JNNP:脑白质高信号进展的发生率和5项危险因素

2021-08-13 MedSci原创 MedSci原创

本文对脑白质高信号随时间变化的纵向研究进行了系统回顾和荟萃分析。计算了WMH病变生长的绝对速率,并确定这些速率如何随研究队列特征而变化。进一步估计了介入试验所需的样本量以及人群因素对这些值的影响。

MRI上检查中的脑白质高信号(WMHs)随着患者年龄的增长,在中风患者中,尤其是在脑小血管病(SVD)患者中变得非常常见。 脑白质高信号是脑小血管病的一种磁共振成像表型,呈现为脑皮质下白质扩散或融合。脑白质高信号早期多无临床表现,病理生理学机制尚未完全阐明。在研究中,WMHs可预测中风和痴呆的风险。神经病理学研究表明,在绝大多数情况下,它们似乎是由SVD引起的,并伴有缺血性脱髓鞘、轴突丢失和神经胶质增生的组织学变化。虽然许多研究评估了WMHs患病率的潜在风险因素,但WMH进展率尚未有相关详细的研究。

因为WMHs的临床相关性,以及可以通过磁共振获得结果,WMHs在SVD和痴呆治疗的实验中越来越多地被用作临床治疗效果标志物。有研究表明,WMH病变可能因年龄和所研究疾病组等特征而不同。此外,WMH与SVD临床症状(包括痴呆)之间的密切关系表明,研究WMH危险因素可能有助于开发中风和痴呆的潜在治疗方法。为了更好地描述WMHd在SVD临床试验中的潜在应用,本文对WMHs随时间变化的纵向研究进行了系统回顾和荟萃分析。计算了WMH病变生长的绝对速率,并确定这些速率如何随研究队列特征而变化。进一步估计了介入试验所需的样本量以及人群因素对这些值的影响。最后,为了确定潜在的治疗方法,评估了WMH进展的个体危险因素。本文发表在《神经病学,神经外科学和精神病学杂志》上()。

首先寻找对WMHs进行纵向评估的研究。在PubMed和Google Scholar上搜索了以下术语 ((‘white matter hyperintens*’ OR WMH OR ‘white matter lesion*’ OR WML OR leukoaraiosis) AND (progress* OR develop* OR penumbra OR evol*) AND (longitudinal OR serial OR ‘follow-up’) AND (MRI OR ‘magnetic resonance’)) 。研究仅限于散发性SVD,不包括可能具有不同病理机制的脑淀粉样血管病或单基因SVD。排除了综述文章、单一病例报告、试验方案和没有数字数据的文章。在描述同一队列的多篇文章的案例中,使用了样本量最大的参考文献。

Figure 1

研究流程图

在可从总脑容量的百分比中提取或计算T2加权成像测量的WMH进展,并将其标准化为每年立方厘米的膨胀率(cc/年)。根据研究人群将研究分为社区队列和特定疾病组:即SVD、卒中、痴呆或轻度认知障碍(MCI)、抑郁/情绪障碍或非特异性心血管疾病(CVD)。图像分析方法分为手动、半自动(使用软件勾勒病变轮廓并手动校正)或自动。同时提取基线WMH病变体积。为了在个体患者基础上检查病变进展的危险因素,提取了人口统计学/不可改变的风险因素(年龄、性别和基线WMH病变体积)和潜在可改变的心血管风险因素(包括高血压、糖尿病、高胆固醇血症、当前吸烟状态)。使用混合效应线性模型评估研究人群选择和图像分析方法对WMH年增长率的影响。对于连续预测变量,使用相关系数标度来表示连续预测变量(以年为单位的年龄或以cc为单位的基线WMH值)。

Figure 2

WMH病变进展直方图(cc/年)

初步搜索结果为924份出版物,最后206项研究纳入了本研究。SVD患者的WMH增长率最高(2.50cc/年),未经选择的卒中患者的WMH增长率中等(1.29cc/年),非卒中心血管疾病和认知障碍患者的WMH增长率较低。对认知障碍、抑郁症和心血管病患者的研究显示,其增长率与总体平均水平相似,这可能反映了社区队列研究中这些风险因素的高患病率。年龄与进展显著相关(相关系数0.15cc/年,95% CI 0.02至0.28cc/年)与基线病变体积也显著闲逛(0.6cc/年,95% CI 0.13至1.06 cc/年)。高血压(或1.72,95% CI 1.19至2.46)和当前吸烟(OR 1.48,95% CI 1.02至2.16)与WMH生长相关。临床试验的样本量因患者群体选择和基线病变体积的不同而有很大差异。高血压对进展有重大影响,这支持了高血压治疗对降低WMH以及由此导致的中风和痴呆风险的重要性。与吸烟和高血压相比,发现高胆固醇血症和糖尿病与WMH进展率之间没有显著相关性。降胆固醇药物的随机对照试验未显示WMHs的减少。

Figure 4

WMH进展与基线体积的气泡图

总之,研究结果表明:年龄、中风,尤其是SVD、高血压和吸烟都是WMHs进展的危险因素。本文对WMHs进展率的估计提供了可靠的数据,可用于计划使用WMH作为替代终点所需的样本量。

 

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    2021-08-13 智慧药

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