Some Patients with Chronic Fatigue Syndrome Have Brain Dysfunction

  • Benjamin H. Natelson


Chronic fatigue syndrome (CFS) is medically unexplained fatigue lasting at least 6 months and accompanied by infectious, rheumatological, and neuropsychiatric symptoms. CFS is primarily a problem in women’s health because approximately 75% of patients seeking care for chronic fatigue are women. Because of complaints of muscle weakness and achiness, early work focused on peripheral mechanisms of fatigue via muscle dysfunction. However, those studies were unable to confirm any consistent anatomical or physiological abnormality. The lack of an obvious peripheral mechanism for fatigue led to a change in focus to central mechanisms. This change was supported by a set of studies, including those from this laboratory, which showed objective evidence of neuropsychological dysfunction.


Single Photon Emission Compute Tomography Chronic Fatigue Syndrome Gray Matter Volume Chronic Fatigue Syndrome Patient Magnetic Resonance Imaging Abnormality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    DeLuca J, Johnson SK, Natelson BH (1993) Information processing efficiency in chronic fatigue syndrome and multiple sclerosis. Arch Neurol 50:301–304PubMedGoogle Scholar
  2. 2.
    Busichio K, Tiersky LA, DeLuca J, Natelson BH (2004) Neuropsychological deficits in patients with chronic fatigue syndrome. J Int Neuropsychol Soc 10:1–8CrossRefGoogle Scholar
  3. 3.
    Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Mores J, Natelson BH (2005) Exercise and cognitive performance in Chronic Fatigue Syndrome. Med Sci Sports Exerc 37:1460–1467PubMedCrossRefGoogle Scholar
  4. 4.
    DeLuca J, Johnson SK, Ellis SP, Natelson BH (1997) Cognitive functioning is impaired in chronic fatigue syndrome patients devoid of psychiatric disease. J Neurol Neurosurg Psychiatr 62:151–155PubMedCrossRefGoogle Scholar
  5. 5.
    Christodoulou C, DeLuca J, Lange G, Sisto S, Natelson BH (1998) Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatr 64:431–434PubMedCrossRefGoogle Scholar
  6. 6.
    Capuron L, Welberg L, Heim C, Wagner D, Solomon L, Papanicolaou DA, Craddock RC, Miller AH, Reeves WC (2006) Cognitive dysfuntion relates to subjective report of mental fatigue in patients with chronic fatigue syndrome. Neuropsychopharmacology 1–8Google Scholar
  7. 7.
    Cook DB, Lange G, DeLuca J, Natelson BH (2001) Relationship of brain MRI abnormalities and physical functional status in CFS. Int J Neurosci 107:1–6PubMedCrossRefGoogle Scholar
  8. 8.
    Lange G, Holodny A, DeLuca J, et al. (2001) Quantitative assessment of cerebral ventricular volumes in CFS. Appl Neuropsychol 8:23–30PubMedCrossRefGoogle Scholar
  9. 9.
    De Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I (2005) Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage 26:777–781PubMedCrossRefGoogle Scholar
  10. 10.
    Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N (2004) Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol 4(10.1186/1471-2377/4/14)Google Scholar
  11. 11.
    Ichise M, Salit IE, Abbey SE, et al. (1992) Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun 13:767–772PubMedCrossRefGoogle Scholar
  12. 12.
    Schwartz RB, Komaroff AL, Garada BM, et al. (1994) SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. Am J Roentgenol 162:943–951Google Scholar
  13. 13.
    Lewis DH, Mayberg HS, Fischer ME, et al. (2001) Monozygotic twins discordant for chronic fatigue syndrome: regional cerebral blood flow SPECT. Radiology 219:766–773PubMedGoogle Scholar
  14. 14.
    Fischler B, D’Haenen H, Cluydts R, et al. (1996) Comparison of 99mTc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. Neuropsychobiology 34:175–183PubMedCrossRefGoogle Scholar
  15. 15.
    Costa DC, Tannock C, Brostoff J (1995) Brainstem perfusion is impaired in chronic fatigue syndrome. Q J Med 88:767–773Google Scholar
  16. 16.
    MacHale SM, Lawrie SM, Cavanagh JTO, et al. (2000) Cerebral perfusion in chronic fatigue syndrome and depression. Br J Psychiatr 176:550–556CrossRefGoogle Scholar
  17. 17.
    Chaudhuri A, Condon BR, Gow JW, Brennan D, Hadley DM (2003) Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Neuroreport 14:225–228PubMedCrossRefGoogle Scholar
  18. 18.
    Siessmeier T, Nix WA, Hardt J, Schreckenberger M, Egle UT, Bartenstein P (2003) Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatr 74:922–928PubMedCrossRefGoogle Scholar
  19. 19.
    Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco P, Ferlin G (1998) Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. Am J Med 105(3A):54S–58SPubMedCrossRefGoogle Scholar
  20. 20.
    Kuratsune H, Yamaguti K, Lindh G, et al. (2002) Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage 17:1256–1265PubMedCrossRefGoogle Scholar
  21. 21.
    Yoshiuchi K, Farkas J, Natelson BH (2006) Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging 26:83–86PubMedCrossRefGoogle Scholar
  22. 22.
    Prasher D, Smith A, Findley L (1990) Sensory and cognitive event-related potentials in myalgic encephalomyelitis. J Neurol Neurosurg Psychiatr 53:247–253PubMedCrossRefGoogle Scholar
  23. 23.
    Gordon R, Michalewski HJ, Nguyen T, Gupta S, Starr A (1999) Cortical motor potential alterations in chronic fatigue syndrome. Int J Molec Med 4:493–499PubMedGoogle Scholar
  24. 24.
    Siemionow V, Fang Y, Calabrese L, Sahgal V, Yue GH (2004) Altered central nervous system signal during motor performance in chronic fatigue syndrome. Clin Neurophysiol 115:2372–2381PubMedGoogle Scholar
  25. 25.
    Lange G, Steffener J, Bly BM, et al. (2005) Chronic fatigue syndrome affects verbal working memory: a BOLD fMRI study. Neuroimage 26:513–524PubMedCrossRefGoogle Scholar
  26. 26.
    Tanaka M, Sadato N, Okada T, et al. (2006) Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study. BMC Neurol 6(9):doi:10.1186/1471-2377-6-9Google Scholar
  27. 27.
    Boda WL, Natelson BH, Sisto SA, Tapp WN (1995) Gait abnormalities in chronic fatigue syndrome. J Neurol Sci 131:156–161PubMedCrossRefGoogle Scholar
  28. 28.
    Ash-Bernal R, Wall C, Komaroff AL, et al. (1995) Vestibular test anomalies in patients with chronic fatigue syndrome. Acta Otolaryngol (Stockholm) 115:9–17PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Benjamin H. Natelson
    • 1
  1. 1.Pain and Fatigue Study Center, Department of NeurosciencesUniversity of Medicine and Dentistry — New Jersey Medical SchoolNewarkUSA

Personalised recommendations