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Chronic Fatigue Syndrome News: AACFS Research Update

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By Lori Flaherty • www.ProHealth.com • November 21, 2001


A report on recent international CFIDS conference

Editor’s Note: The following article is reprinted with permission from The CFIDS Chronicle, Vol. 14 No. 2 Spring 2001.

Researchers, clinicians, and patients met this January in Seattle for three days of presentations, discussion, and networking at The American Association for Chronic Fatigue Syndrome’s (AACFS’s) fifth International Research, Clinical, and Patient Conference.

The conference, held Jan. 27-29, 2001, showcased the latest findings in research and treatment. This year, several areas of emerging science were added to the conference program, including sessions on genetics and the neurological aspects of chronic fatigue and immune dysfunction syndrome (CFIDS). A new international session provided insight on theories being developed outside of the United States.

Following are highlights of some of the hundreds of scientific and clinical presentations from the conference.

Research/Clinical Presentations

Genetics. This area of study in CFIDS was a major focus for the conference. Dr. Charles Shepherd, Director of the ME Association in Essex, England, echoed the sentiments of many attendees when he pronounced the genetic research presented at the meeting as “cutting-edge.”

A registry of twins with CFIDS created by Dr. Dedra Buchwald’s research teams at the University of Washington and Harborview Medical Center in Seattle served as the impetus for several genetic studies presented at the conference.

Dr. Niloo Afari studied the children of twin pairs where just one twin had CFIDS and found that children of ill twins had a higher risk of developing chronic fatigue or CFIDS. Dr. Leslie Aaron studied the prevalence of coexisting conditions such as irritable bowel syndrome, headache, and fibromyalgia (FM) in twins here one member of the pair had CFIDS and the other was healthy. She found coexisting illnesses were significantly higher in the twins with CFIDS.

Dr. Jack Goldberg of the University of Illinois presented a study that used the twin registry database to assess the role of genetic and environmental factors in CFIDS. The study included 146 twin pairs that were classified using three increasingly stringent definitions: chronic not explained by medical conditions; and chronic fatigue not explained by the medical or psychiatric exclusionary criteria of the consensus criteria. The researchers found that the concordance rate for each definition of fatigue is higher in identical twins than in fraternal twins, suggesting that genes do play a role in the development of CFIDS.

Another twin study by Dr. Richard Herrell of the University of Illinois at Chicago examined the relationship between lifetime psychiatric symptoms and current psychiatric co-morbidity in twin pairs. Herrell found that lifetime posttraumatic stress disorder, major depressive episode, and panic disorder were more common in the twins with CFIDS than in healthy twins.

Epidemiology. The U.S. Centers for Disease Control and Prevention (CDC) presented a study that surveyed a fourth of the Wichita, Kan. Population to determine the prevalence of CFIDS. The study is important because it identified patients who had never sought medical care for their illness and then followed them and a group of controls for three years. The CDC found that people who had not sought medical care for CFIDS appeared to have a better prognosis than those who had been receiving medical care, although I t is possible that patients with more severe CFIDS seek medical care more frequently.

Dr. Leonard Jason DePaul University presented a study on illness severity. Researchers examined subgroups of people with CFIDS criteria identified in a community-based prevalence study and found that women tend to have more severe symptoms than men; minorities tend to have more severe symptoms than whites; and nonworking people tend to have more severe illness than working people.

Dr. Pascale De Becker, a Belgian researcher, found that people who met the 1988 CFS definition were more severely ill than those who meet only the 1994 (not the 1988) criteria. Consequently, research findings may not be comparable between the two patient populations and most of the researchers agree that subtyping patients may well lead to more appropriate treatment strategies.

Autonomic nervous system. Three separate presentations at the conference by Drs. Patricia Soetekouw, University Hospital, the Netherlands; Julian Stewart, New York Medical College; and Arnold Peckerman, University of Medicine and Dentistry of New Jersey, showed that although there is no single profile of autonomic nervous system dysfunction in CFIDS, there is compelling evidence that patients’ sympathetic and parasympathetic nervous systems are abnormal.

Dr. James Baraniuk of Georgetown University explained how blood pressure increases and blood vessels constrict when the sympathetic nervous system is activated. He used acoustic rhinometry to measure air volume and blood vessel constriction in the nose to assess sympathetic activity in CFIDS patients. His study also may help explain why people with CFDIS develop nasal irritation, watering, and blockage.

Immunology. Dr. Kevin Maher of the University of Miami examined the role perforin, a protein found in the immune system, plays in CFIDS, because animals genetically engineered to produce low levels of perforin exhibit many the same immune defects as CFIDS patients. The study found that CFIDS patients had lower than normal concentrations of perforin in their natural killer (NK) cells and cytotoxic T cells, which may hinder those cells’ ability to protect the body against infection.

Dr. Eng Tan of the Scripps Research Institute presented a study that looked for the presence of autoantibodies to a cellular protein primarily found on neuronal cells (microtubule associated protein 2, or MAP 2). Blood serum from CFIDS patients showed that antibodies to MAP2 are frequently present. Tan believes this could possibly lead to a new marker for a subset of CFIDS patients, particularly those with neurocognitive problems.

RNase L. The microbiology research presented at the conference concentrated on possible cellular-level abnormalities in CFIDS patients, particularly those involving RNase L, an enzyme that helps the body fight viruses. Researchers hope that RNase L studies will provide an objective biological marker that can be used as a definitive test for the illness because the measurement of the enzyme is consistent with an activated immune system in CFIDS.

Dr. Patrick Englebienne of RED Laboratories in Belgium presented his findings on how RNase L may interact with ATP binding cassette (ABC) transporters, resulting in the visual problems, cognitive difficulties, pain, and other symptoms found in CFIDS patients. ABC transporters are one of the largest families of proteins found in all cells and some may provide resistance to certain diseases.

The role of RNase L in exercise intolerance was explored by Dr. Christopher Snell of the University of the Pacific, whose research indicates elevated levels of RNase L in CFIDS patients are associated with decreased oxygen consumption during exercise. His findings suggest that the RNase L immune system defect in CFIDS may be connected to poor oxidative metabolism and, consequently, low energy levels.

HHV-6. Dr. Dharam Ablashi of Advanced Biotechnologies in Columbia, Md. Theorized that active human herpesvirus 6 (HHV-6) may be invading CFIDS patients’ central nervous systems and triggering neurocognitive problems.
Albashi found active HHV-6 infection in 14 of 24 CFIDS patients, then treated seven of the 14 with three antiviral drugs—foscarnet (Foscavir), ganciclovir (Cytovene), and valacyclovir (Valtrex). The results were mixed; only some patients showed improvement. The patient treated with foscarnet clinically improved, and no HHV-6 infection was detected afterward. Of the four patients treated with ganciclovir, one showed slight clinical improvement, but HHV-6 infection could still be detected, while the other patient tested HHV-6 negative without experiencing any clinical improvement.

Neurology. Dr. Dave Lewis of the University of Washington presented a study of regional cerebral blood flow in pairs of identical twins where just one twin has CFIDS. Lewis used single photon emission computed tomography (SPECT) to construct images of the participants’ active brain regions. He found no evidence of a distinctive pattern of resting cerebral blood flow abnormalities in the CFIDS twins compared to the healthy twins.

Past studies have suggested that fibromyalgia (FM) patients abnormally process painful sensations. Dr. Richard Graceley of the National Institutes of Health showed in his study that the brains of FM patient respond to stimuli more vigorously than healthy people. When FM patients were given the same painful stimulus as the healthy controls, functional MRI scans showed more pain-evoked blood flow changes in their brains.

Dr. Roderick Mahurin from the University of Washington used SPECT scans to look at the activity of different parts of CFIDS patients’ brains during cognitive challenges. He found that when CFIDS patients were given a complex cognitive task to complete, their brains used more neural resources to solve the task than people without CFIDS. The study was not able to discern whether CFIDS patients were working harder at cognitive tasks or if more parts of the brain were required to solve the task.

Dr. Daniel Clauw of the Georgetown University Chronic pain and Fatigue Research Center explored whether Arnold-Chiari malformation and/or cervical spinal stenosis are more common in FM patients than in the general population. Chiari malformation and cervical stenosis involve a narrowing of the opening of the spinal cord. MRI studies showed no significant differences between the controls and the patients, but neurological exams showed significant differences. A substantial number of FM patients manifested abnormalities in sensory processing and reflexes during the neurological exam.

Other research. Dr. Renee Taylor of DePaul University reported on a study that examined whether individuals with CFIDS are more likely to have a history of childhood physical or sexual abuse. Her data shows that CFIDS patients do not appear to report abuse at higher rates than individuals with other fatiguing illnesses.

Dr. Lea Steele of the Kansas Commission on Veterans Affairs discovered a higher prevalence of CFIDS among Gulf War illness patients than in the community at large. Steele’s study also found that Gulf War veterans who met CFIDS criteria had different symptoms than patients with CFIDS alone, more often experiencing headache, diarrhea, and night sweats. Steele discovered that the mean age of onset for CFIDS was a decade earlier in Gulf War veterans than has been reported in civilian CFIDS patients.

Dr. Howard Urnovitz of the Chronic Illness circulating plasma RNA conducted by Dr. Paul Cheney of the Cheney clinic. The study examined the presence or absence of specific RNA bands in individuals with CFIDS, individuals with Gulf War illness, and healthy controls. Cheney found that 77% of CFIDS patients had a band sequence not found in any of the healthy controls. He theorized that identifying disease-specific gene segments may one day be possible and that pharmaceutical therapy to disrupt harmful gene transcription may be on the horizon.

Dr. Lana Tiersky of Fairleigh Dickinson University’s research found no correlation of medically unexplained symptoms and history of psychiatric illness in CFIDS patients. Her work refuted the commonly held perception that patients who have more symptoms that are not part of the international consensus case definition are more likely to have psychiatric illness or somatisation disorder. CFIDS patients studied showed no higher rates of chronic pelvic pain, chronic fatigue, back pain, tinnitus, or psychopathology if they had co-existing psychiatric illness.

Treatment Presentations

Dr. Kottil Rammohan of Ohio State University presented a study on the use of Madafinil, a well-tolerated narcolepsy drug, to treat fatigue in multiple sclerosis (MS) patients. The 72-patient study showed that modafinil (Provigil) significantly improved fatigue in MS and the patients experienced no serious or adverse effects. Research on modafinil in CFIDS could result in a useful treatment option.

Kristin Lambrecht, a physician assistant with the University of Minnesota, presented a study of six CFIDS patients using the drug etanercept (Enbrel), which blocks the action of tumor necrosis factor (TNF), a harmful cytokine produced by the immune system. Patients receiving the drug reported reduced fatigue and pain and improved exercise tolerance. Etanercept is used to treat rheumatoid arthritis, and investigations of its use in CFIDS may be merited, although the drug is expensive ($18,000 to $20,000 a year).

A seven-year follow-up study of CFIDS patients taking gamma globulin presented by Dr. Katherine Rowe of the Royal Children’s Hospital in Australia showed patients experienced significant improvement. However, this treatment for CFIDS is controversial because results of other studies have been mixed and gamma glogulin is costly and difficult to obtain.

Dr. Nancy Klimas of the University of Miami presented an immunotherapy that involved surgically removing the lymph nodes of 13 CFIDS patients, exposing the cells to a bath of chemicals designed to change the physiology of the immune response, than infusing the cells back into the patients. Significant improvement in the patients’ symptoms was reported following the procedure and determine the long-term impact of treatment.

Several poster presentations reported symptomatic improvement using Ampligen, an experimental drug in clinical trials in the United States and Europe. Dr. Christopher Snell of the University of the Pacific presented a study of two patients receiving Ampligen who reported improved cognitive function, vitality, and decreased pain. Dr. David Strayer, of Hemispherex Biopharma, Inc., the company that makes Ampligen, reported that patients receiving the drug reported considerable cognitive improvement. A study of 92 patients with severe CFS treated with Ampligen by Alicia Shillington of EPI-Q in Oakbrook Terrace, Ill. found that the drug significantly reduced the need for health resources, thereby reducing the cost of treatment. Double-blind trials of the intravenous drug continue at numerous sites throughout the United States.

Outgoing AACFS President Dr. Sudhir Gupta summed up the feelings of many patients when he said at the conference, “I am concerned with the pace and quality of research in CFIDS and FM. We have many challenges before us, including defining the pathogenesis of CFIDS, identifying a reliable and reproducible marker, establishing credibility among our scientific community, and educating practicing clinicians.”

Undoubtedly, research is progressing slowly on CFIDS and related illnesses, but the AACFS conference showed that there are many dedicated scientists and clinicians working to advance knowledge and improve the lives of patients.



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