The American Association for Chronic Fatigue Syndrome (AACFS), an organization of research and health 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 are highlights from the research and clinical portions of the meeting.

Epidemiology/natural history
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 strategies.

Leonard Jason, Ph.D., of DePaul University presented data that may assist in subgrouping CFS patients.¹ Factors considered relevant included a stressful life event at the onset of illness and a current or lifetime diagnosis of psychiatric illness.

Leonard’s study also confirmed that more severe symptoms were found in women, minorities, and non-working individuals.

Rosane Nisenbaum, Ph.D., of the U.S. Centers for Disease Control and Prevent-ion examined the natural 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.

Physiology
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., presented data 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.

Microbiology
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 antiviral drugs - foscarnet, ganciclovir, and valciclovir - but most only showed slight improvement.

Immunology
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 a molecular basis for reduced cytotoxicity.

A study of autoimmunity in CFS was presented by Eng Tan, M.D., of the Scripps Research Institute.¹⁰ 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.

Genetics
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 CFS.

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

Neurology
A study examining brain activity in CFS patients and healthy controls was described 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.

Treatment
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 CFS.

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 Children’s Hosp-ital, Australia, presented a follow-up study of 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 immune therapy 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 patients’ lymph nodes and cultured them with anti-CD3 and interleukin-2 to shift the cells from a predominant TH2 to a TH1 immune response. The cells were then infused back into the patients.

The clinician-to-clinician session at the conference provided physicians with the opportunity to brainstorm 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.

References
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.

1. Jason L et al. Subtyping patients with chronic fatigue syndrome in a community-based sample, #11.
2. Nisenbaum R et al. Course of illness among patients with chronic fatigue syndrome in Wichita, Kansas, #49.
3. Steele L. Chronic fatigue and Gulf War illness: Is the case definition of CFS useful in describing health problems associated with service in the Persian Gulf War, #34.
4. Soetekouw P et al. Orthostatic tolerance and sympathoadrenergic reactivity in chronic fatigue syndrome, #85.
5. Peckerman A et al. Baroflex function in CFS: Accentuated decline in the reflex sensitivity during orthostatic but not behavioral challenges, #89.
6. Baraniuk J et al. Sympathetic dysfunction demonstrated by isometric handgrip responses in CFS, #126.
7. Snell C et al. Comparison of maximal oxygen consumption and RNase L enzyme in patients with chronic fatigue syndrome, #26.
8. Eastman H et al. Chronic fatigue syndrome (CFS): HHV-6 reactivation and clinical manifestation before, during, and after antiherpesvirus therapy, #70.
9. Maher K et al. Flow cytometric measurements of perforin and natural killer cell activity, #47.
10. 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.
11. Afari N et al. Chronic fatigue in the offspring of twins with and without chronic fatigue syndrome, #144.
12. Aaron L et al. Co-morbid clinical conditions in chronic fatigue: A co-twin control study, #40.
13. Mahurin R et al. Brain correlates of cognitive efforts in chronic fatigue syndrome and healthy control subjects, #88.
14. Moorkens G et al. Hormonal responses to GHRH and hexarelin in the chronic fatigue syndrome and fibromyalgia, #14.
15. Rammohan K et al. Efficacy and safety of Provogil (modafinil) for the treatment of fatigue in patients with multiple sclerosis, #54.
16. Rowe K. Seven year follow-up of young people with chronic fatigue syndrome following the intravenous gamma globulin trial, #63.
17. 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 Officer’s Working Group on CFS/ME at the U.K. Depart-ment of Health.