Thrombolysis In Acute Stroke Patients Research Articles

Hyperdense middle cerebral artery sign and response to combination of mechanical Thrombectomy plus intravenous thrombolysis in acute stroke patients

Background and purposeCombining intra-arterial mechanical thrombectomy (IAMT) and intravenous thrombolysis (IVT) has shown to have an excellent recanalization rate and better clinical outcome in acute ischemic stroke (AIS) patients. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment non-contrast head CT scan of AIS patients is one of the early ischemic radiological findings in middle cerebral artery territory AIS. We aimed to evaluate whether the presence of HMCAS predicts the outcome of AIS patients receiving combination therapy with IAMT and IVT. MethodsWe retrospectively reviewed medical records and cerebrovascular images of the patients treated with IAMT and IVT for AIS in our center. Patients with occlusion in the terminal internal carotid artery or middle cerebral artery on pretreatment CT angiogram of the head were included. Clinical outcome was compared between subjects with HMCAS and those without. Modified Rankin Score (mRS) and symptomatic intracranial hemorrhage (sICH) were used as measures of efficacy and safety, respectively. ResultsOf 93 patients, 46 (49%) had HMCAS on their initial head CT scan. Both groups had comparable baseline characteristics and stroke severity. After adjusting for age, NIHSS score, time from symptom onset to starting IVT, and history of diabetes mellitus in multivariate logistic regression analysis, there was no difference in terms of a poor outcome (mRS >2) (OR = 0.5 [CI 0.2–1.4], p = 0.188) or rate of sICH (OR = 3.3 [CI 0.6–19.0], p = 0.190) between the two groups. ConclusionsHMCAS is not a predictor of poor outcome in AIS patients receiving combination therapy with IAMT and IVT and does not affect treatment safety.

Stroke Angel: Effect of Telemedical Prenotification on In-Hospital Delays and Systemic Thrombolysis in Acute Stroke Patients

Introduction: Door-to-CT scan time (DCT) and door-to-needle time (DNT) are important process measures in acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). We examined the impact of a telemedical prenotification by emergency medical service (EMS) (called the “Stroke Angel” program) on DCT and DNT and IVT rate compared to standard of care. Patients and Methods: Two prospective observational studies including AIS patients admitted via EMS from 2011 to 2013 (cohort I; n = 496) and from January 1, 2015 to May 31, 2018 (cohort II; n = 349) were conducted. After cohort I, the 4-Item Stroke Scale and a digital thrombolysis protocol were added. Multivariable logistic and linear regression analysis was performed. Results: In cohort I, DCT was lower in the intervention group (13 vs. 26 min using standard of care; p < 0.001), but no significant difference in median DNT (35 vs. 39 min; p = 0.24) was observed. In cohort II, a reduction of DCT (8 vs. 15 min; p < 0.001) and DNT (25 vs. 29 min p = 0.003) was observed in the intervention group. Compared to standard of care, the likelihood of DCT ≤10 min or DNT ≤20 min in the intervention group was 2.7 (adjusted odds ratio [aOR] 2.7; 95% CI: 2.1–3.5) and 1.8 (aOR 1.8; 95% CI: 1.1–2.9), respectively. In cohort II, IVT rate was higher (aOR 1.4; 95% CI: 1.1–1.9) in the intervention group. Conclusion: Although the positive effects of Stroke Angel in AIS provided a rationale for implementation in routine care, larger studies of practice implementation will be needed. Using Stroke Angel in the prehospital management of AIS impacts on important process measures of IVT delivery.

Pre-hospital triage of suspected acute stroke patients in a mobile stroke unit in the rural Alberta

Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.

Intraosseus route for thrombolysing acute stroke is safe and successful.

Use of intraosseous route in thrombolysis of acute stroke patients remains a rare entity. Here, we describe the first such case within UK of a 55-year-old female patient of acute stroke who was thrombolysed with Alteplase administered through intraosseous (IO) route. She initially presented to A&E with severe dysarthria dysphasia and left sided weakness with an NIHSS-8. Failing acquisition of an intravenous access an IO vascular access was secured and thrombolysis was administered She improved remarkably and had no complications. The challenge faced in this case, of acquiring an effective access within the time frame and safely administering the Alteplase without any local or systemic complications was well met with a favourable outcome. IO is an established method of obtaining vascular access in children and adults in acute emergency situations. It can be used for effective thrombolysis in acute stroke patients.

Comparison of Rates and Outcomes of Readmission to Index vs Non-index Hospitals After Intravenous Thrombolysis in Acute Stroke Patients.

National and regional systems of stroke care are designed to provide patients with widespread access to hospitals with thrombolytic capabilities. However, such triaging systems may contribute to fragmentation of care. This study aims to compare rates of readmission and outcomes between index and non-index hospitals for stroke patients following intravenous thrombolytic therapy (IVT). This study utilized a nationally representative sample of stroke patients with IVT from the Nationwide Readmissions Database from 2010 to 2014. Descriptive and regression analyses were performed for patient and hospital level factors that influenced 90-day readmissions and regression models were used to identify differences in mortality, complications, and repeat readmissions between patients readmitted to index (facility where IVT was administered) and non-index hospitals. In the study, 49415 stroke patients were treated with IVT, of whom 21.7% were readmitted within 90 days. Among readmissions, 79.4% of patients were readmitted to index hospitals and 20.6% to non-index hospitals. On multivariate logistic regression analysis, index hospital readmission was independently associated with lower frequency of second readmissions (non-index OR 1.09, 95%CI 1.07-1.11, p<0.0001) but not with increased mortality or major complications (p=ns). Approximately one-fifth of stroke patients treated with thrombolysis were readmitted within 90 days, one-fifth of whom were readmitted to non-index hospitals. Although readmission to index hospital was associated with lower frequency of subsequent readmissions, readmission to non-index hospital was not associated with increased mortality or major complications. This difference may be due to standardized algorithms, mature systems of care, and demanding metrics required of stroke centers.

Intravenous lysis treatment in acute stroke treatment-latest situation

Intravenous (i.v.) thrombolysis and mechanical thrombectomy are two essential pillars of acute stroke treatment in patients with vascular occlusion in the anterior circulation. The issue about using so-called bridging thrombolysis in acute stroke patients is increasingly under discussion. After application of i.v. thrombolysis treatment, stroke patients who were primarily transported to a neurovascular center and underwent timely endovascular treatment, showed alower preinterventional recanalization rate, a lower 90-day mortality but no significant difference in the clinical outcome after 3 months compared with stroke patients with mechanical thrombectomy alone. Higher rates of intracranial hemorrhage could be detected in the bridging thrombolysis group of patients. The i.v. thrombolysis treatment is still an essential treatment concept in acute stroke management. Further studies should be carried out with respect to the application in mothership stroke patients undergoing early endovascular treatment.

Intravenous Thrombolysis for Stroke Patients with G6PD Deficiency

No reports regarding the safety of thrombolysis in acute stroke patients with a G6PD deficiency have been published to date. Here we aimed to evaluate the safety of intravenous thrombolysis for G6PD-deficient stroke patients. We enrolled each patient with acute ischemic stroke who arrived in our stroke unit within the therapeutic window and received systemic thrombolysis using recombinant tissue plasminogen activator (rt-PA), between January 2015 and March 2016. The primary clinical outcome was measured 3 months after treatment, and defined as a "good" outcome by a modified Rankin Scale (mRS) score of 0-2. Major safety outcomes were incidences of intracranial hemorrhage (ICH) or mortality at 90 days. A total of 96 individuals were analyzed, of which 20 patients were G6PD deficient. The rates of ICH after rt-PA treatment were 12% the in G6PD-deficient group versus 15% in G6PD non-deficient group, and the incidences of symptomatic intracranial hemorrhage were also similar between the G6PD-deficient and non-deficient cohorts. No hemolysis crisis occurred, and no significant difference in mortality rate was found between the 2 groups. The overall rate of a good outcome at 3 months after stroke in the whole cohort was 60%, whereas 50% of patients achieved an excellent outcome (mRS 0-1) in the G6PD-deficient cohort, and 42% in the G6PD non-deficient group. Thrombolytic therapy for patients with G6PD deficiency seems to pose a similar risk of ICH and clinical outcome to those with G6PD non-deficiency.

Thrombectomie mécanique de l’infarctus cérébral : pourquoi une prise en charge ultrarapide est nécessaire ?

Intravenous thrombolysis was the only proven effective reperfusion therapy for acute ischemic stroke within 4h30 until December 2014. Stroke management has been revolutionized after the publication of the recent positive trials, such as MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, and THRACE. Each of these demonstrates a clear benefit of stent retriever thrombectomy in association with thrombolysis in acute stroke patients with a documented occlusion of the distal internal carotid or the proximal middle cerebral artery within 6 h of symptoms onset. According to the initial selection, the number of patients to be treated by thrombectomy in order to have one independent patient varies from 3 to 8.To guarantee these results, thrombectomy should be performed by an interventional neuroradiologist within 60–90 min after imaging confirmation, which requires a very fast transfer of patients to hospitals, where interventional neuroradiology is available without delaying thrombolysis. Samu plays a key role in this. In case of contraindication to thrombolysis, early primary thrombectomy should also be considered within 6 h of last seen normal. In acute basilar artery occlusion, thrombectomy should be performed alone or combined with thrombolysis. A close cooperation between all the teams is crucial with the goal of gaining maximum time to the patient.

Multidisciplinary Protocol for Rapid Head Computed Tomography Turnaround Time in Acute Stroke Patients

The door-to-computed tomography (CT) head reporting time is an essential step to determining eligibility for thrombolysis in acute stroke patients, but the specific components of the process have not been reported in detail. We performed a retrospective cross-sectional analysis of the prospectively collected Get-With-The-Guidelines database in our comprehensive stroke center to evaluate the effect of a structured multidisciplinary protocol on head CT times in acute stroke patients under consideration for thrombolysis. The median CT turnaround time in the first 6-month period was 27 (interquartile range [IQR], 27) and decreased in all subsequent periods after implementation of a formal protocol to 18 (IQR, 12; range, 17-20minutes; P<.0001 for all pairwise comparisons). The median CT turnaround time was 18 (IQR, 12) versus 20 (IQR, 14) minutes for patients with admission diagnosis of stroke (n=1123) versus nonstroke (n=685; P<.0001), respectively. A structured multidisciplinary protocol for obtaining acute stroke protocol head CT scan was associated with reduced CT turnaround time over the study period. Prospective studies should be done to determine ifimplementation in other stroke centers confirms the effectiveness of our protocol.

Problems and limitations in thrombolysis of acute stroke patients at a tertiary care center.

Aim:(1) To evaluate the number of patients thrombolysed within 1 h of arrival to emergency room (ER) (2) To identify reasons for delay in thrombolysis of acute stroke patients.Materials and Methods:All patients admitted to ER with symptoms suggestive of stroke from January 2011 to November 2013 were studied. Retrospective data were collected to evaluate ER to needle (door to needle time [DTNt]) time and reasons for delay in thrombolysis. The parameters studied (1) onset of symptoms to ER time, (2) ER to imaging time (door to imaging time [DTIt]), (4) ER to needle time (door to needle) and (5) contraindications for thrombolysis.Results:A total of 695 patients with suspected stroke were admitted during study period. 547 (78%) patients were out of window period. 148 patients (21%, M = 104, F = 44) arrived within window period (<4.5 h.). 104 (70.27%) were contraindicated for thrombolysis. Majority were intracerebral bleeds. 44 (29.7%) were eligible for thrombolysis. 7 (15.9%) were thrombolysed within 1 h. The mean time for arrival of patients from onset of symptoms to hospital (symptom to door) 83 min (median - 47). The mean door to neuro-physician time (DTPt) was 32 min (median - 15 min). The mean DTIt was 58 min (median - 50 min). The mean DTNt 104 (median - 100 min).Conclusion:Reasons for delay in thrombolysis are: Absence of stroke education program for common people. Lack of priority for triage and imaging for stroke patients.

Abstract W P56: Negative FLAIR-based Intravenous Thrombolysis in Acute Stroke Patients With Unknown Onset Time

BACKGROUND AND PURPOSE: Approximately 25% of acute stroke patients were excluded from intravenous thrombolysis using tPA because of the unknown onset time. We previously reported that patients with unknown onset time would be able to receive tPA when showing no ischemia on the FLAIR (negative FLAIR). We assessed the safety and efficacy of tPA for those patients with ICAO and MCAO. METHODS:From June 2009 to June 2013, we prospectively treated stroke patients with unknown onset time using tPA who satisfied following criteria: negative FLAIR, anterior-circulation stroke, presence of major arterial occlusion, and the DWI-ASPECTS ≥5. tPA therapy was performed within 3 h from the first found abnormal time. Early recanalization was defined as new appearance of at least one of the distal branches within 1 h after tPA therapy on MRA. Dramatic recovery at day 7 was defined as ≥ 10-point reduction in the total NIHSS score or score of 0 or 1. A favorable outcome at 3 months was defined as a mRS score of 0-2. RESULTS:Subject comprised 24 patients (median age, 83 [68-90] years; 8 [33%] males). Eight (33%) patients had the ICAO (ICAO group), and 16 (67%) had the MCAO (MCAO group). NIHSS score was slightly higher in the ICAO group than the MCAO group (18 [17-20] vs. 16 [10-20], p=0.085). Median interval between the last seen normal time and admission was similar between patients in the ICAO group and the MCAO group (5.9 h [5.0-12.4] vs. 5.6 h [4.2-12.9], p=0.602). DWI-ASPECTS on admission tended to be higher in the ICAO and the MCAO groups (9 [8-10] vs. 8 [6-9], p=0.086). During the 7 days after stroke, none of the patients with ICAO and the MCAO groups experienced symptomatic cerebral hemorrhage (p=1.000). Regarding efficacy outcome, only 1 (13%) of the 8 patients in the ICAO group and 7 (44%) of the 16 patients in the MCAO group had early recanalization. Thus, the rate of dramatic recovery at day 7 was lower in the ICAO group than the MCAO group (13% vs. 63%, p=0.033). Among 17 patients with pre-morbid mRS 0-2, none (0%) of the 4 patients with ICAO group and 8 (62%) of the 13 patients achieved favorable outcome (p=0.082). Conclusions: Acute MCAO patients with unknown onset time may benefit from tPA therapy when showing no ischemia on FLAIR. Yet, tPA therapy for patients with the ICAO should be ineffective.

Abstract W P245: Process Improvement to Reduce Time Interval From Hospital Arrival to Intravenous Thrombolysis in Acute Stroke

Background: Rapid administration of intravenous recombinant tissue plasminogen (rt-PA) is an effective way to enhance thrombolytic efficacy in stroke patients. We had already shown that a stroke code program based on the computerized physician order entry system could reduce time interval from hospital arrival to IV thrombolysis. We investigated that process improvement, which is an activity to improve existing process by making changes, could further reduce in-hospital time delay in thrombolytic therapy. Methods: During the first period (Jan. 2007 - Dec. 2009), we set the target time from emergency department (ED) arrival to IV thrombolysis at 40 minutes, monitored time intervals to evaluations and treatment at weekly stroke conference and determined the possible factors that were associated with time delay in cases who did not receive IV thrombolysis within 40 minutes. During the second period (Jan. 2010 - Dec. 2012), after review of factors of time delay during the first period, we implemented a tool for explanation to patients and their families, which included a standardized script and a Visual Decision Aid for tPA treatment (developed by UCLA stroke center). Results: After setting the target time and continuous monitoring of the process, median time from ED arrival to IV thrombolysis was reduced from 63 min to 45 min (p&lt;0.001). During the first period, the most common cause of the time delay was delayed decision of family (15.9%). After implementation of the standardized patient explanation tool, the proportion of the time delay due to the delayed decision was significantly reduced from 15.9% to 3.3% (p=0.005), which resulted in further reduction of time interval from ED arrival to IV thrombolysis to 43 min (p=0.001). Conclusion: Continuous process improvement activity was effective in reduction of time intervals from ED arrival to IV thrombolysis in acute stroke patients. Setting target time with continuous monitoring of the performance and a standardized explanation for patients and their families using a script and a Visual Decision Aid were helpful to improve stroke team performance and reduction of time delays.

Process improvement to enhance existing stroke team activity toward more timely thrombolytic treatment.

Background and PurposeProcess improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process.MethodsAfter determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared.ResultsThe median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)].ConclusionsPI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.

Successful Thrombolysis despite Having an Incidental Unruptured Cerebral Aneurysm.

Purpose. To report a case of successful thrombolysis performed in a patient with an incidental unruptured intracranial aneurysm and review the literature. Case Report. Patient admitted for ischemic stroke due to left posterior cerebral artery occlusion, with an incidental right middle cerebral artery aneurysm, who underwent treatment with tissue plasminogen activator (rtPA) resulting in clinical improvement without complications. Conclusion. The presence of unruptured intracranial aneurysms is considered as a contraindication to thrombolysis, due to a potentially higher hemorrhagic risk of aneurysm rupture. Patients, otherwise, eligible for thrombolysis are usually excluded from receiving this emergent treatment, despite its potential benefits. A reevaluation of the strict exclusion criteria for thrombolysis in acute stroke patients should be considered.

Predicting Clinical Outcomes and Response to Thrombolysis in Acute Stroke Patients With Diabetes

OBJECTIVEFew tools are available to evaluate clinical outcomes and response to thrombolysis (tPA) in stroke patients with diabetes. We explored how the iScore (www.sorcan.ca/iscore), a validated risk score, predicts clinical outcomes in stroke patients with and without diabetes.RESEARCH DESIGN AND METHODSWe applied the iScore to stroke patients presenting to stroke centers participating in the Registry of the Canadian Stroke Network. Main outcomes included favorable outcome, defined as a modified Rankin scale (mRS) 0–2 at discharge, and intracerebral hemorrhage (ICH) after tPA.RESULTSAmong 12,686 patients with an acute ischemic stroke, 3,228 (25.5%) had diabetes. Among patients receiving tPA (n = 1,689), those with diabetes had a lower rate of a favorable outcome compared with their counterparts (24.3 vs. 31.1%; RR 0.90 [95% CI 0.82–0.98]). The risk of ICH was not significantly different in patients with or without diabetes (for any type 12.6 vs. 12.5%, RR 1.01 [0.72–1.40]; for symptomatic ICH 7.5 vs. 6.8%, RR 1.11 [0.70–1.72]). The regression analysis revealed a decline in the probability of a favorable outcome after tPA with increments in the iScore (P value for iScore × tPA interaction <0.001). There was no difference in the response to tPA predicted by the iScore between stroke patients with and without diabetes (P value = 0.07).CONCLUSIONSStroke patients with diabetes have poorer outcomes compared with patients without diabetes, which is not explained by ICH. The iScore similarly predicts response to tPA between stroke patients with and without diabetes.

Postthrombolysis Intracranial Hemorrhage Risk of Cerebral Microbleeds in Acute Stroke Patients: A Systematic Review and Meta-Analysis

It has been questioned whether patients with cerebral microbleeds are at a greater risk for the development of symptomatic intracerebral hemorrhage following thrombolytic therapy in the management of acute ischemic stroke. Thus far, observational studies have not shown a statistically significant increased risk; however, these have been limited by small sample size. The aim is to better quantify the risk of postthrombolysis intracerebral hemorrhage in patients with acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A systematic review of controlled studies investigating the presence of microbleeds on magnetic resonance imaging as a risk factor for intracerebral hemorrhage following thrombolysis in acute stroke patients was conducted. A random effects model meta-analysis was performed. In pooled analysis of five studies totaling 790 participants, the prevalence of microbleeds was 17%. The presence of microbleeds revealed a trend toward an increased risk of postthrombolysis symptomatic intracerebral hemorrhage [odds ratio: 1·98 (95% confidence interval, 0·90 to 4·35; P = 0·09), I(2) = 0%]. Adjusted analysis minimizing potential bias resulted in an increased absolute risk of 4·6% for the development of symptomatic intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2·29 (95% confidence interval, 1·01 to 5·17), I(2) = 0%] reaching borderline significance (P = 0·05). A significant relationship between increasing microbleed burden and symptomatic intracerebral hemorrhage (P = 0·0015) was observed. Isolated analysis of studies using exclusively intravenous tissue plasminogen activator was insignificant. Our data suggest that patients with cerebral microbleeds are at increased risk for symptomatic intracerebral hemorrhage following thrombolysis for acute ischemic stroke. However, current data are insufficient to justify withholding thrombolytic therapy from acute ischemic stroke patients solely of the basis of cerebral microbleed presence.

Early infarct FLAIR hyperintensity is associated with increased hemorrhagic transformation after thrombolysis

Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2-175, P = 0.013). Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.

DWI/FLAIR mismatch based intravenous thrombolysis in acute stroke patients with unknown onset time

約25％の急性期脳梗塞例は発症時間が不明であるためt-PA静注療法の対象から除外される．頭部MRI DWIで高信号を呈していてFLAIRで信号変化がない場合（DWI/FLAIRミスマッチ），発症3時間以内と推定できる．我々は発症時間不明の脳梗塞例に対しDWI/FLAIRミスマッチに基づいたt-PA静注療法を行った．2009年6月から2011年10月までに13例［83 （67-90）歳，NIHSSスコア16 （11-20）点］が登録された．最終無事確認時間からt-PA静注療法まで5.6 （5.0-11.6）時間であった．24時間以内の再開通は10例（完全再開通：5例），症候性頭蓋内出血は0例であった．発症7日後の著明改善例は7例で，3カ月後の転帰良好例（mRS 0-2）は5例であった．発症時間が不明であってもDWI/FLAIRミスマッチがあればt-PA静注療法の対象になる可能性がある．

Hemorrhagic complications after systemic thrombolysis in acute stroke patients with abnormal baseline coagulation

As patients with abnormal baseline coagulation were excluded from the large randomized trials, the safety of intravenous thrombolysis after ischaemic stroke in this patient population remains controversial. We assessed the risk of symptomatic intracerebral hemorrhage (SICH) after systemic thrombolysis in patients with elevated baseline international normalized ratios (INRs) (≥1.3) or activated partial thromboplastin times (aPTT) (>37 s) using a prospectively recorded database from 2006 to 2010. An intracerebral hemorrhage leading to a deterioration of ≥4 points on the National Institutes of Health Stroke scale (NIHSS) was classified as symptomatic. Amongst 688 patients (mean age, 72 years; median NIHSS, 11, median onset-to-treatment time, 135 min), 36 patients (5%) had an abnormal baseline coagulation. Twenty-nine of these patients had taken oral anticoagulants leading to elevated baseline INRs (median INR: 1.5; IQR 1.4-1.9), whereas seven patients had elevated aPTTs because of heparin therapy (n = 2), a coagulation disorder (n = 2), or for unknown reasons (n = 3). The rate of SICH did not differ significantly between patients with abnormal and normal baseline coagulation (4.4% vs. 0%; P = 0.6). Moreover, the in-hospital mortality was not significantly different between both treatment groups (8.3% in patients with abnormal baseline coagulation vs. 8.7% in patients with normal baseline coagulation, P = 1.0). The risk of SICH following intravenous thrombolysis after ischaemic stroke does not appear to be increased in patients with abnormal baseline coagulation.

Translati onal challenges of neuroprotection strategy in ischemic stroke

AbstractNeuroprotection is a therapeutic strategy that attempts to save neurons from irreversible injury by modifying the effects of the ischemic cascade or facilitating reperfusion. Although numerous agents have shown neuroprotective effect in preclinical trials, their translation to clinical trials failed to show any meaningful effect. The Stroke Therapy Academic Industry Roundtable (STAIR) guidelines were made for performing research on neuroprotective agents in pre-clinical and clinical trials. Although the STAIR guidelines have been available for more than ten years, we still do not have any adequate neuroprotective agents. Reasons for unsuccessful translation from preclinical to clinical research can be considered along stages of drug development: 1) preclinical, 2) transitional and 3) clinical. By extending the therapeutic window for application of intravenous thrombolysis in acute stroke patients to 4.5 hours, as well as increasing the use intra-arterial thrombolysis and development of mechanical devices for thrombectomy in 6 hour period we may be able to achieve some degree of neuroprotection in acute stroke. Future therapy is likely to add to the current thrombolytic therapy with potential neuroprotective drugs or procedures.