The progression of regional atrophy in premanifest and early Huntington's disease: a longitudinal voxel-based morphometry study
The progression of regional atrophy in premanifest and early Huntington's disease: a longitudinal voxel-based morphometry study
复制标题
DOI：
10.1136/jnnp.2009.190702
复制
发表时间：
2010-07-01
影响因子：
11
通讯作者：
Tabrizi, Sarah J.
中科院分区：
文献类型：
--
作者：
Hobbs, Nicola Z.;Henley, Susie M. D.;Tabrizi, Sarah J.
背景 需要进行无偏见的纵向研究来了解亨廷顿病（HD）的分布式神经退行性变化。它们还可以提供评估疾病缓解干预措施的工具。作者调查了与对照组相比，HD 前期和早期 HD 区域萎缩的进展情况。方法 9 名对照者、17 名 HD 前期受试者和 21 名早期 HD 受试者在基线和 2 年接受了体积 MRI。受试者在预测运动开始前平均 18.1 年出现。使用非线性配准来模拟扫描间隔期间受试者内的变化，并使用统计参数映射来检查组间差异以及与临床变量的关联。 结果在早期 HD 中，与对照组相比，整个皮质下 GM 和选择性皮质区域的灰质 (GM) 萎缩率明显增加。该群体还表现出白质（WM）萎缩率显着普遍增加。作者观察到预表现 HD 和对照组之间没有显着差异。较长的 CAG 与较大的 WM 区域（包括脑干和内囊）以及较小的 GM 区域（包括丘脑和枕叶皮层）的较高萎缩率相关。较差的基线运动评分与丘脑、内囊和枕叶的区域评分增加有关。样本量计算表明，每个治疗组需要 19 名和 24 名早期 HD 受试者完成为期 2 年的试验，才能检测到 WM 和 GM 萎缩率分别降低 50%。 结论 结构连接性退化可能在早期 HD 症状中发挥重要作用。评估 WM 和 GM 变化对于理解 HD 及其治疗的复杂性非常重要。
Background 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.Methods 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.Results 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.Conclusions 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.