Findings from a clinical and laboratory database developed for discovery of pathogenic mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic illness that is often disabling. This paper introduces the Chronic Fatigue Initiative, which conducted a large multi-center study to more fully characterize ME/CFS and ultimately to describe and understand the underlying mechanisms and pathogenesis of this illness. Methods: A total of 203 patients with ME/CFS (cases) and 202 matched healthy controls (HCs) were enrolled from 5 geographically different expert clinical sites to create a well-characterized population linked to a national biorepository. ME/CFS subjects were compared to a one-to-one matched HC population for analyses of symptoms and illness severity. Cases were further evaluated for frequency and severity of symptoms and symptom clusters, and the effects of illness duration and acute vs. gradual onset. Results: This study collected more than 4000 pieces of data from each subject in the study. Marked impairment was demonstrated for cases vs. controls. Symptoms of fatigue were identified, but also, nearly as frequent and severe, were symptoms of cognitive dysfunction, inflammation, pain and autonomic dysfunction. Potential subgrouping strategies were suggested by these identified symptom clusters: sleep, neurocognitive, autonomic, inflammatory, neuroinflammatory, gastrointestinal and endocrine symptoms. Conclusions: Clearly, ME/CFS is not simply a state of chronic fatigue. These data indicate that fatigue severity is matched by cognitive, autonomic, pain, inflammatory and neuroinflammatory symptoms as the predominant clinical features. These findings may assist in the clarification and validation of case definitions. In addition, the data can aid clinicians in recognizing and understanding the overall illness presentation. Framing ME/CFS as a multisystem disorder may assist in developing therapies targeting the multifaceted domains of illness.

Keywords:

• chronic fatigue syndrome
• autonomic
• inflammation
• cohort

Acknowledgements

We wish to thank the Chronic Fatigue Initiative for funding this study and fostering and supporting collaboration among the world's leading medical research, treatment and public health organizations in understanding the causes, therapies and epidemiology of ME/CFS through research grants and collaborative processes across institutions. We thank Scott Carlson, Stella Lee, Peter Wolczynski and Harry Schroeder of CFI for facilitating this project. We also wish to thank our ME/CFS patients and healthy controls who generously gave of their time in order to further research in ME/CFS.

Supplemental data

Supplemental data for this article can be accessed doi:10.1080/21641846.2015.1023652

Additional information

Notes on contributors

N.G. Klimas

Nancy Klimas, MD is a clinical immunologist and director of the Institute for Neuro-Immune Medicine at Nova Southeastern University. She also directs the Gulf War Illness and ME/CFS research program at the Miami VA Medical Center.

G. Ironson

Gail Ironson, MD, PhD is Professor of Psychology (and Board Certified Psychiatrist) at the University of Miami specializing in Behavioral Medicine, the interface between psychological well-being and physical health, coping with chronic illness, and the treatment of trauma.

A. Carter

Aundrea Carter, MS, is a doctoral student studying Educational Research, Measurement, and Evaluation. She serves as a research and evaluation consultant.

E. Balbin

Elizabeth Balbin, with over 20 years of research experience, oversees several research studies as the Clinical Research Director at the Institute for Neuro Immune Medicine, University of Miami, and Miami Veterans Hospital. With a background in immunology, psychology and administration, her professional and academic career takes on a multidisciplinary approach, integrating divergent fields of study.

L. Bateman

Lucinda Bateman is a general internist specializing in the diagnosis and management of chronic fatigue syndrome and fibromyalgia in Salt Lake City, Utah. She also conducts clinical research.

D. Felsenstein

Donna Felsenstein, MD is a senior Staff Physician in Medicine, Division of Infectious Diseases at the Massachusetts General Hospital (MGH). She is Assistant Professor of Medicine at Harvard Medical School and is the medical director of the Sexually Transmitted Disease Unit at the MGH. She has been caring for patients with CFS for more than 35 years.

S. Levine

Susan M. Levine, M.D., graduated from Albert Einstein School of Medicine, completed a residency in Internal Medicine at Montefiore Hospital followed by two fellowships in Infectious Diseases and Allergy and Immunology at Memorial Sloan Kettering Cancer Center and Mt. Sinai Hospital. She currently serves on the Federal Advisory Committee for CFS and remains committed to seeking better treatments for CFS/ME patients.

D. Peterson

Daniel Peterson, MD, is a graduate from the University of Rochester School of Medicine, Rochester, N.Y., in 1976 and was an intern and resident at the University of Utah Medical Center. He has been described as a "pioneer" in the treatment of Chronic Fatigue Syndrome and is the president of Sierran Internal Medicine of Incline Village.

K. Chiu

Korinne Chiu, PhD in Educational Research, Measurement, and Evaluation, served as a database management consultant on this project.

A. Allen

Ali Allen RN, CCRP has 13 years of research experience working with Lucinda Bateman MD in the Fatigue Consultation Clinic in Salt Lake City. During this time she has been clinical lead overseeing multiple research sites in a novel epidemiological study for chronic fatigue syndrome; and primary study coordinator for more than 30 studies on fibromyalgia and chronic fatigue syndrome.

K. Cunningham

Kate Cunningham has her Master's degree in Mental Health Counseling from Boston College. She is currently working as an outpatient therapist in the Boston area, with a focus on working with children and families. Her current interests lay in examining the connection between physical health and mental health.

C.G. Gottschalk

C. Gunnar Gottschalk began working as a Clinical Research Coordinator for Sierra Internal Medicine/Simmaron Research Inc. in July of 2011. He has contributed and co-authored multiple manuscripts in the field of ME/CFS and was lead clinical coordinator for this study. He is currently a medical student at the Graduate College at Rush University in Chicago, IL.

M. Fletcher

Mary Ann Fletcher, PhD is a P.I. and senior scientist in interdisciplinary research on complex multi symptom illnesses funded by the NIH-, VA- and DOD. Fletcher is the Schemel Professor for NeuroImmune Medicine and oversees the proteomic and genomic research at the Institute. She is a member of the Chronic Fatigue Syndrome Advisory Committee that advises the U.S. Secretary of Health and Human Services.

M. Hornig

Mady Hornig, MA, MD is a physician-scientist who directs the translational research programs of the Center for Infection and Immunity at Columbia University Mailman School of Public Health, where she is also associate professor of epidemiology. A board-certified psychiatrist, she has a long-standing interest in how interactions of genes and environmental factors may contribute to the pathogenesis of brain disorders with a potentially immune-mediated component, ranging from autism, AD/HD and PANDAS, to ME/CFS, mood disorders and age-associated cognitive decline.

C. Canning

C. Canning, Principal Associate in Medicine at Harvard Medical School, received her MS and PA-C from Northeastern University. From 1983-2005, she was a member of the research and clinical teams who developed the hematopoietic stem cell transplantation (HSCT) and post-HSCT immunotherapy programs for hematologic malignancies at DFCI. Prior to joining the CDC she served as Technical Director of the DFCI HSCT Program as well as the first Chief of Physician Assistant Services for DFCI.

A.L. Komaroff

A.L. Komaroff is the Simcox-Clifford-Higby Professor of Medicine at Harvard Medical School, and Senior Physician at Brigham and Women's Hospital, in Boston MA. He has spent much of the past 30 years on the problem of ME/CFS, as a clinician and investigator.