Subscribe to eTOC

An IOM Report Gives a New Name, New Diagnostic Criteria to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

ARTICLE IN BRIEF

F1-1

READ MORE about the IOM report here: http://bit.ly/IOM-CFS

An Institute of Medicine panel has proposed a new name, systemic exertion intolerance disease, and new diagnostic criteria for the condition previously referred to as chronic fatigue syndrome/myalgic encephalomyelitis.

When neurologist Thomas Sabin, MD, FAAN, vice chair of neurology at Tufts University School of Medicine, gives talks at medical conferences on the disease that has until recently been referred to as chronic fatigue syndrome or myalgic encephalomyelitis (ME/CFS), he often begins by asking members of the audience to raise their hands if they believe the condition is a true physical disease.

“Generally, only about half raise their hands,” he told Neurology Today.

That lingering skepticism, despite an estimated 810,000 to more than 2.3 million Americans diagnosed with the condition (and millions more worldwide), accompanied by complex and sometimes competing definitions of disease, prompted a host of federal agencies to task the Institute of Medicine (IOM) with developing evidence-based clinical and diagnostic criteria for it.

The IOM report, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, issued in February, distills the overly broad and complicated definitions of the condition that have emerged over the years into a simple set of core symptoms, and also calls for renaming the disease entirely. [See the sidebar, “New Diagnostic Criteria for SEID.”]

MISUNDERSTANDING OF THE DISEASE

Labeling the cluster of symptoms as chronic fatigue syndrome, the report noted, perpetuates misunderstanding of the disease and a dismissive attitude on the part of both physicians and the public, while myalgic encephalomyelitis is inaccurate, since there is no evidence of brain inflammation in these patients and myalgia is not a core symptom of the disease.

The proposed new name, systemic exertion intolerance disease (SEID), on the other hand, “captures a central characteristic of the disease: the fact that exertion of any sort — physical, cognitive, or emotional — can adversely affect patients in many organ systems and in many aspects of their lives. The committee believes systemic exertion intolerance disease appropriately captures the complexity and severity of the illness.”

The report added that “chronic, frequent and moderate or severe symptoms” are necessary to distinguish SEID from other illnesses. The IOM called for the International Classification of Diseases, 10th Edition to add a new code for SEID that is not linked to either chronic fatigue or neurasthenia (emotional disturbance).

Previous criteria stipulated that the patient could not also be diagnosed with another fatiguing disorder such as fibromyalgia or Lyme disease if they were to receive a diagnosis of what was then known as chronic fatigue syndrome or myalgic encephalomyelitis. The new IOM report acknowledged that these comorbid diagnoses can occur in combination with SEID.

“This is a disease with an extremely bad prognosis,” said Dr. Sabin. “We treat it symptomatically, but if you do long-term follow-ups, people have it almost forever.”

Dr. Sabin said that while varying diagnostic criteria may have led to other conditions from almost every medical specialty to be misdiagnosed as chronic fatigue syndrome/myalgic encephalomyelitis, there is a distinctive history to SEID that should be well captured by the new criteria.

F2-1

DR. BENJAMIN NATELSON: “About 30 percent of chronic fatigue syndrome patients also have fibromyalgia, which was also thought to be all in patients heads. Now theyve come up with three FDA-approved drugs that can be used to treat widespread pain syndrome and fibromyalgia, and now doctors believe its real. Thats why so many of us are working so hard to find biomarkers for this disease, which may also ultimately point to targets for treatment.”

Not all neurologists are convinced the condition exists. “Many patients experience a very negative reception at doctor's offices,” said Dr. Sabin. “I had a neurologist friend who, when a patient called for an appointment and said they had chronic fatigue, said, ‘Maybe you ought to make an appointment with a doctor that believes in it.’”

Benjamin H. Natelson, MD, an emeritus professor of neurology and neurosciences at Rutgers University and a professor of neurology at the Icahn School of Medicine at Mount Sinai, heads up the Pain and Fatigue Study Center at Mount Sinai Beth Israel in New York City and served on the IOM committee that issued the report. Dr. Natelson believes that the new name and straightforward diagnostic criteria will reduce the heterogeneity of diagnosis to some degree. “This will be much easier to use for the practicing physician,” he said.

F3-1

DR. THOMAS SABIN said that while varying diagnostic criteria may have led to other conditions from almost every medical specialty to be misdiagnosed as chronic fatigue syndrome/myalgic encephalomyelitis, there is a distinctive history to systemic exertion intolerance disease that should be well captured by the new criteria.

Dr. Sabin noted that the lack of available treatments, as well as doctors' skepticism, has led unscrupulous individuals to take advantage of people with this disease. “They end up looking at the Internet for treatment, and they find queen bee's jelly [called royal jelly] and all kinds of expensive things,” he said. “I had one patient spending $800 a week on various herbal remedies and exotic plants and whatever. Any disease in which the medical profession is failing offers an opportunity for bad people to do financially rewarding things. I hope that part of what happens with this attention is that it will draw more financial support for good research that can lead to treatments.”

Many other diseases in neurology were once thought to be psychiatric or psychosomatic too, Dr. Natelson noted. “Some of the dystonias, for instance,” he said. “I remember reading that because they happened mostly to young men of Ashkenazi Jewish descent, in the psychoanalytic era it was thought to be related to a problem between the child and his mother. Now we know it's a genetic disorder.”

An available treatment, approved by the US Food and Drug Administration (FDA), can often convince previously skeptical doctors that a disease is legitimate, he added. “About 30 percent of chronic fatigue syndrome patients also have fibromyalgia, which was also thought to be all in patients' heads. Now they've come up with three FDA-approved drugs that can be used to treat widespread pain syndrome and fibromyalgia, and now doctors believe it's real. That's why so many of us are working so hard to find biomarkers for this disease, which may also ultimately point to targets for treatment.”

The IOM committee was hindered in further categorizing and defining SEID by the paucity of data in the current literature. Among the questions that remain to be answered: Is it a homogeneous disorder, or does it have distinct subtypes? What are the underlying mechanisms of its development? What are effective treatments?

“Remarkably little research funding has been made available to study the cause of ME/CFS, mechanisms associated with the development and progression of the disease, or effective treatment, especially given the number of people affected,” the authors noted. And they observed that most studies to date have compared SEID patients with healthy control groups, rather than with patients who have other complex diseases that have fatigue as a distinguishing feature.

“As a result, there are very few data to guide clinicians in distinguishing ME/CFS from other disorders — a major impediment to progress in diagnosing and treating the disease,” the report noted.

Researchers have found that patients previously diagnosed with ME/CFS who did not have any psychiatric comorbidities were more likely to have brain abnormalities than those with such comorbidities. Dr. Natelson's current study, which is being funded by the National Institutes of Health, will conduct triple brain studies on all involved patients: lumbar punctures to assess protein and cell count, MR spectroscopy to study brain chemistry, and neuropsychological testing.

“I believe that this disease has multiple causes, but if through this testing we can find a subgroup that has homogeneous biomarkers, we can make progress in diagnosis and treatment, as well as ending the disbelief of some doctors,” he said.

WHERE THE RESEARCH ON SEID IS FOCUSED

Benjamin H. Natelson, MD, an emeritus professor of neurology and neurosciences at Rutgers University and a professor of neurology at the Icahn School of Medicine at Mount Sinai, is involved in a large, multisite study of the phenomenology of systemic exertion intolerance disease (SEID), funded by the Centers for Disease Control and Prevention, in which approximately 500 patients are being followed.

“It should be easy to determine how many of these study patients diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis under earlier definitions fulfill the Institute of Medicine (IOM)'s new SEID criteria,” he said. “That will be important to know.”

He agreed with the IOM report that more research is needed. One of the most promising paths for SEID biomarker discovery lies in studying cerebrospinal fluid, Dr. Natelson said. “A lot of data point to the brain as the organ involved in this ailment. Blood markers would be easier, but there are too many other proteins involved.”

Dr. Natelson was part of a team of researchers led by Steven Schutzer, MD, an immunologist at Rutgers-New Jersey Medical School, that in 2011 reported finding a unique protein signature in the spinal fluid of patients with chronic fatigue syndrome/myalgic encephalomyelitis that was not present in healthy controls. The study was published in the open access journal PLOS One in 2011. But there were limitations to that study.

“At the time we did it, we needed to pool spinal fluid from over 15 patients in order to have an adequate sample to run in order to discover the proteins, and so we didn't know whether the discrete proteins we found were distributed equally among all participants or concentrated in one or two outliers,” Dr. Natelson explained.

“But now that technology has advanced, we are collecting spinal fluid from another 40 patients and 15-20 controls via a major study being funded by the National Institutes of Health, and we are able to do much smaller pooling — maybe groups of just three or four instead of 15 or more.”

The study is still recruiting patients; at press time, at least 15 more participants were needed. Patients are reimbursed for their time, but must be willing to stop taking all brain-active medications for the duration of the study. To find out more, call 212-844-6665 or go to www.painandfatigue.com.

Gina Shaw

NEW DIAGNOSTIC CRITERIA FOR SEID

The IOM established new diagnostic criteria for systemic exertion intolerance disease (SEID) based on three of these five core symptoms:

  • Reduction or impairment in the ability to carry out normal daily activities, accompanied by profound fatigue
  • Post-exertional malaise
  • Unrefreshing sleep

In addition, diagnosis requires one of the following additional symptoms:

  • Cognitive impairment
  • Orthostatic intolerance

LINK UP FOR MORE INFORMATION:

•. Institute of Medicine report: Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness: http://bit.ly/IOM-CFS
    •. Schutzer SE, Angel TE, Liu T, et al. Distinct cerebrospinal fluid proteomes differentiate post-treatment Lyme disease from chronic fatigue syndrome http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017287. PLoS One 2011;6(2):e17287