Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01). Additionally, no significant differences were found between the healthy control subjects and any of the disease comparison groups. The current finding that TGF-beta is significantly elevated among patients with CFS supports the findings of two previous studies examining smaller numbers of CFS patients. In conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS.

Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome.

Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of interest to examine if these two syndromes have pathogenetic as well as clinical features in common. Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy controls. An attractive hypothesis relating sleep disturbance, altered somatotropic neuroendocrine function and fibromyalgia symptoms has been put forward as a plausible pathogenic mechanism for fibromyalgia syndrome. We therefore sought to investigate the level of somatomedin C in patients with chronic fatigue syndrome. Somatomedin C levels were determined by radioimmunoassay in frozen serum specimens from 49 patients with CFS and 30 healthy blood donor control subjects of similar age and gender. Somatomedin C levels were higher in patients with CFS than in healthy control subjects (255.3 +/- 68.5 vs 211.9 +/- 76.2, P = 0.01). There was no effect of gender, use of nonsteroidal anti-inflammatory drugs or tricyclic drugs on levels of somatomedin C. There was a tendency for somatomedin C levels to fall with age. In contrast to patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic neuroendocrine axis.

Immunoglobulin subclass levels in chronic fatigue syndrome.

The levels of immunoglobulin subclasses were determined for 46 patients meeting the original Centers for Disease Control case definition of chronic fatigue syndrome and were compared to values obtained for 50 age- and gender-matched healthy volunteer blood donor controls. The levels of immunoglobulin subclasses in these groups were further compared to a third group of additional chronic fatigue syndrome cases from whom samples had been obtained and frozen prospectively over a period of 7 years. These data do not demonstrate significant immunoglobulin subclass deficiencies in patients with chronic fatigue syndrome.

Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups.

PURPOSE: To measure the functional status and well-being of patients with chronic fatigue syndrome (CFS), and compare them with those of a general population group and six disease comparison groups. PATIENTS AND METHODS: The subjects of the study were patients with CFS (n = 223) from a CFS clinic, a population-based control sample (n = 2,474), and disease comparison groups with hypertension (n = 2,089), congestive heart failure (n = 216), type II diabetes mellitus (n = 163), acute myocardial infarction (n = 107), multiple sclerosis (n = 25), and depression (n = 502). We measured functional status and well-being using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which is a self-administered questionnaire in which lower scores are indicative of greater impairment. RESULTS: Patients with CFS had far lower mean scores than the general population control subjects on all eight SF-36 scales. They also scored significantly lower than patients in all the disease comparison groups other than depression on virtually all the scales. When compared with patients with depression, they scored significantly lower on all the scales except for scales measuring mental health and role disability due to emotional problems, on which they scored significantly higher. The two SF-36 scales reflecting mental health were not correlated with any of the symptoms of CFS except for irritability and depression. CONCLUSION: Patients with CFS had marked impairment, in comparison with the general population and disease comparison groups. Moreover, the degree and pattern of impairment was different from that seen in patients with depression.

Cognitive deficits in patients with chronic fatigue syndrome.

Twenty-nine subjects with chronic fatigue syndrome (CFS) and 25 healthy control subjects were administered a lengthy neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. The primary significant differences between patients and controls were found on tests of learning and memory. These differences remained when the degree of psychiatric symptomatology in the subjects was covaried. Patients on and off psychoactive medications did not differ in their performance on these tasks. These results suggest that at least a subset of CFS patients may experience significant impairments in learning and memory.

An examination of the working case definition of chronic fatigue syndrome.

PURPOSE: Chronic fatigue syndrome (CFS) currently is defined by a working case definition developed under the leadership of the United States Centers for Disease Control and Prevention (CDC) based on a consensus among experienced clinicians. We analyzed the experience from one large center to examine the adequacy of the case definition. PATIENTS AND METHODS: Predefined clinical and laboratory data were collected prospectively from 369 patients with debilitating fatigue, of whom 281 (76%) met the major criteria of the original CDC case definition for CFS: (1) fatigue of at least 6 months' duration, seriously interfering with the patient's life; and (2) without evidence of various organic or psychiatric illnesses that can produce chronic fatigue. The same clinical data were obtained from 311 healthy control subjects and two comparison groups with diseases that can present in a similar fashion; relapsing-remitting multiple sclerosis (n = 25) and major depression (n = 19). RESULTS: All of the minor criteria symptoms from the original CDC case definition distinguished patients with debilitating chronic fatigue from healthy control subjects, and many distinguished the patients with chronic fatigue from the comparison groups with multiple sclerosis and depression: myalgias, postexertional malaise, headaches, and a group of infectious-type symptoms (ie, chronic fever and chills, sore throat, swollen glands in the neck or underarm areas). In addition, two other symptoms not currently part of the case definition discriminated the chronic fatigue patients from the control/comparison groups: anorexia and nausea. Physical examination criteria only infrequently contributed to the diagnosis. Patients meeting the CDC major criteria for CFS also met the minor criteria in 91% of cases. CONCLUSION: Patients meeting the major criteria of the current CDC working case definition of CFS reported symptoms that were clearly distinguishable from the experience of healthy control subjects and from disease comparison groups with multiple sclerosis and depression. Eliminating three symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two others (ie, anorexia and nausea) would appear to strengthen the CDC case definition of CFS.

Absence of parvovirus B19 infection in chronic fatigue syndrome.

OBJECTIVE: To evaluate the presence of infection with parvovirus B19 in patients with chronic fatigue syndrome (CFS) who also had rheumatologic symptoms and mild hematologic abnormalities. METHODS: Seven patients meeting the Centers for Disease Control and Prevention working case definition for CFS who also had mild leukopenia, thrombocytopenia, or anemia were studied. Bone marrow was aspirated from each patient, and examined for morphologic abnormalities, including features seen in marrow infections with parvovirus B19, as well as for parvoviral DNA, using polymerase chain reaction (PCR) amplification. Serum obtained at the time of marrow aspiration was also evaluated for parvoviral DNA, using the PCR method, and was examined for the presence of IgM and IgG antibodies to the virus. RESULTS: No evidence of marrow involvement with parvovirus B19 was found in any patient. One patient had antibody evidence of a transient parvoviral infection, during which time an underlying thrombocytopenia worsened. CONCLUSION: Despite examining a selected group of patients thought most likely to have parvoviral infection, based on clinical and hematologic measures, no evidence of clinically important parvoviral infection was noted. Thus, it seems unlikely that parvovirus B19 plays a role in CFS, even though it has been associated with fibromyalgia, a clinically similar syndrome.

Vestibular function test anomalies in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is distinguished by the new onset of debilitating fatigue that lasts at least 6 months, concomitant with other symptoms to be described later. Many CFS patients complain of disequilibrium, yet the exact type of the balance dysfunction and its function and its location (peripheral vs. central) have not been described. Herein we report results of vestibular function testing performed on 11 CFS patients. These results revealed no predominant pattern of abnormalities. Patients typically performed below average in dynamic posturography testing, with a significant number of falls in the tests requiring subjects to depend heavily on the vestibular system. One patient had abnormal caloric testing, while 3 had abnormally low earth vertical axis rotation (EVA) gains at the higher frequencies tested. As a group, the average gain of EVA was significantly lower than normals in the 0.1 - 1.0 Hz range (p < 0.05). In earth horizontal axis rotation, the CFS group had a higher than normal bias value for the optokinetic (OKN) and eyes open in the dark conditions (p < 0.05), but had normal scores during visual vestibular reflex testing. Five of the 11 subjects had an abnormal OKN bias build up over the course of the run, equal to or actually exceeding the 60 degrees/s target velocity by as much as 14 degrees/s. Altogether, these results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction.