Department of Neurology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Department of Clinical Laboratory, Kitasato University Hospital, Sagamihara, Japan.
J Neurol. 2019 Jun;266(6):1459-1472. doi: 10.1007/s00415-019-09283-3. Epub 2019 Mar 19.
To investigate a diversity of stroke-like episodes (SLEs) in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and report a disseminated form of SLEs (D-SLEs) attributed to a cluster of disseminated small cortical lesions.
We retrospectively reviewed the clinical information of 27 MELAS patients seen at Kitasato University Hospital between January 1990 and April 2018. Among those, we selected 13 patients with m.3243A>G mutation [median age at onset, 35 years (11-68 years), two pediatric onset < 17 years] who had at least one SLE. SLEs were classified into classic or non-classic based on characteristic features of stroke-like lesions.
44 SLEs were identified during a median observational period of 119 months (3-240 months). Among those, 29 (65.9%) were classic SLEs (C-SLEs) mainly attributed to a single continuous lobular lesion incongruent to vascular territory and occasionally accompanied by a gradual spread associated with hyperperfusion and persistent seizure activity. The remaining 15 were non-classic attributed to sparsely distributed (n = 10), disseminated (n = 4) or cerebellar lesions (n = 1). C-SLEs developed in all patients but non-classic SLEs in 5; D-SLEs developed in 4 patients accounting for 4 of 44 SLEs (9.1%). Non-classic SLEs developed more frequently in pediatric-onset than in adult-onset patients (12/15 vs. 3/29, p < 0.0001). SLEs began with acute onset of symptoms in 42 SLEs (95.5%), but D-SLEs of 2 adult-onset patients began with ill-defined subacute-onset fluctuating encephalopathy.
This study showed a diversity of SLEs in patients with m.3243A>G mutation. Further studies are required to elucidate the pathophysiological mechanisms of non-classic SLEs including D-SLEs.
研究线粒体脑肌病伴高乳酸血症和卒中样发作（MELAS）中的多种卒中样发作（SLE），并报告一种由簇状分布的小皮质病变引起的散发型 SLE（D-SLE）。
我们回顾性分析了 1990 年 1 月至 2018 年 4 月期间在桂由美大学医院就诊的 27 例 MELAS 患者的临床资料。在这些患者中，我们选择了 13 例携带 m.3243A>G 突变的患者（发病中位年龄 35 岁[11-68 岁]，2 例儿科发病年龄＜17 岁），这些患者至少有 1 次 SLE。根据卒中样病变的特征，将 SLE 分为经典型或非经典型。
在中位观察期 119 个月（3-240 个月）内共发现 44 次 SLE。其中 29 次（65.9%）为经典型 SLE（C-SLE），主要由单个连续叶状病灶引起，与血管分布不一致，偶尔伴有与高灌注和持续癫痫活动相关的逐渐扩散。其余 15 次为非经典型，其中稀疏分布（n=10）、弥漫性（n=4）或小脑病变（n=1）各占 1 例。所有患者均出现 C-SLE，但仅 5 例患者出现非经典型 SLE；4 例患者出现 D-SLE，占 44 次 SLE 中的 4 次（9.1%）。儿科起病患者中非经典型 SLE 更常见（15/15 比 3/29，p＜0.0001）。42 次 SLE（95.5%）的症状呈急性起病，而 2 例成年起病患者的 D-SLE 呈定义不明确的亚急性起病波动性脑病。
本研究显示 m.3243A>G 突变患者的 SLE 表现多样。需要进一步研究以阐明包括 D-SLE 在内的非经典型 SLE 的病理生理学机制。
