Mitochondrial Leukoencephalopathy

  • Jacob Valk
  • Marjo S. van der Knaap


Mitochondrial dysfunction is central to the pathogenesis of certain rare neurological diseases. Mitochondrial disorders are a clinically and biochemically heterogeneous group of disorders which are characterized by structurally, functionally, or numerically abnormal mitochondria. Although the clinical signs and symptoms and course of disease show considerable variation, three broad clinical categories can be distinguished, as is explained in the introduction on mitochondria and mitochondrial dysfunction. The first two categories comprise the mitochondrial myopathies with limb weakness and fatigability with or without a chronic progressive external ophthalmoplegia. The third category comprises the mitochondrial encephalomyopathies, with the accent on CNS pathology. Usually infants and young children are affected (congenital, early-infantile, infantile variants), but older children and adults may also be affected (juvenile and adult variants). The course of disease may be acute, subacute, chronic and progressive, or remitting.


White Matter Basal Ganglion White Matter Lesion Sensorineural Hearing Loss Mitochondrial Myopathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anzil AP, Wendl A, Struppler A (1981) Ultrastructure of a cerebral white matter lesion in a 41-year-old man with Leigh’s encephalomyelopathy ( LEM ). Acta Neuropathol 7: 233–238Google Scholar
  2. Bardosi A, Creutzfeldt W, DiMauro S, Felgenhauer K, et al. (1987) Myo-, neuro-, gastrointestinal encephalopathy ( MNGIE syndrome) due to partial deficiency of cytochrome-c-oxidase. Acta Neuropathol 74: 248–258Google Scholar
  3. Barth PG (1986) Oligofrenie (deel 22). Soma Psyche 12: 1–6Google Scholar
  4. Bianco F, Floris R, Pozzessere G, Rizzo PA (1987) Subacute necrotizing encephalomyelopathy (Leigh’s disease): clinical correlations with computerized tomography in the diagnosis of the juvenile and adult forms. Acta Neurol Scand 75: 214–217PubMedCrossRefGoogle Scholar
  5. Bril V, Rewcastle NB, Humphrey J (1984) Oculoskeletal myopathy with abnormal mitochondria. Can J Neurol Sci 11: 390–394PubMedGoogle Scholar
  6. Campistol J, Fernandez-Alvarez E, Cusi V (1984) CT scan appearance in subacute necrotising encephalomyelopathy. Dev Med Child Neurol 26: 509–527Google Scholar
  7. Crompton MF (1969) Spongiform subacute necrotising encephalomyelopathy. Acta Neuropath 13: 294–298PubMedCrossRefGoogle Scholar
  8. Daroff RB, Solitare GB, Pincus JH, Glaser GH (1966) Spongiform encephalopathy with chronic progressive external ophthalmoplegia. Neurology 16: 161–169PubMedCrossRefGoogle Scholar
  9. David RB, Mamunes P, Rosenblum WI (1976) Necrotizing encephalomyelopathy (Leigh). In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology, vol 28. Amsterdam: North Holland Publishing Company: 349–363Google Scholar
  10. Davis PC, Hoffman JC, Braun IF, Ahmann P, et al. (1987) MR of Leigh’s disease (subacute necrotizing encephalomyelopathy). AJNR 8: 71–75PubMedGoogle Scholar
  11. Delgado G, Gallego J, Tunon T, Zarranz JJ (1987) Necrotising haemorrhagic encephalomyelopathy in an adult:? Leigh’s disease. J Neurol Neurosurg Psychiatry 50: 224–227PubMedCrossRefGoogle Scholar
  12. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, et al. (1985) Mitochondrial myopathies. Ann Neurol 17: 521–538PubMedCrossRefGoogle Scholar
  13. Egger J, Pincott JR, Wilson J, Erdohazi M (1984) Cortical subacute necrotizing encephalomyelopathy. Neuropediatrics 15: 150–158PubMedCrossRefGoogle Scholar
  14. Erven van PMM, Colon EJ, Gabreëls FJM, Renier WO, et al. (1986) Neurophysiological studies in the Leigh syndrome. Brain Dev 8: 590–595PubMedCrossRefGoogle Scholar
  15. Erven van PMM, Cilessen JPM, Eekhoff EMW, Gabreëls FJM, et al. (1987) Leigh syndrome, a mitochondrial encephalo(myo)pathy. Clin Neurol Neurosurg 89: 217–230PubMedCrossRefGoogle Scholar
  16. Erven van PMM, Ruitenbeek W, Gabrieëls FJM, Renier WO, et al. (1986) Disturbed oxidative metabolism in subacute necrotizing encephalomyelopathy ( Leigh syndrome ). Neuropediatrics 17: 28–32Google Scholar
  17. Feigin I, Kim HS (1977) Subacute necrotizing encephalomyelopathy in a neonatal infant. J Neuropath Exp Neurol 36: 364–372PubMedCrossRefGoogle Scholar
  18. Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T (1980) Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): disease entity or a syndrome? J Neurol Sci 47: 117–133PubMedCrossRefGoogle Scholar
  19. Goebel HH, Bardosi A, Friede RL, Kohlschütter A (1986) Sural nerve biopsy studies in Leigh’s subacute necrotizing encephalomyelopathy. Muscle Nerve 9: 165–173PubMedCrossRefGoogle Scholar
  20. Goebel HH, Bardosi A, Friede RL, Kohlschütter A, et al. (1986) Sural nerve biopsy studies in Leigh’s subacute necrotizing encephalomyelopathy. Muscle Nerve 9: 165–173PubMedCrossRefGoogle Scholar
  21. Gray F, Louarn F, Gherardi R, Eizenbaum JF, et al. (1984) Adult form of Leigh’s disease: a clinico pathological case with CT scan examination. J Neurol Neurosurg Psych 47: 1211–1215CrossRefGoogle Scholar
  22. Hammerstein W, Mortier W, Noack EA, Frenzel H (1983) Klinische morphologische and biochemische Befunde beim Kearns-Sayre-Syndrom. Fortschr Ophthalmol 80: 193–200PubMedGoogle Scholar
  23. Henkes H, Sperner J, Stoltenburg-Didinger G (1987) Kernspintomographischer Aspekt der Enzephalomyopathie. Fortschr Geb Rontgenstr Nuklearmed Erganzungsband 147: 214–216CrossRefGoogle Scholar
  24. Kissel JT, Kolkin S, Chakeres D, Boesel C, et al. (1987) Magnetic resonance imaging in a case of autopsy-proved adult subacute necrotizing encephalomyelopathy ( Leigh’s disease ). Arch Neurol 44: 563–566Google Scholar
  25. Kleber FX, Park JW, Hübner G, Johannes A, et al. (1987) Congestive heart failure due to mitochondrial cardiomyopathy in Kearns-Sayre syndrome. Klin Wochenschr 65: 480–486PubMedCrossRefGoogle Scholar
  26. Koch TK, Yee MHC, Hutchinson HT, Berg BO (1986) Magnetic resonance imaging in subacute necrotizing encephalomyelopathy ( Leigh’s disease ). Ann Neurol 19: 605–607Google Scholar
  27. Machraoui A, Breviere GM, Rey C, Ghalayini Z, et al. (1985) Syndrome de Kearns familial. Ann Pediatr 32: 701–711Google Scholar
  28. Marolda M, Esposito V, Peretti A, Maiupi F, et al. (1984) Ophthalmoplegia plus with late onset. Histochemical. UI-trastructural. Metabolic and electrophysiopathological study of a case. Acta Neurol 6: 264–273Google Scholar
  29. Maso E, Ferrer I, Herraiz J, Roquer J, et al. (1984) Leigh’s syndrome in an adult. J Neurol 231: 253–257PubMedCrossRefGoogle Scholar
  30. Morgan-Hughes JA (1982) Mitochondrial myopathies. In: Mastaglia FL, Walton J, eds. Skeletal Muscle Pathology. Edinburgh: Churchill Livingstone: 309–339Google Scholar
  31. Paltiel HJ, O’Gorman AM, Meagher-Villemure K, Rosenblatt B, et al. (1987) Subacute necrotizing encephalomyelopathy ( Leigh’s disease ): CT study. Radiology 162: 115–118Google Scholar
  32. Pavlakis ST, Philips PC, DiMauro S, De Vivo DC, et al. (1984) Mitochondrial myopathy, encephalopathy. Latic acidoses, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 16: 481–488PubMedCrossRefGoogle Scholar
  33. Petty RKH, Harding AE, Morgan-Hughes JA (1986) The clinical features of mitochondrial myopathy. Brain 109: 915–938PubMedCrossRefGoogle Scholar
  34. Przyrembel H (1987) Therapy of mitochondrial disorders. J Inher Metab Dis 10: 129–146PubMedCrossRefGoogle Scholar
  35. Rakovec P, Starc R, Butinar D, Janezic A (1986) Conduction disturbances in the Kearns-Sayre syndrome. Cor Vasa 28: 294–297PubMedGoogle Scholar
  36. Rheuban KS, Ayres NA, Sellers TD, DiMarco JP(1983) Near-fatal Kearns-Sayre syndrome. Clin Pediatr 22: 822–825Google Scholar
  37. Seitz RJ, Langes K, Frenzel H, Kluitmann G, et al. (1984) Congenital Leigh’s disease: panencephalomyelopathy and peripheral neuropathy. Acta Neuropathol 64: 167–171PubMedCrossRefGoogle Scholar
  38. Simonati A, Laverda AM, Rizzuto N (1986) Multicystic encephalomalacia associated with symmetrical necrotizing brain stem lesions in an infant: a case report. Clin Neuropathol 5: 139–145PubMedGoogle Scholar
  39. Walter GF, Brucher JM, Martin JJ, Ceuterick C (1986) Leigh’s disease: several nosological entities with an identical histopathological complex? Neuropathol Appl Neurobiol 12: 95–107PubMedCrossRefGoogle Scholar
  40. Yoda S, Terauchi A, Kitahara F, Akabane T (1984) Neurologic deterioration with progressive CT changes in a child with Kearns-Shy syndrome. Brain Dev 6: 323–327PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Jacob Valk
    • 1
  • Marjo S. van der Knaap
    • 2
  1. 1.Department of Diagnostic Radiology and NeuroradiologyFree University HospitalAmsterdamThe Netherlands
  2. 2.Department of Child NeurologyAcademic HospitalUtrechtThe Netherlands

Personalised recommendations