Summary
We carried out a histological examination of the extraocular muscles (EOMs) in a case of myoclonus epilepsy associated with ragged-red fibers (MERRF) and two cases of mitochondrial myopathy, encephalopathy, laetic acidosis, and stroke-like episodes (MELAS), which did not manifest external ophthalmoplegia clinically. By light microscopy, many granular and vesicular fibers were seen associated with endomysial fibrosis. Electron microscopy revealed that the fibers showed prominent accumulation of abnormal mitochondria, extensive loss of myofibrils, proliferation of free sarcoplasmic reticulum and an increased amount of lipid vacuoles. These changes were more pronounced in MELAS than in MERRF. Hirano bodies were often seen in the subsarcolemmal area of muscle fibers and also in the intramuscular myelinated nerve fibers and axon terminals. These findings suggest the presence of mitochondrial myopathy of the EOMs in cases of MELAS and MERRF.
Similar content being viewed by others
References
Atsumi T, Yamamura Y, Sato T, Ikuta F (1980) Hirano bodies in the axon of peripheral nerves in a case with progressive external ophthalmoplegia with multisystemic involvements. Acta Neuropathol (Berl) 49:95–100
Carry MR, Ringel SP, Starcevich JM (1986) Mitochondrial morphometrics of histochemically identified human extraocular muscle fibers. Anat Rec 214:8–16
Castaigne P, Lhermitte F, Escourolle R, Chain F, Fardeau M, Hauw JJ, Curet J, Flavigny C (1977) Etude anatomoclinique d'une observation d'“ophthalmoplegia plus” avec analyse des lesions musculaires, nerveuses centrales, oculaires, myoccardiques et thyroidiennes. Rev Neurol (Paris) 133:369–386
Daroff RB, Solitare GB, Pincus JH, Glaser GH (1966) Spongiform encephalopathy with chronic progressive external ophthalmoplegia — Central ophthalmoplegia mimicking ocular myopathy. Neurology 16:161–169
DiMauro S, Bonilla E, Zeviani N, Nakagawa M, DeVivo DC (1985) Mitochondrial myopathies. Ann Neurol 17:521–538
Fukuhara N (1983) Myoclonus epilepsy and mitochondrial myopathy. In: Scarlato G, Cerri C (eds) Mitochondrial pathology in muscle diseases. Piccin Medical Books, Padua, pp 88–110
Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T (1980) Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): disease entity or a syndrome? Light and electron microscopic studies of two cases and review of literature. J Neurol Sci 47:117–133
Groothuis DR, Schulman S, Wollman R, Frey J, Vick NA (1980) Demyelinating radiculopathy in the Kearns-Sayre syndrome: a clinicopathological study. Ann Neurol 8:373–380
Hart MN, Cancilla PA, Eshaghian J, Anderson PL (1978) “Ragged red” fibers in orbicularis oculi. J Neuropathol Exp Neurol 37:623 [abstr]
Hart ZH, Chang C-H, Perrin EVD, Neerunjun JS, Ayyar R (1977) Familial poliodystrophy, mitochondrial myopathy, and lactate acidemia. Arch Neurol 34:180–185
Horwitz SJ, Roessmann U (1978) Kearns-Sayre syndrome with hypoparathyroidism. Ann Neurol 3:513–518
Kearns TP, Sayre GP (1958) Retinitis pigmentosa, external ophthalmoplegia, and complete heart block — Unusual syndrome with histologic study in one of two cases. Arch Ophthal 60:280–289
Kuriyama M, Umezaki H, Fukuda Y, Osame M, Koike K, Tateishi J, Igata A (1984) Mitochondrial encephalopathy with lactate-pyruvate elevation and brain infarctions. Neurology 34:72–77
Martinez AJ, Hay S, McNeer KW (1976) Extraocular muscles. Light microscopy and ultrastructural features. Acta Neuropathol (Berl) 34:237–253
Mukoyama M, Kazui H, Sunohara N, Yoshida M, Nonaka I, Satoyoshi E (1986) Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with aconthocytosis: a clinicopathological study of a unique case. J Neurol 233:228–232
Nakano T, Sakai H, Amano N, Yagishita S, Ito Y (1982) An autopsy case of degenerative type myoclonus epilepsy associated with Friedreich's ataxia and mitochondrial myopathy. No To Shinkei (Tokyo) 34:321–332
Nishizawa M, Tanaka K, Shinozawa K, Kuwabara T, Atsumi T, Miyatake T, Ohama E (1987) A mitochondrial encephalomyopathy with cardiomyopathy. A case revealing a defect of complex I in the respiratory chain. J Neurol Sci 78:189–201
Ohama E, Ohara S, Ikuta F, Tanaka K, Nishizawa M, Miyatake T (1987) Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy. Acta Neuropathol (Berl) 74:226–233
Ohara S, Ohama E, Ikuta F, Nishizawa M, Kuwabara T (1988) An autopsy case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episode). Clin Neurol (Tokyo) 28:303–310
Ohara S, Ohama E, Takahashi H, Ikuta F, Nishizawa M, Tanaka K, Miyatake T (1988) Alterations of oligodendrocytes and demyelination in the spinal cord of patients with mitochondrial encephalomyopathy. J Neurol Sci 86:19–29
Pavlakis SG, Phillips PC, DiMauro S, DeVivo DC, Rowland LP (1984) Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 16:481–488
Ringel SP, Wilson WB, Barden MT (1979) Extraocular muscle biopsy in chronic progressive external ophthalmoplegia. Ann Neurol 6:326–339
Sasaki H, Kuzuhara S, Kanazawa I, Nakanishi T, Ogata T (1983) Myoclonus, cerebellar disorder, neuropathy, mitochondrial myopathy, and ACTH deficiency. Neurology 33:1288–1293
Shapira Y, Cederbaum SD, Cancilla PA, Nielsen D, Lippe BM (1975) Familial poliodystrophy, mitochondrial myopathy, and lactate acidemia. Neurology 25:614–621
Schneck L, Adachi M, Briet P, Wolintz A, Volk BW (1973) Ophthalmoplegia plus with morphological and chemical studies of cerebellar and muscle tissue. J Neurol Sci 19:37–44
Schwarz GA, Liu C-N (1954) Chronic progressive external ophthalmoplegia. A clinical and neuropathologic report. Arch Neurol Psychiatry 71:31–53
Shinozawa K, Nishizawa M, Tanaka K, Atsumi T, Ohama E (1987) A mitochondrial encephalomyopathy: a case of a defect of complex I in the electron transport chain. Clin Neurol (Tokyo) 27:41–48
Takeda S, Wakabayashi K, Ohama E, Ikuta F (1988) Neuropathology of myoclonus epilepsy associated with ragged-red fibers (Fukuhara's disease). Acta Neuropathol (Berl) 75:433–440
Tanaka K, Ueno M, Atsumi T, Fukagawa M, Koike Y (1986) A case of mitochondrial encephalomyopathy with nephrotic syndrome. Clin Neurol (Tokyo) 26:1190–1196
Tomonaga M (1983) Hirano body in extraocular muscle. Acta Neuropathol (Berl) 60:309–313
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takeda, S., Ohama, E. & Ikuta, F. Involvement of extraocular muscle in mitochondrial encephalomyopathy. Acta Neuropathol 80, 118–122 (1990). https://doi.org/10.1007/BF00308913
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00308913