Peters N, Holtmannspötter M, Opherk C, Gschwendtner A, Herzog J, Sämann P, Dichgans M
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Neurology. 2006 May 23;66(10):1517-22. doi: 10.1212/01.wnl.0000216271.96364.50.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL.
The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 +/- 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points.
The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint.
This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.
大脑常染色体显性动脉病伴皮质下梗死和白质脑病（CADASIL）是一种遗传性小血管疾病，可导致中风和皮质下血管性痴呆。最近关于散发性皮质下缺血性血管疾病的研究已将脑萎缩视为疾病进展的一个重要临床指标。然而，关于脑萎缩在CADASIL中的作用及其临床相关性却知之甚少。
作者使用SIENA（基于萎缩标准化的结构图像评估）软件及其用于横断面测量的改编版（SIENAX），测定了76例CADASIL患者（45.1±9.7岁）在2年期间的标准化脑容量（NBV）和脑容量变化百分比（PBVC）。基线评估包括收缩压（SBP）、同型半胱氨酸水平、体重指数（BMI）和载脂蛋白E（APOE）基因分型。在两个时间点均评估了T2病变体积和临床量表。
在两个时间点，NBV均与所有临床评分（Rankin量表、美国国立卫生研究院卒中量表、Barthel指数、阿尔茨海默病痴呆和多发梗死性痴呆诊断结构化访谈、Mattis痴呆评定量表）显著相关，且独立于年龄和性别。PBVC与除Mattis痴呆评定量表外的所有临床评分变化均相关（所有p<0.01）（p = 0.10）。在一个线性回归模型中，年龄（p<0.001）、男性（p<0.01）和SBP（p = 0.07）是基线时NBV较低的主要危险因素。年龄（p<0.001）和SBP（p = 0.01）是随访期间脑容量丢失的危险因素。样本量估计表明，当将PBVC用作终点时，在一项试验中证明治疗效果所需的个体数量可以减少。
本研究确定脑萎缩是CADASIL疾病进程的一个重要方面，并与包括认知在内的多个临床方面建立了显著相关性。年龄和收缩压是随访期间脑容量丢失的危险因素。脑容量变化百分比作为未来干预试验的辅助结局指标似乎很有前景。
