Journal of Chronic Fatigue Syndrome: Volume 5, Issue 3-4, 1999

Volume 5, Issue 3-4, 1999

 * Introduction by Roberto Patarca-Montero
 * U.S. Case Definition of Chronic Fatigue Syndrome: Diagnostic and Theoretical Issues "'Summary - In 1994, researchers from the U.S. Centers for Disease Control and Prevention developed a revised case definition of chronic fatigue syndrome (CFS), a complex illness characterized by debilitating fatigue and a number of accompanying flu-like symptoms. Although Fukuda and associates intended to resolve complexities surrounding the classification of individuals with CFS stemming from previous definitional criteria, significant problems with the revised criteria endure. This article highlights reliability issues and other conceptual and operational difficulties inherent in the current U.S. definition of CFS. We employ case studies derived from a community-based epidemiological study of chronic fatigue syndrome to illustrate examples of the potential for misclassification of individuals with CFS using the current U.S. criteria. Moreover, we suggest alternative approaches to classification and ways to operationalize specific concepts embedded in the current U.S. criteria.'"
 * An Investigation of the Different Phases of the CFS illness"'Summary - The present study examined the factor structure of the Fennell Phase Inventory, an instrument designed to measure the phases of the illness known as chronic fatigue syndrome. Four hundred participants were recruited and randomly assigned to two equally sized groups. A similar three-factor solution emerged for both samples, suggesting that three phases characterize this illness: a Crisis phase, a Stabilization phase, and an Integration phase. Factor scores on the Crisis Factor were significantly related to levels of fatigue and disability. The Fennell Phase Inventory appears to be a promising way of differentiating the different phases that are experienced by patients with CFS. The implications of these findings are discussed.'"
 * Measuring Fatigue in Chronic Fatigue Syndrome: Why and How"'Summary - Fatigue is a common symptom occurring in a wide range of acute and chronic illnesses. It is multidimensional and subjective and because of this it has been difficult to define and quantify. Fatigue is one of several significant symptoms in diseases such as rheumatoid arthritis and multiple sclerosis, but for persons with chronic fatigue syndrome (CFS), it is often the most debilitating symptom. The need for valid and reliable assessments of fatigue is necessary for health care providers as we are increasingly required to document outcomes of care for professional and insurance purposes.'"
 * Clinical and Pathogenetical Characterization of 238 Patients of a Chronic Fatigue Syndrome Italian Center"'Summary - Prolonged fatigue is a common complaint in the community and is usually transitory. If fatigue continues for more than six months, is disabling, and is accompanied by other constitutional and neuropsychiatric symptoms, then a diagnosis of chronic fatigue syndrome (CFS) should be considered. CFS probably is an heterogeneous disease, maybe multifactorial, or it includes different pathologies which manifest with the same symptoms. In some cases, the mode of presentation of the illness implicate the exposure to chemical and/or food toxins as precipitating factors (e.g., ciguatera poisoning, Gulf War Syndrome, etc.). In other CFS cases, the etiology is still unknown: there are various hypotheses on pathogenetic events which, alone or in association with each other, may precipitate the illness. In fact, it is probable an involvement of multiple events in CFS onset where different precipitating factors can interact each other, even if not always all present in the single patient: latent and/or chronic viral infections, immunologic and neuroendocrine dysfunctions, psychological, environmental and mood factors. In accordance to this theory, we consider various subgroups of CFS patients on the basis of the pathway and the mode of presentation of the disease. The Clinic of Infectious Diseases of “G. D'Annunzio” University of Chieti is one of the main National Reference Centers for the CFS Study in Italy. From January 1992 to January 1998, 238 patients came to our observation: 89 of them met CDC criteria for CFS (1994), 127 did not; the other 22 patients are still under evaluation. Our patients underwent physical examination (including tests for searching for the possible coexistence of a fibromyalgia syndrome), psychiatric interview with several neuropsychological tests, laboratory tests (including magnesium determination on serum), neuroendocrine evaluation (circadian rhythm of several hormones, buspirone challenge test), SPECT scans to evaluate cerebral perfusion, and other examinations where necessary in according to the symptomatology of each patient (e.g., orthopedic, ORL, EMG, muscle biopsy, etc.). According to our preliminary results, we subdivided our patients in different subgroups and we studied them comparatively. We report the more significant data collected from this evaluation that might lead to a better understanding of the syndrome and in particular of its pathways course, a knowledge that will help in choosing appropriate therapies for each subgroups.'"
 * Prevalence and Overlap of Chronic Fatigue Syndrome and Fibromyalgia Syndrome Among 100 New Patients with Multiple Chemical Sensitivity Syndrome"'Summary - Background: Several studies have reported on extensive two-way overlaps found among chronic fatigue syndrome (CFS), fibromyalgia syndrome (FMS) and multiple chemical sensitivity syndrome (MCS) but none have yet reported on the overlap of all three. This study assesses the prevalence of pure MCS, MCS-CFS, MCS-FMS and the overlap of all three among 100 consecutive new patients evaluated for MCS in a private practice specializing in occupational and environmental medicine. Methods: Sixty-eight females and 32 males diagnosed with MCS-based on a medical history of multiple chronic symptoms in multiple organs triggered by multiple chemical exposures at or below previously tolerated levels-were also evaluated for CFS and FMS using the diagnostic criteria of the US Centers for Disease Control and the American College of Rheumatology, respectively. Results: Eighty-eight percent of the 100 MCS patients met criteria for CFS, 49% met criteria for FMS, and 47% met both. Slightly more male than female MCS patients had CFS: 91% vs. 87%; while FMS was more than twice as common among female MCS patients: 59% vs. 28%. The majority of women, 56%, met criteria for all three disorders, and an additional 31% had both MCS and CFS. This pattern was reversed in men, only 28% of whom had all three, compared to 63% with MCS and CFS but no FMS. MCS alone was diagnosed in only 10% of the women and 9% of the men. Even rarer was the overlap of MCS and FMS without any CFS, found in just 2 women. Conclusions: At least in this clinic population, MCS seldom occurs alone. The enormous range of diagnostic overlaps reported here and in previous studies of various overlaps among CFS, FMS and MCS highlights the need to screen for all three disorders in studies of any one and to report results in these terms. We recommend this be made standard practice in both clinical settings and research protocols.'"
 * Epidemilogy: Abstracts
 * Five-Year Follow-Up of Young People with Chronic Fatigue Syndrome Following the Double Blind Randomised Controlled Intravenous Gammaglobulin Trial "Summary - Three and 5 year follow-up studies of eighty-nine young people with Chronic Fatigue Syndrome who completed a double blind randomised controlled trial of intravenous gammaglobulin has been conducted to determine whether the improvement following the intravenous gammaglobulin was sustained. Initial telephone contact and a questionnaire that assessed functional outcomes including, physical activity, social activities, work/school attendance and work/school workload was used. Strategies and treatment that were found helpful and ways to improve management were also asked. Follow-up data were obtained on 86 of 89 after the study concluded. The 3-year follow-up yielded a 75% response to the questionnaire. A 78% follow up response rate at 5 years was achieved for those enrolled in the study with 84% (n = 74) of those who completed the study being traced. The mean follow-up time from commencement of illness was 56 months (s.d. 25 months), range 15-112 months. There was no persistent deterioration in function related to CFS in any young person. Four had reported recurrence of symptoms lasting 3-8 months and again improved. Others remained ‘improved’ or continued to improve. Seventeen per cent of those who responded were still moderately unwell with another 23% ‘not back to normal yet.’ Sixty per cent of participants considered they were ‘well’ at the last follow-up with 45% scoring 10/10. Seventeen (20%) had another condition during or after their illness. Anergy or hypoergy did not predict functional outcome at five years after the trial, although an earlier improvement was noted in those who were anergic and who received gammaglobulin. There was no deterioration in overall function over the 5 years following participation in the gammaglobulin trial, and young people continued to improve although a significant number were still disabled. The significance of the abnormal delayed type hypersensitivity reaction for the response to gammaglobulin is uncertain and warrants further investigation."
 * Clinical: Abstracts
 * A Case Series Survey of Silicone Breast Implant Patients"'Summary - Objective: To survey the symptoms of a large group of breast implant patients displaying illness and to determine if any clinical or serological features predominate. Design: A case series survey. Setting: A private internal medicine practice. Patients: A referred sample of 415 patients with fatigue of long duration, followed by muscle/joint pain, cognition problems, polyneuropathy, and localized breast pain. Conclusion: Silicone adjuvant breast disease may be a novel disorder, possibly autoimmune, producing atypical syndromes that do not fit within the classic diagnostic criteria of known conditions. Furthermore, the diversity and distinction of silicone adjuvant breast disease may require the medical community to accept it as a new entity, encompassing a neurological and connective tissue disorder.'"
 * Immunology: Abstracts
 * Premovement and Cognitive Brain Potentials in Chronic Fatigue Syndrome"'Summary - Brain potentials from normals and patients with Chronic Fatigue Syndrome (CFS) were recorded in four different experimental tasks: (1) Auditory target detection, (2) Short-term memory scanning, (3) Fore-warned reaction time (contingent negative variation), and (4) Self-paced movement. In the auditory target detection task, a slow negative potential shift (maximum at Cz), appears prior to stimulus onset in normals, but is markedly reduced in amplitude in patients with CFS. However, all other sensory and cognitive brain potentials do not differ between normals and CFS. Reaction times are slower in CFS compared to normals. In the memory task, a slow negative shift associated with memory scanning is reduced in patients with CFS. For the fore-warned reaction time and self-paced movement tasks, no differences were found between the patients and normals. The finding of premovement related potential abnormalities in CFS supports the concept that central motor preparation and execution are impaired in CFS. In certain tasks, measures of neural processes related to sensory processing and attention are normal for these patients. Results from the memory task suggest that neural processes related to short-term memory are also altered in CFS.'"
 * A Subgroup Analysis of Cognitive-Behavioral Treatment Studies"'Summary - Several studies of graded activity-oriented cognitive behavioral treatment for chronic fatigue syndrome (CFS), all conducted in England, have reported dramatic improvements in functioning and substantial reductions in symptomatology. On the other hand, cognitive behavioral intervention studies conducted in Australia and the United States have not found significant improvements in functioning or CFS symptoms. Based on a review and synthesis of data from these clinical trials, naturalistic outcome investigations, and illness comparison studies, this articles argues that two CFS subgroups, distinguished by functional status and symptom severity, may account, in part, for the differences in outcome in cognitive behavioral treatment studies. It is also argued that differences in treatment duration may have influenced clinical outcomes. This article concludes with recommendations for specific cognitive behavioral interventions in CFS.'"
 * An Overview of Psychometric Assessment"'Summary - The assessment of a number of behavioral and psychoso-cial domains may be important in baseline and outcome evaluations of CFS patients. These domains include mood disturbance, functional status, sleep disturbance, global well-being (i.e., psychiatric status), pain, behavioral coping, social support, locus of control, illness behavior and illness attribution. This article describes a variety of pen-and-paper measures designed to assess these behavioral dimensions and summarizes their psychometric properties and applicability to CFS populations.'"
 * Interdisciplinary: Abstracts
 * Multiplex PCR for the Detection of Mycoplasma fermentans, M. hominis, and M. penetrans in Patients with Chronic Fatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis, and Gulf War Syndrome"'Summary - A multiplex polymerase chain reaction (PCR) was used to detect mycoplasma infection in human DNA samples of patients with CFS and related illnesses. One set of oligonucleotide primers which are specific for a highly conserved region among all members of the genus Mycoplasma along with three other primer sets which are specific for Mycoplasma fermentans, M. hominis, and M. penetrans species were used in this assay. The sensitivity of detection was determined by adding known mycoplasma DNA copy numbers to 1 μg of genomic DNA from healthy subjects. Each sample was subjected to 40 cycles of amplification. The detection level was determined to be 7, 7, 9, and 15 mycoplasma DNA copies per μg of human genomic DNA for M. genus, M. fermentans, M. hominis, and M. penetrans, respectively. The assay was applied to DNA extracted from the PBMCs of individuals suffering from chronic fatigue syndrome (CFS) (n = 100), fibromyalgia (FMS) (n = 40), rheumatoid arthritis (RA) (n = 60), and gulf war syndrome (GWS) (n = 60) and compared to age- and sex-matched healthy individuals (n = 160). The percentage of M. genus infection detected in CFS, FMS, RA, and GWS was 52,54, 49, and 55%, respectively. M. fermentans was detected in 32, 35, 23, and 36%, M. hominis was detected in 9, 8,11, and 5%, and M. penetrans was detected in 6, 4, 7, and 3% of CFS, FMS, RA, and GWS patients, respectively. M. genus, M. fermentans, M. hominis, and M. penetrans were detected in 15, 8, 3, and 2% of healthy matched controls. This assay provides a rapid and cost efficient procedure to screen clinical samples for the presence of three potentially pathogenic species of Mycoplasma with a high level of sensitivity and specificity.'"
 * Borna Disease Virus Proteins in Patients with CFS"'Summary - Bornavirus is a member of a newly recognized virus family, Bornaviridae, and is neurotropic for a wide range of animal species, including birds, rodents, horses, and humans. Although little is known about its mode of transmission and it has not been clearly linked to any human disease, an association between borna viruses and neuro-psychiatric disorders has been suggested. Several researchers have also isolated this organism from patients who meet the clinical criteria for the Chronic Fatigue Syndrome (CFS). However, due to non-standardization of assay protocols, lack of a large study population and the possibility of contamination in certain laboratory settings, the true prevalence of Bornaviral proteins and their possible role in the pathogenesis of at least a subgroup of CFS patients remains undefined. We analyzed the serum immune reactivity to Borna Disease Virus (BDV) in 77 CFS patients and in 33 healthy normal controls using an ELISA based assay of 3 different recombinant BDV proteins. Of the 6 samples that displayed immunoreactivity to 2 or more BDV proteins, 5 were from patients (83.3%). Two samples, both from CFS patients, displayed immunoreactivity to 3 BDV proteins.'"
 * The Relationship Between Chronic Fatigue Syndrome and Chemical Exposure"'Summary - Overlapping symptomatologies between chronic fatigue syndrome (CFS) and chemical sensitivity have been observed by different investigators. Interferon-induced proteins 2-5A synthetase and protein kinase RNA (PKR) have been implicated in the viral induction of CFS. The objective of this study was to measure 2-5A and PKR activity in patients with CFS and toxic chemical exposure. Based on the CDC definition and criteria, twenty CFS patients who were positive for viral genome(s) (mainly HHV6; HTLV II, EBV, and CMV) and did not have any history of exposure to toxic chemicals were included in this study. As a comparison, the second group of patients consisted of twenty individuals from the same geographical area who were negative for viral genomes but had been exposed to methyl tertiary-butyl ether concentration of up to 70 ppb and benzene concentration up to 14 ppb. All patients complained of fatigue and other symptoms overlapping between the two groups. From all 40 patients, blood was drawn, leukocyte extract was prepared and assayed for 2-5A synthetase and PKR activity. Clinical specimens which were positive for viral genomes showed from 2.2-38.7 fold increase in 2-5A activity and 1.3-13.5 fold increase in PKR activities over the background of the healthy controls. Similarly, the second group (negative for viral genomes, but exposed to chemicals) showed a 1.1-29.2 fold increase for 2-5A synthetase and a 1.3-11.6 fold increase for PKR when they were compared to healthy subjects. To elucidate mechanisms involved in viral versus chemical induction of 2-5A synthetase and PKR, MDBK cell lines were cultured either in the presence or absence of HHV6, MTBE, or benzene. 2-5A and PKR activities were measured in all the above conditions. A clear induction of 2-5A and PKR was observed when MDBK cells were exposed to HHV6, MTBE, and benzene indicating that induction of interferon-in-duced proteins are not unique to viruses. We conclude that 2-5A and PKR are not only biomarkers for viral induction of CFS, but biomark-ers to other stressors that include MTBE and benzene.'"
 * Biochemical Dysregulation of the 2-5A Synthetase/RNase L Antiviral Defense Pathway in Chronic Fatigue Syndrome"'Summary - The aim of the current study was to examine the biochemical defects in key components of the 2′,5′-oligoadenylate (2-5A) synthe-tase/RNase L antiviral pathway in an extended cohort of patients with chronic fatigue syndrome (CFS) from two sites. CFS patients, who met the CDC criteria for CFS, and matched controls were assessed with respect to their general health, depression, and pain. Biochemical assays were completed for three blood draws over a period of one year. Analysis of the mean values for bioactive 2-5A, RNase L activity, low molecular weight (LMW) RNase L in CFS PBMC extracts confirmed the statistically significant upregulation of the 2-5A synthetase/RNase L pathway compared to control PBMC extracts (p = .001, .002, and .007, respectively). Clinical correlates to the biochemical findings included a negative correlation between Karnofsky Performance Score and bioactive 2-5A (p = .025) or RNase L activity (p = .002) and positive correlation between Metabolic Screening Questionnaire and RNase L activity (p = .01) and between interferon- and LMW RNase L (p = .05). The evidence presented in this study more firmly establishes the dysregulation of the 2-5A synthetase/RNase L pathway in CFS.'"
 * Microbiology: Abstracts
 * Physiology: Abstracts