Chronic Fatigue Syndrome -- Advancing Research and Education

Addressing ME/CFS

Recently, three important reports about ME/CFS have been published by authoritative agencies.^[1] The Institute of Medicine (IOM) issued a 300-page report in which a panel of physicians and scientists reviewed nearly 9,000 published articles.^[3] They concluded that ME/CFS is a biologically based illness and proposed a new case definition and name (systemic exertion intolerance). The National Institutes of Health (NIH) held a Pathways to Prevention workshop, drawing similar conclusions about the biology of ME/CFS, and the Agency for Healthcare Research and Quality prepared a review of published literature on diagnosis and treatment.^[16,17] The IOM panel concluded that "ME/CFS is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients." Both the IOM and NIH reports conclude that ME/CFS is not primarily a psychological illness, although it might lead to a reactive depression in some patients. Although none of the biologic abnormalities identified in ME/CFS patients are sufficiently sensitive or specific to be used as a diagnostic test, the neurologic and immunologic abnormalities documented emphasize that patients' symptoms are real.

In the absence of a diagnostic test, the IOM report proposes use of a new clinical case definition (Box 2). The new case definition is shorter, easier to apply consistently, and emphasizes that ME/CFS is a diagnosis to be actively made, not simply a diagnosis of exclusion. The IOM report also recommended a new name be considered for the condition: systemic exertion intolerance disease.

It is clear that more basic science research is needed. In September 2015, the NIH intramural program began developing a research protocol to study ME/CFS. The overall hypothesis is that ME/CFS is attributable to an infection that results from immune-mediated brain dysfunction in some patients with acute onset illness. Aim 1 will define the clinical phenotype based on history and physical examination, neurologic assessment, neurocognitive testing, psychiatric evaluation, infectious disease, rheumatologic and neuroendocrine evaluations, and exercise testing. Aim 2 will define the physiologic basis of postexercise fatigue and malaise using functional magnetic resonance imaging, detailed metabolic studies, transcranial magnetic stimulation, and detailed autonomic testing before and after exercise challenge. Aim 3 will determine if there are abnormal immune parameters in the blood and spinal fluid and changes in microbiome profiles. Aim 4 will determine if features of the illness can be reproduced in ex vivo studies using cells or serum from patients and a variety of novel approaches such as induced pluripotent stem cell-derived neurons. Patients will be recruited primarily from well-studied cohorts under the care of clinicians with expertise in diagnosis and management of ME/CFS.

CDC is continuing its efforts to provide evidence-based information about ME/CFS to health care professionals. In 2012 and 2013, CDC partnered with Medscape to present two roundtable discussions that were targeted to primary care physicians. These reached more than 22,000 physicians and more than 6,000 CME credits were issued. CDC provided free online courses about ME/CFS accredited for both physicians, nurses, and other health care professionals. Because the topic of ME/CFS is rarely covered in medical school courses, CDC initiated a project to develop content for the MedEd Portal, a free online service of peer-reviewed content provided by the Association of American Medical Colleges to medical school faculty. To continue communication with the general public and advocacy community, CDC introduced patient-centered outreach and communication calls. These are 1-hour teleconferences held twice a year that are available toll-free in the United States. CDC uses the first 10 minutes to give an update on current activities of the ME/CFS program, and then an outside expert or group of experts presents information on a topic of interest to the community. These are followed by answers to questions submitted to the patient-centered outreach and communication email. Topics have included exercise, infection, and immunity in ME/CFS, ME/CFS and cognitive function, sleep research and ME/CFS, Stanford's research program, and self-management strategies in ME/CFS. Most recently, CDC has begun a new initiative to include broad stakeholder collaboration into developing educational materials. Including the viewpoints of patients, medical professional organizations, medical educators, expert clinicians, and government agencies will help assure the quality and usefulness of these products and facilitate broader dissemination in the medical community. With its demonstrated burden on individual patients and public health, ME/CFS should continue to be an area of active basic science and epidemiologic research, enhanced clinical diagnostic attention and training, and continued outreach, communication, and education.

Box 1. Myalgic encephalomyelitis/chronic fatigue syndrome case history
The patient, aged 37 years, was an internet technologist for a community bank. She had been physically active in sports and working out, and had been maintaining her own household when she experienced a flu-like illness in 2011. She was bedbound at first and slow to recover. Within days she noted an unusual fatigue after minimal activity, then insomnia, achiness in the joints, and generalized muscle pain and weakness. She soon found it difficult to recall recent conversations and events. Reading concentration was limited, and she had trouble comprehending what she had read or even television shows. She would search for words, lose her train of thought, and friends would sometimes have to finish sentences for her. Previously her sleep had always been good, but now she was restless at night and would awaken unrefreshed even after many hours of bed rest. She felt stiff, sore, and foggy for 1–2 hours after awakening. She noted dizziness or lightheadedness on getting up quickly, and on a couple of occasions "saw stars," but did not experience tunnel vision or fainting. The patient was unable to keep up the house, and she had to rely on friends and family to help her with cleaning, laundry, and shopping. She would attempt to keep up at home and at work, but exertion would inevitably make symptoms worse, and if she exerted too much she would end up sick and chairbound for 1–2 days afterward. Evaluation by her primary care physician revealed low blood pressure, but there was no immediate orthostatic blood pressure drop and otherwise the examination was unremarkable. Blood work was unremarkable. Having no explanation for her symptoms despite the profound reduction in her physical abilities, the patient became anxious about her future and both frustrated and discouraged.

Box 2. Institute of Medicine criteria for diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome
Patient has each of the following three symptoms at least half of the time, to at least a moderately severe degree: A substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social, or personal activities that persists for >6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest. Postexertional malaise* Unrefreshing sleep* Plus at least one of the two following manifestations (chronic, severe): Cognitive impairment* Orthostatic intolerance
Source: Institute of Medicine. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, D.C.: The National Academies Press; 2015. https://www.nationalacademies.org/hmd/reports/2015/me-cfs.aspx *Frequency and severity of symptoms should be assessed. The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.