Thrombolysis For Ischemic Stroke Research Articles

Abstract 160: Final Results of the Thrombolysis for Minor Ischemic Stroke With Proven Acute Symptomatic Occlusion Using TNK-tPA (TEMPO-1) Trial

Background: Minor stroke and TIA with an intracranial occlusion are associated with a 20-30% risk of neurological deterioration and subsequent disability. TNK-tPA compared to alteplase is easier to administer, has a longer half-life, higher fibrin specificity and possibly a lower rate of intracranial hemorrhage. Therefore, it may be an ideal thrombolytic agent for recanalization in this population. Methods: TEMPO-1 was a multi-centre, prospective cohort, TNK-tPA dose-escalation, safety and feasibility trial. Patients with an NIHSS < 6, intracranial arterial occlusion on CTA, with no sign of well-evolved infarction who were treated within a 12h treatment window were enrolled. 50 patients were enrolled. The first 25 patients were treated at a dose of 0.1 mg/kg, and a second cohort of 25 patients treated at a dose of 0.25 mg/kg. Primary outcome was the rate of symptomatic intracranial (SICH) and extracranial hemorrhage. SICH was defined as a new ICH with ≥ 2 points worsening on the NIHSS. SITS-MOST definition of SICH was also assessed. Secondary outcomes include complete neurological (NIHSS 0-1) and functional (mRS 0-1) recovery at 90 days, recanalization at 4-8 h on CTA and minor bleeding. Results: Median baseline NIHSS was 2 (SD 1.24) and median age was 71 years (SD 18). Site of intracranial occlusions were: MCA-M1 (13), MCA-M2 (21), MCA-M3 (8), PCA-P1 (1), PCA-P2 (1) branches, vertebral artery/PICA (3) and undetermined (3). There was one SICH seen [2% (1/50), CI95 0.5%-10.6%], which was in the 0.25mg/Kg dose tier. There were no SICH by the SITS-MOST definition. For the 0.1mg/Kg dose tier recanalization between 4-8 hours post drug was complete in 21.7%, partial in 26.1% and no recanalization was seen in 52.2%. For the 0.25mg/Kg dose tier recanalization between 4-8 hours post drug was complete in 56.6%, partial in 13% and no recanalization was seen in 30.4%. 90-day disability and neurological outcome assessment will be available at the time of the International Stroke Conference. Conclusion: We have shown the safety and feasibility of thrombolysis with TNK-tPA in a minor stroke with intracranial occlusion population. Rates of recanalization are high in the 0.25mg/Kg tier and we have chosen this dose to proceed with a randomized controlled trial in this population.

Factors delaying hospital arrival of patients with acute stroke.

Background:Low rates of thrombolysis for ischemic stroke in India and other developing countries have been attributed to delays in presentation to the hospital.Materials and Methods:A prospective study was carried out during a 12-month period ending December 2012 in the department of Neurology, Malabar Institute of Medical Sciences, Kerala, India, to look for the factors contributing to delay in hospital arrival of patients with acute stroke. Patients and or their relatives were interviewed within 48 hours of admission using a structured questionnaire.Results:A total of 264 patients attending the emergency department were included. There were 170 men and 94 women. The mean age was 61.5 ± 12.4 years. A total of 67 (25%) patients presented within 4 hours of stroke onset. Factors associated with early arrival (multivariate logistic regression analysis) were distance 15 km or less from hospital (P 0.03, odds ratio (OR) 2.7), directly reaching the stroke department (P < 0.001, OR 9.7), history of coronary artery disease (P 0.001, OR 3.84), higher educational status (P 0.001, OR 3.7), and presence of hemiplegia (P 0.001, OR 5.5).Conclusions:We found a considerable delay in the early arrival of patients to our stroke department. Health promotion strategies to improve community awareness of early symptoms of stroke, education of local physicians about the importance of early referrals to the stroke centers, and wider availability and use of ambulance services are promising methods to help expedite presentation to hospital post stroke and thereby improve the management of stroke in India.

Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study

Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients. In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13). We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001). During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke. Reformpool of the Tyrolean Health Care Fund.

Stroke : Highlights of Selected Articles

HomeStrokeVol. 45, No. 10Stroke: Highlights of Selected Articles Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBStroke: Highlights of Selected Articles Originally published1 Oct 2014https://doi.org/10.1161/STROKEAHA.114.007187Stroke. 2014;45:2855Copeptin for the Prediction of Recurrent Cerebrovascular Events After Transient Ischemic Attack: Results From the CoRisk StudyCopeptin is a stress hormone that has previously been shown to be associated with recurrent cerebrovascular events after transient ischemic attack (TIA). The ABCD2 (age, blood pressure, clinical features, duration, diabetes) score and the ABCD3-I (ABCD2 plus dual TIA) score both provide risk assessment for recurrent stroke after TIA. The current study aimed to determine the effect of copeptin in the prediction of recurrent cerebrovascular events (stroke or TIA) within 3 months of TIA. In their cohort, 28 of 302 (9.3%) patients had a recurrent cerebrovascular event within 3 months of TIA. There was no statistically significant difference in copeptin levels in patients with or without recurrent cerebrovascular events. A total of 11 patients had recurrent stroke within 3 months. Copeptin levels were >4× higher in patients with recurrent stroke in comparison with those without stroke. A 10-fold increase in copeptin was associated with an odds ratio of stroke of 3.39 after adjustment for the ABCD2 score. Copeptin increased the prognostic ability of the ABCD2 score in predicting recurrent stroke in 31.2% of patients. In sum, copeptin seems to represent a biomarker with strong prediction value for recurrent stroke after TIA. Further validating studies are needed. But at this time it seems to add in risk stratification of patient presenting with TIA. See p 2918.Long-Term Outcomes After Combined Revascularization Surgery in Adult Moyamoya DiseaseMoyamoya disease is an idiopathic condition of progressive occlusions of both internal carotid arteries with abnormal vascular networks. Controversy exists on the optimal revascularization procedure in adults with moyamoya disease. The authors of this study report on the outcomes of combined revascularization surgery (direct bypass between the superficial temporal artery and a cortical branch of the MCA and indirect bypass known as encephalodurogaleosynangiosis) done on 77 hemispheres in 60 patients. The clinical status of patients, as assessed by the modified Rankin Scale and the Karnofsky Performance Scale, improved until 6 months after surgery and stayed stable after that. The relative revascularization area significantly increased in the long-term compared with the short-term follow-up period. The cerebral blood flow as measured by single photon emission computed tomography improved significantly in the short-term compared with the preoperative period and remained stable after that. Perioperative cerebral infarcts occurred in 13% of cases. However, the long-term risk of stroke was low with the annual rates of symptomatic cerebral hemorrhage and infarction in the operated hemispheres as 0.4% and 0.2%, respectively. In sum, this study showed improvement in clinical, angiographic, and hemodynamic states after combined revascularization surgery in moyamoya disease. However, there is no comparative arm. And thus further study will most definitely be needed to best define the optimal surgical procedure in this patient population. See p 2983.Early Deterioration After Thrombolysis Plus Aspirin in Acute Stroke: A Post Hoc Analysis of the Antiplatelet Therapy in Combination With Recombinant t-PA Thrombolysis in Ischemic Stroke TrialAddition of aspirin within 90 minutes after intravenous thrombolysis (IVT) in acute ischemic stroke has previously been shown to increase the risk of symptomatic intracranial hemorrhage (SICH) while having no effect on 3-month functional outcome in the Antiplatelet Therapy in Combination With Recombinant t-PA Thrombolysis in Ischemic Stroke (ARTIS) trial. The authors explored a post hoc analysis on the effect of aspirin on early neurological deterioration (END). END was defined as ≥4 points on the National Institutes of Health Stroke Scale worsening <24 hours after IVT and further divided into SICH and cerebral ischemia. A total of 31 of 640 patients (4.8%) receiving early aspirin after IVT experienced END: 14 because of SICH and 17 because of cerebral ischemia. On univariate analysis, aspirin increased the risk of END because of SICH but not of END because of cerebral ischemia. After multivariate analysis, aspirin remained significantly associated with END because of SICH. In summary, this post hoc analysis of the ARTIS trial shows that early aspirin after IVT is associated with early neurological deterioration because of symptomatic intracranial hemorrhage and has no beneficial effect on early neurological deterioration because of cerebral ischemia. Although the available literature suggests that early aspirin after IVT in acute ischemic stroke is harmful, further study is needed as there may potentially be certain subgroups of patients with stroke who may benefit from its use. See p 3080. Previous Back to top Next FiguresReferencesRelatedDetails October 2014Vol 45, Issue 10 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.114.007187 Originally publishedOctober 1, 2014 PDF download Advertisement

Chronic kidney disease and bleeding complications after intravenous thrombolytic therapy for acute ischemic stroke.

The safety of intravenous thrombolysis in ischemic stroke (IS) patients with chronic kidney disease (CKD) is uncertain. We assessed whether CKD is associated with bleeding complications after intravenous tissue-type plasminogen activator administration to patients with IS. Data were analyzed from 44 410 patients with IS treated with intravenous tissue-type plasminogen activator in the Get With The Guidelines-Stroke Program. Glomerular filtration rate based on admission serum creatinine was categorized as dichotomous (presence of CKD as <60) or as distinct categories: normal (≥90), mild (≥60-<90), moderate (≥30-< 60), severe (≥15-<30), and kidney failure (<15 or dialysis). Primary outcomes evaluated were symptomatic intracranial hemorrhage and serious systemic hemorrhage; secondary outcomes were in-hospital mortality, independent functional status. There were 15 191 of 44 410 (34%) intravenous tissue-type plasminogen activator-treated IS patients with CKD. Presence of CKD (versus no CKD) was not associated with risk-adjusted symptomatic intracranial hemorrhage (adjusted odds ratio, 1.0; 95% confidence interval: 0.91-1.10) or serious systemic hemorrhage (adjusted odds ratio, 0.97; 95% confidence interval: 0.80-1.18) and did not significantly vary by kidney dysfunction stage for either of these primary end points in multivariable analyses. Compared with patients with normal kidney function, those with CKD were more likely to die in the hospital (adjusted odds ratio, 1.22; 95% confidence interval: 1.14-1.32) and have an unfavorable discharge functional status (adjusted odds ratio, 1.13; 95% CI: 1.07-1.19). Presence of CKD among patients with IS treated with intravenous tissue-type plasminogen activator is associated with higher unadjusted odds of symptomatic intracranial hemorrhage or serious systemic hemorrhage, but this is explained by non-CKD related factors.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Dabigatran: patient management in specific clinical settings.

SummaryDabigatran, a direct thrombin inhibitor, is licensed for the prevention of venous thromboembolism after knee and hip replacement, the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for the treatment of acute venous thromboembolism. As dabigatran has a favourable benefit–risk profile, it is being increasingly used. Dabigatran differs from vitamin K antagonists as regards its pharmacological characteristics and its impact on certain laboratory tests, and also in the lack of a direct antagonist that can reverse dabigatran-induced anticoagulation. In emergency settings such as acute bleeding, emergency surgery, acute coronary syndrome, thrombolysis for ischaemic stroke or overdosing, specific strategies are required. A working group of experts from various disciplines has developed strategies for the management of dabigatran-treated patients in emergency settings.

Early deterioration after thrombolysis plus aspirin in acute stroke: a post hoc analysis of the Antiplatelet Therapy in Combination with Recombinant t-PA Thrombolysis in Ischemic Stroke trial.

Aspirin early after intravenous thrombolysis in acute ischemic stroke increases the risk of symptomatic intracranial hemorrhage (SICH), without influencing functional outcome at 3 months. The effect of aspirin on early neurological deterioration (END) was explored as a post hoc analysis of the randomized Antiplatelet Therapy in Combination With Recombinant t-PA Thrombolysis in Ischemic Stroke (ARTIS) trial. END, defined as a ≥4 points National Institutes of Health Stroke Scale worsening ≤24 hours after intravenous thrombolysis, was categorized into SICH (ENDSICH) and cerebral ischemia (ENDCI). Multinomial logistic regression was used to assess the effect of aspirin on END. Of the 640 patients, 31 patients (4.8%) experienced END (14 ENDSICH, 17 ENDCI). Aspirin increased the risk of ENDSICH (odds ratio, 3.73; 95% confidence interval, 1.03-13.49) but not of ENDCI (odds ratio, 1.14; 95% confidence interval, 0.44-3.00). After adjustment for other explanatory variables, the association between aspirin and ENDSICH remained significant. In this trial, there is no evidence of an early antithrombotic effect from the addition of aspirin to intravenous thrombolysis in acute ischemic stroke.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Dramatic recovery after IV thrombolysis in anterior circulation ischemic stroke: Predictive factors and prognosis

Background and purposeDramatic recovery (DR) after thrombolysis is dependent of vessel recanalization and is predictive of favorable clinical outcome. Successful recanalization is not equivalent to DR. Our objective was to assess its frequency and evaluate clinical and biochemical predictors and their prognosis. MethodsWe analyzed prospectively registered data from January 2007 to September 2012. All patients with anterior circulation stroke and NIHSS≥10 were included. Improvement of ≥10 or a score ≤3 24h after thrombolysis was defined as DR. ResultsIn the 230 patients included, DR frequency was 23% (53 patients). DR group had lower admission NIHSS (14 vs 17, p=0.024), less total anterior circulation infarcts (p=0.009), more partial anterior circulation infarcts (p=0.003) and lower blood glucose on admission (118 vs 128mg/dL, p=0.013). All patients with DR had an Alberta Stroke Program Early CT Score (ASPECTS) ≥7, vs 89.3% without DR (p=0.013). Arterial recanalization, defined as hyperdense middle cerebral artery sign disappearance on control CT, was more frequent in the DR group (68.4% vs 14.1%, p<0.001). Intracranial hemorrhage on 24h-control CT scan was less frequent in the DR group (p<0.001). Multinomial logistic regression analysis showed that ASPECTS score was an independent predictor of DR (OR=2.35, 95%CI=1.32–4.16, p=0.003) and CT evidence of recanalization was independently associated with DR (OR=11.60, 95%CI, 3.02–44.53, p<0.001). ConclusionDR is a frequent occurrence. ASPECTS score is an independent predictor of DR, which is also independently associated with CT evidence of middle cerebral artery recanalization.

Thrombolysis in experimental cerebral amyloid angiopathy and the risk of secondary intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most adverse event of thrombolysis in ischemic stroke. Cerebral amyloid angiopathy increases the risk for spontaneous lobar ICH. Although thrombolysis may be performed in cerebral amyloid angiopathy-affected patients, there is still little knowledge available on the risk for secondary ICH. We investigated the effect of recombinant tissue-type plasminogen activator on experimental ischemic stroke in APP23 transgenic mice (n=18) and wild-type littermates (n=15). Focal ischemic stroke was induced in 26-month-old mice by temporal middle cerebral artery occlusion (filament model), followed by treatment with 10 mg/kg recombinant tissue-type plasminogen activator. Twenty-four hours later, a functional score was assessed and the mice were euthanized for histological analysis. ICH was classified as grades 1 to 3 depending on severity. The groups did not differ regarding mortality (P=0.67) and functional deficit (P=0.18). Compared with wild-type mice, the APP23 genotype was associated with a higher appearance for ICH in the infarct area (P=0.05). ICH severity grades 2 and 3 correlated significantly with infarct size (P=0.004 and 0.008, respectively). The APP23 genotype was not associated with increased mortality or worse functional outcome. Our results suggest an increased risk for ICH in the cerebral amyloid angiopathy-affected brain; however, no ICH was observed outside the ischemic area.

Plasmin-dependent modulation of the blood-brain barrier: a major consideration during tPA-induced thrombolysis?

Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood-brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process.

Stroke type differentiation using spectrally constrained multifrequency EIT: evaluation of feasibility in a realistic head model

We investigate the application of multifrequency electrical impedance tomography (MFEIT) to imaging the brain in stroke patients. The use of MFEIT could enable early diagnosis and thrombolysis of ischaemic stroke, and therefore improve the outcome of treatment. Recent advances in the imaging methodology suggest that the use of spectral constraints could allow for the reconstruction of a one-shot image. We performed a simulation study to investigate the feasibility of imaging stroke in a head model with realistic conductivities. We introduced increasing levels of modelling errors to test the robustness of the method to the most common sources of artefact. We considered the case of errors in the electrode placement, spectral constraints, and contact impedance. The results indicate that errors in the position and shape of the electrodes can affect image quality, although our imaging method was successful in identifying tissues with sufficiently distinct spectra.

Determine The Gender Differences In Outcome Following Thrombolysis In Ischemic Stroke. (P3.108)

Determine The Gender Differences In Outcome Following Thrombolysis In Ischemic Stroke. (P3.108)

Intravenous Thrombolysis and Risk Factors for Ischemic Stroke

Thrombolysis is one of the proven potential treatments for the management of acute ischemic stroke. Intravenous recombinant tissue-plasminogen activator (rt-PA) is the only medically approved biological thrombolysing agent for the treatment of acute ischemic stroke within 4.5h of stroke (2.2% symptomatic intracerebral haemorrhage, 12.7% mortality and 58.0% functional independence), but following the guideline and criteria provided by National Institute of Neurological Disorder and Stroke (NINDS) and SITS (Safe Implementation of Thrombolysis in Stroke) studies. Nepal needs to evidently introduce intravenous rt-PA in its clinical setting for treatment of acute ischemic stroke, which has been approved for more than a decade ago in developed countries. Several modifiable and non-modifiable risk factors can affect the outcomes of the treatment with intravenous rt-PA. Early modification of factors predicting the risk outcomes can be a beneficial tool to justify the thrombolytic treatment. This review aims to discuss the major studies on thrombolysis using rt-PA and main factors that can affect the outcomes of treatment in ischemic stroke.

TOF-MRA is reliable to evaluate the degree of MCA obstruction in acute stroke: an inter- and intra- observer study

Introduction: Artery recanalization is one of the best predictors of good clinical outcome after acute ischemic stroke thrombolysis and it could be used as a surrogate marker for outcome if it can be graded reliably. The purpose of this study was to analyze the inter- and intra-observer reliability of the degree of MCA obstruction on TOF-MRA. Methods: 91 patients with a MCA stroke were prospectively included in a multicenter study. They underwent MRI including a TOF-MRA within the first 12 hours after symptoms onset. Two blinded observers quantified the degree of MCA obstruction on TOF-MRA according to a modified TIMI grading system. To assess intra-observer reliability, evaluations by the same investigators were repeated 15 days apart. Dichotomized (TIMI 0-1 versus 2-3) and ordinal TIMI score analyses were performed. Inter- and intra-observer reliability was categorized from poor to excellent based on kappa values. Results: The mean delay between symptom onset and MRI was 6.3 ± 3.3 hours. Analysis of TOF-MRA was impossible in 2.6 % for M1 segment and 6.9% for M2 segment due to technical limitations. The inter- and intra-observer reliability was good to excellent for the dichotomized TIMI score (kappa ranging from 0.77 to 0.91) as well as for the ordinal TIMI score (kappa ranging from 0.82 to 0.96). Conclusion: The substantial reproducibility of the dichotomized and the ordinal TIMI grading system makes the TOF-MRA sequence a reliable tool to evaluate the degree of MCA obstruction and thus recanalization in clinical practice as well as in clinical research.

Intravenous thrombolysis in acute ischemic stroke due to occlusion of internal carotid artery – A Serbian Experience with Thrombolysis in Ischemic Stroke (SETIS)

ObjectiveThe benefit of intravenous thrombolysis in patients with internal carotid artery (ICA) occlusion is still unclear. The aim of this study was to assess the influence on outcome of intravenous thrombolysis in patients with ICA occlusion comparing to those without it. MethodsData were from the national register of all acute ischemic stroke patients treated with intravenous thrombolysis in Serbia. Patients with nonlacunar anterior circulation infarction were included and were divided into two groups, those with and those without ICA occlusion. We compared the differences in demographic characteristics, risk factors, baseline NIHSS score, early neurological improvement, 3-month functional outcome, complications and death between these two groups. ResultsAmong 521 included patients there were 13.4% with ICA occlusion. Group with ICA occlusion had more males (82.9% vs. 60.5%; p=0.0008), and more severe stroke (baseline NIHSS score 15.3 vs. 13.6; p=0.004). Excellent functional outcome (mRS 0–1) at 3 months was recorded in 32.9% patients with ICA occlusion and in 50.6% patients without (p=0.009), while favorable functional outcome (mRS 0–2) was recorded in 50.0% of patients with ICA occlusion vs. 60.1% without (p=0.14). Death occurred in 12.9% patients with ICA occlusion and in 17.3% patients without it (p=0.40). There was no significant difference in rate of symptomatic ICH between the two groups (1.4% vs. 4.2%; p=0.5). Multivariate logistic regression analysis showed that ICA occlusion was associated with the absence of early neurological improvement (p=0.03; OR 1.78, 95% CI 1.05–3.04). However, the presence of ICA occlusion was not significantly associated with an unfavorable outcome at 3-month (p=0.44; OR 1.24, 95% CI 0.72–2.16) or with death (p=0.18; OR 0.57, 95% CI 0.25–1.29). ConclusionThe patients with ICA occlusion treated with intravenous thrombolysis have a worse outcome than patients without it.

Common Questions in Anticoagulation Management in Atrial Fibrillation.

The limitations of the vitamin K antagonists (VKAs) have promoted the development of novel oral anticoagulants (NOACs) to benefit patients with poor predicted anticoagulation control. To assess the probability of good or poor anticoagulation control with VKAs, the SAMe-TT2R2 score has been developed. Trials of stroke prevention have shown a significant reduction in hemorrhagic stroke and intracranial bleeding with the NOACs. Clinicians need to be prepared to manage bleeding complications and patients requiring urgent surgery, systemic thrombolysis for ischemic stroke, or ST elevation myocardial infarction. This article addresses some of these management issues.

Role of Preexisting Disability in Patients Treated With Intravenous Thrombolysis for Ischemic Stroke

Little is known about the effect of thrombolysis in patients with preexisting disability. Our aim was to evaluate the impact of different levels of prestroke disability on patients' profile and outcome after intravenous thrombolysis. We analyzed the data of all stroke patients admitted between October 2003 and December 2011 that were contributed to the Safe Implementation of Treatments in Stroke-Eastern Europe (SITS-EAST) registry. Patients with no prestroke disability at all (modified Rankin Scale [mRS] score, 0) were used as a reference in multivariable logistic regression. Of 7250 patients, 5995 (82%) had prestroke mRS 0, 791 (11%) had prestroke mRS 1, 293 (4%) had prestroke mRS 2, and 171 (2%) had prestroke mRS≥3. Compared with patients with mRS 0, all other groups were older, had more comorbidities, and more severe neurological deficit on admission. There was no clear association between preexisting disability and the risk of symptomatic intracranial hemorrhage. Prestroke mRS 1, 2, and ≥3 were associated with increased risk of death at 3 months (odds ratio, 1.3, 2.0, and 2.6, respectively) and lower chance of achieving favorable outcome (achieving mRS 0-2 or returning to the prestroke mRS; 0.80, 0.41, 0.59, respectively). Patients with mRS≥3 and 2 had similar vascular profile and favorable outcome (34% versus 29%), despite higher mortality (48% versus 39%). Prestroke disability does not seem to independently increase the risk of symptomatic intracranial hemorrhage after thrombolysis. Despite higher mortality, 1 in 3 previously disabled patients may return to his/her prestroke mRS. Therefore, they should not be routinely excluded from thrombolytic therapy.

Abstract W P65: Determinants of Favourable Response to Thrombolysis in Wake-Up Ischaemic Stroke

Background and Purpose: Wake up Ischaemic Stroke (WUIS) patients may have the potential to benefit from thrombolysis. As the duration between stroke onset and treatment, the main determinant of response to thrombolysis, is unknown in these patients, a major consideration is to identify other clinical markers predictive of a favourable response. Methods: Subjects were selected by consecutive sampling of a prospective register a tertiary stroke centre between January 2009 and December 2010. The inclusion criteria were last seen normal &lt;12 hours but &gt;4.5 hours from symptom onset and met thrombolysis criteria apart from time. Data on baseline clinical characteristics, imaging and treatment were extracted from the register. Mortality and modified Rankin Scale (mRS) were assessed at 90 days. Symptomatic intracerebral haemorrhage (sICH) was assessed at 24 hours. Logistic regression was undertaken to identify independent determinants of these outcomes, and those significant at p&lt;0.1 were stratified and assessed using Peto’s fixed odds ratio for thrombolysis versus no thrombolysis. Results: Of the 122 WUIS patients fulfilling inclusion criteria 68 were thrombolysed and 54 (44%) were not thrombolysed. There were no differences in the baseline characteristics between the two groups. Logistic regression showed an independent relationship of age and NIHSS score with 90 day mortality and mRS 0-2 (p&lt;0.01 for all) and with stroke subtype (p&lt;0.1). There were no independent predictors of sICH. Thrombolysis had the best outcomes in WUIS patients aged 80-89 years with cardio-embolic stroke and NIHSS scores of 10-19 (Fig 1). Conclusions: Older WUIS patients and those with embolic stroke appear to benefit most from thrombolysis.