【摘要】 目的探讨线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)的临床、肌肉病理、神经影像及分子病理学特点。方法回顾性分析我科近7年来诊断的31例 MELAS 患者的临床表现、神经影像、肌肉活体组织检查及分子病理学特点,其中13例患者应用限制性片段长度多态性(RFLP)方法对 mtDNA A3243G位点突变进行分析。结果①临床特点:男性18例,女性13例;发病年龄为3～43岁,平均21.9岁;平均病程4.9年。13例有家族史,均符合母系遗传方式。主要临床表现包括:身材矮小(26例),发作性头痛、呕吐(24例),肌无力(22例),癫癎发作(21例),智能减退(19例),视物模糊(17例),听力减退(16例),共济失调(6例),精神异常(8例),眼外肌麻痹(2例),其中9例合并糖尿病。6例患者有肌酶轻度增高。有结果记录的18例患者中有15例空腹血乳酸增高。②神经影像学特点:脑卒中样病灶多位于皮质,常见受累部位依次为:颞叶24例,枕叶21例,顶叶12例,额叶4例,脑深部白质受累者3例,动态检查脑卒中样病灶呈迁移样改变者4例,另外脑萎缩17例,双侧基底节对称性钙化11例。③肌肉活体组织检查病理特点:所有患者改良 Gomori 三色染色均见数量不等的不整红边纤维,27例琥珀酸脱氢酶染色可见强反应性血管,19例患者细胞色素 C 氧化酶染色可见部分酶缺失,20例油红"O"染色示不整红边纤维内脂滴轻度增多。④13例患者 mtDNA 基因突变分析发现9例有 A3243G 点突变。结论发生于中青年和少年儿童的局限于皮质的脑卒中样病灶强烈提示 MELAS 综合征的可能,结合身材矮小、肌无力、神经性耳聋、头痛等伴随症状可做出 MELAS的临床可能诊断,肌肉活体组织检查及 mtDNA 突变分析可为最终确诊提供重要的实验室依据。更多还原

【Abstract】 Objective To investigate the clinical,neuroimaging and myopathological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,neuroimaging and myopathological features of 31 patients with MELAS diagnosed in our Neuromuscular Center in the recent 7 years were retrospectively analyzed.A3243G point mutations were analyzed by RFLP method in 10 patients.Results ①Clinical features:There were 18 male patients and 13 female patients.The age of onset ranged from 3 to 43 years,averaging 21.9 years.The averaged duration was 4.9 years.Thirteen patients in this group had family history of maternal inheritance pattern.The main clinical manifestations included short stature(26 patients),recurrent headache and vomiting(24 patients), muscle weakness(22 patients),epileptic seizure(21 patients),cognitive decline(19 patients),visual disturbance(17 patients),sensorineural deafness(16 patients),ataxia(6 patients),psychiatric symptom (8 patients),external ophathalmoplegia(2 patients)and diabetes mellitus(9 patients).The serum CK level was slightly elevated in 6 patients,and the fasting blood lactic acid was increased in 15 of the 18 detected patients.②Neuroimaging features:The stroke-like lesions were mostly confined to cerebral cortex, including temporal lobe(24 patients),occipital lobe(21 patients),parietal lobe(12 patients)and frontal lobe(4 patients).Three patients had deep white matter involvement.Migrating stroke-like lesions were confirmed in 4 patients by repeated cranial CT/MRI examination.In addition,cerebral atrophy(17 patients)and bilateral basilar ganglion calcification(11 patients)were found.③Myopathological features: Scattered ragged red fibers(RRF)in various number were found in all the patients by MGT staining.Other founding included strongly SDH-reactive blood vessel(27 patients),COX enzyme deficiency(19 patients), and mild to moderate lipid storage in RRF(20 patients).④MtDNA analysis showed 9 patients with A3243G point mutation in all the detected 13 patients.Conclusion The clinical and neuroimaging features may offer important clue to the diagnosis of MELAS,but a definite diagnosis of MELAS relies on the myopathology and mtDNA mutation analysis.更多还原