Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients

 

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS.

Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group.

Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.

 

Source: Peterson PK, Sirr SA, Grammith FC, Schenck CH, Pheley AM, Hu S, Chao CC. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Lab Immunol. 1994 Mar;1(2):222-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/pdf/cdli00002-0112.pdf

 

Chronic fatigue syndrome: have flawed assumptions been derived from treatment-based studies?

Abstract:

Chronic fatigue syndrome is a disabling disorder that has been studied primarily in clinical settings. In the absence of an adequate epidemiological database, cultural stereotypes have influenced the characterization of chronic fatigue syndrome as “the yuppie flu,” similar to the 19th century characterization of neurasthenia as a disease of the affluent. The limited epidemiological data available and the overall medical-sociological literature call this assumption into question. Only a community “true” prevalence study that is unbiased by help seeking and access to health care can provide an accurate assessment of the risk factors for and the public health ramifications of this disease.

 

Source: Richman JA, Flaherty JA, Rospenda KM. Chronic fatigue syndrome: have flawed assumptions been derived from treatment-based studies? Am J Public Health. 1994 Feb;84(2):282-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615008/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615008/pdf/amjph00453-0124.pdf

 

 

High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness

Abstract:

Forty-one patients with chronic fatigue syndrome (CFS), 76 healthy controls matched with the patient group for age range, sex, race, and socioeconomic class, and 22 symptomatic patients with seasonal affective disorder (SAD) had serum sampled for antibodies against 2 Epstein-Barr virus (EBV) replicating enzymes.

Abnormal titers of antibodies were found twice as often in CFS patients as controls (34.1% vs. 17.1%), with SAD patients having an intermediate frequency (27.3%). Stratifying for disease severity sharpened the differences considerably, with the sicker CFS and SAD patients having 52% and 50% abnormal tests, respectively; more mildly afflicted CFS and SAD patients had a frequency of abnormal tests in the normal range.

Antibodies to EBV DNA polymerase (DNAP) were the more sensitive of the two tests in that they were positive in all cases but one. These findings suggest that antibodies against EBV DNAP may be a useful marker in delineating a subset of patients with severe fatiguing illness for appropriate treatment trials and for monitoring their outcomes.

 

Source: Natelson BH, Ye N, Moul DE, Jenkins FJ, Oren DA, Tapp WN, Cheng YC. High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness. J Med Virol. 1994 Jan;42(1):42-6. http://www.ncbi.nlm.nih.gov/pubmed/8308519

 

Chronic fatigue syndrome: a novel disorder with cutaneous manifestations

Abstract:

Persistent and disabling fatigue associated with low-grade fever and other constitutional symptoms, without any known disorder that accounts for it, is recognized as chronic fatigue syndrome (CFS). Skin lesions occur in 10-35% of patients, but their description is inaccurate. Recurrent aphthous stomatitis or persistent Epstein-Barr virus (EBV)-related erythema multiforme have also been reported. Patients may be diagnosed as having CFS only when they fulfill at least 2 major and 8 minor criteria. Major criteria are the presence of debilitating fatigue persisting or recurring for at least 6 months and the absence of any other medical disorder that may explain it. Although different viral or nonviral etiologies have been documented, evidence implicating EBV is gaining support.

 

Source: Rebora A, Drago F. Chronic fatigue syndrome: a novel disorder with cutaneous manifestations. Dermatology. 1994;188(1):3-5. http://www.ncbi.nlm.nih.gov/pubmed/8305753

 

Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome

Abstract:

Levels of 2′,5′-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls.

Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6).

Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.

 

Source: Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, et al. Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. http://www.ncbi.nlm.nih.gov/pubmed/8148461

 

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition.

In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined.

Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance.

After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

 

Source: Strayer DR, Carter WA, Brodsky I, Cheney P, Peterson D, Salvato P, Thompson C, Loveless M, Shapiro DE, Elsasser W, et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S88-95. http://www.ncbi.nlm.nih.gov/pubmed/8148460

 

Cognitive functioning of patients with chronic fatigue syndrome

Abstract:

Neuropsychological problems are a distressing and frequent component of the symptom complex associated with chronic fatigue syndrome. Objective assessment of these difficulties is essential to understanding the nature of this illness. Results of the studies discussed in this paper suggest that impaired information processing, rather than primary memory dysfunction, may be at the root of the cognitive problems that afflict so many patients with CFS.

 

Source: Johnson SK, DeLuca J, Fiedler N, Natelson BH. Cognitive functioning of patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S84-5. http://www.ncbi.nlm.nih.gov/pubmed/8148459

 

Measuring the functional impact of fatigue: initial validation of the fatigue impact scale

Abstract:

The fatigue impact scale (FIS) was developed to improve our understanding of the effects of fatigue on quality of life. The FIS examines patients’ perceptions of the functional limitations that fatigue has caused over the past month. FIS items reflect perceived impact on cognitive, physical, and psychosocial functioning.

This study compared 145 patients referred for investigation of chronic fatigue (ChF) with 105 patients with multiple sclerosis (MS) and 34 patients with mild hypertension (HT). Internal consistency for the FIS and its three subscales was > .87 for all analyses. Fatigue impact was highest for the ChF group although the MS group’s reported fatigue also exceeded that of the HT group. Discriminant function analysis correctly classified 80.0% of the ChF group and 78.1% of the MS group when these groups were compared.

This initial validation study indicates that the FIS has considerable merit as a measure of patient’s attribution of functional limitations to symptoms of fatigue.

 

Source: Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. http://www.ncbi.nlm.nih.gov/pubmed/8148458

 

Psychosocial correlates of illness burden in chronic fatigue syndrome

Abstract:

We related reported physical symptoms, cognitive appraisals (e.g., negative style of thinking), and coping strategies (e.g., denial/disengagement strategies) with illness burden across several functional domains separately in subsets of chronic fatigue syndrome (CFS) patients with (n = 26) and without (n = 39) concurrently diagnosed major depressive disorder (MDD).

In regard to cognitive appraisal measures, automatic thoughts and dysfunctional attitudes were strongly associated with a higher illness burden, as indicated in sickness impact profile (SIP) scores. Active-involvement coping strategies measured on COPE scales (active coping, planning, and positive reinterpretation and growth) were not associated with SIP scores, while other coping strategies (mental disengagement, behavioral disengagement, and denial) were positively correlated with psychosocial and physical SIP scales, especially those pertaining to interpersonal life-style arenas.

After we accounted for the number of different CFS-specific physical complaints reported and DSM-III-R depression diagnosis status, cognitive appraisals and coping strategies predicted a substantial proportion of the variance in the severity of illness burden. For the most part, the magnitude of these relationships between our predictor model variables and illness burden severity was similar in the MDD and non-MDD subgroups.

 

Source: Antoni MH, Brickman A, Lutgendorf S, Klimas N, Imia-Fins A, Ironson G, Quillian R, Miguez MJ, van Riel F, Morgan R, et al. Psychosocial correlates of illness burden in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S73-8. http://www.ncbi.nlm.nih.gov/pubmed/8148457

 

Sleep disorders in patients with chronic fatigue

Abstract:

This prospective, cohort study examined the prevalence of sleep disorders among highly selected patients with chronic fatigue. On the basis of responses suggestive of sleep pathology on a screening questionnaire, 59 patients from a university-based clinic for chronic fatigue who had undergone a medical and psychiatric evaluation underwent polysomnography.

Criteria for chronic fatigue syndrome (CFS) were met by 64% of patients and those for a current psychiatric disorder were met by 41%. Overall, 41% of patients had abnormal results for a multiple sleep latency test and 81% had at least one sleep disorder, most frequently sleep apnea (44%) and idiopathic hypersomnia (12%).

In comparing patients who did and did not meet CFS criteria, no significant differences were found in individual sleep symptoms or sleep disorders. Likewise, symptoms and sleep disorders were unrelated to psychiatric diagnoses. In conclusion, chronically fatigued patients with suggestive symptoms may have potentially treatable coexisting sleep disorders that are not associated with meeting criteria for CFS or a current psychiatric disorder.

 

Source: Buchwald D, Pascualy R, Bombardier C, Kith P. Clin Infect Dis. 1994 Jan;18 Suppl 1:S68-72. http://www.ncbi.nlm.nih.gov/pubmed/8148456