Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University Nijmegen Medical Centre, The Netherlands.
Brain. 2011 Jan;134(Pt 1):73-83. doi: 10.1093/brain/awq343. Epub 2010 Dec 14.
Gait disturbances are common in the elderly. Cerebral small vessel disease, including white matter lesions and lacunars infarcts, is thought to disrupt white matter tracts that connect important motor regions, hence resulting in gait disturbances. Pathological studies have demonstrated abnormalities in white matter that may appear normal on brain imaging. The loss of integrity in such normal-appearing white matter may partly be due to small vessel disease and may play a role in causing gait disturbances. The white matter regions involved in these gait disturbances, both in white matter lesions and normal-appearing white matter, remain unclear. We, therefore, aimed to investigate the relation between the location of white matter lesions and gait using voxel-based morphometry analysis, as well as between white matter integrity and gait by applying tract-based spatial statistics to diffusion tensor imaging parameters. Magnetic resonance imaging was carried out on 429 individuals in the age range of 50 and 85 years, with cerebral small vessel disease without dementia or parkinsonism. Gait was assessed quantitatively. White matter lesions, especially in the centrum semiovale and periventricular frontal lobe, were related to a lower gait velocity, shorter stride length and broader stride width. Loss of white matter integrity, as indicated by a lower fractional anisotropy and higher mean diffusivity, in numerous regions was related to a lower gait performance. Most of these regions were located in the normal-appearing white matter. The strongest significant association was found in the corpus callosum, particularly the genu. Most of the associations in the normal-appearing white matter disappeared after controlling for white matter lesions and lacunar infarcts, except for some in the corpus callosum. In conclusion, our study showed that using a combination of voxel-based morphometry analysis of the white matter lesions and diffusion tensor imaging is of added value in investigating the pathophysiology of gait disturbances in subjects with small vessel disease. Our data demonstrate that, in elderly subjects with small vessel disease, widespread disruption of white matter integrity, predominantly in the normal-appearing white matter, is involved in gait disturbances. In particular, loss of fibres interconnecting bilateral cortical regions, especially the prefrontal cortex that is involved in cognitive control on motor performance, may be important. The most important mechanisms underlying affected normal-appearing white matter are probably a direct effect of small vessel disease or, indirectly, remote effects of white matter lesions and lacunar infarcts.
步态障碍在老年人中很常见。脑小血管病，包括白质病变和腔隙性梗死，被认为会破坏连接重要运动区域的白质束，从而导致步态障碍。病理研究已经证明白质存在异常，这些异常在脑成像上可能表现正常。这种看似正常的白质完整性的丧失部分可能是由于小血管疾病引起的，并且可能在导致步态障碍方面发挥作用。在这些步态障碍中涉及的白质区域，无论是在白质病变还是看似正常的白质中，仍然不清楚。因此，我们旨在通过体素形态计量学分析研究白质病变的位置与步态之间的关系，以及通过应用弥散张量成像参数的基于束的空间统计学研究白质完整性与步态之间的关系。对 429 名年龄在 50 至 85 岁之间、无痴呆或帕金森病的脑小血管病患者进行了磁共振成像检查。对步态进行了定量评估。白质病变，特别是半卵圆中心和脑室周围额叶，与较低的步行速度、较短的步长和较宽的步宽有关。许多区域的白质完整性丧失，表现为较低的各向异性分数和较高的平均扩散系数，与较低的步态表现有关。这些区域大部分位于看似正常的白质中。在胼胝体，特别是胼胝体膝部，发现了最强的显著关联。在控制白质病变和腔隙性梗死后，除了胼胝体的一些区域外，大多数在看似正常的白质中的关联都消失了。总之，我们的研究表明，使用基于体素形态计量学分析白质病变和弥散张量成像的组合，对于研究小血管病患者步态障碍的病理生理学具有额外的价值。我们的数据表明，在患有小血管病的老年患者中，广泛的白质完整性破坏，主要是在看似正常的白质中，与步态障碍有关。特别是，连接双侧皮质区域的纤维的丧失，特别是涉及认知控制运动表现的前额叶，可能很重要。受影响的看似正常的白质的最重要机制可能是小血管疾病的直接作用，或者是白质病变和腔隙性梗死的间接远程作用。
