线粒体脑肌病伴高乳酸血症和卒中样发作的临床特点和生存分析

A clinical and natural history research on mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes

目的 总结线粒体脑肌病伴高乳酸血症和卒中样发作（MELAS）患者的临床特点、生存状况及死亡原因。方法 回顾性分析2005年1月至2017年3月在华山医院神经内科就诊、病程3年及以上（死亡病例除外）的64例MELAS患者的临床资料，并进行生存状况和死亡原因分析。结果 本组患者共64例，男女比例1.3∶1，中位起病年龄20.5（16.8）岁，发病高峰在14～22岁。发作期最常见的症状包括癫痫（48/64，75.0%）、头痛（41/64，64.1%）、皮质盲（37/64，57.8%）、恶心呕吐（27/64，42.1%）、发热（25/64, 39.1%）以及精神行为异常（24/64，37.5%）。实验室检查发现超半数患者存在乳酸脱氢酶（31/60, 51.6%）、静息血乳酸（43/58，74.1%）、脑脊液乳酸（9/9）升高；脑电图、心电图、肌电图异常比例分别为90.0%（36/40）、78.7%（37/47）、61.0%（25/41）。本组患者病程1～21年，其中31.3%（20/64）患者死亡，中位生存时间12年，性成熟前起病（≤14岁）患者中位生存时间为8年，性成熟后起病（〉14岁）患者中位生存时间为21年。性成熟前起病患者病死率更高。主要的死亡原因包括心源性死亡（4/20，20.0%）、呼吸道感染（4/20，20.0%）、乳酸酸中毒（4/20，10.0%）及终末期癫痫及相关并发症（2/20，10.0%）。结论 MELAS是一组好发于青少年的疾病，病死率高，心源性死亡和呼吸道感染是最常见的死亡原因。

Objective To summarize the clinical features, natural history and causes of death of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes （MELAS）.Methods We retrospectively evaluated the clinical findings of 64 patients diagnosed as MELAS more than 3 years （death cases excluded） in Huashan Hospital from January 2005 to March 2017 and analyzed the natural course and the causes of death of the disease.Results Among 64 patients, the male-to-female ratio was 1.3∶1. Median onset age was 20.5 （16.8） years. The peak of incidence age was from 14 to 22 years. The most common features of MELAS in acute phase were seizures （48/64, 75.0%）, headache （41/64, 64.1%）, blurred vision （37/64, 57.8%）, nausea and vomiting （27/64, 42.1%）, fever （25/64, 39.1%）, mental and behavioral disorder （24/64, 37.5%）. Lactate dehydrogenase （31/60, 51.6%）, resting blood lactic acid （43/58, 74.1%） and cerebral spinal fluid lactic acid （9/9） were elevated. Abnormal findings in electroencephalogram （36/40, 90.0%）, electrocardiogram （37/47, 78.7%）, electromyography （25/41, 61.0%） were detected. In this cohort, 20 patients （20/64, 31.3%） with MELAS were dead. A Kaplan-Meier survival curve showed the estimated overall median survival time was 12 years. The median survival time of the group onset before sex maturity （≤14 years） was 8 years and that in the group onset after sex maturity （〉14 years） was 21 years. The causes of death were cardiogenic incidence （4/20, 20.0%）, pulmonary infection （4/20, 20.0%）, lactic acidosis （2/20, 10.0%） and status epilepticus （2/20, 10.0%）.Conclusions MELAS is usually presented in young people associated with high mortality rate. The leading causes of death are cardiogenic, pulmonary infection and lactic acidosis.