Mitochondrial abnormalities in the postviral fatigue syndrome


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.

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  1. 1.

    Acheson ED (1959) The clinical sydrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med 26:569–595

    Google Scholar 

  2. 2.

    Archard LC, Bowles NE, Behan PO, et al (1988) Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase. J R Soc Med 81:326–329

    Google Scholar 

  3. 3.

    Archard LC, Peters J, Behan PO, et al (1988) Detection of Epstein-Barr virus DNA in muscle from patients with postviral chronic fatigue syndrome, myalgic encephalomyelitis. J Exp Clin Cancer Res 7:3 [Suppl]

    Google Scholar 

  4. 4.

    Arnold DL, Radda GK, Bore PJ, et al (1984) Excessive intracellular acidosis of skeletal muscle on exercise in a patient with postviral exhaustion/fatigue syndrome. Lancet 1:1367–1369

    Google Scholar 

  5. 5.

    Astrom E, Friman G, Pilstrom L (1976) Effects of viral and mycoplasma infections on ultrastructure and enzyme activities in human skeletal muscle. Acta Pathol Microbiol Scand 84:113–122

    Google Scholar 

  6. 6.

    Behan PO, Behan WMH (1988) Postviral fatigue syndrome. CRC Crit Rev Neurobiol 4:157–178

    Google Scholar 

  7. 7.

    Byrne E, Trounce I, Dennett X (1985) Chronic relapsing myalgia (?postviral): clinical histological and biochemical studies. Aust N Z J Med 15:305–308

    Google Scholar 

  8. 8.

    Calder BD, Warnock PJ, McCartney RA, Bell EJ (1987) Coxsackie B viruses and the post-viral fatigue syndrome: a prospective study in general practice. J R Coll Gen Pract 37:11–14

    Google Scholar 

  9. 9.

    Cullen MJ, Mastaglia FL (1982) Pathological reactions of skeletal muscle. In: Mastaglia FL, Walton J (eds) Skeletal muscle pathology. Churchill Livingstone, London, pp 88–139

    Google Scholar 

  10. 10.

    Dillon MJ, Marshall WC, Dudgeon JA, et al (1974) Epidemic neuromyasthenia: outbreak among nurses at a children's hospital. Br Med J 1:301–305

    Google Scholar 

  11. 11.

    Di Mauro S, Bonilla E, Zevioni M, Nakagawa M, DeVivo D (1985) Mitochondrial myopathies. Ann Neurol 17:521–538

    Google Scholar 

  12. 12.

    Dubowitz V (1985) The procedure of muscle biopsy and histological and histochemical stains and reactions. In: Muscle biopsy, 2nd edn. Balliere Tindall, London, pp 3–40

    Google Scholar 

  13. 13.

    Fegan KG, Behan PO, Bell EJ (1983) Myalgic encephalomyelitis — report of an epidemic. J R Coll Gen Pract 33:335–337

    Google Scholar 

  14. 14.

    Ghadially FN (1988) Mitochondria. In: Ultrastructural pathology of the cell and matrix, 3rd edn. Butterworths, London, pp 240–249

    Google Scholar 

  15. 15.

    Gow J, Behan WMH, Clements GB, Woodall C, Riding M, Behan PO (1991) Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. Br Med J 302:692–696

    Google Scholar 

  16. 16.

    Hammersen F, Gidlof A, Larsson J, Lewis DH (1980) The occurrence of paracrystalline mitochondrial inclusions in normal human skeletal muscle. Acta Neuropathol (Berl) 49:35–41

    Google Scholar 

  17. 17.

    Henderson DA, Shelokov A (1959) Epidemic neuromyasthenia: clinical syndrome? N Engl J Med 260:757–764

    Google Scholar 

  18. 18.

    Holmes GP, Kaplan JE, Gantz NM, et al (1988) Chronic fatigue syndrome: a working case definition. Ann Intern Med 108:387–389

    Google Scholar 

  19. 19.

    Innes SGB (1970) Encephalomyelitis resembling benign myalgic encephalomyelitis. Lancet I:969–971

    Google Scholar 

  20. 20.

    Jamal GA, Hansen S (1989). Electrophysiological studies in the post-viral fatigue syndrome. J Neurol Neurosurg Psychiatry 48:691–694

    Google Scholar 

  21. 21.

    Jamal GA, Hansen S (1989) Post-viral fatigue syndrome: evidence for underlying organic disturbance in the muscle fibre. Eur Neurol 29:272–276

    Google Scholar 

  22. 22.

    Kamieniecka Z, Schmalbruch H (1980) Neuromuscular disorders with abnormal mitochondria. Int Rev Cytol 65:321–357

    Google Scholar 

  23. 23.

    Miller NA, Carmichael HA, Calder BD, Behan PO, Bell EJ, McCartney RA (1991) Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome. Br Med J 302:140–143

    Google Scholar 

  24. 24.

    Moraes CT, di Mauro S, Zeviani M et al (1989) Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 320:1293–1299

    Google Scholar 

  25. 25.

    Morgan-Hughes JA, Landon DN (1984) Mitochondrial respiratory chain deficiencies in man. Some histochemical and fine-structural observations. In: Serratrice G, et al (eds) Neuromuscular diseases. Raven Press, New York, pp. 23–37

    Google Scholar 

  26. 26.

    Morgan-Hughes JA, Hayes DJ, Clark JB et al (1982) Mitochondrial encephalopathies. Biochemical studies in two cases revealing defects in the respiratory chain. Brain 105:553–582

    Google Scholar 

  27. 27.

    Partin JC, Schubert WK, Partin JS (1971) Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N Engl J Med 285:1339–1343

    Google Scholar 

  28. 28.

    Patten BM, Shabot JM, Alperin J, Dodson RF (1977) Hepatitis-associated lipid storage myopathy. Ann Intern Med 87:417–421

    Google Scholar 

  29. 29.

    Rosenhall U, Johansson G, Orndahl G (1987) (a) Eye motility dysfunction in chronic primary fibromyalgia with dysesthesia. Scand J Rehab Med 19:139–145

    Google Scholar 

  30. 30.

    Rosenhall U, Johannson G, Orndahl G (1987) (b) Neuroaudiological findings in chronic primary fibromyalgia with dysesthesia. Scan J Rehab Med 19:147–152

    Google Scholar 

  31. 31.

    Rowland LP (1983) Molecular genetics, pseudogenetics and clinical neurology. Neurolygy 33:1179–1195

    Google Scholar 

  32. 32.

    Veerkamp JH (1981) The function of muscle mitochondria. In: Busch, HFM, Jennekens F, Scholte HR (eds) Mitochondria and muscle disease. Mefar bv, Beetsterzwaag, The Netherlands, pp 29–50

    Google Scholar 

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Correspondence to P. O. Behan.

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Supported by the Barclay Research Trust

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Behan, W.M.H., More, I.A.R. & Behan, P.O. Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol 83, 61–65 (1991).

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Key words

  • Postviral fatigue syndrome
  • Branching and fusion of mitochondria
  • compartmentalization
  • Mitochondrial vacuolation