Natelson – Page 7 – American ME and CFS Society

Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). We have challenged this notion by examining perceived exertion in civilian females with CFS and expressing the data relative to exercise capacity (%[OV0312]O(2max)). The purpose of the present investigation was to further examine RPE during exercise in a unique population of CFS patients, Gulf veterans (GV).

METHODS: Thirty-four GV (N = 15 CFS, 42 +/- 8 yr; N = 19 healthy, 43 +/- 5 yr) performed a maximal exercise test on a cycle ergometer. After a 3-min warm-up, exercise intensity increased by 30 W every minute until exhaustion. RPE were obtained during the last 15 s of each minute using Borg’s CR-10 scale.

RESULTS: With the exception of peak [OV0312]E, there were no significant differences in any peak exercise variables. Repeated measures ANOVA revealed significantly higher RPE at each power output examined (F(1,32) = 16.4, P < 0.001). Group differences in RPE remained significant when analyzed relative to peak [OV0312]O(2) (F(1,32) = 7.2, P = 0.01). Both group main effects and the interaction were eliminated when self-reported fatigue symptoms were controlled for in the analyses. Power functions for RPE as a function of relative oxygen consumption were not different between groups and were significantly greater than a linear value of 1.0 (1.6 +/- 0.3 for both groups, P < 0.02).

CONCLUSIONS: Our results show that RPE are greater in GV with CFS regardless of whether the data were expressed in terms of absolute or relative exercise intensity. However, self-reported fatigue associated with CFS eliminated the group differences. These results suggest that GV with CFS were unique compared with their civilian counterparts. Future research aimed at determining the influence of preexisting fatigue on RPE during exercise is warranted.

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: Gulf War veterans with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):569-74. http://www.ncbi.nlm.nih.gov/pubmed/12673138

Perceived exertion in fatiguing illness: civilians with chronic fatigue syndrome

Abstract:

PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). However, methodological limitations have rendered this conclusion suspect. The purpose of the present investigation was to examine RPE during exercise in civilians with CFS by comparing subjects at both absolute exercise stage and relative oxygen consumption reference criteria.

METHODS: A sample of 39 civilian females (N = 19 CFS, 34 +/- 7 yr; N = 20 healthy controls, 33 +/- 7 yr) underwent a maximal exercise test on a treadmill. RPE were obtained during the last 15 s of each 3-min stage using Borg’s 6-20 scale.

RESULTS: There were no significant differences in peak [OV0312]O(2), RER, or RPE. However, controls exercised longer (20.0 +/- 1.1 vs 15.9 +/- 1.1 min, P = 0.01, healthy vs CFS) and had higher peak HR (183 +/- 3 vs 174 +/- 2 bpm, P = 0.03, healthy vs CFS). Civilians with CFS reported higher RPE at stages 3 through 5 compared with controls (F(3,111)= 3.6,P = 0.017). Preexercise fatigue ratings were not a significant predictor of perceived exertion during exercise. There were no group differences (F(1,37)= 1.9, P = 0.17) when RPE were expressed relative to peak [OV0312]O(2).

CONCLUSIONS: Our results show that RPE are greater in civilians with CFS when the data are expressed in terms of absolute exercise intensity. However, by examining RPE relative to a common maximum (i.e., peak [OV0312]O(2)) no differences were observed. The findings of the present investigation challenge the notion that RPE are dysregulated in CFS.

Source: Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. Perceived exertion in fatiguing illness: civilians with chronic fatigue syndrome. Med Sci Sports Exerc. 2003 Apr;35(4):563-8. http://www.ncbi.nlm.nih.gov/pubmed/12673137

Comorbid illness in women with chronic fatigue syndrome: a test of the single syndrome hypothesis

Abstract:

OBJECTIVE: Evidence of comorbidity among unexplained illness syndromes raises the possibility that all are variants of a single functional disorder, leading some to suggest that separate case definitions for chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivity (MCS) may be unnecessary. Our objective was to determine whether discrete diagnostic labels provide useful information about physical functioning, symptom severity, and risk of psychiatric illness.

METHODS: The sample consisted of 163 consecutive female referrals with CFS enrolled at a tertiary clinic. Each participant was retrospectively assigned to one of four groups: CFS only, CFS/FM, CFS/MCS, and CFS/FM/MCS. At enrollment, participants gave their history, underwent a physical examination and a standardized psychiatric interview (Diagnostic Interview Schedule), and answered self-report questionnaires.

RESULTS: Additional unexplained syndromes were prevalent: 37% met criteria for FM, and 33% met criteria for MCS. With the exception of FM-related pain and disability, there were few differences between the CFS only and CFS with comorbid illness groups. Patients with additional illness were more likely to have major depression and a higher risk of psychiatric morbidity compared with patients in the CFS only group (p <.01). Rates of lifetime depression increased from 27.4% in the CFS only group to 52.3% in the CFS/FM group, 45.2% in the CFS/MCS group, and 69.2% in the CFS/FM/MCS group.

CONCLUSIONS: The prevalence of comorbid illness in the present CFS sample and the failure to find widespread differences in symptom severity can be seen as support for the single syndrome hypothesis. On the other hand, the existence of discrete syndromes could not be ruled out because of reliable differences between CFS and CFS/FM. Increasing comorbidity was associated with a corresponding increase in risk of major depression.

Source: Ciccone DS, Natelson BH. Comorbid illness in women with chronic fatigue syndrome: a test of the single syndrome hypothesis. Psychosom Med. 2003 Mar-Apr;65(2):268-75. http://www.ncbi.nlm.nih.gov/pubmed/12651994

Blood flow and muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced blood flow and oxidative delivery to skeletal muscle. Patients with CFS according to CDC (Center for Disease Control) criteria ( n =19) were compared with normal sedentary subjects ( n =11). Muscle blood flow was measured with Doppler ultrasound after cuff ischaemia and exercise. Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemic oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous wavelength near-IR spectroscopy. Muscle metabolism was measured using (31)P magnetic resonance spectroscopy. CFS patients and controls were not different in the peak blood flow after cuff ischaemia, the rate of recovery of phosphocreatine after submaximal exercise, and the rate of recovery of oxygen saturation after cuff ischaemia. In conclusion, CFS patients showed no deficit in blood flow or oxidative metabolism. This suggests that CFS symptoms do not require abnormal peripheral function.

Source: McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Blood flow and muscle metabolism in chronic fatigue syndrome. Clin Sci (Lond). 2003 Jun;104(6):641-7. http://www.ncbi.nlm.nih.gov/pubmed/12589704

A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome

Abstract:

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject.

In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.

Source: Yamamoto Y, LaManca JJ, Natelson BH. A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome. Exp Biol Med (Maywood). 2003 Feb;228(2):167-74. http://www.ncbi.nlm.nih.gov/pubmed/12563023

Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome

Abstract:

We explored the relationship between a set of immunological variables and a set of cognitive and functional status measures and a diagnosis of chronic fatigue syndrome (CFS) in civilians and veterans using various regression and factor analytic methods.

Our approach emphasized the extraction of a few distinct factors in order to limit statistical problems associated with doing large numbers of multiple comparisons. This approach led to our finding cytokine data grouping into type 1 and type 2 clusters. A type 2 cluster plus a T and B cell factor predicted CFS caseness for Gulf War veterans but not for civilians with CFS. When a cognitive variable, reaction time, was added into the model, both immunological factors lost statistical significance; this indicates that the cognitive variable reaction time moderated the effects of the immunological factors in predicting patient status.

We did a similar analysis on the roles of the immunological and cognitive variables in functional status using SF-36 data. Higher levels of these same two immunological factors predicted poorer general health as well as poorer physical and social functioning in Gulf War veterans but not in civilians with CFS. When the reaction time factor was added, only the lymphocyte factor remained significant. This implies that lymphocytes are directly related to functional status in Gulf War veterans with CFS, but the Th2 factor produces its effect on functional status via changes in cognitive abilities.

Source: Brimacombe M, Zhang Q, Lange G, Natelson B. Immunological variables mediate cognitive dysfunction in gulf war veterans but not civilians with chronic fatigue syndrome. Neuroimmunomodulation. 2002-2003;10(2):93-100. http://www.ncbi.nlm.nih.gov/pubmed/12372983

Birth order and its association with the onset of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a medically unexplained illness that is diagnosed on the basis of a clinical case definition; so it probably is an illness with multiple causes producing the same clinical picture. One way of dealing with this heterogeneity is to stratify patients based on illness onset. We hypothesized that either the whole group of CFS patients or that group which developed CFS gradually would show a relation with birth order, while patients who developed CFS suddenly, probably due to a viral illness, would not show such a relation. We hypothesized the birth order effect in the gradual onset group because those patients have more psychological problems, and birth order effects have been shown for psychological characteristics.

We compared birth order in our CFS patients to that in a comparison group derived from U.S. demographic data. We found a tendency that did not reach formal statistical significance for a birth order effect in the gradual onset group, but not in either the sudden onset or combined total group. However, the birth order effect we found was due to relatively increased rates of CFS in second-born children; prior birth order studies of personality characteristics have found such effects to be skewed toward first-born children. Thus, our data do support a birth order effect in a subset of patients with CFS. The results of this study should encourage a larger multicenter study to further explore and understand this relation.

Comment in: Response to Brimacombe et al., birth order and its association with the onset of chronic fatigue syndrome. [Hum Biol. 2003]

Source: Brimacombe M, Helmer DA, Natelson BH. Birth order and its association with the onset of chronic fatigue syndrome. Hum Biol. 2002 Aug;74(4):615-20. http://www.ncbi.nlm.nih.gov/pubmed/12371687

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.

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)