Department of Neurosurgery and Spine Surgery (A.N.S., L.R., D.S., B.C., A.H., T.F.D., R.J., K.H.W., U.S., P.D.), University Hospital Essen, Germany.
Institute of Diagnostic and Interventional Radiology and Neuroradiology (Y.L.), University Hospital Essen, Germany.
Stroke. 2022 Mar;53(3):817-824. doi: 10.1161/STROKEAHA.121.035338. Epub 2021 Oct 28.
The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period.
Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage.
One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15-8.63]; =0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04-5.86]; =0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18-8.99]; =0.022 and odds ratio, 2.53 [95% CI, 1.07-5.98]; =0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80-110.39]; =0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%-23.6%) for the entire cohort, 30.2% (20.2%-42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%-51.1%) for children with brain stem CCM.
Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.
本研究旨在探讨儿童脑动静脉畸形（CCM）的自然病程，特别强调 5 年内首次和复发性出血的风险。
我们的机构数据库筛选了 2003 年至 2020 年期间治疗的 CCM 患者。纳入了年龄≤18 岁、有完整磁共振成像数据集、临床基线特征和≥1 次随访检查的患者。手术治疗的患者在 CCM 切除后被删失。我们使用单变量和多变量逻辑回归分析，调整年龄和性别，评估了各种参数对诊断时首次或复发性颅内出血（ICH）的影响。Kaplan-Meier 和 Cox 回归分析用于确定（再）出血的 5 年累积风险。
分析了 129 例儿童 CCM 患者。单变量逻辑回归确定脑干 CCM（比值比，3.15[95%置信区间，1.15-8.63]；=0.026）和 CCM 家族史（比值比，2.47[95%置信区间，1.04-5.86]；=0.041）为 ICH 的统计学显著预测因子。多变量逻辑回归证实了这种相关性（比值比，3.62[95%置信区间，1.18-8.99]；=0.022 和比值比，2.53[95%置信区间，1.07-5.98]；=0.035）。Cox 回归分析确定 ICH 为表现模式（风险比，14.01[95%置信区间，1.80-110.39]；=0.012）是 5 年随访期间再出血的独立预测因子。整个队列的 5 年累积（再）出血风险为 15.9%（95%置信区间，10.2%-23.6%），诊断时有 ICH 的儿科患者为 30.2%（20.2%-42.3%），脑干 CCM 的儿童为 29.5%（95%置信区间，13.9%-51.1%）。
脑干 CCM 和 CCM 家族史的儿科患者ICH 作为首发表现的风险更高。在未经治疗的 5 年随访期间，他们与成年患者相比，（再）出血的风险相似。随着时间的推移，（再）出血的可能性增加，特别是在有 ICH 或脑干定位的情况下。
