The American Association for Chronic Fatigue Syndrome (AACFS), an organization of research
care professionals dedicated to chronic fatigue syndrome (CFS), held its fifth international research,
clinical, and patient conference in Seattle, Jan. 27-29, 2001. The conference attracted researchers and
clinicians from more than 10 countries and included more than 200 presentations and posters.
The conference covered many areas under investigation and clinical treatment tips. Following
from the research and clinical portions of the meeting.
Past research often lumped CFS patients into one
homogenous group. An encouraging trend noted by researchers at this AACFS
meeting was the number of studies presented that used subtyping to shed light on
the pathophysiology of the illness as well as provide targeted treatment
Leonard Jason, Ph.D., of DePaul University presented data that may assist in subgrouping
Factors considered relevant included a stressful life event at the onset of illness and a current or lifetime
diagnosis of psychiatric illness.
Leonardís study also confirmed that more severe symptoms were found in women, minorities,
Rosane Nisenbaum, Ph.D., of the U.S. Centers for Disease Control and Prevent-ion examined
history of a group of CFS patients one year after diagnosis.2 Treatments reported to reduce
their fatigue included traditional medical therapies (77%), vitamins (68%), and changes in diet (73%).
No association was found between illness improvement and type of onset.
A study conducted by Lea Steele, Ph.D., of the Kansas Commission on Veterans Affairs
found a higher
prevalence of CFS in veterans with Gulf War illness (GWI) than in the community at large, but also found
veterans more often experience headache, diarrhea, and night sweats than CFS patients.3 She
also discovered that the mean age of onset of CFS in GWI was a decade earlier than in civilians.
Several studies examined the role that dysfunction of
the autonomic nervous system (ANS) may play in CFS.
A researcher from the University Hospital in the Netherlands, Patricia Soetekouw, M.D.,
showing increased heart rate and blood levels of epinephrine in CFS patients in response to active standing
and head-up tilt, which would indicate increased activity in the sympathetic arm of the ANS.4
Arnold Peckerman, Ph.D., University of Medicine and Dentistry of New Jersey, discussed
how ANS dysfunction
in CFS may involve the baroreceptors that help control and maintain blood pressure and output of blood
from the heart during long periods of standing.5 His data suggests that CFS patients experience
a decline in baroreflex sensitivity during orthostatic challenges.
James Baraniuk, M.D., of Georgetown University described how acoustic rhinomanometry,
a technique that
is used to measure the volume of air inside the nose and reflects the degree of blood vessel constriction,
can be used to assess sympathetic activity in CFS patients.6 His study may also explain why
some people with CFS develop nasal irritation, watering, and blockage.
Christopher Snell, Ph.D., of the University of the Pacific described
a study that
indicates elevated levels of RNase L, an enzyme in the antiviral pathway, are associated with decreased
oxygen consumption during exercise, which could explain exercise intolerance in some CFS patients.7
Dharam Ablashi, M.D., of Advanced Biotechnologies in Columbia, Md., presented data to
support the hypothesis
that active, ongoing infection with human herpesvirus 6 (HHV-6) is involved in the pathogenesis of CFS.8
Using cell culture and polymerase chain reaction analysis, he found cell-free HHV-6
in the blood and
spinal fluid samples of CFS patients and concluded that the virus could be involved in the development
of neurological symptoms.
Seven of the patients showing active HHV-6 infection were treated with three different
- foscarnet, ganciclovir, and valciclovir - but most only showed slight improvement.
Kevin Maher, Ph.D., of the University of Miami focused on the possible
role of perforin,
a natural killer (NK) cell lytic protein, in CFS.9 If perforin is removed in mice, immune
abnormalities similar to CFS result.
Maher found that intracellular perforin was reduced in NK cells and in cytotoxic T cells
in CFS patients
and that intracellular content of perforin correlates with the cytolytic potential of the cell.
The research supports the claim that an NK-associated defect is present in CFS and suggests
basis for reduced cytotoxicity.
A study of autoimmunity in CFS was presented by Eng Tan, M.D., of the Scripps Research
Low titers of auto-nuclear antibodies have been found in CFS patients; this study showed the presence
of autoantibodies to a particular cellular protein, MAP2, which is expressed primarily in neuronal cells.
Autoantibodies directed at brain tissue could help explain some of the neurological and cognitive symptoms
found in CFS.
Niloo Afari, Ph.D., of the University of Washington studied twin pairs
where one twin
has CFS and found that the offspring of the twins with CFS were at substantial risk of developing chronic
fatigue.11 Children of healthy fraternal twins seem to be at
even greater risk than children of identical twins, which may suggest familial
clustering of fatiguing illness in extended families with a member who has
Leslie Aaron, Ph.D., of Harborview Medical Center, Seattle, did a co-twin study that
revealed a high
rate of co-morbidity with irritable bowel syndrome, fibromyalgia (FM), chronic pelvic pain, multiple chemical
sensitivity, and temporomandibular joint disorder in wins who had CFS.12
A study examining brain activity in CFS patients and healthy controls
by Roderick Mahurin, Ph.D., of the University of Washington.13 All subjects had a SPECT scan
of the brain while
performing mental arithmetic; the CFS group showed decreased brain activity in
certain areas and increased activation in other regions of the brain,
particularly the anterior cingulate gyrus. The study provides evidence of brain
inefficiency in CFS, particularly in the area of complex mental processing.
Greta Moorkens, M.D., Ph.D., of the University Hospital, Antwerp, Belgium, presented
data on hormonal
abnormalities in CFS that affect the brain and endocrine systems.14 Her research involved giving
CFS and FM patients neuroendocrine challenge tests using stimulation by growth hormone-releasing hormone
and Hexarelin, a growth hormone secretagogue. The tests showed clear differences between CFS and FM patients,
suggesting different pathological mechanisms for the illnesses.
Kottil Rammohan, M.D., of Ohio State University described a clinical
trial with modafinil
(Provigil) to manage fatigue in multiple sclerosis (MS) patients.15 The drug
improved energy and decreased daytime sleepiness in the MS group. Studies with
CFS patients are needed to determine if modafinil could alleviate fatigue in
A pilot study of another drug, etanercept, was presented by Kristin Lambrecht, PA-C,
of the University
of Minnesota. Etanercept, which blocks the action of tumor necrosis factor, may play a role in the immunological
dysfunction in some CFS patients. The drug significantly decreased the level of fatigue, muscle pain,
headaches, and painful lymph nodes in CFS patients, leading researchers to suggest further studies.
Katherine Rowe, M.D., of the Royal Childrenís Hosp-ital, Australia, presented a follow-up
CFS patients receiving intravenous immunoglobulin.16 Results indicate that patients experienced
significant improvement following treatment, with 75% able to work or study full time. However, it is
unclear whether this was due to the immunoglobulin or the natural history of the illness.
Nancy Klimas, M.D., of the University of Miami Medical School discussed results of an
for CFS that resulted in favorable immunological and clinical results in a small number of patients, indicating
further clinical trials are warranted.17
Researchers surgically removed CFS patientsí lymph nodes and cultured them with anti-CD3
to shift the cells from a predominant TH2 to a TH1 immune response. The cells were then infused back into
The clinician-to-clinician session at the conference provided physicians with the opportunity
together on how to best treat CFS and FM. Practitioners discussed treating pain, headaches, and orthostatic
intolerance, covering non-pharmacologic approaches and proven therapies. For details, see the information
in an accompanying article in this issue.
The following references refer to abstracts presented
at the conference. Program books with abstracts are $20 for AACFS members, $25
for nonmembers. Write to AACFS, c/o Harborview Medical Center, 325 9th Ave., Box
359780, Seattle, WA 98104. Make checks payable to the AACFS.
Jason L et al. Subtyping patients with chronic fatigue syndrome in a community-based
- Nisenbaum R et al. Course of illness among patients with chronic fatigue syndrome in Wichita, Kansas,
Steele L. Chronic fatigue and Gulf War illness: Is the case definition of CFS useful
health problems associated with service in the Persian Gulf War, #34.
- Soetekouw P et al. Orthostatic tolerance and sympathoadrenergic reactivity in chronic fatigue syndrome,
Peckerman A et al. Baroflex function in CFS: Accentuated decline in the reflex sensitivity
orthostatic but not behavioral challenges, #89.
Baraniuk J et al. Sympathetic dysfunction demonstrated by isometric handgrip responses
in CFS, #126.
- Snell C et al. Comparison of maximal oxygen consumption and RNase L enzyme in patients with chronic
fatigue syndrome, #26.
- Eastman H et al. Chronic fatigue syndrome (CFS): HHV-6 reactivation and clinical manifestation before,
during, and after antiherpesvirus therapy, #70.
- Maher K et al. Flow cytometric measurements of perforin and natural killer cell activity, #47.
- Tan E et al. A multi-center study of autoimmunity in CFS: Autoanti-bodies to neuronal microtubule-associated
protein and immunohistochemistry on neuronal cells, #37.
Afari N et al. Chronic fatigue in the offspring of twins with and without chronic
- Aaron L et al. Co-morbid clinical conditions in chronic fatigue: A co-twin control study, #40.
- Mahurin R et al. Brain correlates of cognitive efforts in chronic fatigue syndrome and healthy control
- Moorkens G et al. Hormonal responses to GHRH and hexarelin in the chronic fatigue syndrome and fibromyalgia,
- Rammohan K et al. Efficacy and safety of Provogil (modafinil) for the treatment of fatigue in patients
with multiple sclerosis, #54.
- Rowe K. Seven year follow-up of young people with chronic fatigue syndrome following the intravenous
gamma globulin trial, #63.
Klimas N et al. Experimental therapy results in clinical and immunologic improvement
in chronic fatigue
syndrome patients, #48.
Dr. Charles Shepherd is in private practice in the United Kingdom (U.K.) and is
a member of the
Chief Medical Officerís Working Group on CFS/ME at the U.K. Depart-ment of Health.