Mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the topological organization of brain functional network in MELAS has not been explored. Here, 45 patients with MELAS (22 at acute stage, 23 at chronic stage) and 22 normal controls were studied using resting- state functional magnetic resonance imaging and graph theory analysis approaches. Topological properties of brain functional networks including global and nodal metrics, rich club organization and modularity were analyzed. At the global level, MELAS patients exhibited reduced clustering coefficient, normalized clustering coefficient, normalized characteristic path length and local network efficiency compared with the controls. At the nodal level, several nodes with abnormal degree centrality and nodal efficiency were detected in MELAS patients, and the distribution of these nodes was partly consistent with the stroke-like lesions. For rich club organization, rich club nodes were reorganized and the connections among them were decreased in MELAS patients. Modularity analysis revealed that MELAS patents had altered intra- or inter-modular connections in default mode network, fronto-parietal network, sensorimotor network, occipital network and cerebellum network. Notably, the patients at acute stage showed more obvious changes in these topological properties than the patients at chronic stage. These findings indicated that MELAS patients, particularly those at acute stage, exhibited topological reorganization of the whole-brain functional network. This study may help us to understand the neuropathological mechanisms of MELAS.

线粒体性脑病伴乳酸性酸中毒和中风样发作（MELAS）是一种罕见的母体遗传性疾病。然而，对其潜在的大脑基础知之甚少。此外，尚未探索MELAS中脑功能网络的拓扑组织。在这里，使用静止状态功能磁共振成像和图论分析方法研究了45例MELAS患者（急性期22例，慢性期23例）和22例正常对照。分析了大脑功能网络的拓扑特性，包括全局和节点度量，丰富的俱乐部组织和模块化。在全球范围内，与对照组相比，MELAS患者表现出降低的聚类系数，归一化聚类系数，归一化特征路径长度和局部网络效率。在淋巴结水平上，在MELAS患者中检测到多个具有不同程度的中心度和淋巴结效率的淋巴结，这些淋巴结的分布与中风样病变部分一致。对于富裕的俱乐部组织，在MELAS患者中重组了富裕的俱乐部节点并减少了它们之间的联系。模块化分析表明，MELAS专利已更改了默认模式网络，额顶网络，感觉运动网络，枕骨网络和小脑网络的模块内或模块间连接。值得注意的是，处于急性期的患者比处于慢性期的患者表现出更明显的拓扑学变化。这些发现表明，MELAS患者，特别是急性期患者，表现出全脑功能网络的拓扑重组。