Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1St Youyi Road, Chongqing, 400016, China.
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Neurol Sci. 2024 May;45(5):2171-2180. doi: 10.1007/s10072-023-07221-w. Epub 2023 Nov 28.
Despite previous research suggesting a potential association between cerebral small vessel disease (CSVD) and epilepsy, the precise causality and directionality between cerebral small vessel disease (CSVD) and epilepsy remain incompletely understood. We aimed to investigate the causal link between CSVD and epilepsy.
A bidirectional two-sample Mendelian randomization (MR) analysis was performed to evaluate the causal relationship between CSVD and epilepsy. The analysis included five dimensions of CSVD, namely small vessel ischemic stroke (SVS), intracerebral hemorrhage (ICH), white matter damage (including white matter hyperintensity [WMH], fractional anisotropy, and mean diffusivity), lacunar stroke, and cerebral microbleeds. We also incorporated epilepsy encompassing both focal epilepsy and generalized epilepsy. Inverse variance weighted (IVW) was used as the primary estimate while other four MR techniques were used to validate the results. Pleiotropic effects were controlled by adjusting vascular risk factors through multivariable MR.
The study found a significant association between SVS (odds ratio [OR] 1.117, P = 0.022), fractional anisotropy (OR 0.961, P = 0.005), mean diffusivity (OR 1.036, P = 0.004), and lacunar stroke (OR 1.127, P = 0.007) with an increased risk of epilepsy. The aforementioned correlations primarily occurred in focal epilepsy rather than generalized epilepsy on subgroup analysis and retained their significance in the multivariable MR analysis.
Our study demonstrated that genetic susceptibility to CSVD independently elevates the risk of epilepsy, especially focal epilepsy. Diffusion tensor imaging may help screen patients at high risk for epilepsy in CSVD. Improved management of CSVD may be a significant approach in reducing the overall prevalence of epilepsy.
尽管先前的研究表明脑小血管病（CSVD）与癫痫之间存在潜在关联，但脑小血管病（CSVD）与癫痫之间的确切因果关系和方向性仍不完全清楚。我们旨在探讨 CSVD 与癫痫之间的因果关系。
采用双向两样本 Mendelian 随机化（MR）分析评估 CSVD 与癫痫之间的因果关系。该分析包括 CSVD 的五个维度，即小血管性缺血性卒中（SVS）、颅内出血（ICH）、白质损伤（包括白质高信号[WMH]、各向异性分数和平均弥散系数）、腔隙性卒中和脑微出血。我们还纳入了包括局灶性癫痫和全面性癫痫在内的癫痫。逆方差加权（IVW）作为主要估计值，同时还使用了其他四种 MR 技术来验证结果。通过多变量 MR 调整血管危险因素来控制多效性影响。
研究发现 SVS（优势比[OR]1.117，P=0.022）、各向异性分数（OR 0.961，P=0.005）、平均弥散系数（OR 1.036，P=0.004）和腔隙性卒中（OR 1.127，P=0.007）与癫痫风险增加之间存在显著关联。亚组分析显示，上述相关性主要发生在局灶性癫痫中，而非全面性癫痫中，且在多变量 MR 分析中仍具有显著性。
本研究表明，CSVD 的遗传易感性独立增加了癫痫的风险，尤其是局灶性癫痫。弥散张量成像可能有助于筛选 CSVD 中癫痫高危患者。改善 CSVD 的管理可能是降低癫痫总体患病率的重要方法。
