Elin Bolle Strand

Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease

Background: The Institute of Medicine has recommended a change in the name and criteria for chronic fatigue syndrome (CFS), renaming the illness systemic exertion intolerance disease (SEID). The new SEID case definition requires substantial reductions or impairments in the ability to engage in pre-illness activities, unrefreshing sleep, post-exertional malaise, and either cognitive impairment or orthostatic intolerance. Purpose: In the current study, samples were generated through several different methods and were used to compare this new case definition to previous case definitions for CFS, the International Consensus Criteria for myalgic encephalomyelitis (ME-ICC), the Canadian myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) definition, as well as a case definition developed through empirical methods. Methods: We used a cross-sectional design with samples from tertiary care settings, a BioBank sample, and other forums. Seven hundred and ninety-six patients from the USA, Great Britain, and Norway completed the DePaul Symptom Questionnaire. Results: Findings indicated that the SEID criteria identified 88% of participants in the samples analyzed, which is comparable to the 92% that met the Fukuda criteria. The SEID case definition was compared to a four-item empiric criteria, and findings indicated that the four-item empiric criteria identified a smaller, more functionally limited and symptomatic group of patients. Conclusion: The recently developed SEID criteria appears to identify a group comparable in size to the Fukuda et al. criteria, but a larger group of patients than the Canadian ME/CFS and ME criteria, and selects more patients who have less impairment and fewer symptoms than a four-item empiric criteria.

Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome

Objectives The objective of this study was to examine individuals with myalgic encephalomyelitis and chronic fatigue syndrome who are confined to their homes due to severe symptomatology. The existing literature fails to address differences between this group, and less severe, nonhousebound patient populations. Methods Participants completed the DePaul Symptom Questionnaire, a measure of myalgic encephalomyelitis and chronic fatigue syndrome symptomology, and the SF-36, a measure of health impact on physical/mental functioning. ANOVAs and, where appropriate, MANCOVAS were used to compare housebound and nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome across areas of functioning, symptomatology, and illness onset characteristics. Results Findings indicated that the housebound group represented one quarter of the sample, and were significantly more impaired with regards to physical functioning, bodily pain, vitality, social functioning, fatigue, postexertional malaise, sleep, pain, neurocognitive, autonomic, neuroendocrine, and immune functioning compared to individuals who were not housebound. Discussion Findings indicated that housebound patients have more impairment on functional and symptom outcomes compared to those who were not housebound. Understanding the differences between housebound and not housebound groups holds implications for physicians and researchers as they develop interventions intended for patients who are most severely affected by this chronic illness.

Factor Analysis of the DePaul Symptom Questionnaire: Identifying Core Domains

The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms. The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisting of neuroendocrine, autonomic, and immune dysfunction symptoms. The use of empirical methods could help better understand the fundamental symptom domains of this illness.

Comparing and contrasting consensus versus empirical domains

Background: Since the publication of the CFS case definition, there have been a number of other criteria proposed including the Canadian Consensus Criteria and the Myalgic Encephalomyelitis: International Consensus Criteria. Purpose: The current study compared these domains that were developed through consensus methods to one obtained through more empirical approaches using factor analysis. Methods: Using data mining, we compared and contrasted fundamental features of consensus-based criteria versus empirical latent factors. In general, these approaches found the domain of fatigue/post-exertional malaise as best differentiating patients from controls. Results: Findings indicated that the Fukuda et al. criteria had the worst sensitivity and specificity. Conclusions: These outcomes might help both theorists and researchers better determine which fundamental domains to be used for the case definition.

The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not known, and neither a diagnostic marker nor licensed treatments are available yet. The EUROMENE network of European researchers and clinicians aims to promote cooperation and advance research on ME/CFS. To improve diagnosis and facilitate the analysis of clinical trials surrogate markers are urgently needed. As a first step for developing such biomarkers for clinical use a database of active biomarker research in Europe was established called the ME/CFS EUROMENE Biomarker Landscape project and the results are presented in this review. Further we suggest strategies to improve biomarker development and encourage researchers to take these into consideration for designing and reporting biomarker studies.

Unperturbed cytotoxic lymphocyte phenotype and function in myalgic encephalomyelitis/chronic fatigue syndrome patients

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients. No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators. In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.

Clinical criteria versus a possible research case definition in chronic fatigue syndrome/myalgic encephalomyelitis

ABSTRACT Background: The Institute of Medicine (IOM) recently developed clinical criteria for what had been known as chronic fatigue syndrome. Given the broad nature of the clinical IOM criteria, there is a need for a research definition that would select a more homogenous and impaired group of patients than the IOM clinical criteria. At the present time, it is unclear what will serve as the research definition. Purpose: The current study focused on a research definition which selected homebound individuals who met the four IOM criteria, excluding medical and psychiatric co-morbidities. Methods: Our research criteria were compared to those participants meeting the IOM criteria. Those not meeting either of these criteria sets were placed in a separate group defined by six or more months of fatigue. Data analyzed were from the DePaul Symptom Questionnaire and the 36-item Short-Form Health Survey (SF-36). Due to unequal sample sizes and variances, Welch’s F tests and Games-Howell post-hoc tests were conducted. Results: Using a large database of over 1000 patients from several countries, we found that those meeting a more restrictive research definition were even more impaired and more symptomatic than those meeting criteria for the other two groups. Conclusion: Deciding on a particular research case definition would allow researchers to select more comparable patient samples across settings, and this would represent one of the most significant methodologic advances for this field of study.

Comparing the DePaul Symptom Questionnaire with physician assessments: a preliminary study

Background: Diagnostic assessment of chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) is largely based on a two part process; screening patients who might meet criteria and following up this assessment with physicians’ clinical evaluation of a range of inclusionary symptoms and exclusionary illnesses. Purpose: The aim was to assess how well the DePaul Symptom Questionnaire (DSQ) screened for patients who were ultimately diagnosed by physicians using the Canadian Consensus Criteria (CCC). Methods: Sixty-four patients referred for evaluation of possible CFS or ME were screened initially using the DSQ, and then evaluated and subsequently diagnosed by physicians. To assess the consistency between the self-report DSQ and the physicians’ diagnosis, sensitivity and specificity as well as predictive values were calculated. Results: The DSQ identified 60 and the physicians identified 56 as having a CCC diagnosis. The overall agreement between the two ratings on the diagnostic assessment part was moderate (Kappa = 0.45, p < .001). The sensitivity of DSQ was good (98%) while the specificity was 38%. Positive and negative predictive values were 92% and 75%, respectively. Conclusion: DSQ is useful for detecting and screening symptoms consistent with a CCC diagnosis in clinical practice and research. However, it is important for initial screening of self-report symptoms to be followed up by subsequent medical and psychiatric examination in order to identify possible exclusionary medical and psychiatric disorders.

Case definitions integrating empiric and consensus perspectives

Background: There has been considerable controversy regarding how to name and define the illnesses known as myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). The Institute of Medicine (IOM) report has proposed new clinical criteria and a new name for this illness, but aspects of these recommendations have been scrutinized by patients and scientists. Purpose: It is possible that both empiric and consensus approaches could be used to help settle some of these diagnostic challenges. Using patient samples collected in the USA, Great Britain, and Norway (N = 556), the current study attempted to categorize patients using more general as well as more restricted case definitions. Results: Overall, the outcomes suggest that there might be four groupings of patients, with the broadest category involving those with chronic fatigue (N = 62), defined by six or more months of fatigue which cannot be explained by medical or psychiatric conditions. A second category involves those patients who have chronic fatigue that can be explained by a medical or psychiatric condition (N = 47). A third category involves more specific criteria that have been posited both by the IOM report, Canadian Clinical Case criteria, ME-ICC criteria and a more empiric approach. These efforts have specified domains of substantial reductions of activity, post-exertional malaise, neurocognitive impairment, and sleep dysfunction (N = 346). Patients with these characteristics were more functionally impaired than those meeting just chronic fatigue criteria, p < .05. Finally, those meeting even more restrictive ME criteria proposed by Ramsay, identified a smaller and even more impaired group, p < .05. Conclusion: It is important that scientists world-wide develop consensus on how to identify and classify patients using clinical and research criteria, and ultimately develop subtypes within such categories.

Effectiveness of a group-based self-management program for people with chronic fatigue syndrome: A randomized controlled trial

Objective: To evaluate the effectiveness of a group-based self-management program for people with chronic fatigue syndrome. Design: A randomized controlled trial. Setting: Four mid-sized towns in southern Norway and two suburbs of Oslo. Subjects: A total of 137 adults with chronic fatigue syndrome. Intervention: A self-management program including eight biweekly meetings of 2.5 hours duration. The control group received usual care. Main measures: Primary outcome measure: Medical Outcomes Study-Short Form-36 physical functioning subscale. Secondary outcome measures: Fatigue severity scale, self-efficacy scale, physical and mental component summary of the Short Form-36, and the illness cognition questionnaire (acceptance subscale). Assessments were performed at baseline, and at six-month and one-year follow-ups. Results: At the six-month follow-up, a significant difference between the two groups was found concerning fatigue severity (p = 0.039) in favor of the control group, and concerning self-efficacy in favor of the intervention group (p = 0.039). These significant differences were not sustained at the one-year follow-up. No significant differences were found between the groups concerning physical functioning, acceptance, and health status at any of the measure points. The drop-out rate was 13.9% and the median number of sessions attended was seven (out of eight). Conclusions: The evaluated self-management program did not have any sustained effect, as compared with receiving usual care.