Considerable debate surrounds the search for the defining features of patients with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Current case definitions were created through clinical consensus. Failure to operationalize these case definitions has led to considerable variability in the identification of patients. In addition, some case definitions (e.g., Fukuda et al., 1994) do not require cardinal symptoms of this illness, where as other case definitions do require core symptoms of this illness (Carruthers et al., 2003, 2011), and these latter case criteria appear to identify a more impaired group of patients.
Criterion variance is most likely to occur when operationally explicit criteria do not exist for diagnostic categories (Spitzer, Endicott, & Robins, 1978), or when there are varying criteria for contrasting case definitions, which is an impediment to the research in this field. To deal with this problem, it is possible to differentiate those that meet more loosely defined criteria from those that are more narrowly and defined, thus differentiating CFS from ME.
In order to progress the search for biological markers and effective treatments, essential features need to be operationalized and broadly used in order to increase the probability that individuals included in samples have the same underlying illness.
Source: Jason LA, Sunnquist M, Brown A, Reed J. Defining Essential Features of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. J Hum Behav Soc Environ. 2015;25(6):657-674. Epub 2015 May 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817848/ (Full article)
BACKGROUND: The DePaul Symptom Questionnaire (DSQ) was developed to provide a structured approach for collecting standardized symptomatology and health history information to allow researchers and clinicians to determine whether a patient meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), myalgic encephalomyelitis (ME), and/or chronic fatigue syndrome (CFS).
PURPOSE: The purpose of this study was to examine the test-retest reliability of the DSQ.
METHODS: Test-retest reliability of the measure was examined with a sample of 26 adults self-identifying as having either ME/CFS, ME and/or CFS and 25 adults who did not self-identify as having these illnesses and were otherwise healthy controls.
RESULTS: Overall, the majority of items on the DSQ exhibited good to excellent test-retest reliability, with Pearson’s or kappa correlation coefficients that were 0.70 or higher.
CONCLUSIONS: Thus, the present study suggests that the DSQ is a reliable diagnostic measure that can provide a standardized way of examining illness constructs and symptomatology among patients who identify as having ME/CFS, ME and/or CFS.
Source: Jason LA, So S, Brown AA, Sunnquist M, Evans M. Test-Retest Reliability of the DePaul Symptom Questionnaire. Fatigue. 2015 Jan 1;3(1):16-32. Epub 2015 Jan 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788471/ (Full article)
Living with a chronic illness can be challenging, but the ability to derive benefits and grow from this experience may enhance well-being. However, the possibility of obtaining such benefits may be dependent on the levels of stigmatization and lack of social support experienced by an individual as a result of the illness.
Chronic fatigue syndrome (CFS) and fibromyalgia are chronic conditions that remain largely unexplained and those with these conditions must often contend with stigma and skepticism from others. Individuals with CFS/fibromyalgia often display stress-related biological alterations and the experience of stressful life events has been associated with illness development.
The present study demonstrated that women with CFS/fibromyalgia (n = 40) as well as community participants who were depressed/anxious (n = 37), reported higher stigma levels than healthy women (n = 33). Moreover, women with CFS/fibromyalgia and those with depression/anxiety also reported greater levels of stigma than women with a chronic yet more widely accepted condition (n = 35; rheumatoid arthritis, osteoarthritis and multiple sclerosis).
Secrecy related to stigma among those with CFS/fibromyalgia declined with increased social support, but this was not apparent among those with other chronic conditions. In addition, posttraumatic growth was lower among women with CFS/fibromyalgia compared to those with other chronic conditions.
Qualitative analysis examining both negative impacts and positive changes stemming from illness experience revealed many similarities between women with CFS/fibromyalgia and those with other chronic conditions, including elevated appreciation for life, personal growth and compassion for others. However, women with CFS/fibromyalgia tended to report less positive change regarding interpersonal relationships compared to women with other chronic conditions.
In general, unexplained illnesses were also accompanied by stigmatization which might ultimately contribute to women’s lower ability to derive positive growth from their illness experience.
Source: McInnis OA, McQuaid RJ, Bombay A, Matheson K, Anisman H. Finding benefit in stressful uncertain circumstances: relations to social support and stigma among women with unexplained illnesses. Stress. 2015;18(2):169-77. doi: 10.3109/10253890.2014.1001975. Epub 2015 Jan 23. https://www.ncbi.nlm.nih.gov/pubmed/25544022
BACKGROUND: Cognitive-behavior therapy (CBT) leads to a reduction of fatigue and pain in chronic fatigue syndrome. The processes underlying the reduction in pain have not been investigated. Recently, it was shown that increased self-efficacy, decreased focusing on symptoms, increased physical functioning, and a change in beliefs about activity contribute to the decrease in fatigue.
OBJECTIVES: The present study has 2 objectives: (1) to determine the relationship between the reduction of fatigue and pain during CBT; (2) test to what extent the model for change in fatigue is applicable to the reduction in pain.
MATERIALS AND METHODS: One hundred forty-two patients meeting United States centers for Disease Control and Prevention criteria for chronic fatigue syndrome, currently reporting pain, and starting CBT were included. A cross-lagged analysis was performed to study the causal direction of change between pain and fatigue. Pain and process variables were assessed before therapy, 3 times during CBT, and after therapy. Actual physical activity was also assessed. The model was tested with multiple regression analyses.
RESULTS: The direction of change between pain and fatigue could not be determined. An increase in physical functioning and decrease in focusing on symptoms explained 4% to 14% of the change in pain.
CONCLUSIONS: Pain and fatigue most probably decrease simultaneously during CBT. Pain reduction can partly be explained by a reduction of symptom focusing and increased physical functioning. Additional, yet unknown cognitive-behavioral factors also play a role in the reduction of pain.
Source: Bloot L, Heins MJ, Donders R, Bleijenberg G, Knoop H. The Process of Change in Pain During Cognitive-Behavior Therapy for Chronic Fatigue Syndrome. Clin J Pain. 2015 Oct;31(10):914-21. doi: 10.1097/AJP.0000000000000191. https://www.ncbi.nlm.nih.gov/pubmed/25503595
All twenty-four cytokines were altered in both long- and short-term patients compared to controls.
Press Release: NEW YORK (Feb. 27, 2015)—Researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health identified distinct immune changes in patients diagnosed with chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease. The findings could help improve diagnosis and identify treatment options for the disabling disorder, in which symptoms range from extreme fatigue and difficulty concentrating to headaches and muscle pain.
These immune signatures represent the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages. Results appear online in the new American Association for the Advancement of Science journal, Science Advances.
With funding to support studies of immune and infectious mechanisms of disease from the Chronic Fatigue Initiative of the Hutchins Family Foundation, the researchers used immunoassay testing methods to determine the levels of 51 immune biomarkers in blood plasma samples collected through two multicenter studies that represented a total of 298 ME/CFS patients and 348 healthy controls. They found specific patterns in patients who had the disease three years or less that were not present in controls or in patients who had the disease for more than three years. Short duration patients had increased amounts of many different types of immune molecules called cytokines. The association was unusually strong with a cytokine called interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus (the cause of infectious mononucleosis). Cytokine levels were not explained by symptom severity.
“We now have evidence confirming what millions of people with this disease already know, that ME/CFS isn’t psychological,” states lead author Mady Hornig, MD, director of translational research at the Center for Infection and Immunity and associate professor of Epidemiology at Columbia’s Mailman School. “Our results should accelerate the process of establishing the diagnosis after individuals first fall ill as well as discovery of new treatment strategies focusing on these early blood markers.”
There are already human monoclonal antibodies on the market that can dampen levels of a cytokine called interleukin-17A that is among those the study shows were elevated in early-stage patients. Before any drugs can be tested in a clinical trial, Dr. Hornig and colleagues hope to replicate the current, cross-sectional results in a longitudinal study that follows patients for a year to see how cytokine levels, including interleukin-17A, differ within individual patients over time, depending on how long they have had the disease.
Stuck in High Gear
The study supports the idea that ME/CFS may reflect an infectious “hit-and-run” event. Patients often report getting sick, sometimes from something as common as infectious mononucleosis (Epstein-Barr virus), and never fully recover. The new research suggests that these infections throw a wrench in the immune system’s ability to quiet itself after the acute infection, to return to a homeostatic balance; the immune response becomes like a car stuck in high gear. “It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” says Dr. Hornig. “Early diagnosis may provide unique opportunities for treatment that likely differ from those that would be appropriate in later phases of the illness.”
The investigators went to great lengths to carefully screen participants to make sure they had the disease. The researchers also recruited greater numbers of patients whose diagnosis was of relatively recent onset. Patients’ stress levels were standardized; before each blood draw, patients were asked to complete standardized paperwork, in part to engender fatigue. The scientists also controlled for factors known to affect the immune system, including the time of day, season and geographic location where the samples were taken, as well as age, sex and ethnicity/race.
In 2012, W. Ian Lipkin, MD, director of the Center for Infection and Immunity, and colleagues reported the results of a multicenter study that definitively ruled out two viruses thought to be implicated in ME/CFS: XMRV (xenotropic murine leukemia virus [MLV]-related virus) and murine retrovirus-like sequences (designated pMLV: polytropic MLV). In the coming weeks, Drs. Hornig and Lipkin expect to report the results of a second study of cerebrospinal fluid from ME/CFS patients. In separate ongoing studies, they are looking for “molecular footprints” of the specific agents behind the disease—be they viral, bacterial, or fungal—as well as the longitudinal look at how plasma cytokine patterns change within ME/CFS patients and controls across a one-year period, as noted above.
“This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in ME/CFS and diagnostic biomarkers for disease,” says senior author W. Ian Lipkin, MD, also the John Snow Professor of Epidemiology at Columbia’s Mailman School. “The question we are trying to address in a parallel microbiome project is what triggers this dysfunction.”
Co-authors include Andrew F. Schultz, Xiaoyu Che, and Meredith L. Eddy at the Center for Infection and Immunity; Jose G. Montoya at Stanford University; Anthony L. Komaroff at Harvard Medical School; Nancy G. Klimas at Nova Southeastern University; Susan Levine at Levine Clinic; Donna Felsenstein at Massachusetts General Hospital; Lucinda Bateman at Fatigue Consultation Clinic; and Daniel L. Peterson and Gunnar Gottschalk at Sierra Internal Medicine. The authors report no competing interests.
Support for the study was provided by the Chronic Fatigue Initiative of the Hutchins Family Foundation and the National Institutes of Health (AI057158; Northeast Biodefense Center-Lipkin).
About Columbia University’s Mailman School of Public Health
Founded in 1922, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. For more information, please visit www.mailman.columbia.edu.
# # #
Media contact: Tim Paul, Columbia University’s Mailman School of Public Health, 212-305-2676 or tp2111@columbia.edu.
Note: You can read the full text of the Columbia study HERE.
Press Release: Mailman School of Public Health, March 30, 2015. Scientists at Columbia University’s Mailman School of Public Health have identified a unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that provides insights into the basis for cognitive dysfunction—frequently described by patients as “brain fog”—as well as new hope for improvements in diagnosis and treatment.
In the study published in Molecular Psychiatry, Mady Hornig, MD, and colleagues used immunoassay testing methods to measure levels of 51 immune biomarkers called cytokines in the cerebrospinal fluid of 32 people with ME/CFS for an average of seven years, 40 with multiple sclerosis, and 19 non-diseased controls. The researchers found that levels of most cytokines, including the inflammatory immune molecule interleukin 1, were depressed in individuals with ME/CFS compared with the other two groups, matching what was seen in a blood study in patients who had the disease for more than three years. One cytokine—eotaxin—was elevated in the ME/CFS and MS groups, but not in the control group.
“We now know that the same changes to the immune system that we recently reported in the blood of people with ME/CFS with long-standing disease are also present in the central nervous system,” says Dr. Hornig, professor of Epidemiology and director of translational research at the Center for Infection and Immunity at the Mailman School. “These immune differences may contribute to symptoms in both the peripheral parts of the body and the brain, from muscle weakness to brain fog.”
Implications for Diagnosis and Treatment
“Diagnosis of ME/CFS is now based on clinical criteria. Our findings offer the hope of objective diagnostic tests for disease as well as the potential for therapies that correct the imbalance in cytokine levels seen in people with ME/CFS at different stages of their disease,” adds W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of the Center for Infection and Immunity.
There is precedent for use of human monoclonal antibodies that regulate the immune response in a wide range of disorders from rheumatoid arthritis to multiple sclerosis. However, the researchers note, additional work will be needed to assess the safety and efficacy of this approach.
The study was supported by a grant from the Chronic Fatigue Initiative of the Hutchins Family Foundation and the Edward P. Evans Foundation.
Additional authors include Andrew F. Schultz, Meredith L. Eddy and Xiaoyu Che at the Mailman School; C. Gunnar Gottschalk and Daniel L. Peterson at Sierra Internal Medicine in Incline Village, NV; and Konstance K. Knox at Coppe Health Care Solutions in Waukesha, WI, and Simmaron Research in Incline Village, NV.
Journal Reference: M Hornig, G Gottschalk, D L Peterson, K K Knox, A F Schultz, M L Eddy, X Che, W I Lipkin. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome. Molecular Psychiatry, 2015; DOI: 10.1038/mp.2015.29
Patients with chronic fatigue syndrome (CFS) report difficulties walking for a prolonged period of time. This study compares gait automaticity between women with CFS and nondisabled controls.
The “stops walking with eyes closed with secondary cognitive task” test is based on the classic “stops walking while talking” test but compares walking with eyes closed while performing a secondary cognitive task in a female CFS population (n = 34) and in female nondisabled controls (n = 38).
When initiating gate, 23.5% of patients with CFS looked toward the ground compared with only 2.6% of nondisabled controls. After 7 m, subjects were asked to close their eyes, and after another 7 m, they were asked, “How much is 100 minus 7?” Of the patients with CFS, 55.9% stopped walking compared with 5.3% of nondisabled controls. Less automated walking was observed in patients with CFS than in nondisabled controls (p < 0.001). The test-retest reliability is moderate for global stopping.
This simple test observed reduced gait automaticity in patients with CFS for the first time. Dual tasking could be helpful to address the functional limitations found in this particular study.
Source: Jan b Eyskens, Jo Nijs, Kristien Wouters, Greta Moorkens. Reduced gait automaticity in female patients with chronic fatigue syndrome: Case-control study. Journal of Rehabilitation Research & Development (JRRD), Volume 52 Number 7, 2015, Pages 805 — 814.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous condition of unknown etiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months.
Recently, two clinical trials of B-cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B-cells has therefore been proposed. Studies of the relative percentages of B-cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC).
In order to explore whether more subtle alterations in B-cell subsets related to B-cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B-cells. The panel utilized IgD, CD27 and CD38 (classical B-cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control, and Fukuda ME/CFS criteria and 32 age/sex-matched HC were included.
We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (p<0.01) and expression (MFI; p=0.03) of CD24 on total B-cells, confined to IgD+ subsets. Within memory subsets, a higher frequency of CD21+CD38- B-cells (>20%) was associated with the presence of ME/CFS (Odds ratio: 3.47 (1.15-10.46); p=0.03) compared with HC and there was a negative correlation with disease duration.
In conclusion, we identified possible changes in B-cell phenotype in patients with ME/CFS. These may reflect altered B-cell function and if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab-therapy.
Source: Fane Mensah, Amolak Bansal, Saul Berkovitz, Arti Sharma, Venkat Reddy, Maria J. Leandro and Geraldine Cambridge. Extended B-cell phenotype in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A cross-sectional study. Clin Exp Immunol. 2015 Dec 8. doi: 10.1111/cei.12749. [Epub ahead of print]
This site uses functional cookies and external scripts to improve your experience.
Privacy settings
Privacy Settings
This site uses functional cookies and external scripts to improve your experience. Which cookies and scripts are used and how they impact your visit is specified on the left. You may change your settings at any time. Your choices will not impact your visit.
NOTE: These settings will only apply to the browser and device you are currently using.
Google Analytics
This website uses cookies that do not collect personal information but that do help us collect anonymous information about how people use our website. We use Google Analytics for this purpose. Google Analytics generates statistical and other information about website usage by means of cookies, which are stored on users’ computers. The information collected by Google Analytics about usage of our website is not personally identifiable. The data is collected anonymously, stored by Google and used by us to create reports about website usage.
