脑微出血危险因素及合并相关疾病治疗决策的研究进展

Advances in study on risk factors related to cerebral microbleeds and on treatment decision⁃making when cere⁃bral microbleeds merging related diseases

脑微出血是多种危险因素引起的皮质下或深部脑组织微小血管,属于脑小血管病。近年来,随着影像学的发展和抗栓药物的广泛应用,脑微出血的检出率逐渐提高。尽管目前脑微出血大多被视为无症状性的,但其可能增加认知功能障碍、脑梗死后出血转化、脑出血等的风险。总结脑微出血的流行病学、相关危险因素研究进展,具有重要意义。脑微出血的危险因素包括遗传因素[ApoEε4基因(OR=2.54)、NOTCH3基因突变、HTRA1基因的纯合突变、法布里病]、高龄和男性(P=0.043)、吸烟(OR=5.791)及饮酒(OR=7.306)、高血压(OR=1.049)、糖尿病(P=0.005)、血脂异常(P<0.05)、脑淀粉样血管病(OR=2.210)、高同型半胱氨酸血症(P<0.05)、高尿酸血症(OR:1.98)、肾功能减退及透析(P=0.0041)、危重症[60%的患者在应用体外膜氧合(extracorporeal membrane oxygenation,ECMO)后存在脑微出血],其他罕见危险因素包括心脏手术、感染性心内膜炎、可逆性后部脑病综合征、烟雾病、阻塞性睡眠呼吸暂停综合征、颅脑放射治疗以及创伤性脑损伤。目前,年龄、高血压病和ApoE基因多态性被认为是脑微出血比较肯定的危险因素,其余诸多危险因素是否为脑微出血明确的危险因素,尚未达成一致意见。脑微出血不需要治疗,但在临床实践中,脑梗死或房颤患者合并脑微出血时,需慎重考虑治疗选择。对于合并脑微出血的缺血性卒中/短暂性脑缺血发作患者来说,抗血小板治疗仍然是有益的,脑微出血也不应成为静脉溶栓(intravenous thrombolysis,IVT)或血管内治疗(endovascular therapy,EVT)的禁忌,但对于合并高负荷(>10个)的脑微出血患者,即便符合IVT/EVT治疗适应证,也应该根据情况权衡利弊。对于合并脑微出血的房颤患者,脑微出血数量较多或位于皮质区域,并且脑出血风险较高,建议采用更安全的新型抗凝药。目前关于脑微出血危险因素以及合并脑微出血的缺血性脑卒中的治疗方案和个体化干预方面,国内外医学界尚未达成共识,仍需要大规模的临床研究来进一步探讨。

Cerebral microbleeds,belongs to the category of cerebral small blood vessel disease,is a vascular le-sion of subcortical or deep brain tissue caused by a variety of risk factors.In recent years,with the development of imaging and the wide use of antithrombotic drugs,the detection rate of cerebral microbleeds has gradually increased.Although mostly regarded as asymptomatic,cerebral microbleeds may increase the risk of cognitive dysfunction,hemorrhagic transfor-mation after cerebral infarction,cerebral hemorrhage,etc.It is of great significance to summarize the progress of the epide-miology and related risk factors of cerebral microbleeds.Risk factors for cerebral microbleeds include genetic factors(ApoEε4 gene(OR=2.54),NOTCH3 mutation,homozygous mutation in HTRA 1 gene,Fabry disease),advanced age and male(P=0.043),smoking(OR=5.791)and alcohol consumption(OR=7.306),hypertension(OR=1.049),diabetes(P=0.005),dyslip-idemia(P<0.05),cerebral amyloid angiopathy(OR=2.210),hyperhomocysteemia(P<0.05),hyperuricemia(OR:1.98),renal dysfunction and dialysis(P=0.0041),critical illness(60%of patients had cerebral microhemorrhage after ECMO).Other rare risk factors include cardiac surgery,infective endocarditis,reversible posterior encephalopathy syndrome,moyamoya disease,obstructive sleep apnea syndrome,craniocerebral radiotherapy,and traumatic brain injury can all lead to the occur-rence of cerebral microbleeds.At present,age,hypertension and ApoE gene polymorphism are specific risk factors for cere-bral microhemorrhage.Whether other risk factors has not reached the overwhelming consensus.Cerebral microbleeds does not require treatment,but in clinical practice,patients with cerebral infarction or atrial fibrillation combined with cerebral microbleeds should be carefully considered.For patients with ischemic stroke/TIA complicated with cerebral microbleeds,antiplatelet therapy is still beneficial,and cerebral microbleeds should not be a contraindication to intravenous thromboly-sis(intravenous thrombolysis,IVT)or endovascular treatment(endovascular therapy,EVT).However,for patients with high-load(>10)cerebral microbleeds,even with the IVT/EVT treatment indications,the pros and cons should also be weighed according to the patient′s specific situation.For patients with atrial fibrillation complicated with cerebral microbleeds,when the number of cerebral microbleeds is larger or lesions located in the cortical areas,and the risk of cerebral micro-bleeds is higher,safer new anticoagulants are recommended.At present,there is no consensus between the domestic and foreign medical circles on the risk factors of cerebral microbleeds and the treatment plan and individualized interven-tion of ischemic stroke combined with cerebral microbleeds,and large-scale clinical studies are still needed for further ex-ploration.