Gross Bradley A, Du Rose, Orbach Darren B, Scott R Michael, Smith Edward R
Department of Neurological Surgery, Brigham and Women's Hospital.
Department of Neurological Surgery; and.
J Neurosurg Pediatr. 2016 Feb;17(2):123-128. doi: 10.3171/2015.2.PEDS14541. Epub 2015 Oct 16.
OBJECT Cerebral cavernous malformations (CMs) are a source of neurological morbidity from seizures and focal neurological deficits due to mass effect and hemorrhage. Although several natural history reports exist for adults with CMs, similar data for pediatric patients are limited. METHODS The authors reviewed hospital databases to identify children with CMs who had not been treated surgically and who had clinical and radiological follow-up. Annual hemorrhage rates were calculated in lesion-years, and risk factors were assessed using the Cox proportional hazards model. RESULTS In a cohort of 167 patients with 222 CMs, the mean patient age at the time of diagnosis was 10.1 years old (SD 6.0). Ninety patients (54%) were male. One hundred four patients (62%) presented with hemorrhage from at least 1 CM, 58 (35%) with seizures with or without CM hemorrhage, and 43 (26%) with incidental lesions. Twenty-five patients (15%) had multiple CMs, 17 (10%) had a family history of CMs, and 33 (20%) had radiologically apparent developmental venous anomalies (DVAs). The overall annual hemorrhage rate was 3.3%. Permanent neurological morbidity was 29% per hemorrhage, increasing to 45% for brainstem, thalamic, or basal ganglia CM and decreasing to 15% for supratentorial lobar or cerebellar lesions. The annual hemorrhage rate for incidental CMs was 0.5%; for hemorrhagic CMs, it was 11.3%, increasing to 18.2% within the first 3 years. Hemorrhage clustering within 3 years was statistically significant (HR 6.1, 95% CI 1.72-21.7, p = 0.005). On multivariate analysis, hemorrhagic presentation (HR 4.63, 95% CI 1.53-14.1, p = 0.007), brainstem location (HR 4.42, 95% CI 1.57-12.4, p = 0.005), and an associated radiologically apparent DVA (HR 2.91, 95% CI 1.04-8.09, p = 0.04) emerged as significant risk factors for hemorrhage, whereas age, sex, CM multiplicity, and CM family history did not. CONCLUSIONS Prior hemorrhage, brainstem location, and associated DVAs are significant risk factors for symptomatic hemorrhage in children with CMs. Hemorrhage clustering within the first 3 years of a bleed can occur, a potentially important factor in patient management and counseling.
目的 脑海绵状血管畸形(CMs)是导致神经功能障碍的原因,可引发癫痫以及因占位效应和出血导致的局灶性神经功能缺损。尽管已有多篇关于成年CMs患者的自然史报告,但儿科患者的类似数据有限。方法 作者回顾了医院数据库,以确定未接受手术治疗且有临床和影像学随访的CMs患儿。按病变-年计算年出血率,并使用Cox比例风险模型评估危险因素。结果 在167例患者共222个CMs的队列中,诊断时患者的平均年龄为10.1岁(标准差6.0)。90例(54%)为男性。104例(62%)患者至少有1个CM发生出血,58例(35%)有癫痫发作,伴或不伴有CM出血,43例(26%)为偶然发现的病变。25例(15%)患者有多个CMs,17例(10%)有CM家族史,33例(20%)有影像学可见的发育性静脉异常(DVA)。总体年出血率为3.3%。每次出血导致永久性神经功能障碍的发生率为29%,脑干、丘脑或基底节CM患者这一比例增至45%,幕上叶或小脑病变患者则降至15%。偶然发现的CMs的年出血率为0.5%;出血性CMs的年出血率为11.3%,在最初3年内增至18.2%。3年内出血聚集具有统计学意义(风险比6.1,95%置信区间1.72 - 21.7,p = 0.005)。多因素分析显示,出血表现(风险比4.63,95%置信区间1.53 - 14.1,p = 0.007)、脑干位置(风险比4.42,95%置信区间1.57 - 12.4,p = 0.005)以及相关的影像学可见DVA(风险比2.91,95%置信区间1.04 - 8.09,p = 0.04)是出血的重要危险因素,而年龄、性别、CMs数量和CM家族史则不是。结论 既往出血、脑干位置以及相关的DVA是CMs患儿发生症状性出血的重要危险因素。出血后最初3年内可能发生出血聚集,这在患者管理和咨询中是一个潜在的重要因素。