CADASIL患者脑微出血分布特征及临床意义

目的 探讨伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy，CADASIL）患者脑微出血（cerebral microbleeds，CMBs）的分布特征及临床意义。 方法 回顾性纳入2017年6月-2019年12月北京协和医院基因确诊的连续CADASIL患者21例（CADASIL 组），以及性别匹配的高血压动脉硬化性脑小血管病患者21例（高血压脑小血管病组）。所有患者均 行头MRI 检查（含T2 */SWI序列），盲法读片并记录CMBs的数量和部位，分析两组CMBs分布的差异。 结果 CADASIL组年龄和常见血管病危险因素比例均低于高血压脑小血管病组。CADASIL组47.6% 患者检出CMBs（共计115个），而高血压脑小血管病组高达95.2%（共计218个）。CADASIL组CMBs分 布以丘脑最常受累（45.2%），其次是脑叶（皮层/皮层下，35.7%）、基底节（11.3%）。高血压脑小 血管病组则以丘脑以外的基底节CMBs最多见（35.3%），其次是脑叶（26.6%）、丘脑（19.2%）、脑干 （16.1%）。CADASIL患者丘脑CMBs/总CMBs比例、丘脑CMBs/（基底节CMBs+脑干CMBs）比例均高于高 血压脑小血管病组（均P＜0.001）。 结论 CADASIL患者CMBs分布以丘脑最常见，其次是皮层/皮层下区域，而高血压脑小血管病患者 则以丘脑以外的基底节、脑干更常见。     

伴脑出血的常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病的基因突变及临床特征(附2例报告)

目的探讨伴脑出血的常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病(CADASIL)的基因突变、临床及影像学特征等。方法回顾性分析2例伴脑出血的CADASIL患者的临床和发病特征,并通过文献检索总结分析全球报道的所有伴脑出血的CADASIL患者。结果本研究中1例为46岁男性,出现小脑出血及丘脑出血,有高血压病及口服抗血小板药物史,NOTCH3基因突变为p. R544C;另1例为52岁女性,反复基底节、丘脑、放射冠出血,无相关危险因素,NOTCH3基因突变为p.C388Y,该突变是世界首位报道伴脑出血的CADASIL患者。文献检索共76例伴脑出血的CADASIL报道,其中在有基因说明的65位患者中R544C最常见(65.1%),脑出血部位主要为基底节区(29.1%)、丘脑(29.1%),其次为脑叶(19.0%)、小脑(11.4%)、脑干(6.3%)和放射冠(5.1%),部分患者伴高血压或有口服抗栓药物史。结论 CADASIL可能是脑出血的一种危险因素,临床上需要合理控制CADASIL患者的血压,谨慎使用抗栓药物,并可参考脑微出血MRI扫描情况评估出血风险。     

脑微出血的研究进展

<正>脑微出血(cerebral microbleeds,CMBs)在90年代由Scharf等首次报道,属于脑小血管疾病的影像学表现之一,但健康老年人的磁共振影像上也常常可以发现CMBs。CMBs常常伴随脑白质病变、颅内出血(intracerebral hemorrhage,ICH)和缺血性卒中[1-4]。已有报道CMBs与其他脑小血管病,如脑淀粉样血管病(cerebral amyloid angiopathy,CAA)和高血压性血管病等存     

无高血压病史急性脑梗死患者脑内微出血的临床研究

目的 探讨有、无高血压的急性脑梗死患者中脑内微出血(cerebral microbleeds,CMBs)的危险因素和影像学上分布特点的不同.方法 连续性收集急性脑梗死患者,进行磁共振扫描,包括T1、T2 加权相以及梯度回波序列(gradient-echo T2 *,GRE-T2*).分析患者临床特点、MRI上脑白质病变的严重程度和CMBs病灶的分布特点.结果 共入选998例急性脑梗死患者,CMBs发生于273例患者,其中62例无高血压病史.在无高血压病史的急性脑梗死患者中CMBs发生率为18.5%(62/335),低于有高血压病史的急性脑梗死患者(211/663,31.8%,P＜0.0001).无高血压患者的CMBs局限于皮层和皮层下者占40.3%(25/62),高于有高血压的患者(20.4%,43/211,P=0.001).脑白质病变的严重程度,入院时收缩压是无高血压病史急性脑梗死患者发生CMBs的独立危险因素.结论 有高血压和无高血压的急性脑梗死患者CMBs分布部位有所不同,后者更多地集中于皮层和皮层下.控制血压在有、无高血压病史的CMBs患者均必要.     

脑淀粉样血管病的影像学标志物及临床相关性研究进展

脑淀粉样血管病（cerebral amyloid angiopathy,CAA）是一种多见于老年人群中的脑小血管病, 不同于高血压导致的脑小血管病易累及脑深部区域,CAA多累及皮层及软脑膜小血管。多发脑叶微出 血是CAA患者常见的影像学表现,研究认为其与症状性脑叶出血及进行性认知功能下降相关。随着 近年来对脑小血管病影像学表现的深入研究,发现皮层蛛网膜下腔出血与皮层表面含铁血黄素沉 积是CAA相对特异的影像学表现,并且与短暂性局灶性神经系统症状发作相关。此外,脑白质高信号、 小梗死灶等脑小血管病影像学标志均在CAA患者中出现,提示除外临床较关注的出血性改变,CAA患 者的缺血性损伤也是导致临床症状的重要因素。     

原发性高血压合并脑微出血患者动态血压特征

目的探讨合并脑微出血(cerebral microbleeds,CMBs)的原发性高血压(essential hypertension,EH)患者动态血压特征。方法将81例原发性高血压患者分为两组:46例合并CMBs者为脑微出血组;35例无CMBs者为对照组。全部患者作动态血压测定,比较两组间各动态血压值的差异。结果脑微出血组和对照组随测血压的收缩压和舒张压比较,差异无统计学意义。但两组的随测血压值均明显高于ABPM值,差异有统计学意义(P0.05);在脑微出血组的EH患者中,夜间收缩压水平明显高于对照组的EH患者(P=0.026);在所有EH患者中,无论有无CMBs,其血压昼夜节律均明显异常(收缩压夜间下降率△SBP及舒张压夜间血压下降率△DBP均10%),但脑微出血组△SBP及△DBP均显著低于对照组(P值分别为0.008和0.037)。结论夜间收缩压和夜间血压下降率与CMBs的发生有密切关系,在治疗高血压的同时,应重视血压动态节律的变化。     

Stroke：小脑浅表微出血的临床意义

原发性小脑出血的病因通常被认为是高血压小血管病(small vessel disease,SVD),但也有报道提示也可能与脑淀粉样血管病(cerebral amyloid angiopathy,CAA)有关。鉴别CAA和高血压SVD主要依据幕上区域和脑干的出血影像学标志,特别是微出血。按照病理学确认的Boston标准,脑叶出血和局限于脑叶的多发脑微出血最有可能为CAA,局限于深部的出血或合并幕上脑叶和深部出血(混合-脑出血/微出血)者可能为高血压SVD。有报道显示,CAA患者小脑微出血的可能性显著高于混合和深部脑出血患者。     

磁敏感成像技术在脑微出血诊断中的价值研究

目的分析磁敏感成像(SWI)技术在脑微出血(CMBs)诊断中的应用价值。方法收集南京医科大学康达学院附属连云港中医院2017-01—2018-12经临床及影像学检查确诊的CMBs患者80例,均行磁共振(MRI)常规序列(T_1WI、T_2WI、T_2FLAIR、DWI)及磁敏感成像(SWI)序列检查,探讨MRI常规序列与SWI序列在CMBs检出方面的差异,同时观察CMBs发生部位差异。结果 SWI序列检出CMBs病灶328个,DWI序列(b=1000)检出率为43.3%,T_1WI检出率为9.8%,T_2WI检出率为15.5%,T_2FLAIR检出率为18.9%,SWI序列对于CMBs的检出率明显高于MRI常规序列,差异有统计学意义(P0.05)。CMBs病灶发病部位以基底节区为最多,依次为皮层及皮层下、丘脑、脑干、小脑。结论 SWI序列能够高效显示CMBs,且具有特征性表现,监测方面优势明显。     

缺血性脑血管病并脑微出血相关因素分析及认知功能临床研究

目的分析缺血性脑血管病（ICVD）合并脑微出血（CMBs）的相关因素及对认知功能的影响。方法选取240例ICVD患者为研究对象,根据是否合并CMBs分为CMBs组和非CMBs组,分别纳入62例和178例患者,应用简易精神状况检查表（MMSE）和蒙特利尔认知评估量表（MoCA）评估患者的认知功能。结果 CMBs组患者的年龄、合并高血压比例、脑白质疏松（LA）比例、腔隙性梗死（LI）比例和既往卒中史比例均显著高于非CMBs组患者（P＜0.05）,高龄（OR＝1.376）、合并高血压（OR＝3.965）、合并LI（OR＝3.562）是ICVD患者合并CMBs的危险因素（P＜0.05）;CMBs组MMSE总分、MoCA总分和视空间／执行、注意、延迟回忆等评分均显著低于无CMBs组（P＜0.05）,累及皮层‐皮层下CMBs患者的MMSE总分、MoCA总分及视空间／执行、注意、语言、延迟回忆等评分均显著低于无累及皮层‐皮层下CMBs患者（P＜0.05）。结论 ICVD患者合并CMBs的发病与多种因素具有相关性,可导致患者出现显著的认知功能障碍,可能与累及皮层‐皮层下CMBs病灶具有相关性。     

脑小血管病的病变分布特征与临床表现的关系

目的分析脑小血管病(CSVD)患者病变分布特征与临床表现的关系。方法选取2011-08—2014-08在我院收治的小脑血管疾病患者140例,根据ARWMC评分将病情程度分为轻度组、中度组和重度组;根据病变部位分为皮层下、基底节区以及脑干和小脑区。分析不同病情程度与病变部位的关系以及不同病变部位和临床表现的关系。结果轻度组基底节区发病率12.29%,中度组为32.61%,重度组为52.94%,差异有统计学意义(P0.05),而皮层下及脑干和小脑区发病率无显著差异(P0.05)。不同病变部位的认知功能损害、头晕及眩晕、步态障碍、卒中和TIA史差异有统计学意义(P0.05),尿失禁发生率无显著差异(P0.05)。结论脑小血管疾病的不同病变区域病情程度有所差异,且临床表现有所不同,分析其相关性对临床预防及诊治有重要意义。     

Intracerebral hemorrhages in CADASIL

Intracerebral hemorrhage (ICH) has been described only sporadically for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, cerebral microbleeds (CMBs) were found in 31% to 69% of the patients with CADASIL, and this predicted an increased risk of ICH. In this study, the authors found that 25% of the symptomatic patients with CADASIL had ICHs, and their development was closely related to the number of CMBs.     

Cerebral microbleeds in patients with hypertensive stroke

Abstract. Objective: To analyse the topography of cerebral microbleeds (CMBs) visualized by T2*-weighted gradient-echo MR imaging in the supratentorial brain area, based on the anatomical classification of the regions and the arterial territories. Background: CMBs are associated with hypertension and the risk of intracerebral hemorrhage; however, little is known about the cerebral topography of CMBs. Methods: We examined 164 consecutive patients with hypertensive stroke who underwent T2*-weighted gradient-echo MRI. The anatomical locations and the vascular territories of the CMBs were determined in the subcortical white matter, basal ganglia/internal capsule and thalamus along the standard axial slices. Results: We detected 2,193 CMBs in 98 patients (13.4±39.0 per patient). The CMBs showed a significant predilection for the temporo-occipital area of the subcortical white matter, the posterolateral part of the upper putamen, and the lateral nuclei of the mid-level thalamus. The most common arterial territories were those of the middle-posterior cerebral artery in the white matter, the middle cerebral artery in the basal ganglia, and the thalamogeniculate artery in the thalamus. Conclusions: These findings were quite similar to the cerebral topography of intracerebral hemorrhage described in the literature. Our results suggest that CMBs are regionally associated with intracerebral hemorrhage.     

R558C NOTCH3 Mutation in a CADASIL Patient with Intracerebral Hemorrhage: A Case Report with Literature Review

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small-vessel disease, which is characterized by migraine, recurrent ischemic strokes, psychiatric disorder, progressive cognitive decline, and occasionally intracerebral hemorrhage (ICH). ICH events have been reported in a high proportion of East Asian CADASIL patients with R544C mutation in exon 11 of NOTCH3; however, whether any other specific NOTCH3 mutation determines the ICH phenotype has yet to be explored.Case presentationWe report the case of a 60-year-old male CADASIL patient with a novel R558C mutation in exon 11 of the NOTCH3 gene, who presented with ICH in the basal ganglia and cerebellum. Brain imaging revealed multiple confluent white matter hyperintensities and abundant cerebral microbleeds (CMBs) in the bilateral basal ganglia, thalamus, and cerebellum. The patient had been having recurrent ischemic strokes prior to this ICH event, and had taken antiplatelet and antihypertensive agents for six months. We analyzed the possible reasons for ICH onset in the patient to recommend certain guidelines for the clinic.ConclusionsNovel R558C mutation-related CADASIL vasculopathy and numerous CMBs, uncontrolled hypertension, and antiplatelet therapy could collectively contribute to ICH onset in the patient with CADASIL. These findings suggest that a diagnosis of CADASIL should also be considered when patients present with ICH, whenever MRI imaging reveals typical white matter abnormalities. Furthermore, this case report emphasizes the importance of CMB assessment, appropriate blood pressure control, and cautious assessment of the risk-benefits of antiplatelet medication in patients with CADASIL.     

社区人群脑微出血与基底节区核团体积的相关性研究

目的 探讨社区人群中脑微出血的部位及负荷与基底节区核团体积的相关性。 方法 2013年6月-2016年4月在北京市顺义区5个村进行脑血管病流行病学调查,采集受试者人口 学信息、脑血管病危险因素,通过3T MRI采集全脑体积,并自动分割提取基底节区黑质核团（尾状核、 苍白球、壳核、丘脑）体积,同时由神经科医师评估脑微出血负荷及分布。用多元线性模型分别分析 脑微出血负荷及分布（无脑微出血、1～2个局限皮层脑微出血、≥3个局限皮层脑微出血、1～2个深 部/混合脑微出血及≥3个深部/混合脑微出血）与基底节区核团体积的相关性。 结果 纳入符合标准的受试者997例,平均年龄56.7±9.3岁,男性346例（34.7％）。有脑微出血组 基底节、苍白球、尾状核及丘脑体积所占总脑体积的百分比均较无脑微出血组偏低（均P＜0.05）。随 着脑微出血负荷增加,基底节、苍白球、尾状核及丘脑体积所占总脑体积的百分比降低（均P＜0.05）。 基底节、苍白球、尾状核及丘脑体积所占总脑体积的百分比在不同脑微出血分布三组间差异有统计学 意义（均P＜0.05）。多因素模型分析发现,≥3个深部/混合脑微出血与苍白球体积负相关（β=-0.014, P =0.0027）,该结果经多重比较后差异仍存在统计学意义。 结论 社区人群中,横断面研究发现高负荷的深部/混合脑微出血与较小的苍白球体积紧密相关。     

缺血性脑卒中患者脑微出血与脑白质病变的相关性研究

目的 探讨缺血性脑卒中患者脑微出血与脑白质病变的相关性。方法 选取2018年1月-2019年12月本院收治的缺血性脑卒中患者; 通过核磁共振成像扫描患者头部观察各脑区脑微出血、脑白质病变情况,并对脑微出血情况进行分级,对脑白质病情情况进行评分; 采用Logstic回归分析法分析各危险因素与脑微出血、脑白质病变的关系; 通过spearman相关分析法分析脑微出血分级与脑白质病变评分的相关性。结果 有脑微出血患者中皮质及皮质下出现脑微出血占比61.46%明显高于基底及丘脑23.96%及幕下区41.10%(P<0.05); 有脑白质病变患者中额区脑白质病变占比69.44%明显高于颞区14.81%、顶枕区6.48%、基底节3.70%(P<0.05); Logstic回归分析显示年龄>60岁、有高半胱氨酸血症及合并心房颤动是发生脑微出血的独立危险因素(P<0.05),年龄>60岁是发生脑白质病变的独立危险因素(P<0.05); 脑微出血各级与脑白质病变各评分均呈正相关(r=0.327,0.311,0.401,0.362,P<0.05)。结论 年龄>60岁是缺血性脑卒中患者发生脑微出血及脑白质病变的危险因素; 在缺血性脑卒中患者中脑微出血与脑白质病变呈正相关     

卒中合并脑微出血的影像学研究

目的 探讨ICH和脑梗死患者合并脑微出血（cerebral microbleeds，CMBs）数量分级及部位分布差异。 方法 连续选取2017年8月-2018年12月在北京市大兴区人民医院神经内科病房住院且资料完整的 卒中患者，分为ICH和脑梗死两组。收集患者发病2周内头颅MRI磁敏感加权成像影像，统计ICH与脑梗 死患者中CMBs数量分级及部位分布特点。 结果 共入组患者234例，其中ICH组79例，脑梗死组155例。ICH组合并CMBs 65例（82.3%），其中 CMBs＞5个的患者41例（51.9%）；脑梗死组合并CMBs 73例（47.1%），其中CMBs＞5个的患者21例 （13.6%），两组差异有统计学意义（P＜0.001）。ICH组中，CMBs同时累及脑叶和深部脑组织的患者40例 （50.6%）；脑梗死组中，CMBs同时累及脑叶和深部脑组织的患者25例（16.1%），两组差异有统计学意 义（P＜0.001）。 结论 CMBs病灶＞5个多见于ICH患者；CMBs同时累及脑叶及深部脑组织多见于ICH患者。     

Cerebral microbleeds in CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype. RESULTS: Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.     

缺血性卒中患者脑微出血的相关因素分析

目的 探讨缺血性卒中患者发牛脑微出血(CMBs)的相关因素. 方法 对85例急性缺血性卒中患者进行磁共振检查,其中包括梯度回波T2加权成像(GE-T2~*WI),并对患者的临床资料和影像学特点进行分析. 结果 26例(30.6%)患者中共检出CMBs 124个,每位患者的CMBs数目在1～16个之间.CMBs在基底节丘脑区和皮质一皮质下区分布较多,在幕下区较少见.发生在脑十的CMBs可有相关症状及体征.CMBs数目与年龄、腔隙性梗死数目及白质疏松程度评分有相关性(r=0.243,P=0.025;r=337,P=0.002;r=0.438,P=0.000).CMBs在GE-T2~*WI上显影良好,部分CMBs可在自旋叫波(SE)T2WI及DWI序列上显影. 结论 CMBs是脑微小血管病变标志,主要预测因素有高龄、多发腔隙性梗塞和白质疏松.     

An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL.