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)

Gene mutation and clinical features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with intracerebral hemorrhage(report of 2 cases)

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。

Objective To analyze the gene mutations,clinical and imaging characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL) with intracerebral hemorrhage. Methods Clinical and pathological characteristics of two CADASIL patients who had hemorrhagic strokes were analyzed retrospectively.All reported CADASIL patients with intracerebral hemorrhage ( ICH) worldwide were summarized through literature search.Results One case was a 46-year-old male developed ICH in the cerebellum and thalamus,the patient had hypertension and had taken antithrombotics.NOTCH3 gene analysis revealed mutations of p.R544C.Another case was a 52-year-old female developed recurrent ICH in the basal ganglia , thalamus and corona radiate,the patient had no related risk factors.NOTCH3 gene analysis revealed mutations of p.C388Y,this was the first report of ICH in CADASIL patients with p.C388Y mutation.There were 76 published cases of CADASIL patients with ICH.Among 65 patients with gene explaination,R544C was the most common( 65. 1%).The main sites of cerebral hemorrhage were basal ganglia ( 29. 1%),thalamus ( 29. 1%),cerebral lobe ( 19. 0%),cerebellum ( 11. 4%),brain stem ( 6. 3%) and radiation corona ( 5. 1%).Some patients had history of hypertension or taken oral antithrombotic drugs.Conclusions CADASIL should be considered a risk factor for ICH.The patients need a strict control of hypertension,and the doctors should be careful about the use of antiplatelet agents.MRI screening for cerebal microbleeds may be helpful to evaluate the risk of hemorrhage.