急性缺血性脑卒中早期神经功能恶化诊治进展

急性缺血性脑卒中早期神经功能恶化(early neurological deterioration,END)也称进行性或进展性卒中,指早期阶段病情继续进展、神经功能损伤逐渐加重,其发病机制目前尚未完全阐明,亦缺乏早期识别及治疗的有效手段,死亡率和病残率较高.本文就近年END诊治的相关研究进展做一综述.     

急性缺血性脑卒中患者静脉溶栓后早期神经功能恶化的研究

目的探讨发病6 h内静脉溶栓的急性缺血性脑卒中患者发生早期神经功能恶化(END)的危险因素。方法回顾性分析2017年7月至2019年8月该科收治的151例发病6 h内进行静脉溶栓的急性缺血性脑卒中患者的临床资料,以溶栓后24 h内美国国立卫生研究院卒中量表(NIHSS)较前增加≥4分作为END标准将患者分为恶化组与非恶化组,应用多因素logistic回归分析溶栓后END的危险因素。结果 151例患者中恶化组26例,非恶化组125例。恶化组患者的年龄、NIHSS评分、房颤患病率高于非恶化组(P 0.05);发病到静脉溶栓时间(OTT)低于非恶化组(P 0.05);两组患者的TOAST分型比较,差异具有统计学意义(P 0.05)。logistic回归分析结果显示,NIHSS评分(OR=1.124,95%CI=1.007～1.254)、房颤(OR=6.425,95%CI=1.230～33.561)、收缩压(OR=1.031,95%CI=1.001～1.063)、冠心病(OR=0.072,95%CI=0.006～0.904)与溶栓后END显著相关(P 0.05)。结论高NIHSS评分、房颤及高收缩压患者静脉溶栓后发生END风险大。     

缺血性脑卒中发生早期神经功能恶化(END)的相关因素分析

目的探讨缺血性脑卒中发生早期神经功能恶化(END)的相关因素。方法回顾性分析我院2010-04—2013-01收治的132例缺血性脑卒中患者的临床资料,按是否发生早期神经功能恶化分为早期神经功能恶化组和非早期神经功能恶化组,采用单因素方差分析和多因素Logistic回归分析2组患者一般资料和各项指标,总结发生早期神经功能恶化的相关因素。结果 132例缺血性脑卒中患者发生早期神经功能恶化35例(26.5%)。经多因素Logistic回归分析发现,NIHSS评分高、糖尿病、颈动脉狭窄≥50%、心房颤动以及高血压是影响缺血性脑卒中发生早期神经功能恶化的重要危险因素(P0.05)。结论 NIHSS评分高、糖尿病、颈动脉狭窄≥50%、心房颤动以及高血压都是影响缺血性脑卒中发生早期神经功能恶化的重要危险因素,对合并以上因素的患者应加强干预治疗,积极改善患者预后。     

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA

Objectives: To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA.

Methods: From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events.

Results: We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77–11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41–7.91, p = 0.006) was independently associated with recurrent ischemic events.

Discussion: In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.     

动态血压与缺血性脑卒中早期神经功能恶化的关系

目的分析动态血压与缺血性脑卒中早期神经功能恶化(END)的关系。方法以我院收治的100例缺血性脑卒中患者为研究对象,其中早期神经功能恶化(END)者30例(END组),非早期神经功能恶化者70例(非END组),通过动态血压监测系统对2组血压进行动态监测,分析动态血压与END之间的相关性。结果END组高血压、糖尿病、颈动脉狭窄50%及以上比率分别为63.33%、70.00%、70.00%,与非END组的35.71%、45.71%、42.86%比较差异有统计学意义(P0.05);END患者中反杓型占40.54%,非杓型占33.33%,反杓型与超杓型、反杓型与杓型、非杓型与杓型比率比较差异有统计学意义(P0.05);2组晨峰血压比例比较差异有统计学意义(P0.01);2组nMSBP[(142.26±15.63)mmHg vs(135.55±14.47)mmHg]、nMDBP[(75.28±11.48)mmHg vs(70.41±10.58)mmHg]水平比较差异有统计学意义(P0.05)。结论血压昼夜节律、晨峰血压与缺血性脑卒中END存在一定的关系,需加强早期缺血性脑卒中动态血压监测。     

Multiple sleep–wake disturbances after stroke predict an increased risk of cardio-cerebrovascular events or death: A prospective cohort study

Background and purpose

Contradictory evidence on the impact of single sleep-wake-disturbances (SWD), such as sleep-disorderd breating (SDB) or insomnia, in patients with stroke, on the risk of subsequent cardio- and cerebrovascular events (CCE) and death, exists. Very recent studies in the general population suggest that the presence of multiple SWD increases cardio-cerebrovascular risk. Hence, the aim of this study was to asssess whether a novel score capturing the burden of multiple SWD, a so called "sleep burden index", is predictive for subsequent CCE including death in a prospectively followed cohort of stroke patients.

Methods

Patients with acute ischemic stroke or transient ischemic attack (TIA) were prospectively recruited. Four SWD were analyzed: (i) SDB with respirography; (ii) insomnia (defined using the insomnia severity index [ISI]); (iii) restless legs syndrome (RLS; defined using the International RLS Study Group rating scale); and (iv) self-estimated sleep duration at 1 and 3 months. A “sleep burden index”, calculated using the mean of z-transformed values from assessments of these four SWD, was created. The occurrence of CCE was recorded over a mean ± standard deviation (SD) follow-up of 3.2 ± 0.3 years.

Results

We assessed 437 patients (87% ischemic stroke, 13% TIA, 64% males) with a mean ± SD age of 65.1 ± 13.0 years. SDB (respiratory event index ≥ 5/h) was present in 66.2% of these patients. Insomnia (ISI ≥ 10), RLS and extreme sleep duration affected 26.2%, 6.4% and 13.7% of the patients 3 months post-stroke. Seventy out of the 437 patients (16%) had at least one CCE during the follow-up. The sleep burden index was associated with a higher risk for subsequent CCE, including death (odds ratio 1.80 per index unit, 95% confidence interval 1.19–2.72; p = 0.0056).

Conclusion

The presence of multiple SWDs constitutes a risk for subsequent CCE (including death) within the first 3 years following stroke. Larger systematic studies should assess the utility of the sleep burden index for patients' risk stratification in clinical practice.     

Plasma homocysteine is a risk factor for recurrent vascular events in young patients with an ischaemic stroke or TIA

Objectives Young patients with an ischaemic stroke or transient ischaemic attack (TIA) often have no vascular risk factors. Hyperhomocysteinaemia is an established risk factor for stroke in elderly patients but it is uncertain whether it is also important for the prognosis of young ischaemic stroke and TIA patients. We examined the possible effect of the plasma homocysteine level on the risk of recurrent vascular events in patients between 18 and 45 years of age. Methods The study population consisted of 161 consecutive patients with a recent cerebral infarction or TIA. Data on the primary event and the homocysteine level were collected retrospectively from hospital records. General practitioners and patients were contacted by telephone to record vascular events and the type of medication used during the follow–up period. Vascular events included cerebral infarction, TIA, pulmonary embolism, venous thrombosis, myocardial infarction and peripheral arterial disease. Results A Kaplan- Meier curve showed a dose effect relationship between event-free survival time and tertiles of the homocysteine level (Log rank statistic 5.91; p = 0.05). The Cox hazard ratio, after adjustment for homocysteine lowering treatment, was 1.7 (95 % CI, 1.1 to 2.8) for any vascular outcome event, 1.9 (95% CI, 1.1 to 3.0) for arterial outcome events and 1.8 (95 % CI, 1.1 to 2.9) for cerebral outcome events. Conclusions In spite of our small number of outcome events we found a significant association at the 95% confidence level between homocysteine level and the risk of recurrent vascular events in young patients with an ischaemic stroke or TIA. The association is of the same magnitude as in elderly people.     

缺血性脑卒中患者血清SIRT1水平与早期神经功能恶化的相关性研究

目的 探讨缺血性脑卒中患者血清沉默信息调节因子1(Silent information regulator 1,SIRT1)水平与早期神经功能恶化(Early neurological deterioration,END)的相关性。方法 选取2020年1月-2021年6月于本院就诊的缺血性脑卒中患者136例,根据患者入院72 h内是否出现END,将其分为合并END组(41例)和非END组(95例),检测并比较2组血清SIRT1水平,采用Logistic回归法分析END发生的影响因素,采用受试者工作特征曲线(Receiver operating characteristic curve,ROC)分析SIRT1诊断END发生的临床价值。结果 2组患者年龄、糖尿病占比、冠心病占比、基线美国国立卫生院卒中量表(National institute of health stroke scale,NIHSS)评分比较差异显著(P<0.05); 与非END组比较,合并END组患者血清SIRT1水平较低,超敏C反应蛋白(High sensitivity C-reactive protein,hs-CRP)水平较高(P<0.05); 糖尿病史、年龄、hs-CRP水平及SIRT1水平是缺血性脑卒中患者发生END的独立危险因素(P<0.05); SIRT1预测缺血性脑卒中患者发生END的曲线下面积为0.753[95%CI=0.559～0.903,P<0.05],诊断特异度为81.49%,敏感度为89.15%。结论 SIRT1在缺血性脑卒中早期神经功能恶化患者血清中呈低表达,且其表达水平与缺血性脑卒中患者发生END有关。     

缺血性脑卒中/短暂性脑缺血发作患者脑动脉病变分布相关危险因素分析

目的 探讨缺血性脑卒中(ischemic stroke,IS)/短暂性脑缺血发作(transient ischemic attack,TIA)脑动脉病变分布的相关危险因素.方法 对169例IS/TIA患者行颈部及颅内脑血管检查,记录血管病变危险因素如年龄、性别、高血压、糖尿病、长期吸烟、长期饮酒等病史,同时记录实验室、心电图、超声心动图、腹部B超、胸X片等检查结果.确定单变量与不同狭窄模式的相关性采用单变量Logistic回归分析,确定不同颅内外大动脉狭窄模式的独立危险因素采用多元逐步和多变量多项分类Logistic回归分析.结果 高龄、长期吸烟及高低密度脂蛋白(LDL-C)是颅内外大动脉狭窄的独立危险因素,发生颅内外大动脉狭窄的风险分别增加了1.83、6.918、1.656倍;脑卒中史(OR=4.816)、长期吸烟(OR=121.608)、高LDL-C(OR=3.067)是单纯颅内大动脉狭窄的独立危险因素;高龄(OR =2.486)、长期吸烟(OR=25.072)、高LDL-C(OR=5.160)是颅内外大动脉狭窄并存的独立危险因素;而高纤维蛋白原(OR =4.790)是单纯颅外大动脉狭窄的独立危险因素.结论 不同类型颅内外大动脉狭窄病变的独立危险因素不同.     

Lp-PLA2 as a risk factor of early neurological deterioration in acute ischemic stroke with TOAST type of large arterial atherosclerosis

Introduction: Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a well-known risk factor of atherosclerotic vascular diseases. Nevertheless, its role in the acute phase of ischemic stroke is still unclear. The aim of this study is to identify the relationship between Lp-PLA₂ levels and early neurological deterioration (END) in acute ischemic stroke patients with Trial of Org 10 172 in Acute Stroke Treatment (TOAST) subtype of large arterial atherosclerosis (LAA).

Methods: We enrolled Chinese patients with first ever acute ischemic stroke admitted to Neurology Department of Shenzhen Second People’s Hospital within 48 h from onset of symptoms during January – November 2015. Demographic and laboratory information were collected while END was defined as an increase in the National Institute of Health Stroke Scale score by ≥ 1 point in motor power, or ≥ 2 points in the total score within 10 days after admission.

Results: Overall 181 patients were involved; END was diagnosed in 30 patients within 10 days after admission. The odds ratio for END increased with increasing levels of Lp-PLA₂ (intermediate level, OR = 1.96, 95%CI 1.02–4.27, p = 0.041; high level, OR = 2.99, 95%CI 1.26–5.73, p = 0.023).

Conclution: Intermediate and high level of Lp-PLA₂ was identified as independent predictor of END in multivariate analysis. Lp-PLA₂ could be valued as a risk factor of END in patients with acute ischemic stroke with TOAST subtype of LAA.     

The erythrocyte adhesiveness/aggregation test in the peripheral blood of patients with ischemic brain events

We adopted a simple slide test and image analysis to determine the state of erythrocyte adhesiveness/aggregation in the peripheral blood of 45 patients with acute ischemic stroke, 30 with TIA and 27 matched controls. A highly significant (P=0.005) difference was noted between patients and controls regarding the degree of erythrocyte adhesiveness/aggregation while there was no significant difference for both erythrocyte sedimentation rate or fibrinogen concentrations. We suggest that our slide test might be a low cost and real time method to detect the increased erythrocyte aggregability in the peripheral blood of patients with acute ischemic neurological events. These findings might be relevant in view of recent studies that suggest a favorable effect of therapeutic interventions directed at the improvements of this hemorrheological aspect in individuals with ischemic vascular conditions.     

Early neurological deterioration represents recurrent attack in acute small non-lacunar stroke

The aim of this study was to identify the frequency and possible pathogenic mechanisms of early neurological deterioration in patients with acute small non-lacunar infarction. We studied 46 patients (35 men, 11 women; age, 70.3+/-10.4 years) with acute small non-lacunar infarction. Small non-lacunar infarction was diagnosed using diffusion-weighted magnetic resonance imaging (DWI) as being <15 mm in diameter and located in the cortex and centrum ovale in the middle cerebral artery territory. The patients were divided into two groups; Group D (n=6) had neurological deterioration within 7 days after symptom onset, while Group N (n=40) did not have any neurological deterioration. In Group D, the interval from symptom onset to clinical deterioration was 3.3+/-1.5 days (range 2-6 days). Blood pressure on admission was higher in Group D than in Group N (p<0.05). In Group D, four of these five patients with follow-up DWI had new acute small ischemic lesions in addition to the initial lesions, indicating recurrent attacks of brain infarction. Neurological deterioration occurred within 7 days after symptom onset in 13% of patients. Neurological deterioration was frequently caused by recurrent infarction detected by DWI.     

Long-term mortality and risk of stroke after transient ischemic attack

Background   Stroke and mortality rates in patients with transient ischemic attack (TIA) differ widely between community-based studies and research cohorts. Our aim therefore was to provide a reliable estimate for TIA patients treated in German neurology departments with an acute stroke unit. Methods   A total of 1951 consecutively admitted TIA patients were prospectively documented in 13 centers and 1480 (75.9 %) gave consent for long-term follow-up. During a mean follow-up of 23.4 months, we assessed recurrent cerebrovascular events and cause of death in 1448 patients via standardized telephone interview including confirmation of endpoint events by the treating physician. Results   Overall 94 patients (6.5 %) suffered a stroke and 118 patients (8.1 %) died, 21 due to stroke. The Kaplan-Meier estimate for stroke during the first year was 4.4 % (95 % CI 3.2–5.6 %) which corresponds to a relative risk of 9.5 (95 % CI 7.4–12.3) compared to the population-based stroke incidence in Germany. The annual rates after the first year were 2.2 % (95 % CI 1.7–2.7 %) for stroke and 3.2 % (95 % CI 2.7–3.8 %) for death. Independent predictors for stroke during follow-up were age and previous cerebrovascular events. The ABCD₂ score did not provide any meaningful prediction of stroke risk at 90 days. Conclusion   While the in-hospital risk of stroke was low, long-term stroke rates in our well-defined multicenter hospital-based cohort were comparable to a large randomized trial. In patients with a well-established diagnosis of TIA, only age and previous cerebrovascular events seem to constitute independent predictors for stroke during long-term follow-up. Participating Departments of Neurology (investigator): Ostalbklinikum Aalen (M. Heyden, MD), Klinikum Bernburg (M. Muller, MD), Krankenanstalten Gilead Bielefeld (C. Hagemeister, MD), Krankenhaus Buchholz (K. Luckner, MD), University of Essen (C. Weimar, MD), University of Freiburg (C. Fritzsch, MD), University of Greifswald (A. Khaw, MD), University of Hannover (K. Weissenborn, MC), Klinikum Heidenheim (S. Kaendler, MD), University of Jena (C. Terborg, MD), Krankenhaus Koln-Mehrheim (U. Frost, MD), University of Leipzig (D. Michalski, MD), Landesklinik Lubben (C. Rohrig, MD), University of Magdeburg (M. Goertler, MD), Ruppiner Kliniken Neuruppin (G. Zindler, MD), University of Rostock (A. Kloth, MD), Burgerhospital Stuttgart (T. Mieck, MD), University of Ulm (R. Huber, MD), Heinrich- Braun-Krankenhaus Zwickau (S. Grieshammer MD).