Chronic Fatigue Syndrome

  • Hirohiko Kuratsune
  • Yasuyoshi Watanabe

Abstract

Chronic fatigue syndrome (CFS) is an operational concept for clarifying the unknown etiology of the syndrome characterized by the sensation of abnormally prolonged fatigue. The vast majority of patients with CFS are interrupted in their daily or social lives by prolonged fatigue, headache, myalgia, arthralgia, sleep disturbance, or brain dysfunctions. However, the pathogenesis of CFS remains unclear, and so there are still many medical doctors around the world who are skeptical about the disease.

Recently, we organized a study group of Japanese investigators from various fields, such as virology, immunology, endocrinology, physiology, biochemistry, psychiatry, and neuroscience, and as a result of the efforts of this group the mechanism underlying CFS is now becoming a little clearer. We are now able to suggest that CFS can be understood to be a special condition based on an abnormality of the psycho-neuro-endocrino-immunological system caused by psycho-social stress, and which has some genetic components. A reactivation of various types of herpes virus infections and/or chronic mycoplasma infection might occur as a result of immune dysfunction, causing the abnormal production of several cytokines. A distinctive feature of CFS is thought to be a secondary brain dysfunction caused by the abnormal production of such cytokines.

In this chapter, we would like to introduce not only the recent findings on the pathogenesis of CFS, but also the prevalence, diagnosis, therapy, and prognosis of CFS in Japan.

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References

  1. 1.
    Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Strauss SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, Tosato G, Zegans LS, Purtilo DT, Browh N, Schooles RT, Brus I (1988) Chronic fatigue syndrome: a working case definition. Ann Intern Med 108:387–389PubMedGoogle Scholar
  2. 2.
    Holmes TH, Rahe RH (1967) The social readjustment rating scale. J Psychosom Res 11:213–218PubMedCrossRefGoogle Scholar
  3. 3.
    Narita M, Nishigami N, Narita N, Yamaguti K, Okado N, Watanabe Y, Kuratsune H (2003) Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochem Biophys Res Commun 311(2):264–266PubMedCrossRefGoogle Scholar
  4. 4.
    Klimas NG, Salvato FR, Morgan R, Fletcher MA (1990) Immunologic abnormalities in chronic fatigue syndrome. J Clin Microbiol 28(6):1403–1410PubMedGoogle Scholar
  5. 5.
    Bennett AL, Chao CC, Hu S, Buchwald D, Fagioli LR, Schur PH, Peterson PK, Komaroff AL (1997) Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome. J Clin Immunol 17(2):160–166PubMedCrossRefGoogle Scholar
  6. 6.
    Moss RB, Mercandetti A, Vojdani A (1999) TNF-alpha and chronic fatigue syndrome. J Clin Immunol 19(5):314–316PubMedCrossRefGoogle Scholar
  7. 7.
    Suhadolnik RJ, Reichenbach NL, Hitzges P, Sobol RW, Peterson DL, Henry B, Ablashi DV, Müller WE, Schröder HC, Carter WA, Strayer DR (1994) Upregulation of the 2-5A synthetase/ RNase L antiviral pathway associated with chronic fatigue syndrome. Clin Infect Dis 18(Suppl 1):S96–104PubMedGoogle Scholar
  8. 8.
    Ikuta I, Yamada T, Shimomura T, Kuratsune H, Kawahara R, Ikawa S, Ohnishi E, Sokawa Y, Fukushi H, Hirai K, Watanabe Y, Kurata T, Kitani T, Sairenji T (2003) Diagnostic evaluation for 2′,5′-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan. Microbes Infect 5(12):1096–1102PubMedCrossRefGoogle Scholar
  9. 9.
    Demettre E, Bastide L, D’Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B (2002) Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem 277(38):35746–35751PubMedCrossRefGoogle Scholar
  10. 10.
    Katafuchi T, Kondo T, Yasaka T, Kubo K, Take S, Yoshimura M (2003) Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running-wheel activity and brain interferon-alpha mRNA in rats: a model for immunologically induced fatigue. Neuroscience 120(3):837–845PubMedCrossRefGoogle Scholar
  11. 11.
    Inoue K, Yamazaki H, Manabe Y, Fukuda C, Hanai K, Fushiki T (1999) Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance to central fatigue. Brain Res 846(2):145–153PubMedCrossRefGoogle Scholar
  12. 12.
    Stankovic AK, Dion LD, Parker CR Jr. (1994) Effects of transforming growth factor-beta on human fetal adrenal steroid production. Mol Cell Endocrinol 99(2):145–151PubMedCrossRefGoogle Scholar
  13. 13.
    Chiu KM, Schmidt MJ, Shug AL, Binkley N, Gravenstein S (1997) Effect of dehydroepiandrosterone sulfate on carnitine acetyl transferase activity and L-carnitine levels in oophorectomized rats. Biochim Biophys Acta 1344(3):201–209PubMedGoogle Scholar
  14. 14.
    Kuratsune H, Yamaguti K, Sawada M, Kodate S, Machii T, Kanakura Y, Kitani T (1998) Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med 1:143–146PubMedGoogle Scholar
  15. 15.
    Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T (1994) Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 18(Suppl 1):S62–S67PubMedGoogle Scholar
  16. 16.
    Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y, Tatsumi KI, Takano T, Kanakura Y, Amino N (2003) Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med 12:225–230PubMedGoogle Scholar
  17. 17.
    Levy JA (1994) Viral studies of chronic fatigue syndrome. Clin Infect Dis 18(Suppl 1): S117–120PubMedGoogle Scholar
  18. 18.
    Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, Pearson GR, Whitman JE (2000) Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol 16(3):179–191PubMedCrossRefGoogle Scholar
  19. 19.
    Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW (1998) Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with chronic fatigue syndrome. FEMS Immunol Med Microbiol 22(4):355–365PubMedCrossRefGoogle Scholar
  20. 20.
    Nakaya T, Takahashi H, Nakamura Y, Asahi S, Tobiume M, Kuratsune H, Kitani T, Yamanishi K, Ikuta K (1996) Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett 378:145–149PubMedCrossRefGoogle Scholar
  21. 21.
    Nakaya T, Takahashi H, Nakamur Y, Kuratsune H, Kitani T, Machii T, Yamanishi K, Ikuta K (1999) Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome. Microbiol Immunol 43(7):679–689PubMedGoogle Scholar
  22. 22.
    Evengård B, Briese T, Lindh G, Lee S, Lipkin WI (1999) Absence of evidence of Borna disease virus infection in Swedish patients with chronic fatigue syndrome. J Neurovirol 5(5):495–499PubMedCrossRefGoogle Scholar
  23. 23.
    Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi MJ, Chrousos GP, Gold PW (1991) Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab 73(6):1224–1234PubMedCrossRefGoogle Scholar
  24. 24.
    Roberts AD, Wessely S, Chalder T, Papadopoulos A, Cleare AJ (2004) Salivary cortisol response to awakening in chronic fatigue syndrome. Br J Psychiatr 184:136–131CrossRefGoogle Scholar
  25. 25.
    Gaab J, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U (2004) Associations between neuroendocrine responses to the insulin tolerance test and patient characteristics in chronic fatigue syndrome. J Psychosom Res 56(4):419–424PubMedCrossRefGoogle Scholar
  26. 26.
    Gaab J, Hüster D, Peisen R, Engert V, Schad T, Schürmeyer TH, Ehlert U (2002) Low-dose dexamethasone suppression test in chronic fatigue syndrome and health. Psychosom Med 64(2):311–318PubMedGoogle Scholar
  27. 27.
    Rebouche CJ (1988) Carnitine metabolism and human nutrition. J Appl Nutr 40:99–111Google Scholar
  28. 28.
    Yamaguti K, Kuratsune H, Watanabe Y, Takahashi M, Nakamoto I, Machii T, Jacobsson G, Onoe H, Matsumura K, Valind S, Langstrom B, Kitani T (1996) Acylcarnitine metabolism during fasting and after refeeding. Biochem Biophys Res Commun 225:740–746PubMedCrossRefGoogle Scholar
  29. 29.
    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 (2002) Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage 17(3):1256–1265PubMedCrossRefGoogle Scholar
  30. 30.
    Plioplys AV, Plioplys S (1995) Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Biol Psychiatr 32:132–138Google Scholar
  31. 31.
    Soetekouw PM, Wevers RA, Vreken P, Elving LD, Janssen AJ, van der Veen Y, Bleijenberg G, van der Meer JW (2000) Normal carnitine levels in patients with chronic fatigue syndrome. Neth J Med 57(1):20–24PubMedCrossRefGoogle Scholar
  32. 32.
    Jones MG, Goodwin CS, Amjad S, Chalmers RA (2005) Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome. Clin Chim Acta 360(1–2):173–177PubMedCrossRefGoogle Scholar
  33. 33.
    Vermeulen RC, Scholte HR (2006) Azithromycin in chronic fatigue syndrome (CFS): an analysis of clinical data. J Trans Med 4:34CrossRefGoogle Scholar
  34. 34.
    Vermeulen RC, Scholte HR (2004) Exploratory open label, randomized study of acetyl-and propionylcarnitine in chronic fatigue syndrome. Psychosom Med 66(2):276–282PubMedCrossRefGoogle Scholar
  35. 35.
    Kuratsune H, Yamaguti K, Watanabe Y, Takahashi M, Nakamoto I, Machii T, Jacobson GB, Onoe H, Matsumura T, Valind S, Langstrom B, Kitani T (1997) Acylcarnitine and chronic fatigue syndrome. In: DeSimone C, Famularo G (eds) Carnitine today. Molecular Biology Intelligence Unit, Landes Bioscience, pp 195–213Google Scholar
  36. 36.
    Natelson BH, Cohen JM, Brassloff I, Lee HJ (1993) A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci 120(2):213–217PubMedCrossRefGoogle Scholar
  37. 37.
    Greco A, Tannock C, Brostoff J, Costa DC (1997) Brain MR in chronic fatigue syndrome. Am J Neuroradiol 18(7):1265–1269PubMedGoogle Scholar
  38. 38.
    Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH (1999) Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci 171(1):1–2CrossRefGoogle Scholar
  39. 39.
    Cook DB, Lange G, DeLuca J, Natelson BH (2001) Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome. Int J Neurosci 107(1–2):1–6PubMedCrossRefGoogle Scholar
  40. 40.
    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(1):14PubMedCrossRefGoogle Scholar
  41. 41.
    de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I (2005) Gray matter volume reduction in chronic fatigue syndrome. Neuroimage 26(3):777–781PubMedCrossRefGoogle Scholar
  42. 42.
    Ichise M, Salit IE, Abbey SE, Chung DG, Gray B, Kirsh JC, Freedman M (1992) Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun 13:767–772PubMedCrossRefGoogle Scholar
  43. 43.
    Costa DC, Tannock C, Brostoff J (1995) Brainstem perfusion is impaired in chronic fatigue syndrome. QJM 88:767–773PubMedGoogle Scholar
  44. 44.
    Fischler B, D’Haenen H, Cluydts R, Michiels V, Demets K, Bossuyt A, Kaufman L, De Meirleir K (1996) Comparison of 99m Tc 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
  45. 45.
    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
  46. 46.
    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 Psychiatry 74(7):922–928PubMedCrossRefGoogle Scholar
  47. 47.
    Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y (2004) Reduction of serotonin transporters in patients with chronic fatigue syndrome. Neuroreport 15:2571–2574PubMedCrossRefGoogle Scholar
  48. 48.
    Demettre E, Bastide L, D’Haese A, De Smet K, De Meirleir K, Tiev KP, Englebienne P, Lebleu B (2002) Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem 277(38):35746–35751PubMedCrossRefGoogle Scholar
  49. 49.
    Oliff A, Defeo-Jones D, Boyer M, Martinez D, Kiefer D, Vuocolo G, Wolfe A, Socher SH (1987) Tumors secreting human TNF/cachectin induce cachexia in mice. Cell 50(4):555–563PubMedCrossRefGoogle Scholar
  50. 50.
    Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A (1994) The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 121(12):953–959PubMedGoogle Scholar
  51. 51.
    Bode L, Dietrich DE, Stoyloff R, Emrich HM, Ludwig H (1997) Amantadine and human Borna disease virus in vitro and in vivo in an infected patient with bipolar depression. Lancet 349(9046):178–179PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Hirohiko Kuratsune
    • 1
  • Yasuyoshi Watanabe
    • 2
  1. 1.Department of Health Science, Faculty of Health Science for WelfareKansai University of Welfare SciencesKasiwara, OsakaJapan
  2. 2.Department of PhysiologyOsaka City University Graduate School of MedicineOsakaJapan

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