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Intravenous thrombolysis is more safe and effective for posterior circulation stroke

Data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)

Tong, Xu MD; Liao, Xiaoling MD; Pan, Yuesong PhD; Cao, Yibin MD; Wang, Chunjuan MD; Liu, Liping MD; Zheng, Huaguang MD; Zhao, Xingquan MD; Wang, Chunxue MD; Wang, Yilong PhD; Wang, Yongjun MD

Section Editor(s): Schaller., Bernhard

 on behalf of the Thrombolysis Implementation, Monitor of Acute Ischemic Stroke in China (TIMS-China) Investigators

doi: 10.1097/MD.0000000000003848
Research Article: Observational Study
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We aimed to compare the safety and efficacy of intravenous thrombolysis (IVT) with alteplase for anterior circulation stroke (ACS) and posterior circulation stroke (PCS). From a large multicenter prospective registry—the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China database—all patients who received IVT within 4.5 hours after stroke onset was reviewed. According to the clinical presentations and imaging findings, the eligible patients were divided into ACS and PCS groups. The safety and efficacy outcome measures included post-IVT symptomatic intracranial hemorrhage (sICH), parenchymal hematoma, and all intracranial hemorrhage (aICH) within 7 days, mortality within 90 days, excellent recovery (modified Rankin Scale 0–1), and functional independence (modified Rankin Scale 0–2) at 90 days. For comparing the outcomes between both groups, the odds ratios (ORs) with 95% confidence intervals (CIs) and the adjusted ORs with 95% CIs were analyzed by univariate and multivariate logistic regression models. Of 953 patients enrolled, 829 patients had ACS and 124 had PCS. The patients with PCS had less often atrial fibrillation (11.3% vs 19.8%; P = 0.02), higher blood glucose level (8.31 vs 7.63 mmol/L; P = 0.02), and more white blood cell counts (8.79 vs 7.75 × 109/L; P = 0.001) than those with ACS. After adjustment for the potential confounders, multivariate logistic analysis showed that PCS patients had not only lower rates of sICH (3.2% vs 7.7%; OR 0.28, 95% CI 0.09–0.90), parenchymal hematoma (1.6% vs 9.2%; OR 0.13, 95% CI 0.03–0.57), and aICH (8.1% vs 20.4%; OR 0.26, 95% CI 0.12–0.54), but also higher proportions of excellent recovery (55.7% vs 41.6%; OR 2.27, 95% CI 1.42–3.61) and functional independence (63.9% vs 53.0%; OR 2.33, 95% CI 1.40–3.89) compared with ACS patients. However, there was no significant difference in the occurrence of mortality (OR 0.86, 95% CI 0.39–1.91) between both groups in the multivariate model, although more PCS patients seemed to die within 90 days than did ACS patients (15.6% vs 10.1%; OR 1.64, 95% CI 0.96–2.82) in the univariate analysis. Our study suggests that IVT with alteplase is more safe and effective for PCS.

aDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing

bDepartment of Neurology, Tangshan Gongren Hospital, Hebei Medical University, Tangshan, Hebei

cChina National Clinical Research Center for Neurological Diseases

dTiantan Clinical Trial and Research Center for Stroke, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University

eVascular Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University

fCenter of Stroke, Beijing Institute for Brain Disorders

gNeuro-intensive Care Unit, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University

hDepartment of Neuropsychiatry and Behavioral Neurology and Clinical Psychology, Beijing Tiantan Hospital, Capital Medical University

iBeijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.

Correspondence: Yongjun Wang, Vascular Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; No. 6 Tiantanxili, Dongcheng District, Beijing 100050, China (e-mail: yongjunwang1962@gmail.com); Yilong Wang, Tiantan Clinical Trial and Research Center for Stroke, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No.6 Tiantanxili, Dongcheng District, Beijing 100050, China (e-mail: yilong528@gmail.com).

Abbreviations: ACS = anterior circulation stroke, aICH = all intracranial hemorrhage, AIS = acute ischemic stroke, BAO = basilar artery occlusion, CI = confidence interval, CT = computed tomography, ECASS = European Cooperative Acute Stroke Study, IVT = intravenous thrombolysis, MR = magnetic resonance, mRS = modified Rankin Scale, NIHSS = National Institutes of Health Stroke Scale, NINDS = National Institute of Neurological Disorders and Stroke, OR = odds ratio, PCS = posterior circulation stroke, PH = parenchymal hematoma, sICH = symptomatic intracranial hemorrhage, SITS = Safe Implementation of Thrombolysis in Stroke, TIMS-China = Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China.

Authorship: XT, YW, and YW—study concept and design; XT, XL, CW, and HZ—acquisition of data; YP—analysis of data; YW and YW—interpretation of data; YC, LL, XZ, CW, YW, and YW—study supervision; YC and YW—critical revision of manuscript for intellectual content.

Funding: This study was funded by the National Science and Technology Major Project of China (2011BAI08B02 and 2013BAI09B03), the State Key Development Program of Basic Research of China (2009CB521905), and the Beijing Municipal Science and Technology Commission (D151100002015001).

The authors have no financial conflicts of interest.

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This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

Received April 2, 2016

Received in revised form May 9, 2016

Accepted May 12, 2016

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1 Introduction

Intravenous thrombolysis (IVT) with alteplase is still the first-line therapy for all kinds of acute ischemic stroke (AIS) including anterior circulation stroke (ACS) and posterior circulation stroke (PCS),[1–3] although endovascular treatment recently has achieved the recommendation of class I for carefully selected patients with ACS.[4] In the past 2 decades, several randomized controlled trials and real world registries have demonstrated the safety and efficacy of intravenous alteplase for AIS within 4.5 hours time window.[5–8] Unfortunately, reports on using IVT for PCS are lacking. For example: National Institute of Neurological Disorders and Stroke (NINDS) trial had few PCS patients (5%);[5] European Cooperative Acute Stroke Study (ECASS) I and II only included the patients with ACS, excluding those with PCS;[9,10] ECASS III did not refer to the number of PCS patients if any was enrolled;[7] Safe Implementation of Thrombolysis in Stroke (SITS) was the largest stroke thrombolysis registry in the world, but also did not differentiate the sites of infarction.[6,8] PCS was often overlooked in the previous clinical studies partly because of its low incidence. To be specific, PCS only accounted for 17% to 22% of all AIS in Chinese hospital-based population.[11,12] On the other hand, stroke physicians do not care whether a patient had ACS or PCS at the clinical scene, and thereby PCS is often treated similarly to ACS,[13] but results of anterior circulation trials do not necessarily apply to PCS. To determine whether there is any difference in the post-IVT outcomes between ACS and PCS, we analyzed the data from a large multicenter prospective registry—the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China).

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2 Methods

2.1 Study population

The TIMS-China was a national prospective stroke registry of thrombolytic therapy for patients with AIS in 67 major stroke centers in China.[14] The study protocol was approved by the Ethics Committee of Beijing Tiantan Hospital. The registry was regularly monitored independently by the Quality Monitoring Committee of TIMS-China and the Contract Research Organization. All patients or patients’ care providers were given written informed consents before thrombolysis, and all patients received the alteplase dose of 0.5 to 0.9 mg/kg, with 10% of the total dose given within 1 minute followed by the remainder infused over 60 minutes. The National Institutes of Health Stroke Scale (NIHSS) score was measured at baseline, 2 hours, 24 hours, 7 days (or at discharge, whichever occurs first), and any time of neurological deterioration. The modified Rankin Scale (mRS) score was assessed at 7 days (or at discharge, whichever occurs first) and 90 days. Only the neurologists who were trained and qualified for using NIHSS and mRS recorded the scores. Brain imaging (computed tomography [CT] and magnetic resonance) was performed at baseline, 24 hours, and 7 days (or at discharge, whichever occurs first), but magnetic resonance examination was optional. The imaging findings were interpreted by at least 2 experienced senior radiologists in each participating hospital.

From the TIMS-China database, all patients who received IVT within 4.5 hours time window were screened for this analysis. Based on the clinical presentations and imaging findings, the patients were divided into ACS or PCS group. ACS was defined as acute infarctions involving the territories of internal carotid artery, middle cerebral artery, or anterior cerebral artery. PCS was defined as acute infarctions involving the territories of vertebral artery, basilar artery, or posterior cerebral artery. The patients with unclear stroke territory and acute infarctions in both circulation territories were excluded.

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2.2 Safety and efficacy outcomes

The safety outcomes included post-IVT symptomatic intracranial hemorrhage (sICH), parenchymal hematoma (PH), and all intracranial hemorrhage (aICH) within 7 days, and mortality within 90 days. sICH was evaluated by using the NINDS definition, which was defined as hemorrhage that was not seen on a previous CT scan, and there was subsequently either a suspicion of hemorrhage or any decline in neurological status.[5] Parenchymal hematoma (PH) was defined as a hemorrhage with mass effect: PH1, blood clots not exceeding 30% of the infarcted area with slight space-occupying effect; PH2, blood clots exceeding 30% of the infracted area with substantial space-occupying effect.[10] aICH was verified by the follow-up imaging regardless of clinical deterioration.

The efficacy outcomes included excellent recovery and functional independence at 90 days. Excellent recovery was defined as having a mRS score of 0 to 1, and functional independence was defined as having a mRS score of 0 to 2.[8]

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2.3 Statistical analysis

The baseline data were compared between ACS and PCS groups. The t test or the Mann–Whitney U test was used to compare means or medians for continuous variables. The Pearson chi-square test or continuity correction was used to compare the proportions for categorical variables. For comparing the post-IVT outcomes between both groups, odds ratios (ORs) with 95% confidence intervals (CIs) and the adjusted ORs with 95% CIs were calculated by using univariate and multivariate logistic regression models. The stroke territory (ACS or PCS) was forced in both models as an independent variable. Age, sex, baseline NIHSS score, and the baseline variables showing possible associations with the outcomes in the univariate analysis (P < 0.05) were entered in the multivariate model as confounding factors. Statistical significance was set at P < 0.05. All analyses were performed with SAS statistical software (version 9.3, SAS Institute Inc., Cary, NC).

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3 Results

Between May 2007 and April 2012, 1440 patients with AIS and received IVT with alteplase were registered in the TIMS-China database. Because of delayed treatment (>4.5 hours) and unclear onset-to-thrombolysis time, 312 patients were excluded. Another 165 patients with unclear stroke territory and 10 patients with acute infarctions in both anterior and posterior circulation territories were excluded. Finally, 953 eligible patients were entered into the analysis in this study, which included 829 patients in the ACS group and 124 in the PCS group (Fig. 1).

Figure 1

Figure 1

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3.1 Baseline characteristics

The PCS group had less atrial fibrillation (11.3% vs 19.8%; P = 0.02), but higher blood glucose level (mean 8.31 vs 7.63 mmol/L; P = 0.02) and elevated white blood cell counts (mean 8.79 vs 7.75 × 109/L; P = 0.001) than the ACS group. Whereas other baseline variables, including age, NIHSS score, onset-to-thrombolysis time, and so on, did not have significant differences between the 2 groups (P > 0.05) (Table 1).

Table 1

Table 1

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3.2 Safety and efficacy outcomes

Twenty patients (2.1%) were lost to follow-up (18 cases with ACS and 2 with PCS) at 90 days. The multivariate logistic regression analysis showed that PCS patients had less events of sICH (3.2% vs 7.7%; OR 0.28, 95% CI 0.09–0.90, P = 0.03), PH (1.6% vs 9.2%; OR 0.13, 95% CI 0.03–0.57, P = 0.01), and aICH (8.1% vs 20.4%; OR 0.26, 95% CI 0.12–0.54, P < 0.001) than ACS patients. In addition, the odds of having both excellent recovery (55.7% vs 41.6%; OR 2.27, 95% CI 1.42–3.61, P = 0.001) and functional independence (63.9% vs 53.0%; OR 2.33, 95% CI 1.40–3.89, P = 0.001) were approximately 1.3 times more in the PCS group than in the ACS group. However, there was no significant difference in the rate of mortality (OR 0.86, 95% CI 0.39–1.91, P = 0.72) between the 2 groups after adjusting the prespecified confounders, although PCS patients were more likely to decease within 90 days than ACS patients (15.6% vs 10.1%; OR 1.64, 95% CI 0.96–2.82, P = 0.07) in the univariate analysis (Table 2 and Fig. 2).

Table 2

Table 2

Figure 2

Figure 2

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4 Discussion

The results of this study ran parallel to the previous studies which reported that PCS was associated with a lower risk of hemorrhagic transformations.[15–18] Older age, hyperglycemia, and high NIHSS score are related to poor outcome of post-IVT in all parameters (intracranial hemorrhage, mortality, and independence). High systolic blood pressure and atrial fibrillation are additional predictors of intracranial hemorrhage.[19] In this study, the age, baseline NIHSS score, and systolic blood pressure were similar between ACS and PCS groups. Blood glucose level was higher in the PCS group, whereas atrial fibrillation was less frequent in the PCS patients, potentially affecting the incidence of hemorrhagic transformations in favor of ACS patients. Because the infarction volume on baseline imaging could predict the risk of post-IVT intracranial hemorrhage,[20,21] the smaller infarction volume in PCS compared with ACS might also contribute to the lower rate of hemorrhagic transformations in PCS patients.[22] In addition, the collateral supply in posterior circulation territory might be better than that of anterior circulation.[23] Patients with better collaterals were not prone to having hemorrhagic complications after acute reperfusion therapy.[24,25] Moreover, the brain histopathological changes after stroke onset may be different between both circulation territories. Previous studies have suggested a delayed blood–brain barrier disruption in posterior circulation compared with anterior circulation.[26,27] The greater ischemic tolerance in posterior circulation may partly explain the decreased risk of hemorrhagic complications in PCS.[28]

Inconsistent with previous studies,[16,29–31] our results showed that PCS patients had better responses to alteplase and thereby they had higher odds of excellent recovery and functional independence at 90 days than ACS patients. Possible reasons are as follows: the most devastating stroke—basilar artery occlusion—is seldom seen, only accounting for 8% of PCS.[32] Often PCS locates in the cerebellum, hippocampus, or occipital lobe, whereas the brain stem or thalamus is spared. These patients with vertigo, ataxia, impaired vision, cognitive decline, or mental disorder may not have obvious neurological deficits after medical treatment and rehabilitation.[33] On the other hand, because PCS patients had less often hemorrhagic complications in this cohort, they were more likely to be treated by antiplatelet agents or anticoagulants after IVT without fear of bleeding expansion. The subsequent antithrombotic therapies could consolidate the thrombolytic effect and have a positive impact on the outcome.

Our study had several limitations. Firstly, the design of this study is prospective observational cohort by nature. We presented adjusted OR as final results in multivariate logistic regression analyses. However, the confounding factors may not be completely removed by using the multivariate model. In addition, there may be some hidden confounders (e.g., volume of infarction and collateral circulation) we did not collect in this study. We should be careful to interpret the results. Secondly, the sample size was relatively small, especially in the PCS group, which could have reduced the power of test. Thirdly, we had no information about fetal origin of posterior cerebral artery. These patients could have a stroke from the anterior circulation. And finally, this study was conducted in Chinese population. However, ethnic differences may have an impact on the outcomes observed in this analysis. Our findings should be interpreted with caution and could not easily be extrapolated to other populations.

To the best of our knowledge, this was the first multicenter observational study comparing the safety and efficacy of IVT for ACS and PCS in Chinese population. Our study suggested that PCS patients treated with IVT had a lower risk of developing hemorrhagic transformation within 7 days and better chance of having no major disability at 90 days than ACS patients. In short, IVT might be more safe and effective for PCS. Our results will provide reassurance to the clinicians in using intravenous alteplase to treat all kinds of stroke patients with confidence, including those with PCS.

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Acknowledgments

We thank all participating hospitals, relevant clinicians, statisticians, and imaging and laboratory technicians.

The TIMS-China Co-investigators include: Qi Bi, MD (Beijing Anzhen Hospital, Site investigator); Liying Cui, MD, PhD (Peking Union Medical College Hospital of Peking University, Site investigator); Yuheng Sun, MD (Beijing Jishuitan Hospital, Site investigator); Maolin He, MD (Beijing Shijitan Hospital, Site investigator); Dongsheng Fan, MD, PhD (Peking University Third Hospital, Site investigator); Xiaojun Zhang, MD, PhD (Beijing Tongren Hospital, Site investigator); Yansheng Li, MD, PhD (Shanghai Renji Hospital, Site investigator); Shaoshi Wang, MD (Shanghai First Municipal People's Branch hospital, Site investigator); Wei Fan, MD (Zhongshan Hospital of Fudan University, Site investigator); Chuancheng Ren, MD (The Fifth People's Hospital of Shanghai Affiliated to Fudan University, Site investigator); Zhenguo Liu, MD (Xinhua Hospital Affiliated to Shanghai Jiaotong University, Site investigator); Xiaojiang Sun, MD (The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Site investigator); Xu Chen, MD (Shanghai 8th People's Hospital, Site investigator); Qingke Bai, MD (Pudong New Area People's Hospital, Site investigator); Dexiang Gu, MD (Shanghai Yangpu Area Shidong Hospital, Site investigator); Chunmei Hu, MD (Shanghai Baoshan Area Center Hospital, Site investigator); Xin Li, MD (Shanghai Yangpu Area Center Hospital, Site investigator); Qiang Dong, MD, PhD (Huashan Hospital of Fudan University, Site investigator); Yan Cheng, MD, PhD (Tianjin Medical University General Hospital, Site investigator); Bin Li, MD (Dagang Oilfield General Hospital, Site investigator); Chen Li, MD (Tianjin Fifth Center Hospital, Site investigator); Tongyu Wang, MD (Bohai Oilfield Hospital, Site investigator); Liping Wang, MD (Ninghe County People's Hospital of Tianjin, Site investigator); Kun Zhao, MD (Baodi District People's Hospital of Tianjin, Site investigator); Dingbo Tao, MD, PhD (The First Afflicated Hospital of Dalian Medical University, Site investigator); Fang Qu, MD (Dalian Second People's hospital, Site investigator); Jingbo Zhang, MD (Dalian Third People's hospital, Site investigator); Jianfeng Wang, MD, PhD (Dalian Central hospital, Site investigator); Ying Lian, MD (Dalian Economic and Technological Development District Hospital, Site investigator); Fang Qu, MD (Shenyang Military District General hospital of Chinese People's Liberation Army, Site investigator); Ying Gao, MD (National Traditional Chinese Medicine Thrombus Treatment Center of Liaoning Province, Site investigator); Huashan Sun, MD (Jilin Chemical Industrial Group General Hospital, Site investigator); Jinying Li, MD (Jilin Oilfield General Hospital, Site investigator); Guozhong Li, MD (The First Clinical College of Harbin Medical University, Site investigator); Yulan Zhu, MD (The Second Clinical College of Harbin Medical University, Site investigator); Zichao Yang, MD (The Fourth Clinical College of Harbin Medical University, Site investigator); Jun Zhou, MD (Mudan Jiang Second hospital, Site investigator); Minxia Guo, MD (Shanxi Provincial People's Hospital, Site investigator); Qilin Ma, MD (The First Hospital of Xiamen, Site investigator); Xiaoping Gao, MD (Hunan Provincial People's Hospital, Site investigator); Renbin Huang, MD (Chenzhou First People's Hospital, Site investigator); Bo Xiao, MD, PhD (Xiangya Hospital of Centre-South University, Site investigator); Kangning Chen, MD (Southwest Hospital, Site investigator); Li Gao, MD (Chengdu Third Municipal People's Hospital, Site investigator); Anding Xu, MD, PhD (The First Affiliated Hospital of Jinan University, Site investigator); Ming Shao, MD (The First Affiliated Hospital of Guangzhou Medical University, Site investigator); En Xu, MD (The Second Affiliated Hospital of Guangzhou Medical University, Site investigator); Xiaoping Pan, MD (Guangzhou First Municipal People's Hospital, Site investigator); Yefeng Cai, MD (Guangdong Provincial Hospital of Traditional Chinese Medicine, Site investigator); Yun Xu, MD, PhD (Drum Tower Hospital Affiliated to Nanjing Medical University, Site investigator); KaiFu Ke, MD (The Affiliated Hospital of Nantong University, Site investigator); Yuenan Kong, MD (Wuxi Second People's Hospital, Site investigator); Liangcai Ding, MD (The Third Affiliated Hospital of Suzhou University, Site investigator); Yumin Liu, MD (Zhongnan Hospital of Wuhan University, Site investigator); Kang Xu, MD (Hubei Xinhua Hospital, Site investigator); Chengming Xing, MD (Qingdao Municipal Hospital Group, Site investigator); Shaohua Su, MD (Dezhou People's Hospital, Site investigator); Guiru Zhang, MD (Penglai People's Hospital, Site investigator); Rongyuan Zheng, MD (The First Affiliated Hospital of Wenzhou Medical University, Site investigator); Ming Zhai, MD (The First People's Hospital of Yunnan Province, Site investigator); Yi Zhu, MD (The Xinjiang Autonomous Region People's Hospital, Site investigator); Yuanxin Liu, MD (Autonomous Region Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Site investigator); Xiaoying Zhang, MD (Hospital of Xinjiang Production and Construction Corps, Site investigator); Shizheng Wu, MD (Qinghai Provincial People's Hospital, Site investigator); Jinfeng Liu, MD (Yangquan Coalmine Group General hospital, Site investigator).

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References

[1]. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008;25:457–507.
[2]. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947.
[3]. Minematsu K, Toyoda K, Hirano T, et al. Guidelines for the intravenous application of recombinant tissue-type plasminogen activator (alteplase), the second edition, October 2012: a guideline from the Japan Stroke Society. J Stroke Cerebrovasc Dis 2013;22:571–600.
[4]. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;46:3020–35.
[5]. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333:1581–7.
[6]. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275–82.
[7]. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317–29.
[8]. Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet 2008;372:1303–9.
[9]. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017–25.
[10]. Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352:1245–51.
[11]. Tao WD, Kong FY, Hao ZL, et al. One-year case fatality and disability after posterior circulation infarction in a Chinese hospital-based stroke study. Cerebrovasc Dis 2010;29:376–81.
[12]. Ji R, Wang D, Shen H, et al. Interrelationship among common medical complications after acute stroke: pneumonia plays an important role. Stroke 2013;44:3436–44.
[13]. Nouh A, Remke J, Ruland S. Ischemic posterior circulation stroke: a review of anatomy, clinical presentations, diagnosis, and current management. Front Neurol 2014;5:30.
[14]. Liao XL, Wang CX, Wang YL, et al. Implementation and outcome of thrombolysis with alteplase 3 to 4.5 h after acute stroke in Chinese patients. CNS Neurosci Ther 2013;19:43–7.
[15]. Pagola J, Ribo M, Alvarez-Sabin J, et al. Thrombolysis in anterior versus posterior circulation strokes: timing of recanalization, ischemic tolerance, and other differences. J Neuroimaging 2011;21:108–12.
[16]. Sarikaya H, Arnold M, Engelter ST, et al. Outcomes of intravenous thrombolysis in posterior versus anterior circulation stroke. Stroke 2011;42:2498–502.
[17]. Sung SF, Chen CH, Chen YW, et al. Predicting symptomatic intracerebral hemorrhage after intravenous thrombolysis: stroke territory as a potential pitfall. J Neurol Sci 2013;335:96–100.
[18]. Dornak T, Kral M, Hazlinger M, et al. Posterior vs. anterior circulation infarction: demography, outcomes, and frequency of hemorrhage after thrombolysis. Int J Stroke 2015;10:1224–8.
[19]. Wahlgren N, Ahmed N, Eriksson N, et al. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST). Stroke 2008;39:3316–22.
[20]. Singer OC, Humpich MC, Fiehler J, et al. Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging. Ann Neurol 2008;63:52–60.
[21]. Sairanen T, Strbian D, Ruuskanen R, et al. Symptomatic intracranial haemorrhage after thrombolysis with adjuvant anticoagulation in basilar artery occlusion. Eur J Neurol 2015;22:493–9.
[22]. Lindgren A, Norrving B, Rudling O, et al. Comparison of clinical and neuroradiological findings in first-ever stroke. A population-based study. Stroke 1994;25:1371–7.
[23]. Menon BK, O’Brien B, Bivard A, et al. Assessment of leptomeningeal collaterals using dynamic CT angiography in patients with acute ischemic stroke. J Cereb Blood Flow Metab 2013;33:365–71.
[24]. Bang OY, Saver JL, Kim SJ, et al. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke. Stroke 2011;42:2235–9.
[25]. Chuang YM, Chan L, Lai YJ, et al. Configuration of the circle of Willis is associated with less symptomatic intracerebral hemorrhage in ischemic stroke patients treated with intravenous thrombolysis. J Crit Care 2013;28:166–72.
[26]. Bang OY, Saver JL, Alger JR, et al. Patterns and predictors of blood-brain barrier permeability derangements in acute ischemic stroke. Stroke 2009;40:454–61.
[27]. Lee M, Saver JL, Alger JR, et al. Blood-brain barrier permeability derangements in posterior circulation ischemic stroke: frequency and relation to hemorrhagic transformation. J Neurol Sci 2012;313:142–6.
[28]. Schaller B, Graf R, Jacobs AH. Ischaemic tolerance: a window to endogenous neuroprotection. Lancet 2003;362:1007–8.
[29]. De Marchis GM, Kohler A, Renz N, et al. Posterior versus anterior circulation strokes: comparison of clinical, radiological and outcome characteristics. J Neurol Neurosurg Psychiatry 2011;82:33–7.
[30]. Forster A, Gass A, Kern R, et al. Thrombolysis in posterior circulation stroke: stroke subtypes and patterns, complications and outcome. Cerebrovasc Dis 2011;32:349–53.
[31]. Sarraj A, Medrek S, Albright K, et al. Posterior circulation stroke is associated with prolonged door-to-needle time. Int J Stroke 2015;10:672–8.
[32]. Mattle HP, Arnold M, Lindsberg PJ, et al. Basilar artery occlusion. Lancet Neurol 2011;10:1002–14.
[33]. Searls DE, Pazdera L, Korbel E, et al. Symptoms and signs of posterior circulation ischemia in the new England medical center posterior circulation registry. Arch Neurol 2012;69:346–51.
Keywords:

acute ischemic stroke; anterior circulation; intravenous thrombolysis; outcome; posterior circulation

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