Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the 'single syndrome' hypothesis.

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained syndromes that can and often do co-occur. For this reason, some have posited that the two are part of the same somatic syndrome--examples of symptom amplification. This hypothesis would suggest that few differences exist between the two syndromes. To evaluate this interpretation, we have searched the literature for articles comparing CFS to FM, reviewing only those articles which report differences between the two. This review presents data showing differences across a number of parameters--implying that the underlying pathophysiology in CFS may differ from that of FM. We hope that our review encourages other groups to look for additional differences between CFS and FM. By continuing to preserve the unique illness definitions of the two syndromes, clinicians will be able to better identify, understand and provide treatment for these individuals.

"Mobile Nurse" platform for ubiquitous medicine.

OBJECTIVES: We introduce "Mobile Nurse" (MN) - an emerging platform for the practice of ubiquitous medicine. METHODS: By implementing in a dynamic setting of daily life the patient care traditionally provided by the clinical nurses on duty, MN aims at integral data collection and shortening the response time to the patient. MN is also capable of intelligent interaction with the patient and is able to learn from the patient's behavior and disease sign evaluation for improved personalized treatment. RESULTS: In this paper, we outline the most essential concepts around the hardware, software and methodological designs of MN. We provide an example of the implementation, and elaborate on the possible future impact on medical practice and biomedical science research. CONCLUSIONS: The main innovation of MN, setting it apart from current tele-medicine systems, is the ability to integrate the patient's signs and symptoms on site, providing medical professionals with powerful tools to elucidate disease mechanisms, to make proper diagnoses and to prescribe treatment.

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory.

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT). We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for. Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99). Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome.

OBJECTIVES: Our objectives were to study the temporal correlation of physical activity time series in patients with chronic fatigue syndrome (CFS) during normal daily life and to examine if it could identify the altered physical activity in these patients. METHODS: Fractal scaling exponents of diurnal and nocturnal physical activity time series in 10 CFS patients and 6 healthy control subjects (CON) were calculated by the detrended fluctuation analysis (DFA) and the wavelet transform modulus maxima (WTMM) method. We hypothesized that, due to their illness- and/or fatigue-induced resting episodes, altered physical activity patterns in CFS patients might be observed at the interruption of activity bursts. Thus, we further developed a new method, the wavelet transform negative modulus maxima (WTNMM) method, which could evaluate the temporal correlation at the interruption of activities. We compared the fractal scaling exponents for CFS and CON by each method. RESULTS: Both for CFS and CON, we found the fractal time structures in their diurnal physical activity records for at least up to 35 minutes. No group difference was found in nocturnal activities. The WTNMM method revealed that, in diurnal activities, CFS patients had significantly (p < 0.01) smaller fractal scaling exponent (0.87 +/- 0.03) compared to controls (1.01 +/- 0.03). Such a difference was identified neither by the DFA nor WTMM method. CONCLUSIONS: CFS patients had more abrupt interruptions of voluntary physical activity during diurnal periods in normal daily life, probed by the decreased correlation in the negative modulus maxima of the wavelet-transformed activity data, possibly due to their exaggerated fatigue.

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

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.

Chronic fatigue and sexual dysfunction in female Gulf War veterans.

Chronic fatigue (CF) is one of the most common conditions reported by Gulf War veterans. This study evaluated female sexual dysfunction (FSD) in veterans with or without complaints of CF. Subjects were screened for medical and psychiatric causes of CF. They included 22 healthy subjects and 26 with fatiguing symptoms. FSD was reported by 10% of controls and by 60% of the fatigued (p < .002) while 19% versus 81% (p < .001) noted decreased libido. FSD was more prevalent in fatigued veterans than in the controls. This relationship was not mediated by an Axis I diagnosis. This appears to be the first report of sexual dysfunction in CF.

The perception of dyspnea in patients with mild asthma.

BACKGROUND: Airway function, as assessed by standard spirometry, and the intensity of dyspnea reported by asthmatic patients correlate poorly. OBJECTIVE: This study tests the following two hypotheses: (1) that measures of the tendency of a patient to somatize will reduce the variation in the report of dyspnea not explained by airway function; and (2) that plethysmography is a better tool with which to estimate the degree of dyspnea associated with asthma. DESIGN: A prospective laboratory study carried out over one study session. PARTICIPANTS: Forty asthmatic subjects who had withheld bronchodilator (BD) therapy overnight. INTERVENTIONS: We performed spirometry, plethysmography, and an assessment of dyspnea (ie, modified Borg scale) on all subjects before and after they received BD therapy. Standard questionnaires pertaining to psychological state and trait were administered as well. RESULTS: The change in specific airway conductance with BD therapy correlated with a decline in the Borg score (r = 0.47; p = 0.007). By contrast, neither spirographic measures nor measures of static lung volumes correlated. Correlation with the Borg scale score was not improved by adding indexes of either somatization or psychological state or trait. CONCLUSION: The relief of dyspnea reported by patients with mild asthma after BD therapy is related to dilatation of the central airways.

Quantitative assessment of cerebral ventricular volumes in chronic fatigue syndrome.

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.

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

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.

Persistent hormonal effects of stress are not due to reduced food intake or exposure to stressed rats.

Exposure to inescapable stress elicits persistent effects on the physiology and behavior of rats. Elevated basal plasma corticosterone concentrations have been observed for several days after cessation of stress. In this study, we measured hormonal concentrations in multiple axes at multiple levels, 24 h after one or three consecutive exposures to the same stress paradigm. The data indicated persistent activation of plasma corticosterone and prolactin concentrations, whereas plasma triiodothyronine, thyroxine, luteinizing hormone, and growth hormone concentrations were inhibited after either one or three stress sessions. In addition, we isolated the effects of restraint/tail shock per se from the effects of being moved and exposed to other stressed rats, and from the effects of reduced feeding produced by our stress protocol. The data clearly indicated that the stress paradigm, rather than exposure to stressed rats or decreased nutrient intake, is necessary to induce the persistent physiologic changes we observe after stressor exposures.

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

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.

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

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.

Cognitive functioning in Gulf War Illness.

A comprehensive neuropsychological battery was administered to 48 veterans with Gulf War Illness (GWI) characterized by severe fatigue (GV-F) and 39 healthy veterans (GV-H). Subjects were matched on intelligence and did not differ on age, gender, race, and alcohol consumption. Compared to GVs-H, GVs-F were significantly impaired on four tasks: three attention, concentration, information processing tasks and one measure of abstraction and conceptualization. After considering the presence of post-war Axis I psychopathology, GWI remained a significant predictor of cognitive performance on one of the attention, concentration, and information processing tasks and one abstraction and conceptualization measure. Performance on the remaining two attention, concentration, and information processing tasks was only significantly predicted by Axis I psychopathology with post-war onset. The results suggest that Gulf War Illness is associated with some aspects of cognitive dysfunction in Gulf Veterans, over and above the contribution of psychopathology.

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

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.

Hormonal responses to exercise in chronic fatigue syndrome.

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.

Medical follow-up of Persian Gulf War Veterans with severe medically unexplained fatigue: a preliminary study.

An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans.

Stressors, personality traits, and coping of Gulf War veterans with chronic fatigue.

OBJECTIVES: preliminary surveys of Persian Gulf veterans revealed a significant prevalence of self-reported symptoms consistent with chronic fatigue syndrome (CFS). The purpose of this study was to compare self-reported life stressors, combat, and chemical exposures, personality and coping between Gulf War veterans with CFS and healthy veterans. METHODS: following a complete physical, psychiatric, and neuropsychological evaluation, 45 healthy veterans, 35 veterans with CFS and co-morbid psychiatric disorder, and 23 veterans with CFS and no co-morbid psychiatric disorder completed questionnaires assessing war and non-war-related life stressors, self-reports of environmental exposure (e.g. oil well fires, pesticides), personality, and coping. RESULTS: measures of personality, self-reported combat and chemical exposures, and negative coping strategies significantly differentiated healthy veterans from those with CFS. CONCLUSION: a biopsychosocial model of veterans' illness was supported by the fact that personality, negative coping strategies, life stress after the war, and environmental exposures during the war were significant predictors of veterans' current physical function.

Cardiovascular stress responses and their relation to symptoms in Gulf War veterans with fatiguing illness.

OBJECTIVE: The objective of this study was to examine whether inappropriate cardiovascular responses to stressors may underlie symptoms in Gulf War veterans with chronic fatigue. METHODS: Psychophysiological stress testing was performed on 51 Gulf War veterans with chronic fatigue (using the 1994 case definition of the Centers for Disease Control and Prevention) and 42 healthy veterans. Hemodynamic responses to cold pressor, speech, and arithmetic stressors were evaluated using impedance cardiography. RESULTS: Veterans with chronic fatigue had diminished blood pressure responses during cognitive (speech and arithmetic) stress tests due to unusually small increases in total peripheral resistance. The cold pressor test, however, evoked similar blood pressure responses in the chronic fatigue and control groups. Low reactivity to cognitive stressors was associated with greater fatigue ratings among ill veterans, whereas an opposite relation was observed among healthy veterans. Self-reported neurocognitive decline was associated with low reactivity to the arithmetic task. CONCLUSIONS: These results suggest a physiological basis for some Gulf War veterans' reports of severe chronic fatigue. A greater deficit with responses processed through cerebral centers, as compared with a sensory stimulus (cold pressor), suggests a defect in cortical control of cardiovascular function. More research is needed to determine the specific mechanisms through which the dissociation between behavioral and cardiovascular activities identified in this study may be contributing to symptoms in Gulf War veterans.