PDF(Pubmed)
Abstract：
The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1-27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases.
摘要：
线粒体（m。）3243A>G突变已知与各种线粒体疾病相关，包括线粒体肌病，脑病,乳酸性酸中毒,和中风样发作（MELAS）。据估计，它们的临床症状与线粒体DNA（mtDNA）异质性增加和氧化磷酸化（OXPHOS）复合物的活性降低有关。但是他们在中枢神经系统的趋势仍然未知。本研究纳入了6例尸检突变病例和3例没有突变的疾病对照病例。突变病例的病程为1-27年。6例突变病例中有5例与MELAS相容。在突变病例中，在顶叶经常观察到包括层状坏死在内的皮质病变，颞侧,和枕叶；在额叶包括中央前回的频率较低；在内侧颞叶完全没有。突变病例的脑组织样本中的mtDNA异质性高得惊人，从53.8%到85.2%不等。尽管环境恶劣，mtDNA杂质和乳酸含量很高，但内侧颞叶仍得以保留。OXPHOS复合物I在突变病例中广泛减少。软脑膜上血管平滑肌细胞的肿胀，具有针对线粒体抗体的免疫反应性（IR），在所有突变病例中均观察到脉络膜上皮细胞的核/细胞质比率降低，但没有突变。在突变病例中并不总是观察到常见的神经病理学发现，例如皮质层状坏死和基底节钙化。尽管存在异质性皮质病变，但在整个大脑中仍观察到高水平的mtDNA异质体。缺乏内侧颞部病变，软脑膜上血管的线粒体血管病变，脉络丛上皮细胞的细胞质大小增加可能是神经病理学标志，有助于线粒体疾病的诊断。
