table_3.docx

Background and purposeThe blood–brain barrier (BBB) not only provides a physical obstruction but also recruits and activates neutrophils in cases of infection. Hemorrhagic or ischemic stroke reportedly induces the disruption of the BBB. However, few studies have reported a correlation between the incidence of meningitis in patients with a history of stroke. This study tested the hypothesis that patients with a history of stroke may be more vulnerable to meningitis.
MethodsStroke and age-matched comparison (n = 29,436 and 87,951, respectively) cohorts were recruited from the Taiwan National Health Insurance database (2000–2011). Correlations between the two cohorts were evaluated by Cox proportional hazard regression model, Kaplan–Meier curve, and log-rank tests.
ResultsThe incidence of meningitis was higher in the stroke cohort compared to that in the comparison cohort [hazard ratio (HR), 2.89; 95% confidence interval (CI), 2.23–3.74, p < 0.001]. After adjusting for age, sex, and comorbidities, the estimated HR in the stroke cohort was 2.55-fold higher than that in the comparison cohort (CI, 1.94–3.37; p < 0.001). Notably, patients who had experienced hemorrhagic stroke had a higher incidence rate of meningitis than those with a history of ischemic stroke, except for patients older than 75 years (incidence rates in hemorrhagic/ischemic stroke patients, 3.14/1.48 in patients younger than 45 years, 1.52/0.41 in 45- to 64-year group, 1.15/0.90 in 65- to 74-year group, 0.74/0.93 in patients older than 75 years). Moreover, stroke patients who had undergone head surgery had the highest meningitis risk (adjusted HR, 8.66; 95% CI, 5.55–13.5; p < 0.001) followed by stroke patients who had not undergone head surgery (adjusted HR, 2.11; 95% CI, 1.57–2.82; p < 0.001).
ConclusionOur results indicated that stroke patients have higher risks of meningitis. Compromised BBB integrity in stroke patients may lead to increased vulnerability to infectious pathogens. In summary, our study provided new evidence of the clinical relationship between stroke and meningitis, and our findings suggest the need for precautions to prevent meningitis in stroke patients.

研究背景与研究目的：血脑屏障（blood–brain barrier, BBB）不仅作为物理屏障，还可在感染情况下招募并激活中性粒细胞。已有研究表明，出血性或缺血性脑卒中可导致血脑屏障破坏。但目前鲜有研究报道有脑卒中病史患者的脑膜炎发病率与该人群的相关性。本研究旨在验证这一假说：有脑卒中病史的患者可能更容易罹患脑膜炎。
研究方法：本研究从中国台湾地区国民健康保险数据库（2000-2011年）中招募了脑卒中队列与年龄匹配的对照队列，分别纳入29436例和87951例受试者。采用Cox比例风险回归模型、Kaplan-Meier曲线以及对数秩检验对两个队列的相关性进行分析。
研究结果：脑卒中队列的脑膜炎发病率显著高于对照队列[风险比（HR）=2.89；95%置信区间（CI）=2.23~3.74，P<0.001]。在校正年龄、性别与合并症后，脑卒中队列的估计HR较对照队列升高2.55倍（CI=1.94~3.37；P<0.001）。值得注意的是，除75岁以上人群外，有出血性脑卒中病史的患者脑膜炎发病率高于缺血性脑卒中病史患者：<45岁人群中，出血性/缺血性脑卒中患者的发病率分别为3.14/1.48；45~64岁组为1.52/0.41；65~74岁组为1.15/0.90；75岁以上人群为0.74/0.93。此外，接受过头部手术的脑卒中患者脑膜炎风险最高（校正后HR=8.66；95%CI=5.55~13.5；P<0.001），其次为未接受头部手术的脑卒中患者（校正后HR=2.11；95%CI=1.57~2.82；P<0.001）。
研究结论：本研究结果显示，脑卒中患者罹患脑膜炎的风险更高。脑卒中患者血脑屏障完整性受损，可能使其对感染性病原体的易感性增加。综上，本研究为脑卒中与脑膜炎之间的临床相关性提供了新证据，研究结果提示需对脑卒中患者采取脑膜炎预防措施。