Skip to main content
SpringerLink
Log in

Clinical, morphological, biochemical, and neuroradiological features of mitochondrial encephalomyopathies. Presentation of 19 patients

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Nineteen patients (9 females, 10 males) with mitochondrial encephalomyopathies (ME) were studied. The diagnosis was established according to clinical and histopathological criteria. Leading clinical features were chronic progressive external ophthalmoplegia (CPEO) and muscle weakness in 95% of the patients. Pigmentary retinopathy was seen in 63%, and was always associated with CPEO. Hypacusis was present in 47% and cerebellar ataxia in 63% of patients. Clinical or electrophysiological signs of involvement of the central nervous system (CNS) were found in 21% of the patients. In muscle biopsy ragged red fibers were the predominant histopathological findings (100% of the patients), while COX-negative fibers were seen in 74%, deletions of the mitochondrial DNA in 42%, and defects of the respiratory chain in 32% of the patients. Increased blood lactate levels were found in 79% of the patients. Needle electromyography revealed myopathic features in 74%, features of denervation in 16%, and w as normal in the remainder. Imaging studies showed cerebral atrophy in 58%, cerebellar atrophy in 16%, and hyperintense lesions of the white matter, pyramidal tract or extrapyramidal system in 16% of the cases. It is concluded that the clinical manifestations of ME can be very variable. Diagnosis of ME should be always considered in young patients presenting with CPEO and muscle weakness. In most cases, diagnosis can be made by a few selected investigations, while detection of genetic abnormalities may lead to the diagnosis in the remaining cases. (Mol Cell Biochem 174: 297–303, 1997)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. DiMauro S, Bonilla E, Lombes A, Shanske S, Minetti C, Moraes C: Mitochondrial encephalomyopathies. Neurol Clin 8: 483–606, 1990

    Google Scholar 

  2. Holt IJ, Harding A, Morghan-Hughes J: The clinical features of mitochondrial myopathy. Brain 109: 915–923, 1986

    Google Scholar 

  3. Jackson MJ, Schaefer JA, Johnson MA, Morris AAM, Turnbull DM, Bindorff LA: Presentation and clinical investigation of mitochondrial respiratory chain disease. Brain 118: 339–357, 1995

    Google Scholar 

  4. Shapira Y, Harsel S, Russell A: Mitochondrial encephalomyopathies. A group of neuromuscular disorders with defects in oxidative metabolism. Isr J Med Sci 13: 161–164, 1977

    Google Scholar 

  5. Fukuhara N: Myoclonus epilepsy and mitochondrial myopathy. In: C Gerri, G Scarlato (eds). Mitochondrial Pathology in Muscle Diseases. Padua, Picini Editore, 1988, pp 87–111

    Google Scholar 

  6. Pavalakis S, Phillips S, DiMauro S: Mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like-episodes: a distinctive clinical syndrome. Ann Neurol 16: 481–488, 1984

    Google Scholar 

  7. Bastiaensen LAK, Joosten EMG, de Rooij JAM, Hommes OR, Stadhouders AM, Jaspan HH, Veerkamp JH, Bookelman H, van Huisbergh VW: Ophthalmoplegia plus. A real nosological entity. Acta Neurol Scand 58: 9–34, 1978

    Google Scholar 

  8. Petty RKH, Harding AE, Morghan-Hughes JA: The clinical features of mitochondrial myopathy. Brain 109: 915–938, 1986

    Google Scholar 

  9. Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T: Myoclonus epilepsy associated with ragged red fibers (mitochondrial abnormalities) disease entity or syndrome. J Neurol Sci 47: 117–133, 1980

    Google Scholar 

  10. Pavalakis SG, Phillips PC, DiMauro S, DeVivo DC, Rowland LP: Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 16: 481–488, 1984

    Google Scholar 

  11. Zierz S, Jerusalem F: Mitochondrial myopathy and encephalomyopathy. Nervenarzt 60: 394–400, 1989

    Google Scholar 

  12. Yamamoto M, Nonaka I: Skeletal muscle pathology in chronic progressive external ophthalmoplegia with ragged red fibers. Acta Neuropathol 76: 558–564, 1988

    Google Scholar 

  13. DiMauro S: Mitochondrial encephalomyopathies. In: RN Rosenberg, SB Prusnier, S DiMauro, RI Barchi, LM Kunkel (eds). The Molecular and Genetic Basis of Neurological Disease. Butterworth Heinemann, Boston Wellington, 1993, pp 665–694

    Google Scholar 

  14. Shoffner JM. Lott MT, Lezza AMS, Seikel P, Ballinger SW, Wallace DC: Myoclonic epilepsy and ragged-red fibers (MERRF) is associated with a mitochondrial DNA tRNALys mutation. Cell 61: 931–937, 1990

    Google Scholar 

  15. Goto YI, Nonaka I, Horai SA: A mutation in the tRNALeu[UUR] gene associated with the MELAS sub-group of mitochondrial encephalomyopathies. Nature 384: 651–653, 1990

    Google Scholar 

  16. Kobayashi Y, Momoi MY, Tomianfa K, Nihei K, Yanagisawa M, Kagawa Y: A point mutation in the mitochondrial tRNA Leu[UUR] gene in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Biochem Biophys Res Commun 173: 816–822, 1990

    Google Scholar 

  17. Bindoff LA, Thurnbull DM: Defects of the respiratory chain. In: JB Harris, DM Thurnbull (eds). Muscle Metabolism. Vol. 4. Balliere Tindall, London, 1990, pp 583– 619

    Google Scholar 

  18. Rowland LP, Blake DM, Hirano M, DiMauro S, Schon AP, Hays AP, DeVivo DC: Clinical syndromes associated with ragged-red fibers. Rev Neurol (Paris) 147: 467–473, 1991

    Google Scholar 

  19. Munnic A, Rustin P, Rötig A, Chretien D, Bonnefont JP, Nuttin C, Cormier V, Vassault A, Parvy P, Bardet J: Clinical aspects mitochondrial disorders. J Inhert Metab Dis 15: 448–455, 1992

    Google Scholar 

  20. DiMauro S, Moraes CT: Mitochondrial encephalomyopathies. Arch Neurol 50: 1197–1208, 1993

    Google Scholar 

  21. Lombes A, Bonilla E, DiMauro S: Mitochondrial encephalomyopathies. Rev Neurol (Paris) 145(10): 671–689, 1989

    Google Scholar 

  22. Drachman DA: Ophthalmoplegia plus: A classification of disorders associated with progressive external ophthalmoplegia. In: PJ Vinken, GW Bruyn, JMBV DeJong, HL Klawans (eds). Handbook of Clinical Neurology. Vol. 22. Elsevier, Amsterdam, 1975, pp 203–216

    Google Scholar 

  23. Bastiaensen LAK, Joostens EMS, DeRoou JAM, Hommes OR, Stadhouders AM, Jaspar HH, Veerkamp JH, Bookelman H, Van Hinsberg VW: Ophthalmoplegia plus. A real nosological entity. Acta Neurol Scand 58: 9–34, 1978

    Google Scholar 

  24. Berenberg RA, Pellock JM, DiMauro S: Lumping or splitting? 'Ophthalmoplegia plus' or Kearns-Sayre syndrome? Ann Neurol 1: 37–54, 1977

    Google Scholar 

  25. Holt IJ, Harding AE, Cooper JM, Shapira HV, Toscano A, Clark JB, Morgan-Hughes JA: Mitochondrial myopathy. Clinical and biochemical features of 30 patients with major deletions of muscle mitochondrial DA. Ann Neurology 26: 699–708, 1989

    Google Scholar 

  26. Zeviani M, Gellera C, Pannacci M et al.: Tissue distribution ad transmission of mitochondrial DNA deletions in mitochondrial myopathies. Ann Neurol 28: 94–97, 1990

    Google Scholar 

  27. Goto Y, Koga Y, Horai S et al.: Chronic progressive external ophthalmoplegia: A correlative study of mitochondrial DNA deletions and their phenotype expression in muscle biopsies. J Neurol Sci 100: 168–177, 1991

    Google Scholar 

  28. Degoul F, Nelson I, Lestienne P, Francois D, Romero N, Duboc D, Eymard B, Fardeau M, Ponsot G, Paturneau-Jouas M, Chaussain M, Leroux JPP, Marsac C: Deletions of mitochondrial DNA in Kearns-Sayre-syndrome and ocular myopathies: Genetic, biochemical, and morphological studies. J Neurol Sci 102: 92–99, 1991

    Google Scholar 

  29. Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF, Nakase H, Bonilla E, Werneck LC, Servidei S, Nonaka I, Koga Y, Spiro AJ, Brownwell KW, Schmidt B, Schotland DL, Zupanec M, DeVivo DC, Schon EA, Rowland LP: Mitochondrial DNA deletion in progressive external ophthalmoplegia and Kearns-Sayre-Syndrome. N Engl J Med 320: 1293–1299, 1989

    Google Scholar 

  30. Fukuhara N, Tociguchi S, Shirakawa K, Tsubaki T: Myoclonus epilepsy associated with ragged red fibers (mitochondrial abnormalities): Disease entity or a syndrome? J Neurol Sci 47: 117–133, 1980

    Google Scholar 

  31. Morgan-Hughes JA, Hayes DJ, Clark JB, Landon DN, Swash H, Stark RJ, Rudge P: Mitochondrial encephalomyopathies: Biochemical studies in two cases revealing defects in the respiratory chain. Brain 105: 533–582, 1982

    Google Scholar 

  32. Berkovic SF, Carpenter S, Evans A, Karpati G, Shoubridge EA, Andermann F, Meyer E, Tyler JL, Diksic M, Arnold D, Wolfe LS, Andermann E, Hakim AM: Myoclonus epilepsy and ragged-red fibers (MERRF). A clinical, pathotological, biochemical, magnetic resonance spectrographic and positron emission tomographic study. Brain 112: 1231–1260, 1989

    Google Scholar 

  33. Hammans SR, Sweeny MG, Brockington M, Morgan-Hughes JA, Harding AE: Mitochondrial encephalomyopathies. Molecular genetic diagnosis from blood samples. Lancet 337: 1311–1313, 1991

    Google Scholar 

  34. Wallace DC, Zheng X, Lott MT, Shoffner JM, Hodge JA, Kelley RI, Epstein CHM, Hopkins LC: Familial mitochondrial encephalomyopathy (MERRF): Genetic, pathophysiological and biochemical characterization of a mitochondrial DNA disease. Cell 55: 601–610, 1988

    Google Scholar 

  35. Desnuelle C, Birch-Machin M, Pellisier JF et al.: Multiple defects of the respiratory chain including complex II in a family with myopathy and encephalopathy. Biochem Biophys Res Comm 63: 695–700, 1989

    Google Scholar 

  36. Lombes A, Mendell JR, Nakase H, Barohn RJ, Bonilla E, Zeviani M, Yates AJ, Omerza J, Gales TL, Nakahara K, Rizzuto R, King Engel W, DiMauro S: Myoclonic epilepsy and ragged-red fibers with cytochrome c oxidase deficiency: Neuropathology, biochemistry, and molecular genetics. Ann Neurol 26: 20–33, 1989

    Google Scholar 

  37. Silvestri G, Moraes CT, Shanske S, Oh SJ, DiMauro S: A new mtDNA mutation in the tRNALys gene associated with myoclonic epilepsy and ragged-red fibers (MERRF). Am J Hum Genet 51: 1213–1217, 1990

    Google Scholar 

  38. Zeviani M, Muntoni F, Savarese N, Serra G, Tiranti V, Carrara F, Mariotti C, Di Donato S: Clinical features associated with the A?G transition at nucleotide 8344 of mtDNA ('MERRF' mutation). Neurology 43: 1200–1206, 1993

    Google Scholar 

  39. Pavalakis SG, Rowland LP, DiMauro S, DeVivo DC, Rowland LP: Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Ann Neurol 16: 481487, 1984

    Google Scholar 

  40. Van Hellenberg Hubar JLM, Gabreels FJM, Ruitenberg W, Sengers A, Renier WO, Thijssen HOM, ter Kack HJ: MELAS Syndrome. Report of 2 patients, and comparison with 24 patients derived from the literature. Neuropediatrics 22: 10–14, 1991

    Google Scholar 

  41. Ciafaloni E, Ricci E, Shanske S, Moraes CT, Silvestri C, Hirano M, Simonetti S, Angelini C, Donati MA, Garcia C, Martinuzzi A, Mosewich R, Servidei S, Zamarachi E, Bonilla E, DeVivo DC, Rowland LP, Schon SA, DiMauro S: MELAS: Clinical features, biochemistry, and molecular genetics. Ann Neurol 31: 391398, 1992

    Google Scholar 

  42. Hamans SR, Sweeney MG, Brockington M, Morgan-Hughes JA, Harding AE: Mitochondrial encephalomyopathies: Molecular genetic diagnosis from blood samples. Lancet 337: 1311–1313, 1991

    Google Scholar 

  43. DiMauro S: Mitochondrial encephalomyopathies. In: RN Rosenberg, SB Prusiner, S DiMauro, RL Barchi, LM Kunkel (eds). The Molecular and Genetic Basis of Neurological Diseases. Butterworth Heinemann, Boston Wellington, pp 665–694, 1993

    Google Scholar 

  44. Müller-Höcker J: Cytochrome c oxidase deficient fibers in the limb muscle and diaphragm of a man without muscular disease: an age related alteration. J Neurol Sci 100: 14–21, 1990

    Google Scholar 

  45. Schneck L, Adachi M, Briet P, Wolintz A, Volk BW: Ophthalmoplegia plus with morphological and chemical studies of cerebellar and muscle tissue. J Neurol Sci 19: 37–44, 1973

    Google Scholar 

  46. Bresolin N, Moggio M, Bet L, Gallanti A, Prelle A, Nobile-Obrazio E, Adobbati L, Ferrante C, Pellegrini G, Scarlato G: Progressive cytochrome-c oxidase deficiency in a case of Kearns-Sayre syndrome: morphological, immunological and biochemical studies in muscle biopsies and autopsy tissue. Ann Neurol 21: 564572, 1987

    Google Scholar 

  47. Oldfords A, Fyhr IM, Holme E, Larrson NG, Tulinium M: Neuropathology in Kearns-Sayre syndrome. Acta Neuropathol 80: 541–546, 1990

    Google Scholar 

  48. Leutner G, Layer G, Zierz S, Solymosi L, Dewes W, Reiser M: Cerebral MR in ophthalmoplegia plus. AJNR Am J Neuroradiol 15: 681–67, 1994

    Google Scholar 

  49. Wray SH, Provenzale JM, Johns DR, Thulborn KR: MR of the brain in mitochondrial myopathy. AJNR Am J Neuroradiol 16: 1167–1173, 1995

    Google Scholar 

  50. Taverni N, Delpozzo G, Arnetoli G, Zappoli R: Diagnosis and follow-up of mitochondrial encephalomyopathy: CT and MR studies. J Comput Assist Tomogr 12: 696–697, 1988

    Google Scholar 

  51. Egger J, Kendall BE: Computed tomography in mitochondrial cytopathy. Neuroradiol 22: 73–78, 1981

    Google Scholar 

  52. Hasuo K, Tamura S, Yasumori K, Uchino A, Goda S, Ishimoto S, Kamikaseda K, Wakuta Y, Kishi M, Masuda K: Computed tomography and angiography in MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes): report of 3 cases. Neuroradiol 29: 393–397, 1987

    Google Scholar 

  53. Daroff RB, Solitare GB, Pincus JH, Glaser GH: Spongiform encephalopathy with chronic progressive external ophthalmoplegia. Neurology 16: 161–169, 1966

    Google Scholar 

  54. Horriwitz SJ, Rosessmann V: Kearns-Sayre syndrome with hypoparathyroidism. Ann Neurol 3: 513–518, 1978

    Google Scholar 

  55. Van der Knaap MS, Valk J: Magnetic Resonance of Myelin, Myelination, and Myelin Disorders. Springer, Berlin, Heidelberg, New York, 1995.

  56. Kendall B: Disorders of lysosomes, peroxisomes, and mitochondria. AJNR Am J Neuroradiol 13: 621–653, 1992

    Google Scholar 

  57. Fukuhara N: Myoclonus epilepsy and mitochondrial myopathy. In: C Gerri, G Scarlato (eds). Mitochondrial Pathology in Muscle Diseases. Padua, Piccini Editore, 1988, pp 87–111

    Google Scholar 

  58. Rosen L, Phillips S, Enzmann D: Magnetic resonance imaging in MELAS syndrome. Neuroradiol 32: 168–171, 1990

    Google Scholar 

  59. Suzuki T, Koizumi J, Shiraishi H, Ishikawa N, Ofuku K, Sasaki M, Hori T, Ohkoshi N, Anno I: Mitochondrial encephalomyopathy (MELAS) with mental disorder: CT, MRI and SPECT findings. Neuroradiol 32: 74–76, 1990

    Google Scholar 

  60. DeVolder A, Ghilain S, DeBarsy T, Goffinet AM: Brain metabolism in mitochondrial encephalomyopathy: a PET study. J Comp Assist Tomogr 12: 854–857, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neuroradiology, University of Würzburg, Germany

    Alfred Lindner & Erich Hofmann

  2. Department of Neurology, University of Halle, Germany

    Alfred Lindner

  3. Department of Neurology, University of Würzburg, Germany

    Markus Naumann, Georg Becker & Heinz Reichmann

  4. Department of Neurology, University of Dresden, Germany

    Heinz Reichmann

Authors
  1. Alfred Lindner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erich Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Markus Naumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Georg Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heinz Reichmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lindner, A., Hofmann, E., Naumann, M. et al. Clinical, morphological, biochemical, and neuroradiological features of mitochondrial encephalomyopathies. Presentation of 19 patients. Mol Cell Biochem 174, 297–303 (1997). https://doi.org/10.1023/A:1006823818118

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006823818118

Search

Navigation