脑小血管病:犹如“风暴”过后的全脑灾难

脑小血管病（cerebral small vessel d isease,CSVD）是一种临床及影像综合征,病变累及脑的穿通小动脉、毛细血管及小静脉,临床表现为卒中、痴呆、情感障碍及步态异常,影像学表现为近期皮层下梗死及微梗死灶、腔隙灶、白质高信号（white matter hyperintensitie,WMH）、微出血及出血灶、血管周围间隙扩大及脑萎缩。

Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is unclear.Here,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%CI.Results 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]min.Neuroimaging‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe stroke.Conclusions In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke onset in a systematic review and individual patient data meta-analysis from two randomised controlled tri-als.The Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2)assessed the effect of GTN given prehospital in patients with pre-sumed stroke within 4hours of onset.This subgroup analysis details the effect of GTN in those with clini-cally diagnosed ischaemic stroke.WHAT THIS STUDY ADDS⇒Transdermal GTN did not influence clinical or radio-logical outcomes despite lowering blood pressure compared with sham.GTN may be associated with more death and dependency in those randomised within 1hour of symptom onset and in those with more severe stroke,but these interactions were non-significant.The population recruited in RIGHT-2 was more dependent and frailer(both clinically and radiologically)than in prior trials of transdermal GTN within 6hours of stroke onset performed in hospital,and may account for the differences in results.HOW THIS STUDY MIGHT AFFECT RESEARCH,PRACTICE OR POLICY⇒Transdermal GTN should not be administered to pa-tients with presumed stroke prehospital outside of a trial environment.Clinical and radiological frailty should be taken into consideration in the design and interpretation of future ultra-acute stroke trials.

Update on cerebral small vessel disease: a dynamic whole-brain disease

Cerebral small vessel disease(CSVD)is a very common neurological disease in older people.It causes stroke and dementia,mood disturbance and gait problems.Since it is difficult to visualise CSVD pathologies in vivo,the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities,lacunar ischaemic stroke,lacunes,microbleeds,visible perivascular spaces and many haemorrhagic strokes.However,variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies.A standardised use of terms should be encouraged in CSVD research.These CSVD features have long been regarded as different lesions,but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore,owing to its diffuse nature,CSVD should be regarded as a‘whole-brain disease’.Single antiplatelet(for acute lacunar ischaemic stroke)and management of traditional risk factors still remain the most important therapeutic and preventive approach,due to limited understanding of pathophysiology in CSVD.Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD.Epidemiology of CSVD might differ in Asian compared with Western populations(where most results and guidelines about CSVD and stroke originate),but more community-based data and clear stratification of stroke types are required to address this.

It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis

Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis.

Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke

Background Alteplase improves functional outcomes of patients with acute ischaemic stroke,but its effects on symptomatic infarct swelling,an adverse complication of stroke and the influence of CT hyperdense artery sign(HAS)are unclear.This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.Methods We included stroke patients whose prerandomisation scan was non-contrast CT.Raters,masked to clinical information,assessed baseline(prerandomisation)and follow-up(24-48 hours postrandomisation)CT scans for HAS,defined as an intracranial artery appearing denser than contralateral arteries.Symptomatic infarct swelling was defined as clinically significant neurological deterioration≤7 days after stroke with radiological evidence of midline shift,effacement of basal cisterns or uncal herniation.Results Among 2961 patients,HAS presence at baseline was associated with higher risk of symptomatic infarct swelling(OR 2.21;95% CI 1.42 to 3.44).Alteplase increased the risk of swelling(OR 1.69;95% CI 1.11 to 2.57),with no difference between patients with and those without baseline HAS(p=0.49).In patients with baseline HAS,alteplase reduced the proportion with HAS at follow-up(OR 0.67;95% CI 0.50 to 0.91),where HAS disappearance was associated with reduced risk of swelling(OR 0.25,95% CI 0.14 to 0.47).Conclusion Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS,it was also associated with accelerated clearance of HAS,which in return reduced swelling,providing further mechanistic insights to underpin the benefits of alteplase.

Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease:baseline data and statistical analysis plan for the Lacunar Intervention Trial-2(LACI-2)(ISRCTN14911850)

Background Cerebral small vessel disease(SVD)causes lacunar strokes(25%of all ischaemic strokes),physical frailty and cognitive impairment and vascular and mixed dementia.There is no specific treatment to prevent progression of SVD.Methods The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression.We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol,isosorbide mononitrate,both or neither,in addition to guideline secondary ischaemic stroke prevention,in a partial factorial design.The primary outcome is feasibility of recruitment and adherence to medication;key secondary outcomes include:drug tolerability;recurrent vascular events,cognition and function at 1 year after randomisation;and safety(bleeding,falls,death).Data are number(%)and median(IQR).Results The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised,with the following baseline characteristics:average age 64(56.0,72.0)years,female 112(30.9%),stroke onset to randomisation 79.0(27.0,244.0)days,hypertension 267(73.6%),median blood pressures 143.0(130.0,157.0)/83.0(75.0,90.0)mm Hg,current smokers 67(18.5%),educationally achieved end of school examinations(A-level)or higher 118(32.5%),modified Rankin scale 1.0(0.0,1.0),National Institutes Health stroke scale 1.0(1.4),Montreal Cognitive Assessment 26.0(23.0,28.0)and total SVD score on brain imaging 1.0(0.0,2.0).This publication summarises the baseline data and presents the statistical analysis plan.Summary The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.Trial registration number ISRCTN14911850.

Measures of intracranial compartments in acute intracerebral haemorrhage:data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial(RIGHT-2)

Background and purpose Intracerebral haemorrhage volume(ICHV)is prognostically important but does not account for intracranial volume(ICV)and cerebral parenchymal volume(CPV).We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional outcomes.We also assessed if cistern effacement,midline shift,old infarcts,leukoaraiosis and brain atrophy were associated with outcomes.Methods Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were analysed.Measures included ICHV(using ABC/2)and ICV(XYZ/2)(by independent observers);ICHV,ICV and CPV(semiautomated segmentation,SAS);atrophy(intercaudate distance,ICD,Sylvian fissure ratio,SFR);midline shift;leukoaraiosis and cistern effacement(visual assessment).The effects of these measures on death at day 4 and poor functional outcome at day 90(modified Rankin scale,mRS of>3)was assessed.Results ICV was significantly different between XYZ and SAS:mean(SD)of 1357(219)vs 1420(196),mean difference(MD)62 mL(p<0.001).There was no significant difference in ICHV between ABC/2 and SAS.There was very good agreement for ICV measured by SAS,CPV,ICD,SFR,leukoaraiosis and cistern score(all interclass correlations,n=10:interobserver 0.72-0.99,intraobserver 0.73-1.00).ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90,death at day 4 and acute neurological deterioration(all p<0.05),similar to ICHV.Midline shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts,leukoaraiosis and brain atrophy were not.Conclusions Intracranial compartment measures and visual estimates are reproducible.ICHV adjusted for ICH and CPV could be useful to prognosticate in acute stroke.The presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

痴呆预防的新曙光:通过预防脑血管病预防痴呆

潘岳松及其同事讨论了脑血管疾病与认知障碍的关系,并强调了通过预防脑血管疾病来预防痴呆的新机遇。脑血管病和痴呆是导致老年人脑健康受损和神经功能残疾的两大因素1。近年来,随着人口老龄化和人口增长,这两种神经系统疾病的患病率持续增加。全球范围内,2015年大约有4240万卒中患者2,2018年约有5000万例痴呆患者(包括阿尔茨海默病、血管性痴呆和其他痴呆)3。

皮质下小血管病诊断的共识声明

血管性认知损害是用于描述一组涉及大血管和小血管的散发性和遗传性异质性疾病的诊断术语。皮质下小血管病可导致腔隙性梗死和进行性白质损害。被称为宾斯旺格病（Binswanger＇s disease, BD）的进行性白质损害患者构成了从单纯血管性疾病到合并神经变性病变的疾病谱。BD患者是一个相对同质性的亚组，存在缺氧缺血、腔隙性梗死和炎症，它们协同作用破坏血脑屏障和髓鞘。通过临床、脑脊液、神经心理学和影像学检查获得的多模式疾病标记物能促进该亚组患者的鉴别。本共识声明确定了一系列基于基础病理学改变的潜在生物学标记物，这将有助于诊断以及将来协作性治疗试验的患者选择。

伴颈动脉狭窄的急性缺血性卒中患者应用透皮吸收的硝酸甘油降压是安全的

背景对伴有颈动脉狭窄的急性卒中患者给予降压治疗可能会损害大脑灌注和患者转归,临床上一直对此存在顾虑。我们应用一氧化氮对卒中疗效研究(Efficacy of Nitric Oxide inStroke,ENOS)的数据,评价了硝酸甘油(GTN)对伴颈动脉狭窄的患者的效应。