Scientists Discover Robust Evidence That Chronic Fatigue Syndrome Is a Biological Illness

For those who missed Mady Hornig's talk at the P2P Workshop, the press release below announces the research she discussed. 

Essentially, what the researchers found was an upregulated immune response in ME/CFS patients ill for three years or less, followed by "immune exhaustion." (You can read a summary of her talk HERE. It's half way down the page.)

This research supports Dr. Cheney's early hypothesis that an infectious agent causes increased cytokine production (he focused on interferon alpha), which in turn led to excitotoxicity in the brain. It also supports Dr. Bell's one-two punch theory, in which an original insult sets the stage for immune dysregulation and chronicity.

The Columbia findings not only help establish a natural history of the disease, they also support the theory that the driving mechanism for the illness is CNS inflammation. When cytokines are released in the brain, due to injury or infection, they stimulate microglial activation, which in turn produces inflammation. The recent PET scan study by Nakatomi et al. which found neuroinflammation in the brains of ME/CFS patients due to microglial activation dovetails neatly with the Columbia study. Previous studies conducted by Stanford and other researchers which have found brain abnormalities, implicate CNS inflammation as the underlying driver of symptomatology as well.

You can read the full text of the Columbia study HERE.
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Immune Signatures in Blood Point to Distinct Disease Stages, Open Door to Better Diagnosis and Treatment

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.

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Media contact: Tim Paul, Columbia University’s Mailman School of Public Health, 212-305-2676 or tp2111@columbia.edu.

The IOM Report: The Good, The Bad, and the Absolutely Hideous

Note: I have read the entire report, and I have also looked at the references. Page numbers are listed throughout the commentary below.

Anyone who would like to reprint this post has my permission.

The IOM Report, "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" was released on Tuesday February 10, 2015. (You can read and/or download the report as well as watch the video of the announcement HERE. You can get the gist of the report by reading the Summary at the beginning, or Recommendations on page 209.)

Much like its previous report on Gulf War Illness, the IOM's report on ME/CFS has generated a tremendous amount of media coverage (Time, CBS, NY Times Blog, ABC), as well as spirited discussion in the ME/CFS community. While mainstream organizations have welcomed the report's emphasis on the serious nature of the disease, there are some lingering doubts about the appropriateness of the new name, "systemic exertion intolerance disease" (SEID), as well as the viability of the new definition.

The report made four recommendations:

Recommendation 1: Physicians should diagnose myalgic encephalomyelitis/chronic fatigue syndrome if diagnostic criteria are met following an appropriate history, physical examination, and medical work-up. A new code should be assigned to this disorder in the International Classification of Diseases, Tenth Edition (ICD-10), that is not linked to “chronic fatigue” or “neurasthenia.”

Recommendation 2: The Department of Health and Human Services should develop a toolkit appropriate for screening and diagnosing patients with myalgic encephalomyelitis/chronic fatigue syndrome in a wide array of clinical settings that commonly encounter these patients, including primary care practices, emergency departments, mental/behavioral health clinics, physical/occupational therapy units, and medical subspecialty services (e.g., rheumatology, infectious diseases, neurology).

Recommendation 3: A multidisciplinary group should reexamine the diagnostic criteria set forth in this report when firm evidence supports modification to improve the identification or care of affected individuals. Such a group should consider, in no more than 5 years, whether modification of the criteria is necessary. Funding for this update effort should be provided by nonconflicted sources, such as the Agency for Healthcare Research and Quality, through its Evidence-based Practice Centers process, and foundations.

Recommendation 4: The committee recommends that this disorder be renamed “systemic exertion intolerance disease” (SEID). SEID should replace myalgic encephalomyelitis/chronic fatigue syndrome for patients who meet the criteria set forth in this report. [Italics mine throughout]

Some Background: The IOM's Charge

The IOM is an independent nonprofit organization founded in 1970. As health arm of the National Academy of Sciences, it works outside of the federal government to provide "unbiased and authoritative advice" to decision makers and the public. Because it is not part of the federal government, its decisions to not constitute policy. No branch of HHS is obliged to follow its recommendations.

In 2013, HHS contracted the IOM to evaluate the current criteria for diagnosis of ME/CFS and recommend clinical diagnostic criteria that would "address the needs of health care providers, patients, and their caregivers."

Specifically, the committee was asked to:

• conduct a study to identify the evidence for various clinical diagnostic criteria for ME/CFS using a process with input from stakeholders, including practicing clinicians and patients;

• develop evidence-based clinical diagnostic criteria for ME/CFS for use by clinicians, using a consensus-building methodology;

• recommend whether new terminology for ME/CFS should be adopted; and

• develop an outreach strategy for disseminating the new criteria nationwide to health professionals.

The committee was also asked to distinguish among disease subgroups, develop a plan for updating the new criteria, and make recommendations for the plan’s implementation.

With the exception of the CAA (now Solve ME/CFS Initiative) the immediate reaction to the million-dollar IOM contract was negative. Fifty of the world's leading experts in ME/CFS wrote a letter to then Secretary of HHS Kathleen Sebelius endorsing the Canadian Consensus Criteria (CCC) a definition based on "scientific knowledge gained from decades of research. " The letter also warned that the contract "would move ME/CFS science backward by engaging non-experts in the development of a case definition for a complex disease about which they are not knowledgeable." (You can read the letter HERE.) The letter was supported by hundreds of advocates, as well as petitions which garnered 10,000 signatures.

Analysis in a nutshell

Pros:

• The report clearly states that ME/CFS is a complex a "serious, chronic, complex, multisystem disease that frequently and dramatically limits the activities of affected patients.

• The report recommends abandoning the name "chronic fatigue syndrome."

• The report recognizes that research funding has been inadequate.

Cons:

• The report recommends a definition that is simplistic, undermining the statement that ME/CFS is a "complex, multi-system disease."

• By limiting diagnosis to four or five non-specific symptoms, the IOM definition, like the Fukuda definition, will capture people without ME/CFS.

• The core symptoms of the new diagnosis fit into the clinical definition for depression (fatigue, insomnia) with anxiety (symptoms made worse by stress).

• Exertion intolerance has been, and will be, interpreted by physicians as a psychosomatic manifestation of "fear avoidance" of exercise.

• The name "systemic exertion intolerance disease" reduces ME/CFS to a single symptom.

• The inclusion of "systemic" in the name is meaningless. All diseases are systemic.

• Exclusionary diagnoses are no longer ruled out, which means patients with early MS, Hashimoto's, lupus, mitochondrial disease, Ehlers-Danlos and other treatable but hard-to-detect illnesses may receive a false diagnosis of SEID.

In-depth analysis of the report

The Good

Excellent overview of the research

On the whole, the report did a very good job of discussing the research pertaining to diagnosis, subgroups, symptoms clusters, as well as documenting key problems such as lack of funding for research, and inadequate coverage in medical schools. Anyone taking the time to read the entire report would have a clear view of the types of problems faced by the ME/CFS community. (One of those problems is the constant confusion between "chronic fatigue" and CFS, a problem which the IOM perpetuated by citing studies on "chronic fatigue.") 

Abandonment of chronic fatigue syndrome

After a healthy discussion of all the reasons why CFS is a poor name for the disease, the IOM concluded that "the term 'chronic fatigue syndrome' often results in stigmatization and trivialization and should no longer be used as the name of this illness" (p 60).  The report goes on to say that "ME/CFS should not be considered merely a point on the fatigue spectrum or as being simply about fatigue. [...] Other factors, such as orthostatic intolerance, widespread pain, unrefreshing sleep, cognitive dysfunction, and immune dysregulation, along with secondary anxiety and depression, contribute to the burden imposed by fatigue in this illness."

Recognition of 2-day CPET as an objective measure of ME/CFS

The IOM report recognizes PEM as one of the defining characteristics of ME/CFS (though the report also mentions that PEM is experienced by patients with MS and major depression). Citing the Keller and Snell studies, the report supported the 2-day CPET protocol "as an objective indicator that physical exertion may decrease subsequent function in some ME/CFS patients. By contrast, a single CPET may be insufficient to document the abnormal response of ME/CFS patients to exercise" (p 84).

Recognition of cognitive impairment and brain abnormalities

The IOM reviewed the past ten years of research on neurocognitive impairment and brain abnormalitites, and did a credible job of summarizing them. While the IOM did not draw any conclusions from the brain studies it examined (including the recent Nakatomi study on brain inflammation, but omitting the Stanford study) the committee did state that "There is sufficient evidence that slowed information processing is common in patients with ME/CFS, and a growing body of evidence shows that it may play a central role in overall neurocognitive impairment associated with the disease. Such a deficit may be responsible for the disability that results in loss of employment and loss of functional capacity in social environments" (p 106).

Recognition of immune dysfunction

After a review of NK cell toxicity and immune activation studies the IOM concluded that "Sufficient evidence supports the finding of immune dysfunction in ME/CFS" (p 153).

Acknowledgment of pediatric ME/CFS

"There is sufficient evidence that orthostatic intolerance and autonomic dysfunction are common in pediatric ME/CFS; that neurocognitive abnormalities emerge when pediatric ME/CFS patients are tested under conditions of orthostatic stress or distraction; and that there is a high prevalence of profound fatigue, unrefreshing sleep, and post-exertional exacerbation of symptoms in these patients. There also is sufficient evidence that pediatric ME/CFS can follow acute infectious mononucleosis and EBV" (p 201).

Recognition that research funding has been inadequate

"Remarkably little research funding has been made available to study the etiology, pathophysiology, and effective treatment of this disease, especially given the number of people afflicted" (p 9).


The Bad: Non-Specific Definition

The IOM report sends mixed messages to medical professionals. On the one hand, it states that ME/CFS is a "serious, complex" disease. But on the other, it presents diagnostic criteria that are oversimplified, giving the impression that this is not a serious, much less potentially fatal, illness. Of the two messages, the second will have the greater weight. Regardless of the encouraging language used in the report, medical professionals are much more likely to read a short definition than a 282-page document.

The new IOM definition is a highly reduced version of the Canadian Consensus Criteria, consisting of three non-specific (i.e. common to many illnesses) required symptoms, and two non-specific optional symptoms. Because it consists of non-specific symptoms, the IOM definition will capture a number of illnesses in addition to ME/CFS, making it useless for research and too broad for diagnosis. (This is precisely the problem with the Fukuda definition.)

IOM Definition

Diagnosis of ME/CFS requires that a patient have the following three core symptoms:

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of activities that persists for more than six months and is accompanied by fatigue - which is often profound - of new or definite onset, not the result of ongoing excessive exertion and not substantially alleviated by rest 
2. The worsening of patients’ symptoms after any type of exertion - such as physical, cognitive, or emotional stress - known as post-exertional malaise 
3. Unrefreshing sleep

At least one of the two following manifestations is also required:

1. Cognitive impairment 
2. The inability to remain upright with symptoms that improve when lying down - known as orthostatic intolerance

Fatigue

The first symptom is still six months of fatigue. The IOM report states, "This 6-month requirement is supported by Nisenbaum and colleagues (1998), who showed that unexplained fatigue lasting for more than 6 months was related to symptoms included in the ME/CFS case definitions and that most other causes of similar fatigue do not last beyond 6 months." This implies that most cases of "similar fatigue" are self-resolving. In fact, the Nisenbaum study did not find that similar fatigue from other causes resolved within six months, because other causes of fatigue were not explored. The only conclusion Nisenbaum et al. reached was that six months appeared to be a "threshold" for severity of CFS symptoms. However, their data indicated that this threshold was relatively modest, with percentages varying only slightly between the 1-5 month range and the 6-month or longer range. 

Nevertheless, six months of "fatigue" is still required, which will miss all the sudden onset cases. This is problematic, because the initial "acute" phase of the disease is what is most puzzling to physicians. Patients who come to their doctors horribly ill several weeks after a "flu" are taken seriously, because the acute phase is quite dramatic. This is the phase in which test results (including ECGs and CBCs) are often abnormal, and in which physicians write prescriptions for numerous medications, none of which help and many of which harm patients. A case definition for a disease that can develop with such speed and severity should include a provision for sudden onset.

Ultimately, six months of fatigue is still the predominant symptom in this definition, and because there are so few others, physicians will retain "chronic fatigue" as the go-to symptom for diagnosis. And because chronicity is established after six months, it is likely that physicians will dismiss patients with long-term fatigue who do not have measurable signs (and who complain of non-specific symptoms) as having psychological disorders.

PEM

The second symptom, PEM, will inevitably be interpreted as "exercise intolerance" by physicians. Exercise intolerance is a term that physicians understand, as it is commonly used in association with cardiopulmonary illnesses. Physicians may also interpret PEM as "avoidance of exercise," which, when combined with fatigue, sleep disorder, and cognitive problems (the result of lack of sleep) will lead them to think that a patient presenting these symptoms needs therapy or antidepressants.

PEM is non-specific. Contrary to popular belief, PEM is not unique to ME. Patients with early MS, B12 deficiencies, Hashimoto's disease, and lupus all experience a worsening of symptoms after exertion. Regardless of the severity and permutations of PEM, physicians will not investigate the fine points. Nor will they ever consider a worsening of symptoms after emotional or cognitive stress to be anything other than psychosomatic.

Doctors are taught in medical school to look for horses, not zebras, "horses" being common ailments, and "zebras" the more exotic or rare illnesses. In 2008, Drs. Philip R. Fischer, Jonathan N. Johnson, and Chad K. Brands wrote an an excellent article titled, "Fatigue, Exercise Intolerance, and Weakness: Lessons on Herding Zebras" in which they presented case studies demonstrating why physicians need to look beyond the obvious diagnosis. Of three pediatric cases in which the patients presented with typical symptoms of CFS, one had POTS, one had pheochromocytoma (benign adrenal tumor), and one had undiagnosed dermatomyositis (an inflammatory disease). All of these patients would meet the criteria for SEID.

Unrefreshing Sleep

Waking up tired, even after what may be considered adequate sleep, is universal in ME/CFS.  It is also common in hypothyroidism, low adrenal function, fibromyalgia, narcolepsy, Lyme disease, allergies, sleep apnea and depression. Most doctors seeing a patient with the triumvirate of fatigue, unrefreshing sleep, and cognitive problems will conclude that the patient has depression, especially if standard blood tests are negative. The addition of "exertion intolerance" does not exclude depression, or distinguish ME/CFS from any number of illnesses in which an exacerbation of symptoms after exertion is a feature.

Cognitive Impairment and OI

The IOM included cognitive impairment as an optional symptom, even though "Impairments in cognitive functioning are one of the most frequently reported symptoms of ME/CFS" (p 96). Why cognitive impairment is optional is not clear, as it is one of the cardinal symptoms of ME/CFS.

Orthostatic intolerance was also included as an optional symptom, which is also puzzling. OI is usually included under autonomic dysregulation, which can also include other symptoms, such as migraine, temperature and blood pressure fluctuations, and other manifestations of autonomic dysfunction, all of which are found in patients with ME/CFS. There is also a tremendous overlap in symptoms between POTS (postural orthostatic tachycardia syndrome - the most common form of dysautonomia), and ME/CFS. (Anyone with POTS will fit the IOM definition of SEID, and vice versa,)

Although the committee did not examine etiology, they would have greatly benefited from reading Dr. Jay Goldstein's book, The Limbic Hypothesis, in which he theorizes (with substantial evidence) that injury to the limbic system causes the symptoms of ME/CFS. The hypothalamus, which controls the autonomic nervous system, is located in the limbic system. It is a tiny organ, easily damaged by high fevers, hypoxia, and neurotoxins, It would have aided the IOM to understand some of the major theories behind the symptoms that they chose to include in their definition, even if it was not part of their charge. As the experts predicted, the IOM lacked "the needed expertise to develop “clinical diagnostic criteria” for ME/CFS."

Pain

The IOM stated that "Pain is a defining characteristic of ME/CFS ... The majority of ME/CFS patients experience some type of pain" (p 141). However, it rejected pain as a core symptom because of the "less prominent role of myalgia in these patients relative to more core symptoms" (p 11). In making this statement, the IOM is overlooking their own research review. According to the studies the IOM reviewed, pain appeared with equal frequency to core symptoms.

The ultimate reason for rejecting pain was "while pain worsens ME/CFS when present, there is no conclusive evidence that the pain experienced by ME/CFS patients can be distinguished from that experienced by healthy people or those with other illnesses. Further, pain may be experienced in many areas, and while comprehensively assessing a patient’s pain symptoms is a challenging task, it is not specific to ME/CFS" (p 147).

Rejecting pain because it is non-specific ignores the fact that fatigue, exertion intolerance, sleep disorder, and the two optional symptoms are also not specific to ME/CFS. It also exhibits a failure to understand the basic physiology of pain. All pain is processed via the same neurological pathways, regardless of whether it is experienced by healthy people, or by people who are ill. Pain is a universal, and completely subjective, indicator that something is wrong in the body. The fact that so many people with ME/CFS experience pain cannot, and should not, be overlooked. To those who cannot escape it, the constant intractable pain of ME is an unbearable symptom, and can lead to addiction to painkillers, and, in some cases, suicide. Failing to include it as a significant feature of the illness basically relegates pain to "it's all in your head" (which, ironically, it is).

Exclusionary diagnoses not ruled out

Another major problem with the new criteria is that exclusionary diagnoses are no longer ruled out. Dr. Clayton was correct when she stated that there is nothing that says you can't get two conditions at the same time. You can have ME and hypothyroidism, or ME and cancer. Although Dr. Clayton was right in her assertion, a problem arises when you combine a lack of exclusionary diagnoses with a definition that requires only four non-specific symptoms. When patients present with these four symptoms, one of which is common to all diseases (fatigue), AND there is no requirement that illnesses that match those symptoms (leukemia, Hashimoto's, Ehlers-Danlos, MS, lupus) be ruled out, there is the danger that patients who are "zebras" will be misdiagnosed.

There is also the strong probability that patients with major depression (MD) will be simultaneously diagnosed with SEID, which will be a roadblock for researchers as well as patients. Depression is a catchall for busy physicians who are presented with patients who primarily report fatigue and sleep disturbance. (And when their doctors ask, "Do you exercise regularly?" sleep-deprived patients usually say, "No, I am too tired.") As a number of studies have shown, patients with MD do not test the same as patients with ME/CFS. Because MD is not excluded from the diagnostic criteria, and because, like ME/CFS, there is no biomarker for depression, these patients will be included in studies. Some will then be shown to improve with exercise and therapy. (But not all. Because depression is a symptom of many underlying illnesses - hypothyroidism, autoimmune disease, cancer, diabetes - patients diagnosed with depression don't necessarily improve with exercise, therapy, or antidepressants.) Meanwhile, patients with ME will mistakenly be given antidepressants, which will only make them worse.

To prevent medical mismanagement of ME any diagnostic criteria must exclude major depression. And to secure appropriate treatment for diseases that are treatable, illnesses with similar symptoms must be ruled out.

Pediatric definition same as adult definition

It is a mistake to use the same definition for children and adults.

Pediatric ME is not the same as adult ME. Hypersomnia (sleeping round the clock) is more common in children than in adults. Symptoms present in equal severity (particularly stomach and headaches). Listlessness, ADD-like symptoms, double vision and other visual disturbances. and fever are also more common than in adults. Because their immune systems are ramped up, flu-like symptoms persist for much longer in children than in the adult population. All of these symptoms are easily observed by parents.

Six months of undiagnosed illness in a child can be devastating. It is also crushing to children when adults accuse them of "making up" their illness. The consequences of disbelief on the part of medical professionals and officials are that children are maligned and dismissed, and possibly removed from their homes to be placed in psychiatric institutions or foster care, where they are forced to suffer exercise and deprivation regimes that only make their illness worse. Any definition of ME for children needs to take all of those factors and risks into account.

Bottom line

The IOM has described ME/CFS as a "serious, chronic, complex, multisystem disease," therefore it cannot, by its own description, reduce that "serious, complex" disease to four or five symptoms. To do so is a great disservice to the patients whose lives have been, and will continue to be, ruined by doctors who do not understand the illness, in part due to vague definitions.

What the IOM Should Have Done

Rather than invent a new definition, the IOM should have operationalized the algorithm devised by Jason's group, which has been tested and can identify patients with ME/CFS with 90% accuracy. The algorithm can be easily used by physicians as an initial screening tool once treatable conditions have been ruled out.

The second step in the diagnostic process should be the Canadian Case Definition, which not only provides enough detail to assess the illness, but utilizes the DePaul Symptom Questionnaire (DSQ) for additional information on severity and frequency of symptoms.

Until such time as we have a generally accepted biomarker, researchers should also rely on the CCC. It has been used in research for years, and has a verifiable track record.

The Absolutely Hideous

If the IOM failed in its charge to define the illness, it crashed and burned where naming it is concerned. Systemic Exertion Intolerance Disease is a name that means nothing. It is inappropriate, not just for this illness, but for any illness, for the following reasons:

1) All diseases are systemic, therefore the inclusion of "systemic" is meaningless. (The immune system, the endocrine system, and the nervous system all share cell receptors. Anything that affects one will affect the other two.)

2) "Exertion intolerance" will inevitably be translated into the more familiar term "exercise intolerance," which is seen in a number of illnesses. "Exertion intolerance" in this instance will be interpreted as either deconditioning or an "aversion" to exercise by general medical practitioners.

In addition to being useless, "SEID" represents a complete lack of familiarity with how diseases are normally named. Illnesses can be named according to a variety of traditions:

• Place where the  illness was first identified: ex. Lyme Disease, Gulf War Illness
• Person, or people, who first described the illness: ex. Guillain-Barre, Alzheimer's
• Major organs or systems affected: ex. kidney disease, heart disease
• Primary mechanism or process: ex. muscular dystrophy
• Famous person with illness: ex. Lou Gehrig's
• Historical continuity: ex. Malaria (which means "bad air")

Illnesses are never named after a single non-specific symptom. If they were, we would have Coughing Disease, Diarrhea Disease, Itchy Skin Disease. Naming this illness after a non-specific symptom is what has caused so much damage over the past three decades. "SEID" repeats the error, reducing an illness that is complex, of unknown or varied etiology, and with no generally accepted biomarker to a single non-specific symptom. "Exertion intolerance," in this context, is no better than "fatigue,"

(For those who are keeping track, this is the IOM's second naming fiasco in recent memory. The first was in 2012 when it re-named Gulf War Illness - another complex illness without an accepted biomarker - as "chronic multisymptom illness." Objections raised to that name ultimately culminated in a retraction.)

What the IOM Should Have Done

There were two viable options open to the IOM for naming this disease.

1) Keep the historical name myalgic encephalomyelitis. This would have lent continuity to both research and diagnosis. And, in spite of all protestations to the contrary, the name is accurate. The IOM itself stated that pain is "a defining characteristic of ME/CFS" (p 141). There is also clear evidence of CNS damage.

2) Call it Ramsay's Disease. This would have honored the first person to extensively describe, and treat, the illness, Dr. Melvin Ramsay, as well as putting to rest to all the arguments about whether there is or is not inflammation in the brain.

Other options (such as picking a few prominent symptoms out of the pile. e.g. "systemic-fatigue-sleep-disorder-exercise-intolerance-cognitive-impairment-disease") are not practical or medically accurate and should not be considered.

In sum: Be careful what you wish for

For decades patients and ME/CFS specialists have complained about the derogatory name "chronic fatigue syndrome." The discussion of what to call this disease has raged since the term CFS was first coined in the 1980s, leading many people to assume that no matter what you called this illness it had to be preferable to CFS. "Get rid of CFS," they said. "Anything is better."

Now we have a new name, and it is no better - possibly even a little worse - than CFS.

For years, physicians and researchers have said that the Fukuda definition is too broad, and captures patients with other illnesses. They devised a new definition, the CCC, which they used for 10 years. But, it was "too long." Now we have a new definition that is even more non-specific than the Fukuda definition, and, because the IOM does not rule out illnesses with overlapping symptoms, it will capture even more people without ME, making it useless for both diagnosis and research.

The IOM has lived up to the phrase "A camel is a horse designed by a committee." In the attempt to reach a consensus among bureaucrats, stakeholders and physicians, it has designed an ungainly beast.

To quote Jim Binns (chair of the Research Advisory Committee on Gulf War Veterans' Illnesses) after the IOM similarly failed in its charge to define GWI, "The conclusions of the report show that it was a waste of money. The committee never had the expertise or the process to do a case definition."

The King and Martin: A Boy With ME Writes the King of Norway

Will King Harald listen to the children?

This touching letter was originally posted on fryvil.com. Reprinted with permission.


It is hard enough when adults are dismissed, but it is beyond cruel when children, who have no defenses against adults, are accused of “making up” their illness.

_____________________




Letter to King Harald of Norway from Martin and 58 other young people with M.E.

ME mum’s confessions proudly presents an important letter to King Harald from Martin (17). The letter is also signed by 58 other children and youngsters with M.E. (Norwegian original)

A shortened version of the letter was published in the leading Norwegian newspaper aftenposten.no and was also in the printed paper. In the paper, this was an important contribution to the ongoing debate on M.E. We recommend reading the full version. Both the letter and the following quotes make a strong impression.

In addition to the letter, the King received all the senders’ names and how long they’ve been sick, a list of 47 quotes and 5 pages with photos of the young ones. We have chosen to remove personalia here. The original was sent to the royal castle December 7th 2014.

Martin has important things to say, and we hope that he, and the other children, will receive a reply from the King.

____________________

Dear King Harald,


I write to You because You are our King and have shown that you care about the weak in our society. I also know that you are concerned about children’s and young peoples’ situation in Norway. I write primarily on behalf of my brother and me, but also for many other children and young people suffering from the disease M.E. or myalgic encephalopathy. Having lived with this disease most of my life, I increasingly ask myself the question:

Is Norway really the best country in the world to live in for everyone?

Living with M.E. is a terrible situation by itself, but that’s not why I’m writing to you. I write because especially children with M.E. and their parents today are terribly distrusted and misjudged

M.E. is a very severe disease that affects the entire body, but unfortunately it’s cause has not yet been found. The only thing that helps is to have peace, caring people and symptom-relieving drugs. Yet, today it is regarded by CPS that the disease is caused by over-protection by the mother. Yes, hard to believe, mom, who always takes the right considerations and tends to us when we are at our worst, and that is not an easy task…

We in our family have so far been through two CPS cases and both have fortunately been closed without action. Our mom is a doctor and this might have been of help, but what a burden this has been to all of us. It is hard to fight against people who don’t understand and only have faith in child protection proceedings and care orders.

(This was as far as I got when I started to write a letter to You two years ago. Since then I gradually have become worse, and I have understood that there are many other children and young people with M.E. who are struggling with the same problems as I am. So now I want to continue on the letter and hope I manage to finish it this time.)

I would like to tell you a little about what I’ve learned about M.E.

M.E. is a very complex disease that affects many children and young people in increasing numbers. One assumes that approximately 2,000 children under the age of 18 are affected by this disease in Norway. There are often several who become ill in the same family, as my brother and me. Actually, our mom is also a M.E. sufferer.

This is a disease that «does not take your life, but robs it”, because the body somehow does not allow you to live your life anymore. There is almost nothing you can do without the body becoming overloaded and more ill. It can be compared to training resistance or a «blasted horse».

There are unfortunately many who don’t understand this disease. They think that because they can’t find anything wrong in the normal tests, we are not really ill. Some even say that M.E. is a disease from which you can think yourself better or even healthy.

Luckily, there are many researchers especially abroad who are investigating what happens in the body of M.E. patients and they find many changes, especially in the brain. Most are now convinced it is a form of encephalitis or autoimmune disease and because many with M.E. are very ill, a researcher has called the disease «non-HIV AIDS.» I think this is a good description, because our body feels so fragile that it can almost not tolerate anything. Some are actually so ill that they have to live completely isolated in dark rooms, almost like living deads.

Initially my illness felt like having «chronic flu» with many infections and body aches. I almost never felt really fit. In addition I wasn’t able to do much, and got tired much more rapidly than other children. I also had trouble falling asleep and getting up in the morning, and even then I never felt refreshed. As the time has passed, I’ve got more and more symptoms and my body feels as if I should be very old.

At Haukeland hospital [in Bergen, Norway] some people do research using a cancer medicine as treatment for M.E., but the research will probably take a long time. So for now, we have to live with a disease for which there is no effective treatment.

What is the worst?

The worst thing about having M.E. is not just that you are deprived of your old life and must live most of the life at home and be cared for by your parents. I think actually it’s even worse when we experience not to be believed when we tell we are ill and feel it in our body. It is insulting not to be taken seriously, especially when the doctors do not want to listen to us, but rather tell us what they think about this disease. I sometimes wish that these doctors could feel in their own bodies how we are feeling, before they begin to speculate, judge and make theories about our disease.

I think it’s terrifying when the leading physician for M.E. children in Norway says that he believes our brains are hung up in a stress reaction and that the brain must have «gone in deadlock». I don’t think there are many doctors abroad with knowledge about this disease who believe that. Such statements feel very offensive!

A few years ago, my hospital doctor recommended me a 3-day «quick-fix course» for recovery, I should just change my thoughts and decide to stay healthy. This course is called LP or the Lightening Process. Although I had no particular wish to attend to the course, I felt pushed and participated together with my mom. It was a strange experience to be there and be asked to tell myself over and over again that I was healthy even though I was not. At the course I was also told that it was my own fault if I failed to get well, which I think was a very serious accusation. It amazes me, therefore, that this course is recommended by Norwegian doctors. I know that there are several who have become much worse after these courses, and there have also been suicides. Not long ago, a 13 year-old boy was rescued after a suicide attempt because he felt guilty after taking the LP course without getting well.

School and friends

Getting to school has been a big challenge for me, and it’s been years since I’ve been able to get there. The same goes for my brother. This is not only because we are too weak and get worse by overdoing, but also because our brains suffer from cognitive dysfunction. I know some children with M.E. manage to attend a few hours of school and some manage to have home schooling. That depends on how affected you are by the disease.

It is sad not to be able to live normally and sometimes I miss my friends. But when I’m as ill as I am now, I can’t think so much about this, since I have to save my strength just to survive. I use all my energy to eat and sleep and rest. And that’s hard enough when my body not will cooperate. When I have a lot of pain, I can hardly think of anything else. But luckily I have my brother who is also ill. We understand each other and can do pleasant things together when we are able to. It’s probably a lot worse for those who are suffering alone.

In a way we are lucky to have become ill in the «cyberage» because then we have television and the internet where we can learn a lot and be a little social without too much efforts. There is also a separate forum for M.E. suffering children and youths on Facebook. It is important to find others who understand, because after I became ill with M.E., very few of my previous friends have cared much about me. Instead, I have become close to a few friends and especially to my family, and to me that is equally valuable. It has been an important lesson to discover who my real friends are and I don’t think it’s so important to have many friends as long as you have someone who really cares.

On the positive side, I will also mention that since life has become a bit quiet, I have got more time to think about what really matters in life and I have become more engaged in human values. I have got more time to reflect deeply than many other youths who are often constantly stressed since they have too much to do. In good periods I get the time to delve into things that really interest me and thus I learn a lot in spite of my condition. I hope that I someday may use what I have experienced as ill out in the society.

The future

I must admit that I’m very worried about the future. Not only because of my health, but I am seriously afraid that the Norwegian society will not give M.E. sufferers like my brother and me the opportunity to have dignified lives as adults. When the society constantly focuses on the work-line and that it shall pay off to work, that signals little compassion and respect for those who actually are not able to contribute. I simply miss a more human and fair society.

My mom does a great job along with several other M.E. mums making the M.E. disease better known. They have formed an “M.E. mum group” which has the blog fryvil.com and they have written several letters where they complain about how badly we are met and treated both in health care and society. My letter to You have been presented in the M.E. mom group and 58 of their children and adolescents with M.E. personally support this letter. These other young ME sufferers have contributed to the letter with an attachment containing their own quotations and pictures of themselves to illustrate the disease.

My intention with this letter has been to describe for You the worrisome situation M.E. suffering children and youngsters’ experience in Norway. It is my hope that You will help us to achieve a better understanding and respect in the Norwegian society for this highly misunderstood disease. Then perhaps Norway one day could become the best country in the world to live in, also for M.E. patients?

Finally, I will use this opportunity to wish You and Your family a Merry Christmas and a Happy New Year!

Yours sincerely,
Martin Qvist Giercksky
(age 17, ME sufferer for 8 years)

Copies for:
Prime minister Erna Solberg
Minister of Health Bent Høie
Minister of Children, Equality and Social Inclusion Solveig Horne
Minister of Education and Research Torbjørn Røe Isaksen
Leader of the Labour Party Jonas Gahr Støre
The Ombudsman for children’s rights, Anne Lindboe
The Norwegian ME Organisation

Attachment 1 – Quotations

Quotes from the 58 ME children and youth that support the content of the letter to King Harald:

”I don’t really remember what it is like to be healthy any more.” (girl, 15, with ME)

”I wish that some of those who think I should do more than my body can manage, get a sick child too, then they would understand what it is like for me. – But then I don’t wish anybody to suffer like I do.» (Boy 12, with ME)

”I was at school today. School is the best for me. At school I feel different than at home. I don’t feel sick and everything is very positive, but even when I feel healthy and strong during the lesson at school, I get exhausted afterwards. It is so nice to be at school. Sometimes I get restless inside and all I want is to go to school, but then I can’t because it is to exhausting, so I can’t go all the time. Imagine if you were eating your favourite food, only multiplied by ten, but between every little bite you take you have to wait 5 minutes before you take the next, this is what it is like.” (Boy, 12, with ME)

”I do not understand the point of living anymore. Mom, will I ever get help?” (Boy, 15, with ME)

”I feel bad now (nauceous, dizzy, feverish, pains in the entire body), but it is worth it. This was the best day ever – a normal day! (This ”normal” day was two hours at school, a little bit of homework and a short hour at a friend’s house). I look forward to days like this”. (Boy, 12, with ME)

“Mom, at least I don’t need a wheelchair.” (girl, 14, with ME)

”I feel like a zombie.” (girl, 18, with ME)

”I am not able to eat any cake at parties, I get exhausted just by being there.” (boy, 11, with ME)

”Everybody keeps asking me what i do all day, it is strange that they never ask how I am doing…” (girl, 13 with ME)

“Grandpa said I am spoiled, but mom, I am not!» (girl, 9, when she started getting ill with ME)

”I don’t have a life, I am just here at home with you and dad all the time.” (girl, 15 with ME)

”Mom, can you think instead of me, I don’t have the strength to think for myself, could you talk about something I enjoy?” (girl, 13, with ME)

”Today I had a lot of good stuff to eat.» Mom: «Do you remember?» – «I remember what it looks like, but not the names. I don’t remember any of the words.” (girl, 13, with ME)

”But when am I supposed to get better? I didn’t know it was even possible to be sick for this long.” (boy, 8 with ME, after being sick for 6 weeks)

”I am better, but I never feel free, mom. It will catch me again soon.” (boy, 8, with ME)

”But how will we know then, if he is well again, won’t he just fall down again?” (healthy sister, 10, talking about her brother, 8, with ME)

“My cousin just ran up the stairs carrying suitcases, I felt like an 85-year-old. It is not normal that a girl of 15 can’t walk up the stairs!” (girl, 15 with ME)

“I trust my body more than I trust the doctors.” (boy, 13, with ME)

”Mom, when I get well, I will do everything for you! I will be your servant! – But I am not sure I will have the time then.” (girl, 13 with ME)

”I used to be the sporty one, who am I now?” (girl, 13 with ME)

”I know what I want to be when I get healthy, I want to be an archeologist. I want two children, a girl and a boy. What I miss the most is a girlfriend, but that is not possible right now, as I spend most of the time in bed at home.” (boy, 15, with ME)

”I would like the King to see my interview at the Children’s TV News May 12th 2014.” http://tv.nrksuper.no/serie/supernytt/MSUB02008314/12-05-2014 (girl, 12, with ME)

”I think there is something wrong with me, my body is not quite in shape.” (boy, 4 with ME)

”Kill me before I lay eggs.” (boy, 15 with ME)

”The only place I don’t have any pain is at the tip of my nose.” (girl, 15, with ME)

“There is no point in going to see the doctor, he can’t do anything to help anyway.” (girl, 17 with ME)

”What if I never get well, mom. I lay here in bed and year after year of my life just pass by.” (boy, 17, with ME)

”Can I get the education I want when I dont have any grades because of the disease?” (girl, 15, with ME)

”I am freezing and sweating at the same time. I need hot pads on my body and a fan to cool my head, arms and legs. This is exhausting.» (boy, 17, with ME)

”To have ME is like walking on stilts. If you walk too fast you will fall” (boy, 12, with ME)

”Most children in Norway have to go to school and daycare from they are very small. Most of them do not want to start again after summer vacation. It would be nice if school was something you looked forward to, you would learn even more. When you are forced to learn, I think you get more tired and remember less. I’ve got ME and i haven’t been to school for a long time, but i learn a lot anyway, maybe because I really want to learn the little I do? My learning is more natural than at school and then I don’t need to use so much time. In a way the learning happens all by itself. I think this is something to consider.” (boy, 11, with ME)

“I feel like a living dead.” (girl, 17, with ME)

”I was strong enough to dream last night, but now I can’t even think. Did I use all my strength on the dream?” (girl, 13, with ME)

“I feel my future looks bad.” (girl, 18, with ME)

“I don’t want to have children until I am certain that ME is not hereditary. I would not want my children to suffer like I do.” (girl, 26, with ME)

”To ride my bike for 7 minutes going home from school (2 km up hill) was easier for me before than walking the stairs is now.” (girl, 13, with ME)

“I wish doctors could experience how we live with this disease, then they might not just speculate and believe so much about this disease.” (boy, 15, with ME)

“I don’t want to go to day care, granny, they don’t take so good care of me when I get tired as you do.” (boy, 4, with ME)

“This disease has taught me more about how the body works than I would have learned in medical school.” (boy, 13, with ME)

“To have ME feels like constantly having to work the night shift. It is quiet and dark and the body and mind has enough peace to function a little bit better. During the day it is better to sleep.” (boy, 17, with ME)

“I feel like my entire childhood is ruined.” (girl, 18, with ME)

“It feels like I am in a space ship in the dark on Mars. I lay here wondering if I will ever return to Earth and if I will ever see daylight again.” (young man, 27, with ME – in the darkness in a nursing home)

“You roll yourself up like a ball. Pull the knees up and put your arms around them. Let your head rest on the knees. Say you cannot talk right now. Have to breathe. When you look up after a while, I can see your tears running… You cry without a sound. “Mummy, I’m not ready to become a grown-up yet. I’m not ready to turn 18. I still need to be a little girl. I need you, mummy. My life stopped when I was nine. The last time I played – I was nine. I want to be nine and play again… Give me the time… I need to learn to live again, at the same time as I’m afraid not having the strength to live…” (girl, soon 18, with ME)

“When I first started going to school, I was well and healthy. But three months later, I had a throat inflammation and they gave me penicillin. I had to take many cures with penicillin but I didn’t get well. I only got worse and worse. And my strength sort of disappeared from my body. At the end I was so ill that I had to lay in a dark room for 1,5 years. I remember being sad and missing my friends and school. And hugs from mummy and daddy. For a while, I couldn’t get hugs, it hurt too much. Anything that touched me was painful. And light and sound became painful. That’s why I was lying in the dark. It was taken a lot of blood samples. The doctors found that I had mononucleosis and another virus I cannot remember the name. Mononucleosis isn’t dangerous. It’s an infection that passes. Unfortunately some may get a disease after mononucleosis.” (girl, 12, with ME)

“Oh, mum, if I could manage having only two friends for a small birthday celebration! The first time I had two numbers (turned 10), I couldn’t even get out of bed and have any cake. And now it doesn’t look like my body will get better before I turn 11…” (girl, soon 11, with ME)

”If ME had been a visible disease, it would have looked really bad. Then people would have understood how serious this disease is.” (girl, 13, with ME)

”The doctors don’t do anything to help me, they just let me lie here and they don’t care.” (girl, 22, with ME)

”I have relatively good days. I think I must be one of the few who have been well adviced from the beginning, help from a foreign ME doctor and a school who really do their best to help me function and not become more ill. ME has given me a new perspective on life: I appreciate the little things more than I used to. And I really look forward to getting the strength to take showers and wash my hair without the help of mum.» (girl, 16, with ME)

IOM Will Present Findings at Public Briefing on Feb 10

Announcement:

Chronic Fatigue Syndrome – IOM Report Presents New Diagnostic Criteria

Myalgic encephalomyelitis/chronic fatigue syndrome -- commonly known as ME/CFS -- is a debilitating condition that burdens millions of people in the U.S. and around the world. The disease is characterized by profound fatigue, cognitive dysfunction, sleep abnormalities, pain, and other symptoms that are made worse by exertion of any sort. 

Although health care providers are aware of ME/CFS, many misunderstand the disease or lack the knowledge on how to diagnose and treat it. Less than one-third of medical school curricula and less than half of medical textbooks include information about ME/CFS.

A new report from the Institute of Medicine presents new criteria to diagnose ME/CFS and examines whether a new name for the condition is warranted.

DETAILS: 

                  

Members of the authoring committee will present their findings and recommendations at a public briefing beginning at 11 a.m. EST on Tuesday, Feb. 10, in Room 100 of the National Academies’ Keck Center, 500 Fifth St., N.W., Washington, D.C. Those who cannot attend may view a live video webcast of the event at http://www.iom.edu/Activities/Disease/DiagnosisMyalgicEncephalomyelitisChronicFatigueSyndrome/2015-FEB-10.aspx.

Advance copies of Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness will be available to reporters only beginning at noon EST Monday, Feb. 9. The report is embargoed and not for public release before 11 a.m. EST Tuesday, Feb 10.  To obtain a copy of the report or to attend the event, reporters should contact the National Academies' Office of News and Public Information; tel. 202-334-2138 or e-mail news@nas.edu.

Survey Establishes Need for ME/CFS Centers of Excellence

Wanted: Patient Participation in Quality of ME/CFS Medical Care Survey

The Chronic Fatigue Syndrome Advisory Committee’s Centers of Excellence Working Group invites the participation of all ME/CFS patients, 18 years of age and older, worldwide, but particularly within the United States, to participate in an online survey the purpose of which is to determine the ease of patient access to ME/CFS Specialists and to assess the quality of medical care received by individuals with ME/CFS from all of their healthcare providers. While it is of primary importance to establish the quality of care received by patients on a country-by-country basis, the intent of this survey is to establish the need for improved care within the United States based upon the quality of their care when compared to that of other illnesses within the United States, and based upon the comparison of their care to that received elsewhere in the world. The more robust the patient participation in this survey, the more significant the data and the more convincing the results drawn from it will be. We are hoping to obtain a minimum of 1,000 respondents in the United States. If you know ME/CFS patients, please encourage their participation. The results of this survey will inform us of the magnitude of need for ME/CFS Centers of Excellence, the services they should provide, and where they should be located.

This online survey is anonymous. Participant identity will not be revealed. Patients will be asked about their experiences with: access to ME/CFS specialists, barriers to access to ME/CFS specialists, the quality of care they have received from ME/CFS specialists, and the quality of care they have received from healthcare providers who are not ME/CFS specialists.

Patients will be asked to provide information, anonymously, about their current living circumstances (such as age, gender, and employment status), their ME/CFS diagnosis, ability to perform tasks of daily living, and illness onset characteristics. Patients will be provided with an opportunity to describe their medical care in their own words.

To access the survey please follow the link: https://redcap.is.depaul.edu/surveys/?s=wGI2stCALK