Neuropathology of white matter disease in Leber's hereditary optic neuropathy
Neuropathology of white matter disease in Leber's hereditary optic neuropathy
复制标题
DOI：
10.1093/brain/awh310
复制
发表时间：
2005-01-01
期刊：
影响因子：
14.5
通讯作者：
Jakab, G
中科院分区：
文献类型：
--
作者：
Kovács, GG;Höftberger, R;Jakab, G
Leber遗传性视神经病变（LHON）与编码线粒体呼吸链复合物I亚基的线粒体DNA（mtDNA）中的点突变相关。其特征是双侧的，通常是顺序性的，视神经病变，并可能与多发性硬化样白色病变同时发生。尽管反复的临床报告，包括MRI和视觉系统的组织病理学检查，LHON与多发性硬化样综合征相关的神经病理学描述是缺乏的。我们在这里提出的情况下，一位女性患者的核苷酸位置T14484C的点突变，谁患有复发性发作的视力丧失的双眼和连续发展桥本甲状腺炎以及广泛的脱髓鞘中枢神经系统病变的视觉系统外。她在44岁时死于支气管肺炎，患病时间为19年，伴有进行性恶化、癫痫发作和不动。福尔马林固定和石蜡包埋组织的免疫组织化学分析显示了一系列神经病理学变化，包括白色物质和视神经中的活动性和非活动性脱髓鞘斑块、额叶中的CD8阳性T细胞空泡化和囊性坏死、轴突损伤和白色物质空泡化。组织破坏与病变内线粒体锰超氧化物歧化酶的上调以及巨噬细胞和小胶质细胞内诱导型一氧化氮合酶表达的增加有关。这种可变表型的视外LHON疾病表明，mtDNA突变可能会影响神经系统的共同代谢的基础上，偶尔可能会加重或启动自身免疫性病理。
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.