On this page: Muscle Research
Articles of increased importance are highlighted in green *O*
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*O* Alterations in muscles of CFS patients at morphological, biochemical and molecular level. Pizzigallo E, Di Girolamo A, Montanari G, Dragani L, Vecchiet J, Calella G. Journal of Chronic Fatigue Syndrome 1996; 2(2/3) 76-77. Abstract: OBJECTIVES. The peripheral origin of symptoms related to CFS has been hypothesized from various AA and is still under investigation to determine if symptoms can be related to muscular damage. Our studies aimed to look for specific alterations in muscles of CFS patients, followed in our Clinic and enrolled according to the 1988 CDC criteria (Holmes et al.) revised in 1994 by Fukuda et al. (CDC). METHODS. Fourteen CFS patients, 3 male and 11 females, 17 to 60 years old (mean 34.6), mean illness duration 49.9 months, post viral onset in 10 cases, underwent muscular biopsy of the vastus lateralis according to Edwards, et al., using a UCH needle. We analyzed the specimens by electron (EM) and light (LM) microscopy. Moreover, we performed histochemical and quantitative analysis of enzymatic activities and studies of mitochondrial DNA (mtDNA) deletions. RESULTS. All specimens showed: hypotrophy, especially of the type 11 (a and b) fibres; fibres fragmentation, red ragged fibres and fusion events with nuclei centralisation; and fatty and fibrous degeneration. EM observations confirmed these alterations, showed degenerative changes in the I band, and allowed us to detect the poli/pleiomorphism and cristae thickening of the mitochondia. The alterations of the fibres always began from an I band of a sarcomere. The histochemical and quantitative determination of the enzymatic activities showed important reduction, in particular of the cytochrome-oxydase and citrate-synthetase. Finally, the "common deletion" of 4977 bp of the mtdna was increased as high as 3,000 times the normal values in 3 patients. CONCLUSIONS. Our results agree with those of other AA (Behan et al., 1991; Gow et al., 1994). The alterations are compatible with a myopathy of probable mitochondrial origin. This could explain the drop in the functional capability of the muscle as a reduction in potency but, above all, as a reduction in resistance. In conclusion, even if CFS seems to be attributable to mitochondrial and/or muscular alterations, a damage in the central nervous system cannot be excluded. This could explain the neurophychological, behavioral, and neuroendocrinological alterations often found in these patients.
The effects of CBT and GET on patients with Myalgic Encephalomyelitis by Jodi Bassett This paper looks at the physical effects of CBT (psychotherapy) and GET (exercise) on patients with M.E. Dr. Paul Cheney on Mitochondrial Myopathy, MRS Brain Scans and Chronic Fatigue Syndrome by Carol Sieverling CFS ‘a mitochondrial disease’ I asked Cheney about mitochrondrial myopathy and CFS. He confirmed what I suspected: in CFS there is so much injury to the mitochondria that CFS could be called a mitochrondrial disease. I recall seeing a photo Cheney showed me at my first visit in '96. A study of mitochondria in CFS patients was done at UNC. The photo showed a mitochondria from a healthy person. It was lit up like a thunderstorm on a radar screen - some blues and greens, but a lot of yellow and red – high energy production. The mitochondria from the CFS patients was such a contrast: mostly blues and green with a tiny bit of yellow in it. No where near the energy being produced. The Heart of the Matter: CFS and Cardiac Issues - Dr Paul Cheney by by Carol Sieverling
Etiology (Cause) What is the etiology, the cause, of this cardiac output problem? The short version is that cardiac muscles have lost power because their mitochondria are dysfunctional. They're not functioning well because of a redox-state problem. [Redox: a reversible chemical reaction in which one reaction is an oxidation and the reverse is a reduction. Look for a future article explaining redox states.] *O* Profits Before Patients? Eileen Marshall and Margaret Williams, 15th April 2005 The fourth affected system is the brain: Cheney posits that there is a devastating effect in the brain as a result of liver / gut dysfunction, which can quickly toxify the brain, resulting in disturbances of memory and of processing speed. Also, the hypothalamus begins to destabilise the patient from the autonomic nervous system perspective. In all probability, the brain and heart suffer simultaneous compromise, but patients usually notice the brain being affected much earlier than the heart – this is because heart muscle cells have the greatest mitochondrial content of any tissue in the body, so when the mitochondria are impaired, the heart muscle has the greatest reserve. Even if the patient is sedentary with not too much demand on the heart, s/he can still think and make great demands on the brain, and energy is energy, whether it is being used physically or cognitively. *O* CRITICAL CONSIDERATIONS by Margaret Williams, 1st November 2004 The issue is whether or not compulsory exercise regimes and “rehabilitative programmes” may be harmful to those with ME / CFS. In 1999 Professor Paul Cheney from the US went on record as stating: “The most important thing about exercise is not to have (patients with ME / CFS) do aerobic exercise. I believe that even progressive aerobic exercise is counter-productive. If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA” (Lecture given in Orlando, Florida at the International Congress of Bioenergetic Medicine, 5th-7th February 1999). Significantly, there is now further supportive evidence that has emerged from the 7th AACFS International Conference held in Madison, Wisconsin, from 8-10th October 2004: “An analysis of metabolic features using MRSI (magnetic resonance spectroscopy imaging) showed elevated lactate levels, which suggests mitochondrial metabolic dysfunction similar to mitochondrial encephalomyopathy”. Given this evidence, how can forced aerobic exercise be beneficial to such patients? The Three Phases of CFS Dr. Paul Cheney's Theory By Carol Sieverling, May 1999 What does Phase III sound like? "Within my boundaries, I don't feel too bad. I'm pretty comfortable. My problem is that every time I try to exceed those boundaries, I crash. I get worse. So I haul back within my boundaries, and I'm now comfortable again." With the loss of dynamic hormone response, patients cannot cross boundaries. Crossing boundaries requires dynamic response capability, and they no longer have it. In addition to the problems with dynamic hormone response, Phase III may also involve damage to the DNA of energy producing mitochondria. The loss of a portion of mitochondria puts an energy ceiling on patients.The extent of the boundaries can vary among patients, depending on the amount of injury done during the first two phases. By no means is everyone home-bound or bedridden. And there is hope. Dr. Cheney does not believe the endpoint of Phase III is totally fixed. There is a good deal of plasticity to the central nervous system, and there can be significant resuscitation of brain function, and perhaps even the mitochondria may not be completely lost. How Serious is ME The Committee for Justice and Recognition of M.E. Metabolic disturbance is another major area of the disease. A key factor is the damage to the mitochondria which leads to the pathological extreme exhaustion. This damage to the principal metabolic source of energy has profound effects throughout the body, starving the muscles, brain and immune system of energy for function and repair. The abnormal metabolism includes altered body chemistry that can also lead to severe chemical sensitivity to general toxification from common exogenous chemicals. Metabolic and chemistry changes for example can also lead to osteoporosis, disc and spinal degeneration. Most patients may be affected by all these factors to varying degrees. Most patients will have a particular pattern of these symptoms that will predominate their experience. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Plioplys AV, Plioplys S. Neuropsychobiology. 1995;32(3):132-8. Chronic Fatigue Syndrome Center, Mercy Hospital and Medical Center, Chicago, Ill. 60616, USA.
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. *O* Enteroviruses and postviral fatigue syndrome. Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S.Department of Neurology, University of Glasgow, UK.
Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them. The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome. We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy. An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism. A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS. Muscles, mitochondria and myalgia. Behan WM J Pathol. 1992 Mar;166(3):213-4.
*O* Mitochondrial abnormalities in the postviral fatigue syndrome. Behan WM, More IA, Behan PO. Acta Neuropathol (Berl). 1991;83(1):61-5. Department of Pathology, University of Glasgow, Scotland.
We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection. Acylcarnitine deficiency in chronic fatigue syndrome. Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T.Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7.Osaka University Medical School, Japan. [Postviral fatigue syndrome] [Article in Norwegian] Haukenes G, Aarli JA. Avdeling for mikrobiologi og immunologi Gades Institutt, Universitetet i Bergen, Armauer Hansens hus. The post-viral fatigue syndrome occurs sporadically and in local outbreaks (Los Angeles, Akureyri, Royal Free Hospital). The clinical picture is marked by long-lasting muscular fatigue directly following an acute infection. Other conditions associated with pronounced fatigue must be excluded. The diagnostic criteria set up by Centers for Disease Control (CDC) are the ones most commonly used. Aetiology and pathogenesis are unknown. Coxsackie B-virus seems to be associated with some cases at least. Immunological and endocrinological aberration, morphological changes in mitochondria and reduced cerebral blood perfusion have been demonstrated in some patients. There is no specific therapy. It is important for the patient that the symptoms be accepted by the doctor and society in general. Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome. Vecchiet L, Montanari G, Pizzigallo E, Iezzi S, de Bigontina P, Dragani L, Vecchiet J, Giamberardino MA. Institute of Medical Pathophysiology, 'G. D'Annunzio' University of Chieti, Italy.
Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects. Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values. By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripberal mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis. *O* Role of mitochondria in neurodegenerative diseases Cassarino DS, Bennett JP Jr. University of Virginia Health Sciences Center, Charlottesville 22908, USA. Brain Research Reviews, 1999, Vol 29, Iss 1, pp 1-25
There is mounting evidence for mitochondrial involvement in neurodegenerative diseases including Alzheimer's, Parkinson's, and Lou Gehrig's Disease (ALS). Mitochondrial DNA mutations, whether inherited or acquired, lead to impaired electron transport chain (ETC) functioning. Impaired electron transport, in turn, leads to decreased ATP (energy) production, formation of damaging free-radicals, and altered calcium handling. These toxic consequences of ETC dysfunction lead to further mitochondrial damage including oxidation of mitochondrial DNA, proteins, and lipids, and opening of the mitochondrial permeability transition pore, an event linked to cell death. Although protective nuclear responses such as antioxidant enzymes may be induced to combat these pathological changes, such a vicious cycle of increasing oxidative damage may insidiously damage neurons over a period of years, eventually leading to neuronal cell death. This article's hypothesis, a synthesis of the mitochondrial mutations and oxidative stress hypotheses of neurodegeneration, is readily tested experimentally, and points out many potential therapeutic targets for preventing or ameliorating these diseases. PMID: 9974149 Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome Russell J M Lane,a Michael C Barrett,b David Woodrow,b Jill Moss,b Robert Fletcher,b Leonard C Archardc a Division of Neuroscience and Psychological Medicine, b Division of Diagnostic and Investigative Sciences, c Division of Biochemical Sciences, Imperial College School of Medicine, Charing Cross Hospital, London, UKJ Neurol Neurosurg Psychiatry 1998;64:362-367 OBJECTIVES To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy and hypertrophy in patients with chronic fatigue syndrome in relation to lactate responses to exercise, and to determine to what extent any abnormalities found might be due to inactivity. The role of mitochondria in the pathogenesis of neurodegenerative diseases. Manfredi G, Beal MF Department of Neurology and Neuroscience, Weill Medical College of Cornell University and the New York Hospital, Cornell Medical Center, New York 10021, USA. gim2004@mail.med.cornell.edu Brain Pathol 2000 Jul;10(3):462-72 A growing body of evidence indicates that mitochondrial dysfunction may play an important role in the pathogenesis of many neurodegenerative disorders. Because mitochondrial metabolism is not only the principal source of high energy intermediates, but also of free radicals, it has been suggested that inherited or acquired mitochondrial defects could be the cause of neuronal degeneration as a consequence of energy defects and oxidative damage. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities, and also as a consequence of mutations in nuclear genes directly involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin. Defects of oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to primary mitochondrial abnormalities. In these cases, the mitochondrial dysfunction is likely to be an epiphenomenon, which, nevertheless, could be of importance in precipitating a cascade of events leading to cell death. In either case, understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could be important for the development of therapeutic strategies in these disorders. United Mitochondrial Disease Foundation Mission: To promote research and education for the diagnosis, treatment and cure of mitochondrial disorders and to provide support to affected individuals and families.
Skeletal muscle function and mitochondrial function suggests a defect in oxidative metabolism with a residual acceleration of glycolysis in the working skeletal muscles in CFS. There is also reduced oxidative muscle metabolism (shown by MRI), and muscle recovery is delayed. |
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*O* Alterations in muscles of CFS patients at morphological, biochemical and molecular level. Pizzigallo E, Di Girolamo A, Montanari G, Dragani L, Vecchiet J, Calella G. Journal of Chronic Fatigue Syndrome 1996; 2(2/3) 76-77. Abstract: OBJECTIVES. The peripheral origin of symptoms related to CFS has been hypothesized from various AA and is still under investigation to determine if symptoms can be related to muscular damage. Our studies aimed to look for specific alterations in muscles of CFS patients, followed in our Clinic and enrolled according to the 1988 CDC criteria (Holmes et al.) revised in 1994 by Fukuda et al. (CDC). METHODS. Fourteen CFS patients, 3 male and 11 females, 17 to 60 years old (mean 34.6), mean illness duration 49.9 months, post viral onset in 10 cases, underwent muscular biopsy of the vastus lateralis according to Edwards, et al., using a UCH needle. We analyzed the specimens by electron (EM) and light (LM) microscopy. Moreover, we performed histochemical and quantitative analysis of enzymatic activities and studies of mitochondrial DNA (mtDNA) deletions. RESULTS. All specimens showed: hypotrophy, especially of the type 11 (a and b) fibres; fibres fragmentation, red ragged fibres and fusion events with nuclei centralisation; and fatty and fibrous degeneration. EM observations confirmed these alterations, showed degenerative changes in the I band, and allowed us to detect the poli/pleiomorphism and cristae thickening of the mitochondia. The alterations of the fibres always began from an I band of a sarcomere. The histochemical and quantitative determination of the enzymatic activities showed important reduction, in particular of the cytochrome-oxydase and citrate-synthetase. Finally, the "common deletion" of 4977 bp of the mtdna was increased as high as 3,000 times the normal values in 3 patients. CONCLUSIONS. Our results agree with those of other AA (Behan et al., 1991; Gow et al., 1994). The alterations are compatible with a myopathy of probable mitochondrial origin. This could explain the drop in the functional capability of the muscle as a reduction in potency but, above all, as a reduction in resistance. In conclusion, even if CFS seems to be attributable to mitochondrial and/or muscular alterations, a damage in the central nervous system cannot be excluded. This could explain the neurophychological, behavioral, and neuroendocrinological alterations often found in these patients.
Impaired oxygen delivery to muscle in chronic fatigue syndrome. McCully KK, Natelson BH Department of Medicine, Medical College of Pennsylvania and Hahnemann University, Philadelphia, PA 19129, USA. kmccully@coe.uga.edu The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced oxygen delivery to muscles. Patients with CFS according to CDC (Center for Disease Control) criteria (n=20) were compared with normal sedentary subjects (n=12). Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemia oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous-wavelength near-IR spectroscopy. Phosphocreatine resynthesis was measured simultaneously using (31)P magnetic resonance spectroscopy. The time constant of oxygen delivery was significantly reduced in CFS patients after exercise (46.5+/-16 s; mean+/-S.D.) compared with that in controls (29.4+/-6.9 s). The time constant of oxygen delivery was also reduced (20.0+/-12 s) compared with controls (12.0+/-2.8 s) after cuff ischaemia. Oxidative metabolism was also reduced by 20% in CFS patients, and a significant correlation was found between oxidative metabolism and recovery of oxygen delivery. In conclusion, oxygen delivery was reduced in CFS patients compared with that in sedentary controls. This result is consistent with previous studies showing abnormal autonomic control of blood flow. Reduced oxidative delivery in CFS patients could be specifically related to CFS, or could be a non-specific effect of reduced activity levels in these patients. While these results suggest that reduced oxygen delivery could result in reduced oxidative metabolism and muscle fatigue, further studies will be needed to address this issue. *O* Post-viral fatigue syndrome: evidence for underlying organic disturbance in the muscle fibre. Jamal GA, Hansen S. European Neurology 1989; 29: 273-276. Abstract: Ten patients with post-viral fatigue syndrome and abnormal serological, virological, immunological and histological studies were examined by the single-fibre electromyographic (EMG) technique after excluding concurrent problems in the neuromuscular system. No abnormality of fibre density was noted but all patients had abnormal jitter values. Very high jitter values were not associated with impulse or concomitant blocking. The findings confirm the organic nature of the disease. A muscle membrane disorder probably arising from defective myogenic enzymes is the likely mechanism for the fatigue and the single-fibre EMG abnormalities. This muscle membrane defect may be due to the effects of a persistent viral infection.*O* Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome. Preedy VR, Smith DG, Salisbury JR, Peters TJ. Journal of Clinical Pathology 1993; 46(8): 722-6. 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.*O* Enteroviruses and postviral fatigue syndrome. Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S.Department of Neurology, University of Glasgow, UK.
Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them. The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome. We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy. An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism. A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS. *O* Mitochondrial abnormalities in the postviral fatigue syndrome. Behan WM, More IA, Behan PO. Acta Neuropathol (Berl). 1991;83(1):61-5. Department of Pathology, University of Glasgow, Scotland.
We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection. [Postviral fatigue syndrome] [Article in Norwegian] Haukenes G, Aarli JA.
Avdeling for mikrobiologi og immunologi Gades Institutt, Universitetet i Bergen, Armauer Hansens hus. The post-viral fatigue syndrome occurs sporadically and in local outbreaks (Los Angeles, Akureyri, Royal Free Hospital). The clinical picture is marked by long-lasting muscular fatigue directly following an acute infection. Other conditions associated with pronounced fatigue must be excluded. The diagnostic criteria set up by Centers for Disease Control (CDC) are the ones most commonly used. Aetiology and pathogenesis are unknown. Coxsackie B-virus seems to be associated with some cases at least. Immunological and endocrinological aberration, morphological changes in mitochondria and reduced cerebral blood perfusion have been demonstrated in some patients. There is no specific therapy. It is important for the patient that the symptoms be accepted by the doctor and society in general. Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome. Vecchiet L, Montanari G, Pizzigallo E, Iezzi S, de Bigontina P, Dragani L, Vecchiet J, Giamberardino MA. Institute of Medical Pathophysiology, 'G. D'Annunzio' University of Chieti, Italy.
Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects. Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values. By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripberal mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis. Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome Russell J M Lane,a Michael C Barrett,b David Woodrow,b Jill Moss,b Robert Fletcher,b Leonard C Archardc a Division of Neuroscience and Psychological Medicine, b Division of Diagnostic and Investigative Sciences, c Division of Biochemical Sciences, Imperial College School of Medicine, Charing Cross Hospital, London, UKJ Neurol Neurosurg Psychiatry 1998;64:362-367 OBJECTIVES To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy and hypertrophy in patients with chronic fatigue syndrome in relation to lactate responses to exercise, and to determine to what extent any abnormalities found might be due to inactivity. In vivo magnetic resonance spectroscopy in chronic fatigue syndrome. Chaudhuri A, Behan PO.Division of Clinical Neurosciences, Institute of Neurological Sciences, Southern General Hospital, University of Glasgow, 1345 Govan Road, Glasgow G51 4TF, UK. ac54p@udcf.gla.ac.uk Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion fatigue syndrome. Arnold DL, Radda GK, Bore PJ, Styles P, Taylor DJ. Lancet 1984; 1: 1367-9. Abstract: A patient with prolonged post-viral exhaustion and excessive fatigue was examined by 31P nuclear magnetic resonance. During exercise, muscles of the forearm demonstrated abnormally early intracellular acidosis for the exercise performed. This was out of proportion to the associated changes in high-energy phosphates. This may represent excessive lactic acid formation resulting from a disorder of metabolic regulation. The metabolic abnormality in this patient could not have been demonstrated by traditional diagnostic techniques.Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome Stefania Fulle (a), Patrizia Mecocci (b), Giorgio Fano (c), Iacopo Vecchiet (d), Alba Vecchini (e), Delia Racciotti (d), Antonio Cherubini (b), Eligio Pizzigallo (d), Leonardo Vecchiet (c), Umberto Senin (b) and M. Flint Beal (f). Address correspondence to: Dr. M. Flint Beal, Chairman, Neurology Department, New York Hospital-Cornell Medical Center, 525 East 68th Street, New York, NY 10021, USA; Tel: (212) 746-6575; Fax: (212) 746-8532; email: fbeal@mail.med.cornell.edu Free Radical Biology and Medicine Dec 15, 2000, Vol. 29, No. 12, 1252-59Chronic 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. 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.
Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. The authors attempted to confirm the consistent report by patients with the CFS of delay in recovery of peripheral muscle function after exercise. They tested the quadriceps muscle group of 10 patients and 10 controls. Recovery was prolonged in the patient group, with a significant difference between the two groups after exercise and after 24 hours. These findings support the clinical complaint of delayed recovery after exercise in patients with CFS. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. Plus a discussion of the text. "Thus, as in inherited muscular dystrophy in which a variety of cellular abnormalities can be accounted for by free radical-mediated damages including abnormal functions of the sarcolemma and an altered activity of membrane-bound enzymes involved in excitation-contraction coupling, an increased level of free radical damage in CFS may be a contributor to the underlying functional defects and symptom presentation. This should promote further researches towards the goal of an effective treatment of CFS-suffering patients."
Skeletal muscle metabolism in the chronic fatigue syndrome - In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Wong R, Lopaschuk G, Zhu G, Walker D, Catellier D, Burton D, Teo K, Collins-Nakai R, Montague T. Chest 1992; 102(6): 1716-22. Abstract: BACKGROUND: Previous study of patients with chronic fatigue syndrome (CFS) has demonstrated a markedly reduced dynamic exercise capacity, not limited by cardiac performance and in the absence of clinical neuromuscular dysfunction, suggesting the possibility of a subclinical defect of skeletal muscle. METHODS: The in vivo metabolism of the gastrocnemius muscles of 22 CFS patients and 21 normal control subjects was compared during rest, graded dynamic exercise to exhaustion and recovery, using 31P nuclear magnetic resonance (NMR) spectroscopy to reflect minute-to-minute intracellular high-energy phosphate metabolism. RESULTS: Duration of exercise was markedly shorter in the CFS patients (8.1 ± 2.8 min) compared with the normal subjects (11.3 ± 4.3 min) (p = 0.005). There were large changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH from rest to clinical fatigue in all subjects, reflecting the high intensity of the exercise. The temporal metabolic patterns were qualitatively similar in the CFS patients and normal subjects. There were early and continuous changes in PCr and Pi that peaked at the point of fatigue and rapidly reversed after exercise. In contrast, pH was relatively static in early exercise, not declining noticeably until 50 percent of total exercise duration was achieved, and reaching a nadir at 2 min postexercise, before rapidly reversing. There were no differences in pH at rest (7.08 ± 0.04 vs 7.10 ± 0.04), exhaustion (6.85 ± 0.17 vs 6.76 ± 0.17) or early (6.64 ± 0.25 vs 6.56 ± 0.24) or late recovery (7.09 ± 0.04 vs 7.10 ± 0.05), CFS patients vs normal subjects, respectively (NS). Neither were there intergroup differences (NS) in PCr or Pi. Although, quantitatively, the changes in PCr, Pi, and pH were marked and similar in both groups from rest to exhaustion, the changes all occurred much more rapidly in the CFS patients. Moreover, adenosine triphosphate (ATP) was significantly (p = 0.007) less at exhaustion in the CFS group. CONCLUSIONS: Patients with CFS and normal control subjects have similar skeletal muscle metabolic patterns during dynamic exercise and reach similar clinical and metabolic end points. However, CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients. This metabolic defect may contribute to the reduced physical endurance of CFS patients. Its etiology is unknown. Whether CFS patients' overwhelming tiredness at rest has a similar metabolic pathophysiology or etiology also remains unknown.Muscle performance, voluntary activation, twitch properties and perceived exertion in normal subjects and patients with chronic fatigue syndrome. Lloyd AR, Gandevia SC, Hales JP. Brain 1991; 114: 85-98. Abstract: The decrease in maximal force-generating capacity, the degree of central activation of the muscle, and the subjective perception of effort were measured during prolonged submaximal isometric exercise in 12 male patients suffering from the 'chronic fatigue syndrome' and 13 naive, healthy male subjects. Maximal voluntary isometric torque generated by the elbow flexors was measured before, and at 5 min intervals during an endurance sequence of 45 min of repetitive isometric contractions (6 s duration, 4 s rest interval) producing 30% of the initial maximal voluntary torque. Electrical stimuli were also delivered to the elbow flexors to measure the contractile force in the intervals between voluntary contractions. The degree of central motor activation during maximal voluntary contractions was assessed using a sensitive method of twitch interpolation. In addition, the perceived effort required to achieve the target submaximal contractions was recorded using a standardized self-report scale. A high degree of central activation was achieved in maximal contractions during the endurance sequence both in the patients (mean of maximal force 93.6%; SD 7.8%), and in the control subjects (mean 90.9%; SD 9.5%). The relative torque produced by either voluntary or electrically stimulated contractions was not significantly different between patients and control subjects throughout the test. There was no significant difference in the perceived exertion between the patients and control subjects. These findings support the concept that neither poor motivation, nor muscle contractile failure is important in the pathogenesis of 'fatigue' in patients with the chronic fatigue syndrome. |
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*O* The Clinical and Scientific Basis of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Edited by Byron Hyde, M.D. , Nightingale Research Foundation, Ottawa, Canada
Mitochondrial Cytopathies: A Primer written by Dr. Bruce Cohen, MD
The Sinatra Solution produced by metabolic cardiologist, Dr Stephen Sinatra Enteroviral and Toxin Mediated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Other Organ Pathologies by John Richardson
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition. Carruthers et al
Hard copies of the Canadian Guidelines are available for purchase from Haworth Press
*O* Engaging with M.E. (DVD format and printed format) Professor Malcolm Hooper
*O* What is ME? What is CFS? Information for Clinicians and Lawyers (Online format and printed format) by Professor Malcolm Hooper, Margaret Williams and Eileen Marshall Faces of CFS by David S. Bell MD.
Available as a free PDF download
The Doctor's Guide to CFIDS by David S. Bell MD A Parents Guide to CFIDS by David S. Bell MD The Disease of a Thousand Names by David S. Bell MD ME: The New Plague by Jane Colby America's Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS by Neenyah Ostrom The Polio Paradox: Understanding and Treating "Post-Polio Syndrome" and Chronic Fatigue [Syndrome] by Richard L. Bruno Note: Links given with certain book titles are for informational purposes only and are not recommendations of any particular book seller. It is recommended that you shop around for the best prices at a number of stores for any books you might wish to purchase. |