Muscle fatigability: Difference between revisions

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==Prevalence==
==Prevalence==
*In a 2001 Belgian study, 84.3% of patients meeting the [[Fukuda criteria]] and 88.3% of patients meeting the [[Holmes criteria]], in a cohort of 2073 [[Chronic fatigue syndrome|CFS]] patients, reported [[Paresis|muscle weakness]].<ref>{{Cite journal | last = De Becker | first = Pascale | author-link=Pascale De Becker | last2 = McGregor | first2 = Neil | authorlink2 = Neil McGregor | last3 = De Meirleir | first3=Kenny | author-link3=Kenny De Meirleir | date = December 2001 | title = A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2796.2001.00890.x?sid=nlm%3Apubmed|journal=Journal of Internal Medicine|volume=250|issue=3|pages=234–240|doi=10.1046/j.1365-2796.2001.00890.x|quote=|via=}}</ref>
*In a 2001 Belgian study, 84.3% of patients meeting the [[Fukuda criteria]] and 88.3% of patients meeting the [[Holmes criteria]], in a cohort of 2073 [[Chronic fatigue syndrome|CFS]] patients, reported [[Paresis|muscle weakness]].<ref>{{Cite journal | last = De Becker | first = Pascale | authorlink = Pascale De Becker | last2 = McGregor | first2 = Neil | authorlink2 = Neil McGregor | last3 = De Meirleir | first3 = Kenny | author-link3 = Kenny De Meirleir | date = December 2001 | title = A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2796.2001.00890.x?sid=nlm%3Apubmed|journal=Journal of Internal Medicine|volume=250|issue=3|pages=234–240|doi=10.1046/j.1365-2796.2001.00890.x|quote=|via=}}</ref>


*[[Katrina Berne]], PhD, reports a prevalence of 85-95% for [[Paresis|muscle weakness]].<ref>{{Cite book | last = Berne | first = Katrina | author-link=Katrina Berne | date = Dec 1, 1995  | title =  Running on Empty: The Complete Guide to Chronic Fatigue Syndrome (CFIDS)|edition= 2nd |url= https://www.amazon.co.uk/Running-Empty-Complete-Chronic-Syndrome/dp/0897931912/ |publisher= Hunter House  | page =  59 |isbn= 978-0897931915}}</ref>
*[[Katrina Berne]], PhD, reports a prevalence of 85-95% for [[Paresis|muscle weakness]].<ref>{{Cite book | last = Berne | first = Katrina | authorlink = Katrina Berne | date = Dec 1, 1995  | title =  Running on Empty: The Complete Guide to Chronic Fatigue Syndrome (CFIDS)|edition= 2nd |url= https://www.amazon.co.uk/Running-Empty-Complete-Chronic-Syndrome/dp/0897931912/ |publisher= Hunter House  | page =  59 |isbn= 978-0897931915}}</ref>


==Symptom recognition==
==Symptom recognition==
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== Possible causes==
== Possible causes==
* Muscle biopsies have shown evidence of mitochondrial degeneration,<ref>{{Cite journal | last = Behan | first = W. M. H. | authorlinklink= | last2 = More | first2=I.A. R.|authorlink2 = | last3 = Behan | first3=P. O. | authorlinklink3=Peter Behan | date = Dec 1991 | title = Mitochondrial abnormalities in the postviral fatigue syndrome|url=http://link.springer.com/10.1007/BF00294431|journal=Acta Neuropathologica|language=en|volume=83|issue=1 | pages = 61–65|doi=10.1007/BF00294431|issn=0001-6322|pmc=|pmid=|access-date=|quote=|via=}}</ref> deletions of [[mitochondrial DNA]],<ref>{{Cite journal | last = Vecchiet | first = L. | last2 = Montanari | first2 = G. | last3 = Pizzigallo | first3 = E. | last4 = Iezzi | first4 = S. | last5 = de Bigontina | first5=P. | last6 = Dragani | first6 = L. | last7 = Vecchiet | first7 = J. | last8 = Giamberardino | first8 = M.A. |date = 1996-04-19 | title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8859904|journal=Neuroscience Letters|volume=208|issue=2|pages=117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940|pmid=8859904}}</ref><ref>{{Cite journal | last = Zhang | first = C. | authorlinklink= | last2 = Baumer | first2=A.|authorlink2 = | last3 = Mackay | first3 = I.R. | authorlinklink3= | last4 = Linnane | first4=A. W. | authorlink4 = | last5 = Nagley | first5 = P. | authorlink5 =  | date = Apr 1995 | title = Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/7633428|journal=Human Molecular Genetics|volume=4|issue=4 | pages = 751–754|doi=10.1093/hmg/4.4.751|issn=0964-6906|pmc=|pmid=7633428|access-date=|quote=|via=}}</ref> and the reduction of mitochondrial activity.<ref>{{Cite journal | last = Vecchiet | first = L. | last2 = Montanari | first2 = G. | last3 = Pizzigallo | first3 = E. | last4 = Iezzi | first4 = S. | last5 = de Bigontina | first5=P. | last6 = Dragani | first6 = L. | last7 = Vecchiet | first7 = J. | last8 = Giamberardino | first8 = M.A. |date = 1996-04-19 | title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8859904|journal=Neuroscience Letters|volume=208|issue=2|pages=117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940|pmid=8859904}}</ref>
* Muscle biopsies have shown evidence of mitochondrial degeneration,<ref>{{Cite journal | last = Behan | first = W.M.H. | authorlink = | last2 = More | first2 = I.A.R. | authorlink2 = | last3 = Behan | first3 = P.O. | author-link3 =Peter Behan | date = Dec 1991 | title = Mitochondrial abnormalities in the postviral fatigue syndrome|url=http://link.springer.com/10.1007/BF00294431|journal=Acta Neuropathologica|language=en|volume=83|issue=1 | pages = 61–65|doi=10.1007/BF00294431|issn=0001-6322|pmc=|pmid=|access-date=|quote=|via=}}</ref> deletions of [[mitochondrial DNA]],<ref>{{Cite journal | last = Vecchiet | first = L. | last2 = Montanari | first2 = G. | last3 = Pizzigallo | first3 = E. | last4 = Iezzi | first4 = S. | last5 = de Bigontina | first5 = P. | last6 = Dragani | first6 = L. | last7 = Vecchiet | first7 = J. | last8 = Giamberardino | first8 = M.A. | date = 1996-04-19 | title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8859904|journal=Neuroscience Letters|volume=208|issue=2|pages=117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940|pmid=8859904}}</ref><ref>{{Cite journal | last = Zhang | first = C. | authorlink = | last2 = Baumer | first2 = A. | authorlink2 = | last3 = Mackay | first3 = I.R. | authorlink3 = | last4 = Linnane | first4 = A.W. | authorlink4 = | last5 = Nagley | first5 = P. | authorlink5 =  | date = Apr 1995 | title = Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/7633428|journal=Human Molecular Genetics|volume=4|issue=4 | pages = 751–754|doi=10.1093/hmg/4.4.751|issn=0964-6906|pmc=|pmid=7633428|access-date=|quote=|via=}}</ref> and the reduction of mitochondrial activity.<ref>{{Cite journal | last = Vecchiet | first = L. | last2 = Montanari | first2 = G. | last3 = Pizzigallo | first3 = E. | last4 = Iezzi | first4 = S. | last5 = de Bigontina | first5 = P. | last6 = Dragani | first6 = L. | last7 = Vecchiet | first7 = J. | last8 = Giamberardino | first8 = M.A. | date = 1996-04-19 | title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8859904|journal=Neuroscience Letters|volume=208|issue=2|pages=117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940|pmid=8859904}}</ref>


* In addition, evidence of oxidative damage to muscles has been found in CFS.<ref>{{Cite journal | last = Fulle | first = S. | last2 = Mecocci | first2 = P. | last3 = Fanó | first3 = G. | last4 = Vecchiet | first4=I. | last5 = Vecchini | first5 = A. | last6 = Racciotti | first6 = D. | last7 = Cherubini | first7 = A. | last8 = Pizzigallo | first8 = E. | last9 = Vecchiet | first9 = L. | date = 2000-12-15 | title = Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11118815|journal=Free Radical Biology & Medicine|volume=29|issue=12|pages=1252–1259|doi=10.1016/s0891-5849(00)00419-6|issn=0891-5849|pmid=11118815}}</ref>
* In addition, evidence of oxidative damage to muscles has been found in CFS.<ref>{{Cite journal | last = Fulle | first = S. | last2 = Mecocci | first2 = P. | last3 = Fanó | first3 = G. | last4 = Vecchiet | first4 = I. | last5 = Vecchini | first5 = A. | last6 = Racciotti | first6 = D. | last7 = Cherubini | first7 = A. | last8 = Pizzigallo | first8 = E. | last9 = Vecchiet | first9 = L. | date = 2000-12-15 | title = Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11118815|journal=Free Radical Biology & Medicine|volume=29|issue=12|pages=1252–1259|doi=10.1016/s0891-5849(00)00419-6|issn=0891-5849|pmid=11118815}}</ref>


* Studies have found reduced levels of serum [[carnitine]] which return to normal after recovery and correlate with symptom severity.<ref>{{Cite journal | last = Kuratsune | first = H. | authorlinklink= | last2 = Yamaguti | first2 = K.|authorlink2 = | last3 = Takahashi | first3 = M. | authorlinklink3= | last4 = Misaki | first4 = H. | authorlink4 = | last5 = Tagawa | first5=S. | authorlink5 = |last6 = Kitani | first6 = T. | authorlink6 =  | date = Jan 1994 | title = Acylcarnitine deficiency in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8148455|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 | issue = Suppl 1|pages=S62–67|doi=10.1093/clinids/18.supplement_1.s62|issn=1058-4838|pmc=|pmid=8148455|access-date=|quote=|via=}}</ref>
* Studies have found reduced levels of serum [[carnitine]] which return to normal after recovery and correlate with symptom severity.<ref>{{Cite journal | last = Kuratsune | first = H. | authorlink = | last2 = Yamaguti | first2 = K. | authorlink2 = | last3 = Takahashi | first3 = M. | authorlink3 = | last4 = Misaki | first4 = H. | authorlink4 = | last5 = Tagawa | first5 = S. | authorlink5 = |last6 = Kitani | first6 = T. | authorlink6 =  | date = Jan 1994 | title = Acylcarnitine deficiency in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8148455|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 | issue = Suppl 1|pages=S62–67|doi=10.1093/clinids/18.supplement_1.s62|issn=1058-4838|pmc=|pmid=8148455|access-date=|quote=|via=}}</ref>


* Exercise has also been found to induce both early and excessive [[lactic acid]] formation in the muscles<ref>{{Cite journal | last = Plioplys | first = A.V. | last2 = Plioplys | first2 = S. | date = 1995 | title=Serum levels of carnitine in chronic fatigue syndrome: clinical correlates|url=https://www.ncbi.nlm.nih.gov/pubmed/8544970|journal=Neuropsychobiology|volume=32|issue=3|pages=132–138|doi=10.1159/000119226|issn=0302-282X|pmid=8544970}}</ref> with a reduced intraceullar concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref>{{Cite journal | last = McCully | first = K. K. | authorlinklink= | last2 = Natelson | first2=B. H.|authorlink2 = Benjamin Natelson | last3 = Iotti | first3 = S. | authorlinklink3= | last4 = Sisto | first4 = S. | authorlink4 = | last5 = Leigh | first5 = J. S. | authorlink5 =  | date = May 1996 | title = Reduced oxidative muscle metabolism in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8618560|journal=Muscle & Nerve|volume=19|issue=5 | pages = 621–625|doi=10.1002/(SICI)1097-4598(199605)19:53.0.CO;2-Q|issn=0148-639X|pmc=|pmid=8618560|access-date=|quote=|via=}}</ref>
* Exercise has also been found to induce both early and excessive [[lactic acid]] formation in the muscles<ref>{{Cite journal | last = Plioplys | first = A.V. | last2 = Plioplys | first2 = S. | date = 1995 | title=Serum levels of carnitine in chronic fatigue syndrome: clinical correlates|url=https://www.ncbi.nlm.nih.gov/pubmed/8544970|journal=Neuropsychobiology|volume=32|issue=3|pages=132–138|doi=10.1159/000119226|issn=0302-282X|pmid=8544970}}</ref> with a reduced intraceullar concentrations of [[ATP]] and acceleration of [[glycolysis]].<ref>{{Cite journal | last = McCully | first = K.K. | authorlink = | last2 = Natelson | first2 = B. H. | authorlink2 = Benjamin Natelson | last3 = Iotti | first3 = S. | authorlink3 = | last4 = Sisto | first4 = S. | authorlink4 = | last5 = Leigh | first5 = J.S. | authorlink5 =  | date = May 1996 | title = Reduced oxidative muscle metabolism in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8618560|journal=Muscle & Nerve|volume=19|issue=5 | pages = 621–625|doi=10.1002/(SICI)1097-4598(199605)19:53.0.CO;2-Q|issn=0148-639X|pmc=|pmid=8618560|access-date=|quote=|via=}}</ref>


* Neurologist [[Peter Behan]] noted that ME patients were found to lack an important muscle enzyme called [[myoadenylate deaminase]]. A small peer-reviewed study found this present in only 5.5% of patients, and associated primarily with [[myalgia|muscle pain]] rather than fatigue.<ref name="Edwards1993">R.H. Edwards, H. Gibson, J.E. Clague, T. Helliwell [https://books.google.co.uk/books?id=uXISpTK0mHMC&pg=PA102&lpg=PA102&dq=Muscle+histopathology+and+physiology+in+chronic+fatigue+syndrome+CIBA&source=bl&sa=X#v=onepage&q&f=false Muscle histopathology and physiology in chronic fatigue syndrome]. CIBA Found. Symp., 173 (1993), pp. 102-117
* Neurologist [[Peter Behan]] noted that ME patients were found to lack an important muscle enzyme called [[myoadenylate deaminase]]. A small peer-reviewed study found this present in only 5.5% of patients, and associated primarily with [[myalgia|muscle pain]] rather than fatigue.<ref name="Edwards1993">R.H. Edwards, H. Gibson, J.E. Clague, T. Helliwell [https://books.google.co.uk/books?id=uXISpTK0mHMC&pg=PA102&lpg=PA102&dq=Muscle+histopathology+and+physiology+in+chronic+fatigue+syndrome+CIBA&source=bl&sa=X#v=onepage&q&f=false Muscle histopathology and physiology in chronic fatigue syndrome]. CIBA Found. Symp., 173 (1993), pp. 102-117
(discussion 117–131)</ref> Myoadenylate deaminase has since been ruled out as the sole cause of ME/CFS.<ref name="Ch7">{{Citation | title = Muscle Histopathology and Physiology in Chronic Fatigue Syndrome | date = 2007-09-28|url=https://onlinelibrary.wiley.com/doi/10.1002/9780470514382.ch7|work=Ciba Foundation Symposium 173‐Chronic Fatigue Syndrome|pages=102–131 | last = Edwards | first = R. H. T. | authorlinklink= | last2 = Gibson | first2 = H.|authorlink2 = | last3 = Clague | first3 = J. E. | authorlinklink3= | last4 = Helliwell | first4 = T. | authorlink4 = |isbn=978-0-470-51438-2|location=Chichester, UK|publisher=John Wiley & Sons, Ltd.|pmc=|pmid=|access-date=|quote=|via=}}</ref>
(discussion 117–131)</ref> Myoadenylate deaminase has since been ruled out as the sole cause of ME/CFS.<ref name="Ch7">{{Citation | title = Muscle Histopathology and Physiology in Chronic Fatigue Syndrome | date = 2007-09-28|url=https://onlinelibrary.wiley.com/doi/10.1002/9780470514382.ch7|work=Ciba Foundation Symposium 173‐Chronic Fatigue Syndrome|pages=102–131 | last = Edwards | first = R. H.T. | authorlink = | last2 = Gibson | first2 = H. | authorlink2 = | last3 = Clague | first3 = J.E. | authorlink3 = | last4 = Helliwell | first4 = T. | authorlink4 = |isbn=978-0-470-51438-2|location=Chichester, UK|publisher=John Wiley & Sons, Ltd.|pmc=|pmid=|access-date=|quote=|via=}}</ref>


==Potential treatments==
==Potential treatments==

Latest revision as of 14:01, July 25, 2023

Muscle fatigability in ME is a symptom in which muscles become weaker after minor exertion and a long period (3-5 days or longer) may elapse before full muscle power is restored. According to Melvin Ramsay, it is the defining feature of myalgic encephalomyelitis, without which a diagnosis of ME should not be made,[1] though this symptom is noted to improve during remission. Similar muscle effects are known to occur in other neurological diseases such as multiple sclerosis[2] and post-polio syndrome.[3]

Prevalence[edit | edit source]

Symptom recognition[edit | edit source]

  • In the Holmes criteria, unexplained generalized muscle weakness is an optional criteria for diagnosis, under the section Minor Symptom Criteria.[6]

Notable studies[edit | edit source]

Possible causes[edit | edit source]

  • Muscle biopsies have shown evidence of mitochondrial degeneration,[7] deletions of mitochondrial DNA,[8][9] and the reduction of mitochondrial activity.[10]
  • In addition, evidence of oxidative damage to muscles has been found in CFS.[11]
  • Studies have found reduced levels of serum carnitine which return to normal after recovery and correlate with symptom severity.[12]
  • Exercise has also been found to induce both early and excessive lactic acid formation in the muscles[13] with a reduced intraceullar concentrations of ATP and acceleration of glycolysis.[14]
  • Neurologist Peter Behan noted that ME patients were found to lack an important muscle enzyme called myoadenylate deaminase. A small peer-reviewed study found this present in only 5.5% of patients, and associated primarily with muscle pain rather than fatigue.[15] Myoadenylate deaminase has since been ruled out as the sole cause of ME/CFS.[16]

Potential treatments[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. "Ramsay's Definition of M.E., 1986". cfids-me.org. Retrieved August 28, 2019.
  2. Managing MS Symptoms - Fatigue and Fatigability
  3. "The Late Effects of Polio: An Overview". post-polio.org. Retrieved August 28, 2019.
  4. De Becker, Pascale; McGregor, Neil; De Meirleir, Kenny (December 2001). "A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome". Journal of Internal Medicine. 250 (3): 234–240. doi:10.1046/j.1365-2796.2001.00890.x.
  5. Berne, Katrina (December 1, 1995). Running on Empty: The Complete Guide to Chronic Fatigue Syndrome (CFIDS) (2nd ed.). Hunter House. p. 59. ISBN 978-0897931915.
  6. "Holmes Definition of Chronic Fatigue Syndrome, U.S. CDC 1988". cfids-me.org. Retrieved August 28, 2019.
  7. Behan, W.M.H.; More, I.A.R.; Behan, P.O. (December 1991). "Mitochondrial abnormalities in the postviral fatigue syndrome". Acta Neuropathologica. 83 (1): 61–65. doi:10.1007/BF00294431. ISSN 0001-6322.
  8. Vecchiet, L.; Montanari, G.; Pizzigallo, E.; Iezzi, S.; de Bigontina, P.; Dragani, L.; Vecchiet, J.; Giamberardino, M.A. (April 19, 1996). "Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome". Neuroscience Letters. 208 (2): 117–120. doi:10.1016/0304-3940(96)12559-3. ISSN 0304-3940. PMID 8859904.
  9. Zhang, C.; Baumer, A.; Mackay, I.R.; Linnane, A.W.; Nagley, P. (April 1995). "Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome". Human Molecular Genetics. 4 (4): 751–754. doi:10.1093/hmg/4.4.751. ISSN 0964-6906. PMID 7633428.
  10. Vecchiet, L.; Montanari, G.; Pizzigallo, E.; Iezzi, S.; de Bigontina, P.; Dragani, L.; Vecchiet, J.; Giamberardino, M.A. (April 19, 1996). "Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome". Neuroscience Letters. 208 (2): 117–120. doi:10.1016/0304-3940(96)12559-3. ISSN 0304-3940. PMID 8859904.
  11. Fulle, S.; Mecocci, P.; Fanó, G.; Vecchiet, I.; Vecchini, A.; Racciotti, D.; Cherubini, A.; Pizzigallo, E.; Vecchiet, L. (December 15, 2000). "Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome". Free Radical Biology & Medicine. 29 (12): 1252–1259. doi:10.1016/s0891-5849(00)00419-6. ISSN 0891-5849. PMID 11118815.
  12. Kuratsune, H.; Yamaguti, K.; Takahashi, M.; Misaki, H.; Tagawa, S.; Kitani, T. (January 1994). "Acylcarnitine deficiency in chronic fatigue syndrome". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 18 (Suppl 1): S62–67. doi:10.1093/clinids/18.supplement_1.s62. ISSN 1058-4838. PMID 8148455.
  13. Plioplys, A.V.; Plioplys, S. (1995). "Serum levels of carnitine in chronic fatigue syndrome: clinical correlates". Neuropsychobiology. 32 (3): 132–138. doi:10.1159/000119226. ISSN 0302-282X. PMID 8544970.
  14. McCully, K.K.; Natelson, B. H.; Iotti, S.; Sisto, S.; Leigh, J.S. (May 1996). "Reduced oxidative muscle metabolism in chronic fatigue syndrome". Muscle & Nerve. 19 (5): 621–625. doi:10.1002/(SICI)1097-4598(199605)19:53.0.CO;2-Q. ISSN 0148-639X. PMID 8618560.
  15. R.H. Edwards, H. Gibson, J.E. Clague, T. Helliwell Muscle histopathology and physiology in chronic fatigue syndrome. CIBA Found. Symp., 173 (1993), pp. 102-117 (discussion 117–131)
  16. Edwards, R. H.T.; Gibson, H.; Clague, J.E.; Helliwell, T. (September 28, 2007), "Muscle Histopathology and Physiology in Chronic Fatigue Syndrome", Ciba Foundation Symposium 173‐Chronic Fatigue Syndrome, Chichester, UK: John Wiley & Sons, Ltd., pp. 102–131, ISBN 978-0-470-51438-2