Chronic Fatigue Syndrome: Maryland

Shoemaker RC, House DE. · Chronic Fatigue Center, 500 Market Street, Suite 103, Pocomoke City, MD 21851, United States. · Neurotoxicol Teratol. · Pubmed #15681119 No free full text.

Abstract: The human health risk for chronic illnesses involving multiple body systems following inhalation exposure to the indoor environments of water-damaged buildings (WDBs) has remained poorly characterized and the subject of intense controversy. The current study assessed the hypothesis that exposure to the indoor environments of WDBs with visible microbial colonization was associated with illness. The study used a cross-sectional design with assessments at five time points, and the interventions of cholestyramine (CSM) therapy, exposure avoidance following therapy, and reexposure to the buildings after illness resolution. The methodological approach included oral administration of questionnaires, medical examinations, laboratory analyses, pulmonary function testing, and measurements of visual function. Of the 21 study volunteers, 19 completed assessment at each of the five time points. Data at Time Point 1 indicated multiple symptoms involving at least four organ systems in all study participants, a restrictive respiratory condition in four participants, and abnormally low visual contrast sensitivity (VCS) in 18 participants. Serum leptin levels were abnormally high and alpha melanocyte stimulating hormone (MSH) levels were abnormally low. Assessments at Time Point 2, following 2 weeks of CSM therapy, indicated a highly significant improvement in health status. Improvement was maintained at Time Point 3, which followed exposure avoidance without therapy. Reexposure to the WDBs resulted in illness reacquisition in all participants within 1 to 7 days. Following another round of CSM therapy, assessments at Time Point 5 indicated a highly significant improvement in health status. The group-mean number of symptoms decreased from 14.9+/-0.8 S.E.M. at Time Point 1 to 1.2+/-0.3 S.E.M., and the VCS deficit of approximately 50% at Time Point 1 was fully resolved. Leptin and MSH levels showed statistically significant improvement. The results indicated that CSM was an effective therapeutic agent, that VCS was a sensitive and specific indicator of neurologic function, and that illness involved systemic and hypothalamic processes. Although the results supported the general hypothesis that illness was associated with exposure to the WDBs, this conclusion was tempered by several study limitations. Exposure to specific agents was not demonstrated, study participants were not randomly selected, and double-blinding procedures were not used. Additional human and animal studies are needed to confirm this conclusion, investigate the role of complex mixtures of bacteria, fungi, mycotoxins, endotoxins, and antigens in illness causation, and characterize modes of action. Such data will improve the assessment of human health risk from chronic exposure to WDBs.

Kop WJ, Lyden A, Berlin AA, Ambrose K, Olsen C, Gracely RH, Williams DA, Clauw DJ. · Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. · Arthritis Rheum. · Pubmed #15641057 links to  free full text

Abstract: OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are associated with substantial physical disability. Determinants of self-reported physical disability are poorly understood. This investigation uses objective ambulatory activity monitoring to compare patients with FM and/or CFS with controls, and examines associations of ambulatory activity levels with both physical function and symptoms during activities of daily life. METHODS: Patients with FM and/or CFS (n = 38, mean +/- SD age 41.5 +/- 8.2 years, 74% women) completed a 5-day program of ambulatory monitoring of physical activity and symptoms (pain, fatigue, and distress) and results were compared with those in age-matched controls (n = 27, mean +/- SD age 38.0 +/- 8.6 years, 44% women). Activity levels were assessed continuously, ambulatory symptoms were determined using electronically time-stamped recordings at 5 time points during each day, and physical function was measured with the 36-item Short Form health survey at the end of the 5-day monitoring period. RESULTS: Patients had significantly lower peak activity levels than controls (mean +/- SEM 8,654 +/- 527 versus 12,913 +/- 1,462 units; P = 0.003) and spent less time in high-level activities when compared with controls (P = 0.001). In contrast, patients had similar average activity levels as those of controls (mean +/- SEM 1,525 +/- 63 versus 1,602 +/- 89; P = 0.47). Among patients, low activity levels were associated with worse self-reported physical function over the preceding month. Activity levels were inversely related to concurrent ambulatory pain (P = 0.031) and fatigue (P < 0.001). Pain and fatigue were associated with reduced subsequent ambulatory activity levels, whereas activity levels were not predictive of subsequent symptoms. CONCLUSION: Patients with FM and/or CFS engaged in less high-intensity physical activities than that recorded for sedentary control subjects. This reduced peak activity was correlated with measures of poor physical function. The observed associations may be relevant to the design of behavioral activation programs, because activity levels appear to be contingent on, rather than predictive of, symptoms.

Razumovsky AY, DeBusk K, Calkins H, Snader S, Lucas KE, Vyas P, Hanley DF, Rowe PC. · Departments of Anesthesiology/Critical Care Medicine, Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · J Neuroimaging. · Pubmed #12593133 No free full text.

Abstract: BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress. METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD. RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002). CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. · Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, NIH, 10 Center Drive, Building 10, Room 9D42, MSC 1583, Bethesda, MD 20892-1583, USA. · Hum Reprod. · Pubmed #12351553 links to  free full text

Abstract: BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.

Barron DF, Cohen BA, Geraghty MT, Violand R, Rowe PC. · Department of Pediatrics, and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA. · J Pediatr. · Pubmed #12219066 No free full text.

Abstract: OBJECTIVE: To determine whether children with chronic fatigue syndrome (CFS) have a higher prevalence of joint hypermobility than gender-matched controls.Study design: Matched case-control study comparing the Beighton joint hypermobility scores in 58 consecutive children with CFS (incident cases) with 58 otherwise healthy controls referred to a dermatology clinic for evaluation of common skin problems. A second group of 58 patients previously diagnosed with CFS (prevalent cases) was matched by gender to the incident cases to evaluate temporal changes in referral patterns. RESULTS: Of the 58 patients in each group, 71% were female. The median Beighton scores were higher in incident CFS cases than in healthy controls (4 vs 1, P <.001). More incident CFS cases had Beighton scores >/=4 (consistent with joint hypermobility), 60% versus 24%, P <.0001. Incident and prevalent CFS cases had similar Beighton scores. The odds ratio for hypermobility in all patients with CFS versus healthy controls was 3.5 (P <.001; 95% CI, 1.6-7.5). CONCLUSIONS: Joint hypermobility is more common in patients with CFS than in otherwise healthy children with common skin disorders. The etiologic significance of the observed association remains to be defined.

Arnold MC, Papanicolaou DA, O'Grady JA, Lotsikas A, Dale JK, Straus SE, Grafman J. · National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1440, USA. · Psychol Med. · Pubmed #12214788 No free full text.

Abstract: BACKGROUND: Individuals with acute infections experience a range of symptoms including fatigue, malaise, muscle aches, and difficulties with concentration and memory that are usually self-limited. This cluster of symptoms is otherwise, similar to those that characterize chronic fatigue syndrome (CFS). The goal of the present study was to evaluate the cognitive and psychological functioning of CFS patients and normal controls (NCs) when they both were experiencing acute influenza-like symptoms. To induce influenza-like symptoms, we administered interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase immunological and endocrine responses. METHODS: Nineteen patients who met the 1994 International CFS Study Group Criteria and ten normal controls (NCs) completed routine clinical evaluations, neuropsychological tests of short-term memory, selective attention, and executive control, and self-ratings of somatic symptoms and psychological mood before, shortly following, and 1 day after IL-6 administration. RESULTS: CFS patients consistently reported more somatic symptoms, even when both groups perceived that they were ill. Both groups somatic symptoms increased during the IL-6 challenge, but the CFS patients symptoms increased more rapidly than controls. In general, the CFS patients performed similarly to NCs on the cognitive measures before, during, and after the IL-6. In contrast to predictions, IL-6 provocation did not impair the cognitive performance of either CFS patients or NCs. CONCLUSIONS: The IL-6 provocation exacerbated the patients self-reported symptoms but did not reveal notable cognitive impairments between patients and controls during cytokine-induced acute influenza-like symptoms.

Leng S, Chaves P, Koenig K, Walston J. · Division of Geriatric Medicine and Gerontology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · J Am Geriatr Soc. · Pubmed #12133023 No free full text.

Abstract: OBJECTIVES: To determine specific physiological correlates of the geriatric syndrome of frailty that warrant further investigation. DESIGN: Population-based case-control study. SETTING: General Clinical Research Center at Johns Hopkins Bayview Medical Center. PARTICIPANTS: Community-dwelling adults aged 74 and older from Baltimore, Maryland. MEASUREMENTS: Frailty status was determined using a recently validated screening tool that consists of weight loss, fatigue, low levels of physical activity, and measurements of grip strength and walking speed. Serum interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay, and standard complete blood count was performed using a Coulter counter. RESULTS: Eleven frail and 19 nonfrail subjects with mean age +/- standard deviation of 84.9 +/- 6.7 vs 81.3 +/- 4.1 years, respectively, completed the study. The frail subjects had significantly higher serum IL-6 levels and significantly lower hemoglobin and hematocrit than the nonfrail subjects (4.4 +/-2.9 vs 2.8 +/- 1.6 pg/mL, 12.1 +/- 1.1 vs 13.9 +/- 1.0 g/dL, and 35.8% +/- 3.1% vs 40.6% +/- 2.8%, respectively). No significant difference was observed in mean corpuscular volume, red blood cell distribution width, or white blood cell and platelet counts between the frail and nonfrail groups. Furthermore, there was an inverse correlation between serum IL-6 level and hemoglobin (Pearson's correlation coefficient: -0.46) and hematocrit (-0.48) in the frail group but not in the nonfrail group. CONCLUSION: These results suggest that frail subjects have evidence of inflammation and lower hemoglobin and hematocrit levels. This subclinical anemia is normocytic and is hence unlikely due to myelosuppression or iron deficiency and is potentially related to the increased chronic inflammatory state marked by serum IL-6 elevation. Further studies are indicated to better characterize the immune and hematological changes that underlie frailty.

Pastel RH. · Radiation Pathophysiology and Toxicology Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. · Mil Med. · Pubmed #11873498 No free full text.

Abstract: The primary health effect of Chernobyl has been widespread psychological distress in liquidators (workers brought in for cleanup), evacuees, residents of contaminated areas, and residents of adjacent noncontaminated areas. Several psychoneurological syndromes characterized by multiple unexplained physical symptoms including fatigue, sleep and mood disturbances, impaired memory and concentration, and muscle and/or joint pain have been reported in the Russian literature. These syndromes, which resemble chronic fatigue syndrome and fibromyalgia, are probably not due to direct effects of radiation because they do not appear to be dose related to radiation exposure and because they occur in areas of both high and low contamination.

Morgen K, Martin R, Stone RD, Grafman J, Kadom N, McFarland HF, Marques A. · Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1400, USA. · Neurology. · Pubmed #11739813 No free full text.

Abstract: OBJECTIVE: To determine patterns of abnormalities on cerebral MRI that may characterize subgroups of patients with post-treatment Lyme disease syndrome (PTLDS) and to help identify pathomechanisms of disease. METHODS: The authors analyzed the distribution of cerebral lesions in a cohort of 27 patients with PTLDS. A subgroup of eight patients with PTLDS was further studied using whole-brain magnetization transfer ratio measures to identify abnormalities not seen on T2-weighted images. RESULTS: Four patients had focal neurologic deficits, relapsing-remitting disease, and lesions in a distribution typical of MS. Twenty-three patients presented with nonfocal symptoms such as fatigue, subjective memory deficits, and mood disturbance. Twelve of these patients had normal MRI, including the more sensitive fluid-attenuated inversion recovery sequence, 10 had primarily punctate and subcortical lesions, and one patient had multiple periventricular lesions. CONCLUSIONS: In a portion of patients with post-treatment Lyme disease syndrome, white-matter hyperintensities tend to occur in subcortical arteriolar watershed areas and are not specific. Magnetization transfer ratio analysis did not provide evidence for structural abnormalities of the brain parenchyma in patients with nonfocal disease.

Addington AM, Gallo JJ, Ford DE, Eaton WW. · Department of Mental Hygiene, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA. · Psychol Med. · Pubmed #11513371 No free full text.

Abstract: BACKGROUND: Fatigue is a common, non-specific, subjective symptom associated with several medical and psychiatric illnesses. The purpose of this investigation was to explore further the epidemiology of unexplained fatigue in the general population and the relationship between fatigue and depression. METHODS: The design was a prospective population-based study. Subjects included community-dwelling adults who were participants of the Baltimore sample of the Epidemiologic Catchment Area Program in 1981 and who were reinterviewed 13 years later. Lay interviewers using the Diagnostic Interview Schedule interviewed subjects. RESULTS: Number of somatization symptoms and history of a dysphoric episode at baseline were the two strongest predictors of both new onset of fatigue as well as recurrent/chronic fatigue over the 13-year follow-up interval. In addition, individuals who reported a history of unexplained fatigue at baseline as well as during the follow-up, were at markedly increased risk for new onset major depression as compared to those who never reported such fatigue, (RR = 28.4, 95% CI) (11.7, 68.0). Similarly, respondents who developed new fatigue or had remitted fatigue after 1981 were also at increased risk for developing major depression. CONCLUSIONS: Somatization was the strongest predictor of both new and chronic fatigue with unknown cause. In addition, fatigue was both predictive and a consequence of the depression syndrome.

Curt GA. · National Cancer Institute, National Institutes of Health, Clinical Center, Oncology Program, Building 10, Room 12N214, 9000 Rockville Pike, Bethesda, Maryland 20892, USA. · Recenti Prog Med. · Pubmed #11433722 No free full text.

Abstract: As oncologists have become more effective in alleviating pain, nausea and depression, fatigue has emerged as the most important symptom suffered by cancer patients. Indeed, the current literature suggests that fatigue is currently the most important untreated symptom in cancer medicine. In recent surveys of patients and their caregivers, fatigue is more important for the quality of life than pain, nausea or depression. Yet these same surveys confirm that oncologists underestimate the importance of cancer related fatigue. This may be partly because patients often do not fully share the full nature of their concerns. When patients do raise the issue of fatigue, the physicians' recommendations are often non specific. However, recent research has shown that fatigue is not inevitable and untreatable, but a symptom amenable to differential diagnosis and specific intervention. Like pain, fatigue is intrinsically a subjective problem where the doctor relies on the patient's reporting. Weakness, exhaustion, lethargy and asthenia are all used as functional descriptions of fatigue. While these are descriptive terms, clinical research in the measurement and alleviation of fatigue requires reproducible measurement tools. Several studies already exist and have begun to explore this important area of symptom management.

Shoemaker RC, Hudnell HK. · McCready Outpatient Services Center, Pocomoke City, Maryland, USA. · Environ Health Perspect. · Pubmed #11401768 links to  free full text

Abstract: The human illness designated as possible estuarine-associated syndrome (PEAS) by the Centers for Disease Control and Prevention (CDC) has been associated with exposure to estuaries inhabited by toxin-forming dinoflagellates, including members of the fish-killing toxic Pfiesteria complex (TPC), Pfiesteria piscicida and Pfiesteria shumwayae. Humans may be exposed through direct contact with estuarine water or by inhalation of aerosolized or volatilized toxin(s). The five cases reported here demonstrate the full spectrum of symptoms experienced during acute and chronic stages of this suspected neurotoxin-mediated illness. The nonspecific symptoms most commonly reported are cough, secretory diarrhea, headache, fatigue, memory impairment, rash, difficulty in concentrating, light sensitivity, burning skin upon water contact, muscle ache, and abdominal pain. Less frequently encountered symptoms are upper airway obstruction, shortness of breath, confusion, red or tearing eyes, weakness, and vertigo. Some patients experience as few as four of these symptoms. The discovery that an indicator of visual pattern-detection ability, visual contrast sensitivity (VCS), is sharply reduced in affected individuals has provided an objective indicator that is useful in diagnosing and monitoring PEAS. VCS deficits are present in both acute and chronic PEAS, and VCS recovers during cholestyramine treatment coincident with symptom abatement. Although PEAS cannot yet be definitively associated with TPC exposure, resolution with cholestyramine treatment suggests a neurotoxin-mediated illness.

Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Anonymous00007. · Center on Aging and Health, The John Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. · J Gerontol A Biol Sci Med Sci. · Pubmed #11253156 No free full text.

Abstract: BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

Nawab SS, Miller CS, Dale JK, Greenberg BD, Friedman TC, Chrousos GP, Straus SE, Rosenthal NE. · Section on Biological Rhythms, National Institute of Mental Health, Bethesda, MD 20892-1390, USA. · Psychiatry Res. · Pubmed #10904124 No free full text.

Abstract: Two hundred and twenty-five subjects, including normal volunteers and patients with previously documented seasonal affective disorder (SAD), chronic fatigue syndrome (CFS), Cushing's syndrome, Addison's disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported sensitivity to various chemical exposures. Patients with CFS, Addison's disease and SAD self-reported more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity than men. This report suggests that chemical sensitivity may be a relevant area to explore in certain medical and psychiatric populations. A possible relationship between reported chemical sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed.

Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT. · Department of Pediatrics, Center for Hereditary Eye Diseases, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · J Pediatr. · Pubmed #10518084 No free full text.

Abstract: OBJECTIVE: To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. STUDY DESIGN: Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. RESULTS: Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. CONCLUSIONS: Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.