Clinical laboratory test findings in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects.

METHODS: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests.

RESULTS:Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful.

CONCLUSIONS: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Comment in: Clinical laboratory test findings in patients with chronic fatigue syndrome. [Arch Intern Med. 1995]

 

Source: Bates DW, Buchwald D, Lee J, Kith P, Doolittle T, Rutherford C, Churchill WH, Schur PH, Wener M, Wybenga D, et al. Clinical laboratory test findings in patients with chronic fatigue syndrome. Arch Intern Med. 1995 Jan 9;155(1):97-103. http://www.ncbi.nlm.nih.gov/pubmed/7632202

 

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome

Abstract:

A simian cytomegalovirus-related stealth virus, isolated from a patient with the chronic fatigue syndrome, induced an acute neurological illness when inoculated into cats. Histological examination of brain tissue showed foci of cells with cytoplasmic vacuolization and an absence of any inflammatory reaction. Electron microscopy confirmed the presence of herpes-like viral particles and viral-like products in the brain of an inoculated animal. These findings support the role of stealth viruses in the pathogenesis of human neurological diseases and provide an animal model to evaluate potential antiviral therapy.

 

Source: Martin WJ, Glass RT. Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. Pathobiology. 1995;63(3):115-8. http://www.ncbi.nlm.nih.gov/pubmed/8821627

 

Parvovirus B19 infection–persistence and genetic variation

Abstract:

53 patients with acute B19 infection were studied; symptoms at acute infection were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine fetal death (n = 1). These patients were followed for 26-85 months (mean 57 months) and re-assessed for persistent symptoms, anti-B19 antibodies, and B19 DNA. At follow-up, 7 individuals were positive for serum B19 DNA, compared with none of the controls (2-tailed p value = 0.016). All 7 of those persistently infected were women, 3 of whom had symptoms; 1 had a chronic haemolytic anaemia (initial presentation was aplastic crisis); 1 had persistent arthralgia in both knees (initial presentation was bilateral knee arthralgia); and 1 had arthralgia in one knee and chronic fatigue syndrome (initial presentation was bilateral arthralgia in knees and shoulders). For the 7 persistently infected patients, serum from the time of diagnosis of acute B19 infection was available for 4, all of which contained B19 DNA. With single-stranded conformational polymorphism (SSCP) assay of these 11 PCR products, identical SSCP types were demonstrated in 5 of 7 follow-up isolates. In 2 of the 4 cases for which both acute and follow-up PCR product was available, the SSCP type of the follow-up product was different from that of the acute product. Two B19 virus types were demonstrated in one patient (with persistent arthralgia and chronic fatigue syndrome) at follow-up assessment.

 

Source: Kerr JR, Curran MD, Moore JE, Murphy PG. Parvovirus B19 infection–persistence and genetic variation. Scand J Infect Dis. 1995;27(6):551-7. http://www.ncbi.nlm.nih.gov/pubmed/8685632

 

The Epstein-Barr virus and chronic fatigue syndrome

Abstract:

Lately discovered chronic fatigue syndrome is associated with Epstein-Barr virus infection. The objective of this paper was to detect this syndrome in our patients. 31 patients with cured acute infective mononucleosis were examined by questionnaire, physical check-up and laboratory analyses in order to detect disorders characteristic for chronic fatigue syndrome. Six months after they had been cured, out of 7 patients 5 patients complained of frequent sore throat, fatigue and exhaustion, and a year later, all 5 patients were sleepy and tired all the time. More than a year after the acute illness 19 patients were examined and in 5.6% frequent sore throat and enlarged neck lymph nodes occurred. The gathered results point to disorders characteristic for chronic fatigue syndrome in a high percentage. This pilot study should only be the beginning of examinations of this kind.

 

Source: Jovanović J, Cvjetković D, Brkić S, Madle-Samardzija N. The Epstein-Barr virus and chronic fatigue syndrome. Med Pregl. 1995;48(11-12):391-3. [Article in Croatian] http://www.ncbi.nlm.nih.gov/pubmed/8643052

 

Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) suffer from disabling physical and mental fatigue. Abnormalities in mitochondrial function can lead to fatigue and weakness. Ultrastructural mitochondrial abnormalities have been reported to be present in CFS patients.

We obtained percutaneous needle muscle biopsies from 15 CFS patients and 15 age- and sex-matched controls. We investigated previously reported ultrastructural abnormalites in CFS: subsarcolemmal mitochondrial aggregates, intermyofibrillar mitochondrial aggregates, mitochondrial circumference, area, pleomorphism and the presence of compartmentalization of the inner mitochondrial membrane. All of the steps of tissue processing, electron microscopy and data abstracting and analysis were performed in a totally blinded fashion. All of our data were rigorously quantified.

We found no difference in any of these studied parameters between CFS patients and controls. Although there is no ultrastructural mitochondrial abnormality in CFS patients, other lines of evidence suggest the presence of a possible functional mitochondrial abnormality.

 

Source: Plioplys AV, Plioplys S. Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome. Neuropsychobiology. 1995;32(4):175-81. http://www.ncbi.nlm.nih.gov/pubmed/8587699

 

Fatigue brought on by malfunction of the central and peripheral nervous systems

Abstract:

Increased fatigability necessarily occurs in every patient with muscle weakness, regardless of whether the latter is due to a central or peripheral neurological disorder. The tendency for disuse to increase fatigability, as a secondary phenomenon, must also be considered; disuse affects both motoneuron recruitment and the biochemical and physiological properties of the muscle fibers. In recent studies impaired recruitment has been observed in postpolio patients, while patients with multiple sclerosis or spinal cord injury have shown, in addition, altered neuromuscular function. Findings are also presented in ALS and the chronic fatigue syndrome. In general, the most dramatic increases in fatigability take place in disorders of the peripheral nervous system and almost any cell component can be incriminated. There is a need to study fatigability systematically in neurology and rehabilitation.

 

Source: McComas AJ, Miller RG, Gandevia SC. Fatigue brought on by malfunction of the central and peripheral nervous systems. Adv Exp Med Biol. 1995;384:495-512. http://www.ncbi.nlm.nih.gov/pubmed/8585475

 

Serum levels of carnitine in chronic fatigue syndrome: clinical correlates

Abstract:

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in chronic fatigue syndrome (CFS) patients. One previous investigation has reported decreased acylcarnitine levels in 38 CFS patients.

We investigated 35 CFS patients (27 females and 8 males); our results indicate that CFS patients have statistically significantly lower serum total carnitine, free carnitine and acylcarnitine levels, not only lower acylcarnitine levels as previously reported. We also found a statistically significant correlation between serum levels of total and free carnitine and clinical symptomatology. Higher serum carnitine levels correlated with better functional capacity.

These findings may be indicative of mitochondrial dysfunction, which may contribute to or cause symptoms of fatigue in CFS patients.

 

Source: Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology. 1995;32(3):132-8. http://www.ncbi.nlm.nih.gov/pubmed/8544970

 

Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

To examine the degree and nature of cognitive impairments in chronic fatigue syndrome, a comprehensive neuropsychological battery was given to patients with chronic fatigue syndrome, multiple sclerosis, depressed patients, and healthy controls. The battery included tests of attention and concentration, information processing speed, verbal and visual memory, intellectual ability, and concept formation. Measures of depression and anxiety were also obtained.

The chronic fatigue syndrome group did not differ from the depressed group in overall neuropsychological performance, but differed from the multiple sclerosis and control groups. The most significant impairment was in information processing speed in the chronic fatigue syndrome group. Depression and anxiety were not related to neuropsychological performance. The influence of reduced information processing on other areas of cognition is discussed.

 

Source: DeLuca J, Johnson SK, Beldowicz D, Natelson BH. Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression. J Neurol Neurosurg Psychiatry. 1995 Jan;58(1):38-43. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073266/ (Full article)

 

Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome

Abstract:

The justification for disordered chronobiology for fibromyalgia and chronic fatigue syndrome (CFS) is based on the following evidence: The studies on disordered sleep physiology and the symptoms of fibromyalgia and CFS; the experimental studies that draw a link between interleukin-1 (IL-1), immune-neuroendocrine-thermal systems and the sleep-wake cycle; studies and preliminary data of the inter-relationships of sleep-wakefulness, IL-1, and aspects of peripheral immune and neuroendocrine functions in healthy men and in women during differing phases of the menstrual cycle; and the observations of alterations in the immune-neuroendocrine functions of patients with fibromyalgia and CFS (Moldofsky, 1993b, d). Time series analyses of measures of the circadian pattern of the sleep-wake behavioural system, immune, neuroendocrine and temperature functions in patients with fibromyalgia and CFS should determine whether alterations of aspects of the neuro-immune-endocrine systems that accompany disordered sleep physiology result in nonrestorative sleep, pain, fatigue, cognitive and mood symptoms in patients with fibromyalgia and CFS.

 

Source: Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. Adv Neuroimmunol. 1995;5(1):39-56. http://www.ncbi.nlm.nih.gov/pubmed/7795892

 

Vestibular function test anomalies in patients with chronic fatigue syndrome

Abstract:

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.

 

Source: Ash-Bernal R, Wall C 3rd, Komaroff AL, Bell D, Oas JG, Payman RN, Fagioli LR. Vestibular function test anomalies in patients with chronic fatigue syndrome. Acta Otolaryngol. 1995 Jan;115(1):9-17. http://www.ncbi.nlm.nih.gov/pubmed/7762393