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Chronic fatigue syndrome [CFS] may occur alone or with fibromyalgia. This has led some to believe the two occur along a common illness spectrum. Evaluating whether this is the case is important as differences in burden or severity of CFS with fibromyalgia (FM) would suggest different underlying pathophysiological processes. To determine if Insomnia Severity Index [ISI] scores differ between patients with CFS and those with CFS plus FM. In addition, we aim to determine if insomnia severity is impacted by other comorbid medically unexplained diagnoses. 247 patients with CFS completed the ISI and the Centers for Epidemiological Study – Depression. Patient groups were stratified on CFS severity and the presence of FM. A secondary analysis was conducted to evaluate insomnia severity related to the number of comorbid medically unexplained diagnoses including, FM, multiple chemical sensitivity and/or irritable bowel syndrome. When controlling for depressed mood, ISI did not differ significantly across patient groups defined by CFS severity and FM status. However, independent of mood, ISI was sensitive to multiple diagnoses showing a significant increasing trend from CFS alone to CFS plus one, two or three comorbid diagnoses. Although CFS severity and FM status do not impact insomnia severity, increased illness burden as manifested by multiple medically unexplained diagnoses does appear to influence insomnia. In contrast to our earlier studies, this study did not find that a comorbid diagnosis of FM in patients with CFS is related to a worse outcome in the variable of interest. [ABSTRACT FROM AUTHOR]

Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients' standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case–control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms. [ABSTRACT FROM AUTHOR]

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n = 15) and one without (n = 15) fibromyalgia. We quantified a total of 2083 proteins using immunoaffinity depletion, tandem mass tag isobaric labelling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p value <.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities. ME/CFS and fibromyalgia as currently defined are not distinct entities. Unbiased quantitative mass spectrometry-based proteomics can be used to discover cerebrospinal fluid proteins that are biomarkers for a condition such as we are studying. [ABSTRACT FROM AUTHOR]

The diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is generally reached based on meeting the criteria of a case definition and eliminating other conditions that could be causing the patient's symptoms. Investigators in the ME/CFS field are currently confronted with 139 medical exclusionary conditions listed among the various ME/CFS case definitions. There is a need to standardize the illnesses/diagnoses that should be excluded. Exclusionary conditions were listed for several prominent ME/CFS case definitions. From this list, symptoms were also identified as exclusionary by several physicians with experience in diagnosing ME/CFS. Input was also solicited from representatives from the patient community for a consensus list of exclusionary comorbid conditions. Once overlapping illnesses were eliminated, a consensus was reached on a briefer set of exclusionary conditions. The final set of exclusionary conditions is divided into 14 categories with 53 specific examples. It is important for ME/CFS researchers to select uniform medical conditions to exclude from their studies so that samples across different studies are consistent and generate generalizable ME/CFS findings. This list can be applied to ME/CFS case definitions in order to enhance the reproducibility of identifying patients with ME/CFS for research studies. [ABSTRACT FROM AUTHOR]

Physiological and/or pathological implications of the dynamics of sleep stage transitions have not, to date, been investigated. We report detailed duration and transition statistics between sleep stages in healthy subjects and in others with chronic fatigue syndrome (CFS); in addition, we also compare our data with previously published results for rats. Twenty-two healthy females and 22 female patients with CFS, characterized by complaints of unrefreshing sleep, underwent one night of polysomnographic recording. We find that duration of deep sleep (stages III and IV) follows a power-law probability distribution function; in contrast, stage II sleep durations follow a stretched exponential and stage I, and REM sleep durations follow an exponential function. These stage duration distributions show a gradually increasing departure from the exponential form with increasing depth of sleep toward a power-law type distribution for deep sleep, suggesting increasing complexity of regulation of deeper sleep stages. We also find a substantial number of REM to non-REM sleep transitions in humans, while this transition is reported to be virtually nonexistent in rats. The relative frequency of this REM to non-REM sleep transition is significantly lower in CFS patients than in controls, resulting in a significantly greater relative transition frequency of moving from both REM and stage I sleep to awake. Such an alteration in the transition pattern suggests that the normal continuation of sleep in light or REM sleep is disrupted in CFS. We conclude that dynamic transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with pathophysiological implications. sleep stage dynamics; relative transition frequency; duration distribution; power-law

Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such 'normal-flow' POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.]), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70[degrees]. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POT[S.sub.HC]) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POT[S.sub.HC] and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POT[S.sub.HC] compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POT[S.sub.HC]. vasoconstriction; hypocapnia; orthostatic intolerance doi:10.1152/ajpheart.01359.2005

A noninvasive study was conducted on intact awake humans to characterize the dynamic response of the heart to the vagus during slow-, comfortable-, and fast-paced respiration (8, 12, and 18 breaths/min), under both sitting and standing conditions. The respiration response curve (RRC) of respiration-associated vagal effects on the heart was estimated, and characteristics of entrainment and frequency dependence on respiration were demonstrated. It was shown that the degree of entrainment and magnitude of phase resetting decrease with increase of pacing rate from 8 to 18 breaths/min. Further, the RRC was examined by overlapping equivalent phase shifts in different respiration cycles. This examination of the RRC can help us not only to find the common pattern underlying the RRC during different respiration cycles but also to perceive its variation related to degree of entrainment. Index Terms - Heart rate variability, phase resetting, respiration response curve.

The most consistent deficit observed in individuals with Chronic Fatigue Syndrome has been in efficiency of information processing. To examine the possibility of a modality-specific impairment, the present study examined subjects with Chronic Fatigue Syndrome, multiple sclerosis, and healthy controls on an auditory-versus visual-paced serial-addition test. 20 subjects with Chronic Fatigue Syndrome, 20 subjects with clinically definite Multiple Sclerosis, and 20 sedentary healthy controls were compared. One-half of the subjects in each group were administered the Paced Auditory Serial Addition Test and the other half were administered the Paced Visual Serial Addition Test. The group with Chronic Fatigue Syndrome was differentially impaired on the auditory relative to the visual processing task. The group with Multiple Sclerosis was equally impaired on both versions of the task. The results are discussed within the framework of Baddeley's model of working memory.

Objective: To determine if presence of co-existing medically unexplained syndromes or psychiatric diagnoses affect symptom frequency, severity or activity impairment in Chronic Fatigue Syndrome. Patients: Sequential Chronic Fatigue Syndrome patients presenting in one clinical practice. Design: Participants underwent a psychiatric diagnostic interview and were evaluated for fibromyalgia, irritable bowel syndrome and/or multiple chemical sensitivity. Main Measures: Structured Clinical Interview [SCID] for DSM-IV; SF-36, Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Short Form; Patient Health Questionnaire-8; Multidimensional Fatigue Inventory (MFI-20), CDC Symptom Inventory Results: Current and lifetime psychiatric diagnosis was common (68%) increasing mental fatigue/health but no other illness variables and not with diagnosis of other medically unexplained syndromes. 81% of patients had at least one of these conditions with about a third having all three co-existing syndromes. Psychiatric diagnosis was not associated with their diagnosis. Increasing the number of these unexplained conditions was associated with increasing impairment in physical function, pain and rates of being unable to work. Conclusions: Patients with Chronic Fatigue Syndrome should be evaluated for current psychiatric conditions because of their impact on patient quality of life, but they do not act as a symptom multiplier for the illness. Other co-existing medically unexplained syndromes are more common than psychiatric co-morbidities in patients presenting for evaluation of medically unexplained fatigue and are also more associated with increased disability and the number and severity of symptoms. When physicians see patients with medically unexplained fatigue, they often infer that this illness is due to an underlying psychiatric problem. This paper shows that the presence of co-existing psychiatric diagnoses does not impact on any aspect of the phenomenology of medically unexplained fatigue also known as chronic fatigue syndrome. Therefore, psychiatric status is not an important causal contributor to CFS. In contrast, the presence of other medically unexplained syndromes (irritable bowel syndrome; fibromyalgia and/or multiple chemical sensitivity) do impact on the illness such that the more of these that co-exist the more health-related burdens the patient has. [ABSTRACT FROM AUTHOR]