Thursday, June 26, 2008

A doctor speaks out

"The best doctors are the ones who aren’t afraid to say ‘I don’t know’ or ‘I’m not sure.’ The most dangerous are the ones who think they know but don’t."

      – Anonymous oncologist, Santa Cruz CA

         Reader’s Digest 7/08

Every CFS patient can tell you horror stories about doctors "who think they know but don’t." I’m not alone in having dealt with a doctor who thought he recognized a couple of symptoms and gave me a wrong diagnosis based on that partial information.

What made that doctor especially dangerous was the fact that he thought he knew more than the specialists who’d already given me the correct diagnosis. He took it upon himself to overrule their expertise, to prescribe something the experts say doesn’t work for what I really have, and to blame the patient when treating what I don’t have didn’t cure me.

I told him at every appointment what the experts recommend, and at every appointment he came up with something else he wanted to try first. It became apparent that this was an ego game: he’s the doctor, I don’t have a medical degree. Even if the patient learned from experts in the field, she’s still not a doctor and therefore he doesn’t have to listen to anything she says about expert-recommended treatments. (Although we have patients who are medical professionals, and they also report their doctors playing Blame The Patient. See Dr. Ryll’s history of the Mercy San Juan Hospital epidemic, where CDC investigators concluded the doctors and nurses were "just too lazy to work.")

When the subject of the misdiagnosis came up after the fact, Dr. Thinks He Knows Everything’s explanation was "nothing you said made sense." And that comment made all the sense in the world ... the symptoms I described don’t make sense in the context of what he wanted to diagnose, and he didn’t know enough about CFS to make sense of them. They were specifically intended to not make sense for his desired diagnosis: I know what symptoms differentiate CFS from depression, and I make sure to recite those to be sure that I get the right diagnosis, so that a doctor who might be thinking depression stops short and thinks "that doesn’t make sense" and looks for another diagnosis that matches the symptoms. But, that requires the doctor to know what all the symptoms of depression are, and not just "tired and listless" (depression also requires an emotional component – crying, low self-esteem, thoughts of suicide – which I don’t have).

The very first doctor in 1987 who wanted to diagnose "hypochondriac female" insisted on a psych evaluation; a professor of counseling explained to us that without the required emotional involvement, the symptoms of depression/anxiety were the same as those of physical illness, and since I was running a fever, it would make more sense to him to refer my problem to an MD instead of a psychiatrist, because it sounded to him like I had the flu. In his professional opinion, nothing that was described sounded like a psychological problem. That doctor, too, didn’t want to hear that I had a clean psychiatric bill of health, and was in favor of sending me to as many shrinks as it took to get the opinion he wanted to hear.

As the Griffith/Zarrouf article posted earlier today says, the best diagnostic tool is a good history. They’re not popular among doctors because it takes time to take a good history, whereas you can slap an erroneous depression label on a patient as soon as she says "I’m tired". But "my symptoms started with a virus" will lead you along the path to CFS, as will inquiring into the patient’s emotional state, instead of taking the short-cut of assuming you know what she’s thinking: the circular reasoning that "if" the patient has depression, therefore the patient has the emotional symptoms of depression, and therefore, the patient must have depression, without ever asking the patient about those required emotional components. (As with any other debilitating illness, some patients develop depression as a result of being ill and unable to continue life as they knew it, but again, a good history will reveal that the patient was not depressed until after months of physical illness and reduced quality of life. In which case, anti-depressants can help the overlay of depression, though they won’t do a thing for the underlying physical illness, whether that’s CFS or cancer.)

I have respect for the doctor who told me "I don’t know much about CFS." I have respect for the doctor who told me "I’m not sure what to do for you, because there’s no magic pill." But I don’t have respect for doctors whose ego won’t allow them to say "I don’t know" or "I’m not sure" or "you’ve read a lot about this over the years since you were diagnosed, what do the experts say?"

My current doctor is not a CFS expert – it’s a full day’s journey to get to the nearest CFS expert and my health isn’t up to full days out of bed – but he’s open-minded enough to accept that I’m an intelligent, educated human being who can read English and tell the difference between snake oil and published research. If I bring him a research abstract or an article by one of the experts, he will discuss it with me; I know he’s not going to just write a prescription, we’re going to talk about the pros and cons, the potential side effects, but if I tell him "this expert says to try that pill" he’ll consider it, and not just dismiss it out of hand because it was my suggestion and not his own idea. And that’s really all I ask of a doctor: to admit that he can still learn a few things. Even the experts occasionally get together at conferences to learn from each other.

The problem is, the dangerous doctors will never admit to you or to themselves that they don’t know. They think they know, and therefore, they don’t think they need to seek outside expertise. If you ask them, they will tell you that they know about CFS; it takes time to see the proof that they don’t know as much as they think they do, and by then, the damage may be done.

I can never erase the erroneous comments in my medical records describing the fictional "long history of depression", the lie "never diagnosed by any doctor", the disparaging remarks that I "refuse to get better" so I don’t have to go back to work. The best I can do is to demand that anyone reviewing those records look at other records to try to find where anyone was prescribing all those anti-depressants I supposedly took non-stop for years and years, look at the proof that I was diagnosed with CFS by a CFS specialist in 1988 (and diagnosed again by rheumatologists in 2000, 2001, 2003, 2004...), and read the experts’ comments that support my stance that the reason I didn’t get better was because anti-depressants are totally useless for CFS.

At the time I was accused of not wanting to work, I had a business of my own and a second business started with a partner; what really doesn’t make sense is that accusation that I don’t want to work, because I’ve always either been looking for a job or running my own business. The real problem with work is that, without doctors addressing my actual disease, my health got worse and no one would hire someone who came into their office looking and acting deathly ill (one interviewer described me as "a worker’s comp claim waiting to happen" because the symptoms the doctor refused to see were so obvious to someone who was not in deep denial about the physical nature of my ailment).

As Dr. Katrina Berne writes, "Some problems are just not easily fixed, even when the motivation is strong." Most CFS patients have a strong motivation to get well and return to work, but the lack of proper medication means that their problem is not easily fixed. The lack of proper medication to fix the problem should not be blamed on the patient – it’s a direct result of the fact that many in the medical profession either don’t know or refuse to believe that CFS and depression are not the same thing, and the dearth of research funding resulting from CFS not being taken seriously. (According to Dorothy Wall, "In 2003, more than twenty years after the first CFS patients ... the total federal expenditure for CFS research – from both the NIH and CDC – was still a paltry $16 million. By contrast, according to its own documents, the NIH alone spent $99 million on multiple sclerosis in 2003, an illness affecting half as many people." Yet, the experts are clear that the level of disability in CFS is equivalent to the disability of MS, and therefore, it would seem fair that CFS should receive at least equal research funding.)

And as long as there are doctors who don’t know how to tell the difference between CFS and depression, yet insist on treating CFS patients anyway, there will be patients whose future health is in danger due to the doctor’s inability to say "I don’t know."


Figures and Tables at  

The Primary Care Companion to the Journal of Clinical Psychiatry Vol. 10, #2, pp. 120-128

March 2008

A systematic review of Chronic Fatigue Syndrome:

Don't assume it's depression

James P. Griffith, M.D., F.A.C.P., and Fahd A. Zarrouf, M.D. - From the Internal Medicine/Psychiatry Residency Program, West Virginia University, Charleston. - Corresponding author and reprints: Fahd A. Zarrouf, M.D., Medicine/ Psychiatry Residency Program, West Virginia University, 501 Morris St., 4 West, Charleston, WV 25326  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.



Chronic fatigue syndrome (CFS) is characterized by profound, debilitating fatigue and a combination of several other symptoms resulting in substantial reduction in occupational, personal, social, and educational status. CFS is often misdiagnosed as depression. The objective of this study was to evaluate and discuss different etiologies, approaches, and management strategies of CFS and to present ways to differentiate it from the fatigue symptom of depression.

Study Selection and Data Extraction

CFS definitions, etiologies, differential diagnoses (especially depression) and management strategies were extracted, reviewed, and summarized to meet the objectives of this article.

Data Synthesis

CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression. Genetic, immunologic, infectious, metabolic, and neurologic etiologies were suggested to explain CFS. A biopsychosocial model was suggested for evaluating, managing, and differentiating CFS from depression.


Evaluating and managing chronic fatigue is a challenging situation for physicians, as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.

"She is depressed," her physician wrote when referring Ms. A, a 65-year-old married woman, for a psychiatric consult. "She has been feeling tired for more than a year and described being exhausted most of the time, with headaches, joint pain, and problems with her concentration and memory. Her fatigue is frustrating for her and for her family; she cannot function well even in the morning. She denied being depressed, and does not have any previous mental or medical illnesses. Every lab I checked was normal. I still think that she is hiding her depression and manifesting it with all these somatic complaints."

Prolonged fatigue is defined as self-reported, persistent fatigue of 1 month or longer.1 Chronic fatigue syndrome (previously known as myalgic encephalomyelitis2 or neurasthenia3) is characterized by profound, debilitating fatigue and a combination of symptoms resulting in substantial reduction in occupational, personal, social, and educational status1,2,4-7 (see Table 1). Diagnosis of the chronic fatigue syndrome (CFS) can be made only after alternate medical and psychiatric causes of chronic fatiguing illness have been excluded.

At least 1 million Americans have CFS,1,8 more than have lung cancer or multiple sclerosis; yet more than 80% go undiagnosed. In the primary care setting, the prevalence of CFS ranges from 3% to 20% and from 80% to 90% at the end of life.9,10 There are no ethnic or racial differences. Previous reports have mentioned a female:male ratio of 1.3:1,6 but a recent report by the U.S. Centers for Disease Control and Prevention (CDC) showed a female:male ratio of 4:1. It occurs most often in the 40- to 59-year age group and in the geriatric population.1,9,10

Although the concept of neurasthenia was introduced in 1869 by George Miller Beard,3 CFS was defined in 1988 by the CDC, and while more than 3000 research studies have been done in this field, there is still some debate about the existence of this syndrome.1,11,12 The uncertainty about its existence and the lack of a specific laboratory test or marker to identify it, associated with hesitancy about making a diagnosis without knowing exactly how to treat it, all act as barriers to the diagnosis and treatment of CFS by primary care practitioners and psychiatrists.

Unlike the uncertainty about its existence, there is strong certainty about the impact of CFS. CFS patients, by definition, are functionally impaired and as disabled as patients with multiple sclerosis, heart disease, end-stage renal disease, and similar chronic conditions. The annual economic impact of CFS in the United States is estimated to be $9.1 billion in lost productivity.1


A MEDLINE search was conducted to identify existing information about CFS and depression using the headings chronic fatigue syndrome AND depression. The alternative terms major depressive disorder and mood disorder were also searched in conjunction with the term chronic fatigue syndrome. Additionally, MEDLINE was searched using the term chronic fatigue. All searches were limited to articles published within the last 10 years, in English. A total of 302 articles were identified by these searches. Also, the term chronic fatigue syndrome was searched by itself. This search was limited to articles published within the last 5 years, in English, and resulted in an additional 460 articles. Additional publications were identified by manually searching the reference lists of the articles from both searches.


CFS cannot be considered either physical or psychological but instead requires a biopsychosocial approach to the illness. Numerous studies have tried to pinpoint specific etiologies by considering the following fields.

Genetic Etiologies

CFS is sometimes seen in members of the same family,13,14 but there is no evidence that it is contagious; instead, there may be a familial predisposition or a genetic link. The concordance rate was higher in monozygotic than in dizygotic female twins for chronic fatigue.15 Hickie et al.16 evaluated genetic and environmental determinants of prolonged fatigue in a twin study and found 44% (95% CI=25% to 60%) of the genetic variance for fatigue was not shared by the other forms of psychological distress, and also found that environmental factors made negligible contributions to fatigue. On the other hand, Cho et al.17 found evidence of a partly genetic influence, but environmental effects continued to be predominant. Clearly, further research is needed to explore these possible relationships.

Immunologic Etiologies

Abnormal natural killer cell cytotoxicity,18 increase immune activation markers,19 greater numbers of CD16+/CD3- natural killer cells,20 and the presence of interferon in serum and cerebrospinal fluid in CFS patients21 have been identified. Staines22 suggested the loss of immunologic tolerance to vasoactive neuropeptides or their receptors following infection, other events, or de novo as a mechanism.

Infectious Etiologies

Possible infectious etiologies have generated the most interest among CFS researchers. It has been postulated that chronic fatigue is a continuum ranging from cases with chronic viremia on the one hand to instances of frank psychiatric illness on the other.23 Multiple infectious agents have been linked to CFS, including Borna disease virus,24,25 parvovirus B19,26,27 glandular fever,28 Enterovirus,29 human herpesviruses 4, 6, and 7,30-32 infectious mononucleosis,33 Nipah virus encephalitis,34 and Q fever.35

Infections have not only played important etiologic roles, but also have been considered predictors of better prognoses when compared to noninfectious CFS cases.36 Human herpesvirus 6 reactivation has been suggested as an objective biomarker for fatigue.30

Endocrinology/Metabolism Etiologies

Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been studied as potential biological tests to diagnose CFS. Studies have shown HPA hypoactivity and higher chronic adrenocorticotropic hormone (ACTH) autoantibody levels as significant pathologic factors in CFS.37-39 Also reduced area under the ACTH response curve in CFS patients undergoing insulin tolerance test was significantly associated with the duration of CFS symptoms (r=-0.592, p=.005) and the severity of fatigue symptomatology.40 Other studies have suggested upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression.41 However, another study showed no etiologic role for deficiency in central opioids or the HPA axis in the symptoms of CFS.42 Other biological factors have been investigated and considered as biological markers in CFS, including low magnesium level,43 low arachidonic acid level, low L-carnitine level,25 serum dehydroepiandrosterone (DHEA) sulfate deficiency,44 and impairments of the 2',5'-oligoadenylate (2-5A) synthetase/RNase L pathway.45 Other studies showed no role of linoleic acid, eicosatrienoic acid (both p>.05),25 ferritin, vitamin B12, folate, or serum erythropoietin levels.46

Mental/Neurologic Etiologies

Psychosocial factors are frequently thought to contribute to fatigue. Rangel et al.13 found that CFSin childhood and adolescence is associated with higher levels of parental mental distress, emotional involvement, and family illness burden than those observed in association with juvenile rheumatoid arthritis, a chronic pediatric physical illness. Endicott14 described stressors including earlier mortality age and increased prevalence of cancer, autoimmune disorders, and CFS-like conditions in parents of psychiatric patients with CFS as compared to control groups. Thirty percent of the CFS patients and none of the controls reported dilemmas in the 3 months prior to the CFS onset in one study.47 History of abuse, particularly during childhood, may play a role in the development and perpetuation of chronic fatigue,48 and childhood trauma was associated with a 3- to 8-fold increased risk for CFS across different trauma types in one study.49 Sleep is also an interesting etiologic factor, as many patients with CFS have sleep disorders, and those with sleep disorders showed greater functional impairment independent of their psychiatric disorders.50-52


Fatigue is a part of a wide spectrum of diagnoses ranging from being a symptom in depression, anxiety, seasonal affective disorder,53 and multiple other diagnoses to being a full syndromal disorder in CFS, yet CFS goes undiagnosed in 80% of cases and is often misdiagnosed as depression. The Diagnostic and Statistical Manual of Mental Disorders doesn't list CFS as a diagnosis although the International Classification of Diseases, 10th Revision, does.12 In clinical practice, CFS presentations range from complicated cases associated with a psychotic state resulting in multiple murders in one case report54 to noncomplicated presentations with multiple psychiatric disorders, primarily depression.55 It is very important to understand the distinctive features between chronic fatigue and depressive disorder when evaluating a patient with a main complaint of fatigue. A full detailed history accompanied by questionnaire forms can be very helpful to differentiate CFS from major depressive disorder. There is still no specific test that can confidently differentiate between them. Multiple studies have tried to find distinctive factors and they are listed in Table 2.


Diagnosing CFS can be challenging for health care professionals for many reasons; the most important one is finding fatiguein a large number of illnesses and disorders. We reviewed information available about evaluation of chronic fatigue and discuss it in 3 parts: history, exam, and diagnostic tests.

History and Differentials

Because CFS is a diagnosis of exclusion,1 a full detailed history is considered essential. The history should include a detailed account of the symptoms, the associated disability, the choice of coping strategies, and importantly, the patient's own understanding of his/her illness.65 Every patient should be carefully evaluated for certain medical, psychiatric, and neurologic diseases that can cause fatigue as the most prominent symptom (Table 3). Two of the important differential diagnoses are depression and fibromyalgia. Although it is difficult to differentiate CFS from fibromyalgia confidently depending on the history or other reported differences of cognitive dysfunction components or clinical pain measures,66,67 CFS and fibromyalgia commonly co-occur within the concept of central sensitivity syndromes or functional somatic syndromes.68 This co-occurring increases functional impairment when compared to CFS individuals alone.69,70 Some of the distinguishing features between CFS and fibromyalgia include evidence for triggering viral infection and lower level of serum acylcarnitine observed in CFS patients, which is lacking in the majority of patients with fibromyalgia;71 slower information-processing in CFS patients compared to impaired control of attention in fibromyalgia patients;66 and lacking of the characteristic diffuse soft tissue pain and pain on palpation in at least 11 of 18 paired tender points in CFS patients.


Every CFS evaluation should include a mental status examination to identify abnormalities in mood, intellectual function, memory, and personality. Particular attention should be directed toward current symptoms of depressive, anxious, self-destructive thoughts and observable signs such as psychomotor retardation.1 Although there is no definite physical finding, a full and thorough physical examination may be helpful in excluding other conditions. Multiple studies have suggested dysautonomia with greater increase in heart rate together with a more pronounced systolic blood pressure fall on standing in CFS patients compared to healthy individuals.46, 72 Other studies found no statistically significant differences in either heart rate or galvanic skin resistance both during a normal day and before, during, and after exercise testing.73


The CDC has recommended the following initial screening tests when evaluating patients with CFS: urinalysis, total protein, glucose, C-reactive protein, phosphorus, electrolyte, complete blood count with leukocyte differential, alkaline phosphatase, creatinine, blood urea nitrogen, albumin, antinuclear antibody and rheumatoid factor, globulin, calcium, alanine aminotransferase or aspartate transaminase serum level, and thyroid function tests (thyroid stimulating hormone and free T4).1 Further tests or referral to specialists may be indicated to confirm or exclude a diagnosis that better explains the fatigue state or to follow up on results of the initial screening tests.

Multiple other studies have tried to find biomarkers or radiological markers for CFS. Erythrocyte sedimentation rate was normal in all 23 CFS patients in one study.74 Another study found that concentrations of C-reactive protein, beta_2-microglobulin, and neopterin were higher in patients with CFS (p=<.01).75 On the other hand, a study by Swanink et al.76 found that complete blood cell count, serum chemistry panel, C-reactive protein, and serologic tests were not different in 88 patients with CFS when compared to a control group. A potential role for DHEA in CFS, both therapeutically and as a diagnostic tool, was suggested in one study.64

Magnetic resonance imaging studies have been inconsistent, with some of them suggesting larger ventricular volumes.77-84 Functional magnetic resonance was more promising, as it showed quantitative and qualitative differences in activation of the working memory network,85 attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing tasks,86 utilization of more extensive regions of the network associated with the verbal working memory system,87 impaired functioning and reduced gray-matter volume in the bilateral prefrontal cortex,88 and inactive ventral anterior cingulate after making an error.89

Single-photon emission computed tomography (SPECT) and brain electrical activity mapping scans were promising in one study,90 and SPECT scans showed more abnormalities than did magnetic resonance scans in one study (p<.025).91 Siessmeier et al.92 detected abnormalities in 18-fluorodeoxyglucose positron emission tomography in approximately half the CFS patients examined, but found that no specific pattern for CFS could be identified. Positron emission tomography showed an alteration of the serotonergic system in the rostral anterior cingulate in one study, which was suggested as an etiology.93 Recently, Puri94 described the application of proton neurospectroscopy and 31-phosphorus neurospectroscopy in chronic fatigue syndrome. It is essential to mention that evidence to date does not support routine use of the imaging modalities discussed above in evaluating potential CFS patients.

Finally, it is important to remember that a good history is more important than any available test to diagnose CFS and differentiate it from depression. The algorithm shown in Figure 1, which is based on the CDC recommendations and the results of the studies reviewed, is suggested for evaluating chronic fatigue.

Don't Assume It's Depression (Part 2)


It is important to manage fatigue in the context of each patient suffering with it. Treatment of CFS, with its various major clinical and functional impacts, should be associated with a "biopsychosocial model" of management. Educating patients about their diagnoses is crucial. Physicians should emphasize distinction among factors that may have predisposed patients to develop, trigger, or perpetuate the illness.65 Progressive muscular rehabilitation, combined with behavioral and cognitive treatment, and appropriate choice of medications are essential parts of therapy.8

We will review the major concepts of CFS management and the evidence behind them.

Supportive and Symptomatic Treatment

Educating patients about CFS and validating their illness experience in addition to establishing a working alliance are the initial steps in the treatment.1,65 Direct the treatment toward the most problematic symptoms, as prioritized by the patient,1 and other illness-perpetuating factors.65 Encourage a well-balanced diet, and discuss with patients their nutritional habits. Advice about preventing over- and under-activity is essential. "Start low and go slow" is the correct advice for activities and exercise, the same as for using medications. Gear activities toward improving function in areas that are of greatest importance in achieving activities of daily living and remain open-minded about alternative therapies (electroacupuncture was helpful in one study95) and discuss them with your patients when appropriate.1 Consider referring or asking for consults and discuss that with patients early in the treatment.

Cognitive Behavioral Therapy

The short-term studies of cognitive behavioral therapy (CBT) in CFS have shown improvement in function and symptom management, especially in conjunction with other treatment modalities and in comparison to relaxation controls.96-99 Reports about good outcome following CBT ranged from 70%99 to none or even worsening of the symptoms.100 CBT was effective in treating symptoms of fatigue, mood, and physical fitness, but no improvement in cognitive function or quality of life was noticed in one study.101 Other studies showed limited effect on pain and fatigue.1 When treating CFS patients, the CBT therapist needs to be familiar with CFS, to be aware of the evidence for CFS as a biologically based disorder, and to validate the patient's experience of living with a misunderstood illness.


CFS patients are very sensitive, and any treatment modality including exercise should start low and advance slowly. All exercises need to be followed by a rest period at a 1:3 ratio (i.e., 10 minutes of exercise: 30 minutes of rest). Review of the studies showed that exercise decreased the psychological stress102 and improved fatigue, functional capacity, and fitness significantly better than flexibility treatment,103 especially when associated with mood-enhancing, stress-reducing activities.104,105

Pharmacologic Treatment

Multiple studies have evaluated different treatment interventions, including recombinant erythropoietin, psychostimulants, corticosteroids, anti-inflammatory drugs, L-carnitine, and others.10,106 Antidepressants are the most common medications used in this regard; selegiline had a small but significant therapeutic effect independent of its antidepressant effect.107 Fluoxetine has been shown to improve overall symptoms and measures of immune function in one study,108 but failed in randomized, double-blind studies against placebo109 and graded exercise.110 Bupropion was effective for treatment of the fatigue and depressive symptoms associated with CFS in 9 fluoxetine-resistant patients111 and was also helpful in augmenting paroxetine in one case report.112 Venlafaxine was effective in 2 case reports.113 Moclobemide up to 600 mg a day for 6 weeks showed significant but small reductions in fatigue, depression, anxiety, and somatic amplification, as well as a modest overall improvement.114 Duloxetine may have a theoretical therapeutic benefit because of its characteristic of targeting pain. We could not find any study evaluating it in CFS patients. It is essential to mention that evidence to date does not support superiority of one medication over the others.

Other medications have been studied also. Clonidine enhanced both growth hormone (p=.028) and cortisol release (p=.021) and increased speed in the initial stage of a planning task (p=.023) only without affecting hormonal, physiologic, symptomatic, or neuropsychological measures.115 Low-dose hydrocortisone therapy caused increases in plasma leptin levels, with this biological response being more marked in those CFS subjects who showed a positive therapeutic response to hydrocortisone therapy.116 Essential fatty acid supplement rich in eicosapentaenoic acid was beneficial in a case report.117 Carnitine supplementation has been shown to reduce chronic inflammation and oxidative stress in hemodialysis patients and, in cancer patients, reduce fatigue and improve outcome.118 Treatment with modafinil was not beneficial in patients with CFS in one study.119

No therapeutic effects were found for natural killer cell stimulant,120 low-dose combination therapy of hydrocortisone and fludrocortisone,121 immunologic and antiviral substances, melatonin, or bright-light phototherapy.122


Evaluating and managing chronic fatigue is a challenging situation for physicians as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.

Drug names: bupropion (Wellbutrin and others), duloxetine (Cymbalta), clonidine (Catapres, Duraclon, and others), fluoxetine (Prozac and others), hydrocortisone (Cortef, Texacort, and others), modafinil (Provigil), paroxetine (Paxil, Pexeva, and others), selegiline (Eldepryl, Emsam, and others), venlafaxine (Effexor).

Tuesday, June 24, 2008

The case for inequality

Over the past few weeks, 600 people have gotten salmonella from tomatoes, and the government has launched an international search for the source of the infection.

Over the past 25 years, 1,000,000 Americans have gotten CFS, and the government seemingly could not care less.  Money designated for CFS research was used for something else, discovered, repaid, and then a second time used for something else!

Why does salmonella -- which is usually just a matter of a few days of digestive problems -- deserving of this multi-million-dollar investigation, while a disease that results in permanent disability has to beg for every research dollar?

The answer is clear to anyone who has read "Osler's Web" ...  one of the experts eventually realized "they don't WANT to find anything."  Finding proof that CFS exists would result in proof that CDC lied all along.

Monday, June 23, 2008

Self Help: Pacing

This week we begin a new eight-part series: "Pacing: What It Is and How to Do
It." The first article describes how to define your Energy Envelope.

Our website contains many articles on topics such as coping strategies, pacing
and support. In addition, there are patient success stories and information for
family and friends. In addition to our website, we offer self-help courses
online. Founded in 1998 as a 501(c)(3) non-profit organization, we have
conducted nearly 250 self-help courses and groups.

Bruce Campbell, Ph.D., Executive Director
CFIDS & Fibromyalgia Self-Help Program

* * *

Dr. Ellen Goudsmit (one of our many patients with the academic qualifications to also be an expert) has written extensively on pacing.  Some of those articles appear in this blog, others can readily be googled.

The key to pacing is that you never push yourself to the point that causes you to relapse.  Ideally, you would work for a short time, rest for 2-3 times that period (e.g., 20 minutes work/60 minutes rest) then work a little more.  By working in short increments, you never get over-tired, you're continually topping off your tank.

Obviously, there are times you can't do that -- grocery stores take a dim view of people napping in the aisles -- but I find that I feel better if I work in short bursts throughout the day, for a total of 2 hours, than if I work for 2 hours all at once. 

There's nothing that says you can't load the top rack of the dishwasher, take a nap, then load the bottom rack.  At my worst, on Day 1 I would strip the bed and load up the laundry basket; on Day 2 I'd carry the basket to the washer; on Day 3 I'd load the washer....  It took me a full week to do one load of laundry, but it was done, and I hadn't made myself worse.

I hope all CFS patients reading this blog take the opportunity to sign up for this series on pacing.  Research has shown that you won't accomplish more with pacing, you'll just feel better.  And the key with this disease is to avoid making yourself worse.  Stay well within your limits, and you may start to recover. 

I was able to work full-time for 12 years after diagnosis because of pacing: if I wasn't at work, I was resting.  I missed a lot of parties, festivals, plays, museum exhibitions, etc.,  because of my need to rest evenings and weekends, but I was able to put off the day when I had no choice but to swallow my pride and apply for SSDI benefits. 

Pain and Therapy

From acute musculoskeletal pain to chronic widespread pain and
fibromyalgia: Application of pain neurophysiology in manual therapy practice.

Man Ther. 2008 May 27. [Epub ahead of print]

Nijs J, Van Houdenhove B.

Department of Human Physiology, Faculty of Physical Education and
Physiotherapy, Vrije Universiteit Brussels, Belgium; Division of
Musculoskeletal Physiotherapy, Department of Health Care Sciences,
University College Antwerp, Van Aertselaerstraat 31, B-2170 Merksem, Belgium.

PMID: 18511329

During the past decade, scientific research has provided new insight
into the development from an acute, localised musculoskeletal
disorder towards chronic widespread pain/fibromyalgia (FM). Chronic
widespread pain/FM is characterised by sensitisation of central pain
pathways. An in-depth review of basic and clinical research was
performed to design a theoretical framework for manual therapy in
these patients.

It is explained that manual therapy might be able to influence the
process of chronicity in three different ways.

(I) In order to prevent chronicity in (sub)acute musculoskeletal
disorders, it seems crucial to limit the time course of afferent
stimulation of peripheral nociceptors.

(II) In the case of chronic widespread pain and established
sensitisation of central pain pathways, relatively minor
injuries/trauma at any locations are likely to sustain the process of
central sensitisation and should be treated appropriately with manual
therapy accounting for the decreased sensory threshold. Inappropriate
pain beliefs should be addressed and exercise interventions should
account for the process of central sensitisation.

(III) However, manual therapists ignoring the processes involved in the development and maintenance of chronic widespread pain/FM may
cause more harm then benefit to the patient
by triggering or
sustaining central sensitisation.

* * *

If you're looking for a massage therapist or a physical therapist, always ask about their familiarity with fibromyalgia or CFS before you sign on with them.  The wrong type of massage can cause more pain, and a personal trainer or physical therapist who believes "no pain, no gain" will likely push a CFS patient beyond her limits, which could result in permanent disability.

Your body is not normal and should not be treated in the normal manner, because it will react abnormally.  The therapist must be willing to stop when you say "ow" or "enough", because the best expert on what your body can handle is YOU. 

Restoration of ADA

ADA Restoration & a Potential Deal with the Business Community

Summary of Current Status on ADA Restoration

This is a key week for ADA Restoration. After thirteen weeks of negotiations with the business community, endless drafting and redrafting of legislative language, and numerous meetings and calls for internal vetting within our own community, we have potential deal language. This language can radically improve the legal outcomes of people with disabilities who have tried to bring employment discrimination cases but who have been turned away by the courts for almost ten years now.

Time is of the essence. In order to have any chance of passing this legislation in this Congress given the full Congressional calendar and the upcoming focus on the elections, we must know where we stand as we enter this holiday weekend to enable us to put things into motion early next week. For that reason, both the disability and business communities have agreed to come to a decision on whether or not we will accept and support the proposed deal language by close of business this Thursday, May 22.

Why do we need ADA Restoration?

Almost eighteen years ago, Congress passed and President H.W. Bush signed the Americans with Disabilities Act (ADA), a civil rights law promising freedom and equality for people with disabilities in public transportation, businesses, public programs and services, and the workplace. Borrowing the definition of disability from Section 504 of the Rehabilitation Act, Congress intended the ADA to stop employers from making employment decisions based on a person's current, past, or perceived disability.

Under current law, the ADA defines an individual with a disability as an individual with a physical or mental impairment that substantially limits a major life activity, an individual with a history of such an impairment, or an individual who is regarded or perceived as having such an impairment.

Unfortunately, since 1999, the courts have dramatically scaled back the ADA definition to the point where it bears little resemblance to the robust civil rights law that Congress passed in 1990. In a series of Supreme Court cases, the Court decided that the use of medication, prosthetics, hearing aids, auxiliary devices, etc. must be considered when a court is determining if someone is protected under the law. That means that people with all kinds of disabilities who enjoy greater independence (including the ability to work) on account of medication, hearing aids, specific diets, prosthetics, etc., are often no longer protected under the ADA because the courts view their limitations as no longer substantial "enough." Courts have even denied ADA protection to those whose employers have freely admitted that they terminated the individuals because of their disabilities!

The ADA was meant to be just like other civil rights laws that address employment discrimination - when someone experiences discrimination because of disability, the sole focus of the legal case should be on whether the actions of the employer were unlawful. However, the Courts have created an extra hoop for people with disabilities to challenge an employer's actions. First, people with disabilities must "prove" their disability by providing highly personal and often wholly irrelevant information about their lives. Only if they have satisfied this difficult standard are they then permitted to present the facts of the discrimination they encountered. Increasingly, fewer and fewer people are able to get to this point.

Instead of following Congress's clear intention that the definition of "disability" in the ADA be interpreted broadly, the Supreme Court decided to ignore Congressional intent and directed that the definition of disability needed to be interpreted narrowly. As a result, there have been hundreds of court cases with bizarre and devastating outcomes -- with the courts siding with employers rather than individuals facing discrimination more than 90% of the time. People with epilepsy, muscular dystrophy, multiple sclerosis, diabetes, cancer, HIV, intellectual disabilities (formerly known as "mental retardation"), hearing loss, major depression, PTSD, bipolar disorder, and many other disabilities are consistently being told that they are not "disabled enough" and therefore not protected by the ADA.

By watering down civil rights protections for people with disabilities, the courts have created an unacceptable U-turn in the progress that people with disabilities have made to date. Courts have made it legal for an employer to say "You are not welcome here" to people with disabilities who have skills and who want to work.

We knew we needed to act.

What have we done to fix these problems?

In 2004, the National Council on Disability (NCD), the same independent federal agency that drafted the original ADA, published a report entitled "Righting the ADA", which harshly criticized the Supreme Court decisions referenced above. In its recommendations, NCD included proposed legislative language to remedy the problems created by the Courts' narrow interpretations of the definition of disability in the ADA.

While the devastation created by the courts was obvious to everyone, there was widespread concern within the community that "opening" the ADA up for legislative fixes would result in opponents of the law would attempting to water down other protections. For several years, internal discussions within the community revolved around when and how to best address the damage done by the courts.

Then, in September of 2006, after much discussion with the community and using the NCD report language as a basis, then House Judiciary Committee Chairman Jim Sensenbrenner and House Minority Whip Steny Hoyer introduced H.R. 6258, the ADA Restoration Act of 2006. While the legislation did not receive any action, advocates used its introduction to strategize for the next Congress.

A short time later, on July 26, 2007, the 17th anniversary of the signing of the original ADA, Congressman Sensenbrenner and now Majority Leader Hoyer introduced H.R. 3195, the ADA Restoration Act of 2007 (the companion bill, S. 1881, was introduced in the Senate on the same day by Sens. Tom Harkin and Arlen Specter). Due to the tireless efforts of disability advocates, there were 143 original co-sponsors in the House on the day of the bill's introduction. That number has since risen to 245 co-sponsors.

Why did we even enter into negotiations with the business community in the first place?

At the same time that the disability community has been visiting the offices of Members of Congress to urge co-sponsorship and support of ADA Restoration, members of the business community were also hard at work, delivering a message to many of the same offices that the legislation goes "too far" and would hurt businesses.

Concerned that Members of Congress who are sympathetic to the business community's interests would attempt to alter or amend the legislation in damaging ways, including some of the bill's own co-sponsors, Congressional champions of the bill, including Majority Leader Steny Hoyer, encouraged the disability community to meet with the business community to discuss the legislation in the hope that mutually agreed-upon language would emerge. The understanding and goal of both sides was to attempt to craft language that could be mutually defended through the entire legislative process to increase the likelihood of successful passage of a "clean" bill - one free of amendments or other unforeseen changes - in the House and Senate during this year.

Since February 19, 2008, the disability community, with leadership from the American Association of People with Disabilities (AAPD), the National Council on Independent Living (NCIL), the Bazelon Center on Mental Health Law, the National Disability Rights Network (NDRN), and the Epilepsy Foundation, has been in negotiations with the business community around the legislative language. . These groups have met with the understan.ding that, if a deal is reached, both sides will defend the deal and that if any minor clarifications or amendments are put forward during the legislative process, both sides must agree to them.

How does the proposed deal change the ADA?

The proposed deal language:

a.. Requires that the definition of disability be interpreted broadly;

b.. Prohibits courts from considering the effects of medication, prosthetics, hearing aids, etc. when determining whether a person meets the ADA's definition of disability;

c.. Defines "disability" as any actual, past, or perceived physical or mental impairment that "substantially limits a major life activity" and then defines this phrase to mean "materially restricts a major life activity;"

d.. Includes a broad definitional section listing a wide range of major life activities that is intended to restore coverage for many of the groups who have been interpreted out of the ADA by the courts, and

e.. Includes a broad "regarded as" prong that will provide civil rights protection to anyone who is adversely treated based on a physical or mental impairment

The proposed deal provides examples of "major life activities" in its definition section which helps to set the record straight where the courts have wrongly interpreted the term narrowly in the past. The non-exhaustive list includes but is not limited to: "caring for oneself, seeing, hearing, eating, sleeping, walking, standing, lifting, bending, speaking, breathing, learning, reading, concentrating, thinking, communicating, and working." The language also includes a list of "major bodily functions" as part of the definition of "major life activities."

In addition, the proposed deal language expressly rejects the Supreme Court cases which have created the mess which we seek to remedy. It also makes clear that for someone whose disability is episodic (such as with epilepsy) or in remission (such as with cancer), for purposes of establishing their eligibility for the ADA's protections, they are to be considered when their disabilities are active, meaning they will not be shut out of protections if they are discriminated against because of their disabilities simply because they are not currently experiencing the symptoms associated with their disabilities in their active state.

Under the proposed deal, people with a wide range of conditions like epilepsy, diabetes, depression, cancer, and muscular dystrophy will be able to come into the scope of the law's protection through a number of avenues. They can come in under a much broader "regarded as" prong, they can come in under a reconfigured first prong that includes the operation of important bodily functions as part of the definition of major life activities. And, probably most importantly, they can come in under the clarification that their conditions are to be assessed in the absence of any mitigating measures for purposes of deciding if they are substantially limited in a major life activity. For people with episodic conditions, the deal language also makes it clear that their conditions are to be assessed when their conditions are manifesting themselves, not when they are dormant or in remission. In sum, the proposed deal gives people with a wide range of disabilities many more tools for asserting their civil rights protections than they have under current law.

In summary, under the deal language, if a person is discriminated against because of an actual, past, or perceived physical or mental impairment, regardless of severity (except for transitory and minor impairments like the common cold or flu), s/he is eligible for protection under the ADA but not for a reasonable accommodation. However, if a person requests a reasonable accommodation and is materially restricted in a major life activity, s/he would be eligible for a reasonable accommodation.

How does the proposed deal help the disability community?

Right now, all across America, a multitude of people with a wide range of disabilities are denied their civil rights protections on account of the Supreme Court's narrow interpretation of what was intended to be our great civil rights law. As referenced earlier, more than 90% of the time, courts throw out the legal cases of people with disabilities before they even have a chance to prove the facts of discrimination because the courts decide that they are not "disabled enough" to warrant the law's protections in the first place. If we don't pass ADA Restoration legislation, it is not clear how much further the courts will go in narrowing the scope of the ADA's protected class. Any person with a disability who is able to work and live independently is at risk of being found not disabled "enough" for civil rights protections in the workplace given the decisions that we have seen in the federal courts.

In fact, just days after one of the Supreme Court's devastating ADA decisions, cases of disability employment discrimination- some of which involved employers who openly admitted to discriminating on the basis of disability - were thrown out of court because of the Supreme Court's decision. Disability advocates around the country have for years reported the "chilling effect" of the Supreme Court's decisions on efforts to bring disability employment discrimination cases, with lawyers often telling them that there is little hope in winning such cases.

Given the current political climate, the proposed deal language gives us our best shot at fixing the definition of "disability" under the ADA in this Congress and restoring the civil rights of people from across our community who have been told they don't have any rights. Advocates at NCIL, AAPD and others who have worked on this legislation are not convinced that we will do better in the next Congress, in part because the business community's views will be taken seriously by many Democrats and Republicans in any Congress.

The deal language is in line with the goal of ADA Restoration, which is to restore Congress' intent under the ADA by shifting the focus from whether a person is "truly" disabled, to whether the person was treated unfairly on the basis of disability - whether actual, past, or perceived.

What happens if we accept the deal?

If the disability community agrees to this deal language, we will work closely with our Congressional champions to move quickly to pass the revised legislation in the House of Representatives and the Senate. Our goal is to have the legislation passed by this Congress and signed by President Bush before October.

Please direct any questions, comments, or concerns to Anne Sommers at .

* * *

I am one of many people who employers and VocRehab consider "too disabled to work", but the courts consider "not bad enough to qualify as 'disabled'."  People who fall into the cracks are denied the help they need -- Social Services acknowledges that I clearly need assistance, but the law says they can't give it to me because I'm not officially "disabled"; you have to be either "disabled" or over 65 to qualify for In Home Support Services, and it looks like I'll get it by virtue of turning 65 long before any judge agrees with VocRehab that I'm not employable due to disability.

On the one side, a judge ruling on ADA-required accommodations said that a CFS patient who required "work when able" was too disabled to work.  On the other side, judges ruling on Disability applications have repeatedly stated that a CFS patient who can "work when able" is not disabled because they can occasionally work.

My SSDI judge has repeatedly said that "with your qualifications and experience, anyone should be happy to hire you and make any necessary accommodations."  Yet, when I talked to an attorney with ADA expertise about getting the accommodations I needed in order to be able to work, he gave me a list of cases to read that make it clear that the accommodations I need are far beyond what employers are required to give me.  In the current "bottom line first and foremost" business climate, it's not likely I'll find an employer willing to go above and beyond what the law mandates, so I remain too disabled to use ADA to get a job, but apparently not disabled enough to get SSDI benefits. 

Text of ADA Restoration Bill

The proposed deal language follows below:


To restore the intent and protections of the Americans with Disabilities Act of 1990. Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled,

SECTION 1. SHORT TITLE. This Act may be cited as the 'ADA Restoration Act of 2008'.

SEC. 2. FINDINGS AND PURPOSES. (a) Findings- Congress finds that-

(1) in enacting the Americans with Disabilities Act of 1990 (ADA), Congress intended that the Act 'establish a clear and comprehensive prohibition of discrimination on the basis of disability' and provide broad coverage;

(2) in enacting the ADA, Congress recognized that physical and mental disabilities in no way diminish a person's right to fully participate in all aspects of society, but that people with physical or mental disabilities are frequently precluded from doing so because of prejudice, antiquated attitudes, or the failure to remove societal and institutional barriers;

(3) while Congress expected that the definition of disability under the ADA would be interpreted consistently with how courts had applied the definition of handicap under the Rehabilitation Act of 1973, that expectation has not been fulfilled;

(4) the holdings of the Supreme Court in Sutton v. United Airlines, Inc., 527 U.S. 471 (1999), Murphy v. United Parcel Service, Inc., 527 U.S. 516 (1999), Albertson's, Inc. v. Kirkingburg, 527 U.S. 555 (1999), and Toyota Motor Manufacturing, Kentucky, Inc. v. Williams, 534 U.S. 184 (2002) have narrowed the broad scope of protection intended to be afforded by the ADA, thus eliminating protection for many individuals whom Congress intended to protect; and

(5) as a result of these Supreme Court cases, lower courts have incorrectly found in individual cases that people with a range of substantially limiting impairments are not people with disabilities.

(b) Purpose- The purposes of this Act are-

(1) to carry out the ADA's objectives of providing 'a clear and comprehensive national mandate for the elimination of discrimination' and 'clear, strong, consistent, enforceable standards addressing discrimination' by reinstating a broad scope of protection to be available under the ADA;

(2) to reject the requirement enunciated by the Supreme Court in Sutton v. United Airlines, Inc., 527 U.S. 471 (1999), Murphy v. United Parcel Service, Inc., 527 U.S. 516 (1999), and Albertson's, Inc. v. Kirkingburg, 527 U.S. 555 (1999), that whether an impairment substantially limits a major life activity is to be determined with reference to the ameliorative effects of mitigating measures;

(3) to reject the Supreme Court's reasoning in Sutton v. United Airlines, Inc., 527 U.S. 471 (1999) with regard to coverage under the third prong of the definition of disability and to reinstate the reasoning of the Supreme Court in School Board of Nassau County v. Arline, 480 U.S. 273 (1987) which set forth a broad view of the third prong of the definition of handicap under the Rehabilitation Act of 1973;

(4) to reject the standards enunciated by the Supreme Court in Toyota Motor Manufacturing, Kentucky, Inc. v. Williams, 534 U.S. 184 (2002), that the terms 'substantially' and 'major' in the definition of disability under the ADA 'need to be interpreted strictly to create a demanding standard for qualifying as disabled,' and that to be substantially limited in performing a major life activity under the ADA 'an individual must have an impairment that prevents or severely restricts the individual from doing activities that are of central importance to most people's daily lives'; and

(5) to provide a new definition of "substantially limits" to indicate that Congress intends to depart from the strict and demanding standard applied by the Supreme Court in Toyota Motor Manufacturing, Kentucky, Inc. v. Williams and by numerous lower courts.

SEC. 3. CODIFIED FINDINGS. Section 2(a) of the Americans with Disabilities Act of 1990 (42 U.S.C. 12101) is amended-

(1) by amending paragraph (1) to read as follows:

'(1) physical or mental disabilities in no way diminish a person's right to fully participate in all aspects of society, yet many people with physical or mental disabilities have been precluded from doing so because of discrimination; others who have a record of a disability or are regarded as having a disability also have been subjected to discrimination;'

(2) by striking paragraph (7).


Section 3 (42 U.S.C. §§12102) is amended:

By revising subsection (2) to read as follows:

(2) Disability -- The term "disability" means -

(A) a physical or mental impairment that substantially limits a major life activity;

(B) a record of an impairment that falls under (A); or

(C) being regarded as having an impairment that falls under (A) or (B).

By inserting after subsection (2) the following new subsections:

(3) Substantially Limits -

The term "substantially limits a major life activity" means materially restricts a major life activity.

(4) Major Life Activities -

a) Non-Exhaustive List of Major Life Activities -- Major life activities include, but are not limited to, caring for oneself, seeing, hearing, eating, sleeping, walking, standing, lifting, bending, speaking, breathing, learning, reading, concentrating, thinking, communicating and working. b) Major Bodily Functions -- A major life activity also includes the operation of a major bodily function. Major bodily functions include, but are not limited to, functions of the immune system, normal cell growth, digestive, bowel, bladder, neurological/brain, respiratory, circulatory, endocrine and reproductive functions.

(5) Regarded as -

(a) In General -- Subject to subsection (b), an individual meets the requirement of "being regarded as having an impairment that falls under (a)-(b)" if the individual establishes that he or she has been subjected to an action prohibited under this Act because of an actual or perceived physical or mental impairment, whether or not the impairment actually substantially limits a major life activity or whether or not the individual actually has the perceived impairment.

(b) Transitory and Minor Impairments -- This subsection shall not apply to transitory and minor impairments where "transitory" means an impairment with an actual or expected duration of six months or less.

(c) Reasonable Accommodation -- An employer is not required to provide a reasonable accommodation to an individual who meets the definition of disability solely under 2(C).

(6) Standards for Applying the Definition of Disability -

(A) To achieve the remedial purposes of this Act, the definition of "disability" shall be construed broadly.

(B) An impairment that materially restricts one major life activity need not limit other major life activities in order to be considered a disability.

(C) An impairment that is episodic or in remission is a disability if it would materially restrict a major life activity when active.

(D) (a) When determining whether an impairment materially restricts a major life activity, such determination shall be made without regard to the ameliorative effects of mitigating measures such as:

(i) medication, medical supplies, equipment or appliances, low vision devices (which do not include ordinary eyeglasses or contact lenses, as defined in (b)), prosthetics including limbs and devices, hearing aids and cochlear implants or other implantable hearing devices, mobility devices, or oxygen therapy equipment and supplies; (ii) use of assistive technology; (iii) reasonable accommodations or auxiliary aids or services; or (iv) learned behavioral or adaptive neurological modifications.

(b) The term "ordinary eye glasses or contact lenses" means lenses that are designed to fully correct visual acuity or eliminate refractive error.

(c) Low vision devices are devices that magnify, enhance, or otherwise augment a visual image.

(E) The ameliorative effects of the mitigating measures of ordinary eyeglasses or contact lenses shall be considered in determining whether an impairment materially restricts a major life activity.

(F) Nothing in this Act alters the standards for determining eligibility for benefits under state worker's compensation laws or under state and federal disability benefit programs.


(a) Section 102 of the Americans with Disabilities Act of 1990 (42 U.S.C. 12112) is amended--

(1) in subsection (a), by striking `with a disability because of the disability of such individual' and inserting `on the basis of disability'; and

(2) in subsection (b) - (A) in the matter preceding paragraph (1), by striking `discriminate' and inserting `discriminate against a qualified individual on the basis of disability'; and

(B) by adding at the end the following:

(8) Notwithstanding any other provision of law, using qualification standards, employment tests, or other selection criteria based on an individual's uncorrected vision or unaided hearing under this Act unless the standard, test, or other selection criteria, as used by the covered entity, is shown to be job-related for the position in question and consistent with business necessity.

(b) Section 101(8) is amended -

(1) in the paragraph heading, by striking "With a Disability"; and (2) by striking "with a disability" after "individual" both places it appears.


Title V of the Americans with Disabilities Act of 1990 (42 U.S.C. 12201) is amended by adding at the end the following:


The authority to issue regulations granted to the Equal Employment Opportunity Commission, the Attorney General, and the Secretary of Transportation under this Act, includes the authority to issue regulations implementing the definitions contained in section 3.


This Act shall become effective on January 1, 2009.

Gait Abnormality in CFS

Gait characteristics of subjects with Chronic Fatigue Syndrome and
controls at self-selected and matched velocities.

Journal: J Neuroeng Rehabil. 2008 May 27;5(1):16. [Epub ahead of print]

Authors: Lorna Paul [1], Danny Rafferty [2*], Leslie Wood [3] and
William Maclaren [4]

[1] Nursing and Health Care  Faculty of Medicine, University of
Glasgow, Glasgow, UK
[2] School of Health & Social Care, Glasgow Caledonian University, Glasgow, UK
[3] School of Life Sciences, Glasgow Caledonian University, Glasgow, UK
[4] School of Engineering and Computing, Glasgow Caledonian
University, Glasgow, UK

* Corresponding author

Glasgow Caledonian University,
Cowcaddens Road,
G4 0BA,

NLM Citation: PMID: 18505580

BACKGROUND: Gait abnormalities have been reported in individuals with
Chronic Fatigue Syndrome (CFS) however no studies exist to date
investigating the kinematics of individuals with CFS in over-ground
gait. The aim of this study was to compare the over-ground gait
pattern (sagittal kinematics and temporal and spatial) of individuals
with CFS and control subjects at their self-selected and at matched

METHODS: Twelve individuals with CFS and 12 matched controls
participated in the study. Each subject walked along a 7.2m walkway
three times at each of three velocities: self-selected, relatively
slow (0.45 ms-1) and a relatively fast (1.34 ms-1). A motion analysis
system was used to investigate the sagittal plane joint kinematics
and temporal spatial parameters of gait.

RESULTS: At self-selected velocity there were significant differences
between the two groups for all the temporal and spatial parameters
measured, including gait velocity (P=0.002). For the kinematic
variables the significant differences were related to both ankles
during swing and the right ankle during stance. At the relatively
slower velocity the kinematic differences were replicated. However,
the step distances decreased in the CFS population for the temporal
and spatial parameters. When the gait pattern of the individuals with
CFS at the relatively fast walking velocity (1.30 +/- 0.24ms-1) was
compared to the control subjects at their self-selected velocity
(1.32+/- 0.15ms-1) the gait pattern of the two groups was very
similar, with the exception of both ankles during swing.

CONCLUSIONS: The self-selected gait velocity and/or pattern of
individuals with CFS may be used to monitor the disease process or
evaluate therapeutic intervention. These differences may be a
reflection of the relatively low self-selected gait velocity of
individuals with CFS rather than a manifestation of the condition itself.

[Note: This is an Open Access article  The full text
is available for free in PDF at ]

* * *

With regard to speed, I find normal walking speed exhausts me quickly, but I can "mosey" for a longer distance.

One of the original Incline Village patients has noted that the local residents could easily identify CFS patients by their unusual gait, therefore, this obvious abnormality has been "known" for over 25 years, but apparently has only been researched now.  He describes one of the telltale characteristics as foot drop ... a neurological problem.

CDC acknowledges CFS and ME distinction

A surprising nugget of information surfaced when I recently searched for
Myalgic Encephalomyelits on the CDC's website. Evidently, even the
CDC acknowledges that ME is *not* CFS!

From the overview chapter of the CDC's CFS provider education course:

"Various terms are incorrectly used interchangeably with CFS. CFS has
an internationally accepted case definition that is used in research
and clinical settings. The name chronic fatigue and immune
dysfunction syndrome (CFIDS) was introduced soon after CFS was
defined; there is no case definition for CFIDS, and the name implies
an understanding about the pathophysiology of CFS that is not fully
supported in the medical literature.

***The name myalgic encephalomyelitis (ME) was coined in the 1950s to
clarify well-documented outbreaks of disease; however, ME is
accompanied by neurologic and muscular signs and has a case
definition distinct from that of CFS." *** (emphasis and paragraph
break added)

* * *

After decades of CDC having abolished ME by executive fiat and having it subsumed into their ever-changing definition of CFS, such that it was almost impossible to get an ME diagnosis in the US because CDC said ME didn't exist, they are now acknowledging the neurologic nature of the disease as separate from their new watered-down version of CFS (a definition that apparently does not include those of us who have the disease discovered in Incline Village). 

Maybe now we can get respect and research funding!

New way to block inflammation in autoimmune disease

Posting this because some consider CFS/FMS to be autoimmune diseases

U.S. Department of Health and Human Services
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
National Institute of Allergy and Infectious Diseases (NIAID))
Embargoed For Release: Thursday, June 19, 2008, 12:00 pm EDT

CONTACT: Trish Reynolds, NIAMS, 301-496-8190, e-mail:


Researchers from the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases (NIAMS), a part of the National 
Institutes of Health (NIH), have identified a promising new target 
for autoimmune disease treatment -- a cell-surface receptor called 
DR3. Their research in mice, published on line in the journal 
"Immunity," suggests that blocking this receptor could slow or stop 
the damaging inflammation characteristic of autoimmune diseases, 
potentially without leaving the body vulnerable to serious 
infections, as many current therapies do.

DR3 is a protein on the surface of cells. It is a member of the tumor 
necrosis factor (TNF) family of receptors, which bind to molecules 
related to TNF, a cell-signaling protein that promotes inflammation. 
Many of today's most potent treatments for inflammatory diseases, 
such as rheumatoid arthritis and psoriasis, interfere with the action 
of TNF, thereby blocking inflammation. Since current anti-TNF 
therapies don't work in all autoimmune diseases, however, the 
researchers turned to the study of DR3, which is a close relative of 
TNFR1, the main receptor for TNF.

Working with mouse models of asthma and multiple sclerosis, both 
immune system diseases, the researchers found that mice engineered to 
lack DR3 were resistant to those diseases. "The implication is that 
blocking DR3 in mice, and possibly in humans, is a potential therapy 
for these diseases and perhaps others in which the immune system goes 
awry," said Richard Siegel, M.D., Ph.D., a scientist in the NIAMS' 
Immunoregulation Group, who led the research effort.

While closely related to TNFR1, DR3 is expressed in T cells, a 
different kind of immune cell (a white blood cell that identifies and 
fights infection) than those that express TNFR1, Dr. Siegel said. The 
NIAMS group collaborated with a laboratory in Cardiff, Wales, which 
had generated genetically engineered mice deficient in DR3, as well 
as with a research group at the NIH's National Institute of Allergy 
and Infectious Diseases (NIAID), which has developed mouse models of 
disease with strong T cell components, such as asthma and multiple 
sclerosis. "These findings open up new avenues for therapy of these 
two diseases as well as to other autoimmune diseases in which T cells 
play a role in causing or perpetuating the disease," said Siegel.

The researchers hope that DR3-blocking agents will be effective anti-
inflammatory treatments someday. Siegel noted that if they were to be 
used in rheumatic diseases, they would be a complement to strategies 
that block TNF because they hit a different arm of the immune system. 
"It could be potentially synergistic or complementary," he said.

Of critical importance, the NIAMS scientists found that removing DR3 
did not appear to suppress the immune response or the ability to 
fight infection within the mice -- a problem with many other 
treatments for autoimmune disease. "We could see the effect of DR3 
deficiency in the diseased organ, but when we looked systemically at 
the immune response at other places in the mouse, it was barely 
affected," said Dr. Siegel. The group's findings suggest that DR3-
blocking agents might be more effective at specifically treating 
autoimmune disease without breaking down the body's defenses against 
infections, a long-sought goal of researchers in the field.

For more information about the NIAMS' Immunoregulation Group within 
the Autoimmunity Branch of the Intramural Research Program, visit the 
NIAMS Web site at

For more information about autoimmune diseases, visit the Medline 
Plus Web site, a service of the NIH's National Library of Medicine, 

NIAID is a component of the National Institutes of Health. NIAID 
supports basic and applied research to prevent, diagnose and treat 
infectious diseases such as HIV/AIDS and other sexually transmitted 
infections, influenza, tuberculosis, malaria and illness from 
potential agents of bioterrorism. NIAID also supports research on 
basic immunology, transplantation and immune-related disorders, 
including autoimmune diseases, asthma and allergies. News releases, 
fact sheets and other NIAID-related materials are available on the 
NIAID Web site at

The mission of the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases (NIAMS), a part of the Department 
of Health and Human Services' National Institutes of Health (NIH), is 
to support research into the causes, treatment, and prevention of 
arthritis and musculoskeletal and skin diseases; the training of 
basic and clinical scientists to carry out this research; and the 
dissemination of information on research progress in these diseases. 
For more information about NIAMS, call the information clearinghouse 
at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web 
site at

The National Institutes of Health (NIH) -- The Nation's Medical 
Research Agency -- includes 27 Institutes and Centers and is a 
component of the U.S. Department of Health and Human Services. It is 
the primary federal agency for conducting and supporting basic, 
clinical and translational medical research, and it investigates the 
causes, treatments, and cures for both common and rare diseases. For 
more information about NIH and its programs, visit
Meylan F, et al. The TNF-family receptor DR3 is essential for diverse 
T cell-mediated inflammatory diseases. "Immunity" 29, 1-11, July 2008.

Cheney's 2008 Lectures: Cell Therapy and Oxygen Toxicity

Paul Cheney, MD, PhD was the opening speaker at the 15th International Symposium of Functional Medicine in Carlsbad, CA on Thursday, May 22. He spoke for almost three hours.

His presentation, "Chronic Fatigue Syndrome, Oxidative Stress, and Pain: A Physician's Personal and Professional Journey Through the Functional Medicine Model" received a five-minute standing ovation from the over 600 physicians and researchers in attendance from 14 countries.

The Institute of Functional Medicine will be offering a DVD within 30 to 60 days through

Cell Associated Therapy for Chronic Fatigue Syndrome: Is this the Next Frontier?

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a disorder of unknown cause characterized by significant functional disability associated with fatigue, pain and neuropsychological complaints. For over twenty years since the first clear clinical presentation of CFS in the United States by Straus(1) and Jones(2) and the first epidemic of CFS was reported in Lake Tahoe(3), the therapeutic domain for CFS has been dominated by pharmaceutical, nutriceutical, herbaceutical, or alternative medical interventions. After these twenty-plus years, there is no consensus on what optimal therapy looks like and many reasons to believe that this situation will continue as it has for years to come. With the advent of stem cell therapy in chronic illness, we are entering a new era in medicine where the old therapeutic ideas are being challenged if not rejected, in favor of newer ideas about therapies that are more appropriate for the treatment of complex chronic illness.

Low molecular weight, cell signaling peptides or factors (CSF's) from human bone cell cultures have been used as implants to successfully heal non-union bone fractures at UCLA as far back as 1982(4). More recently, implanted human fetal brain tissue(5) as well as cultured human stem cell transplants(6) have been used to successfully (at least initially) treat younger (though interestingly not older) patients with Parkinson's disease. Other studies have shown that donor embryonic cells need not be human to work(7). It has additionally been shown that injected low molecular weight cell signaling factors alone can induce functional recovery from Parkinson's-like syndromes induced by drugs in monkeys(8). Finally, human bone marrow derived CSF therapy via intra-coronary IV infusion for acute myocardial infarction was shown to produce a significant improvement (67%) in myocardial left ventricular performance as compared to untreated patients who only had a marginal improvement (7%) over a six month time period(9).

In Europe, cell associated therapies known as "live cell" products have been used as injections for over seventy years in health spas as rejuvenation therapy and by physicians for the treatment of chronic disease(10). Pope Pius XII received live cell injections on his deathbed by the leading Swiss proponent at that time, Dr. Paul Niehans, and lived another four years(11). There is over a half century long history of their safe use in humans. In the U.S., this type of therapy was first legitimized in 1981 with the publication of a 59% remission rate of an immunosuppressive disease of childhood in the New England Journal of Medicine using intramuscular injections of thymus extract from 5-day-old calves(12). In the case of CFS, the first successful use of CSF's was reported by Steinbach in 1994 with the use of an injected low molecular weight extract of porcine Liver (Kutapressin)(13). We completed a six month pilot study of nine patients in 2000 using oral, frozen extracts from porcine sourced, multiple organ extracts with mixed though promising results. This present study explores further the potential for cell associated therapy using low molecular weight peptides derived from mammalian tissue extracts in CFS. METHODS: Eighteen patients from a national referral practice, meeting the 1994 case definition for CFS, were enrolled in a prospective, one year therapeutic protocol using porcine cell signaling factors derived from heart and liver tissue homogenates. In the 18 patient study cohort, the average age was 42.6 (range 15-63) with 10 females (55.5%) and 8 males (44.4%). The average length of illness was 15 years (3-21 range). At the start of the study, the average Karnofsky Performance Scale (KPS) score was 60 (40-70) and only two patients were employed (part-time) out of 18. The rest were disabled.

The study length was one year consisting of two parts, each six months long. The primary endpoint was KPS as determined by physician interview at study conclusion. Primary studies with pre- and post-interrogations included echocardiography, both with and without oxygen, impedance cardiography, urine organic acid analysis and 24-hour hormone analysis. Secondary testing included a set of routine blood test panels.

In the initial six month trial period, the primary therapy was a transdermal, porcine liver extract applied to the skin along with low dose hGH at 0.2 mg SQ per week. This therapy had previously been used in our pilot study of 2000 except that a different porcine liver extract was given as an oral frozen extract. For the final six months, the patients received an oral, frozen porcine extract consisting of 50% porcine adolescent heart extract and 50% porcine mesenchymal or fetal extract. Patients were evaluated at six months for KPS and echocardiography and impedance cardiography as well as at study endpoint.

As support therapy, a standard group of therapies, mostly anti-oxidant nutriceuticals and pharmaceuticals for sleep, used by this clinic for ten years or more was also part of the study protocol but was not a significant shift from the patients' normal therapeutic routine, pre-study. All the patients had been on most of these therapies for a year or more pre-therapy and therefore represented a baseline therapy. Additional therapies were allowed on a case-by-case basis for symptom management but patients were asked to limit the addition of any new therapies during the study period.

RESULTS: Sixteen of eighteen patients completed the study. Two patients failed to complete the study due to intolerances and are not part of the final analysis but remain on parts of the protocol due to some favorable aspects of the therapy for them. Both these patients had a strong history of environmental illness and previous intolerances to many other agents. There were no severe reactions reported.

Through the first six months of therapy, there was no significant improvement in functional measures (KPS) but some notable changes were seen in both echocardiography (drop in IVRT, p < 0.00006) and in impedance cardiography (rise in stroke volume, p < 0.00004). However, during the next six months, notable improvement was reported by some patients attributable, by most participants, to the heart/mesenchyme porcine extract. Final endpoint KPS scores, compared to pre-study KPS scores, showed a significant improvement of an average of 10 KPS points (p < 0.006). Furthermore, almost all the improvement was reported in the oxygen tolerant subgroup compared to the non-responders who were mostly oxygen toxic. Because the discovery of near universal oxygen toxicity in CFS came after the start of the study, we were only able to establish in two patients, who were late getting started, that they converted from oxygen toxic to oxygen responsive while on therapy and both were responders.

CONCLUSION: Therapy with low molecular weight peptides from cell associated, mammalian tissue homogenates appear to offer a significant benefit in CFS, especially where it counts the most, namely function. A 10-point rise in KPS score will change lives and the response over baseline function was shown to be highly significant (p < 0.0005). The use of several tissue extracts as opposed to only one appears to be more effective though this cannot be known with certainty from this study. Both tissue extracts (liver and heart/mesenchyme) appeared to be bioactive but especially the heart. Intolerance was observed in 2 of 18 or 11% and was observed in the most environmentally challenged (EI) of the 18 who were treated. Both patients had a history of intolerance to other therapies and the subsequent finding of porcine liver toxicity in a subsequent study, especially in EI patients, may help explain their failure to respond well and their intolerance to this protocol. It is likely, therefore, that future, mixed CSF protocols based on this and other studies will have even better outcomes, including EI patients.

1. Straus,SE., Tosato,G., Armstrong,G., Lawley,T., Preble,OT., Henle,W., Davey,R., Pearson,G., Epstein,J., Brus,I. and Blaese,RM., "Persisting Illness and Fatigue in Adults with Evidence of Epstein-Barr Virus Infection", Ann. Intern. Med.,102:7-16,1985.

2. Jones,JF., Ray,CG., Minnich,LL., Hicks,MJ., Kibler,R. and Lucas,DO., "Evidence for Active Epstein-Barr Virus Infection in Patients with Persistent, Unexplained Illnesses; Elevated Anti-Early Antigen Antibodies",Ann. Intern. Med.,102:1-7,1985

3. Buchwald,D., Cheney, PR., Peterson,DL., Henry,B., Wormsley,SB., Geiger,A., Ablashi,DV., Salahuddin,Z., Saxinger,C., Biddle,R., Kikinis,R., Jolesz,FA., Folks,T., Balachandran,N., Peter,JB., Gallo,RC.,and Komaroff,AL., "A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus-6 Infection", Annals of Internal Medicine, Jan.15,1992:116(2),pp.103-113.

4. Demers C, Hamdy R "Bone morphogenic proteins" Science & Medicine Nov/Dec 1999; Vol 6, No 6: 8- 17.

5. Lindvall O, Brundin P, Widner H "Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease" Science 1990; 247: 574-577

6. Cowley, G. "The new war on Parkinson's disease" Newsweek 2000; 22 May issue: 52-58

7. Isacson O, Deacon T, Pakzaban P, Galpern WR, Dinsmore J and Burns LH. "Transplanted exogenic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth paterns of glial and axonal fibers" Nature Medicine 1995;1: 1189-1194.

8. Gash DM and eleven others "Functional recovery in Parkinsonian monkeys treated with GDNF" Nature 1996; 380: 252-255

9. Dexler et al "Intracoronary autologous bone-marrow transfer after myocardial infarction: the BOOST controlled clinical trial Lancet (2004 Jul 10); 364 (9429); 141-8

10. Niehans, Paul., Introduction to Cellular Therapy NY: Coopers Square Publ., 1960

11. Culbert, ML in Live Cell Therapy for the 21st Century Chula Vista, CA: The Robert W. Bradford Foundation - Publ., 1993

12. Osmond ME, et al, "Demonstration of abnormal immunity, T-cell histamine H-2 receptor deficiency, and successful therapy with thymic extract", N. Eng. J. Med., Jan 15, 1981

13. Steinbach,T., Hermann,W., Lawyer,C., Montefiore,D., Wagle,S., Gawish,A., and Ferguson,D., "Subjective Reduction in Symptoms Following Long Term Treatment with a Porcine Liver Extract: A Phase I Trial", Clin. Inf. Dis., Volume 18, Suppl. I, pgs. S114, January, 1994.

Oxygen Toxicity as a Locus of Control for Chronic Fatigue Syndrome

BACKGROUND Chronic Fatigue Syndrome is a disorder of unknown cause characterized by significant functional disability associated with fatigue, pain and neuropsychological complaints. The subject of oxygen utilization, and especially the lack of it in CFS, has been the focus of many investigations(1,2). Indeed, the response of oxygen utilization in CFS to maximum exercise (VO2 max) was used as an FDA approved end-point marker in the multi-center trial of Ampligen, a biological response modifier(3). These studies demonstrate that CFS patients use oxygen at a reduced rate for a normalized peak exercise activity.

The oxygen response deficit with exercise in CFS is very appealing as an avenue of explanation for fatigue. Whether it is cause or effect, however, is unknown. We began our studies on oxygen itself by noting with echocardiography that patients with CFS had a much higher incidence of diastolic dysfunction than control groups(4). Diastolic dysfunction, especially in a younger cohort such as CFS, is most likely related to an underlying energy deficit(5). In addition,diastolic dysfunction, which is known to lower cardiac output, was shown to be associated with low cardiac output (CI < 3.0) in 80% of our CFS patients. Other studies have correlated (p<0.002) low cardiac output with CFS dysfunction and especially post-exertional fatigue(6). Low cardiac output can certainly cause lowered oxygen consumption but whether low cardiac output alone is responsible for low oxygen utilization is uncertain.

Further echocardiography investigations of CFS in this clinic revealed, using saline contrast bubble studies, evidence of patent foramen ovale (PFO) in a shocking 90%(7), 4-5 times the expected result by chance alone and much higher than any other known PFO association. Such a finding raised the possibility of oxygen toxicity physiology in CFS. This study extends the relationship of oxygen utilization disorders common in CFS and examines the concept of oxygen toxicity as it might apply to CFS.

METHODS: During a ten-month period, 67 consecutive patients presenting for either initial or follow-up evaluation for CFS were evaluated using echocardiography coupled to a series of varied interrogations on the echo table in real time. After routine, though expanded echocardiography, each patient was evaluated for IVRT response before, during and after oxygen administration for 5 minutes each, initially at 4 lpm NC and then typically at progressively higher doses up to 40% FIO2 mask oxygen at 10 lpm flow rate if they were non-toxic to 4 lpm NC. IVRT or isovolumetric relaxation time is an internal timing measurement in milliseconds (msec) on echocardiography, which is inversely related to cellular free energy in myocardial cells. IVRT was measured in triplicate using continuous wave (cw) doppler and averaged for each result.

In the 67 patient cohort, the average patient age was 49.3 (range 17-67). There were 48 females (71.6%) and 19 males (28.4%). Almost all the patients were fully or partially disabled and all had been ill for at least 5 years with the average length of illness being 14 years. Three patients did not meet severity criteria for CFS at the time they were evaluated and three were deemed atypical for CFS on clinical grounds. These six outliers were evaluated separately from the group. All 67 patients were categorized as either new patients or patients on various treatment algorithms if they were follow-up patients. The various treatment algorithms are complex as well as novel and cannot be fully discussed here but serve to illustrate the power of the proposed oxygen toxicity model to discriminate among various treatments.

Controls (N=17) were selected to approximately match the CFS patients' age and sex distribution and were largely selected from the community. The average age was 45.0 (range 19-75). There were 10 females (59%) and 7 males (41%). All were either working or in school full time though 2 were non-medically retired and all were deemed functionally normal for age with no prior history of CFS though only a minority had unblemished medical histories. RESULTS: Because results depended on treatment status, the 67 patient cohort, as well as an additional 24 patients from a more limited evaluation cohort for a total of 91 patients, were segregated into a) new patients, b) patients treated in this clinic with standard therapies, c) patients treated in this clinic with standard therapies plus one novel, low molecular weight (LMW), cell signaling factor (CSF) peptide in a transdermal gel and d) patients treated in this clinic with standard therapies plus an expanded set of LMW, cell signaling factor gels. Of the 67 consecutive patients, less those who did not meet criteria for CFS and/or were deemed atypical (6 were so categorized), 26 were new patients and 25 of 26 or 96.1% were toxic to oxygen as evidenced by a rise in IVRT on exposure to oxygen and indicating a reduction in myocardial cellular energetics. It took three minutes or less to see this IVRT response take effect and 3-5 minutes to return to baseline once off oxygen. 26 of 26 new patients or 100% were toxic to 40% mask oxygen. This contrasts to 6 of 17 or 35% of the controls that were toxic to oxygen at 4 lpm and 11 of 17 or 65% of controls that were toxic to 40% mask oxygen. When patients from the group of 67 consecutive cases, excluding the 6 outliers as well as treatment responders, were statistically compared (N = 53) in their IVRT response on oxygen to the controls (N = 17) on oxygen at 4 lpm NC, there was almost no chance they could have been the same group (p < 0.0004). With respect to treated groups b), c) and d), there were 9 of 12 patients or 75% on standard therapy for at least three months who were toxic at 4 lpm and 12 of 12 or 100% toxic at 40% mask oxygen. There were 15 of 23 or 65% toxic on a single CSF gel therapy for at least three months and 23 of 23 or 100% toxic at 40% mask oxygen. Finally, there were 9 of 30 or 30% toxic on an expanded set of CSF gel therapies for at least three months and 8 of 14 or 57% toxic at 40% mask oxygen. Of special note in those patients receiving the expanded set of CSF's, was the fact that in a separate prospective study lasting one year of 16 patients on an expanded CSF therapy protocol, there was a 75% (12 of 16) clinical response rate with a mean Karnofsy Performance Scale (KPS) improvement of 10 points (p<0.006) in which the responders had an oxygen tolerance rate on 4 lpm of 92% (11 of 12) whereas the non-responders (25%) had a 75% rate of oxygen toxicity (3 of 4).

There were a total of six patients out of the consecutive group of 67 fully evaluated patients who either did not fully meet the severity criteria for CFS (three were working full time but were otherwise typical for CFS) or were clinically atypical (three). From these two groups of outliers, all were tolerant to 4 lpm though 4 of 6 (2 from each group) or 67% were toxic to 40% mask oxygen, a result similar to controls. The interesting thing about the atypical group was that they all three had significant environmental illness and could be distinguished from controls by their real-time IVRT response to porcine liver derived CSF's suggesting that a defect in detoxification underlies their illness apart from oxygen toxicity.

CONCLUSION: These results demonstrate that within certain well defined limits of the case definition for CFS, the relative cardiac cellular energetic response to oxygen in CFS (strongly negative) compared to controls (strongly positive to weakly negative) is significantly different (p < 0.0004). Furthermore, that the absolute response to oxygen (toxic vs. tolerant) yields 96% sensitivity (CFS being essentially a strongly oxygen toxic state) and 65% specificity compared to controls (35% are weakly toxic) at 4 lpm NC. At 40% mask oxygen, 100% of CFS cases are toxic, but so were 65% of controls. When patients were sub-categorized according to increasingly powerful treatment algorithms, they were increasingly transformed to an oxygen tolerant state, which in the case of the most powerful algorithm, was associated with a significantly (p<0.006) improved clinical status. We conclude that CFS is an oxygen toxic state and that oxygen toxicity status appears to determine outcome in therapeutic trials and is therefore, a locus of control in chronic fatigue syndrome.

DISCUSSION: While it could be argued that this study simply reveals different levels of aerobic conditioning, there are several arguments against this including 1) the most oxygen responsive control had had a cardiac transplant five years ago and hasn't been able to do significant aerobic activity for five years and 2) this doesn't explain the oxygen tolerance found in the 6 atypical cases, all of whom were moderately to severely deconditioned, nor an oxygen toxic control who is a college athlete. Finally, the ability to transform the oxygen toxic state with ever more effective therapies, without an exercise program in place, suggests that the oxygen toxic state is related to some fundamental problem inherent to CFS. These findings appear to force a narrowing of potential causes of CFS because whatever pathophysiology one puts forth must explain universal oxygen toxicity in chronic fatigue syndrome and must explain a 90% incidence of PFO. In fact, it is the relative oxygen toxic state of fetal physiology, which is indirectly responsible for PFO, that is a key argument for the study interpretation. The missing piece to this puzzle may be that we see a super-select group of CFS patients at our clinic. While it is possible that we are masked off from other possibly non-oxygen toxic and less severe cases of CFS, this is not likely if they are disabled since we do see a wide spectrum of disabled patients from all parts of the US and abroad.

It is also important to view oxygen toxicity as less a cause of CFS but rather a final common pathway whose presence is downstream from the issue of etiology or etiologies, though it appears to determine outcome. I strongly suspect that the emerging model of CFS as an oxygen toxic state will not be an etiologic based model but rather a model much like the cancer model. For example, there are many etiologies for cancer and many downstream complications and presentations, but only the cancer cell matters and ultimately determines outcome. Oxygen toxicity is analogous to the cancer cell in CFS and once established, may be independent of etiology but nevertheless, determines outcome.

1. De Becker et al. "Exercise capacity in Chronic Fatigue Syndrome", Arch. Intern. Med. 2000 : 160 ; 3270

2. Stevens,SR, "Using Exercise Testing to Document Functional Disability in CFS", Journal of Chronic Fatigue Syndrome", 1995:Vol 1, Numbers ¾; 127-129

3. Strayer,DR., Carter,WA., Brodsky,I., Cheney,PR., Peterson,DL., Salvato,P., Thompson,C., Loveless,MO., Shapiro,D., Elsasser,W., and Gillespie,D., "A Controlled Clinical Trial with a Specifically Configured RNA Drug, Poly (I): Poly (C12U) in Chronic Fatigue Syndrome", Clin. Inf. Dis., Volume 18, Suppl. I, S88-95, January, 1994.

4. Cheney,PR and Lucki,NC "Evidence for Diastolic Dysfunction in the Chronic Fatigue Syndrome enhanced by Tilt-Echocardiography: A study of ninety consecutive cases." IACFS Meetings, Jan 2007, Ft Lauderdale, FL

5. Morgan,JP, "Abnormal modulation of calcium as a major cause of cardiac contractile dysfunction" NEJM 1991;325:625-632

6. Peckerman,A,"Abnormal Impedance Cardiography Predicts Syndrome Severity in Chronic Fatigue Syndrome",The American Journal Of The Medical Sciences, 2003:Vol326,No2;

7. Cheney,PR and Lucki,NC, "Evidence of Increased Frequency of Patent Foramen Ovale (PFO) in the Chronic Fatigue Syndrome with Enriched Oxygen Modulation of the PFO" IACFS Meetings, Jan 2007, Ft Lauderdale, FL