Category: Pathophysiology

Blood flow and muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced blood flow and oxidative delivery to skeletal muscle. Patients with CFS according to CDC (Center for Disease Control) criteria ( n =19) were compared with normal sedentary subjects ( n =11). Muscle blood flow was measured with Doppler ultrasound after cuff ischaemia and exercise. Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemic oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous wavelength near-IR spectroscopy. Muscle metabolism was measured using (31)P magnetic resonance spectroscopy. CFS patients and controls were not different in the peak blood flow after cuff ischaemia, the rate of recovery of phosphocreatine after submaximal exercise, and the rate of recovery of oxygen saturation after cuff ischaemia. In conclusion, CFS patients showed no deficit in blood flow or oxidative metabolism. This suggests that CFS symptoms do not require abnormal peripheral function.

 

Source: McCully KK, Smith S, Rajaei S, Leigh JS Jr, Natelson BH. Blood flow and muscle metabolism in chronic fatigue syndrome.  Clin Sci (Lond). 2003 Jun;104(6):641-7. http://www.ncbi.nlm.nih.gov/pubmed/12589704

 

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome

Abstract:

In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation.

A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.

 

Source: Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA. Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett. 2003 Jan 2;335(3):151-4. http://www.ncbi.nlm.nih.gov/pubmed/12531455

 

Chronic fatigue syndrome: what role does the autonomic nervous system play in the pathophysiology of this complex illness?

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races and socioeconomic groups and both genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the autonomic nervous system (ANS). A symposium was organized in December 2000 to explore the possibility of an association between ANS dysfunction and CFS, with special emphasis on the interactions between ANS dysfunction and other abnormalities noted in the immune and endocrine systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Copyright 2002 S. Karger AG, Basel

 

Source: Gerrity TR, Bates J, Bell DS, Chrousos G, Furst G, Hedrick T, Hurwitz B, Kula RW, Levine SM, Moore RC, Schondorf R. Chronic fatigue syndrome: what role does the autonomic nervous system play in the pathophysiology of this complex illness? Neuroimmunomodulation. 2002-2003;10(3):134-41. http://www.ncbi.nlm.nih.gov/pubmed/12481153

 

Chronic fatigue syndrome: a risk factor for osteopenia?

Abstract:

No data documenting a possible depletion of bone mineral density in patients with chronic fatigue syndrome (CFS) are currently available. However, recent pathophysiological observations in CFS patients may have deleterious consequences on bone density.

Firstly, the deregulation of the 2,5A synthetase RNase L antiviral pathway and its associated channelopathy, implicates increased demands for calcium and consequent increased calcium-re-absorption from the skeletal system.

Secondly, Mycoplasma fermentans which has been frequently associated with CFS, produces a lipopeptide, named 2-kDa macrophage-activating lipopeptide (MALP-2), which stimulates macrophages. MALP-2 has been shown to enhance bone resorption in a dose-dependent manner, at least in part by stimulating the formation of prostaglandins.

Thirdly, decreased levels of insulin-like growth factor I (IGF-I) have been reported in CFS-patients. IGF-I is critical to the proliferation of osteoblasts. Consequently, depleted levels of IGF-I may shift the balance between osteoclastic and osteoblastic activity towards bone resorption.

 

Source: Nijs J, De Meirleir K, Englebienne P, McGregor N. Chronic fatigue syndrome: a risk factor for osteopenia? Med Hypotheses. 2003 Jan;60(1):65-8. http://www.ncbi.nlm.nih.gov/pubmed/12450768

 

High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients

Abstract:

Prevalence of Mycoplasma species infections in chronic fatigue syndrome (CFS) has been extensively reported in the scientific literature. However, all previous reports highlighted the presence of Mycoplasmas in American patients. In this prospective study, the presence of Mycoplasma fermentans, M. penetrans, M. pneumoniae and M. hominis in the blood of 261 European CFS patients and 36 healthy volunteers was examined using forensic polymerase chain reaction.

One hundred and seventy-nine (68.6%) patients were infected by at least one species of Mycoplasma, compared to two out of 36 (5.6%) in the control sample (P<0.001). Among Mycoplasma-infected patients, M. hominis was the most frequently observed infection (n=96; 36.8% of the overall sample), followed by M. pneumoniae and M. fermentans infections (equal frequencies; n=67; 25.7%). M. penetrans infections were not found. Multiple mycoplasmal infections were detected in 45 patients (17.2%). Compared to American CFS patients (M. pneumoniae>M. hominis>M. penetrans), a slightly different pattern of mycoplasmal infections was found in European CFS patients (M. hominis>M. pneumoniae, M. fermentansz.Gt;M. penetrans).

 

Source: Nijs J, Nicolson GL, De Becker P, Coomans D, De Meirleir K. High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients. FEMS Immunol Med Microbiol. 2002 Nov 15;34(3):209-14. http://femsim.oxfordjournals.org/content/34/3/209.long (Full article)

 

Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain

Abstract:

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation.

Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate.

When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann’s area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum.

These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

 

Source: Kuratsune H, Yamaguti K, Lindh G, Evengård B, Hagberg G, Matsumura K, Iwase M, Onoe H, Takahashi M, Machii T, Kanakura Y, Kitani T, Långström B, Watanabe Y. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage. 2002 Nov;17(3):1256-65. http://www.ncbi.nlm.nih.gov/pubmed/12414265

 

Chronic fatigue syndrome: neurological findings may be related to blood–brain barrier permeability

Abstract:

Despite volumes of international research, the etiology of chronic fatigue syndrome (CFS) remains elusive. There is, however, considerable evidence that CFS is a disorder involving the central nervous system (CNS).

It is our hypothesis that altered permeability of the blood-brain barrier (BBB) may contribute to ongoing signs and symptoms found in CFS. To support this hypothesis we have examined agents that can increase the blood-brain barrier permeability (BBBP) and those that may be involved in CFS.

The factors which can compromise the normal BBBP in CFS include viruses, cytokines, 5-hydroxytryptamine, peroxynitrite, nitric oxide, stress, glutathione depletion, essential fatty acid deficiency, and N-methyl-D-aspartate overactivity. It is possible that breakdown of normal BBBP leads to CNS cellular dysfunction and disruptions of neuronal transmission in CFS. Abnormal changes in BBBP have been linked to a number of disorders involving the CNS; based on review of the literature we conclude that the BBB integrity in CFS warrants investigation.

Copyright 2001 Harcourt Publishers Ltd.

 

Source: Bested AC, Saunders PR, Logan AC. Chronic fatigue syndrome: neurological findings may be related to blood–brain barrier permeability. Med Hypotheses. 2001 Aug;57(2):231-7. http://www.ncbi.nlm.nih.gov/pubmed/11461179

 

Chronic fatigue syndrome following a toxic exposure

Abstract:

Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc.

In the National Reference Center for CFS Study at the Department of Infectious Diseases of ‘G. D’Annunzio’ University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression.

All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS.

 

Source: Racciatti D, Vecchiet J, Ceccomancini A, Ricci F, Pizzigallo E. Chronic fatigue syndrome following a toxic exposure. Sci Total Environ. 2001 Apr 10;270(1-3):27-31. http://www.ncbi.nlm.nih.gov/pubmed/11327394

 

Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome

Abstract:

The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms.

In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight-matched and were known to have normal basal metabolic rates and thyroid function.

CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. CBT time series were analysed by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and sigma2. Average parameters for each group were compared by Student’s t-test.

By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0.02). The optimal harmonic-regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant.

We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.

 

Source: Hamilos DL, Nutter D, Gershtenson J, Ikle D, Hamilos SS, Redmond DP, Di Clementi JD, Schmaling KB, Jones JF. Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome. Clin Physiol. 2001 Mar;21(2):184-95. http://www.ncbi.nlm.nih.gov/pubmed/11318826

 

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism.

In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses.

Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

 

Source: Fulle S, Mecocci P, Fanó G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF. Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radic Biol Med. 2000 Dec 15;29(12):1252-9. http://www.ncbi.nlm.nih.gov/pubmed/11118815