Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
J Neurol Neurosurg Psychiatry. 2010 Jul;81(7):756-63. doi: 10.1136/jnnp.2009.190702. Epub 2009 Dec 1.
Unbiased longitudinal studies are needed to understand the distributed neurodegenerative changes of Huntington's disease (HD). They may also provide tools for assessing disease-modifying interventions. The authors investigated the progression of regional atrophy in premanifest and early HD compared with controls.
Nine controls, 17 premanifest and 21 early HD subjects underwent volumetric MRI at baseline and 2 years. Premanifest subjects were on average 18.1 years before predicted motor onset. Non-linear registration was used to model within-subject change over the scanning interval, and statistical parametric mapping was used to examine group differences and associations with clinical variables.
In early HD, increased grey-matter (GM) atrophy rates were evident throughout the subcortical GM and over selective cortical regions compared with controls. This group also demonstrated strikingly widespread increases in white-matter (WM) atrophy rates. The authors observed no significant differences between premanifest HD and controls. Longer CAG was associated with higher atrophy rates over large WM areas including brainstem and internal capsule and over small GM regions including thalamus and occipital cortex. Worse baseline motor score was associated with regionally increased rates in the thalamus, internal capsule and occipital lobe. Sample-size calculations indicate that 19 and 24 early HD subjects per treatment arm would need to complete a 2-year trial in order to detect a 50% reduction in WM and GM atrophy rates respectively.
Degeneration of structural connectivity may play an important role in early HD symptoms. Assessment of WM and GM changes will be important in understanding the complexity of HD and its treatment.
为了了解亨廷顿病（HD）的神经退行性变的分布情况，需要进行无偏的纵向研究。这些研究还可能为评估疾病修饰干预措施提供工具。作者研究了与对照组相比，在无症状和早期 HD 中区域萎缩的进展情况。
9 名对照者、17 名无症状前和 21 名早期 HD 受试者在基线和 2 年后接受了容积 MRI 检查。无症状受试者的平均发病前时间为 18.1 年。使用非线性配准来模拟扫描间隔内的个体内变化，使用统计参数映射来检查组间差异和与临床变量的关联。
在早期 HD 中，与对照组相比，整个皮质下 GM 和选择性皮质区域的 GM 萎缩率明显增加。该组还显示出广泛的 WM 萎缩率增加。作者没有观察到无症状 HD 与对照组之间的显著差异。较长的 CAG 与包括脑干和内囊在内的大 WM 区域以及包括丘脑和枕叶皮质在内的小 GM 区域的更高萎缩率相关。基线运动评分较差与丘脑、内囊和枕叶区域的区域性萎缩率增加相关。样本量计算表明，每个治疗组需要 19 名和 24 名早期 HD 患者完成 2 年的试验，才能分别检测到 WM 和 GM 萎缩率降低 50%。
结构连接的退化可能在早期 HD 症状中起重要作用。评估 WM 和 GM 变化对于理解 HD 的复杂性及其治疗方法将非常重要。
