Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome

Abstract:

Post-exertional exacerbation of symptoms is one of the major characteristics of chronic fatigue syndrome (CFS). In this study, we evaluated the hypothesis that disturbances in circadian chronobiological regulation may play a role in generating this phenomenon.

We recorded physical activity for 6-day periods in 16 women (10 CFS and 6 sedentary healthy controls, CON) before and after performing a maximal treadmill test. We calculated activity rhythms by computing autocorrelation coefficients by cutting 1 day apart from the data as a template and sliding it sequentially through each of the other days; all of 6 days were used as the templates. The peak value of autocorrelation coefficient (R) and the time between peak R’s (circadian period, CP) were calculated. CFS patients had a lengthening (P < .05) of mean circadian period (MCP) that was longer than 24 h (P < .05), while MCP in CON remained unchanged. No difference was found in the standard error of each subject’s MCP (circadian period variability, CPV) before and after exercise for both groups.

We interpret this increase in circadian rest-activity period seen in CFS patients following exercise to indicate that exhaustive exercise interferes with normal entrainment to 24-h zeitgeber(s). This effect may be associated in part with the common patient complaint of symptom worsening following exertion.

Copyright 2002 Elsevier Science Inc.

 

Source: Ohashi K, Yamamoto Y, Natelson BH. Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome. Physiol Behav. 2002 Sep;77(1):39-44. http://www.ncbi.nlm.nih.gov/pubmed/12213500

 

A status report on chronic fatigue syndrome

Abstract:

Medical history has shown that clinical disease entities or syndromes are composed of many subgroups–each with its own cause and pathogenesis. Although we cannot be sure, we expect the same outcome for chronic fatigue syndrome (CFS), a medically unexplained condition characterized by disabling fatigue accompanied by infectious, rheumatological, and neuropsychiatric symptoms. Although the ailment clearly can occur after severe infection, no convincing data exist to support an infectious (or immunologic) process in disease maintenance. Instead, data point to several possible pathophysiological processes: a covert encephalopathy, impaired physiological capability to respond to physical and mental stressors, and psychological factors related to concerns about effort exacerbating symptoms. Each of these is under intense investigation. In addition, some data do exist to indicate that environmental agents also can elicit a state of chronic fatigue. We expect data to accumulate to support the belief that CFS has multiple causes.

 

Source: Natelson BH, Lange G. A status report on chronic fatigue syndrome. Environ Health Perspect. 2002 Aug;110 Suppl 4:673-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241224/ (Full article)

 

Evidence for the presence of immune dysfunction in chronic fatigue syndrome

Chronic fatigue syndrome is a medically unexplained ailment characterized by new onset of fatigue accompanied by rheumatological, infectious, and neuropsychiatric symptoms. Because the ailment often begins suddenly with a flu-like presentation, early pathophysiological ideas as to cause included viral infection and immune activation. When early reports identified putative immunological abnormalities in this illness, it was given the name of chronic fatigue and immune dysfunction syndrome, or CFIDS.

The purpose of this review is to evaluate the immunological literature to determine if strong evidence to support this notion exists. We collected and reviewed 239 published papers, of which only 72 fulfilled a set of criteria for use in this review. For this review, we developed the following criteria: papers had to be published in the peer review literature; patients had to be from a group with substantial fatigue lasting at least 6 months (the vast majority fulfilled either the 1988 or the 1994 case definition of chronic fatigue syndrome [CFS]); papers had to compare CFS patients to healthy controls; and actual data had to be shown with evidence of testing for statistical significance. So, for example, when a paper reported no difference between patients and controls for some immunological variables but actual data were not included, we did not include it. Also, if a report compared patient data to normative values rather than to the study’s own control group, we did not include it.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/

 

Source: Natelson BH, Haghighi MH, Ponzio NM. Evidence for the presence of immune dysfunction in chronic fatigue syndrome.  Clin Diagn Lab Immunol. 2002 Jul;9(4):747-52. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC120010/ (Full article)

 

Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise

Abstract:

OBJECTIVE: The purpose of this study was to compare the cardiovascular responses of patients with chronic fatigue syndrome (CFS) to healthy control subjects when performing stressful cognitive tasks before and after strenuous exercise.

METHOD: Beat-by-beat blood pressure and electrocardiogram were recorded on 19 women with CFS and 20 healthy nonexercising (ie, sedentary) women while they performed cognitive tests before, immediately after, and 24 hours after incremental exercise to exhaustion.

RESULTS: Diminished heart rate (p <.01) and systolic (p <.01) and diastolic (p <.01) blood pressure responses to stressful cognitive testing were seen in patients with CFS when compared with healthy, sedentary controls. This diminished stress response was seen consistently in patients with CFS across three separate cognitive testing sessions. Also, significant negative correlations between self-ratings of CFS symptom severity and cardiovascular responses were seen (r = -0.62, p <.01).

CONCLUSIONS: Women with CFS have a diminished cardiovascular response to cognitive stress; however, exercise did not magnify this effect. Also, the data showed that the patients with the lowest cardiovascular reactivity had the highest ratings of CFS symptom severity, which suggests that the individual response of the patient with CFS to stress plays a role in the common complaint of symptoms worsening after stress.

 

Source: LaManca JJ, Peckerman A, Sisto SA, DeLuca J, Cook S, Natelson BH. Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise. Psychosom Med. 2001 Sep-Oct;63(5):756-64. http://www.ncbi.nlm.nih.gov/pubmed/11573024

 

Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome

Abstract:

The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated.

The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months).

Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

 

Source: Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH. Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):41-50. http://www.ncbi.nlm.nih.gov/pubmed/11388123

 

Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome

Abstract:

Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS. The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings.

In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance. Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.

 

Source: Lange G, Holodny AI, DeLuca J, Lee HJ, Yan XH, Steffener J, Natelson BH. Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):23-30. http://www.ncbi.nlm.nih.gov/pubmed/11388120

 

Detection of immunologically significant factors for chronic fatigue syndrome using neural-network classifiers

Abstract:

Neural-network classifiers were used to detect immunological differences in groups of chronic fatigue syndrome (CFS) patients that heretofore had not shown significant differences from controls. In the past linear methods were unable to detect differences between CFS groups and non-CFS control groups in the nonveteran population.

An examination of the cluster structure for 29 immunological factors revealed a complex, nonlinear decision surface. Multilayer neural networks showed an over 16% improvement in an n-fold resampling generalization test on unseen data. A sensitivity analysis of the network found differences between groups that are consistent with the hypothesis that CFS symptoms are a consequence of immune system dysregulation.

Corresponding decreases in the CD19(+) B-cell compartment and the CD34(+) hematopoietic progenitor subpopulation were also detected by the neural network, consistent with the T-cell expansion. Of significant interest was the fact that, of all the cytokines evaluated, the only one to be in the final model was interleukin-4 (IL-4). Seeing an increase in IL-4 suggests a shift to a type 2 cytokine pattern. Such a shift has been hypothesized, but until now convincing evidence to support that hypothesis has been lacking.

 

Source: Hanson SJ, Gause W, Natelson B. Detection of immunologically significant factors for chronic fatigue syndrome using neural-network classifiers. Clin Diagn Lab Immunol. 2001 May;8(3):658-62. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC96120/ (Full article)

 

Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome (CFS) is an unexplained illness that is characterized by severe fatigue. Some have suggested that CFS is a “functional somatic syndrome” in which symptoms of fatigue are inappropriately attributed to a serious illness. However, brain magnetic resonance imaging (MRI) data suggest that there may be an organic abnormality associated with CFS.

To understand further the significance of brain MRI abnormalities, we examined the relationship between MRI identified brain abnormalities and self-reported physical functional status in 48 subjects with CFS who underwent brain MR imaging and completed the Medical Outcomes Study SF-36. Brain MR images were examined for the presence of abnormalities based on 5 general categories previously shown to be sensitive to differentiating CFS patients from healthy controls.

There were significant negative relationships between the presence of brain abnormalities and both the physical functioning (PF) (rho=-.31, p=.03), and physical component summary PCS (rho=-.32, p=.03) subscales of the SF-36. CFS patients with MRI identified brain abnormalities scored significantly lower on both PF (t(1,46) =2.3, p=.026) and the PCS (t(1,41) =2.4, p=.02) than CFS subjects without an identified brain abnormality. When adjusted for age differences only the PF analysis remained significant. However, the effect sizes for both analyses were large indicating meaningful differences in perceived functional status between the groups.

These results demonstrate that the presence of brain abnormalities in CFS are significantly related to subjective reports of physical function and that CFS subjects with MRI brain abnormalities report being more physically impaired than those patients without brain abnormalities.

 

Source: Cook DB, Lange G, DeLuca J, Natelson BH. Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome. Int J Neurosci. 2001 Mar;107(1-2):1-6. http://www.ncbi.nlm.nih.gov/pubmed/11328679

 

Clinicopathological findings consistent with primary Sjögren’s syndrome in a subset of patients diagnosed with chronic fatigue syndrome: preliminary observations

Abstract:

OBJECTIVE: Some patients diagnosed with chronic fatigue syndrome (CFS) have symptoms commonly observed in Sjögren’s syndrome (SS), particularly xerophthalmia and xerostomia, leading to speculation that some patients with CFS might have primary SS or that the 2 disorders share common pathophysiological features. We investigated the prevalence of symptoms of mucosal dryness, salivary gland pathology, lacrimal hyposecretion, and autoantibodies (antinuclear antibody, SSA/SSB) among patients diagnosed with CFS.

METHODS: Twenty-five subjects with CFS and 18 healthy control subjects were interviewed and examined, had a Schirmer test and fluorescein tear dilution, and underwent minor salivary gland (MSG) biopsy. Antibody to nuclear antigen as well as anti-La (SSA) and anti-Ro (SSB) antibody were available for subjects with CFS. Pathologists unaware of the subject group assignment examined labial salivary gland biopsy specimens and calculated a standard MSG score for each specimen.

RESULTS: Mucosal dryness was reported by 13/25 (52%) subjects with CFS, of which 8 (32%) also had MSG score, low Schirmer test value, and symptoms consistent with primary SS (p = 0.05). No control subject met diagnostic criteria for primary SS. MSG focus scores < or =1 were common among both groups (CFS 14/25; controls 15/18). MSG results without pathological alteration were rare, seen in only one control and no CFS patients. Low Schirmer values were found in 10/25 (40%) CFS patients and 1/18 (6%) control (p = 0.01).

CONCLUSION: A subset of patients with CFS may have primary SS.

 

Source: Sirois DA, Natelson B. Clinicopathological findings consistent with primary Sjögren’s syndrome in a subset of patients diagnosed with chronic fatigue syndrome: preliminary observations. J Rheumatol. 2001 Jan;28(1):126-31. http://www.ncbi.nlm.nih.gov/pubmed/11196514

 

Hormonal responses to exercise in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease characterized by severe, unexplained fatigue and postexertional exacerbation of symptoms. We examined basal endocrine function in a group of CFS patients and a carefully matched group of sedentary controls. The subjects then completed a graded, maximal exercise test on a treadmill, and additional blood samples were drawn 4 min and a day after the end of exercise.

There were no differences in basal hormone levels before exercise. Plasma adrenocorticotropin, epinephrine, prolactin and thyrotropin responses 4 min after exercise were lower in the CFS group, but the growth hormone response may have been exaggerated, and the plasma norepinephrine response was similar to that in controls.

The next day, there were no differences in hormone levels between the groups, which suggests that long-term changes in endocrine function are unlikely to be a cause of the prolonged fatigue that occurs in CFS patients after a bout of exertion.

 

Source: Ottenweller JE, Sisto SA, McCarty RC, Natelson BH. Hormonal responses to exercise in chronic fatigue syndrome. Neuropsychobiology. 2001 Jan;43(1):34-41. http://www.ncbi.nlm.nih.gov/pubmed/11150897