Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions

Abstract:

The subjective symptom of “fatigue” is one of the most widespread in the general population and is a major source of healthcare utilization. Prolonged fatigue is often associated with neuropsychological and musculoskeletal symptoms that form the basis of several syndromal diagnoses including chronic fatigue syndrome, fibromyalgia, and neurasthenia, and is clearly not simply the result of a lack of force generation from the muscle.

Current epidemiologic research in this area relies predominantly on self-report data to document the prevalence and associations of chronic fatigue. Of necessity, this subjective data source gives rise to uncertain diagnostic boundaries and consequent divergent epidemiologic, clinical, and pathophysiologic research findings.

This review will highlight the impact of the case definition and ascertainment methods on the varying prevalence estimates of chronic fatigue syndrome and patterns of reported psychological comorbidty. It will also evaluate the evidence for a true postinfective fatigue syndrome.

 

Source: Lloyd AR. Chronic fatigue and chronic fatigue syndrome: shifting boundaries and attributions. Am J Med. 1998 Sep 28;105(3A):7S-10S. http://www.ncbi.nlm.nih.gov/pubmed/9790475

 

Self-efficacy as a psychological moderator of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue and a variety of somatic symptoms. Few studies have examined psychological aspects of CFS. In the present study, self-efficacy is shown to be a significant predictor of CFS symptoms beyond the variance accounted for by demographic variables and distress. Further psychological CFS research is encouraged by (1) identifying dimensions that are salient in the experience and study of CFS, (2) providing preliminary psychometric data for measures of those dimensions, and (3) identifying psychological variables that serve as moderators of the experience of CFS.

 

Source: Findley JC, Kerns R, Weinberg LD, Rosenberg R. Self-efficacy as a psychological moderator of chronic fatigue syndrome. J Behav Med. 1998 Aug;21(4):351-62. http://www.ncbi.nlm.nih.gov/pubmed/9789165

 

A naturalistic study of the chronic fatigue syndrome among women in primary care

Abstract:

Chronic fatigue syndrome (CFS), a controversial illness without clear etiology, causes profound debilitation in its sufferers. This study explored subjects’ perceptions of the variables that mediated the course of their illness and identified coping strategies in 15 women with CFS referred from the practice of a primary care physician.

Exploratory semistructured interviews were adapted from Kleinman’s Illness Narratives. Four instruments were used: the Beck Depression Inventory, the Sickness Impact Profile, a modified Karnofsky scale, and the Defense Mechanism Rating Scale. Of the 15 women, 60% reported improvement and/or recovery at the time of the interview.

Improvement was associated with social support and lower levels of depressive symptoms. Health status was influenced by how subjects perceived their illness, their future, and the doctor’s prognosis; and by the physician’s early diagnosis, validation of the CFS, and intensive medical follow-up. Obsessional and healthy neurotic defense levels predominated, which differs from historical comparison groups with dysthymia and panic disorder.

Psychological adaptation to CFS is similar to adaptive coping in other chronic illnesses: subjective perceptions of health status can predict functional status. Physician validation is particularly important given the controversial status of CFS. Maintaining relationships with others–doctor, work, family, and group/spiritual activities reflected healthy coping strategies that promoted hope and attitudinal shifts.

The finding of a mixture of neurotic and healthy defenses and a low proportion of defenses associated with personality disorders has not been previously reported in the CFS literature and warrants further investigation.

 

Source: Saltzstein BJ, Wyshak G, Hubbuch JT, Perry JC. A naturalistic study of the chronic fatigue syndrome among women in primary care. Gen Hosp Psychiatry. 1998 Sep;20(5):307-16. http://www.ncbi.nlm.nih.gov/pubmed/9788031

 

Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome

Abstract:

A multiplex polymerase chain reaction (PCR) was initially developed to detect the presence of mycoplasma genus DNA sequences in cell cultures and to differentiate between three human pathogenic mycoplasma species simultaneously. The assay in turn, proved to be a useful tool for the detection of mycoplasma infection in human DNA samples.

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, Mycoplasma hominis andMycoplasma penetrans species were used in this assay. The sensitivity of detection was determined by infecting peripheral blood mononuclear cells (PBMC) of healthy individuals with known bacterial copy numbers from each species, extracting the DNA, and subjecting 1 microgram of DNA from each sample to 40 cycles of amplification. By using agarose gel electrophoresis the detection level was determined to be 7, 7, 9 and 15 mycoplasma cells per microgram 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) as determined by the Center for Disease Control (CDC) criteria, and compared to healthy individuals (n=100).

The percentage of M. genus infection was found to be 52% in CFS patients and only 15% in healthy individuals. Mycoplasma fermentans, M. hominis andM. penetrans were detected in 32, 9 and 6% of the CFS patients while they were detected in 8, 3 and 2% of the healthy control subjects, respectively.

This assay provides a rapid and cost efficient procedure to screen either cell cultures or clinical samples for the presence of three potentially pathogenic species of mycoplasma with a high level of sensitivity and specificity.

Copyright 1998 Academic Press.

 

Source: Choppa PC, Vojdani A, Tagle C, Andrin R, Magtoto L. Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome. Mol Cell Probes. 1998 Oct;12(5):301-8. http://www.ncbi.nlm.nih.gov/pubmed/9778455

 

Evaluating neuropsychological impairment in chronic fatigue syndrome

Abstract:

This study was designed to provide an estimate of the prevalence of neuropsychological impairment in chronic fatigue syndrome (CFS), to evaluate the concordance between impairment found on standardized tests and self-reported neuropsychological problems, and to study the relationship between neuropsychological functioning and fatigue severity and psychological processes.

We adopted an individual approach to determine neuropsychological impairment as contrasted with the group-comparisons approach used in previous studies. Also, correction for premorbid functioning and confounders was done on an individual basis.

The results show that a minority of participants were impaired in neuropsychological functioning. There was no relationship between neuropsychological impairment on standardized tests and self-reported memory and concentration problems. Neuropsychological functioning was not related to fatigue or depression. Slowed speed of information processing and motor speed were related to low levels of physical activity.

 

Source: Vercoulen JH, Bazelmans E, Swanink CM, Galama JM, Fennis JF, van der Meer JW, Bleijenberg G. Evaluating neuropsychological impairment in chronic fatigue syndrome. J Clin Exp Neuropsychol. 1998 Apr;20(2):144-56. http://www.ncbi.nlm.nih.gov/pubmed/9777468

 

Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management

Abstract:

There has been a resurgence of interest in recent years in both chronic fatigue syndrome and fibromyalgia. These perplexing and common clinical conditions are a source of significant patient morbidity and frame one of the more enduring dilemmas of contemporary Western medical thought, namely the ambiguous interface between mind and body. In this article, the current definitions are reviewed, and a framework for an emerging psychobiological model of these syndromes is presented. These issues are synthesized into a pragmatic approach to clinical management.

 

Source: Demitrack MA. Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management. Psychiatr Clin North Am. 1998 Sep;21(3):671-92, viii. http://www.ncbi.nlm.nih.gov/pubmed/9774804

 

Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression

Abstract:

OBJECTIVES: Patients with chronic fatigue syndrome complain of physical and mental fatigue that is worsened by exertion. It was predicted that the cognitive and motor responses to vigorous exercise in patients with chronic fatigue syndrome would differ from those in depressed and healthy controls.

METHODS: Ten patients with chronic fatigue syndrome, 10 with depressive illness, and 10 healthy controls completed cognitive and muscle strength testing before and after a treadmill exercise test. Measures of cardiovascular functioning and perceived effort, fatigue, and mood were taken during each stage of testing.

RESULTS: Depressed patients performed worst on cognitive tests at baseline. During the treadmill test, patients with chronic fatigue syndrome had higher ratings of perceived effort and fatigue than both control groups, whereas patients with depression reported lower mood. After exertion, patients with chronic fatigue syndrome showed a greater decrease than healthy controls on everyday tests of focused (p=0.02) and sustained (p=0.001) attention, as well as greater deterioration than depressed patients on the focused attention task (p=0.03). No between group differences were found in cardiovascular or symptom measures taken during the cognitive testing.

CONCLUSIONS: Patients with chronic fatigue syndrome show a specific sensitivity to the effects of exertion on effortful cognitive functioning. This occurs despite subjective and objective evidence of effort allocation in chronic fatigue syndrome, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both. Further insight into the pathophysiology of the core complaints in chronic fatigue syndrome is likely to be realised by studying the effects of exercise on other aspects of everyday functioning.

 

Source: Blackwood SK, MacHale SM, Power MJ, Goodwin GM, Lawrie SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):541-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/ (Full study)

 

Screening instruments for psychiatric morbidity in chronic fatigue syndrome

Abstract:

Physicians require a screening instrument to detect psychiatric disorders in patients with chronic fatigue syndrome (CFS). Different threshold scores on the Hospital Anxiety and Depression scale (HAD) and the mental health scale of the Medical Outcome Survey (MOS) were compared with two gold standards for the presence or absence of psychiatric disorder, standard diagnostic criteria (DSM-III-R) and a threshold score for the number of psychiatric symptoms at a standardized psychiatric interview (Revised Clinical Interview Schedule total cut-off score of 11/12). They were compared by use of validating coefficients and receiver operating characteristics in 136 consecutive CFS medical outpatients.

The HAD scale at cut-off of 9/10 was a valid and efficient screening instrument for anxiety and depression by comparison with both gold standards. The MOS mental health scale at its recommended cut-off score of 67/68 yielded too many false-positives to be recommended as a psychiatric screening instrument in CFS patients.

 

Source: Morriss RK, Wearden AJ. Screening instruments for psychiatric morbidity in chronic fatigue syndrome. J R Soc Med. 1998 Jul;91(7):365-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1296809/ (Full article)

 

Propagation and characterization of human herpesvirus-7 (HHV-7) isolates in a continuous T-lymphoblastoid cell line (SupT1)

Abstract:

After initial culture of HHV-7 in PHA-stimulated human cord blood mononuclear cells (HCBMC), six HHV-7 isolates were propagated successfully in an immature continuous T-lymphoblastoid cell line SupT1. All six isolates infected efficiently the SupT1 cells, and the infected cells became grossly enlarged and multinucleated 7-21 days post-infection. Various stages of HHV-7 morphogenesis were detected.

Cell-free supernatants from HHV-7-infected SupT1 cells were infectious to HCBMC as well as to SupT1 cells. The HHV-7-infected SupT1 and HCBMC cell lysates contained more infectious virus than the centrifuged cell culture fluid supernates from the same culture. The HHV-7 isolates H7-2, H7-3, JHC, and JB, concentrated 500 times, had average infectivity titers of 10(3.0) TCID50/ml while strains H7-4 and KHR titered approximately 1-2 logs higher. When all six HHV-7 isolates were propagated in SupT1 and culture fluid supernatants were examined 14-21 days post-infection by negative stain electron microscopy they contained an average of 1.9 x 10(9) virus particles/liter.

IFA and ELISA, using HHV-7/SupT1 cell lysate as an antigen, seem to correlate well in detecting high and low HHV-7 antibody in sera from chronic fatigue patients and healthy donors as controls. HHV-7 from SupT1 cell culture was free of HHV-6 and other human herpesviruses as tested by PCR, and the HHV-7 PCR signal was still strong when the viral preparation was diluted to 4.82 x 10(2) genome copies.

Since HCBMC are expensive to obtain and available in only small amounts, it is difficult to obtain large quantities of HHV-7 antigen. On the other hand, the SupT1 cell is an excellent source to produce consistently sufficient quantities of HHV-7 for purification studies, development of immunodiagnostics, in vivo infectivity studies, evaluation of antiviral drugs, and molecular biological studies.

 

Source: Ablashi DV, Handy M, Bernbaum J, Chatlynne LG, Lapps W, Kramarsky B, Berneman ZN, Komaroff AL, Whitman JE. Propagation and characterization of human herpesvirus-7 (HHV-7) isolates in a continuous T-lymphoblastoid cell line (SupT1). J Virol Methods. 1998 Aug;73(2):123-40. http://www.ncbi.nlm.nih.gov/pubmed/9766884

 

Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial

Abstract:

CONTEXT: Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia.

OBJECTIVE: To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS.

DESIGN: A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996.

SETTING: A single-center study in a tertiary care research institution.

PATIENTS: A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications.

INTERVENTION: Oral hydrocortisone, 13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon, or placebo, for approximately 12 weeks.

MAIN OUTCOME MEASURES: A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist.

RESULTS: The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P =.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001).

CONCLUSIONS: Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS.

 

Source: McKenzie R, O’Fallon A, Dale J, Demitrack M, Sharma G, Deloria M, Garcia-Borreguero D, Blackwelder W, Straus SE. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. JAMA. 1998 Sep 23-30;280(12):1061-6. http://www.ncbi.nlm.nih.gov/pubmed/9757853