Presentation by Dr. Lerner given to physicians  in August of 2007 on the topic of Chronic Fatigue Syndrome: Click on link to access video.

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Graded exercise for chronic fatigue syndrome

January 16, 2007 Cynthia Tank Content provided by Healthwise

You may be thinking, "How can I exercise when I'm so tired I can barely get through the day?" You can do it, as long as you start out very slowly and are careful not to overexert yourself. Most important, it will make you feel better.

Studies show that light aerobic exercise, such as walking, helps people with (CFS)feel more energetic and less tired. Maybe you have avoided exercise because you're afraid it will make you feel worse, but the opposite is true. Total rest leaves your body in worse shape. It can also hurt your self-image by making you feel like an invalid.

What is graded exercise?

Graded exercise is exercise that starts out slowly and increases in very small steps. It means you have a plan for your exercise and you stick to it, even when you're having a good day and feel like doing more. Increasing your exercise very slowly lets your body make the changes it needs to cope with activity and exercise. People with (Chronic Fatigue Syndrome often have an exercise program designed for them by a health expert called a physiologist who can create a tailor-made plan and carefully watch the person's progress.

For example, you might start by walking, bicycling or swimming as little as 5 minutes every other day for 2 weeks. If you feel strong enough at the end of 2 weeks, you might add 2 to 5 minutes to your exercise for another 2 weeks, and so on.

Why do I need a graded exercise program?

If you have (CFS) you may have days when you feel pretty good and days when you can barely get out of bed. On your good days, you may decide you can do twice as much, but that may cause a relapse of your symptoms. Those relapses may make you afraid to exercise at all. But if you avoid exercising altogether, your body grows weaker and less able to fight off fatigue as well as illness. People with CFS often feel like they have no control over their bodies, as if they are invalids. By starting a carefully controlled exercise plan, you can begin taking back control.

In combination with good sleep habits and careful scheduling of activities, a gentle, graded exercise program can help you feel better. You must start with very brief activities and gradually increase the frequency, duration, and intensity of exercise as you feel able. This kind of exercise plan can be extremely helpful in relieving and controlling symptoms of chronic fatigue syndrome.

How can I start an exercise program?

You should work with your doctor to draw up a specific plan for your needs and abilities, but there are things you can do on your own.

Walking is an excellent form of aerobic exercise for people with (CFS). Other gentle exercises, such as riding a bicycle or stationary bike or swimming, are also good. You need to find a balance so that you are exercising enough to benefit from it but not exercising so much that you become overtired. Here are some things to consider:

• Adopt a positive attitude toward exercise. Try to put aside your doubts and your worries that it will cause a relapse.
• Start very slowly. If you have not been very active lately, it is a bad idea to jump into a vigorous exercise program. Start with just a few minutes of very gentle exercise, such as stretching. When you are comfortable with stretching exercises, add very short periods of a mild aerobic activity such as walking or swimming.
• Increase very gradually. Once you know that your body can tolerate this level of exercise over the course of several sessions, increase the length of your exercise session by only 1 minute. Rest frequently, and gradually increase your exercise intensity a little bit at a time until you can exercise for 20 to 30 minutes without becoming overtired. Try to exercise 3 to 4 times a week.
• Don't push yourself too hard. You can easily become overtired, which will defeat the purpose of exercise.
• Don't exercise within 2 hours of bedtime. Exercising just before you go to bed may make it harder to fall asleep.
• Take a few days off when you need to. There may be periods of time when stress or other physical activities make exercise too difficult. When this happens, take a little time off, and then try to get back into your exercise routine as soon as possible. Keep track of your exercise

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New Therapy For Chronic Fatigue Syndrome To Be Tested

Science Daily — A preliminary study suggests there may be hope in the offing for some sufferers of chronic fatigue syndrome with a new therapy being tested by researchers at the Stanford University School of Medicine.José Montoya, MD, associate professor of medicine (infectious diseases), and postdoctoral scholar Andreas Kogelnik, MD, PhD, have used the drug valganciclovir - an antiviral often used in treating diseases caused by human herpes viruses - to treat a small number of CFS patients.

The researchers said they treated 25 patients during the last three years, 21 of whom responded with significant improvement that was sustained even after going off the medication at the end of the treatment regimen, which usually lasts six months. The first patient has now been off the drug for almost three years and has had no relapses. A paper describing the first dozen patients Montoya and Kogelnik treated with the drug was published in the December issue of Journal of Clinical Virology.

"This study is small and preliminary, but potentially very important," said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, who was not involved in the study. "If a randomized trial confirmed the value of this therapy for patients like the ones studied here, it would be an important landmark in the treatment of this illness."

Montoya has received a $1.3 million grant from Roche Pharmaceutical, which manufactures the drug under the brand name Valcyte, to conduct a randomized, placebo-controlled, double-blind study set to begin this quarter at Stanford. The study will assess the effectiveness of the drug in treating a subset of CFS patients.

Montoya is speaking about his efforts at the biannual meeting of the International Association for Chronic Fatigue Syndrome in Fort Lauderdale on Jan. 11 and 12.

Chronic fatigue syndrome has baffled doctors and researchers for decades, because aside from debilitating fatigue, it lacks consistent symptoms. Although many genetic, infectious, psychiatric and environmental factors have been proposed as possible causes, none has been nailed down. It was often derided as "yuppie flu," since it seemed to occur frequently in young professionals, though the Centers for Disease Control and Prevention says it's most common in the middle-aged. But to those suffering from it, CFS is all too real and its effects are devastating, reducing once-vigorous individuals to the ranks of the bedridden, with an all-encompassing, painful and sleep-depriving fatigue.

More than 1 million Americans suffer from the disorder, according to the CDC. The disease often begins with what appears to be routine flulike symptoms, but then fails to subside completely - resulting in chronic, waxing and waning debilitation for years.

Valganciclovir is normally used against diseases caused by viruses in the herpes family, including cytomegalovirus, Epstein-Barr virus and human herpes virus-6. These diseases usually affect patients whose immune systems are severely weakened, such as transplant and cancer patients. Montoya, who had used the drug in treating such patients for years, decided to try using it on a CFS patient who came to him in early 2004 with extremely high levels of antibodies for three of the herpes family viruses in her blood. At the time, she had been suffering from CFS for five years.

When a virus infects someone, the levels of antibodies cranked out by the immune system in response typically increase until the virus is overcome, then slowly diminish over time. But Montoya's patient had persistently high antibodies for the three viruses. In addition, the lymph nodes in her neck were significantly enlarged, some up to eight times their normal size, suggesting her immune system was fighting some kind of infection, even though a comprehensive evaluation had failed to point to any infectious cause.

Concerned about the unusual elevations in antibody levels as well as the swelling of her lymph nodes, Montoya decided to prescribe valganciclovir. "I thought by giving an antiviral that was effective against herpes viruses for a relatively long period of time, perhaps we could impact somehow the inflammation that she had in her lymph nodes," said Montoya.

Within four weeks, the patient's lymph nodes began shrinking. Six weeks later she phoned Montoya from her home in South America, describing how she was now exercising, bicycling and going back to work at the company she ran before her illness. "We were really shocked by this," recalled Montoya.

Of the two dozen patients Montoya and Kogelnik have since treated, the 20 that responded all had developed CFS after an initial flulike illness, while the non-responders had suffered no initial flu.

Some of the patients take the drug for more than six months, such as Michael Manson, whose battle with CFS has lasted more than 18 years. The former triathlete was stricken with a viral infection a year after his marriage. After trying unsuccessfully to overcome what he thought were lingering effects of the flu, he had no choice but to drastically curtail all his activities and eventually stop working.

During his longest period of extreme fatigue, 13 1/2 weeks, Manson said, "My wife literally thought I was passing away. I could hear the emotion in her voice as she tried to wake me, but I couldn't wake up to console her. That was just maddening."

Now in his seventh month of treatment, Manson is able to go backpacking with his children with no ill after-effects. Prior to starting the treatment, Manson's three children, ages 9 to 14, had never seen him healthy.

Montoya and Kogelnik emphasized that even if their new clinical trial validates the use of valganciclovir in treating some CFS patients, the drug may not be effective in all cases. In fact, the trial will assess the effectiveness of the medication among a specific subset of CFS patients; namely, those who have viral-induced dysfunction of the central nervous system.

"This could be a solution for a subset of patients, but that subset could be quite large," said Kristin Loomis, executive director of the HHV-6 Foundation, which has helped fund a significant portion of the preparatory work for the clinical trial. "These viruses have been suspected in CFS for decades, but researchers couldn't prove it because they are so difficult to detect in the blood. If Montoya's results are confirmed, he will have made a real breakthrough."

"What is desperately needed is the completion of the randomized, double-blind, placebo-controlled clinical trial that we are about to embark on," Montoya said.

Note: This story has been adapted from a news release issued by Stanford University

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Chronically tired? Help may be at hand

Reuters - July 20, 2005

Help may finally be at hand for sufferers of Chronic Fatigue Syndrome (CFS) thanks to a group of British researchers who have found abnormalities in
the white blood cells of the afflicted.

If the early results are borne out by wider research -- and initial indications are that they will be -- it could lead not only to a blood test
for the condition but possibly a drug to treat it, New Scientist magazine reported on Wednesday.

"We have shown that a significant part of the pathogenesis resides in the white blood cells and in their activity," team leader Jonathan Kerr told
the magazine.

"It will open the door to development of pharmacological interventions," he added.

It will be welcome news to CFS sufferers whose symptoms of acute fatigue, headaches, disrupted sleep patterns and an inability to think clearly are
often dismissed as being all in the mind.

Kerr's team, which is moving to St George's Hospital at the University of London, found that a group of genes in the white blood cells of CFS
sufferers were up to four times more active than those without the affliction while one was less active.

"The involvement of such genes does seem to fit with the fact that these patients lack energy and suffer from fatigue," Kerr said.

It is unclear how widespread CFS is generally, but the U.S. Centers for Disease Control and Prevention said on its web site that it is estimated
that as many as 500,000 people in the United States alone are suffering from a CFS-like condition.

Copyright 2005 Reuters Limited.

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Chronic fatigue is not all in the mind

23 July 2005  * NewScientist.com news service * Rowan Hooper

AT LONG last, we are beginning to get to grips with chronic fatigue syndrome.Differences in gene expression have been found in the immune cells of people
with the disease, a discovery that could lead to a blood test for the disorder and perhaps even to drugs for treating it.

The symptoms of chronic fatigue syndrome have been compared to those of a really bad hangover: extreme weakness, inability to think straight, disrupted
sleep and headache. But unlike a hangover, the symptoms linger for years, devastating people's lives.

While nobody doubts CFS exists, just about every aspect of it is controversial. Some say it is the same as myalgic encephalomyelitis, or ME; others disagree.
Many specialists are convinced it does have a biological basis, but pinning down physical abnormalities common to all patients has proved tough. People
with CFS have often received little sympathy from doctors who dismiss it as "all in the mind".

Now Jonathan Kerr's team, which is moving to St George's University of London, has compared levels of gene expression in the white blood cells of 25 healthy
individuals with those in 25 patients diagnosed as having CFS according to strict criteria. The researchers found differences in 35 of the 9522
genes they analysed using DNA chip technology.

The few similar studies done in the past have produced conflicting results, so the team double-checked their results using a more accurate method called
real-time PCR. That confirmed that 15 of the genes were up to four times as active in people with CFS, while one gene was less active. The results will
appear in the Journal of Clinical Pathology next month.

Kerr is repeating the study in 1000 CFS patients and healthy controls, this time looking at 47,000 gene products. So far, the larger study backs up the
earlier results, he told New Scientist.

If Kerr really has succeeded where many have failed, and identified clear physical changes in people with CFS, the lingering opinion that it is "all in
the mind" could finally be laid to rest. "This exciting new work shows that some aspects of this complex illness may be understandable in molecular terms,
and that CFS is not a 'made up' illness," says Russell Lane, a neurologist at Charing Cross Hospital in London.

It should also be possible to develop a blood test for CFS. The team has already discovered differences in blood proteins related to the
changes in gene expression.

Kerr hopes the work might even lead to treatments. "We have shown that a significant part of the pathogenesis resides in the white blood cells and in
their activity," he says. "It will open the door to development of pharmacological interventions."

Several of the genes identified by the team in CFS play important roles in mitochondria, the power factories of our cells. "The involvement of such genes
does seem to fit with the fact that these patients lack energy and suffer from fatigue," Kerr says.

One of these gene products, EIF4G1, is involved in protein production in mitochondria. It is hijacked by some viruses, so cells may compensate by
ramping up gene expression. "I am excited by the paper," says Basant Puri, a CFS expert at Hammersmith Hospital in London. "The group's finding of
upregulation of EIF4G1 is consistent with subclinical persistent viral infection."

This fits in with the idea that CFS is sometimes triggered by viruses such as Epstein-Barr, Q fever, enteroviruses and parvovirus B19. "CFS often
begins with a flu-like illness which never goes away," Kerr says.

Of the other genes whose expression varies in CFS patients, some are involved in regulating the activity of the immune system. Others play
important roles in nerve cells, including a gene called NTE, which codes for an enzyme affected by
organophosphates and nerve gases.

Journal reference: Journal of Clinical Pathology (vol 58, p 823, 860)

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Nutritional Program for Fatigue

When patients come to me for advice about specific medical problems, they usually have been told that they need medication or surgery, and they are seeking ways to avoid those treatments. Sometimes they have already tried medications, which have produced significant side effects.

Usually, they have many treatment alternatives but they have no information about their choices. One example of effective alternatives is the reduction in blood pressure that meditation produces. Others are the dietary changes and exercise programs that lead to lowered cholesterol. Since the medical treatments for these two conditions are often more dangerous than the problems, it is worth seeking safer alternatives.

Dr. Dean Ornish has shown that patients with heart disease can often avoid surgery and reverse their heart disease with a combination of a low-fat diet, meditation, and exercise. Norman Cousins healed his ankylosing spondylitis (a form of arthritis of the spine) with laughter and high doses of vitamin C. He wrote about his experience in the New England Journal of Medicine, and followed this article with a book, The Anatomy of an Illness. Many patients have cured their digestive disturbances simply by avoiding certain foods.

Over and over, we are seeing the results of lifestyle changes in health care. A recent scientific medical conference put on by the American College for Advancement in Medicine was entitled: Lifestyle Medicine—Medicine for the Nineties. Researchers and physicians both attended and taught at this scientific meeting. Much of it related to the role of dietary supplements in medical therapy.

Dietary supplements are among the safest and most effective choices in health care. They are almost free of side effects, they are easy to take, they are relatively inexpensive, and they usually enhance many life functions besides the specific condition for which they are being given. Following is an example of how nutritionally oriented physicians might use supplements as part of the treatment for a specific health problem. This is a suggestion that is supported in the medical literature and in the experience of many physicians.

Remember this is an example, not a prescription for you, and the supplement list is in addition to many other health practices. Other supplements may be helpful, and you may not need all of these to get results. For more information on any one supplement, look for its description in Dietary Supplements. No one program is appropriate for everybody, but these suggestions are good starting points from which individual programs can be modified.

The complete article may be found at: http://www.healthy.net/scr/Article.asp?Id=2116

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To exercise or not to exercise in chronic fatigue syndrome?

  Journal: MJA 2004; 181 (10): 578-580 Authors: Garry C Scroop,* Richard B Burnet
  Affiliations: * Visiting Associate Professor in Exercise Physiology,
  Department of Thoracic Medicine; =86 Endocrinologist, Royal Adelaide
  Hospital, SA 5000 gscroop@mail.rah.sa.gov.au

  To the Editor: A recent editorial1 and article2 continue to promulgate and
  link the unproven concepts that patients with chronic fatigue syndrome
  (CFS) are "deconditioned" and exercise is beneficial in treatment. The
  cited study by Fulcher and White3 is open to opposite conclusions,
  depending on their use of the outcome descriptor "better". If the term is
  restricted to "much better" and "very much better", then, as cited by
  Lloyd,1 16 of 29 people with CFS rated themselves as "better" after a
  graded exercise program, compared with only 8 of 30 in the control group
  who completed a flexibility treatment regimen. However, if the "better"
  descriptor combines "a little better", "much better" and "very much
  better", which is the interpretation used by Wallman et al,2 then the
  scores for the exercise versus flexibility groups are not different, being
  27 of 29 and 26 of 30, respectively, agreeing with the conclusion of
  Wallman et al.2

  Whichever interpretation is applied, any beneficial effect of the graded
  exercise program in people with CFS in these studies must be independent of
  any training effect or change in level of "conditioning", as this was
  reported in one study,2 but not in the other.

  A fundamental flaw with most exercise studies in CFS is the use of
  submaximal or symptom-limited tests, which provide notoriously misleading
  data when compared with maximal exercise testing procedures.4,5 Wallman etal correctly
  identify maximal oxygen consumption as the "gold standard"
  measure of exercise capacity, yet such measurements were not made in the
  three articles they cited. When such procedures are applied, the exercise
  capacity of people with CFS is not significantly different from either
  measured or age-predicted values for healthy sedentary people.6 Wallman etal suggested that
  maximal testing procedures could favour the recruitment
  of "more robust or healthier" patients and provide misleading information.
  In the first place this is denied by the study of Sargent et al,6 in which
  the illness status reported by patients who completed the maximal tests was
  similar to that in previous CFS studies. In the second place, the maximal
  test protocol chosen for a given population should be designed to exclude
  any influence of fatigue on the metabolic measurements. This is confirmed
  by the results from the study cited,6 in which the metabolic measurements
  met the published criteria of a maximal test.

  In summary, patients with CFS are not "deconditioned". Neither their muscle
  strength nor their exercise capacity is different from that of other
  sedentary members of the community (> 70%). We remain unaware of any
  incontrovertible evidence that the various "exercise training" programs
  suggested in previous articles improve either the physiological or clinical
  status of people with CFS.

      1. Lloyd AR. To exercise or not to exercise in chronic fatigue
  syndrome? No longer a question [editorial]. Med J Aust 2004; 180: 437-438.
  <eMJA full text> <PubMed>
      2. Wallman KE, Morton AR, Goodman C, et al. Randomised controlled trial
  of graded exercise in chronic fatigue syndrome. Med J Aust 2004; 180:
  444-448. <eMJA full text> <PubMed>
      3. Fulcher KY, White PD. Randomised controlled trial of graded exercise
  in patients with the chronic fatigue syndrome. BMJ 1997; 314: 1647-1652.
  <PubMed>
      4. Sargent C, Scroop GC. Defining exercise capacity, exercise
  performance and a sedentary lifestyle. Med Sci Sports Exerc 2002; 34:
  1692-1693.
      5. Sargent C, Scroop GC. Vo2peak versus Vo2max? An important
  distinction. Med Sci Sports Exerc 2002; 34: 1215-1216. <PubMed>
      6. Sargent C, Scroop GC, Nemeth PM, et al. Maximal oxygen uptake and
  lactate metabolism are normal in chronic fatigue syndrome. Med Sci Sports
  Exerc 2002; 34: 51-56. <PubMed>
  ____________________

  Authors: Ellie Stein,* Christine Hunter=86

  Affiliations: * Psychiatrist, 4523  16A St SW, Calgary,
  Alberta, Canada; =86 Consumer advocate,
  Alison Hunter Memorial Foundation, Sydney, NSW espcATshaw.ca

  To the Editor: The claim in Lloyd's editorial1 that "the criteria for
  diagnosis are well accepted internationally" ignores the recent publication
  of the Canadian consensus guidelines for the diagnosis and management of
  myalgic encephalomyelitis/chronic fatigue syndrome,2 which were sponsored
  by Health Canada and written by an international group of well published
  researchers. The Canadian definition of chronic fatigue syndrome (CFS)
  requires the concurrent presence for six months of fatigue, post-exertional
  fatigue, sleep dysfunction, pain (including headaches) and
  neurological/cognitive manifestations, as well as at least one symptom
  from two of autonomic, neuroendocrine and immune manifestation categories (pp213).
  These requirements add clinical specificity to the Fukuda criteria
  and exclude subjects who may have chronic fatigue for other reasons, such
  as psychiatric disorder without multiple physical symptoms.

  Lloyd refers to the "recent refinements to improve reliability" in the
  revision of the research case definition by Reeves et al.3 The SPHERE
  screening instrument recommended by that article was designed for
  psychiatric screening in primary care. It arbitrarily classifies people
  with multiple physical symptoms, often severe in degree and associated with
  major disability, as having somatisation disorder. This is akin to
  subclassifying people with severe multiple sclerosis as having somatoform
  disorder and those with fewer and less severe symptoms as the "core"
  multiple sclerosis group, a finding which is not supported by the evidence.

  Conclusions from the article by Wallman et al4 cannot be generalised to the
  severely ill. Recruitment was from "notices placed in medical surgeries and
  by advertisements in local newspapers". Patients with severe CFS, who can
  barely venture outside their homes and are often too ill to read, would be
  unlikely to participate. Loblay, Chair of the Royal Australasian College of
  Physicians Working Group for CFS Clinical Practice Guidelines, urges
  caution about generalising from exercise studies, which never include
  people with severe CFS: "All these studies involve people willing and able
  to participate. The people who find it makes them feel lousy drop out."

  Lloyd asserts exercise is no longer a question (". . . graded physical
  exercise should become a cornerstone of the management approach for
  patients with CFS"). To promote such a strong, unqualified message to busy
  general practitioners who may be unfamiliar with the range of severity in
  CFS risks serious harm to patients.

      1. Lloyd AR. To exercise or not to exercise in chronic fatigue
  syndrome? No longer a question [editorial]. Med J Aust 2004; 180: 437-438.
  <eMJA full text> <PubMed>
      2. Carruthers BM, Jain AK, De Meirleir K, et al. Myalgic
  encephalomyelitis/chronic fatigue syndrome: clinical working case
  definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr
  2003; 11: 7-116. Available at: www.mefmaction.net/documents/journal.pdf
  (accessed Sep 2004).
      3. Reeves WC, Lloyd A, Vernon SD, for the International Chronic Fatigue
  Syndrome Study Group. Identification of the ambiguities in the 1994 chronic
  fatigue syndrome research case definition and recommendations for
  resolution. BMC Health Serv Res 2003; 3: 25. <PubMed>
      4. Wallman KE, Morton AR, Goodman C, et al. Randomised controlled trial
  of graded exercise in chronic fatigue syndrome. Med J Aust 2004; 180:
  444-448. <eMJA full text> <PubMed>
      5. Maegraith D. Pros and cons of exercise in fighting CFS. The Weekend
  Australian 2004; Jul 3-4: C32.
  __________

  Reply:

  Author: Andrew R Lloyd

  Professor, Inflammation Research Unit,
  School of Medical Sciences, University of New South Wales, Kensington,NSW,
  2052  alloyd@unsw.edu.au

  In reply: Scroop and Burnet correctly identify the vagaries of the
  necessarily subjective measurement of outcomes in intervention studies of
  chronic fatigue syndrome (CFS). Given that muscle strength, endurance and
  recovery are essentially normal in patients with CFS,1 rather than become
  too focused on the best approach to measurement of exercise capacity the
  key issue is whether patients benefit in terms of self-reported symptom
  severity or functional status.

  The weight of evidence indicates that graded physical exercise does provide
  such benefits. Whether this occurs via improvements in aerobic fitness or
  via the well-recognised psychological and social benefits of exercise is
  something of a side-issue.

  Stein and Hunter draw attention to the recently published Canadian
  consensus guidelines for the diagnosis and management of myalgic
  encephalomyelitis/CFS. Although this document may provide a welcome
  recognition for Canadian patients with the disorder, unlike the Australian
  guidelines,2 it is devoid of an evidence base for the recommendations.
  Sadly, rather than "add[ing] clinical specificity", it is also highly
  likely that the modified diagnostic criteria fall into the trap of
  preferentially identifying patients with somatisation disorder,3 as such
  individuals often report large numbers of unexplained symptoms, and hence
  the addition of 20 or more symptoms to the diagnostic criteria may well
  bias towards inclusion of such patients.

  Stein and Hunter are incorrect in the assertion that SPHERE was designed
  for psychiatric screening in primary care, as the instrument arose out of
  our studies in CFS specifically seeking to identify clinically significant
  fatigue states.4

  I support the recommendation about caution in generalising from existing
  published data regarding graded exercise to patients who are severely ill,
  as such patients are indeed likely to be under-represented in published
  studies. Nevertheless, it is noteworthy that the recommendations made in
  the Canadian document cited by Stein and Hunter also clearly support the
  notion of graded physical exercise: "Patients should gently and gradually
  increase their level of activity." Thus, rather than leave the severely
  affected to continue to "barely venture outside their homes", I would
  recommend a carefully designed graded exercise program in the home, with a
  goal of improving functional performance sufficiently to escape those confines.

      1. Lloyd AR, Gandevia SC, Hales JP. Muscle endurance, twitch
  properties, voluntary activation and perceived exertion in normal subjects
  and patients with chronic fatigue syndrome. Brain 1991; 114: 85-98. <PubMed>
      2. Royal Australasian College of Physicians Working Group. Chronic
  fatigue syndrome  Clinical practice guidelines 2002. Med J Aust 2002; 176:
  S17-S55. <eMJA full text>
      3. Katon W, Russo J. Chronic fatigue syndrome criteria: a critique of
  the requirement for multiple physical complaints. Arch Intern Med 1992;
  152: 1604-1609. <PubMed>
      4. Hadzi-Pavlovic D, Hickie IB, Wilson AJ, et al. Screening for
  prolonged fatigue syndromes: validation of the SOFA scale. Soc Psychiatry
  Psychiatr Epidemiol 2000; 35: 471-479. <PubMed>

   =A9The Medical Journal of Australia 2004 www.mja.com.au ISSN: 0025-729X


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Association between serotonin transporter gene polymorphism and chronic fatigue syndrome.
Biochem Biophys Res Commun. 2003 Nov 14;311(2):264-6.
Narita M, Nishigami N, Narita N, Yamaguti K, Okado N, Watanabe Y,
Kuratsune H.
Institute of Basic Medical Sciences, University of Tsukuba, Tennoudai
1-1-1, Tsukuba, 305-8575, Ibaraki, Japan

Interaction between the hypothalamo-pituitary-adrenal axis and the
serotonergic system is thought to be disrupted in chronic fatigue
syndrome (CFS) patients. We examined a serotonin transporter (5-HTT)
gene promoter polymorphism, which affects the transcriptional efficiency
of 5-HTT, in 78 CFS patients using PCR amplification of the blood
genomic DNA. A significant increase of longer (L and XL) alleic variants
was found in the CFS patients compared to the controls both by the
genotype-wise and the allele-wise analyses (both p<0.05, by chi(2) test
and Fisher's exact test). Attenuated concentration of extracellular
serotonin due to longer variants may cause higher susceptibility to CFS.

PMID: 14592408

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Chronic Fatigue May Respond to Friendly Bacteria.
Canadian specialists contend that lactic acid bacteria may be effective in treating chronic fatigue syndrome.

Often referred to as "probiotics," these bacteria help to maintain a healthy intestinal tract. They are sometimes called "friendly" or "good" bacteria.

They cite research that shows that chronic fatigue patients had much more fecal E. coli (harmful bacteria) than the control subjects. They also found that the control subjects had a much higher percentage of friendly bacteria, such as Bifidobacterium.

They also cite research that found that pain and fatigue were associated with a high harmful bacteria count. What’s more, they discovered that the higher the harmful bacteria count, the more severe the neurological and cognitive deficits, associated with nervousness, memory loss, forgetfulness and confusion .

Normal bacteria, they note, are vital to good health for a number of reasons.

“Bacteria that are normally found in high numbers, such as bifidobacteria and lactobacilli (lactic acid bacteria),” they say, “are involved in vitamin synthesis, stimulation of the immune response, prevention of pathogenic and opportunistic bacterial colonization, protection of the intestinal barrier defense system, production of short chain fatty acids for enterocyte energy, and metabolism of carcinogenic (cancer causing) substances.”

They point out that antibiotics “have been shown to cause marked alterations in gut flora and can have long term effects on intestinal bifidobacteria.

"In the case of irritable bowel syndrome, they note, prior antibiotic use appears to be a risk factor in the development of the illness.”

They also cite research in both humans and animals showing that emotional stress can be a negative factor. Anger and fear, especially, increase bacteroides (an irregularly shaped bacterium) from 2-4 percent of the total bacteria in the intestine to 20-30 percent.

They conclude by saying that “the findings of low levels of bifidobacteria in chronic fatigue syndrome are of particular significance, as the available evidence suggests that this specific group of lactic acid bacteria, when reduced or diminished, indicates an unhealthy state.

"The microbes of the gastrointestinal tract appear intricately involved with the systemic immune and nervous systems and perhaps their role in functional conditions such as chrinic fatigue syndrome is currently underestimated.”   April 22, 2003

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New findings on Chronic Fatigue Syndrome

People with Chronic Fatigue Syndrome (CFS) often show low blood pressure readings, especially after standing from a sitting position. A New York state study found that 15 CFS patients had significantly lower (p<0.0001) systolic (heart pumping) and diastolic (heart filling) blood pressure than 15 health-matched controls. Standing heart rates were significantly increased in the CFS patients (p<0.01).

When 11 of these patients wore Military Anti Shock Trousers (MAST), which increased blood pressure on their legs and moved blood up to the brain, 10 patients (91%) reported improvement of their CFS symptoms.

In addition, red blood cell volume was significantly decreased in plasma and norepinephrine levels were significantly higher in the CFS patients. Low blood pressure, especially in the brain, can cause fatigue and lack of concentration. Another study published in JAMA (1985; 274:961-7) noted that many CFS patients with low pressure reported reduction in symptoms when given a diet high in water and sodium. (Source: Tired - So Tired and the 'Yeast Connection' by William G. Crook, M.D.)

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Measure Aids Chronic Fatigue Syndrome Assessment
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
Retrieve&db=PubMed&list_uids=12528078&dopt=Abstract Semin Arthritis Rheum 2002 Dec;32(3):141-8. "Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome." 01/23/2003 10:47:14 AM By Anne MacLennan

A particular and quantifiable abnormality in the cardiovascular reactivity of most patients with chronic fatigue syndrome provides an new objective tool for assessing this disorder, suggest researchers in Israel. Using a method they developed of giving numerical expression to degree of blood pressure and heart rate lability, the investigators had previously found this 'haemodynamic instability score' (HIS) in CFS patients differs significantly from that in healthy subjects. In the current investigation, they found the large majority of CFS patients exhibit an abnormality which is characterised by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS, report Dr J E Naschitz and colleagues from the Bnai Zion Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel. This study compared the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope. Twenty patients with CFS, 24 with non-CFS chronic fatigue, 44 with syncope of unknown cause and 21 age and sex-matched healthy controls were all evaluated with a standardised head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified 'clinical outcomes' (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and 'HIS endpoint', ie HIS >-0.98. Highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%) and healthy controls (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of non-CFS chronic fatigue patients and 43% of those with recurrent syncope. Average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0) and healthy = -2.48 (4.07). Odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients and 34.8 compared with healthy controls. The investigators point out the cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. However, apart from these shared responses, most patients with CFS exhibit this particular abnormality, which is characterised by HIS values >-0.98, lending objective criteria to CFS assessment, these authors conclude.

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Understanding Chronic Fatigue Syndrome
Source: AmericasDdoctor:  http://www.americasdoctor.com/

Chronic Fatigue Syndrome, or CFS, is still not completely understood by
both the general public and the medical community. Everyone feels tired
from time to time, but how can we tell if our fatigue is more than just
fatigue?

To better understand CFS, AmericasDoctor spoke to Dr. Inam Ur Rahman, a
private practicing physician specializing in general internal medicine,
family practice, sports medicine, acute injuries, obesity treatment and
sexual dysfunction.

Q. Dr. Rahman, how does Chronic Fatigue Syndrome differ from just being
tired?

A. Fatigue or tiredness is a part of CFS just as it is part of many
other illness, such as congestive heart failure, anemia, hypothyroidism
and sleep apnea. Someone with complaints of fatigue that persist beyond
six months may be suspected of having CFS if they display any four of
the following symptoms:
- difficulty with short-term memory
- loss of concentration that interferes with daily activities
- waking in the morning not feeling refreshed, regardless of the quality
of sleep
- sore throat
- swollen lymph glands in the neck or under the arms
- muscle pains (myalgia)
- joint pain without swelling or redness
- inability to exercise, even mildly, without being tired for up to 24
hours later
The symptoms, if part of CFS, should have begun at the onset of the
fatigue or later, not before.

Q. When was CFS recognized as a distinct problem?

A. CFS has probably existed as far back as the time of Aristotle. It was
even attributed to witchcraft in the 15th century, although physician
Johann Weyer tried to address the syndrome at the time. Unfortunately,
the dilemma of recognizing CFS as a distinct entity lies in how it
presents and its overlap of symptoms with other disorders such as
migraines, premenstrual syndrome and irritable bowel syndrome. Many
physicians are still not ready or willing to handle this
difficult-to-treat and time-consuming disease.

Q. Do you see many new patients with CFS?

A. Actually, patients don't usually come into the office with obvious
CFS. I have to recognize it. Chronic Fatigue Syndrome is still
underdiagnosed. Many patients with the signs and symptoms of CFS don't
complain to their doctors because they feel that their fatigue is due to
their busy lives; they hesitate to 'bother' the doctor.

Q. What makes you suspicious that CFS may be a patient's problem?

A. Chronic Fatigue Syndrome must be kept in the back of your mind, even
while you are ruling out other disorders that cause fatigue, such as
hypothyroidism. This is especially important when you are presented with
a patient who may seem like a 'typical' CFS patient. This would be a
patient who is:
- Caucasian
- female
- between the ages of 20 and 50 years old
- has complained of chronic fatigue and associated symptoms for more
than six months
- has no identifiable medical or psychological problem
A good patient history and medical examination are very important in
leading you to the proper diagnosis.

Q. Are there specific tests for CFS or is it a diagnosis that is made
when all others are ruled out?

A. Since CFS is a functional disorder, there are no specific tests to
detect it. For example, blood tests may show high cholesterol and low
cortisol levels but these are not specific to CFS and can be present in
many other diseases as well. Testing that uncovers fibromyalgia, sleep
disorders, anemia, hypothyroidism, stress disorders or major depression
can sometimes rule out CFS but what makes this even more difficult is
that CFS can actually co-exist with these conditions.

Q. Is CFS treatable?

A. Yes, CFS is treatable but it is very difficult and patients'
responses to treatment can vary widely. If there are any underlying
causes, they should be treated first. Patients should make lifestyle
changes such as quitting smoking, drinking and any use of illicit drugs.
They should also be encouraged to lose weight if necessary, eat a
balanced diet and exercise regularly if they can. A multi-specialty
approach may be the best in treating CFS. This would include behavior
modification, stress reduction, psychological counselling and a physical
therapy program in addition to medical intervention.

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Treatment of chronic fatigue with neurofeedback and self-hypnosis.
Hammond DC.

Department of Physical Medicine & Rehabilitation, University of Utah School
of Medicine, Salt Lake City, UT, USA.

A 21 year old patient reported a relatively rapid onset of serious chronic fatigue syndrome (CFS), with her worst  symptoms being cognitive impairments. Congruent with research on rapid onset CFS, she had no psychiatric  history and specialized testing did not suggest that somatization was likely. Neuroimaging and EEG research has  documented brain dysfunction in cases of CFS. Therefore, a quantitative EEG was done, comparing her to a  normative data base. This revealed excessive left
frontal theta brainwave activity in an area previously implicated in  SPECT research. Therefore, a novel treatment approach was utilized consisting of a combination of EEG  neurofeedback and self-hypnosis training, both of which seemed very beneficial. She experienced considerable  improvement in fatigue, vigor, and confusion as measured pre-post with the Profile of Mood
States and through  collaborative interviews with both parents. Most of the changes were maintained at 5, 7, and 9 month follow-up  testing. NeuroRehabilitation 2001;16(4):295-300
PMID: 11790917 [PubMed - in process]
www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=6&db=m&uid=11790917 <a
href="http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?form=6&db=m&uid=11
790917"></a>

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Fresh Approach to Chronic Fatigue Syndrome Urged
ImmuneSupport.com 02-05-2003

Patients with chronic fatigue syndrome or ME should receive both medical and
psychological treatment for the condition, say experts. The root cause of
ME -which is also referred to as chronic fatigue syndrome - is still a matter of debate.
Some doctors believe that it is principally a psychological illness, while
others say that it should be regarded as a physical condition. Patients
often accuse doctors of ignoring the physical aspects of their illness while
some doctors say patients are often unwilling to consider any psychological
causes.

This latest report calls on both sides to drop their polarized positions.
They suggest that disagreement between the medical profession and patients
has seriously interfered with good treatment.

The report, which was launched at the Royal College of Physicians in London,
urges doctors not to rule out a physical cause of ME. But it also calls on
patients to be open to the idea of psychological treatment.

It states: "Some doctors and health practitioners wish to deny or discount
the physical aspects, just because they are not clearly understood and some
patients are so angry having psychological problems wrongly ascribed to them
that they dismiss as irrelevant any consideration of psychological aspects,
however sympathetic and careful that consideration may be."

'Whole person' approach

Dr Richard Sykes, author of the report and a consultant to Action for ME,
said a "whole person" approach is needed. He said this involved viewing ME
"as a physical illness which can be influenced, as other physical illnesses,
by psychological and social factors."

The report calls for further research into the condition but warns that it
may be years before a physical cause is found. It states: "It is important
that research is pursued on the physical basis of CFS/ME and on physical
treatments for it. "It is also important that sensitive and sympathetic
psychological help, based on a careful understanding of each individual
patient and their illness, is provided."

Dr Charles Shepherd, medical adviser at the ME Association, welcomed the
report. "This report recognizes that whilst physical aspects of CFS/ME are
extremely important, the illness can also produce quite profound
psychological distress. "At present, the psychological and social aspects of
CFS/ME are often neglected or badly managed by health professionals. "There
can also be occasions when patients themselves fail to recognize that these
aspects are exerting an adverse effect on any possible recovery process."

Source: BBC News (http://news.bbc.co.uk/2/hi/health/2660963.stm).Thursday,
16 January, 2003, 00:05 GMT

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A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome.
Olson LG, Ambrogetti A, Sutherland DC. Jan. 4, 2002.

This study determined whether dexamphetamine improved symptoms and quality of
life in patients with chronic fatigue syndrome. The setting was a specialized
clinic within a tertiary referral hospital. This was a 6-week parallel-group,
placebo-controlled trial with random allocation. There was a 2-week
dose-adjustment phase and a 4-week stable treatment period. Outcome measures
were the Fatigue Severity Scale, the Medical Outcomes Study 36-item
Short-Form Health Survey, and two patient-determined outcomes. Ten patients
were randomly assigned to dexamphetamine, and 10 were assigned to placebo.
Fatigue Severity Scale scores improved in nine of 10 dexamphetamine and four
of 10 placebo patients. The change in mean score was statistically
significant. There were large but statistically nonsignificant changes in
scores for the Short-Form Health Survey domains vitality and physical
functioning. Dexamphetamine may be useful in the management of chronic
fatigue syndrome; a larger and longer trial is justified by these results. PMID: 12515836 Return to Table of Topics.

Neurotoxin Discovered in Chronic Fatigue Syndrome Needham, MA November 17, 2002 -- Research sponsored by the National CFIDS Foundation was formally announced at the International Symposium on Toxins and Natural Products in Okinawa, Japan on November 17-19, 2002 by Dr. Yoshitsugi Hokama. The research, for the first time, discovered: ciguatoxin, a potent neurotoxin, in the blood of Chronic Fatigue Syndrome patients.

"Chronic ciguatera poisoning has already been suggested as a scientific model for Chronic Fatigue Syndrome (CFS)," stated Dr. Hokama. Ciguatoxins are potent, heat stabile, non-protein, lipophilic sodium channel activator toxins and are recognized as some of the most potent biological toxins known. They produce dramatic neurological manifestations, such as peripheral sensory or motor symptoms (including paresthesias, pain, burning, numbness), central symptoms such as headache, autonomic dysfunction and also affect multiple body systems (gastrointestinal, immune, hepatic, cardiovascular) and the muscles.

Many CFS patients in the study had higher levels of the toxin than the patients with cancer, hepatitis or acute ciguatera poisoning.
Quantitative assay results range from 1:5, the lowest toxin level, to 1:160, the highest toxin level. All CFS samples gave titres of at least 1:20, with the majority of titres from 1:40 to 1:160. Dr. Hokama presented his preliminary findings in a lecture titled "Acute phase lipids in sera of various diseases: Chronic Fatigue Syndrome, ciguatera, hepatitis, and various cancer with antigentic epitope
resembling ciguatoxin as determined with Mab-CTX."

Dr. Hokama is a Professor in the Department of Pathology at the John A. Burns School of Medicine at the University of Hawaii at Manoa.  He is a world expert in the area of fish toxins with hundreds of peer reviewed publications to his credit. Hokama developed the Membrane Immunobead Assay test for patient sera, using a specific monoclonal antibody for ciguatera toxin (Mab-CTX). His current research into Chronic Fatigue Syndrome and a ciguatera toxin connection was funded by the National CFIDS Foundation's research grant program.

Gail Kansky, President of the National CFIDS Foundation, said, "We believe this to be a significant breakthrough. CFS, which has come to include myalgic encephalomyelitis, is a very severe illness that has not received adequate funding or appropriate medical attention. Although there are
still many unanswered questions and much work to be done, research efforts will ultimately turn the tide in the understanding of this disease and allow patients to receive appropriate medical therapies.  We are indebted to Dr. Hokama and his colleagues for providing this monumental first step."
For more information on this study or Chronic Fatigue Syndrome, please contact: The National CFIDS Foundation 103 Aletha Road Needham, MA 02492 phone: 781-449-3535 fax: 781-449-8606

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RNase L Proteolysis in Chronic Fatigue Syndrome: A Diagnostic Marker?

In this promising new research by Kenny De Meirleir, M.D., Ph.D., et al, it is shown that a 37 kDa binding polypeptide accumulates in peripheral blood mononuclear cells (PBMC) extracts from Chronic Fatigue Syndrome (CFS) patients, and is being considered as a potential diagnostic marker for the disease. (you will have to register at the site,for free, to view this article)

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Caffeine, fatigue, and cognition. Brain Cogn. 2003 Oct;53(1):82-94.
Lorist MM, Tops M. Experimental and Work Psychology, University of Groningen, Groningen,
The Netherlands

Effects of caffeine and fatigue are discussed with special attention to
adenosine-dopamine interactions. Effects of caffeine on human cognition
are diverse. Behavioural measurements indicate a general improvement in
the efficiency of information processing after caffeine, while the EEG
data support the general belief that caffeine acts as a stimulant.
Studies using ERP measures indicate that caffeine has an effect on
attention, which is independent of specific stimulus characteristics.
Behavioural effects on response related processes turned out to be
mainly related to more peripheral motor processes. Recent insights in
adenosine and dopamine physiology and functionality and their
relationships with fatigue point to a possible modulation by caffeine of
mechanisms involved in the regulation of behavioural energy expenditure.

PMID: 14572506

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Patients' perceptions of medical care in chronic fatigue syndrome.
1: Soc Sci Med 2001 Jun;52(12):1859-64 Deale A, Wessely S.
Academic Department of Psychological Medicine, Guy's, King's and St  Thomas's School of Medicine, Kings College, University of London, UK. alicia.deale@kcl.ac.uk

This study investigated perceptions of medical care among patients with chronic fatigue syndrome (CFS) referred to a specialist clinic. Sixty-eight patients completed a questionnaire survey on their overall satisfaction with medical care received since the onset of their illness, and their views on specific aspects of care. Two-thirds of patients were dissatisfied with the quality of medical care received. Dissatisfied patients were significantly more likely to describe delay, dispute or confusion over diagnosis; to have received and rejected a psychiatric diagnosis; to perceive doctors as dismissive, skeptical or not knowledgeable about CFS and to feel that the advice given was inadequate or conflicting. Satisfied patients were significantly more likely to perceive doctors as caring, supportive and interested in their illness; to state that they did not expect their doctors to cure CFS and to perceive their GP or hospital doctor as the source of greatest help during their illness. Many patients were critical of the paucity of treatment, but this was not associated with overall satisfaction. The findings suggest that medical care was evaluated less on the ability of doctors to treat CFS, and more on their interpersonal and informational skills. Dissatisfaction with these factors is likely to impede the development of a therapeutic doctor-patient alliance, which is central to the effective management of CFS. The findings suggest a need for better communication and better education of doctors in the diagnosis and management of CFS. PMID: 11352411

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Sleep Dysfunction in CFS By Richard Podell, MD, MPH

Many patients with chronic fatigue syndrome (CFS) feel sleepy as well as
tired. Whether or not they have difficulty falling asleep (sleep onset
insomnia) or difficulty staying asleep (sleep maintenance insomnia),
most CFS patients feel that their sleep is not refreshing. They wake up
in the morning feeling as if they haven't really rested.

Improving sleep is a realistic goal. As clinicians know, this is often a
complex and difficult task. Even modest improvement in sleep can have
important positive effects on the patient's sense of well-being.

Read this article at
http://www.cfids.org/archives/2002rr/2002-rr4-article01.asp

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Virus Seen in Muscle from Chronic Fatigue Syndrome Patients

01-06-2004   By Will Boggs, MD

A persistent enterovirus infection in muscles may be to blame for some cases of chronic fatigue syndrome (sometimes called fibromyalgia) and others with chronic inflammatory muscle disease, a French team reports.

They detected genetic material (specifically RNA) from enteroviruses in 20
percent of muscle biopsies from patients with chronic inflammatory muscle
diseases and 13 percent of patients with fibromyalgia/chronic fatigue
syndrome, but not from healthy volunteers.

The findings favor a persistent infection involving defective viral
replication as a cause of these conditions.

"The persistence of defective or infectious enteroviruses is well
established for a lot of organs," Dr. Bruno Pozzetto from the University
Hospital Center of Saint-Etienne, France, told Reuters Health.

Such infections have been documented in the heart, with possible involvement in heart enlargement; in pancreatic cells, possibly linked to juvenile diabetes; and in the central nervous system in association with a syndrome that afflicts aging survivors of polio, the researcher explained. "However, the link between these diseases, as well as chronic inflammatory muscle diseases, and viral persistence is not clear."

Pozzetto and colleagues investigated the presence of enterovirus in skeletal muscle biopsies from 15 patients with chronic inflammatory muscle diseases, 30 patients with fibromyalgia/chronic fatigue syndrome, and 29 healthy subjects to test their hypothesis that skeletal muscle may play host to persistent enteroviral infection.

Three patients with chronic inflammatory muscle disease and four patients with fibromyalgia/chronic fatigue syndrome were positive for enterovirus RNA, the team reports in the Journal of Medical Virology.

None of the muscle biopsies in this study contained a particular viral
protein, the researchers note, which "suggests a defective viral
replication."

It is too early to derive implications for treatment from these results,
Pozzetto said.

However, he noted that so-called Coxsackie B viruses seem to play a key role in persistent muscular infections. "To prevent this persistence, an
inactivated vaccine directed toward these viruses could be indicated."

Also, an antiviral agent called pleconaril, "acting during the early phases
of the viral cycle, could also be useful in muscular diseases clearly
associated with enterovirus." This is being tried in some cases of
heart-muscle enlargement, Pozzetto said, but "it is too early to answer for muscular diseases."
SOURCE: Journal of Medical Virology, December 2003.
(Distributed by Yahoo! from Reuters news service).

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Combining Hydrocortisone and Fludrocortisone: An effective treatment for Chronic Fatigue Syndrome?

By Dr. Charles Shepherd

The cause and significance of hypocortisolism in ME/CFS (i.e. decreased
production of the hormone cortisol from the adrenal glands) remains the
subject of debate. All of the evidence so far indicates that the cause is
more likely be central (i.e. in the brain) rather than peripheral (i.e. at
the level of the adrenal glands, where the hormone is produced). In other
words, the adrenal glands don't seem to be receiving enough in the way of stimulatory messages from higher centers in the brain (in particular, the hypothalamus gland - the 'leader of the hormonal orchestra'), and this
results in a reduced output of cortisol.

Low levels of cortisol also occur in an interesting and rare condition known as Addison's disease, but are much more severe and potentially
life-threatening. Even so, Addison's disease has a number of very similar
clinical features to ME/CFS (i.e. fatigue, muscle weakness, dizziness and
hypotension/low blood pressure). As a result, there have been a number of attempts to see if the type of hormonal treatments used in Addison's disease (i.e. effective in ME/CFS.

Two clinical trials have examined the use of hydrocortisone alone in ME/CFS patients. An American trial (ref: Journal of the American Medical
Association, 1998, 280, 1061 - 1066) reported an improvement in general
health but not in activity, depression, mood or symptom measures. A UK Trial (ref: Lancet 1999, 353, 455 - 458), using a lower dose of hydrocortisone, also reported some degree of improvement in fatigue, symptoms, and disability level. Of some concern was the fact the American trial found evidence of adrenal gland suppression (i.e. the output of natural cortisol had been suppressed by the synthetic hormone).

Two trials (refs: Archives of Internal Medicine, 1998, 158, 908 - 914;
Journal of the American Medical Association, 2001, 285, 52 - 59) have also assessed fludrocortisone alone. Neither have reported any benefits.

A research group from Belgium have now reported results from a clinical
trial involving a combination of hydrocortisone (5mg/day) and
9-alphafludrocortisone (50 micrograms/day) in ME/CFS patients (ref: American Journal of Medicine, 2003, 114, 736 - 741). The trial involved 100 patients who met Fukada et al research criteria for CFS. It was randomized, placebo-controlled, doubled-blinded and crossover (i.e. they had three months active treatment followed by three months placebo) in design. 8O/100 patients completed the trial.

Overall, there was no difference in the various outcomes - including fatigue levels, general well-being, and blood pressure measurements (which the fludrocortisone may have helped to raise) - even in those patients that had the lowest of the baseline cortisol levels.

Although these results suggest that the type of combination therapy used to treat Addison's disease is not going to be helpful in ME/CFS, the research group wisely point out that ME/CFS is a heterogeneous condition and that there could well be a subset of patients with disturbances in the
hypothalamic-pituitary-adrenal axis that could respond to hormonal
treatments. So further research in this area of therapeutic intervention is
clearly warranted - possibly by using a more carefully selected group of
patients who have evidence of significant adrenal gland suppression
[research by Professor Ted Dinan et al using CT scanning has shown that some ME/CFS patients have quite a significant degree of adrenal gland atrophy: Psychoneuroimmunology, 1999, 24, 759 - 768].

In the meantime, most doctors (myself included) will continue to err on the side of caution and remain reluctant to prescribe either low doses of
hydrocortisone (mainly because of fears about adrenal gland suppression - even when using a very low dose) or fludrocortisone (because of its
potential side-effects).

Source: Co-Cure

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In Some Patients with CFS,LeftVentricular Function May Be At The Heart Of The Matter

April 9, 2003 (San Diego) - Chronic fatigue syndrome (CFS) is a baffling
disorder. Some 20 years ago, it was dubbed "the yuppie flu," because the
complaints of a similar constellation of problems were reported primarily by
women in their 30s and 40s who were well educated and in upper-income
brackets. Since the 1980s, CFS has become better understood, which is good news for the estimated 500,000 Americans of all ages, genders, ethnic origins, and earning capacities who are believed to suffer from a CFS-like condition. Even today, however, the causes of this illness remain a mystery.

Background: CFS is today a clinically defined illness of still unknown
origin. The minimum criteria for a CFS diagnosis are unremitting, disabling
fatigue, accompanied by several other neuropsychological, rheumatological, and influenza-like symptoms.

Patients frequently report an infection as an antecedent event.
Unfortunately, efforts to find infectious or immunological causes have not
been successful.

Growing evidence, however, points to a possible problem with circulation.
Previously reported findings include autonomic dysfunction, lower plasma
volume and/or red call mass, as well as abnormalities in neurohormonal
systems of circulatory control. Other studies have found that CFS patients may have reduced blood flow in exercising muscles.

A New Study: The main symptom of the CFS patient (i.e., chronic fatigue that is greatly exacerbated by even minor effort) is similar to that of a patient with left ventricular dysfunction. A team of researchers thus hypothesized that some patients with left ventricular dysfunction who do not show overt signs of cardiac insufficiency may nevertheless develop persistent, disabling fatigue and become diagnosed with CFS. To explore this possibility, they conducted special tests on CFS patients and healthy
controls.

The authors of a new study, "Left Ventricular Function in Chronic Fatigue
Syndrome (CFS): Data From Nuclear Ventriculography Studies of Response to Exercise and Postural Stress," are Arnold Peckerman, Rahul Chemitiganti, Caixia Zhao, Kristina Dahl, Benjamin H. Natelson, Lionel Zuckier, Nasrin Ghesani, Samuel Wang, Karen Quigley and S. Sultan Ahmed. All are affiliated with the Departments of Neurosciences and Radiology, University of Medicine and Dentistry of New Jersey, Newark, NJ, as well as with the War-Related Illnesses and Injuries Study Center, VA Medical Center, East Orange, NJ. They will present their findings at the American Physiological Society conference, Experimental Biology 2003, being held April 11-15, 2003, at the San Diego Convention Center, San Diego, CA.

Methodology: Sixteen patients meeting case definition for CFS established by the Centers for Disease Control and Prevention (CDC) and 4 control subjects participated in the study. The control subjects were sedentary individuals, gender and age-matched to the CFS group. The researchers used the radioisotopic multiple gated acquisition (MUGA) blood pool method of ventriculography to perform a series of dynamic studies of the heart to assess for evidence of abnormalities with myocardial function.

MUGA ventriculography uses a radionuclide tracer to label red blood cells,
allowing visualization of cardiac blood pools with a gamma camera. The
emission counts are processed to estimate volumes of blood in the left
ventricle (the heart's main chamber) at the end of relaxation and at the end of contraction periods. Their ratio (called the ejection fraction, or EF) is a measure of myocardial contractility, and is considered to be the best
non-invasive indicator of left ventricular function.

Protocol: MUGA studies were performed under 2 experimental conditions: (1) maximal exercise; (2) an active postural change. Maximal exercise
ventriculography is commonly used for evaluation of possible heart disease. Postural testing was done in addition to exercise because many CFS patients report worsening of symptoms during standing.

Exercise: Testing was performed lying down on a cycle ergometer table. The initial workload was set at 200 kilopond meters (kpm)/min (40 watts), and was increased by 200 kpm/min every 3 min until the subject was no longer able to maintain the pedal speed due to fatigue, muscle pain, or shortness of breath. Blood pressure, heart rate, and ratings of perceived exertion were obtained at each stage. Failure to increase EF during maximal exercise stage indicates possible abnormalities with left ventricular function.

Postural Change: Measurements of cardiac functioning were taken in the
supine and standing positions. EF is expected to increase in the standing
position to counteract the effects of gravity on reduced blood flow to the
heart.

Results - Researchers observed the following:

The two groups had similar resting ejection fraction (EF). During maximal
exercise, EF increased in controls, but declined in CFS patients. The
decreases in EF tended to be greater in patients with more severe symptoms.
Using a decline in EF as a criterion, 13 CFS patients (81 percent) and 0
control subjects had positive tests. There were no group differences in
levels of exertion, as indicated by similar cumulative work output, maximal
heart rate, and increases in lactate levels.

A similar pattern of changes in EF (i.e., increases in controls and declines
in CFS patients) was observed in response to postural stress. Conclusions
This study provides a preliminary indication of reduced cardiac function in
some patients with CFS. It raises the possibility that some CFS patients may have cardiac disorders that are subtle enough to escape the current net of clinical cardiological diagnoses, but may be significant enough in some patients -- perhaps in conjunction with other factors -- to lead to the clinical syndrome of CFS.

The researchers note that their findings may also be explained by
abnormalities other than those with the heart, including problems with the
distribution of cardiac output, reduced blood volume, and neurogenic and
endocrinologic abnormalities. Accordingly, further studies capable of
defining more precisely the causes of altered cardiac stress responses are
required.

The American Physiological Society (APS) is one of the world's most
prestigious organizations for physiological scientists. These researchers
specialize in understanding the processes and functions underlying human
health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.

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Diagnosing Chronic Fatigue? Check for Sinusitis

Washington, D.C. - A new study published in the August 11 issue of the
Archives of Internal Medicine demonstrates a possible link between unexplained chronic fatigue and sinusitis, two conditions previously not associated with each other. Also newly noted was a relationship between sinusitis and unexplained body pain. These findings offer new hope to
patients lacking a diagnosis and treatment for fatigue and pain.

Sinus disease is seldom considered as a cause of unexplained chronic fatigue or pain, despite recent ear, nose, and throat (otolaryngology) studies documenting significant fatigue and pain in patients with sinusitis and dramatic improvement after sinus surgery.

A Harvard study showed that fatigue and pain scores of sinusitis patients
were similar or worse than a group 20 years older with congestive heart
failure, lung disease, or back pain.

"Chronic fatigue is a condition that frustrates both doctors and their
patients since treatments directed at just the symptoms without knowing the cause are typically ineffective," said Alexander C. Chester, M.D., clinical professor of medicine at Georgetown University Medical Center and principal investigator of the pilot study. "While sinusitis will not be the answer for everyone who comes to an internist with unexplained fatigue or pain, this study does suggest that it should be considered as part of a patient's medical evaluation."

Through his private internal medicine practice, Chester questioned 297
patients, noting unexplained chronic fatigue in 22%, unexplained chronic
pain in 11%, and both in 9%. While these numbers are consistent with
previous studies, Chester observed an unusual connection between patients with chronic pain or fatigue: prevalent sinus symptoms. Sinus symptoms were nine times more common on average in patients with unexplained chronic fatigue than the control group, and six times more common in patients with unexplained chronic pain.

In addition, sinus symptoms were more common in patients with unexplained fatigue than in patients with fatigue explained by a mental or physical illness, suggesting the syndrome of unexplained fatigue is more closely associated with sinusitis than are other types of fatigue.

The CDC approximates that sinusitis affects 32 million Americans. Rates are highest among women and people living in the South. Women comprised 46% of the participants in this study, but represented 60% of the group with fatigue, predominance also noted in most prior studies.

15 out of the 65 patients in Chester's study met criteria for chronic
fatigue syndrome (CFS), a severe form of unexplained chronic fatigue
associated with body pains and other symptoms. Most CFS patients had sinus symptoms and many noted a sudden onset of their illness, similar to people with sinusitis.

"We clearly need to do more research to see if sinus treatments alleviate
fatigue and pain. This study does, however, offer hope for possible help in
the future." said Chester.

Georgetown University Medical Center is an internationally recognized
academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis--or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Cancer Center.

SOURCE: Georgetown University Medical Center. On the Web at
ttp://gumc.georgetown.edu/communications/releases/release.cfm?ObjectID=657

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Chronic Fatigue Syndrome & Thyroid Function: Seeking Appropriate Treatment

By Dr. Charles Shepherd

Following a recent discussion on several UK lists around the controversial
subject of thyroid function and the use of thyroxine to treat myalgic
encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), here are a few key points on which I feel the vast majority of doctors involved in the
management of ME/CFS patients would agree:

1. Before a diagnosis of ME/CFS is confirmed, thyroid function tests must
form part of the routine (blood) investigations, because defective
production of thyroid hormone/thyroxine (also known as
hypothyroidism/myxoedema) can cause a number of ME/CFS-like symptoms. In a few people both conditions co-exist.

2. At the diagnostic stage, checking the blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) is usually all that is necessary. The TSH test is very sensitive and measures the level of a hormone produced by the anterior pituitary gland in the brain, whose function it is to stimulate the thyroid gland (in the neck) to produce thyroxine. If natural production of thyroxine starts to fall, this is quickly picked up by thyroid hormone sensors and the TSH level starts to rise.

However, in the case of the much rarer secondary hypothyroidism (which is caused by problems with the pituitary or hypothalamus glands in the brain) there is a reduced level of T4 and a TSH level which is normal or below normal. Abnormalities in thyroid function tests can also be caused by drugs and other illnesses (including low levels of cortisol). As such, the
interpretation of these test results isn't always easy for the non-expert.

3. Other types of thyroid function tests - such as measuring the level of T3 (tri-iodothyronine) and looking for thyroid peroxidase antibodies - may be helpful in certain circumstances.

For example, people who have autoimmune thyroid disease may present with ME/CFS-like symptoms. And a recent journal report described the disturbing case of an adolescent who had been misdiagnosed as having ME/CFS but turned out to have a severe autoimmune thyroiditis which required urgent treatment with steroids (ref: Lancet, 2003, 361, 572 - 'An organic cause of neuropsychiatric illness in adolescence'). But some of the other tests on offer in the private sector (e.g., the urine test) are highly speculative and not yet accepted by mainstream medicine here in the UK.

4. So if there's any doubt about thyroid status, it's worth asking for a
referral to an endocrinologist (hormone expert) at a hospital.

5. At present, there is no reliable evidence to indicate that any type of
thyroid disease is more common in people with ME/CFS although a few doctors (mainly in private practice) claim that this is the case.

6. Although there is an on-going debate in the medical journals about
whether people can have defective thyroid function but normal thyroid
function blood test results, I am not aware of any specialist or
endocrinologist who supports the prescribing of thyroid supplements to
people with normal test results. Consequently, NHS GPs and consultants are unlikely to agree with such an approach. This is a controversial form of treatment that is largely carried out in the private sector.

7. Thyroxine supplementation always has to be prescribed with great care and carefully monitored as this hormone stimulates activity in various parts of the body, in particular the heart. The problem is that even at very low doses some people are extremely sensitive to thyroxine supplementation and so develop potentially serious (even fatal) heart rhythm disturbances such as atrial fibrillation. There are also a number of potential long-term problems including suppression of the thyroid gland's natural output of thyroxine and increasing the risk of osteoporosis.

8. An additional potential problem in people with ME/CFS, who may already have low levels of the hormone cortisol, is that prescribing thyroxine in this situation can lead to additional stress on the adrenal glands and produce what is called an Addisonian crisis.

So before starting treatment with thyroxine (for whatever reason) people
with ME/CFS ought have their cortisol level checked to make sure there is no significant degree of adrenal insufficiency (ref: BMJ, 1996, 313, 427 -
'Adrenal insufficiency should be excluded before thyroxine replacement is
started').

9. Thyroid function is an area of medicine where more research is clearly
needed and it would be worthwhile carrying out a proper research study to look at TSH, T4 and T3 levels in people with ME/CFS. In the meantime, many doctors will take the view that giving thyroid hormones to people with normal biochemical profiles remains dubious and potentially dangerous on both scientific and medicolegal grounds.

10. To follow up both sides of the debate in a little more detail, consult:
BMJ, 1997, 314, 1764 - 'Thyroxine should be tried in clinically hypothyroid,
but biochemically euthyroid patients' - the case in favor. BMJ, 1997, 315,
813-814 - responses from Professor Garth Williams ('Distinguishing
hypothyroid symptoms from common non-specific complaints is difficult');
Professor A. Toft, President of British Thyroid Association (Giving thyroid
hormones to clinically euthyroid but biochemically euthyroid patients'), and myself (Long term treatment is being used') - the case against. [There is public access to BMJ material: use the archive facility on their website at http://www.bmj.com]
Source: This article was distributed via Co-Cure.

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Could Antidepressants Help Those with Chronic Fatigue Syndrome/ME?

12-10-2003

By Dr. James Le Fanu

It is always a pleasure to pass on readers' personal tips and remedies, but
what follows is in a rather different league - with the potential to
transform the lives of thousands. Chronic Fatigue Syndrome (also known as ME - Myalgic Encephalomyelitis) must be one of the most argued over medical conditions of all time.

Doctors in the past have been less than sympathetic, pointing out how the wide range and severity of symptoms complained of seems quite incompatible with the lack of objective evidence of impairment. Chronic Fatigue [Syndrome], it has been alleged, is either a psychological disorder such as hypochondriasis, or even a "malingerer's charter", an unprovable
pseudo-scientific diagnosis much favoured by the indolent and work-shy.

Then, without apologising for the offence previously given, the medical
profession changed its tune. Doctors conceded that there was clear evidence of some abnormality of brain functions: patients sleeping patterns were often chaotic and their "hypochondriac symptoms" were due to a disturbance of the autonomic nervous system, which controls such crucial things as blood pressure, body temperature and so on. But what to do about it?

It seemed logical to prescribe something that might improve the brain
function, such as the anti-depressant drug Prozac which boosts the levels of the neurotransmitter serotonin in the brain. This did not mean that those with Chronic Fatigue [Syndrome] were depressed (surprisingly, in view of their misfortune, they tend not to be), but rather "just in case" boosting the serotonin levels might work for them as it does for those with depression.

Well, it did not, and quite unequivocally so. "Prozac has no beneficial
effect on any characteristic of Chronic Fatigue [Syndrome]", concluded one of several groups of researchers, writing in The Lancet. And that was pretty much the end of that.

Thus doctors treating the condition had little alternative other than to
fall back on one or other "coping strategy", such as cognitive therapy or
graded exercises, which it was presumed must at least be better than doing nothing. And both do appear to help a little, although not to any great effect, and some patients quite rightly find such approaches onerous, as they do not address the underlying problem.

This preamble is the necessary background to appreciate the significance of a recent letter from Mrs. Cynthia Floud from Hampstead, north London - erstwhile director of an adoption agency, Justice of the Peace and wife of a polytechnic director. Her busy life was rudely interrupted when, following a walking holiday in Skye, she contracted 'flu from which she never fully recovered. As a result, she spent the best part of a decade "lying in bed listening to Radio 4, unable even to read novels as it tired me too much".

She knew all about this as, unfortunately, a couple of years earlier her
daughter had also been struck down by Chronic Fatigue [Syndrome], forced to pack in her university course and return home. "We both had so little energy that if we got upset or, conversely, quite elated, we would have to pay for it with several days of feeling very ill."

They then read a piece in their local paper, The Ham and High, concerning D. Ian James from the Royal Free Hospital, who was seeking patients for a research project into their condition. Dr. James had become fascinated with the effects of drugs on the brain ever since he had earned the gratitude of legions of musicians by demonstrating the value of betablocker drugs in overcoming the effects of stage fright.

Dr. James's take on Chronic Fatigue [Syndrome] was straightforward: here was a disorder of brain function for which the best treatment must be some drug that could correct whatever was disordered. To be sure Prozac hadn't worked, but that did not mean that some similar drug, such as sertraline, might not do the trick if one got the dosage right. It was all a matter of fine-tuning.

Cynthia Floud and her daughter willingly volunteered to be his guinea-pigs, starting intially with a low dose and increasing gradually to 100mg daily. "Nothing happened for eight weeks. Then I woke one morning feeling I had slept heavily, just like I used to do before I was ill," Mrs Floud writes. "My daughter was a week behind me, and I had a worrying time fearing it might not also work for her."

Over the following weeks, as their energy levels surged, so their other
symptoms resolved as well. They then seemed to reach a plateau, but
continued to improve, albeit more slowly. It took five years in all before
"that blissful day when once again I could ride my bike through Regent's
Park hell for leather".

So why is this not common knowledge? Sadly, Dr. James died before he had the opportunity to write up his findings, which remain hidden from view, smothered by the blanket of the prevailing medical orthodoxy which holds that "antidepressant-type drugs do not work for Chronic Fatigue [Syndrome]".

Cynthia Floud, now firing on all cylinders, has been vigorously promoting
his cause - but to no avail. Perhaps those intrigued by this story could
persuade their family doctor to let them give sertraline a trial. If just
half a dozen people echoed Mrs. Floud's experience, I could then summarise the results in a letter to the British Medical Journal - and who knows how many people around the world might be grateful?

© Copyright of Telegraph Group Limited 2003. Source: The Telegraph, online at http://www.telegraph.co.uk.

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Salivary cortisol response to awakening in chronic fatigue syndrome