From the Neuroimaging of Epilepsy Laboratory (B.W., S.-J.H., B.C.B., F.F., N.B., A.B.), McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal; Department of Clinical and Experimental Epilepsy (B.W., C.V., M.J.K.), UCL Institute of Neurology, London, UK; Epilepsy Center, Department of Neurology (C.V.), Klinikum Großhadern, University of Munich, Germany; and Multimodal Imaging and Connectome Analysis Lab (B.C.B.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
Neurology. 2019 Sep 24;93(13):e1272-e1280. doi: 10.1212/WNL.0000000000008173. Epub 2019 Aug 29.
MRI studies of genetic generalized epilepsies have mainly described group-level changes between patients and healthy controls. To determine the endophenotypic potential of structural MRI in juvenile myoclonic epilepsy (JME), we examined MRI-based cortical morphologic markers in patients and their healthy siblings.
In this prospective, cross-sectional study, we obtained 3T MRI in patients with JME, siblings, and controls. We mapped sulco-gyral complexity and surface area, morphologic markers of brain development, and cortical thickness. Furthermore, we calculated mean geodesic distance, a surrogate marker of cortico-cortical connectivity.
Compared to controls, patients and siblings showed increased folding complexity and surface area in prefrontal and cingulate cortices. In these regions, they also displayed abnormally increased geodesic distance, suggesting network isolation and decreased efficiency, with strongest effects for limbic, fronto-parietal, and dorsal-attention networks. In areas of findings overlap, we observed strong patient-sibling correlations. Conversely, neocortical thinning was present in patients only and related to disease duration. Patients showed subtle impairment in mental flexibility, a frontal lobe function test, as well as deficits in naming and design learning. Siblings' performance fell between patients and controls.
MRI markers of brain development and connectivity are likely heritable and may thus serve as endophenotypes. The topography of morphologic anomalies and their abnormal structural network integration likely explains cognitive impairments in patients with JME and their siblings. By contrast, cortical atrophy likely represents a marker of disease.
遗传性全面性癫痫的 MRI 研究主要描述了患者和健康对照之间的组水平变化。为了确定青少年肌阵挛癫痫（JME）结构性 MRI 的表型潜在性，我们检测了患者及其健康兄弟姐妹的基于 MRI 的皮质形态学标志物。
在这项前瞻性、横断面研究中，我们对 JME 患者、兄弟姐妹和对照组进行了 3T MRI 检查。我们绘制了沟回复杂度和表面积、脑发育形态学标志物以及皮质厚度图。此外，我们还计算了平均测地线距离，这是皮质皮质连接的替代标志物。
与对照组相比，患者和兄弟姐妹在前额和扣带回皮质中表现出折叠复杂度和表面积增加。在这些区域，他们还表现出异常增加的测地线距离，表明网络隔离和效率降低，边缘、额顶和背侧注意网络的影响最强。在发现重叠的区域，我们观察到患者与兄弟姐妹之间存在强烈的相关性。相反，仅在患者中出现新皮质变薄，与疾病持续时间有关。患者在心理灵活性、额叶功能测试以及命名和设计学习方面存在轻微障碍。兄弟姐妹的表现介于患者和对照组之间。
大脑发育和连接的 MRI 标志物可能是遗传性的，因此可能作为表型。形态异常的拓扑结构及其异常的结构网络整合可能解释了 JME 患者及其兄弟姐妹的认知障碍。相比之下，皮质萎缩可能是疾病的标志物。
