Neuropathology of white matter disease in Leber's hereditary optic neuropathy

Gábor G. Kovács, Romana Höftberger, K. Majtényi, Rita Horváth, P. Barsi, S. Komoly, Hans Lassmann, Herbert Budka, Gábor Jakab

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Leber's hereditary optic neuropathy (LHON) is associated with point mutations in the mitochondrial DNA (mtDNA), coding for a mitochondrial respiratory chain complex I subunit. It is characterized by bilateral, usually sequential, optic neuropathy and may co-occur with multiple sclerosis-like white matter lesions. Despite repeated clinical reports including MRI and histopathological examination of the visual system, neuropathological descriptions of LHON associated with multiple sclerosis-like syndrome are lacking. We present here the case of a female patient with a point mutation at nucleotide position T14484C, who suffered from relapsing episodes of visual loss of both eyes and consecutively developed Hashimoto thyroiditis as well as widespread demyelinating CNS lesions outside the visual system. She died of bronchopneumonia at the age of 44 years, after a disease duration of 19 years, with progressive deterioration, epileptic seizures and immobility. Immunohistochemical analysis on formalin-fixed and paraffin-embedded tissue reveals a spectrum of neuropathological changes, including actively and inactively demyelinating plaques in the white matter and optic nerve, vacuolation and cystic necrosis with CD8-positive T cells in the frontal lobe, axonal damage, and vacuolation of white matter. Tissue destruction is associated with upregulation of mitochondrial manganese superoxide dismutase within the lesions and an increase in the expression of inducible nitric oxide synthase within macrophages and microglia. This variable phenotype of extraoptic LHON disease suggests that mtDNA mutations may affect the nervous system on a common metabolic basis and occasionally may aggravate or initiate autoimmune pathology.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalBrain
Volume128
Issue number1
DOIs
Publication statusPublished - Jan 2005

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Leber's Hereditary Optic Atrophy
Leukoencephalopathies
Mitochondrial DNA
Point Mutation
Multiple Sclerosis
Electron Transport Complex I
Bronchopneumonia
Hashimoto Disease
Optic Nerve Diseases
Microglia
Frontal Lobe
Nitric Oxide Synthase Type II
Optic Nerve
Electron Transport
Paraffin
Nervous System
Formaldehyde
Superoxide Dismutase
Epilepsy
Necrosis

Keywords

  • CD8-positive T cells
  • Demyelination
  • LHON
  • Mitochondrial disease
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuropathology of white matter disease in Leber's hereditary optic neuropathy. / Kovács, Gábor G.; Höftberger, Romana; Majtényi, K.; Horváth, Rita; Barsi, P.; Komoly, S.; Lassmann, Hans; Budka, Herbert; Jakab, Gábor.

In: Brain, Vol. 128, No. 1, 01.2005, p. 35-41.

Research output: Contribution to journalArticle

Kovács, GG, Höftberger, R, Majtényi, K, Horváth, R, Barsi, P, Komoly, S, Lassmann, H, Budka, H & Jakab, G 2005, 'Neuropathology of white matter disease in Leber's hereditary optic neuropathy', Brain, vol. 128, no. 1, pp. 35-41. https://doi.org/10.1093/brain/awh310
Kovács, Gábor G. ; Höftberger, Romana ; Majtényi, K. ; Horváth, Rita ; Barsi, P. ; Komoly, S. ; Lassmann, Hans ; Budka, Herbert ; Jakab, Gábor. / Neuropathology of white matter disease in Leber's hereditary optic neuropathy. In: Brain. 2005 ; Vol. 128, No. 1. pp. 35-41.
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