Dr. Benjamin Natelson is 2012 keynote speaker at Mass CFIDS/ME & FM Association : Lumper or Splitter

Details

Last Updated: 23 November 2015 23 November 2015

Common symptoms and lumping chronic conditions together

In a lecture called "CFS Diagnosis: Are You a Lumper or a Splitter" co-sponsored by the Massachusetts CFIDS/ME & FM Association (MassCFIDS) and the Massachusetts Department of Public Health on April 28, 2012 Dr. Benjamin Natelson, Director of the Pain and Fatigue Center at Beth Israel Medical Center in New York City, presented twenty years of research and work with Chronic Fatigue Syndrome (CFS) patients. Dr. Natelson's wife, Dr. Gudrun Lange, Ph.D., a Clinical Neuropsychologist accompanied Dr. Natelson to Massachusetts, and in a surprise double-header, also spoke about the process of neuropsychological testing for CFS patients.

What's a syndrome?

Dr. Natelson explained that in CFS, as well as such other syndromes as Irritable Bowel Syndrome (IBS), Temporal Mandibular Joint Syndrome (TMJ), Migraine, Depression and Schizophrenia, there are common symptoms that seem similar and therefore, the medical professionals label it a syndrome. A syndrome is a cluster of symptoms that can have multiple causes. "We need to figure out ways to reduce the variability. CFS is the tip of the iceberg" he said. Fatigue can be related to many pain syndromes but whether the fatigue is a result of sleep problems or if the fatigue itself produces pain needs to be sorted out.

Fatigue is the most common symptom in medicine

There are many medical conditions and syndromes that are associated with severe fatigue. These conditions can include Chronic Fatigue Syndrome (CFS), Fibromyalgia (FM), Irritable Bowel Syndrome (IBS), heart failure, Multiple Sclerosis (MS) and Chronic Obstructive Pulmonary Disease (COPD). In fact, fatigue is the most common symptom in medicine, and there are multiple causes, including sleep disorders, infection or any number of other conditions. Dr. Natelson stressed that in CFS there is severe fatigue marked by a substantial decrease in activity.

Dr. Natelson presented statistics to drive his point home. A person has a 9% chance of developing CFS within 6 months after a bad infection, but not necessarily lasting for more than 6 months. About 15% of breast cancer survivors fulfill the criteria for CFS. Fatigue is often the first symptom in Multiple Sclerosis (MS), and many Parkinson's patients are often debilitated by fatigue.

Lumper's approach

The lumper's approach groups all chronic conditions, such as CFS or FM, in which a person has physical symptoms that involve more than one part of the body but seemingly without physical cause, as a somatization disorder. Doctors are inclined to diagnose pain and fatigue related syndromes, which currently have no diagnostic test, as Somatic Amplification, a tendency to psychologically perceive normal sensations as overly intense.

Dr. Natelson feels that Somatic Amplification has a derogatory connotation and should be replaced with Medically Unexplained Symptoms. In fact, the rate of somatic disorder reported in CFS patients depends entirely on whether the cause of the symptoms is interpreted as psychological or physical by the physician who is making the diagnosis.

---

Splitting patients into subgroups and looking for more ways to differentiate

The splitter's approach

When it comes to determining a cause for Chronic Fatigue Syndrome, is it better to lump CFS patients together with other chronic conditions causing pain and fatigue, or is it better to split patients into subgroups?

Dr. Natelson takes the splitter's approach and identifies patient subgroups in order to determine the cause, or causes, of Chronic Fatigue Syndrome. Dr. Natelson's research for biomarkers, a biological characteristic that can be objectively measured as an indicator of abnormal biological processes, has pointed in the direction of a brain dysfunction in a specific subset of CFS patients.

As there are most likely several causes for CFS, the subgroups help to narrow the pool of patients in order to determine specific causes. This process is called Stratification Strategy.

While FM is another way to split out a diagnosis, FM is tenfold more common than CFS because FM is a diagnosis that is made without any exclusions.

CFS is a diagnosis of exclusion, which requires ruling out all possibilities causing fatigue such as thyroid disease, MS, Lupus, diabetes, etc. and hoping the fatigue will be resolved.

The prevalence rate for FM is 3%, being mostly a women's health issue breaking down to 75% women to 25% men. The prevalence rate for CFS is 0.3%— again favoring women.

In a research paper Natelson published 10 years ago regarding sudden onset, it looks at CFS patients and charts the dates when they became ill. Looking at the chart shows the onset was not random because if random, the charted line would have been straight across. This line went up all around the same time, in winter, suggesting an infection-related trigger.

Stratification Strategy

Co-morbidity is the existence of another diagnosis along with CFS. Dr. Natelson looked at several ways of splitting CFS patients: CFS patients with and without Fibromyalgia; sudden or gradual onset of symptoms; severe or non-severe symptoms; cognitive impairment versus normal cognition; and patients with and without a psychiatric diagnosis—usually depression. About 35% of patients in Dr. Natelson's center reported a sudden onset of symptoms, while the balance report fatigue and symptoms that increased gradually.

Are CFS and FM the same?

In his clinical sample, Dr. Natelson compared CFS and FM to determine if they are the same condition. While overlaps do exist, there are medical differences as well.

About 40% of the CFS patients fulfill the criteria for FM. About 20% of FM patients had CFS. The spinal fluid of FM patients shows an elevation of Substance P (responsible for pain), but that is not the case in CFS patients.

Another study had shown that CFS was common in patients with obstructive sleep apnea, while FM was not. Also, FM pain responds to some anti-depressant medications, but CFS fatigue does not.

Natelson concluded that CFS and FM are not the same and therefore do not have the same causes, nor should they have the same treatments.

Twenty years of research shows possible brain dysfunction

In the past twenty years, Dr. Natelson has conducted a number of studies to determine the differences, and possibly determine the causes, for CFS as compared to other syndromes, such as FM, Sjögren's and post-Lyme. 

In a recently published study looking at sleep, CFS-only patients have increased rates of REM to wakefulness (tends toward awake) while CFS-plus-FM patients tend to fall asleep, but their sleep is disrupted by transitions to wakefulness. These marked differences may prove helpful in determining treatment approaches.

In a study looking at the blood prolactin (a hormonal surrogate for brain serotonin neuron activity) response to a tryptophan infusion, CFS patients showed increased brain response to the tryptophan infusion but not those with CFS-plus-FM or healthy controls. Studies done with depressed patients show an under-response to tryptophan infusion.

His conclusion was that CFS and FM are not the same, as the lumpers believe, and patients may not respond in the same way to commonly prescribed treatments.

Natelson's hypothesis

Natelson's hypothesis is that some CFS patients, especially those that have no accompanying psychological disorders, have brain dysfunction or encephalopathy. Furthermore, Natelson believes that further study will identify biomarkers to accurately diagnose that subset of CFS patients.

In his first study, twenty years ago, Natelson compared the cognitive dysfunction in patients with CFS, MS and healthy patients. He found that CFS patients function worse than controls on timed complex attentional tasks, and that those with the most impairment could have an underlying encephalopathy, or brain dysfunction.

As an example, he offered that a CFS patient in a quiet room talking to one person would be ok, but in a room with four people talking at once, the CFS patient would have a problem.

---

Research, ongoing studies, and use of new technology

Research finding

He is now looking at the brain by studying spinal fluid—the fluid that bathes the brain—and using brain imaging techniques.

Brain MRIs showed more abnormalities in CFS subjects with no psychiatric disorder as compared to CFS with a psychiatric disorder or to healthy controls. This finding again points to encephalopathy, especially in CFS patients without a coexisting psychiatric disorder.

The study also found significantly more abnormalities in the frontal lobe of the brain, as well as a reduction of the brain blood flow than the other groups.

Spinal taps on forty-four CFS patients showed that 30% of those patients had spinal fluid outside the norm, including elevated protein and increased white blood cells. Again, there were more spinal fluid abnormalities in patients without psychiatric comorbidities and 27% of the normal spinal fluid patients had depression.

While one-third of CFS patients experience a sudden flu-like onset of symptoms, Dr. Natelson looked for viral infections while studying the spinal fluid and found no convincing data for persistent viral infections. Only a small fraction of patients had shown evidence of reactivated Epstein Barr Virus (EBV).

He also found that Xenotropic Murine Leukemia Retrovirus (XMRV) was negative in the spinal fluid. Once an exciting possible cause for CFS, Natelson did not find the presence of the retrovirus in the spinal fluid. "That story is behind us," said Natelson.

He was also unsuccessful in replicating studies that showed immune activation, in which the immune system is turned on by a virus and then keeps running in CFS patients.

The search for biomarkers

Over time, reduced natural killer cells seem to be the only evidence of a reduced immune system that holds true across many studies. However, Natelson has found evidence for the opposite.

While the pro-inflammatory cytokines make you feel sick, he has found evidence that one of the anti-inflammatory cytokines, IL-10, was elevated and may contribute to disturbing sleep.

With today's technology, Dr. Natelson has come closer to finding biological abnormalities that could be used to unequivocally identify and diagnose Chronic Fatigue Syndrome in a specific subset of patients.

Using MRIs to look at chemicals in the brain, Natelson compared Ventricular Lactate in CFS and controls as a possible biomarker. He found that CFS patients without a coexisting psychiatric disorder had higher lactate, and he has now replicated this study.

Natelson also believes that 15% of CFS patients have an autoimmune disorder that is being missed.

He discussed Sjögren's Syndrome, another autoimmune illness, the main early symptoms of which are dry eyes and dry mouth but also include prolonged fatigue. A lip biopsy is the definitive way to diagnose Sjögren's, in which the body attacks its own tear and salivary glands.

In his small study, all the patients had a negative result to Sjögren's antibody blood test, but about half of the 25 patients reported dry eyes and mouth. Then the tear production was measured and it was found 10 of those 13 patients had abnormal tear production.

When lip biopsies were done on those patients, 1/3 were found to have an abnormal biopsy. Dr. Natelson thinks even though this was a small study, it may prove to be reliable in predicting autoimmune disease.

New technology

New technology now allows researchers to identify all the proteins in the spinal fluid. Through the use of mass spectrometry, an analyzer that separates proteins and breaks them down further and further than ever before, Natelson compared the proteins in spinal fluid between healthy controls, CFS patients and those with Post Lyme Fatigue Syndrome.

There are 305 proteins common to both CFS and Post-Lyme disease.

Natelson found 738 proteins unique to those with CFS. He is now working to identify three or four of those proteins that are specific to CFS to be used as a biomarker to diagnose at least a subset of CFS patients.

Findings so far

Some CFS patients have poorer neuropsychological test results, abnormal brain MRI imaging, poorer function in health related quality of life, wider reduction in brain blood flow, more abnormal spinal fluid results, and higher levels of ventricular lactate, all which point to a brain disease.

Ongoing studies

Natelson is looking to better define the subgroup with a neurological cause and develop specific treatments and medications for them. In order to complete this new study, the National Institutes of Health (NIH) has awarded him a grant to repeat all of his past studies, including neuroimaging, neuropsychology and spinal taps, but all on the same group of patients.

There is also a new grant from the CDC to find out if the diagnosis of CFS is the same across centers.

This has never been done. This study will compare how Dr. Natelson, a neurologist from NY, Dr. Nancy Klimas, an immunologist from Florida, and a leading CFS researcher/clinician, and another large group of practitioners expert in CFS make the CFS diagnosis.

There is a pharmaceutical industry study on using Milnacipran (brand name Savella) to see if it proves useful in reducing fibro-fog in FM patients. Milnacipran is a class of medications called selective serotonin and norepinephrine reuptake inhibitors.

Colleagues of Dr. Natelson's from Cornell have just recently received notice that a study to try to improve brain chemistry with an available food supplement will be funded.

---

Advice for treatment of chronic illness

Chronic illness treatment

Dr. Natelson's advice for treatment of any chronic illness has four components:

• education
• medication
• very gentle physical conditioning
• behavioral therapy, which can help the patient to learn new techniques to handle the illness.

He stressed that this last technique is difficult to do on your own and best learned from a professional.

If patients are interested in joining the studies described above, they will need to be off all medications that may alter brain chemistry or functioning. The study is also recruiting healthy controls and volunteers get a free work-up and are reimbursed for their time. The study is being conducted in New York City but the food study involves travel to Weill-Cornell's Imaging Center.

To participate in this momentous work, go to www.painandfatigue.com or call (212) 844-6747.

[2015 note: Both studies are still soliciting participants as of late 2015.]

Cytokines and CFS article on the CDC website

Details

Last Updated: 23 November 2015 23 November 2015

Cytokines are immune system signaling molecules that encourage the blood cells of the immune system to move toward the site of inflammation.

The CDC has an article Cytokines and the Symptoms of CFS (Centers for Disease Control and Prevention,  December 6, 2011) which describes research determining some symptoms of ME/CFS that can come from the release of cytokines. Most of the study centered on the effects of alpha-interferon.

Love and Fatigue in America

Details

Last Updated: 21 January 2016 21 January 2016

Reviewed by Jean Zimmer

On April 23, 1991, at 8 p.m., a 40-year-old British economist, international consultant, novelist, and university instructor collapsed on the floor of the Sta-Fit gym in Spokane, Washington. He describes the moment:

It’s funny how the sitting down doesn’t end the going down—like gravity does not know where to stop, and its giant hand persists in pushing on my shoulders, insisting I go right through the floor, or failing that, to be flattened on it like paint. I cannot let this happen. It would look bad. It might attract attention. I concentrate on the countervailing force offered by friction, back pressed against the wall, feet pulled up and flat on the carpet. I stare with unseeing eyes—they are busy playing their own game of light and dark—a hint of a smile on my lips. Not ridiculous, I hope.

Thus begins the narrator’s 21-year journey with chronic illness. King’s just-released autobiographical novel is a heart-baring exploration of what it is to lose the classic measures of success—a thriving career, prospects of a family, and financial security—when they are supplanted by illness. In poignant parcels, the narrator describes his comic-tragic journey as he navigates, in faltering steps, the strange and unfamiliar landscape of our profit-driven healthcare system.

Occasional illness is a fact of life for most of us. As I write this, my teenage son lies in bed, red-nosed and sneezing, sequestered with a book and a box of Kleenex. He awaits, with full expectation of attainment, the return of health—in his ideal world, before his friends’ Frisbee game begins this afternoon.

Others don’t rebound so quickly or completely. My family practice physician once referred to them, not unkindly, as his “fat file” patients—the ones whose medical files overflow with test orders and memos from repeated office visits. Most of us have known a “fat file” person: the cousin diagnosed with multiple sclerosis; the teacher who left her job when she came down with Lyme; the guy up the street with diabetes and a gimp knee; or the coworker medicated for chronic depression. For these people, the problems don’t go away. Often, they seem to compound.

If we are decent (and most of us are), we feel sorry for them, in their pain or debilitation. We do what we can: We bring them supper, we drive them to doctor’s appointments, we rake leaves from their lawn, or we listen while they talk about their problems.

If their illness lingers, and especially if their complaints mount, our helping hands might falter. We lose patience. Could they be malingering? Nothing we do seems to help much. Perhaps their disability insurance runs out. Their stories of an uncaring healthcare system scare us. We may drift away, breathing excuses about our busy lives. We might run.

In Love and Fatigue in America, the narrator muses about the person he has become:

You look well/You are not dying/Your complaint is modest/You are going to be trouble for a long time/Your brain does not work/Your charm has gone with it/You are inconsistent/Sometimes perversely well./You are unreliable/You explain your unreliability/Which is like whining/You cannot explain your illness/You are inconvenient, thoughtless, boorish, charmless, witless/And don’t do your share/You are not yourself./There is no place for people who are not themselves/You are not good at being ill…

Prior to his “profound overturning,” the narrator is, by most contemporary measures, at the top of his game. He has risen from a blue-collar background in a London suburb to earn a Ph.D. in agricultural economics. His first career in Africa and Asia as a socio-economist and institutions expert is supplanted by a second career as an award-winning novelist. Fit, seemingly fearless, and 40, he has negotiated world continents, closed on impressive contracts, won at love, and acquired an impressive, supportive community of friends.

His metaphorical crash-landing, with symptoms of what first seems like a bone-crushing flu, upends his life and career. As his illness persists from weeks to months to years, his girlfriend, friends, and colleagues drop away, one by one, from his life. Ironically, those who don’t abandon him use him—prone, sick, silent, but also sympathetic—as a sounding board for their own stories of emotional and physical suffering.

After receiving a diagnosis of chronic fatigue syndrome (CFS), the narrator follows the advice of a parade of doctors and alternative health practitioners, many of whom are portrayed as comically incompetent. Who knew that a story of getting sick could be funny? King weaves humor through his novel.

Unflappable college students meet with the narrator during his academic office hours, offering threats, attempts at coercion, or intimate details of their sex lives. His alternative medical practitioner in Santa Fe drives a red BMW with crash damage, which he soon replaces with a second vehicle that soon shows up with crash damage. At one point, the narrator kisses a potential murderess, “but, hello, this is California.”

Many people afflicted with CFS express frustration that the descriptor “chronic fatigue” reduces the syndrome to an undeserved simplicity. Outside the U.S., CFS goes by the weightier name “myalgic encephalopathy.” Beyond incapacitating fatigue, classic symptoms of CFS include impaired concentration and memory; muscle and joint pain; sleep disturbances; tender lymph nodes; sore throat; headache; and worsening of health following physical or mental exertion. The syndrome crosses lines of education, affluence, race, and gender.

No one knows how people get CFS, but a brain-targeting virus, genetic susceptibility, and a compromised immune system are suspected contributors.

The narrator seeks a recovery that, for a while, he does not doubt. As years pass and his condition deteriorates, however, his bewilderment, humiliation, and suffering increase while his hope diminishes.

With each remission I am convinced that the recovery will be permanent, and each time I am proved wrong. This never changes. Health is unable to imagine being ill; illness cannot recall a state of health.

Although he is a world traveler accustomed to harsh conditions, the narrator finds himself at a loss when he faces the foreign and confusing landscape of illness in the United States. He compares the U.S. healthcare system with the nationalized medical system of his homeland, England—a system that requires of its patients much less paperwork, permissions, and payments.

You remember visits to the doctor as blithe affairs. The burden of management customary to Americans strikes you as astonishing—staggering—in its complexity, trickery, and venality. You wonder that such a situation could ever be taken as normal.

The narrator points out “the labor of being sick in America,” a country where the more a person is weak and compromised, the more he must advocate for himself. Because he is so ill that he is limited to his sofa, that is the site from which he conducts his business. He stashes medical bills and insurance receipts in cracks between cushions and on the floor beside him. Using a telephone balanced on his chest, he works daily, until sickness and exhaustion overwhelm him, to clarify, defend, and understand his condition and his health benefits.

The narrator struggles to keep his university job, but he has numerous setbacks, such teaching “a horrific class” during which his head falls onto his desk and will not come up.

Over time, the narrator learns to ration his energy. He learns to cope with his incredulous coworkers. He describes the paradox of trying to maintain his job and maintain an appearance of a normal life:

The intermittent need to prove to doctors that my illness is not in my mind-when clearly my mind is affected—and to prove to the company’s private investigators that I am not disabled—when every day is taken up by trying to seem not disabled—causes paroxysms of internal conflict.

Over time, quietness, solitude, and low-grade panic overtake him. “It’s hard not to blame yourself for illness,” he writes, in perhaps his closest admission of self-pity. His income and savings dwindle. He struggles to maintain his job. He longs for a home and family.

Remarkably, he achieves love, in noncontiguous chunks: tender affection for a woman and her daughter, sex for money, and a more tenacious love from his dog Arthur.

King’s book was written from within the bounds of his own illness, and the format might be taken as evidence for his labor in writing it. It is crafted as a series of dozens of short chapters, some as short as a single page. They include narrative, essays, lists, and poems. King’s narrator is an appealing character: His illness seems to have made him, patient, kind, and wise—he inhabits a shrunken world, yet he maintains a wide worldview.

The book is fiction, but King’s use of first-person captures a real man—one with authentic, flawed retrospective recall. The novel reads a little bit like a diary, including a few steamy love scenes and witty, observant notes on topics as diverse as strippers, military life, and ambition.

Although the book weighs in at 254 pages, it’s hard not to want a little more about the main character’s origins. Who were his barely-mentioned parents? What was life like in suburban London for an introspective child? What series of events turned a provincial lad into a globetrotting economist?

The story opens with an exuberant and hopeful narrator circling in a jet above the city of Spokane, Washington. It concludes in a small town in western Massachusetts, with the narrator contemplating the gains and losses of his quiet existence.

From his place of retreat, the former world traveller and international problem-solver describes his “horizontal life” as peaceful, with appreciation for small beauties and subtleties. In a section titled “Lost and Found,” he comments

I have had pressed on me by illness the eternal good sense and wisdom of being present in my body, and relaxing the self in something larger … the nature of CFS is an object lesson in oneness. Which is an object lesson in love. You are lost, yet you are found.

An account of being sick could be a hard sell in today’s book market. If the daily news itself can be a downer, why read a narrative about illness and disability?

Answer: Because fate is fickle. The book’s publication follows closely on the U.S. Supreme Court’s review of President Obama’s healthcare law. King’s well-crafted book raises important questions about how our society treats sick people. What happened to the narrator could happen to anyone. Perhaps the book could help inspire a remedy for a healthcare system that doesn’t seem very caring.

 

Roger King is the author of four previous novels: Horizontal Hotel, Written on a Stranger’s Map, Sea Level, and A Girl from Zanzibar. He lives in Leverett, Massachusetts.

Jean Zimmer is a freelance writer and editor based in western Massachusetts.

Reporting of Harms Associated with GET and CBT in ME/CFS

Details

Last Updated: 24 November 2015 24 November 2015

Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, T. Kindlon, Bull. IACFS/ME: 19 (2), Fall 2011

Note: Click on the title above to link to the full article.

Abstract:
Across different medical fields, authors have placed a greater emphasis on the reporting of efficacy measures  rather than harms in randomised controlled trials (RCTs), particularly of nonpharmacologic interventions.

To rectify this situation, the Consolidated Standards of Reporting Trials (CONSORT) group and other researchers have issued guidance to improve the reporting of harms.

Graded Exercise Therapy (GET) and Cognitive Behavioural Therapy (CBT) based on increasing activity levels are often recommended for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

However, exercise-related physiological abnormalities have been documented in recent studies and high rates of adverse reactions to exercise have been recorded in a number of patient surveys.

Fifty-one percent of survey respondents (range 28-82%, n=4338, 8 surveys) reported that GET worsened their health while 20% of respondents (range 7-38%, n=1808, 5 surveys) reported similar results for CBT.

Using the CONSORT guidelines as a starting point, this paper identifies problems with the reporting of harms in previous RCTs and suggests potential strategies for improvement in the future.

Issues involving the heterogeneity of subjects and interventions, tracking of adverse events, trial participants’ compliance to therapies, and measurement of harms using patient orientedand objective outcome measures are discussed.

The recently published PACE (Pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation) trial which explicitly aimed to assess “safety”, as well as effectiveness, is also analysed in detail.

Healthcare professionals, researchers and patients need high quality data on harms to appropriately assess the risks versus benefits of CBT and GET.

Ed. note: See also the IACFS/ME Statement on the PACE Trial.

MassCFIDS 2011 Fall Meeting Highlights Part 2--Dr. Kenneth Friedman

Details

Last Updated: 24 November 2015 24 November 2015

A note from the Editors about the use of initials/acronyms in this article:

Most of the slides prepared by Dr. Kenneth Friedman, the guest speaker for the second part of this forum, displayed "ME/CFS" in reference to the illness. However, during their verbal co-presentations, Dr. Friedman and Dr. Gurwitt often used "CFS", which still designates the name most used in the medical research community, i.e. Chronic Fatigue Syndrome. Therefore, this summary will show both acronyms, relatively in sync with their use throughout this program. Elsewhere on this website the illness may be called CFS/CFIDS/ME, for Chronic Fatigue Syndrome/Chronic Fatigue and Immune Dysfunction Syndrome /Myalgic Encephalomyelitis. Similarly, MassCFIDS, a shorter, long-standing form of the Association's name, is frequently used in longer articles for clarity and brevity.

The Massachusetts CFIDS/ME & FM Association (Mass CFIDS) held its Fall 2011 educational forum, co-sponsored by the Massachusetts Department of Health, on November 5, 2011, at the UMass-Hinton State Laboratory Institute Auditorium in Jamaica Plain, MA. The second segment of this forum focused on developments and discussions from the September 2011 International Association for Chronic Fatigue Syndrome /Myalgic Encephalomyelitis (IACFS/ME) Conference held in Ottawa, Canada, which could have considerable impact on ME/CFS patients. The guest speaker, Dr. Kenneth Friedman, and Dr. Alan Gurwitt, president of MassCFIDS, shared the presentation and spoke about these topics with insight, conviction and optimism.

Dr. Friedman, a recently retired Professor of Pharmacology and Physiology from the University of Medicine and Dentistry of New Jersey, is a fervent and outspoken advocate for CFS, a working member of the IACFS/ME, scientific advisor to several ME/CFS patient groups, and a longstanding friend of Mass CFIDS.

Dr. Friedman briefly described how he became involved with CFS and the Association many years ago. While his daughter was attending Tufts University, during the early 1990s, she came down with infectious mononucleosis and eventually went on to develop CFS. He spoke appreciatively about the information and support that he and his daughter received from the Association during that difficult time.

Dr. Friedman singled out developments and studies from the Ottawa conference which he considered to be important to ME/CFS patients, not only from a research standpoint, but also their impact on patient care. The key points in Dr. Friedman's lecture (taken from the slides that he had prepared for this forum) are as follows:

• Is it time to get beyond ME/CFS case definitions?
• Should we use exercise testing in lieu of a biomarker?
• Investigating the efficacy of anti-viral and antibiotic therapy
• Stepping up to the plate by the Private Sector

---

Is it time to get beyond ME/CFS case definitions?

Dr. Friedman started by drawing attention to the uncertainty and debate which now surrounds the three most popular case definitions for CFS, ME or ME/CFS. As chairperson for the session on "Case Definitions for Research and Practice" at the Ottawa conference, Dr. Friedman noticed some researchers/clinicians were unsure about the case definitions or not in agreement with each other, while others sought ways to get beyond these case definitions.

He thought some researchers were positively influenced by the approach being taken by Dr. Leonard Jason at DePaul University in Chicago, IL.  In order to arrive at the most suitable definition for the illness, Dr. Jason focused on identifying the most appropriate features in the illness and identifying the most appropriate case definition and criteria for CFS. (At the Ottawa conference, Dr. Jason's study described a statistical technique, data mining, which was used to help determine which questions and items would provide the most effective data).

The use of Electronic Medical Records (EMR's) affords a practical way to record and characterize patients' symptoms along with other relevant information. Patients' medical data could be compared to case definitions or other data along an infinite array of parameters. Dr. Friedman stated that the technology exists and it continues to become increasingly more accessible.

So, it would be possible to assess patients in this manner and determine if they met at least one the case definitions. Furthermore, he thought that if the patient would meet "one or any" of the illness criteria, that would suffice.

What Dr. Friedman described was the relationship of case definitions, EMR's and patient registries that could lead to a system with many possibilities for ME/CFS research.

Another approach that could help facilitate diagnosis of ME/CFS and selection of treatments, would be the switch from the "single definition/single cause" model to one that supports subsets.

Dr. Friedman made the analogy of ME/CFS to breast cancer, to the extent that breast cancer is described not as a disease but a category of disease in which there can be multiple types of breast cancer (or subsets). In this approach, treatments will often depend on the specific type of cancer that the individual patient has.

Dr. Friedman mentioned how this model for breast cancer was recently reviewed on the Doctor's Radio, a satellite radio station, which led him to see this as a viable and appropriate strategy for ME/CFS. There already exists considerable evidence to support multiple causes and subsets in ME/CFS, and the benefits that patients would gain from more individualized treatments is obvious.

---

Should exercise testing be used in lieu of a biomarker?

There is also debate over the expressed need for a biomarker-that is, in order to confirm the illness in patients, a biomarker must be found. Dr. Friedman proposed the consideration of exercise challenge tests for their proven ability to measure and identify distinctive features of ME/CFS.

More specifically, exercise testing like the Stevens Protocol (i.e., the method developed by Staci Stevens at the University of the Pacific, Stockton, CA) has effectively detected multiple abnormalities unique to ME/CFS and objectively measured the reduced ability of ME/CFS patients to perform exercise and certain activities (i.e., those needed for sedentary work or activities of daily living).

Exercise testing can induce postexertional malaise (PEM)-now being recognized as the hallmark symptom of ME/CFS, and then it can quantify the effects of PEM on the patients' functional capacity.

As a result, this method is able to confirm the presence of this illness in patients. Having a tool available that could confirm or document ME/CFS could also facilitate the disability review process, and possibly accelerate the approval of the applicants and the release of their benefits. Dr. Friedman empathized with patients in how this is often a long and difficult process.

Furthermore, this type of tool could help to demonstrate efficacy of potential treatments, especially those which require FDA approval (i.e., Ampligen was mentioned as one treatment that needs to be pushed through). Therefore, Dr. Friedman has recommended the acceptance and utilization of exercise tests as a valid protocol in lieu of a biomarker.

---

Investigating the efficacy of antiviral and antibiotic therapy

Going beyond anecdotal evidence for use of antiviral or antibiotic treatments, several research papers at the Ottawa conference reviewed positive responses to antiviral therapy and antibiotic therapy in CFS—in particular, for those patients who had high antibodies to enteroviruses or in CFS precipitated by the Epstein Barr Virus (EBV).

Dr. Jose Montoya (at the Stanford School of Medicine, Palo Alto, CA) has been studying an antiviral regimen which he has developed for treatment of ME/CFS, but the actual protocol has had limited circulation. Dr. Montoya has agreed to prepare a paragraph for inclusion in the IACFS/ME Physician's Primer which suggests that an approach and rationale could (and perhaps, should) be developed for the use of particular agents for ME/CFS patients who demonstrate particular viral loads.

The efficacy of treatments with antivirals or antibiotics needs to be further investigated. It also needs to be determined what would prompt a well-planned, carefully executed clinical trial.

A study showing positive response to antibiotic treatment in ME/CFS was presented by Dr. Sam Shor, from the Washington, D.C. area. Dr. Shor placed his ME/CFS patients on the same treatment regimen—a combination of multiple, long-term antibiotics—which he used for his chronic Lyme Disease patients. Patients with ME/CFS met the international case definition and were negative for Lyme Disease (LD).

Improvement of symptoms was found in 66% of ME/CFS patients even though they were seronegative for LD. Several possible interpretations of these results, according to Dr. Friedman, would be: 1) the possibility of these CFS patients having LD, 2) viewing the improvements as potentially due to the immunomodulatory effects of the antibiotics, or 3) an infection that could be at the root of their CFS was responding to the treatment.

Similarly, a Norwegian study discovered that a cancer agent, rituximab, had reduced symptoms of CFS, raising the same questions with regard to that drug's immunomodulatory effects. Dr. Friedman explained these agents work on the same system (the immune system) and felt that research of drugs with these particular properties would be worthwhile for ME/CFS.

---

Stepping up to the plate by the Private Sector

Dr. Friedman wrapped up his presentation with very encouraging news about several new private initiatives which are being set up for CFS research. He reported there were now three non-federal funded sources for ME/CFS research:

• the Whittemore Peterson Institute (WPI) which is well recognized by the ME/CFS community
• the Chronic Fatigue Initiative, Inc. (CFI), an organization funded by a $10 million donation from a private family (the donation will be used on multiple CFS studies, after investigators determine "critical" questions and areas in ME/CFS research)
• the Simmaron Research Foundation, an organization of friends and patients of Dr. Daniel Peterson that will donate an as-yet-to-be-determined amount of money to support Dr. Peterson's research done in collaboration with other research groups.

---

Developments in pediatric ME/CFS

Dr. Alan Gurwitt was particularly interested in news and developments in pediatric ME/CFS and had attended a workshop on the same, chaired by Dr. Miike from Hyogo, Japan. Dr. Gurwitt was pleased to see that the workshop was very well attended by researchers and clinicians from literally all corners of the world. He found this most encouraging, given the shortcomings in pediatric diagnosis and treatment during earlier years.

Diagnosing pediatric ME/CFS

Evaluating children with CFS has been a challenge for quite some time, especially since the 1994 U.S. Fukuda criteria was developed for adults and adult manifestations of the illness. It was really not adequate for use in children and adolescents, explained Dr. Gurwitt.

Approximately 6 years ago, an international group of ME/CFS researchers and clinicians was formed and they co-authored criteria specifically intended for children called, Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome (Dr. Leonard Jason, et al).

He stated there are differences in the characteristics of CFS between children and adults. In particular, children tend to have more abdominal pain and rashes.

Lack of understanding of ME/CFS in schools

Part of the pediatric criteria includes references that could be used by school personnel. However, Dr. Gurwitt finds that schools still show limited knowledge and understanding about CFS in children and their tendency is to suspect "school phobia" in children ill with ME/CFS.

At the workshop, he discovered the situation was not much better for children with ME/CFS in many other countries. Another terrible situation faced by some families has been the faulty accusation of Munchausen syndrome by proxy (i.e., the child's illness is assumed to be fictitious and to be caused by the parent or parents).

Dr. Gurwitt is very disturbed by such occurrences of pure ignorance and undue hardships to families, and urged action by ME/CFS organizations to find ways to educate physicians and school personnel in how to distinguish phobias from legitimate illness such as ME/CFS.

Precipitating events in pediatric ME/CFS

The pediatric workshop reported a variety of news, such as how infectious mononucleosis was found to be a fairly common pre-illness event in children and youth who developed CFS (i.e., in about half of the cases); in some cases, immunizations were thought to be the precipitators of CFS-like conditions (i.e., no particular vaccines were identified but Dr. Nancy Klimas is working to clarify this); mold exposure was reported by some families as another CFS trigger; and Japanese researchers identified chronic sleep deprivation in children and teenagers as a major precipitator of CFS. Children as well as adults in Japan appear to be at a higher risk for sleep deprivation.

Treatment

Melatonin was the sleep agent most used in children. Though Ritalin was used fairly often, many researchers/clinicians are quite concerned about its use in children with CFS. The Japanese research group described an intense treatment regimen they created for children/youth with CFS, which usually included hospitalization and intensive sleep-wake circadian rhythm treatment to help restore their circadian rhythms—good results were reported on improvements made with their sleep disturbance, but not of all their CFS-related symptoms.

Dr. Katherine (Kathy) Rowe was recognized for the program that she had helped to develop and implement at the Royal Children's Hospital in Melbourne, Australia. Dr. Gurwitt described the Australian program as being "sophisticated and methodical" and unlike anything that other countries are doing.

This program has followed close to 800 children (pediatric patients) for over 15 years, which has allowed them to create a history of the illness. The extensive information collected at scheduled intervals throughout this period of time included duration, recovery, education, work, treatments/diets, and other events and changes in these patients' lives. Although the average duration of illness was 5 years, this level of follow-up and ongoing support continued for many years.

The Australian program requires that new patients undergo a very careful evaluation for ME and the evaluation process include the parents-both parents, with a special emphasis about not leaving fathers out.

Once a diagnosis has been made and appropriate treatments started (i.e., standard medications or therapies), other interventions also include family counseling, maintaining close contact with schools, and helping with necessary adaptations for the patient's/student's educational needs.

---

A brief, informal overview of the Physician's Primer

Both Drs. Friedman and Gurwitt informed the audience that the IACFS/ME Physician Primer was nearing completion and its release is expected during early 2012. A few things which they could share about the Primer, at this time, was why it was created, who it is intended for, what is its purpose, and its content (in a very general sense), as follows:

• it is a practice manual, written by a group of physicians, specifically for primary care physicians so they would have the necessary information to be able to diagnose ME/CFS
• it offers specific treatment recommendations, informs a physician of his/her responsibilities to the patient, and makes recommendations when it is appropriate to refer the patient to specialists
• it is geared for adult patients and does not include any information for pediatric care, but future plans are to compile a pediatric version
• it will be recommending the Canadian Case Definition for ME/CFS and it will not be using the 2011 International Consensus Criteria for ME because it is new and not clear how it will compare or do clinically (referring to what Dr. Friedman mentioned earlier in his presentation)

Drs. Friedman and Gurwitt reiterated the Physician Primer is a concise, very dense and highly technical handbook-for physicians and not intended for patient use.

When the IACFS/ME is ready to release the Physician Primer, MassCFIDS will send out an announcement via our E-newsletter and post the news on the website.

---

Advocacy—its importance and its impact

What is MassCFIDS? was the title of a report prepared and presented for members and guests in attendance by Ms. Charmian Proskauer. Since MassCFIDS was founded and registered as non-profit charity 501(c)3 organization more than a quarter of a century ago, many newer members and guests have asked to learn more about its past, current work, and future goals.

MassCFIDS is the short name for the Massachusetts CFIDS/ME & FM Association. Fibromyalgia (FM) was added to the Association's mission (and name) during the 1990's. The history of the Association is available on the website, under the topic "History of the Association."

MassCFIDS has an all-volunteer Board (currently of 14 members) which holds bi-monthly meetings. Officers are elected from within the Board. All the work of the Association is done by volunteers.

Ms. Proskauer shared with the audience how she had been initially recruited several years ago to help create a new website for Association. Eventually, she was elected to the Board and now oversees several committees. She also spoke about her desire to become an advocate for the illness; she is a family member of someone who has CFS. Finding herself with a little extra time, she wanted to work with others towards something that would make a difference-the Association fulfilled this need.

MassCFIDS is the oldest patient-run CFS organization in the country and its mission has remained the same, although the organization has evolved over time. Our members and volunteers continue to work and advocate for patients and their families in many ways: conveying information through the website and an E-newsletter; responding to questions by emails or phone calls; providing community outreach/patient services; speaking out (or writing) on issues which may negatively impact patients; and sponsoring educational events.

A note about the patient and/or patient's family contacts we receive—70% of these are requests for services and 2/3 are for physician referrals. To be able to provide patient outreach and programs, it is important that we continue to build up our membership; but there is also strength in numbers which really matters when it comes to advocacy.

Dr. Gurwitt and Ms. Proskauer echoed the same message—the impact of advocacy may not be immediately realized, but it can have a far-reaching effect and pay off in many ways. Statistics collected on the Association's website traffic reveal the extent of its global reach-during the past 12 months there were 20,000 unique visitors from 151 different countries.

The video of Dr. Anthony Komaroff's April 2010 lecture has been viewed from around the world and translated into 4 languages. It has served as a catalyst for important advocacy initiatives, like those embarked on by the Norwegian health ministry.

The Association also played a direct role in helping Japan form its first national ME/CFS conference.

It maintains close contact with the CDC, through Dr. Elizabeth Unger, and overall, it has shown a good, strong reach into a lot of areas, concluded Ms. Proskauer.

MassCFIDS will evaluate on-going advocacy initiatives, participate selectively, and provide opportunities for patients AND their family members, relatives or friends to participate. Our goal is to expand advocacy in Massachusetts.