Leucoaraiosis, nigrostriatal denervation and motor symptoms in Parkinson's disease
Leucoaraiosis, nigrostriatal denervation and motor symptoms in Parkinson's disease
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DOI：
10.1093/brain/awr139
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发表时间：
2011-08-01
期刊：
影响因子：
14.5
通讯作者：
Albin, Roger L.
中科院分区：
文献类型：
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作者：
Bohnen, Nicolaas I.;Mueller, Martijn L. T. M.;Albin, Roger L.
在其他方面正常的老年人中，白化病与运动症状有关。据预测，合并症白质变也会导致帕金森病患者的运动特征，但之前对帕金森病患者白质变化的研究显示出不同的结果。目前还没有研究直接比较白化病和黑质纹状体多巴胺能失神经支配程度对运动特征的影响。我们研究了白化严重程度对帕金森病运动损伤的影响，该影响与黑质纹状体多巴胺能去神经支配的程度无关。73名帕金森病患者（Hoehn和Yahr期1-3）接受了脑磁共振和[C-11]二氢四苯那嗪囊泡单胺转运蛋白2型正电子发射断层成像。以小脑白质为强度参考，对幕上流体衰减反演恢复磁共振高强度白质体素进行自动评估。脑容量对白质信号高强度负荷进行对数变换和归一化。统一帕金森病评定量表的总评分和分评分被评估以确定运动障碍。接受多巴胺能药物治疗的受试者在临床定义的“关闭”状态下接受检查。以白质信号高强度负荷和黑质纹状体去神经支配为自变量的多变量回归分析表明，总的运动统一帕金森病评定量表评分（F = 11.4, P < 0.0001）具有显著的整体模型，白质信号高强度负荷（t = 2.0, β = 0.22, P = 0.045）和纹状体单胺能结合（t = -3.5, β = -0.38, P = 0.0008）具有显著的回归效应。轴向运动障碍与纹状体单胺能结合（t = -2.1, β = 0.22, P = 0.043）相比，与白质信号高强度负荷（t = 4.0, β = 0.43, P = 0.0001）有很强的相关性。白质信号高强度负荷消退对运动迟缓的影响具有临界意义。在强直或震颤评分中没有发现明显的白质信号高强度负荷效应。与震颤为主的亚组相比，姿势不稳定和步态困难亚组的白质信号高强度负担明显更高，尽管年龄或疾病持续时间没有显著差异。这些发现表明，帕金森病患者白质信号高负荷的增加与运动表现的恶化有关，与黑质纹状体多巴胺能去神经支配的程度无关。与黑质纹状体多巴胺能失神经支配相比，共病性白质疾病是轴向运动损伤的更大决定因素。
Leucoaraiosis is associated with motor symptoms in otherwise normal older adults. Comorbid leucoaraiosis is predicted to contribute also to motor features in Parkinson's disease but previous studies of white matter changes in Parkinson's disease show variable results. No prior studies have compared directly the effects of both leucoaraiosis and the degree of nigrostriatal dopaminergic denervation on motor features. We investigated the effect of leucoaraiosis severity on motor impairment independent of the degree of nigrostriatal dopaminergic denervation in Parkinson's disease. Seventy-three subjects with Parkinson's disease (Hoehn and Yahr stages 1-3) underwent brain magnetic resonance and [C-11]dihydrotetrabenazine vesicular monoamine transporter type 2 positron emission tomography imaging. Automated assessment of supratentorial fluid-attenuated inversion recovery magnetic resonance hyperintense white matter voxels was performed using cerebellar white matter as the intensity reference. White matter signal hyperintensity burden was log-transformed and normalized for brain volume. Unified Parkinson's Disease Rating Scale total and subscore ratings were assessed to determine motor impairment. Subjects receiving dopaminergic medications were examined in the clinically defined 'OFF' state. Multivariate regression analysis with measures of white matter signal hyperintensity burden and nigrostriatal denervation as independent variables demonstrated a significant overall model for total motor Unified Parkinson's Disease Rating Scale scores (F = 11.4, P < 0.0001) with significant regression effects for both white matter signal hyperintensity burden (t = 2.0, beta = 0.22, P = 0.045) and striatal monoaminergic binding (t = -3.5, beta = -0.38, P = 0.0008). Axial motor impairment demonstrated a robust association with white matter signal hyperintensity burden (t = 4.0, beta = 0.43, P = 0.0001) compared with striatal monoaminergic binding (t = -2.1, beta = 0.22, P = 0.043). White matter signal hyperintensity burden regression effects for bradykinesia had borderline significance. No significant white matter signal hyperintensity burden effects were found for rigidity or tremor subscores. White matter signal hyperintensity burden was significantly higher in the subgroup with postural instability and gait difficulties compared with the tremor-predominant subgroup despite no significant differences in age or duration of disease. These findings indicate that increased white matter signal hyperintensity burden is associated with worse motor performance independent of the degree of nigrostriatal dopaminergic denervation in Parkinson's disease. Comorbid white matter disease is a greater determinant of axial motor impairment than nigrostriatal dopaminergic denervation.