Brussels conference presents wide range of research
By Vicki Walker

The Second World Congress on Chronic Fatigue Syndrome (CFS) and Related Disorders was held September 9-12 in Brussels, Belgium. The meeting was organized by Dr. Kenny DeMeirleir, who has done considerable research on chronic fatigue and immune dysfunction syndrome (CFIDS), most notably on the RNase-L antiviral pathway and the drug Ampligen. 

Fifty-five different presentations were made over the four days and the proceedings will be published in the peer-reviewed Journal of Chronic Fatigue Syndrome, distributed by Haworth Press. Following are summaries of just a few of the research presentations made at this meeting.

RNase-L research
Research on the RNase-L antiviral pathway continues to be fruitful, according to reports by Bernard Lebleu, PhD, Robert Suhadolnik, PhD, and Kenny DeMeirleir, MD, PhD, on studies partially funded by The CFIDS Association of America. Both research teams-Dr. Suhadolnik in Philadelphia and Dr. Lebleu in France-have found a new 37 kilodalton (kDa) form of RNase-L in CFIDS patients. RNase-L, which normally weighs 80 kDa, fights infection by degrading viral DNA. The low molecular weight form of RNase-L found in CFIDS patients may reflect dysfunction in the antiviral pathway or immune system.

Dr. Lebleu reported on a study that will be published in the December issue of American Journal of Medicine. The ratio of 37 kDa RNase-L to 80 kDa RNase-L was computed for 57 CFIDS patients, 11 fibromyalgia patients, 14 depressed patients and 28 healthy controls. He found that having a ratio above 0.5 distinguished CFIDS patients from the control groups. Nearly all the CFIDS patients-50 of 57-had the 37 kDa form of RNase-L and 41 of 57 had a ratio above 0.5. None of the depressed or fibromyalgia (without CFIDS) patients had ratios that high. Two of 28 healthy controls had a ratio above 0.5, but both of them had regular contact with CFIDS patients, lending credence to the theory that at least some cases of CFIDS may be caused or triggered by a pathogen that is transmittable.

Drs. Lebleu and Suhadolnik use different probes in their RNase-L assays, but the two methods are comparable, reported Dr. Suhadolnik. Both doctors tested the same 90 CFIDS patients from Dr. Daniel Peterson's clinic in Nevada and controls from a local college. Dr. Suhadolnik correctly identified 93% and Dr. Lebleu correctly identified 100% of the CFIDS patients using their independent RNase-L assays. The test can assist in the identification of CFIDS patients but it cannot yet be considered a diagnostic marker, Dr. Suhadolnik emphasized, because people with other illnesses may have a ratio above 0.5 as well.

Dr. DeMeirleir talked about the clinical significance of the 37 kDa RNase-L finding. He does not think that everyone who meets the Centers for Disease Control and Prevention (CDC) 1994 criteria for CFIDS will have this marker, but that there will be a subgroup who have it. According to DeMeirleir, those in this subgroup most commonly meet the 1988 CDC criteria for CFS, have bronchial hyper-reactivity and respond well to the experimental drug Ampligen.

Neil McGregor, MD, reported that elevated RNase-L, which was found in 75% of CFIDS patients and 14% of controls, correlated with elevated levels of interleukin-6 and with the symptoms of headache, fatigue, muscle pain and concentration problems, while elevated levels of interleukin-2 were more often found in patients with mood disorders. Interleukins are chemicals in the body that permit the cells of the immune system to communicate and coordinate the immune response, so these findings indicate that depression in CFIDS may have an immunological basis.

Subgrouping patients
Researchers from the University of Newcastle, Australia, were quite visible at this conference. They have made significant strides in their efforts to stratify CFIDS and chronic pain patients based on biochemical markers (see the RNase-L section on previous page). The group is working to sub-categorize patients based on biochemical findings so that individual management plans can be devised.

Myofascial pain seems to be a secondary or "opportunistic" condition that occurs in conjunction with CFIDS and may be caused by a toxin-producing, cell membrane-damaging staphylococcal infection, said Newcastle researcher H.L. Butt, PhD.

Treatment
Dr. DeMeirleir reported on the benefits of Ampligen, noting that 24 weeks of taking the drug produces positive results for several years. Two to four years after treatment, Dr. DeMeirleir's CFIDS patients who took Ampligen had better exercise capacity, memory and cognitive ability compared to those who did not.

David Strayer, MD, of Hemispherx Biopharma (which owns Ampligen), presented data on health care utilization related to Ampligen. The company's research found that Ampligen patients had fewer emergency room visits and hospitalizations compared to patients who were given a placebo. The Ampligen patients had 70% fewer emergency room or hospital admissions (seven vs. 23) and 83% fewer days in the hospital (19 vs. 114) compared to the placebo group.

Resetting the immune system may be an effective treatment for CFIDS, reported Nancy Klimas, MD. In a study that was partially funded by The CFIDS Association, lymph node cells were surgically removed from 11 patients, cultured for 12 days and surgically replaced. Nine patients responded positively to the treatment with improved cognitive function, quality of life and lowered immune activation. This treatment seems to be effective against many different viruses, said Dr. Klimas; determining the virus(es) involved in CFIDS is next on her agenda.

Memory and learning
The primary reason CFIDS patients have difficulty remembering things is because they have neurological impairments that hinder both learning and retrieving memories from storage, reported John Deluca, PhD, of Kessler Hospital in New Jersey.

In a recent study he conducted, 51 CFIDS patients required more time and study to commit facts to memory than healthy individuals. Once they had memorized those facts, their ability to recall them was also impaired. Deluca confirmed that the implications of this finding for students with CFIDS could be dramatic.

CFIDS in adolescents
Katherine Rowe, MD, presented her research proving CFIDS definitely exists in adolescents and is not a form of somatization disorder, a condition of recurring unexplained symptoms with no physical basis.

Using a statistical test, she found five symptom categories that, combined, seemed to be reflective of CFIDS in adolescents: muscle pain and fatigue, neurocognitive, abdominal, head and chest pain, neurophysiological, and immunological. She also found that the immunological dimension seemed to be the most significant factor, as it had both direct and indirect effects on the other four symptom factors.

Exercise capacity
CFS patients have an impairment in their exercise capacity that is not due to deconditioning, said Pascal DeBecker, PhD. The degree of impairment was moderate in women and mild in men. Dr. DeBecker hypothesized that reduced exercise capacity may be caused by autonomic dysfunction, which results in a lowered resistance to physical stress and/or metabolic disturbances.

Gulf war illness (GWI)
Benjamin Natelson, MD, who runs federally-funded CFS and GWI research centers, compared GWI patients with and without post-traumatic stress disorder (PTSD) and healthy controls. He was surprised to find that the GWI patients with PTSD had a subnormal cardiovascular response to laboratory stressors. Typically, PTSD patients have a normal response to lab stressors and over-respond to trauma-related stressors. Dr. Natelson hypothesized that exposure to toxins or other pathogens during the Gulf war may have altered these veterans' stress response.

Paul Levine, MD, reported on a cluster analysis of GWI patients that showed the combination of four neurologic symptoms-blurred vision, balance/dizziness, tremors/shaking and speech difficulty-were significantly more common in Gulf War veterans than in non-Gulf veterans. Among the Gulf veterans, 2.4% had all four symptoms and 7.8% had three symptoms, while in non-Gulf veterans only 0.46% had all four symptoms. People with all four symptoms also had higher rates of blackouts/seizures (22% vs. 0.4%) and pain/inflammation of nerves (32.1% vs. 1.7%). He said this "supports the possibility that environmental factors could be responsible" for the illness.

Garth Nicolson discussed mycoplasma infections in GWI patients. As reported in the September/October issue of The CFIDS Chronicle, Dr. Nicolson has found that 45% of GW veterans and 65% of CFIDS and fibromyalgia patients have mycoplasma infections, which can be treated with antibiotics although they are difficult to cure.

Patient meeting
The final day of the conference was devoted to CFIDS patient issues. I moderated a discussion on the proposed name change for chronic fatigue syndrome (CFS). Attendees from the newly formed European alliance of ME/CFS organizations strongly objected to the name chronic fatigue syndrome, but were even more opposed to renaming the illness defined by the U.S. CDC critera as myalgic encephalopathy/encephalomyelitis (ME), as ME defines only a subset of the CFS population.

Members of the alliance argued that CFS is a more heterogeneous population than ME, and one that allows people with psychological conditions to be diagnosed with CFS. The Europeans indicated that the only way they would accept U.S. adoption of the name ME would be if the ME definition were used along with it, in place of the CDC's criteria. 

During the final day Simon R. Molesworth, a member of the Queen's Council (composed of the top attorneys in Australia) and the parent of a young son with CFIDS, gave a rousing speech in favor of civil rights protections for CFIDS patients and their caregivers.

Molesworth, along with the Allison Hunter Memorial Foundation based in Australia, then proposed the formation of an International Council of CFS/ME Associations. The charter of this organization is:

1. To provide an international voice to represent the needs of people with CFS/ME and their caregivers in all parts of the world including, in particular, representation to international and national organizations.
2. To be a public advocate to achieve justice for people with CFS/ME and their caregivers (including providers of supportive professional services) in accordance with principles of human rights consistent with the United Nations Universal Declaration of Human Rights.
3. To achieve responsible support from national governments for the needs of people with CFS/ME and their caregivers.
4. To promote and support responsible medical research and treatment to overcome CFS/ME as a serious international health issue.
5. To be a public advocate for individuals with CFS/ME when their own human rights are in jeopardy by actively supporting them.
6. To promote public education as a means of achieving a better understanding of CFS/ME as an illness and the needs of all those associated with it.

CFIDS advocates at the Brussels conference were very supportive of the charter. The international council is still in the very early planning stages, but the Chronicle will report on its proposed activities and membership when more details become available.

Vicki Walker, Research and Public Policy Project Manager, is in her sixth year of service with The CFIDS Association of America. This is the eighth CFIDS conference she has covered for The CFIDS Chronicle since 1993, but the first time she has ever traveled overseas.