JNNP:烟雾病间接血运重建术后新生血管生成的预测因素:一项10年随访研究

2021-04-12 MedSci原创 MedSci原创

烟雾病(Moyamoya disease,MMD)是一种罕见的慢性进行性脑血管疾病,其特征是远端颈动脉狭窄和闭塞,近端大脑中动脉和前动脉,并伴有小侧支血管网的形成。脑动脉硬化症(EDAS)已成为MMD

烟雾病(Moyamoya disease,MMD)是一种罕见的慢性进行性脑血管疾病,其特征是远端颈动脉狭窄和闭塞,近端大脑中动脉和前动脉,并伴有小侧支血管网的形成。脑硬膜颞浅动脉血管融通术(EDAS)已成为MMD患者公认的治疗策略,但影响EDAS后侧支循环形成的因素尚不清楚。本研究选择术后至少5年行脑血管造影的患者,探讨包括RNF213变异的影响术后侧支循环形成的相关因素。

选取了2002年1月至2015年1月在中国人民解放军总医院第五医学中心神经外科接受EDAS治疗的所有MMD患者。选择接受长期术后数字减影血管造影(术后血管重建至最新随访血管造影时间≥5年)的患者。研究中所有MMD患者均接受EDAS治疗。收集基本临床资料。根据本文研究中描述的系统评估血管造影侧枝分级。 最后一次随访是在EDAS之后至少5年进行的。根据Matsushima等人描述的系统对大脑中动脉(MCA)旁路侧支循环的发展进行分级。4个随访事件包括复发性脑出血、脑梗塞和死亡。

2002年1月至2015年1月,在中国人民解放军总医院第五医学中心神经外科接受EDAS治疗的83例MMD患者被纳入本研究。表格总结了研究对象的临床特征。携带RNF213 p.R4810K的病例的突变率为24.1%(20/83)。所有变异的p.R4810K基因型均携带杂合突变(鸟嘌呤-腺嘌呤,GA),未检测到纯合突变(腺嘌呤-腺嘌呤,AA)。在150个大脑半球(16例单侧大脑半球患者)中,最后一次随访血管造影是在外科血管重建术后10.4年进行的。杂合子突变在侧支期不良组发生率明显高增(p=0.003),其神经功能状态大多较差(p=0.006)。与鸟嘌呤-鸟嘌呤(GG)组相比,GA组最常见的临床表现为脑梗死(42.1%对20.5%,p=0.022)。

共有150个大脑半球接受EDAS治疗。术后长期血管造影结果显示,良好的分级与较低的术前侧支循环期相关(p=0.001)。单因素分析显示,发病年龄越小,Matsushima分级越好(p=0.044),GA组术后侧支形成好于GG组(p=0.005)。多变量分析显示,只有年龄、术前侧支循环分期和p.R4810K变异与EDAS术后侧支循环良好显著相关(分别为p=0.039、p=0.017和p=0.023)。患者的平均随访时间为10.4±2.1(5.1-18.3)年,总体上有显著的临床改善。然而,83例患者中有9例(10.8%)在EDAS后发生脑卒中。其中脑梗死5例,脑出血4例。GA组有两个半球(5.3%)发生脑卒中,无一个半球再出血。GG组有7个半球(6.3%)出现脑卒中,其中4个半球出现再出血。虽然GG组的年发病率高于GA组,但根据Kaplan-Meier分析,这种差异无统计学意义(对数秩检验p=0.914)。

患者的基线特征

EDAS是MMD外科治疗的重要组成部分。然而,关于这个治疗还有很多未知的地方。小样本和短期随访血管造影的有限研究集中于间接血运重建后新生血管生成的因素。这是第一篇探讨影响长期(10.4±2.1年)术后侧枝形成的相关因素的报告。

在这项研究中,发现良好的Matsushima分级在发病年龄较小、后循环受累、神经系统状况差、自发侧支循环差和RNF213 p.R4810K(GA)杂合突变的患者中发生的频率明显更高。显然,除了发病年龄和RNF213 p.R4810K杂合子突变外,所有其他影响因素都可以指示MMD脑缺血的严重程度,尤其是本文新提出的侧支循环评估系统。MMD患者大脑前动脉和MCA区缺血皮质的侧支供应以自发侧支循环为主,尤其是软脑膜系统。Willis环内存在经后交通动脉(PComA)的侧支血流也与边缘区梗死的低发生率有关。因此,较低的侧支循环评分往往意味着更严重的脑缺血。本文的研究还发现,杂合子突变与自发侧支循环不良显著相关,这可能是导致严重症状和神经状况恶化的原因。作者推测RNF213杂合子突变的患者有更严重的脑缺血,缺氧的脑环境调动血管内皮细胞的增殖和活化,从而在术后获得更好的侧支循环。

在本文研究的长期随访中,无论基因型如何,复发性卒中的频率都很低,Kaplan-Meier曲线表明p.R4810K基因型之间复发性卒中没有显著差异。尽管杂合子突变在侧支循环不良期组发生率明显增高,且神经功能状态大多较差,表明手术治疗后缺血更严重,预后较差,但患者侧支循环形成较好,从而有效地预防了中风的发生。这些发现表明,不仅纯合而且杂合的p.R4810K可作为严重MMD的特异性生物标志物,标志着需要早期介入血运重建手术。

Wang QYang RZou Z, et al Predictors of neoangiogenesis after indirect revascularisation in moyamoya disease: a 10-year follow-up study

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    2022-04-15 ms4000001336959158

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