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Fall
2003
Research Briefs
Exercise test could yield CFS
marker
Exercise challenge in people with chronic fatigue syndrome
(CFS) appears to lead to increased production of a specific immune system
protein — a finding that could lead to a diagnostic marker for the illness.
Researchers at the National Jewish Medical and Research Center
and the University of Colorado looked at post-exercise immune changes in 32 CFS
patients and 29 age-matched, normal control subjects. Both groups exercised for
20 minutes on stationary bicycles at 70 percent of their predicted maximum work
loads. Blood samples were taken prior to exercise, and additional samples were
collected at four intervals after the test was completed.
A significant increase in the split complement protein C4a was
detected in the CFS group at the six-hour post-exercise measuring point.
Com-plement proteins are a key component of the immune system response; they
perform tasks ranging from stimulation of phagocytosis to initiating
inflammation and B-cell activation.
In normal subjects, C4a generation is only stimulated at much
higher exercise levels, and levels return to normal within three hours of the
cessation of exercise.
The authors note that the exercise challenge allowed them to
study CFS patients in an exacerbated state of illness. It is worth mentioning
that the patients showed significant increases in symptoms following the
challenge; this is consistent with post-exertional relapse, a hallmark symptom
of CFS. Symptom diaries revealed significant increases in "reduced activity" and
"mental fatigue" after the exercise challenge; the control subjects reported no
adverse effects as a group.
The increases in C4a also correlated with the post-exercise
symptom reports. The authors state: "The detection of this single protein (C4a)
after exercise in conjunction with increased symptoms makes the development of a
diagnostic test with an exercise challenge a real possibility."
Sorensen B et al. "Complement activation in a model of
chronic fatigue syndrome." J Allergy Clin Immunol. Aug 2003;
112:397-403.
Muscle structures altered in patients with
CFS
Rapid muscle fatigue and ensuing muscle pain are hallmarks of
CFS. A new study from Italy has found more support for the hypothesis that
altered structures within muscles may play a role in the development of these
symptoms.
Researchers examined biopsied samples of striated muscle from
four CFS patients and four other subjects with fibromyalgia, looking
specifically at sarcoplasmic reticulum (SR) membranes. These structures release
calcium ions that induce muscle contraction, and also re-absorb the ions to
elicit muscle relaxation.
The authors report increased fluidity in the SR membranes
(confirming earlier results). This could result in changes in the flow of ions
across the membranes. In addition, there are also changes in the actions of
dihydropyridine receptors, which control the release of calcium ions. Other
changes noted affect the activity of enzymes that catalyze the release and
re-absorption of calcium ions.
Many of these changes mimic the behavior of muscles in aging
people. The authors speculate that oxidative tissue damage may occur at an
increased rate in CFS patients, a phenomenon that has been reported in other
research.
Fulle S et al. "Modi-fication of the functional capacity
of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue
syndrome." Neuromuscu-lar Disorders. 2003; 13:479-484.
Another study from New York Medical College and Washington
State University related to oxidative stress finds that protein carbonyl levels
— a measure of overall protein oxidation — were significantly higher in the sera
of patients with CFS when compared to control subjects. The total protein levels
in the patients, by contrast, were similar to controls. The authors state that
the findings are consistent with the theory that elevated nitric
oxide/peroxynitrite levels play a role in CFS pathology.
Smirnova IV et al. "Elevated levels of protein carbonyls
in sera of chronic fatigue syndrome patients." Mol Cell Biochem. Jun 2003;
248(1-2): 93-5.
Reaction times linked to motor deficits in
CFS
Along with muscle fatigue, patients with CFS often exhibit
slower simple reaction times (SRT) and simple movement times (SMT). New research
from Imperial College in London shows that this phenomenon may be related to
deficits in the motor preparatory areas of the brain, according to a study
published in The International Journal of Clinical Practice.
The study’s authors tested 10 CFS patients twice over a period
of two years, measuring both SRT and SMT. Transcranial magnetic stimulation was
applied to the palms of test subjects to measure the level of corticospinal
excitability at the times of the tests.
The results show that corticospinal excitability often varied
in subjects from one testing period to the other. This variability correlated
with changes in SRT and SMT; the more stimulus required to provoke corticospinal
excitability, the lower the overall reaction time scores. The authors say their
work "provides evidence that the changing motor deficits in CFS have a
neurophysical basis."
Davey NJ et al. "Deficit in motor performance correlates
with changed corticospinal excitability in patients with chronic fatigue
syndrome." Int J Clin Pract. 2003; 57(4): 262-264.
REM sleep differs in CFS
subjects
Patients with CFS appear to have a higher percentage of
rapid-eye movement (REM) sleep than their non-CFS mono-zygotic twins, according
to research from the Univer-sity of Washington.
Twenty-two sets of CFS-discordant twins were used in the
study. All subjects completed the Sleep Disorders Questionnaire prior to the
testing, and then were given continuous polysomnography tests, which measure
physiological activity during sleep. A post-polysomnography survey also was
completed by each of the participants.
The twin pairs did not differ significantly on most objective
measures of sleep, including total sleep time, sleep efficiency and percentage
of Stage 1, 2 or 3-4 (delta) sleep. However, the CFS twin showed statistically
significant increases in the percentage of REM sleep compared to the non-CFS
twin (27.7% of overall sleep vs. 24.4%).
On the post-test survey, the CFS twins generally reported
worse subjective results, including sleeping fewer hours (6.2 vs. 6.7) and
feeling less well rested. Because the subjective reports did not match the
objective findings, the authors suggest that the CFS patients "suffer from an
element of sleep-state misperception." The higher percentage of REM sleep in the
CFS twins may play an unknown role in this phenomenon, and in the illness in
general, according to the study.
Watson NF et al. "Comparison of subjective and objective
measures of insomnia in monozygotic twins discordant for chronic fatigue
syndrome." Sleep. 2003; 26(3): 324-8.
Exercise test could stratify CFS
patients
CFS research efforts are complicated by the heterogeneity
of the patient population. Attempts are being made to stratify patient groups
based on a number of factors, from immune system anomalies to severity and onset
of illness. A new study from the University of the Pacific points to exercise
testing results as a possible means to stratify patients in hopes of better
studying and treating them.
The study looks at 189 people with CFS, ranging in age from 19
to 60 years. All were recruited for another study on the efficacy of the
immunomodulatory drug Ampligen. The patients were tested on a treadmill, with
increasing difficulty settings over a 22-minute period, and asked to continue
until they felt they could no longer maintain their position on the device.
Results show that nearly half the subjects tested (n=92) were
classified under American Medical Association guidelines as having moderate to
severe functional impairment. Worth noting is that 10 percent of subjects showed
no impairment and 35 percent showed mild impairment. Multiple measurements
factor into the AMA classifications, including peak and predicted VO2.
Three other measurements reached statistical significance when
differentiating the four subgroups: peak heart rate, peak systolic blood
pressure and total respiratory quotient. Peak heart rate was lower in groups
that showed more impairment, as was peak systolic blood pressure. The authors
note that the blunted heart rate and blood pressure responses are similar to
those found in patients with chronic heart failure (an exclusionary criteria in
the current study).
Gender differences also were apparent. A higher percentage of
women than men fell into the moderate and severe categories. But the women in
these groups consistently achieved a peak VO2 level that was closer to the
maximal predicted levels. The authors say these gender differences warrant
further study.
Exercise testing may eventually help clinicians determine the
etiology and pathogenesis of individual cases of CFS, the authors note. Because
each category displayed unique cardiovascular profiles, cardiac autonomic
dysfunction could play a role in some CFS cases. But the authors say that other
factors, ranging from neuroendocrinological or metabolic function to postviral
immune system activation, could also be factors in the exercise test results.
Vanness JM et al. "Subclassifying Chronic Fatigue Syndrome
through Exercise Testing." Med Sci Sports Exerc. 2003; 35(6): 908-13.
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