The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Objectives: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) typically perform worse on cognitive tasks compared to controls. The present study explored the independent associations of fatigue and pain symptoms with cognitive performance in a large sample of patients who met CDC criteria of CFS (n = 1375), of whom most also met NICE/ IOM criteria (n = 1072). Moreover, we tested the hypothesis that these associations become stronger with older age and longer symptom duration.

Methods: Questionnaires and diaries were employed assessing fatigue and pain severity, together with the impact of health problems on daily life (using the SF-36 ‘Physical Functioning’ and ‘Bodily Pain’ subscales). Cognitive outcomes consisted of speeded performance measures, namely the Symbol Digit Test, motor speed, simple and choice reaction time (RT), and response inhibition. Categorical regression with lasso penalization was employed to identify relevant correlates of cognitive performance.

Results: Fatigue severity remained as only correlate of response inhibition. For the other cognitive outcomes, fatigue severity consistently emerged together with contributions of pain severity, bodily pain and/or physical functioning. Restricting these analyses to those patients meeting NICE/IOM criteria revealed overall similar results. Age, not symptom duration, moderated several relationships, showing more pronounced associations between cognitive performance and pain severity, physical functioning, and bodily pain with older age.

Conclusions: This study highlights that a multidimensional nature of symptoms, including fatigue and pain severity, and the impact on daily-life functioning, relate to lower cognitive performance in patients with ME/CFS. Studies are needed to identify the direction and potential causality of these associations.

Source: Oosterman JM, van der Schaaf M, de Kleijn WPE, Kuut TA, Brazil IA, Knoop H. The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome. J Psychosom Res. 2025 Oct 3;199:112401. doi: 10.1016/j.jpsychores.2025.112401. Epub ahead of print. PMID: 41101039. https://www.sciencedirect.com/science/article/pii/S0022399925003654 (Full text)

Preliminary ICF Core Set for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Rehabilitation Medicine

Abstract:

Objective: To create and evaluate a preliminary ICF Core Set for myalgic encephalomyelitis/chronic fatigue syndrome using a team-based approach.

Design: Observational study.

Subjects/patients: A total of 100 consecutive patients (mean age 45 years, standard deviation (SD) 9 years) were assessed by a rehabilitation team and included in the study.

Methods: A preliminary International Classification of Functioning, Disability and Health (ICF) Core Set was created, based on literature studies, and on discussion forums between the team and the researchers. Patients were assessed by a rehabilitation medicine team regarding impairments in body function, activity limitations, and restrictions in participation.

Results: Clinical assessments of the component Body Functions found impairments in energy, fatigue, physical endurance, fatigability, sleep and pain in 82-100% of patients. At least half of the patients had impairments in higher cognitive functions, attention, and emotions, as well as sound and light hypersensitivity, general hyper-reactivity and thermoregulatory functions. For the component Activity/Participation, the most frequent limitations and restrictions were in doing housework (93%), assisting others (92%), acquisition of goods and services (90%), remunerative employment (87%), handling stressful situations (83%), preparing food (83%), recreation and leisure (82%), informal socializing (78%) and carrying out daily activities (77%). The most frequent degrees of impairments/limitations/restrictions assessed were light and moderate, except for remunerative employment, for which restrictions were severe.

Conclusion: Using unconventional methods, this study sets out a preliminary ICF Core Set list for patients with myalgic encephalomyelitis/chronic fatigue syndrome. Further studies are required to improve and test this Core Set in myalgic encephalomyelitis/chronic fatigue syndrome populations.

Source: Bileviciute-Ljungar I, Schult ML, Borg K, Ekholm J. Preliminary ICF core set for patients with myalgic encephalomyelitis/chronic fatigue syndrome in rehabilitation medicine [published online ahead of print, 2020 May 28]. J Rehabil Med. 2020;10.2340/16501977-2697. doi:10.2340/16501977-2697 https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-2697 (Full text)

Deviations in daily physical activity patterns in patients with the chronic fatigue syndrome: a case control study

Abstract:

OBJECTIVES: Deviations in daily physical activity patterns may play an important role in the development and maintenance of fatigue in the chronic fatigue syndrome (CFS). The aim of this study is to gain insight into the objective daily physical activity pattern of patients with CFS in comparison with healthy controls. The secondary objective is studying the awareness in performing physical activities.

METHODS: The objective daily physical activity pattern was measured with a tri-axial accelerometer in 35 patients with CFS and in 35 age- and gender-matched healthy controls. The objective daily physical activity level and distribution of physical activities at low, medium and high intensity levels during the day were measured. Moreover, variability in performing physical activities within and between subjects was computed. Subjective ratings of self-reported daily physical activity levels were assessed at a visual analog scale.

RESULTS: CFS patients were significantly less physically active in the afternoon and evening, and spent fewer activities at high intensity levels and more at low intensity levels. Moreover, CFS patients showed more variability in their own physical activity pattern during the afternoon. The heterogeneity in the physical activity pattern between subjects within the CFS and control group did not differ. Finally, CFS patients were more aware about their daily physical activity level than healthy controls.

CONCLUSION: CFS patients showed deviations in the objectively measured daily physical activity pattern. Future research should elucidate the relation between impaired balances in daily physical activity patterns and fatigue severity in CFS.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Evering RM, Tönis TM, Vollenbroek-Hutten MM. Deviations in daily physical activity patterns in patients with the chronic fatigue syndrome: a case control study. J Psychosom Res. 2011 Sep;71(3):129-35. doi: 10.1016/j.jpsychores.2011.04.004. Epub 2011 May 18. https://www.ncbi.nlm.nih.gov/pubmed/21843746

 

Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance

Abstract:

This study examined possible interactions between immunological abnormalities and symptoms in CFS. Sixteen CFS patients filled in a battery of questionnaires, evaluating daily functioning, and underwent venous blood sampling, in order to analyse immunological abnormalities.

Ribonuclease (RNase) L cleavage was associated with RNase L activity (rs=0.570; p=0.021), protein kinase R (PKR) (rs=0.716; p=0.002) and elastase activity (rs=0.500; p=0.049). RNase L activity was related to elastase (rs=0.547; p=0.028) and PKR activity (rs=0.625; p=0.010). RNase L activity (rs=0.535; p=0.033), elastase activity (rs=0.585; p=0.017) and RNase L cleavage (rs=0.521; p=0.038) correlated with daily functioning.

This study suggests that in CFS patients an increase in elastase activity and subsequent RNase L cleavage is accompanied by increased activity of both the PKR and RNase L enzymes. RNase L and elastase activity are related to daily functioning, thus evidence supporting the clinical importance of these immune dysfunctions in CFS patients was provided.

 

Source: Meeus M, Nijs J, McGregor N, Meeusen R, De Schutter G, Truijen S, Frémont M, Van Hoof E, De Meirleir K. Unravelling intracellular immune dysfunctions in chronic fatigue syndrome: interactions between protein kinase R activity, RNase L cleavage and elastase activity, and their clinical relevance. In Vivo. 2008 Jan-Feb;22(1):115-21. http://iv.iiarjournals.org/content/22/1/115.long (Full article)

 

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition.

In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined.

Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance.

After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

 

Source: Strayer DR, Carter WA, Brodsky I, Cheney P, Peterson D, Salvato P, Thompson C, Loveless M, Shapiro DE, Elsasser W, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S88-95. http://www.ncbi.nlm.nih.gov/pubmed/8148460