Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
Department of Neurology, Toyohashi Municipal Hospital, Toyohashi, Japan.
Neuropathology. 2019 Jun;39(3):212-217. doi: 10.1111/neup.12551. Epub 2019 Apr 10.
We present an autopsied case with A8344G-mutated myoclonus epilepsy with ragged red fibers (MERRF)/mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) overlap syndrome accompanied by stroke-like episodes localized to the precentral gyrus. A 16-year-old Japanese woman suddenly experienced repetitive consciousness disturbances with increased serum lactate and creatine kinase levels. Magnetic resonance imaging showed abnormal intensity of bilateral precentral gyrus. She was clinically diagnosed as having a mitochondrial disorder and the A8344G mutation was detected in mitochondrial DNA. At 17 years of age, she died from congestive heart failure secondary to a third episode of lactic acidosis. Neuropatho-logically, multifocal laminar necrosis, which is responsible for stroke-like episodes in MELAS, was seen in the frontal cortex including the precentral gyrus, but there was no neuronal loss and gliosis in the basal ganglia, cerebellum, and brainstem, which were compatible with MERRF. Hypertrophy of the vascular smooth muscle and choroidal epithelium were seen, and were strongly visualized by an anti-mitochondrial antibody. Skeletal muscles showed uneven muscular diameters, increased central nuclei, and ragged red fibers (RRFs). Decreased cytochrome c oxidase (COX) activity and strongly succinate dehydrogenase (SDH)-reactive blood vessels were also noted. Stroke-like episodes in MERRF/MELAS overlap syndrome are thought to be rare in the frontal cortex including the precentral gyrus. Only two cases of MERRF/MELAS overlap syndrome with A8344G mutation, including this case, have shown stroke-like episodes in the frontal lobes. Other than the A8344G mutation and frontal lobe involvement, they had a high degree of similarity in terms of presence of RRFs, gastrointestinal dysfunction, and lack of typical MERRF neuropathology. In conclusion, this is an important case describing the clinical spectrum associated with A8344G-mutated MERRF/MELAS overlap syndrome.
我们报告了一例 A8344G 突变型肌阵挛性癫痫伴破碎红纤维（MERRF）/线粒体脑肌病伴乳酸酸中毒和卒中样发作（MELAS）重叠综合征合并卒中样发作局限于中央前回的尸检病例。一名 16 岁的日本女性突然出现反复意识障碍，伴有血清乳酸和肌酸激酶水平升高。磁共振成像显示双侧中央前回异常信号。她被临床诊断为线粒体疾病，检测到线粒体 DNA 的 A8344G 突变。17 岁时，她因第三次酸中毒引起充血性心力衰竭死亡。神经病理学检查显示，前中央回包括在内的额皮质存在多灶性层状坏死，这是 MELAS 中卒中样发作的原因，但基底节、小脑和脑干无神经元丢失和神经胶质增生，符合 MERRF。血管平滑肌和脉络膜上皮肥大，抗线粒体抗体强烈显示。骨骼肌表现为不均匀的肌纤维直径、中央核增多和破碎红纤维（RRF）。还观察到细胞色素 c 氧化酶（COX）活性降低和强烈的琥珀酸脱氢酶（SDH）反应性血管。MERRF/MELAS 重叠综合征中的卒中样发作在包括中央前回在内的额叶中被认为很少见。仅有两例 A8344G 突变的 MERRF/MELAS 重叠综合征，包括本例，在前额叶出现卒中样发作。除了 A8344G 突变和额叶受累外，它们在存在 RRF、胃肠道功能障碍和缺乏典型 MERRF 神经病理学方面具有高度相似性。总之，这是一个重要的病例，描述了与 A8344G 突变型 MERRF/MELAS 重叠综合征相关的临床谱。
