Category: Pathophysiology

Sympathetic overactivity in subjects complaining of unexplained fatigue

Abstract:

Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate.

Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively.

We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest.

The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.

 

Source: Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A. Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci (Lond). 1994 Dec;87(6):655-61. http://www.ncbi.nlm.nih.gov/pubmed/7874856

 

Chronic fatigue syndrome–a controlled cross-sectional study

Abstract:

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals.

Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range.

All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Comment in: [Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. Chronic fatigue syndrome–a controlled cross-sectional study. Ugeskr Laeger. 1994 Nov 14;156(46):6836-40. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839498

 

Neurasthenic fatigue, chemical sensitivity and GABAa receptor toxins

Abstract:

Following observation of fatigue syndromes in people who have been occupationally exposed to pesticides and insecticides which exert their toxicity through the GABAa receptor, we have formulated the hypothesis that fatigue syndromes in general may be secondary to altered sensitivity of the GABAa receptor. We discuss the possible involvement of organochlorine compounds which are widespread in the environment. Organophosphate compounds may have similar toxic effects through damaged cholinergic input to the dentate gyrus of the hippocampus where cholinergic and GABAergic transmission are closely linked.

 

Source: Corrigan FM, MacDonald S, Brown A, Armstrong K, Armstrong EM. Neurasthenic fatigue, chemical sensitivity and GABAa receptor toxins. Med Hypotheses. 1994 Oct;43(4):195-200. http://www.ncbi.nlm.nih.gov/pubmed/7838000

 

Single fibre EMG studies in chronic fatigue syndrome: a reappraisal

Comment on: Single fibre EMG studies in chronic fatigue syndrome: a reappraisal. [J Neurol Neurosurg Psychiatry. 1994]

 

We were interested in the short report from Roberts and Byrne concerning single fibre EMG studies in chronic fatigue syndrome. They concluded that there was no evidence of abnormality at the terminal axon, neuromuscular junction, or muscle membrane in patients with chronic fatigue syndrome-a finding that concurs with our own of essentially normal jitter in 34 of 35 patients with chronic unexplained fatigue. We did detect some evidence of raised fibre density in a small subgroup of patients with pronounced myalgia who also had mild abnormalities on muscle biopsy.

Raised fibre density is usually a result of collateral sprouting after reinnervation, but can also be due to fibre splitting as can occur in some myopathic states. Therefore we believe that fibre density estimation performed in addition to jitter measurement adds considerably to the information obtained from single fibre EMG studies.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073160/pdf/jnnpsyc00039-0137a.pdf

 

Source: Connolly S, Fowler CJ. Single fibre EMG studies in chronic fatigue syndrome: a reappraisal. J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1157. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073160/

 

Fatigue syndromes revisited: the possible role of porphyrins

Abstract:

The author sees many patients with chronic oral problems of unknown etiology. It has been noticed that many of these patients also have complex medical histories. Fatigue and pain are two of the most common features observed. Some, but not all, also have other definitive medical diagnoses. Those patients with appropriate symptoms have been tested for porphyrins and porphyrin enzyme activity. Advances in molecular biology have led to the availability of a number of porphyrin enzymes for routine testing. The results are interesting and suggest abnormal porphyrin metabolism may be more prevalent than is currently thought.

 

Source: Downey DC. Fatigue syndromes revisited: the possible role of porphyrins. Med Hypotheses. 1994 May;42(5):285-90. http://www.ncbi.nlm.nih.gov/pubmed/7935069

 

The ocular signs and symptoms of chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic Fatigue syndrome (CFS) is a relatively newly defined clinical entity that affects multiple systems including the ocular system. These effects have not been well documented.

METHODS: 25 consecutive CFS patients were evaluated and the ocular signs and symptoms were described.

RESULTS: Significant ocular symptoms were present in all 25 patients. The most common clinical findings were abnormalities of the preocular tear film and ocular surface (19 patients) and reduced accommodation for age (18 patients).

CONCLUSIONS: CFS affects the ocular system in many ways. Eye care practitioners should pay particular attention to accommodative needs, ocular surface disease and tear film dysfunction when examining these patients. Further research into the pathophysiology of these ocular findings may lead to a better understanding of the pathophysiology of CFS.

 

Source: Caffery BE, Josephson JE, Samek MJ. The ocular signs and symptoms of chronic fatigue syndrome. J Am Optom Assoc. 1994 Mar;65(3):187-91. http://www.ncbi.nlm.nih.gov/pubmed/8201170

 

Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients

 

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS.

Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group.

Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.

 

Source: Peterson PK, Sirr SA, Grammith FC, Schenck CH, Pheley AM, Hu S, Chao CC. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Lab Immunol. 1994 Mar;1(2):222-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/pdf/cdli00002-0112.pdf

 

Clinical studies with the NOVA ISE for IMg2+

Abstract:

The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISE’s for IMg2+ in the diagnosis and treatment of disease states.

 

Source: Altura BT, Burack JL, Cracco RQ, Galland L, Handwerker SM, Markell MS, Mauskop A, Memon ZS, Resnick LM, Zisbrod Z, et al. Clinical studies with the NOVA ISE for Img2+. Scand J Clin Lab Invest Suppl. 1994;217:53-67. http://www.ncbi.nlm.nih.gov/pubmed/7939386

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214

 

 

Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome

Abstract:

AIMS: To investigate in detail various biochemical and pathophysiological indices of muscle pathology in acute onset post-viral fatigue syndrome (PVFS).

METHODS: Twenty three patients with PVFS (of mean duration 4.6 years) were subjected to needle biopsy for histomorphometry and total RNA contents. Plasma analysis included serology and creatine kinase activities. Indices of whole body mass were also measured–namely, whole body potassium content and plasma carnosinase activities.

RESULTS: About 80% of the patients had serology indicative of persistent enteroviral infection as determined by VP1 antigen assay. Only about 10% of that same group of patients had serological indications of current enterovirus infection by IgM assay; a separate subset of 10% showed antibody changes suggestive of reactivation of Epstein-Barr virus. Quantitative morphometric analysis of skeletal muscle fibres indicated that the quadriceps muscle was normal or displayed only minor abnormalities in 22 patients. The Quetelet’s Index (body mass index) and whole-body potassium values (index of lean body mass) were not affected in PVFS. The mean plasma carnosinase and creatinine kinase activities were also generally normal in these patients. The mean muscle RNA composition–mg RNA/mg DNA: was significantly reduced in acute onset PVFS by about 15%. The protein:DNA ratio was not significantly affected.

CONCLUSIONS: Patients with acute onset PVFS, therefore, lose muscle protein synthetic potential, but not muscle bulk. Histopathology is consistent with these observations. These perturbations may contribute to the apparent feature of perceived muscle weakness associated with the persistent viral infection in the muscle themselves.

 

Source: Preedy VR, Smith DG, Salisbury JR, Peters TJ. Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome. J Clin Pathol. 1993 Aug;46(8):722-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501456/