Struck Aaron F, Garcia-Ramos Camille, Prabhakaran Vivek, Nair Veena, Adluru Anusha, Philibert Rosas Santiago, Almane Dace, Adluru Nagesh, Jones Jana E, Hermann Bruce P
Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Department of Neurology, William S. Middleton Veterans Administration Hospital, Madison, Wisconsin, USA.
Epilepsia. 2025 Jul 19. doi: 10.1111/epi.18571.
This study was undertaken to determine the thalamic nuclei that are different between juvenile myoclonic epilepsy (JME) and healthy controls from the Juvenile Myoclonic Epilepsy Connectome Project and then to determine their relationship with other subcortical gray matter volumes, disease covariates, and motor performance.
Sixty-two patients with JME and 41 age-matched controls (mean age = 20 years) were examined using T1-weighted images. Thalamic nuclei volumes were compared after normalization to total intracranial volume. The relationship between thalamic nuclei volumes and age, duration of epilepsy, number of antiseizure medications, and age at onset were examined using linear models with relative assessment of regressors. Correlation with other subcortical volumes was undertaken to identify a potential network effect. Nuclei volumes were related to a task of speeded fine-motor dexterity.
Ventral motor-associated thalamic nuclei (ventral anterior, ventral lateral anterior, and ventral lateral posterior) as well as one intralaminar nucleus (parafascicular) volumes were reduced in JME. These thalamic nuclei volume reductions were correlated with cerebellar and ventral diencephalon volume reductions. The reduction in thalamic volumes was associated with age (which differed from controls) in only the ventral thalamic nuclei. Duration of epilepsy also had an effect. JME was associated with decreased dominant and nondominant hand speeded dexterity, with greater deficits relative to reduction of thalamic nuclei volume than in controls. The findings suggest a baseline decrease in ventral thalamic volume with an inability to make efficiency gains because of disordered adolescent synaptic pruning.
Motor-related ventral thalamic nuclei appear to be a core factor in JME pathogenesis. These motor-associated nuclei have known connections with premotor cortex, basal ganglion, and cerebellar pathways that are related to motor control. Their dysregulation may account for the myoclonus seen in JME and interictal motor effects. Further longitudinal investigation and comparison with other cohorts are needed. Targeted neuromodulation of JME may be possible.
本研究旨在确定青少年肌阵挛癫痫（JME）与青少年肌阵挛癫痫连接组项目中的健康对照之间存在差异的丘脑核团，然后确定它们与其他皮质下灰质体积、疾病协变量和运动表现的关系。
使用T1加权图像对62例JME患者和41例年龄匹配的对照（平均年龄 = 20岁）进行检查。将丘脑核团体积归一化至总颅内体积后进行比较。使用带有回归因子相对评估的线性模型检查丘脑核团体积与年龄、癫痫持续时间、抗癫痫药物数量和发病年龄之间的关系。与其他皮质下体积进行相关性分析以确定潜在的网络效应。核团体积与快速精细运动灵巧性任务相关。
JME患者中与运动相关的腹侧丘脑核团（腹前核、腹外侧前核和腹外侧后核）以及一个板内核（束旁核）体积减小。这些丘脑核团体积减小与小脑和腹侧间脑体积减小相关。仅腹侧丘脑核团的体积减小与年龄（与对照不同）相关。癫痫持续时间也有影响。JME与优势手和非优势手的快速灵巧性下降有关，相对于丘脑核团体积减小，其缺陷比对照组更大。研究结果表明腹侧丘脑体积基线下降，由于青少年突触修剪紊乱而无法提高效率。
与运动相关的腹侧丘脑核团似乎是JME发病机制中的核心因素。这些与运动相关的核团与运动控制相关的运动前皮质、基底神经节和小脑通路有已知的连接。它们的失调可能解释了JME中出现的肌阵挛和发作间期运动效应。需要进一步的纵向研究并与其他队列进行比较。对JME进行有针对性的神经调节可能是可行的。
