Adult-onset MELAS - Evidence for involvement of neurons as well as cerebral vasculature in strokelike episodes
Adult-onset MELAS - Evidence for involvement of neurons as well as cerebral vasculature in strokelike episodes
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DOI：
10.1161/01.str.27.8.1420
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发表时间：
1996-08-01
期刊：
影响因子：
8.3
通讯作者：
Shanske, S
中科院分区：
文献类型：
--
作者：
Gilchrist, JM;Sikirica, M;Shanske, S
背景我们报告一位46岁的女性，其发病机制与MELAS（线粒体脑肌病、乳酸酸中毒和卒中样发作）卒中样发作有关。她有10个月的发作性癫痫、中风、认知能力下降、呕吐和肠梗阻病史。她还患有感音神经性听力损失、持续数年的胰岛素依赖型糖尿病和持续性乳酸酸中毒。家族史是有关的一个类似的综合征在她已故的母亲（发病在她六十多岁），听力损失和糖尿病在两个兄弟，听力损失在她唯一的孩子，一个son.Case描述系列MRI的大脑显示严重的，但短暂的大脑皮质异常。进行左颞部脑活检以排除脑炎。光学显微镜检查显示弥漫性神经胶质增生伴大量反应性Gemistocytes，局部缺血性神经元损伤和水肿。电子显微镜检查显示奇异的线粒体增大和细胞水肿的变化。琥珀酸脱氢酶染色在脑血管和神经元内反应强烈。随后在外周血白细胞和脑中发现线粒体tRNA（Leu（UUR））基因的nt 3243处发生点突变，证实了MELAS的临床诊断。定量显示，82%的脑线粒体携带的疾病突变，表明大多数，如果不是全部，组织受到影响。结论我们的研究结果表明，中风发作MELAS导致神经元代谢缺陷，以及在脑血管。
Background We report a 46-year-old woman with implications regarding pathogenesis of strokelike episodes in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). She had a 10-month history of episodic seizures, strokes, cognitive decline, vomiting, and ileus. She also had sensorineural hearing loss, insulin-dependent diabetes mellitus of several years' duration, and persistent lactic acidosis. Family history was pertinent for a similar syndrome in her deceased mother (onset in her sixties), for hearing loss and diabetes mellitus in two brothers, and for hearing loss in her only child, a son.Case Description Serial MRIs of the brain revealed severe but evanescent cerebral cortical abnormalities. A left temporal brain biopsy was performed to exclude encephalitis. Light microscopy revealed a diffuse fibrillary gliosis with abundant reactive gemistocytes, focal evidence of ischemic neuronal injury, and edema. Electron microscopy revealed bizarre enlarged mitochondria and changes consistent with cellular edema. Succinate dehydrogenase staining was strongly reactive within cerebral blood vessels and within neurons. A point mutation was subsequently found at nt 3243 of the mitochondrial tRNA(Leu(UUR)) gene in peripheral leukocytes and in brain, confirming the clinical diagnosis of MELAS. Quantitation revealed that 82% of brain mitochondria carried the disease mutation, indicating that most, if not all, tissues were affected.Conclusions Our findings suggest that strokelike episodes in MELAS result from defects in neuronal metabolism, as well as in cerebral vasculature.