Summary
We report the clinical and autopsy findings in a young man of 18 with a chronic progressive disorder comprised of lactic acidosis, mental deterioration, and epileptic seizures which were sometimes accompanied by stroke-like episodes with transient hemiparesis and cortical blindness. He died of congestive heart failure. The autopsy showed lesions of the gray matter of the brain. Both the putamen and parieto-occipital cortex showed loss of neurons and proliferation of macrophages, astrocytes and vessels. There was marked loss of neurons in the inferior olives, and slight reduction of the number of Purkinje cells. Skeletal muscle studies revealed ragged-red fibres and structurally abnormal mitochondria. The heart was enlarged: accumulations of mitochondria occurred in the muscle fibers. The liver exhibited marked fatty degeneration. Biochemical analyses showed normal activities of pyruvate dehydrogenase in thrombocytes, pyruvate carboxylase in lymphocytes, biotinidase in serum as well as succinate dehydrogenase and cytochrome c oxidase. The features of this disorder differ in many respects from cases of mitochondrial encephalomyopathy previously reported and cannot be assigned to any specific disease entity.
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References
Alpers BJ (1931) Diffuse progressive degeneration of the grey matter of the cerebrum. Arch Neurol Psychiatry 25:469–505
Atkin BM, Utter MF, Weinberg MB (1979) Pyruvate carboxylase and phosphoenol-pyruvate carboxykinase activity in leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency. Pediatr Res 13:38–43
Bishop SP, Cole CR (1969) Ultrastructural changes in the canine myocardium with right ventricular hypertrophy and congestive heart failure. Lab Invest 20:219–229
Blass JP, Cederbaum SD, Kark RAP (1977) Rapid diagnosis of pyruvate and ketoglutarate dehydrogenase deficiencies in platelet-enriched preparations from blood. Clin Chim Acta 75:21–30
Bogousslavsky J, Perentes E, Deruaz JP, Regli F (1982) Mitochondrial myopathy and cardiomyopathy with neurodegenerative features and multiple brain infarcts. J Neurol Sci 55:351–357
Boyd SG, Harden A, Egger I, Pampiglione G (1986) Progressive neuronal degeneration at childhood with liver disease (Alpers' disease): characteristic neurophysiological features. Neuropediatrics 17:75–80
Castaigne P, Laplane D, Escourolle R, Augustin P, Recondo J de, Martinez Lage GI, Villanueva Eusa JA (1971) Ophtalmoplégie externe progressive avec spongiose de noyaux du tronc cérébral. Rev Neurol (Paris) 124:454–466
Castaigne P, Lhermitte F, Escourolle R, Chain F, Fardeau M, Hauwe JJ, Curet J, Flavigny C (1977) Etude anatomoclinique d'une observation d' “ophtalmoplegia plus” avec analyse des lésions musculaires, nerveuses centrales, oculaires, myocardiques et thyroidiennes. Rev Neurol (Paris) 133:369–386
Cederblad G, Lindstedt S (1972) A method for the determination of carnitine in the picomole range. Clin Chim Acta 37:235–243
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, Mendell JR, Sahenk Z, Bachman D, Scarpa A, Scofield RM, Reiner C (1980) Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome c oxidase deficiency. Neurology 30:795–804
DiMauro S, Bonilla E, Zeviani M, Nakagawa M, De Vivo D (1985) Mitochondrial myopathies. Ann Neurol 17:512–538
Fukuhara N (1983) Myoclonus epilepsy and mitochondrial myopathy. In: Scarlato G, Cerri C (eds) Mitochondrial pathology in muscle diseases. Piccin Medical Books, Padua, pp 87–111
Fukuhara N (1985) Stroke-like episodes in MERFF. Ann Neruol 18:368
Fukuhara N, Tokigushi S, Shirakawa K, Tsubaki T (1980) Myoclonus epilepsy associated with ragged red fibres (mitochondrial abnormalities): disease entity or a syndrome? J Neurol Sci 47:117–123
Hart ZH, Chang C-H, Perrin EVD, Neerunjun JS, Ayyar R (1977) Familial poliodystrophy mitochondrial myopathy and lactate acidemia. Arch Neurol 34:180–185
Hübner G, Grantzow R (1983) Mitochondrial cardiomyopathy with involvement of skeletal muscles. Virchows Arch [A] 399:115–125
Hug G, Schubert WR (1970) Idiopathic cardiomyopathy. Mitochondrial and cytoplasmic alterations in heart and liver. Lab Invest 22:541–552
Huttenlocher PR, Solitare GP, Adams G (1976) Infantile diffuse cerebral degeneration with hepatic cirrhosis. Arch Neurol 33:186–192
Isaacs H, Muncke G (1975) Idiopathic cardiomyopathy and skeletal muscle abnormality. Am Heart J 90:767–773
Kalimo H, Lundberg PO, Olsson Y (1979) Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh syndrome). Ann Neurol 6:200–206
Karlsson J (1971) Lactate and phosphogen depletion in working muscle of man. Acta Physiol Scand [Suppl] 358
Kearns TP, Sayre GP (1958) Retinitis pigmentosa, external ophthalmoplegia and complete heart block. Arch Ophthalmol 60:280–287
Knappe J, Brümmer W, Biederbick K (1963) Reinigung und Eigenschaften der Biotinidase aus Schweinenieren undLactobacillus casei. Biochem Z 338:599–613
Kuriyama M, Umezaki H, Fukuda Y, Osame M, Koike K, Tateishi J, Igata A (1984) Mitochondrial encephalomyopathy with lactate puryvate elevation and brain infarctions. Neurology 34:72–77
Leigh D (1951) Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry 14:216–221
Logigian EL, Kolodny EH, Griffith JF, Filipek PA, Richardson EP (1986) Myoclonus epilepsy in two brothers. Clinical features and neuropathology of a unique syndrome. Brain 109:411–429
Mastaglia FL, Thompson PL, Papadimitriou JM (1980) Mitochondrial myopathy with cardiomyopathy, lactic acidosis and response to prednisone and thiamine. Aust NZ J Med 10:660–664
Meerson FZ, Zaletayeva TA, Lagutchev SS, Pshennikova MG (1964) Structure and mass of mitochondria in the process of compensatory hyperfunction and hypertrophy of the heart. Exp Cell Res 36:568–578
Miyabayashi S, Ito T, Narisawa K, Iinuma K, Tada K (1985) Biochemical study in 28 children with lactic acidosis in relation to Leigh's encephalomyelopathy. Eur J Pediatr 143:278–283
Morgan-Hughes JA, Hayes DJ, Clark JB, Landon DN, Swash M, Stark RJ, Rudge P (1982) Mitochondrial encephalomyopathies. Biochemical studies in two cases revealing defects in the respiratory chain. Brain 105:553–582
Mukoyama M, Kazui H, Sunohura N, Yoshida M, Nonaka I, Satoyoshi E (1986) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes with acanthocytosis: a clinicopathological study of a unique case. J Neurol 233:228–232
Neustein HB, Lurie PR, Dahms B, Takahas M (1979) An X-linked recessive cardiomyopathy with abnormal mitochondria. Pediatrics 64:24–29
Olson W, Engel WK, Walsh GO, Einaugler R (1972) Oculocraniosomatic neuromuscular disease with “ragged-red” fibres. Arch Neurol 26:193–199
Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP (1984) Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distictive clinical syndrome. Ann Neurol 16:481–488
Pelosi G, Agliati G (1968) The heart muscle in functional overload and hypoxia. Lab Invest 18:86–93
Pincus JH, Cooper JR, Piros K, Turner V (1974) Specificity of the urine inhibitor test for Leigh's disease. Neurology 24:885–890
Plaitakis A (1982) The olivopontocerebellar atrophies. Semin Neurol 2:334–341
Prick MJJ, Gabreëls FJM, Trijbels JMF, Janssen AJM, Coultre R le, Dam K van, Jaspar HHJ, Ebels EJ, Op de Coul AAW (1983) Progressive poliodystrophy (Alpers' disease) with a defect in cytochrome aa3 in muscle: a report of two unrelated patients. Clin Neurol Neurosurg 85:57–70
Rosing HS, Hopkins LC, Wallace DC, Epstein CM, Weideheim K (1985) Maternally inherited mitochondrial myopathy and myoloni cepilepsy. Ann Neurol 17:228–237
Rowland LP, Hays AP, DiMauro S, De Vivo DC, Behrens M (1983) Diverse clinical disorders associated with morphological abnormalities of mitochondria. In: Scarlato G, Cerri C (eds) Mitochondrial pathology in muscle diseases Piccin Medical Books, Padua, pp 141–158
Sengers RCA, TerHaar BGA, Trijbels JMF, Willems JL, Daniëls O, Stadhouders AM (1975) Congenital cataract and mitochondrial myopathy of skeletal and heart muscle associated with lactic acidosis after exercise. J Pediatr 86:873–880
Sengers RCA, Stadhouders AM, Jaspar HHJ, Trijbels JMF, Daniëls O (1976) Cardiomyopathy and short stature associated with mitochondrial and/or lipid storage myopathy of skeletal muscle. Neuropädiatrie 7:196–208
Sengers RCA, Stadhouders AM, Trijbels JMF (1984) Mitochondrial myopathies. Clinical, morphological and biochemical aspects. Eur J Pediatr 141:192–207
Servidei S, Zeviani M, DiMauro S, DiRocco M, De Vivo D, DiDonato S, Vzíel G, Berry KE, Norman MG, Hoganson G, Johnsen SD, Johnson PF (1986) Cytochrome oxidase deficiency in Leigh's syndrome. Ann Neurol 20:400
Shapira Y, Cederbaum SD, Cancilla PA, Nielsen D, Lippe BM (1975) Familial poliodystrophy, mitochondrial myopathy and lactate acidemia. Neurology 25:614–621
Sheu K-FR, Blass JP (1984) Puruvate dehydrogenase phosphate (PDHb) phosphatase activity in fibroblasts from Leigh's disease. Neurology 34:1187–1191
Stacpoole PW, Harman EM, Curry SH, Bahmgartnel TG, Misbin RI (1983) Treatment of lactic acidosis with dichloroacetate. N Engl J Med 309:390–395
Tang TT, Good TA, Dyken PR, Johnsen SD, McCreadie SR, Sy ST, Lardy HA, Rudolph FB (1972) Pathogenesis of Leigh's encephalomyelopathy. J Pediatr 81:189–190
Tridon P, Martin J-J, Vidailhet M, Floquet J, Philippart M, Neimann N (1974) Spongiose cérébrale juvénile. Pediatrie 29:235–247
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Supported by grants from the First of May Flower Annual Campaign for Childrens Health and the Swedish Medical Research Council (proj no 07122)
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Oldfors, A., Tulinius, M., Holme, E. et al. Mitochondrial encephalomyopathy. Acta Neuropathol 74, 287–293 (1987). https://doi.org/10.1007/BF00688194
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DOI: https://doi.org/10.1007/BF00688194