The evolving role of acute stroke imaging in intravenous thrombolytic therapy: patient selection and outcomes assessment

In early trials of thrombolysis, unenhanced CT was used to exclude patients with brain hemorrhage or large infarctions but was insensitive to stroke pathophysiology or early signs of cerebral ischemia or infarction. Currently, CT angiography, CT perfusion, and MR imaging can provide information about stroke mechanisms and prognosis, quantify penumbral tissue, and support risk stratification and patient selection. This article reviews the role of neuroimaging in the original intravenous thrombolytic trials, current application of these technologies, and the potential future role of imaging to extend the time window for thrombolysis and to augment therapeutic success.     

Feasibility of acute thrombolytic therapy for stroke

BACKGROUND: Thrombolysis is an expensive medical intervention for ischemic stroke and hence there is a need to study the feasibility of thrombolysis in rural India. Aims: To asses the feasibility and limitations of providing thrombolytic therapy to acute ischemic stroke patients in a rural Indian set-up. MATERIAL AND METHODS: The first 64 consecutive patients registered under the Acute Stroke Registry in a university referral hospital with a rural catchment area were studied as per a detailed protocol and questionnaire. RESULTS: Of the 64 patients 44 were ischemic strokes, and 20 were hemorrhagic. Thirteen (29.55%) patients with ischemic stroke reached a center with CT scan facility within 3 hours, of whom only 7 (15.91%) were eligible to receive thrombolytic therapy as per the existing clinical and radiological criteria, but none received the therapy. Of the remaining 31 (70.45%) who arrived late, 11 (25%) had no clinical and radiological contraindications for thrombolysis, except the time factor. All the patients belonged to a low socioeconomic status and a rural background. CONCLUSION: Though a large proportion of ischemic stroke patients were eligible to receive thrombolytic therapy, the majority could not reach a center with adequate facilities within the recommended time window. More alarmingly, even for those patients who reached within the time window, no significant attempt was made to initiate thrombolysis. These data call not only for attention to improve existing patient transport facilities, but also for improving the awareness of efficacy and therapeutic window of thrombolysis in stroke, among the public as well as primary care doctors.     

Evaluation of the role of susceptibility-weighted imaging in thrombolytic therapy for acute ischemic stroke

We inspected low-intensity venous signals and microbleeds in patients with acute ischemic stroke (AIS) using susceptibility-weighted imaging (SWI) before and after administration of within-thrombolytic-time-window thrombolytic therapies, and observed their prognosis and safety, in order to guide individualized thrombolytic therapies. Patients with AIS were divided into groups A or B according to the presence of symmetric or asymmetric veins on SWI, and were re-inspected by SWI after intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA). The National Institutes of Health stroke scale (NIHSS) score before treatment and at 1-h and 24-h posttreatment in the two groups were 11.9, 7.3, and 7.1 in group A, 12.4, 8.2, and 7.9 in group B, significant difference was detected between the two groups after treatment. The 90-day mortality rate was 0, and the incidences of cerebral microbleeds (CMBs) and symptomatic cerebral hemorrhage (SCH) were 17.6%, and 0% in group A, 25.6% and 0% in group B, respectively. The incidences of CMBs and SCH in group A were lower than those in group B, but the intergroup differences were not statistically significant (P > 0.05). The 90-day neurological improvement rates in the two groups were 70.2% and 58.1%, respectively, and group A showed a significantly better prognosis than group B (P < 0.05). Thus, low-intensity venous signals in SWI can be used to evaluate a low level of perfusion, post-thrombolytic prognosis, and bleeding indexes, and can therefore be used to guide individualized thrombolytic therapies.     

Intraarterial thrombolytic therapy in acute stroke

Intraarterial thrombolytic therapy by means of urokinase has proved to be effective and safe in certain instances of acute thromboembolic occlusion of the vertebral and/or the basilar artery. Small hemorrhages have not led to deterioration in the patients' neurological state. In the territory of the carotid artery local thrombolytic therapy may be effective in very selected cases of acute thromboembolic occlusion. There is a high risk of intracerebral hemorrhage. Possibly intravenous administration of tPA will replace local intraarterial thrombolysis, provided a strict regimen is established for selection of patients, determination of dosage and time constraints for the application of this therapy.     

An update on thrombolytic therapy for acute stroke

PURPOSE OF REVIEW: Stroke is the third leading cause of death after myocardial infarction and cancer, and is the leading cause of permanent disability and disability-adjusted loss of independent life-years in western countries. Thrombolysis is the treatment of choice for acute stroke within 3 h after the onset of symptoms. We present an overview of a diagnostic approach to acute stroke management that allows the individualization of patient management based on pathophysiological reasoning and not rigid time windows established by randomized controlled trials. RECENT FINDINGS: This review concentrates in the first part on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke, and in the second part develops a treatment algorithm based on pathophysiological information rendered by a multiparametric stroke magnetic resonance imaging protocol. SUMMARY: Thrombolysis is an effective therapy for ischemic stroke, whether performed intravenously within 3 h or intra-arterially within 3-6 h. Meta-analyses have provided evidence of an effect of intravenous thrombolysis beyond the 3 h time window, especially when improved selection criteria such as modern magnetic resonance imaging protocols are applied. Sadly, thrombolysis is still underused. Positive results from studies currently underway may encourage more centers to offer this therapy to an increasing number of stroke patients, and thereby reduce the considerable socioeconomic burden of stroke.     

时间窗超过3h急性缺血性卒中患者动脉溶栓治疗观察

目的 评价时间窗超过3 h的急性缺血性卒中患者动脉溶栓治疗的疗效及影响因素.方法 选择法国南锡大学中心医院神经影像科自2008年1月至2009年1月收治的16例急性缺血性卒中患者(时间窗均达到或超过3 h,颈内动脉系统卒中时间窗不超过6 h,椎基底动脉系统卒中时间窗不超过24h.昏迷不超过6 h),行动脉内药物联合机械溶栓治疗,分析不同因素对疗效的影响.结果 7例患者闭塞血管达到完全再通,7例达到部分再通,另有2例闭塞血管未再通,再通率为87.5%.患者动脉溶栓后与溶栓前NIHSS评分比较明显降低.时间窗大于5 h的前循环系统闭塞患者溶栓前后NIHSS评分无改善,与时间窗较短患者相比较,出院时mRS评分明显较高.5例颈内动脉闭塞患者溶栓前后NIHSS评分无改善,与9例大脑中动脉闭塞患者、2例基底动脉闭塞患者相比预后较差.4例患者溶栓后24h出现症状性颅内出血,3例为颈内动脉闭塞,1例死亡.1例溶栓后发生血管再闭,但因侧支循环血流丰富,最终临床预后仍较好.结论 对于时间窗超过3 h大脑中动脉和基底动脉闭塞急性缺血性卒中患者,动脉溶栓可使闭塞血管达到较高的再通率,短期内使临床神经功能恢复,改善临床结局.临床应用动脉溶栓时应注意个体化选择性治疗,评价其疗效需结合时间窗、血管闭塞部位、侧支循环、并发症等因素,避免出血等并发症.     

时间窗超过3h急性缺血性卒中患者动脉溶栓治疗观察

目的 评价时间窗超过3 h的急性缺血性卒中患者动脉溶栓治疗的疗效及影响因素.方法 选择法国南锡大学中心医院神经影像科自2008年1月至2009年1月收治的16例急性缺血性卒中患者(时间窗均达到或超过3 h,颈内动脉系统卒中时间窗不超过6 h,椎基底动脉系统卒中时间窗不超过24h.昏迷不超过6 h),行动脉内药物联合机械溶栓治疗,分析不同因素对疗效的影响.结果 7例患者闭塞血管达到完全再通,7例达到部分再通,另有2例闭塞血管未再通,再通率为87.5%.患者动脉溶栓后与溶栓前NIHSS评分比较明显降低.时间窗大于5 h的前循环系统闭塞患者溶栓前后NIHSS评分无改善,与时间窗较短患者相比较,出院时mRS评分明显较高.5例颈内动脉闭塞患者溶栓前后NIHSS评分无改善,与9例大脑中动脉闭塞患者、2例基底动脉闭塞患者相比预后较差.4例患者溶栓后24h出现症状性颅内出血,3例为颈内动脉闭塞,1例死亡.1例溶栓后发生血管再闭,但因侧支循环血流丰富,最终临床预后仍较好.结论 对于时间窗超过3 h大脑中动脉和基底动脉闭塞急性缺血性卒中患者,动脉溶栓可使闭塞血管达到较高的再通率,短期内使临床神经功能恢复,改善临床结局.临床应用动脉溶栓时应注意个体化选择性治疗,评价其疗效需结合时间窗、血管闭塞部位、侧支循环、并发症等因素,避免出血等并发症.     

时间窗超过3h急性缺血性卒中患者动脉溶栓治疗观察

目的 评价时间窗超过3 h的急性缺血性卒中患者动脉溶栓治疗的疗效及影响因素.方法 选择法国南锡大学中心医院神经影像科自2008年1月至2009年1月收治的16例急性缺血性卒中患者(时间窗均达到或超过3 h,颈内动脉系统卒中时间窗不超过6 h,椎基底动脉系统卒中时间窗不超过24h.昏迷不超过6 h),行动脉内药物联合机械溶栓治疗,分析不同因素对疗效的影响.结果 7例患者闭塞血管达到完全再通,7例达到部分再通,另有2例闭塞血管未再通,再通率为87.5%.患者动脉溶栓后与溶栓前NIHSS评分比较明显降低.时间窗大于5 h的前循环系统闭塞患者溶栓前后NIHSS评分无改善,与时间窗较短患者相比较,出院时mRS评分明显较高.5例颈内动脉闭塞患者溶栓前后NIHSS评分无改善,与9例大脑中动脉闭塞患者、2例基底动脉闭塞患者相比预后较差.4例患者溶栓后24h出现症状性颅内出血,3例为颈内动脉闭塞,1例死亡.1例溶栓后发生血管再闭,但因侧支循环血流丰富,最终临床预后仍较好.结论 对于时间窗超过3 h大脑中动脉和基底动脉闭塞急性缺血性卒中患者,动脉溶栓可使闭塞血管达到较高的再通率,短期内使临床神经功能恢复,改善临床结局.临床应用动脉溶栓时应注意个体化选择性治疗,评价其疗效需结合时间窗、血管闭塞部位、侧支循环、并发症等因素,避免出血等并发症.

Abstract：

Objective To evaluate the efficacy of intra-arterial hrombolytic therapy in patients with acute ischemic stroke having their time window over 3 h and analyze its influencing factors.Methods Sixteen patients with acute ischemic stroke having their time window over 3 h, admitted to Department of Neuroradiology of Central Hospital of Nancy University from January 2008 to January 2009, were treated by intra-arterial thrombolysis using chemical (rt-PA) and mechanical technique. These patients had carotid stroke for less than 3 h, vertebrobasilar stroke for less than 24 h or coma for less than 6 h. According to the images of DSA, the recanalization after thrombolysis was evaluated by thrombolysis in cerebral infarction (TICI) grades. CT scans 24 h after thrombolysis were operated to detect the hemorrhage complications. NIHSS at baseline and 24 h after thrombolysis and modified Rankin Scale (mRS) were recorded to evaluate the clinical efficacy. Results After intra-arterial thrombolysis, 7 (43.75%) in 16 patients got totally recanalization (TICI grade 3), another 7 partial recanalization (TICI grade 2), and the left 2 patients failed in recanalization (TICI grade 1); the total recanalization rate was 87.5%. A significant reduction of NIHSS scores after the thrombolysis was noted as compared with that before the thrombolysis. The atients with occlusion of anterior ciculation having time window over 5 h enjoyed no reduction of NIHSS scores after thrombolysis; mRS scores in patients having time window over 5 h were ignificantly higher as compared with those in patients having time window less than 5 h.The patients having ICA occlusion (n=5) had no reduction of NIHSS scores after thrombolysis, and enjoyed poorer prognosis as compared with whose occlusion lay in the middle cerebral artery (MCA,n=9) and basilar artery (BA, n=2). By CT scan 24 h after thrombolysis, 4 patients were detected with symptomatic intra cerebral hemorrhage (ICH, 25%) and all of them with occlusion in the internal carotid artery system: 1 patient with occlusion in MCA died of cerebral hernia causing by the large hematoma;the other 3 were all occlusion in ICA. Although reocclusion after thrombolysis occurred, 1 patient was benefitted from the affluent collateral perfusion and got a good prognosis. Conclusion For patientswith BA and MCA occlusion having time window over 3 h, intra-arterial thrombolytic therapy is effective and selective resulting from their high recanalization rate, improvement of neurological function and clinical end. The therapy should be individually chosen; mutiple factors as time window of stroke,location of stroke, ompensatory circulation and complications should be considered in evaluating the efficacy; and the hemorrhage complications should be avoided.     

Intra-arterial thrombolytic therapy for acute anterior spinal artery stroke

Background and importanceSpinal cord infarction is rare but can be extremely disabling. Prompt diagnosis and treatment of these infarcts is important for patient outcomes. While intravenous thrombolytic therapy is a well-established form of treatment in circumstances of cerebral stroke, it has only recently been successfully used in a few incidents of spinal cord ischemia. We present a case of anterior spinal artery (ASA) territory ischemia treated with ASA intra-arterial thrombolytic therapy.Clinical presentationA 52-year-old male presented with acute onset of severe lumbar pain, rapidly progressing paraplegia and loss of pain and temperature sensation, with preservation of proprioception and vibratory sensation at the L1 level and below on the right and at the L3 level and below on the left. MRI showed restricted diffusion involving the cord at and below L1 level, with normal cord T2 signal. Digital subtraction spinal angiography showed ASA cutoff in the descending limb at the level of L1. Intra-arterial tissue plasminogen activator (t-PA) combined with verapamil and eptifibatide was administered within the ASA and the patient had significant neurological improvement immediately postoperatively and at 8-month clinical follow-up.ConclusionDirect ASA intra-arterial thrombolysis is feasible, and this drug combination might be an effective therapy for spinal stroke.     

应重视影像学指导下急性缺血性脑卒中的溶栓治疗

急性缺血性脑卒中占所有急性脑卒中的80％左右，通过循证医学的手段证明，目前只有溶栓治疗、抗血小板治疗和卒中单元是公认有效的方法，而溶栓治疗是其中最迅速和最直接的手段，有效的溶栓可使闭塞血管再通、血流恢复，从而迅速恢复缺血半暗带（ischaemic penumbra）脑组织的血液供应和正常的生理功能，可以对患者起到“立竿见影”的成效。缺血半暗带的存在是溶栓治疗的理论基础。     

Reasons for exclusion from thrombolytic therapy following acute ischemic stroke

Despite evidence for the efficacy of thrombolytic therapy in acute ischemic stroke, only 1 to 7% of patients receive this therapy. The authors sought to determine the reasons for exclusion from tissue plasminogen activator (tPA) in an acute setting and found avoidable causes in 18% of patients. Improvements in intrahospital coordination would increase the number of patients who might benefit from tPA treatment at the authors' center.     

Emergency physician attitudes toward thrombolytic therapy in acute stroke

Background: Intravenous use of tissue plasminogen activator (TPA) is the only currently approved treatment for acute ischemic stroke. Methods: To determine emergency physician attitudes and practices with regard to thrombolysis for ischemic stroke, a questionnaire was sent to program directors of accredited emergency medicine residencies in the United States. Results: There were 73 program directors who responded to the survey; 71% of medical centers have used TPA for treatment of stroke. The reported major complication rate for cerebral hemorrhage and death averaged 7%. For nontreating centers, two major factors cited were lack of appropriate patients and concerns regarding the safety of TPA; 48% of the facilities do not have an acute stroke team. Delayed patient arrival and the perceived narrow risk/benefit ratio of TPA were identified as the two greatest obstacles to more widespread use of TPA. Conclusion: Although the majority of medical centers that responded in this study have some experience with thrombolytic therapy for acute ischemic stroke, almost one half do not have an acute stroke team and considerable uncertainty exists regarding the safety of intravenous TPA. More uniform national treatment of acute stroke will require greater consensus among emergency physicians and further analysis of the risk/benefit ratio of thrombolytic treatment.