AACFS Conference 1998
new areas for exploration
Dr. Anthony Komaroff, conference chair,
gave what he described as
a cook's tour of the research conference to begin the patient conference. The more than 90 research presentations
representing work from 27 different countries were exciting, he said, compared to a decade ago when there
was very little research of any kind going on to study this disorder.
"The message from this meeting for
me was that now the disease is
being studied by people all over the world, and that can only be grounds for hope that as a result of
those studies and future studies, we will soon have better answers to this very important problem," Dr.
He cited as particularly interesting
studies of circadian rhythms
and the activation of the immune system. The evidence that calcium ion levels within cells may be a factor
in cellular energy production supports a previously observed potassium deficiency in heart muscle tissue
and below-normal pumping action. Studies such as one that found differences in the gait of CFS patients
may give other researchers clues to develop new hypotheses. Some studies confirmed and expanded knowledge
of the autonomic nervous system function in CFS, and others demonstrated a potential role for a reactivated
herpes virus and other more exotic viruses.
The group of papers on the RNase L
2'-5'A anti-viral pathway still
need to be confirmed with studies of more patients and in other diseases before that can be put forward
as a diagnostic test, he said.
Several studies examined new approaches
to treatment, notably NADH
and growth hormone. The studies are plausible, but they are all small studies, with none of them "even
close to reaching the level of maturity or size that would make them serious candidates for treatment
of this illness, but they are nevertheless interesting because they represent new approaches."
Dr. Komaroff said the various presentations
were all provocative,
and some of them, particularly the epidemiological studies from the CDC of Wichita and DePaul University
of Chicago (described in the Nov./Dec. 1998 Chronicle), were "pretty solid and conclusive." However,
those studies that relate to what's going wrong in the body and to treatments are all very preliminary
studies, "most of which I think are quite exciting but which I think are a long way from providing solid
answers to what causes the illness or solid approaches to treatment."Physiology
to many doctors' beliefs, CFS patients are not physically deconditioned, said Ellen Bazelmans of the Netherlands.
Exercise does increase fatigue and muscle pain in CFS a day later, but does not result in activity reduction.
Other than the 24% of CFS patients
who said they avoided activity
to prevent fatigue, day-to-day activity and rest patterns in CFS patients are similar to those of healthy
people, found Gijs Bleijenberg, of the same research group in the Netherlands. The CFS patients do rest
more following high levels of activity, but cognitive behavioral therapy might help them moderate their
activity levels to stop the activity-relapse cycle.
The CFS fatigue may result from cell
membranes that are leaking ions,
similar to that seen in the neurological disorder Syndrome X, reported Peter O. Behan of Glasgow, Scotland.
CFS patients require more energy than usual to maintain essential body function, he found. Thirty percent
of normal resting energy expenditure is used for ion transport, so leaky cell membranes would increase
a person's energy requirements, even at rest.
During exercise, CFS patients walk
slower and take smaller steps
than sedentary controls, but otherwise their gaits are similar, said Lorna Paul, who works with Dr. Behan
CFS in adolescents is related to delayed-onset
Julian Stewart of New York Medical College. In many patients, this autonomic defect is related to blood
pooling in the extremities and postural orthostatic tachycardia syndrome (POTS).
Severely and moderately ill CFS patients
may have different cardiovascular
causes for their symptoms, announced Benjamin Natelson of the New Jersey CFS Center. The most severely
ill patients seem to have extremely low blood volume, but the moderately ill patients appear to have a
neurological defect that interferes with the body's ability to regulate blood pressure.
CFS patients don't have the expected
rise in blood pressure in response
to either cognitive stress or exercise, said Sue Ann Sisto also of the New Jersey CFS Center. The low
systolic blood pressure common in CFS may be related to an inability to exhibit a normal range of blood
studies dealt with disability. David Klonoff of the University of California, San Francisco, looked at
the effect on ability to work of a 12-month comprehensive treatment program that included exercise, stress
reduction and dietary changes, along with assorted drugs. He found that the factors that most predicted
whether a patient would be able to return to work were not any specific treatment but rather beginning
treatment within a brief period of work disability (less than four months) and being below age 30. Norma
Ware, a researcher at Harvard Medical School, reported that work disability could be reduced by workplace
accommodations that eliminated unnecessary physical demands, allowed for flexible schedules and made part-time
work economically viable.
NADH (reduced nicotinamide adenine dinucleotide),
a natural substance known to trigger energy production through generation of ATP and to alleviate symptoms
of depression, may be a useful treatment in the management of CFS. In a four-week trial by Joseph Bellanti
at Georgetown University, eight of 26 patients showed more than 10% improvement with the treatment, while
over a year's use, 18 of 25 patients reported clinically significant improvement in symptoms and energy
levels. The treatment reduced elevated levels of serotonin metabolites in the urine.
Treatment with growth hormone produced
significant changes in body
composition and metabolism of amino acids but no measurable improvement in quality of life, according
to Greta Moorkens of Belgium, who noted the similarity of symptoms in CFS and patients with a growth hormone
Nancy Klimas of
the University of Miami is investigating a
procedure in which activated and functional T-cells are injected into lymph nodes. The procedure has been
tried in only a handful of patients, but there have been no adverse reactions and patients have experienced
a sharp increase in the number of CD4 and CD8 cells.
In a study of patients with acute infections
(specifically EBV, Ross
River virus and Q-fever), Andrew Lloyd of Australia found that symptoms suggestive of CFS persist after
the classic symptoms of infection are resolved. Resolution of the prolonged fatigue is associated with
improvement in immune function. The 75 subjects have been followed for more than a year and the study
Abnormal daily patterns in the immune
and endocrine system seem to be related to abnormal sleep-wake patterns and associated with the severity
of CFS symptoms, said Harvey Modolfsky of the University of Toronto. Compared to people with no symptoms
and people with a low level of fatigue or pain, CFS patients had altered cycles of the hormones cortisol
and prolactin and the natural killer cells of the immune system.
CFS patients seem to have a unique
form of autoimmune disease, concluded
Eng Tan of Scripps Research Institute. CFS patients seem to react to a different part of the lamin-B1
protein than patients with lupus and other autoimmune diseases.
CFS patients immune status is related
to the severity of their symptoms,
reported Stacy Wagner of the University of Miami. In addition to the data in Table 1, sleep disorders
were associated with a high number of activated cytotoxic (suppressor) T cells and overall sickness was
associated with a low percentage of cytotoxic T cells and a high CD4/CD8 ratio (see chart below).
Gulf War veterans with CFS seem to
have more immune dysfunction than
civilians with CFS, but the civilians with CFS are sicker, said Benjamin Natelson of the New Jersey CFS
and Gulf War research centers. The multiple vaccinations given to the vets prior to the war may have made
their immune systems similar, although stress, sleep and activity differences between the ill vets and
other groups may also have produced the unique immune profile.
Despite claims to the contrary,
researchers are learning a lot about the biology of CFIDS.
Ted Dinan studies
the hypothalamic-pituitary-adrenal (HPA)
axis in Peter Behan's CFS lab in Scotland. CFS patients have significantly lower adrenal gland volume
compared to depressed patients, who typically have elevated adrenal gland volume, he said. Even the depressed
CFS patients he studied had low adrenal gland volume, indicating that depression in CFS has a different
biological basis than regular depression.
John DeLuca, a
neurocognitive specialist at Benjamin Natelson's
CFS center in New Jersey, reported that CFS patients have very similar problems to multiple sclerosis
patients on neuropsychological tests. Although the CFS patients have cognitive impairments that are also
found in depression patients, the people with the worst cognitive problems were the CFS patients without
depression. Additionally, the patients with the most abnormalities on MRI tests were non-depressed CFS
patients. Dr. DeLuca therefore concluded that the cognitive problems in CFS are not related to depression.
Nancy Klimas, an immunologist from
the University of Miami, hypothesized
about the factors that may cause CFS to persist. The most important thing in this type of research, she
said, is to carefully define the study population. Dr. Klimas believes that lack of definitional rigor
may be the reason study results have conflicted so widely. As an example, she stated that 60-80% of CFS
patients and 18% of fibromyalgia patients report that their illness started acutely. If an investigator
mixes these two populations (s)he risks getting different results, especially with immune-related research.
Dr. Klimas also talked about four possible
causes of persistent immune
activation: a persistent virus, bacteria or toxin (i.e., HHV-6, Lyme, etc.), autoimmune disease, a "super
antigen" which turns on the entire immune system (i.e., silicone), or allergy. She also advised researchers
to avoid drawing conclusions from a one-time immune test (called cross-sectional research) because the
degree of immune upregulation in CFS seems to cycle with the degree of illness. What is unknown, however,
is whether the immune upregulation causes latent infections to emerge, or whether the infections cause
the immune system to become upregulated. Finally, because the immune, endocrine and neurological systems
are interdependent, she recommended that scientists integrate their research findings with possible effects
on the other body systems.
Psychiatric patients who develop
CFS have a different pre-CFS pattern of brain organization than psychiatric patients who do not develop
CFS, said Noble Endicott of the N.Y. State Psychiatric Institute. This study focused on such indicators
of brain organization as speech and learning disorders, migraine headaches and handedness, and Dr. Endicott
said it indicated that the same brain patterns associated with susceptibility to CFS also indicate a propensity
Stressful life events appear to play
a role in the onset of CFS,
but those who develop CFS following such an event may have been predisposed to illness by a period of
infection or pain or elevated fatigue for the preceeding four to 10 months, according to a study by Brigitta
Evengard of Sweden.
CFS patients demonstrate slowed information
processing in a number
of specific ways that indicated the inner workings of the brain are weak, according to Denise Fairhurst
of Canada compared patients with CFS and fibromyalgia
with those who have chronic pain and found similarities in psychological and behavioral characteristics.
He concluded that treatments that focused on patients' coping styles and behavioral and cognitive responses
to their difficulties would be most helpful.