12例伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病的临床及影像学特征

Clinical and image features for 12 cases of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy

目的:分析伴有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 the subcortical infarcts and leukoencephalopathy,CADASIL)患者的临床和影像学特征。方法:收集2013年1月至2018年12月在中南大学湘雅医院通过基因确诊的CADASIL患者12例,回顾性分析其临床表现、危险因素、MRI影像学特征和Notch3基因突变。结果:12例患者年龄为(47.25±9.49)岁,临床表现以认知障碍(75%)和脑卒中事件(58.3%)最常见,2例表现为脑出血。合并偏头痛少见(25%)。MRI均存在累及脑室旁和深部白质的脑白质高信号(white matter hyperintensities,WMH)和腔隙及血管周围间隙(perivascular spaces,PVS)扩大。WMH主要累及额顶叶(100%)、颞叶(83.3%)、外囊(66.7%)、枕叶(41.6%)、胼胝体(41.6%)和颞极(33.3%);腔隙主要累及额叶(91.6%)、顶叶(83.3%)、颞叶(66.7%)、基底节区(66.7%)、脑干(41.6%)、枕叶(33.3%)、小脑(8.3%);扩大的PVS均位于基底节区(100%),部分累及皮层下(45.4%)。脑出血患者WMH程度较轻(Fezakas评分为1～2分),且外囊无受累。16.7%患者存在颅内大动脉狭窄。12例患者中共检测到8种不同的Notch3基因突变,位于6号外显子的c.1013G>C p.(Cys338Ser)为CADASIL新的致病突变。结论:本组以脑出血为表现的患者脑白质病变较轻,基因型亦有特异性,其临床表型可能与影像学、基因表型相关。

Objective:To analyze the clinical and image features for 12 patients of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy(CADASIL).Methods:A total of 12 CADASIL patients were collected in Xiangya Hospital of Central South University from January 2013 to December 2018.The clinical manifestation,risk factors,MRI imaging data and NOTCH3 mutations were analyzed retrospectively.Results:The mean age of 12 patients was(47.25±9.49)years.The clinical manifestation was most common in cognitive impairment(75%)and stroke events(58.3%),and 2 cases showed cerebral hemorrhage.Migraine was only seen in 25%patients.All MRI showed white matter hyperintensity(WMH),lacune and enlarged perivascular space(PVS).WMH mainly occurred in the frontal parietal lobe(100%),temporal lobe(83.3%),external capsule(66.7%),occipital lobe(41.6%),callosum 41.6%and the temporal pole(33.3%),while lacune mainly appeared in frontal lobe(91.6%),parietal lobe(83.3%),temporal lobe(66.7%),basal ganglia(66.7%),brain stem(41.6%),occipital lobe(33.3%),cerebellum(8.3%).Enlarged PVS located in the basal ganglia(100%),partly under the cortex(45.4%).WMH of the patient with intracerebral hemorrhage was mild(Fezakas score 1–2),which was not found in external capsule.16.7%of the patients had intracranial arterial stenosis.In 12 patients,8 different Notch3 mutations were detected.The c1013 G>c p.(Cys338 Ser)located in exon 6,which was a new pathogenic mutation of CADASIL.Conclusion:The patients with cerebral hemorrhage have mild WMH and specific genotype,indicating that the clinical characteristics of CADASIL with cerebral hemorrhage may be related to image features and genotype.