MELAS综合征和Leigh病患者临床对比

Clinical differential study on the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes and Leigh disease

目的对比研究和总结线粒体脑肌病伴乳酸血症和脑卒中样发作（mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes，MELAS）综合征和Leigh病患者的l临床、影像学以及病理学特点。方法对10例MELAS综合征、7例Leigh病和1例MELAS综合征Leigh病叠加患者的临床、影像学及组织病理学特点进行系统分析。结果10例MELAS综合征患者主要临床表现为运动不耐受、发作性头痛和脑卒中样发作，脑CT及MRI检查结果示病灶多位于枕、顶、颞叶皮质及皮质下，光镜下观察肌肉组织可见不整红边纤维（ragged red fiber，RRF），抗线粒体抗体（anti—mitoehondrial antibody，AMA）免疫组化染色可见大量破碎样棕褐色肌纤维（ragged brown fibers，RBFs），3例MELAS综合征患者行脑活检可见棕色AMA阳性的小血管及神经细胞。7例Leigh病患者主要临床表现为眼外肌麻痹、视力下降、肌阵挛样发作及智力发育迟缓，头颅MRI检查结果示双侧底节区、脑干异常信号，肌肉活检未见RRF。4例MELAS综合征、4例Leigh病患者以及1例MELAS综合征-Leigh病叠加患者行MRS检查结果示病变区乳酸水平明显增高。结论MELAS综合征和Leigh病的临床及影像学特点相比存在明显差别，前者脑部病灶以脑叶皮质及皮质下受累为主，同时表现为脑和肌肉受累症状，肌肉活检可发现RRF；Leigh病患者主要表现为脑干、基底节及视神经受累表现，肌肉活检未见RRF．

Objective To compare and summarize the clinical, neuroimaging and pathological features in patients of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （MELAS） and Leigh disease. Methods Systemic study was performed on the clinical, neuroimaging and pathological features of 19 patients including 10 MELAS, 7 Leigh, and 1 overlapping features of the 2 syndromes. Results The main clinical features of 10 MELAS patients were characterized by intolerance to exercise, recurrent headache and stroke-like episodes. Cranial CT showed calcification in the basal ganglia and MRI showed lesions in the cerebral cortex and subcortex of patients with MELAS. Muscle biopsy showed the ragged red fiber （RRF）. Brain biopsy showed the laminar necrosis of the cerebral cortex, astrocytosis, diffused microvascular proliferation and some calcification. A large number of ragged brown fibers （RBFs） were observed by light microscopy of the antimitochondrial antibody （AMA） immunohistochemical staining in the muscle tissues of patients with MELAS. The main clinical manifestations of 7 Leigh disease patients included the external ophthalmoplegia, decreased vision, myoclonus epilepsy and the intelligence retardation. MRI indicated that symmetric abnormal signals presented in the bilateral basal ganglia and the brain stem of Leigh patients. MRS of 4 MELAS and 4 Leigh disease and 1 overlapping patients suggested that lactic acid level increased in affected areas. Conclusions The clinical and imaging features of MELAS and Leigh disease were significantly different. Lesions were easily referred to the cerebral cortex and subcortex in MELAS patients. At the same time, the brain and muscle symptoms were co-existed. Muscle biopsy had abnormal RRF. However, the lesions in Leigh were shown symmetric abnormal signals in the bilateral basal ganglia, the brain stem and the optic nerve. No RRF was found in muscle tissue with Leigh disease.