Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia
Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia
复制标题
阵发性运动源性运动障碍的神经解剖异常与运动症状之间的关联
DOI：
10.1016/j.parkreldis.2018.12.029
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发表时间：
2019-05-01
影响因子：
4.1
通讯作者：
Wang, Zheng
中科院分区：
文献类型：
--
作者：
Li, Hong-Fu;Yang, Liqin;Wang, Zheng
简介：阵发性运动诱发性运动障碍（PKD）的病理生理机制尚不清楚。基底神经节-丘脑-皮质回路受累被认为是PKD病理生理学的基础。然而，在PKD的运动电路的微结构的变化需要进一步elucidation.Methods：扩散张量成像和高分辨率T1加权成像进行了30例PKD患者（15 PRRT 2载体，15 PRRT 2非载体）和15个匹配的健康对照。对扩散指数进行基于区域的空间统计，以检查白色物质的微观结构完整性。基于体素的形态学分析用于检查灰质的体积变化。采用多元回归来检验人口统计学、疾病持续时间和PRRT 2状态对脑结构病理变化的贡献。六在PKD患者中鉴定了PRRT 2突变（包括两种新的），这些患者主要沿着左侧皮质脊髓束表现出显著降低的平均扩散率，前辅助运动区（pre-supplementary motor area，preSMA）和右额下回盖部（right opercular portion of the inferior frontal gyrus，IFGoperc）的灰质体积减少。前SMA的灰质体积减少和异常白色物质的扩散指数与疾病持续时间呈负相关。基因型-表型分析显示，PRRT 2突变携带者有较早的发病年龄，较长的攻击，和更大比例的双边症状比non-carriers.Conclusions：我们观察到，PRRT 2突变与疾病的严重程度，而神经解剖异常与PKD患者的疾病持续时间。前SMA和IFG区域的异常微结构变化，独立于突变状态，指向患者的运动抑制失调，并为PKD运动症状的神经生物学机制提供了新的见解。
Introduction: The pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation.Methods: Diffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls. Tract-based spatial statistics were conducted on diffusion indices to examine microstructural integrity of white matter. Voxel-based morphometry analysis was used to examine volumetric changes of gray matter. Multiple regression was employed to test the contribution of demography, disease duration, and PRRT2 status to pathological changes in brain structure.Results: Six (including two novel) PRRT2 mutations were identified in PKD patients who exhibited significantly reduced mean diffusivity mainly along the left corticospinal tract, and reduced gray matter volume in pre-supplementary motor area (preSMA) and right opercular part of inferior frontal gyrus (IFGoperc), compared to healthy controls. Both gray matter volume reductions in preSMA and diffusion indices of abnormal white matter negatively correlated with disease duration. Genotype-phenotype analysis revealed that PRRT2 mutation carriers had earlier onset age, longer attacks, and a larger proportion of bilateral symptoms than non-carriers.Conclusions: We observed that PRRT2 mutations were associated with disease severity, while neuroanatomical abnormality was associated with disease duration in patients with PKD. Aberrant microstructural changes in preSMA and IFG areas, independent of mutation status, point to dysregulated motor inhibition in patients and provide new insights into neurobiological mechanisms underlying motor symptoms of PKD.