fatigue, postexertional malaise, cognitive dysfunction, sleep disturbances, and widespread pain. A pilot, online survey was used to determine the common presentations of CFS patients in the emergency department (ED) and attitudes about their encounters., Methods: The anonymous survey was created to score the severity of core CFS symptoms, reasons for going to the ED, and Likert scales to grade attitudes and impressions of care. Open text fields were qualitatively categorized to determine common themes about encounters., Results: Fifty-nine percent of respondents with physician-diagnosed CFS (total n=282) had gone to an ED. One-third of ED presentations were consistent with orthostatic intolerance; 42% of participants were dismissed as having psychosomatic complaints. ED staff were not knowledgeable about CFS. Encounters were unfavorable (3.6 on 10-point scale). The remaining 41% of subjects did not go to ED, stating nothing could be done or they would not be taken seriously. CFS subjects can be identified by a CFS questionnaire and the prolonged presence (>6 months) of unremitting fatigue, cognitive, sleep, and postexertional malaise problems., Conclusion: This is the first investigation of the presentation of CFS in the ED and indicates the importance of orthostatic intolerance as the most frequent acute cause for a visit. The self-report CFS questionnaire may be useful as a screening instrument in the ED. Education of ED staff about modern concepts of CFS is necessary to improve patient and staff satisfaction. Guidance is provided for the diagnosis and treatment of CFS in these challenging encounters., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24-h repeated exercise test., Methods: Ten CFS, seven MS and 17 age- and gender-matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR)., Results: On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml   kg   min -1 ). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC., Conclusion: These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions., (© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.