Electron microscopic immunocytological profiles in chronic fatigue syndrome

Abstract:

Structures consistent in size, shape and character with various stages of a Lentivirus replicative cycle were observed by electron microscopy in 12-day peripheral-blood lymphocyte cultures from 10 of 17 Chronic Fatigue Syndrome patients and not in controls. Attempts to identify a lymphoid phenotype containing these structures by immunogold labelling failed and the results of reverse-transcriptase assay of culture supernatants were equivocal. The study was blind and case-controlled, patients being paired with age, sex and ethnically matched healthy volunteers. Prescreening of subjects included the common metabolic and immunological disorders, functional conditions and a virus-screen against hepatitis B and C, Epstein-Barr Virus, Cytomegalovirus and Human Immunodeficiency Virus.

 

Source: Holmes MJ, Diack DS, Easingwood RA, Cross JP, Carlisle B. Electron microscopic immunocytological profiles in chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):115-22. http://www.ncbi.nlm.nih.gov/pubmed/9201653

 

Fatiguing illness among employees in three large state office buildings, California, 1993: was there an outbreak?

Abstract:

The objective was to determine if a cluster of chronic fatigue syndrome (CFS)-like illness had occurred among employees in two large state office buildings in northern California, and to identify risk factors for and features of fatiguing illness in this population.

DESIGN: case-control study.

POPULATION AND SETTING: Over 3300 current employees in two state office buildings and employees in a comparable “control” building. Information was collected on demographic and occupational variables, the occurrence of fatiguing illness for at least one month in the previous year, and the presence of 36 symptoms. A total of 3312 (82%) of 4035 employees returned questionnaires. Overall, 618 (18.7%) persons reported fatigue lasting at least one month; including 382 (11.5%) with fatigue of at least six months’ duration and 75 (2.3%) with symptoms compatible with a CFS-like illness.

Independent risk factors for fatigue lasting one month or longer were found to be Native American ethnicity (OR 2.4, CI 1.1,5.3), Hispanic ethnicity (OR 1.7, CI 1.3,2.3), female sex (OR 1.5, CI 1.2,1.9), gross household incomes of less than $50,000 (OR 1.3, CI 1.1,1.6), and less than a college education (OR 1.3, CI 1.1,1.6). Similar risks were observed for persons who reported fatigue lasting six months or longer. Female sex (OR 3.2, CI 1.7, 6.4) was the only independent risk factor found for those persons classified as having a CFS-like illness. Case prevalence rates for all three categories of fatigue, as determined by multivariate analysis, were not significantly different among buildings.

Despite finding a substantial number of employees with fatiguing illness in the two state office buildings, the prevalence was not significantly different than that for a comparable control building. Previously unidentified risk factors for fatigue of at least one month and at least six months identified in this population included Hispanic ethnicity, not having completed college, and income below $50,000.

 

Source: Shefer A, Dobbins JG, Fukuda K, Steele L, Koo D, Nisenbaum R, Rutherford GW. Fatiguing illness among employees in three large state office buildings, California, 1993: was there an outbreak? J Psychiatr Res. 1997 Jan-Feb;31(1):31-43. http://www.ncbi.nlm.nih.gov/pubmed/9201645

 

Sleep anomalies in the chronic fatigue syndrome. A comorbidity study

Abstract:

Polysomnographic findings were compared between a group of patients with the chronic fatigue syndrome (CFS; n = 49) and a matched healthy control (HC) group (n = 20).

Sleep initiation and sleep maintenance disturbances were observed in the CFS group. The percentage of stage 4 was significantly lower in the CFS group. A discriminant analysis allowed a high level of correct classification of CFS subjects and HC. Sleep-onset latency and the number of stage shifts/hour contributed significantly to the discriminant function.

The presence of these anomalies as well as the decrease in stage 4 sleep were not limited to the patients also diagnosed with fibromyalgia or with a psychiatric disorder. No association was found between sleep disorders and the degree of functional status impairment. The mean REM latency and the percentage of subjects with a shortened REM latency were similar in CFS and HC.

 

Source: Fischler B, Le Bon O, Hoffmann G, Cluydts R, Kaufman L, De Meirleir K. Sleep anomalies in the chronic fatigue syndrome. A comorbidity study. Neuropsychobiology. 1997;35(3):115-22. http://www.ncbi.nlm.nih.gov/pubmed/9170115

 

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome

Abstract:

PURPOSE: To assess possible triggers and cofactors for chronic fatigue syndrome (CFS) and to compare levels of selected cytokines between cases and an appropriately matched control group.

PATIENTS AND METHODS: We conducted a case-control study of 47 cases of CFS obtained through a regional CFS research program maintained at a tertiary care medical center. One age-, gender-, and neighborhood-matched control was identified for each case through systematic community telephone sampling. Standardized questionnaires were administered to cases and controls. Sera were assayed for transforming growth factor-beta (TGF-beta), interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and antibody to Borrelia burgdorferi and Babesia microti.

RESULTS: Cases were more likely to have exercised regularly before illness onset than controls (67% versus 40%; matched odds ratio (MOR) = 3.4; 95% CI = 1.2 to 11.8; P = 0.02). Female cases were more likely to be nulliparous prior to onset of CFS than controls (51% versus 31%; MOR = 8.0; 95% CI = 1.03 to 170; P = 0.05). History of other major factors, including silicone-gel breast implants (one female case and one female control), pre-morbid history of depression (15% of cases, 11% of controls) and history of allergies (66% of cases, 51% of controls) were similar for cases and controls. However, cases were more likely to have a diagnosis of depression subsequent to their diagnosis of CFS compared to a similar time frame for controls (MOR = undefined; 95% CI lower bound = 2.5; P < 0.001). Positive antibody titers to B burgdorferi (one case and one control) and B microti (zero cases and two controls) were also similar.

CONCLUSIONS: Further investigation into the role of prior routine exercise as a cofactor for CFS is warranted. This study supports the concurrence of CFS and depression, although pre-morbid history of depression was similar for both groups.

Comment in: Etiology of chronic fatigue syndrome. [Am J Med. 1997]

 

Source: MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK. A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med. 1996 May;100(5):548-54. http://www.ncbi.nlm.nih.gov/pubmed/8644768

 

Seroepidemiology of chronic fatigue syndrome: a case-control study

Abstract:

We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.

 

Source: Mawle AC, Nisenbaum R, Dobbins JG, Gary HE Jr, Stewart JA, Reyes M, Steele L, Schmid DS, Reeves WC. Seroepidemiology of chronic fatigue syndrome: a case-control study. Clin Infect Dis. 1995 Dec;21(6):1386-9. http://www.ncbi.nlm.nih.gov/pubmed/8749620

 

Case control study of chronic fatigue in pediatric patients

Abstract:

OBJECTIVE: To determine the demographic characteristics, medical features, psychological profile, and natural history of children with chronic fatigue.

DESIGN: Case control study.

SETTING: Pediatric Infectious Diseases Clinic of Kosair Children’s Hospital, 1990 to 1992.

PARTICIPANTS: Forty-four patients referred for persistent fatigue were evaluated. Twenty patients participated in a psychological study; 20 healthy controls of similar age and gender were recruited from community pediatric practices and 20 matched depressed controls were recruited from university psychiatry services (subjects were treated as groups in the analyses).

MEASURES: Demographic data were obtained for all referred patients. Those with fatigue for at least 2 months and no alternative diagnosis received a detailed history, physical, and battery of laboratory tests (complete blood count, sedimentation rate, chemistry panel, chest X-ray thyroid stimulating hormone, thyroxine, anti-nuclear antibodies, urinalysis, immunoglobulins, and Epstein-Barr virus (EBV), toxoplasma, and cytomegalovirus serologies). Psychological study participants completed the following: background structured interview; Kaufman Brief Intelligence Test; Children’s Depression Inventory; Child Behavior Checklist; Youth Self Report; Diagnostic Interview for Children and Adolescents-Revised; mail-in follow-up survey.

RESULTS: The median age of fatigue patients was 14.3 years; 60% were female, 96% white, and 87% from the mid/upper socioeconomic status (SES). Fatigue patients were demographically similar to 21 patients referred for infectious mononucleosis (IM) but were older than other clinic patients (P < .0001). White race (P = .0568) and mid/upper SES (P = .0403) were over-represented among fatigue patients compared to patients referred for other diagnoses. Of 36 patients meeting criteria for further study, 5 had an IM-like illness including evidence of recent EBV infection. For the remaining 31 patients, clinical and laboratory evaluations were unrevealing. Psychological study subjects reported marked declines in quality-of-life and scored high on measures of internalizing, withdrawal, and social isolation. Nine met diagnostic criteria for depression, although depressive symptoms were not as prominent as those reported by depressed controls. Fatigue subjects scored higher on somatization than both control groups. The follow-up survey indicated symptomatic improvement in most patients.

CONCLUSIONS: Chronic fatigue was a common reason for referral, with over-representation of white children from mid/upper SES. After exclusion of EBV-associated IM, screening laboratory tests were not helpful in establishing specific organic diagnoses. Whereas the natural history was favorable, chronic fatigue resulted in major quality-of-life changes and was associated with significant levels of psychosocial distress.

IMPLICATIONS: Psychological evaluation is warranted in these patients, as some may have treatable psychological conditions. Given the absence of proved medical therapies, psychosocial interventions to improve quality-of-life should be studied.

 

Source: Carter BD, Edwards JF, Kronenberger WG, Michalczyk L, Marshall GS. Case control study of chronic fatigue in pediatric patients. Pediatrics. 1995 Feb;95(2):179-86. http://www.ncbi.nlm.nih.gov/pubmed/7838632

 

A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome

Abstract:

Two neuroradiologists compared the brain MR scans of 52 patients with the CDC criteria for the chronic fatigue syndrome (CFS) with those of 52 age and sex matched controls who had undergone imaging because of histories of head trauma or headache.

CFS patients had significantly more abnormal scans than controls–27% vs 2%. Abnormalities seen were foci of increased white matter T2 signal in 9 CFS patients and one control and ventricular or sulcal enlargement in 5 CFS patients. Follow up of patients with subcortical signal hyperintensities revealed 3 who had symptoms suggestive of other known medical causes of what appeared to be CFS.

The data indicate that some CFS patients have some organic problem manifesting itself on neuroimaging. But, finding MR abnormalities should warn the physician that the patient’s symptoms may be secondary to some other medical illness and not simply primary CFS.

 

Source: Natelson BH, Cohen JM, Brassloff I, Lee HJ. A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci. 1993 Dec 15;120(2):213-7. http://www.ncbi.nlm.nih.gov/pubmed/8138812

 

Information processing efficiency in chronic fatigue syndrome and multiple sclerosis

Abstract:

OBJECTIVE: To compare the cognitive performance of subjects with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and healthy controls. All subjects were matched for age, education, and verbal intelligence, as previous neuropsychological studies of CFS had not used appropriate control groups.

DESIGN: Case-control design. All subjects were given a neuropsychological battery and the test scores were compared among the groups.

SETTING: Subjects with CFS and subjects with MS were recruited from private and institutional practice and from the community. Healthy subjects were recruited from the community.

PATIENTS/OTHER PARTICIPANTS: Twelve subjects (all female) with CFS participated in the study. Chronic fatigue syndrome was diagnosed in these patients in accordance with the requirements outlined by the Centers for Disease Control as modified subsequently to not exclude patients with concurrent depression and/or anxiety. All subjects with CFS were referred for a neuropsychological examination to assess persistent cognitive complaints. Eleven subjects (10 female, one male) with the diagnosis of clinically stable MS were chosen from clinics and the community because of complaints of mild to moderate cognitive impairment. The subjects with MS and 11 healthy volunteers (10 female, one male) were matched to the group with CFS by age, education, and estimated verbal intelligence (based on the Vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised). The subjects with MS had a mean Kurtzke Expanded Disability Status Scale score of 4.95 (SD, 1.95; range, 2.0 to 7.5). As a result of the matching procedure, there were no differences among the three groups in age (F[2,31] = 0.32), education (F[2,31] = 0.80), and verbal intelligence (F[2,31] = 0.31).

INTERVENTIONS: None.

MAIN OUTCOME MEASURES: These measures included the Beck Depression Inventory (BDI), the Paced Auditory Serial Addition Test (PASAT), Digit Span Test, and the Similarities Test of Verbal Abstract Reasoning.

RESULTS: The mean number of correctly identified responses collapsed across the four PASAT trials was significantly different across groups (F[2,31] = 4.03; P < .05). While the CFS and MS groups did not differ from each other, subjects with CFS (SEM, 124.2 +/- 6.4) and subjects with MS (SEM, 112.9 +/- 10.9) scored significantly below controls (SEM, 146.4 +/- 6.4) (Fisher’s Protected Least Significant Difference test; P < .05). There were significant differences among the three groups on mean Digit Span Test performance (F[2,31] = 5.5; P < .01). While the CFS and MS group did not differ significantly from each other, only the CFS group was significantly lower than control (Fisher’s Protected Least Significant Difference test; P < .05). Mean performance on the Similarities test did not differ among the three groups (F = 0.58). In addition, there were significant differences among the three groups in mean BDI scores (F[2,31] = 7.6; P < .01). The CFS and MS groups did not differ significantly from each other, and both groups showed a statistically significantly elevated mean BDI score relative to the control group (Fisher’s Protected Least Significant Difference test; P < .05). No significant correlations were found between BDI scores and PASAT total scores (CFS, r = -.21; MS, r = .13; control, r = .27), or between BDI and Digit Span Test (CFS, r = -.32; MS, r = -.40; control, r = -.19). Results of the PASAT and Digit Span Test were significantly correlated in the CFS group (r = .71; P < .01), but not in the MS (r = .06) or control groups (r = .49).

CONCLUSIONS: These results indicate that subjects with CSF and subjects with MS show significant impairment on a test of complex concentration when compared with appropriate controls. The data suggest that subjects with CFS and subjects with MS have difficulty on tasks that require the simultaneous processing of complex cognitive information. Selective impairment in information processing efficiency may lie at the root of other cognitive complaints made by patients with CFS.

 

Source: DeLuca J, Johnson SK, Natelson BH. Information Processing Efficiency in Chronic Fatigue Syndrome and Multiple Sclerosis.Arch Neurol. 1993;50(3):301-304. doi:10.1001/archneur.1993.00540030065016. http://archneur.jamanetwork.com/article.aspx?articleid=592247

 

Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults

Abstract:

OBJECTIVE: To assess whether the human T-lymphotropic virus type II (HTLV-II) gag gene sequence, a purportedly new laboratory marker of the chronic fatigue syndrome (CFS), and other possible risk factors for CFS, particularly those associated with retroviral transmission, are associated with well-characterized CFS.

DESIGN: Two matched case-control studies.

SETTING: The metropolitan Atlanta area.

PATIENTS: Twenty-one patients with CFS who were identified by the Centers for Disease Control and Prevention CFS surveillance system; 21 CDC employee controls (laboratory study) and 42 neighborhood controls (risk-factor study) who were matched to patients by age, race, and gender.

MEASUREMENTS: Peripheral blood lymphocytes and leukocytes were assayed for the HTLV-II gag gene sequence by polymerase chain reaction and specific Southern blot hybridization. Questionnaires elicited demographic and clinical information and a history of exposures associated with retrovirus transmission (for example, blood transfusions, sexual practices, intravenous drug use).

RESULTS: All patients were white and 86% were female. The median age at illness onset was 34 years (range, 16 to 51 years). The HTLV-II gag gene sequence was not identified in the blood of any patient or control under conditions in which the appropriate assay controls were positive. No statistical differences were observed between patients and controls in frequency of blood transfusions (10% compared with 7%), median number of sex partners before illness (3 compared with 3), bisexual or homosexual behavior (14% compared with 7%), intravenous drug use (0% compared with 0%), and other factors associated with retroviral infection.

CONCLUSIONS: The HTLV-II gag gene sequence was not a marker for CFS in this small study of well-defined patients, nor did other characteristics of the patients and controls support the hypothesis that a retrovirus, transmitted by usual modes, was a cause of CFS.

 

Source: Khan AS, Heneine WM, Chapman LE, Gary HE Jr, Woods TC, Folks TM, Schonberger LB. Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults. Ann Intern Med. 1993 Feb 15;118(4):241-5. http://www.ncbi.nlm.nih.gov/pubmed/8420441

 

Red blood cell magnesium and chronic fatigue syndrome

Abstract:

The hypotheses that patients with chronic fatigue syndrome (CFS) have low red blood cell magnesium and that magnesium treatment would improve the wellbeing of such patients were tested in a case-control study and a randomised, double-blind, placebo-controlled trial, respectively.

In the case-control study, 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15).

In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17).

Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved from the maximum to the minimum.

By contrast, 3 of the 17 patients on placebo said that they felt better (difference 62%, 95% CI 35 to 90), and 1 patient had a better energy score. Red cell magnesium returned to normal in all patients on magnesium but in only 1 patient on placebo. The findings show that magnesium may have a role in CFS.

Comment in:

Magnesium and chronic fatigue. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Magnesium and chronic fatigue syndrome. [Lancet. 1991]

Intravenous magnesium loading in chronic fatigue syndrome. [Lancet. 1992]

 

Source: Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991 Mar 30;337(8744):757-60. http://www.ncbi.nlm.nih.gov/pubmed/1672392