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Background and Purpose: Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large-artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy., Methods: All patients in the Bernese stroke registry (2008-2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively., Results: A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip-and-ship patients compared with mother-ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT (P = 0.046)., Conclusions: Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone., (© 2017 EAN.)

Background and Purpose: Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear., Methods: We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2., Results: From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group., Conclusions: In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted., (© 2016 American Heart Association, Inc.)

Background and Purpose: Lesion volume on diffusion-weighted magnetic resonance imaging (DWI) before acute stroke therapy is a predictor of outcome. Therefore, patients with large volumes are often excluded from therapy. The aim of this study was to analyze the impact of endovascular treatment in patients with large DWI lesion volumes (>70 mL)., Methods: Three hundred seventy-two patients with middle cerebral or internal carotid artery occlusions examined with magnetic resonance imaging before treatment since 2004 were included. Baseline data and 3 months outcome were recorded prospectively. DWI lesion volumes were measured semiautomatically., Results: One hundred five patients had lesions >70 mL. Overall, the volume of DWI lesions was an independent predictor of unfavorable outcome, survival, and symptomatic intracerebral hemorrhage (P<0.001 each). In patients with DWI lesions >70 mL, 11 of 31 (35.5%) reached favorable outcome (modified Rankin scale score, 0-2) after thrombolysis in cerebral infarction 2b-3 reperfusion in contrast to 3 of 35 (8.6%) after thrombolysis in cerebral infarction 0-2a reperfusion (P=0.014). Reperfusion success, patient age, and DWI lesion volume were independent predictors of outcome in patients with DWI lesions >70 mL. Thirteen of 66 (19.7%) patients with lesions >70 mL had symptomatic intracerebral hemorrhage with a trend for reduced risk with avoidance of thrombolytic agents., Conclusions: There was a growing risk for poor outcome and symptomatic intracerebral hemorrhage with increasing pretreatment DWI lesion volumes. Nevertheless, favorable outcome was achieved in every third patient with DWI lesions >70 mL after successful endovascular reperfusion, whereas after poor or failed reperfusion, outcome was favorable in only every 12th patient. Therefore, endovascular treatment might be considered in patients with large DWI lesions, especially in younger patients., (© 2015 American Heart Association, Inc.)

Background and Purpose: The use of thrombolysis in patients with minor neurological deficits and large vessel occlusion is controversial., Methods: We compared the outcome of patients with low National Institutes of Health Stroke Scale (NIHSS) scores and large vessel occlusions between thrombolysed and non-thrombolysed patients., Results: 88 (1.7%) of 5312 consecutive patients with acute (within 24 h) ischaemic stroke had occlusions of the internal carotid or the main stem of the middle cerebral artery and baseline NIHSS scores ≤5.47 (53.4%) were treated without thrombolysis, and 41 (46.6%) received intravenous thrombolysis, endovascular therapy or both. Successful recanalisation on MR or CT angiography at 24 h was more often observed in thrombolysed than in non-thrombolysed patients (78.9% versus 10.5%; p<0.001). Neurological deterioration (increase of NIHSS score ≥1 compared to baseline) was observed in 22.7% of non-thrombolysed versus 10.3% of thrombolysed after 24 h (p=0.002), in 33.3% versus 12.5% at hospital discharge (p=0.015) and in 41.4% versus 15% at 3 months (p<0.001). Symptomatic intracerebral haemorrhage occurred in two (asymptomatic in five) thrombolysed and in none (asymptomatic in three) non-thrombolysed. Thrombolysis was an independent predictor of favourable outcome (p=0.030) but not survival (p=0.606) at 3 months., Conclusions: Non-thrombolysed patients with mild deficits and large vessel occlusion deteriorated significantly more often within 3 months than thrombolysed patients. Symptomatic intracerebral haemorrhages occurred in less than 5% of patients in both groups. These data suggest that thrombolysis is safe and effective in these patients. Therefore, randomised trials in patients with large vessel occlusions and mild or rapidly improving symptoms are needed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy., Methods: Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy., Results: Two-hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions., Conclusions: Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions., (© 2015 S. Karger AG, Basel.)

Background: Stroke patients with diabetes and admission hyperglycaemia have worse outcomes than non-diabetics, with or without intravenous thrombolysis. Poor vessel recanalization was reported in diabetics treated with intravenous thrombolysis., Aims: This study aimed to determine the impact of admission glucose and diabetes on recanalization and outcome after intra-arterial thrombolysis., Methods: We analysed 389 patients (213 men, 176 women) treated with intra-arterial thrombolysis. The association of diabetes and admission glucose value with recanalization, outcome, mortality, and symptomatic intracranial haemorrhage was determined. Recanalization was classified according to thrombolysis in myocardial infarction grades. Outcome was measured using the modified Rankin Scale at three-months and categorized as favourable (modified Rankin Scale 0-2) or poor (modified Rankin Scale 3-6)., Results: The rate of partial or complete recanalization (thrombolysis in myocardial infarction 2-3) did not differ between patients with and without diabetes (67% vs. 66%; P = 1·000). Mean admission glucose values were similar in patients with poor recanalization (thrombolysis in myocardial infarction 0-1) and patients with partial or complete recanalization (thrombolysis in myocardial infarction 2-3; 7·3 vs. 7·3 mmol/l; P = 0·746). Follow-up at three-months was obtained in 388 of 389 patients. Clinical outcome was favourable (modified Rankin Scale 0-2) in 189 patients (49%) and poor (modified Rankin Scale 3-6) in 199 patients (51%). Mortality at three-months was 20%. Diabetics were more likely to have poor outcome (72% vs. 48%; P = 0·001) and to be dead (30% vs. 19%; P = 0·044) at three-months. After multivariable analysis, there remained an independent relationship between diabetes and outcome (P = 0·003; odds ratio 3·033, 95% confidence interval 1·452-6·336), but not with mortality (P = 0·310; odds ratio 1·436; 95% confidence interval 0·714-2·888). Moreover, higher age (P = 0·001; odds ratio 1·039; 95% confidence interval 1·017-1·061), higher baseline National Institutes of Health Stroke Scale score (P < 0·0001; odds ratio 1·130; 95% confidence interval 1·079-1·182), location of vessel occlusion as categorical variable (P < 0·0001), poor collaterals (P = 0·02; odds ratio 1·587; 95% confidence interval 1·076-2·341), poor vessel recanalization (P < 0·0001; odds ratio 4·713; 95% confidence interval 2·627-8·454), and higher leucocyte count (P = 0·032; odds ratio 1·094; 95% confidence interval 1·008-1·188) were independent baseline predictors of poor outcome. Higher admission glucose was associated with poor outcome (P = 0·006) and mortality (P < 0·0001). After multivariate analyses, glucose remained independently associated with poor outcome (P = 0·019; odds ratio 1·150; 95% confidence interval 1·023-1-292) and mortality (P = 0·005; odds ratio 1·183; 95% confidence interval 1052-1·331). The rate of symptomatic intracranial haemorrhage was similar in diabetics and non-diabetics (6·7% vs. 4·6%; P = 0·512). Mean admission glucose was higher in patients with symptomatic intracranial haemorrhage than without (8·58 vs. 7·26 mmol/l; P = 0·010). Multivariable analysis confirmed an independent association between admission glucose and symptomatic intracranial haemorrhage (P = 0·027; odds ratio 1·187; 95% confidence interval 1·020-1·381)., Conclusions: Diabetes and glucose value on admission did not influence recanalization after intra-arterial thrombolysis; nevertheless, they were independent predictors of poor outcome after intra-arterial thrombolysis and a higher admission glucose value was an independent predictor of symptomatic intracranial haemorrhage. This indicates that factors on the capillary, cellular, or metabolic level may account for the worse outcome in patients with elevated glucose value and diabetes., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Background and Purpose: Patients with prior stroke within 3 months have been mostly excluded from randomized thrombolysis trials mainly because of the fear of an increased rate of symptomatic intracerebral hemorrhage (sICH). The aim of this study was to compare baseline characteristics and clinical outcome of thrombolyzed patients who had a previous stroke within the last 3 months with those not fulfilling this criterion (comparison group)., Methods: In all, 1217 patients were included in our analysis (42.2% women, mean age 68.8 ± 14.4 years)., Results: Patients with previous stroke within the last 3 months (17/1.4%) had more often a basilar artery occlusion (41.2% vs. 10.8%) and less frequently a modified Rankin scale (mRS) score 0-1 prior to index stroke (88.2% vs. 97.3%) and a higher mean time lapse from symptom onset to thrombolysis (321 min vs. 262 min) than those in the comparison group. Stroke severity was not different between the two groups. Rates of sICH were 11.8% vs. 6%. None of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. At 3 months, favorable outcome (mRS ≤ 2) in patients with previous stroke within 3 months was 29.4% (vs. 48.9%) and mortality 41.2% (vs. 22.7%)., Conclusions: In patients with prior stroke within the last 3 months, none of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. The high mortality was influenced by four patients, who died until discharge due to acute major index stroke. It is reasonable to include these patients in randomized clinical trials and registries to assess further their thrombolysis benefit-risk ratio., (© 2014 The Author(s) European Journal of Neurology © 2014 EAN.)

Background and Purpose: The question whether cerebral microbleeds (CMBs) visible on MRI in acute stroke increase the risk for intracerebral hemorrhages (ICHs) or worse outcome after thrombolysis is unresolved. The aim of this study was to analyze the impact of CMB detected with pretreatment susceptibility-weighted MRI on ICH occurrence and outcome., Methods: From 2010 to 2013 we treated 724 patients with intravenous thrombolysis, endovascular therapy, or intravenous thrombolysis followed by endovascular therapy. A total of 392 of the 724 patients were examined with susceptibility-weighted MRI before treatment. CMBs were rated retrospectively. Multivariable regression analysis was used to determine the impact of CMB on ICH and outcome., Results: Of 392 patients, 174 were treated with intravenous thrombolysis, 150 with endovascular therapy, and 68 with intravenous thrombolysis followed by endovascular therapy. CMBs were detected in 79 (20.2%) patients. Symptomatic ICH occurred in 21 (5.4%) and asymptomatic in 75 (19.1%) patients, thereof 61 (15.6%) bleedings within and 35 (8.9%) outside the infarct. Neither the existence of CMB, their burden, predominant location nor their presumed pathogenesis influenced the risk for symptomatic or asymptomatic ICH. A higher CMB burden marginally increased the risk for ICH outside the infarct (P=0.048; odds ratio, 1.004; 95% confidence interval, 1.000-1.008)., Conclusions: CMB detected on pretreatment susceptibility-weighted MRI did not increase the risk for ICH or worsen outcome, even when CMB burden, predominant location, or presumed pathogenesis was considered. There was only a small increased risk for ICH outside the infarct with increasing CMB burden that does not advise against thrombolysis in such patients., (© 2014 American Heart Association, Inc.)

Systemic thrombolysis with alteplase is the only approved medical treatment for patients with acute ischaemic stroke. Thrombectomy is also increasingly used to treat proximal occlusions of the cerebral arteries, but has not shown superiority over systemic thrombolysis with alteplase. Many patients with acute ischaemic stroke are pretreated with antiplatelet or anticoagulant drugs, which can increase the bleeding risk of thrombolysis or thrombectomy. Pretreatment with aspirin monotherapy increases the bleeding risk of alteplase in both observational and randomised trials with no effect on clinical outcome, and the risk of intracerebral haemorrhage is increased with the combination of aspirin and clopidogrel. Antiplatelet drugs should not be given in the first 24 h after alteplase treatment. Data from pooled randomised trials and a large observational study show that thrombolysis can probably be done safely in patients given vitamin-K antagonists if the international normalised ratio is less than 1·7, although bleeding risk is slightly raised. Almost no data are available for the safety of alteplase in patients with atrial fibrillation who have been given novel oral anticoagulants (NOAC) for stroke prevention. Some coagulation parameters could help to identify patients treated with NOAC who might be eligible for thrombolysis. Thrombectomy can be done in patients given antiplatelets and probably in those given anticoagulants; however, conclusions about anticoagulants are based on findings from observational studies with small patient numbers., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Purpose: Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest., Methods: From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra-arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively., Results: There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA-T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2-3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2-3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91 = 86% and 64/78 = 82%) compared with pharmacological thrombolysis only (15/32 = 47%; P < 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3-month outcome was favourable [modified Rankin score (mRS) 0-2] in 54/28% patients and moderate (mRS 0-3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA-T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (P = 0.001). In multivariate analysis age [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93-0.98], NIHSS on admission (OR = 0.9, 95% CI = 0.83-0.98) and functional ICA-T occlusion (OR = 0.35, 95% CI = 0.16-0.77) were non-modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (OR = 9.30, 95% CI = 2.03-42.63)., Conclusions: The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Background and Purpose: Intra-arterial treatment (IAT) is effective when performed within 6 h of symptom onset in selected stroke patients ('T < 6H'). Its safety and efficacy is unclear when the patient has had symptoms for more than 6 h ('T > 6H') or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups., Methods: Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0-2] or mortality 3 months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage., Results: Six-hundred and fifty-four patients were treated before (T < 6H) and 205 after 6 h or an unknown time (128 T > 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in T < 6H patients, vertebrobasilar occlusion was more common in T > 6H and UOS patients, and middle cerebral artery occlusions less common in T > 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis., Conclusions: Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6 h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

The aim of the study was to assess the influence of white matter lesions in patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). From September 2003 to January 2010, we treated 400 patients with IAT at our institution. Of these patients, 292 were evaluated with MRI scans and included in this observational study. Clinical data were collected prospectively. Outcome after 3 months was measured with the modified Rankin Scale (mRS); mRS 0-1 was considered as favorable outcome. White matter lesions were scored visually by two observers using the semiquantitative Scheltens and Fazekas scores. Logistic regression analysis was used to identify the association of white matter lesions and clinical outcome, recanalization, and cerebral hemorrhage. The severity of white matter lesions was inversely correlated with favorable outcome, survival and successful recanalization. White matter lesions were an independent predictor of outcome (OR 0.569, p = 0.007) and survival (OR 0.550, p = 0.018) and a weak but independent predictor for recanalization (OR 0.949, p = 0.038). Asymptomatic intracerebral bleeding after IAT was associated with white matter lesions in the basal ganglia in the univariate analysis (p = 0.036), but not after multivariable analysis. The severity of white matter lesions independently predicts clinical outcome and survival in patients treated with IAT. White matter lesions are also a weak but independent predictor for recanalization. Symptomatic intracranial bleeding after IAT are not associated with white matter lesions. Therefore, white matter lesions should not be considered as a contraindication against IAT.

Background and Purpose: Thrombolysis improves outcome of patients with acute ischemic stroke, but it is unknown whether thrombolysis has a measurable effect on long-term outcome in a defined population., Methods: We prospectively assessed demographic data, management, and outcome of acute ischemic stroke patients admitted within 48 hours to 18 primary care hospitals of the canton of Bern (969 299 inhabitants) during 12 months. Blinded follow-up was obtained at 3 and 12 months. Predictors of mortality and favorable outcome (modified Rankin Scale score ≤2) at 3 and 12 months using logistic regression were analyzed., Results: From December 2007 to December 2008, 807 patients (mean age, 72 years) were included. Median National Institutes of Health Stroke Scale score on admission was 5; 107 patients (13%) received intravenous, intra-arterial, or mechanical thrombolysis. Estimated cumulative mortality at 3 months was 20.6% and at 12 months 27.4%. Age 75 years or older, higher National Institutes of Health Stroke Scale scores, and higher Charlson comorbidity index were independent predictors of mortality at 3 and 12 months. Estimated favorable outcome at 3 months was 48.2% and at 12 months was 44.6%. Thrombolysis was the only modifiable independent predictor of favorable outcome at 3 (relative risk, 1.49; 95% CI, 1.18-1.89) and 12 months (relative risk, 1.59; 95% CI, 1.24-2.04), whereas age younger than 75 years, male gender, National Institutes of Health Stroke Scale score <4, and lower Charlson comorbidity index were nonmodifiable predictors., Conclusions: Thirteen percent of acute ischemic stroke patients admitted within 48 hours to Bernese hospitals underwent thrombolysis, which exerted a measurable effect on 3-month outcome in this population. This effect was sustained at 12 months. Age, stroke severity, Charlson comorbidity index, and male gender were independent nonmodifiable predictors of outcome.

Background and Purpose: Endovascular therapy of acute ischemic stroke has been shown to be beneficial for selected patients. The purpose of this study is to determine predictors of outcome in a large cohort of patients treated with intra-arterial thrombolysis, mechanical revascularization techniques, or both., Methods: We prospectively acquired data for 623 patients with acute cerebral infarcts in the carotid artery territory who received endovascular treatment at a single center. Logistic regression analysis was performed to determine predictors of outcome., Results: Median National Institutes of Health Stroke Scale (NIHSS) at admission was 15. Partial or complete recanalization was achieved in 70.3% of patients; it was independently associated with hypercholesterolemia (P=0.02), absence of coronary artery disease (P=0.023), and more proximal occlusion site (P<0.0001). After 3 months, 80.5% of patients had survived, and 48.9% of patients reached favorable outcome (modified Rankin scale score 0-2). Good collaterals (P<0.0001), recanalization (P=0.023), hypercholesterolemia (P=0.03), lower NIHSS at admission (P=0.001), and younger age (P<0.0001) were independent predictors for survival. More peripheral occlusion site (P<0.0001), recanalization (P<0.0001), hypercholesterolemia (P=0.002), good collaterals (P=0.002), lower NIHSS (P<0.0001), younger age (P<0.0001), absence of diabetes (P=0.002), and no previous antithrombotic therapy (P=0.036) predicted favorable outcome. Time to treatment was only a predictor of outcome, when collaterals were excluded from the model. Symptomatic intracerebral hemorrhage occurred in 5.5% and was independently predicted by poor collaterals (P=0.004)., Conclusions: Several independent predictors for outcome and complications were identified. Unlike in intravenous thrombolysis trials, time to treatment was a predictor of outcome only when collaterals were excluded from the model, indicating the important role of collaterals for the time window.

Background: It is unclear whether octogenarians benefit from intra-arterial thrombolysis (IAT) for the treatment of acute ischemic stroke (AIS). The aim of the present study was to compare baseline characteristics, clinical outcome and complications of patients aged ≥80 with those of patients aged <80 years., Methods: Forty-three octogenarians and 524 younger patients with AIS were treated with IAT. The modified Rankin scale (mRS) score was used to assess 3-month outcome., Results: There was a female preponderance among octogenarians (63 vs. 37%, p = 0.015). Stroke severity, occlusion site, and time from stroke onset to IAT did not differ between the groups. Good recanalization (TIMI 2-3) was achieved in 65% of older and in 71% of younger patients (p = 0.449). Rates of symptomatic intracranial hemorrhage (ICH) were 6% in patients <80 years and 2% in octogenarians (p = 0.292). Favorable outcome (mRS 0-2) was less frequent among octogenarians (28 vs. 46%, p = 0.019), while mortality was higher (40 vs. 22%, p = 0.008). Octogenarians died more often from extracerebral complications than younger patients (59 vs. 27%, p = 0.008)., Conclusions: Compared with younger patients, octogenarians did not have a significantly increased risk of symptomatic ICH after IAT. Although favorable outcome was less frequent and mortality rates were higher, IAT appeared to be safe in octogenarians. It seems reasonable to include octogenarians in randomized clinical trials to assess the balance of risk and benefit of IAT in this patient group., (Copyright © 2011 S. Karger AG, Basel.)

Background and Purpose: Use of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke is restricted to patients with an international normalized ratio (INR) less than 1.7. However, a recent study showed increased risk of symptomatic intracranial hemorrhage after IV tPA use in patients with oral anticoagulants (OAC) even with an INR less than 1.7. The present study assessed the risk of symptomatic intracranial hemorrhage, clinical outcome, and mortality after intra-arterial therapy (IAT) in patients with and without previous use of OAC., Methods: Consecutive patients treated with IAT from December 1992 to October 2010 were included. Clinical outcome and mortality were assessed 90 days after stroke onset. Patients with and without previous use of OAC were compared., Results: Overall, 714 patients were treated with IAT. Twenty-eight patients (3.9%) were under OAC at time of symptom onset. Median INR in the OAC group was 1.79 (interquartile range [IQR], 1.41-2.3) and 1.01 (IQR, 1.0-1.09; P<0.0001) in the group without OAC. Patients treated with OAC at admission underwent more often mechanical-only IAT than did patients without OAC (46.4% versus 12.8%; P<0.0001). Comparing patients with and without previous use of OAC, we did not find any statistical difference in the rate of symptomatic intracranial hemorrhage (7.1% versus 6.0%; P=0.80), unfavorable outcome (modified Rankin Scale score, 3-6; 67.9% versus 50.9%; P=0.11), and mortality (17.9% versus 21.6%; P=0.58)., Conclusions: Previous use of OAC did not significantly increase the risk of symptomatic intracranial hemorrhage after IAT or the risk of unfavorable outcome and mortality 90 days after IAT.

Objectives: Data on decompressive craniectomy (DC) after intra-arterial thrombolysis (IAT) for treatment of malignant middle cerebral artery (MCA) stroke are lacking., Methods: The authors compared consecutive patients with middle cerebral artery (MCA) strokes who underwent decompressive craniectomy (DC) after IAT with DC patients without prior thrombolysis., Results: Thirty of 2395 consecutive patients with acute ischaemic stroke or transient ischaemic attack were treated with DC because of space-occupying oedema 12-72 h after symptom onset. Fifteen patients underwent intra-arterial thrombolysis (IAT) prior to DC. Baseline characteristics did not differ between thrombolysed and non-thrombolysed patients except for lower National Institute of Health Stroke Scale score in non-thrombolysed patients (median National Institute of Health Stroke Scale 17 vs. 14, p=0.033). The outcome at 3 months was favourable (modified Rankin scale 0-3) in seven (47%) thrombolysed patients and in four (27%) non-thrombolysed patients (p=0.45). Mortality and major complications after DC did not differ between the two groups (p>0.05). Older age (p=0.037) and previous hypertension (p=0.047) independently predicted unfavourable outcome in DC patients, but not IAT prior DC., Conclusions: There was no difference of outcome of patients with DC with or without prior IAT. DC after IAT did not cause any more complications than DC without prior thrombolysis.

Background and Purpose: Intra-arterial thrombolysis can be used for treatment of basilar artery occlusion. Predictors of outcome before initiation of treatment are of special interest., Methods: From 1992 to 2010, we treated 106 consecutive patients with basilar artery occlusion with intra-arterial thrombolysis. Baseline characteristics, treatment, clinical course, and 3-month and long-term outcomes (≥12 months) were assessed. Outcome parameters were vessel recanalization after treatment, complications, modified Rankin scale (mRS) score, and mortality after 3 months and in the long-term., Results: At 3 months, clinical outcome was good (mRS score, 0-2) in 33.0% of the patients and moderate (mRS score, 3) in 11.3%. Mortality was 40.6%. Partial or complete recanalization was achieved in 69.8% of the patients, and symptomatic intracranial hemorrhage occurred in 1 patient (0.9%). Between 3-month and long-term follow-up, 22 survivors (40.8%) showed clinical improvement of at least 1 point on the mRS score, 29 (53.7%) were functionally unchanged, and 3 (5.7%) showed functional worsening (P<0.0001). Multivariate analysis identified diabetes as a predictor of poor vessel recanalization (P=0.028). Low baseline National Institutes of Health Stroke Scale score was identified as a predictor of good or moderate clinical outcome (P<0.0001) and survival (P=0.001) at 3 months, and younger age was identified as an additional predictor of survival (P=0.012). For prediction of long-term clinical outcome, age was also an independent predictor (P=0.018)., Conclusions: In our series, intra-arterial thrombolysis as treatment of basilar artery occlusion was safe. National Institutes of Health Stroke Scale score at admission and age were identified as predictors of outcome, and these predictors should be considered for treatment allocation in future randomized trials.

Background: Intra-arterial thrombolysis (IAT) can improve clinical outcome in patients with acute basilar artery occlusion (BAO). The purpose of this study was to determine whether the severity of neurological symptoms, the extent of early ischemic damage on pretreatment diffusion-weighted MRI (DWI), and the lesion progression or regression on post-treatment MRI can predict functional outcome in patients with BAO treated with IAT., Methods: Thirty-six BAO patients (13 women, 23 men; mean age 60 years) treated with IAT within 12 h of symptom onset were studied. Early ischemic damage on DWI was assessed by applying 4 DWI scoring systems, including a proposed DWI score developed for this study. The latter was used for evaluation of lesion dynamics on post-treatment MRI. The association of pretreatment DWI, severity of symptoms (National Institutes of Health Stroke Scale, NIHSS, and Glasgow Coma Scale, GCS, scores), vessel recanalization, and lesion progression or regression after IAT with clinical outcome at 3 months was analyzed., Results: Median NIHSS and GCS scores on admission were 17 and 10, respectively. In univariate analysis, NIHSS and GCS scores (on admission) and all 4 DWI scores were significantly associated with clinical outcome. After regression analysis for each DWI score, the DWI score proposed herein was the only score that remained independently associated with clinical outcome at 3 months (p = 0.004). A decrease in DWI score was observed in 3 of 23 patients with post-IAT MRI. Successful recanalization was significantly associated with lesion regression (p = 0.044)., Conclusions: BAO patients with less extensive tissue damage on DWI and milder neurological deficits (lower NIHSS and higher GCS) have a better clinical outcome following IAT. The introduced DWI score reliably quantified the pretreatment ischemic damage and was an independent predictor of functional outcome. Lesion regression on DWI score after IAT was associated with vessel recanalization (p = 0.44), but had no impact on clinical outcome., (Copyright © 2011 S. Karger AG, Basel.)

Background: To date, there is limited data on intra-arterial thrombolysis (IAT) and intravenous thrombolysis (IVT) for isolated posterior cerebral artery (PCA) occlusion. We aimed to evaluate recanalization, outcome and quality of life in patients who undergo thrombolysis for isolated PCA occlusion., Methods: Analysis of 9 patients treated with IAT and 9 patients treated with IVT with short-term (3 months) outcome and long-term (median 23 months) outcome after IAT., Results: 9 of 546 patients treated with IAT (4 women and 5 men; median age 66 years) had isolated PCA occlusion. Median baseline National Institute of Health Stroke Scale (NIHSS) score on admission was 9. Eight patients presented with visual field defects and variable additional symptoms. One patient suffered bithalamic infarction. Median time to treatment was 5.8 h. Recanalization was complete in 2, partial in 2, minimal in 2, and not achieved in 3 patients. Recanalization tended to be better when the microcatheter was placed in or close to the thrombus. We observed no major complications, and 3 months outcome was favorable (modified Rankin Scale score 0-2) in 67% of the patients after IAT. During the same period, 9 patients with PCA occlusion were treated with IVT with 89% favorable clinical outcomes at 3 months. At long-term follow-up after IAT, neuropsychological domains were more severely impaired than other neurologic functions., Conclusion: IAT is a feasible treatment of isolated PCA strokes. Clinical outcome was favorable in the majority of patients after IAT and IVT. No major complications were observed. Further studies are needed to compare IAT and IVT for isolated PCA stroke., (Copyright © 2011 S. Karger AG, Basel.)

Background and Purpose: There are only limited data on whether prior statin use and/or cholesterol levels are associated with intracranial hemorrhage (ICH) and outcome after intra-arterial thrombolysis. The purpose of this study was to evaluate the association of statin pretreatment and cholesterol levels with the overall frequency of ICH, the frequency of symptomatic ICH, and clinical outcome at 3 months., Methods: We analyzed 311 consecutive patients (mean age, 63 years; 43% women) who received intra-arterial thrombolysis., Results: Statin pretreatment was present in 18%. The frequency of any ICH was 20.6% and of symptomatic ICH 4.8%. Patients with any ICH were more often taking statins (30% versus 15%, P=0.005), more often had atrial fibrillation (45% versus 30%, P=0.016), had more severe strokes (mean National Institute of Health Stroke Scale score 16.5 versus 14.7, P=0.022), and less often good collaterals (16% versus 24%, P=0.001). Patients with symptomatic ICH were more often taking statins (40% versus 15%, P=0.009) and had less often good collaterals (0% versus 24%, P<0.001). Any ICH or symptomatic ICH were not associated with cholesterol levels. After multivariate analysis, the frequency of any ICH remained independently associated with previous statin use (OR, 3.1; 95% CI, 1.53 to 6.39; P=0.004), atrial fibrillation (OR, 2.5; CI, 1.35 to 4.75; P=0.004), National Institutes of Health Stroke Scale score (OR, 1.1; CI, 1.00 to 1.10; P=0.037), and worse collaterals (OR, 1.7; CI, 1.19 to 2.42; P=0.004). There was no association of outcome with prior statin use, total cholesterol level, or low-density lipoprotein cholesterol level., Conclusions: Prior statin use, but not cholesterol levels on admission, is associated with a higher frequency of any ICH after intra-arterial thrombolysis without impact on outcome.

Intravenous thrombolysis (IVT) is the evidence-based treatment of acute ischemic stroke in the first 3 h after symptom onset (IVT 3-4.5 h: off-label use with informed consent of the patient). However, intra-arterial thrombolysis (IAT) results in higher recanalization rates of the middle cerebral artery compared to IVT. Therefore it seems reasonable to apply IAT in addition or instead of IVT up to 6 h after symptom onset.

Background and Purpose: No controlled, randomized trial has investigated whether intravenous, intra-arterial (IAT), or mechanical thrombolysis is beneficial in children with ischemic stroke. We report 2 children who underwent IAT for acute ischemic stroke and include them in a review about intravenous thrombolysis, IAT, and mechanical thrombolysis for childhood stroke., Methods: We searched in MEDLINE and EMBASE for studies that reported on treatment of childhood stroke with intravenous thrombolysis, IAT, or mechanical thrombolysis in the presence of occlusion of the basilar artery, sphenoidal, or insular middle cerebral artery. To be included in this review, the following findings had to be reported: (1) stroke severity at presentation; (2) cerebral imaging findings before thrombolysis; (3) time to treatment; (4) dose of the thrombolytic agent; (5) pre- and postinterventional angiographic findings in IAT; and (6) outcome assessed at hospital discharge or within 12 months after thrombolysis., Results: Adequate data were available in 17 children (including our 2 own cases) who underwent intravenous thrombolysis (n=6), IAT (n=10), or mechanical thrombolysis (n=1). No symptomatic intracranial hemorrhage occurred, but 2 asymptomatic intracranial hemorrhages were present. Sixteen children (94%) survived, and 12 (71%) had a good outcome (modified Rankin Scale score 0 or 1)., Conclusions: The available data about thrombolysis in pediatric stroke are limited. They suggest that this treatment may be beneficial in children with ischemic stroke. Controlled, randomized trials are needed to determine whether thrombolysis is useful in childhood stroke.

Acute ischemic stroke is a major cause of morbidity and mortality in industrialized nations. The sequel of stroke ranges from mild to severe disability and even death. Since the impairment may be permanent, the costs to society from work incapacity and the need for long-term care can be high. Additionally, the burden of suffering associated with the disease may have devastating effects on individuals and families. Following the occlusion of a cerebral vessel, the full extent of the infarction may not become clinically and radiologically apparent until days after. By then, the surrounding watershed zone, or penumbra, either survives or succumbs to necrosis over time. The natural history of this "tissue at risk" is determined by two factors: the collateralization from other vascular territories and the possible occurrence of spontaneous recanalization of the occluded vessel. The current treatment options for acute ischemic stroke are aiming at an early and sustained restoration of flow to the penumbra. The effect of the treatment is therefore time-dependent and the neurologic outcome is a function of the time span between onset of symptoms and recanalization therapy as well as of the recanalization rate associated with a specific treatment. This report summarizes the results of the major trials on catheter-based interventions, either using thrombolytic drugs or novel mechanical approaches being developed to treat patients with acute ischemic stroke.

Background and Purpose: For selected stroke patients, intra-arterial thrombolysis (IAT) has been shown to be an effective treatment option. However, knowledge of safety and efficacy of IAT in patients with acute stroke as a complication of arterial catheter interventions is limited., Methods: We analyzed clinical radiological findings and functional outcomes in consecutive patients 3 months after treatment with IAT for peri-procedural strokes occurring during neuroendovascular or cardiac catheter interventions. To measure outcome, the modified Rankin scale score was used., Results: Of a total of 432 patients treated with IAT, 12 (4 women and 8 men; mean age, 60 years) were treated because of an ischemic stroke after a neuro-endovascular procedure (n=6) or coronary angiography (n=6). The median baseline National Institutes of Health Stroke Scale score was 15. Recanalization was complete (thrombolysis in myocardial infarction grade 3) in 6, partial (thrombolysis in myocardial infarction 2) in 5, and minimal (thrombolysis in myocardial infarction 1) in 1. Nine patients (75%) had a favorable outcome (modified Rankin scale score, 0 to 2), and 3 had a poor outcome (modified Rankin scale score, 3 or 4). All patients with complete recanalization had a favorable outcome, whereas only 3 of 6 patients with partial or minimal recanalization (P=0.18) had a favorable outcome. Follow-up brain imaging was normal in 2 and showed new ischemic lesions in 10 patients. Two patients (17%) had a symptomatic intracerebral hemorrhage., Conclusions: In acute stroke attributable to arterial catheter interventions, IAT is feasible and has the potential to improve outcome in these patients. A high recanalization rate could be achieved.

Background and Purpose: It is unclear whether intraarterial (IAT) or intravenous (IVT) thrombolysis is more effective for ischemic stroke with hyperdense middle cerebral artery sign (HMCAS) on computed tomography (CT). The aim of this study was to compare IAT and IVT in stroke patients with HMCAS., Methods: Comparison of data from 2 stroke units with similar management of stroke associated with HMCAS, except that 1 unit performed IAT with urokinase and the other IVT with plasminogen activator. Time to treatment was up to 6 hours for IAT and up to 3 hours for IVT. Outcome was measured by mortality and the modified Rankin Scale (mRS), dichotomized at 3 months into favorable (mRS 0 to 2) and unfavorable (mRS 3 to 6)., Results: One hundred twelve patients exhibited a HMCAS, 55 of 268 patients treated with IAT and 57 of 249 patients who underwent IVT. Stroke severity at baseline and patient age were similar in both groups. Mean time to treatment was longer in the IAT group (244+/-63 minutes) than in the IVT group (156+/-21 minutes; P=0.0001). However, favorable outcome was more frequent after IAT (n=29, 53%) than after IVT (n=13, 23%; P=0.001), and mortality was lower after IAT (n=4, 7%) than after IVT (n=13, 23%; P=0.022). After multiple regression analysis IAT was associated with a more favorable outcome than IVT (P=0.003) but similar mortality (P=0.192)., Conclusions: In this observational study intraarterial thrombolysis was more beneficial than IVT in the specific group of stroke patients presenting with HMCAS on CT, even though IAT was started later. Our results indicate that a randomized trial comparing both thrombolytic treatments in patients with middle cerebral artery occlusion is warranted.

Background: We aimed to assess quality of life (QOL) and its predictors in stroke survivors after local intra-arterial thrombolysis (IAT) as well as to measure QOL according to the site of pretreatment vessel occlusion., Methods: From January 2000 to April 2004, 175 consecutive patients underwent IAT for acute ischemic stroke. Clinical and radiological data were collected prospectively. We contacted 135 stroke survivors after a mean of 923 (+/-431) days, 132 responded. QOL, assessed with EuroQol (EQ-5D), and functional abilities, measured with the modified Rankin Scale (mRS) and the Barthel Index, were compared, and predictors of QOL were analyzed., Results: Measured with EQ-5D, 56% of the patients reported a good QOL (EQ-5D Index >or=70). Low mRS and high Barthel Index scores at follow-up were associated with better overall QOL (Kendall's tau >0.5). Nevertheless, 25% of the functionally independent patients (mRS 0-2) indicated a markedly impaired QOL (EQ-5D Index <70) and 10% of disabled patients indicated good QOL. QOL was significantly lower in patients with occlusion of the internal carotid artery compared to patients with occlusion of the basilar artery or the M1, M2 or M3/4 segment of the middle cerebral artery (EQ-5D Index: p = 0.005). A high National Institute of Health Stroke Scale score on admission and occlusion of the internal carotid artery were independent predictors of impaired QOL (p < 0.05)., Conclusion: More than half of the stroke survivors treated with IAT reported a good QOL, mostly survivors with mild disabilities. QOL assessment gives information that is not provided by traditional outcome scores. Our results support guidelines to measure QOL in stroke research., ((c) 2008 S. Karger AG, Basel.)

Background and Purpose: Recent studies have reported sex differences in recanalization and outcome after intravenous thrombolysis (IVT) in acute ischemic stroke., Methods: We analyzed sex differences in outcome in consecutive patients with middle cerebral artery (MCA) M1 or M2 and internal carotid artery (ICA) occlusion treated with intra-arterial thrombolysis (IAT). Recanalization immediately after thrombolysis and outcome after 3 months were assessed., Results: Two hundred five patients (111 men) with MCA and 43 (22 men) with ICA occlusion were identified. Baseline variables did not differ between the sexes except for a higher prevalence of smokers among men in the MCA group (31% vs 12%; P=0.001). Partial or complete recanalization (TIMI flow 2 or 3) of the MCA was observed in 71 (75%) women and 80 (72%) men (P=0.488). In the ICA group, 14 (67%) women and 11 men (50%) showed TIMI 2 or 3 recanalization (P=0.425). Favorable outcome (modified Rankin Scale score 0 to 2) was seen in 57 women (61%) and 63 men (57%) with MCA occlusion (P=0.512) and in 6 women (28%) and 4 men (18%) with ICA occlusion (P=0.656). After multiple-regression analyses, there was still no association between sex and outcome (P=0.763 for MCA and P=0.813 for ICA occlusion) or recanalization (P=0.488 for MCA and P=0.104 for ICA occlusion)., Conclusions: There was no association between sex and recanalization or outcome after IAT. These findings are in contrast to previous studies reporting better recanalization and outcome after IVT in women and might have implications in the selection of patients for IAT or IVT.

Background: The PROACT II trial showed that intra-arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%., Objective: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions., Methods: 294 patients with stroke treated with intra-arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors., Results: sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH., Conclusions: With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.

Background and Purpose: Thrombolysis has been shown to improve the 3-month outcome of patients with ischemic stroke, but knowledge of the long-term effect of thrombolysis is limited., Methods: The present study compares the long-term outcome of stroke patients who were treated with intra-arterial thrombolysis (IAT) using urokinase with the outcome of patients treated with aspirin. The modified Rankin Scale (mRS) was used to assess the outcome; 173 patients treated with IAT and 261 patients treated with aspirin from the Bernese Stroke Data Bank were eligible for the study. A matching algorithm taking into account patient age and stroke severity on admission (as measured by the National Institute of Health Stroke Scale [NIHSS]) was used to assemble an IAT and an aspirin group., Results: One hundred and forty-four patients treated with IAT and 147 patients treated with aspirin could be matched and included in the comparative analysis. The median NIHSS score was 14 in each group. At 2 years, 56% of the patients treated with IAT and 42% of the patients treated with aspirin achieved functional independence (mRS, 0 to 2; P=0.037). Clinical outcome was excellent (mRS, 0 to 1) in 40% of the IAT and in 24% of the aspirin patients (P=0.008). Mortality was 23% and 24%, respectively., Conclusions: The present study provides evidence for a sustained effect of IAT when assessed 2 years after the stroke.

Background: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6 hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce., Methods: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center., Results: 76 patients (33.0%) presented within 3 hours, 69 (30%) between 3 and 6 hours of symptom onset and 85 (37%) later than 6 hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6 hours did not undergo arteriography and thrombolysis, mostly because of mild (n=44) or rapidly improving neurological deficits (n=13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n=7), limiting comorbidty (n=7) and baseline international normalized ratio>1.7 (n=1)., Conclusions: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6 hours time window and mild or rapidly improving symptoms.

Background and Purpose: Transient elevation of arterial blood pressure (BP) is frequent in acute ischemic stroke and may help to increase perfusion of tissue jeopardized by ischemia. If this is true, recanalization may eliminate the need for this BP elevation., Methods: We analyzed BP in 149 patients with acute ischemic stroke on admission to the hospital and 1 and 12 hours after intraarterial thrombolysis. BP values of patients with adequate recanalization were compared with BP values of patients with inadequate recanalization. Recanalization was determined on cerebral arteriography after thrombolysis using thrombolysis in myocardial infarction grades., Results: Systolic, mean, and diastolic arterial BP decreased significantly from admission to 12 hours after thrombolysis in all patients (P<0.001). Before thrombolysis, patients with adequate and inadequate recanalization showed equal systolic (147.4 and 148.0 mm Hg), mean (102.1 and 104.1 mm Hg), and diastolic (79.5 and 82.1 mm Hg) BP values. Twelve hours after thrombolysis, patients with adequate recanalization had lower values than those with inadequate recanalization (systolic BP, 130 versus 139.9 mm Hg; mean BP, 86.8 versus 92.2 mm Hg; and diastolic, BP 65.2 versus 68.3 mm Hg). Two-way repeated ANOVA analysis showed a significant group x time interaction for systolic BP, indicating a larger systolic BP decrease when recanalization succeeded (P=0.019)., Conclusions: The course of elevated systolic but not diastolic BP after acute ischemic stroke was found to be inversely associated with the degree of vessel recanalization. When recanalization failed, systolic BP remained elevated longer than when it succeeded.

Background: Several case series and a recent meta-analysis indicate that intra-arterial thrombolysis (IAT) is effective for the treatment of acute central retinal artery occlusion (CRAO)., Methods: A total of 37 patients with acute monocular blindness because of unilateral thromboembolic CRAO were treated with IAT using urokinase within six hours of the onset of symptoms. Visual outcome was compared with a control group of 19 patients, also seen within six hours, who did not undergo thrombolytic treatment. In both groups some patients were treated by paracentesis and/or acetazolamide. Predictors of visual outcome were evaluated., Results: Visual improvement was more likely with IAT (p = 0.01) as were the chances to regain visual acuity of >0.6 significantly better (p = 0.04): 8/37 patients (22%) regained visual acuity of >0.6 in the IAT group and none (0/19) in the control group. Younger patients were more likely to regain some vision with (p = 0.012) or without IAT (p = 0.026). Three patients had minor treatment related cerebral ischaemic events, two had transient ischaemic attacks and one a minor stroke. There were no haemorrhagic complications., Conclusions: This series of patients with CRAO demonstrated that IAT enhanced the chances of visual improvement compared with conventional treatment only. Furthermore, younger patients have a better chance to achieve some visual recovery.

Background and Objectives: Randomized trials have demonstrated the benefit of intra-arterial thrombolysis (IAT) for treatment of acute ischemic stroke, if performed within 6 hours of symptom onset., Methods: We report our experience with 350 acute stroke patients who were treated with IAT using urokinase at a single center. Predictors of favorable outcome were low National Institute of Health Stroke Scale (NIHSS) at admission (p<0.001), good collaterals (p<0.001) and successful endovascular recanalization (p<0.001). Recanalization rates of more than 75% could be achieved, when additional endovascular techniques such as mechanical fragmentation of the thrombus, thromboaspiration, percutaneous transluminal angioplasty, and implantation of stents were used., Results and Conclusions: Predictors of unfavorable outcome were diabetes mellitus (p<0.001) and symptomatic hemorrhages (p<0.001). The latter occurred in 5% of our population. Preliminary results of new techniques including sonothrombolysis, angiojet aspiration, and laser recanalization of thromboembolic occlusions are discussed.

Intra-arterial thrombolysis (IAT) is the only treatment that has demonstrated benefit in patients with acute basilar artery occlusions (ABAO). IAT may be difficult to perform when access to the occluded basilar artery (BA) is prevented by pathology of the vertebral arteries (VA). We report on two patients with ABAO due to embolism from the dominating VA. Catheter navigation through the occluded VA and thromboaspiration enabled access to the BA. Thromboaspiration alone or in addition to IAT resulted in a complete recanalization of the BA and a favorable clinical outcome. A stent was deployed at the site of the stenosis in the VA either prior to or immediately after BA recanalization.

Objective: To define predictors of recanalisation and clinical outcome of patients with acute basilar artery occlusions treated with local intra-arterial thrombolysis (IAT)., Methods: Vascular risk factors, severity of the neurological deficit graded by the National Institutes of Health stroke scale (NIHSS), and radiological findings were recorded at presentation. Outcome was measured using the modified Rankin scale (mRS) three months later and categorised as favourable (mRS 0-2), poor (mRS 3-5), or death (mRS 6)., Results: 40 patients were studied. Median NIHSS on admission was 18. Mean time from symptom onset to treatment was 5.5 hours (range 2.3 to 11). Outcome was favourable in 14 patients (35%) and poor in nine (23%); 17 (42%) died. There were two symptomatic cerebral haemorrhages (5%). Recanalisation of the basilar artery was achieved in 32 patients (80%); it was complete (TIMI grade 3) in 20% and partial (TIMI grade 2) in 60%. In multivariate logistic regression analysis, low NIHSS score on admission (p = 0.002) and vessel recanalisation (p = 0.005) were independent predictors of favourable outcome. Recanalisation occurred more often with treatment within six hours of symptom onset (p = 0.003) and when admission computed tomography showed a hyperdense basilar artery sign (p = 0.007). In a univariate model, quadriplegia (p = 0.002) and coma (p = 0.004) were associated with a poor outcome or death., Conclusions: Low baseline NIHSS on admission and recanalisation of basilar artery occlusions predict a favourable outcome after intra-arterial thrombolysis. Early initiation of IAT and the presence of a hyperdense basilar artery sign on CT were associated with a higher likelihood of recanalisation.

Objectives: To determine the safety, efficacy, and predictors of favourable outcome of intra-arterial thrombolysis in acute stroke attributable to internal carotid "T"occlusion, Methods: The authors analysed 24 consecutive patients with T occlusions of the internal carotid artery treated by local intra-arterial thrombolysis using urokinase., Results: The median baseline National Institutes of Health Stroke Scale was 19. The average time from symptom onset to treatment was 237 minutes. Four patients (16.6%) had a favourable (modified Rankin Scale score (mRS

Background and Purpose: Thrombolysis for treatment of acute ischemic stroke should be administered as fast as possible after symptom onset. The aim of this study was to examine, in our tertiary care center, the time intervals preceding intra-arterial thrombolysis in order to accelerate and optimize the management of acute strokes., Methods: Between January 1, 2000, and April 30, 2002, 597 patients with acute stroke were admitted to our stroke center. One hundred forty-eight patients underwent diagnostic arteriography, and 100 (16.8%) received intra-arterial thrombolysis. For all patients, we prospectively recorded and analyzed the time of symptom onset, admission, CT and/or MRI scan, diagnostic arteriography, and, if performed, intra-arterial thrombolysis., Results: The mean time to arrival in the emergency department was 99 minutes for patients who were admitted directly (Bern patients), 127 minutes for those who were referred from community hospitals without a CT scanner (non-Bern/-CT patients), and 210 minutes for patients from hospitals with imaging facilities (non-Bern/+CT patients). The mean delay from symptom onset to treatment was 234 minutes for Bern patients, 269 minutes for non-Bern/-CT patients, and 302 minutes for non-Bern/+CT patients. The patients from the last group needed longer to receive intra-arterial thrombolysis than did patients who were admitted directly (P=0.002) or who were transferred from a hospital without a CT scanner (P=0.03)., Conclusions: This prospective study indicates that direct referral without prior imaging at community hospitals shortens the time until intra-arterial thrombolysis. In addition, our in-hospital delay preceding intra-arterial thrombolysis is longer than the delays reported for intravenous thrombolysis and indicates potential for improvement.

Background: Results of recently published studies suggest that intravenous thrombolysis (IVT) and local intra-arterial thrombolysis (LIT) are feasible procedures in acute stroke after cervical artery dissection (CAD)., Objectives: To describe 9 patients with acute stroke caused by CAD who were treated by LIT (n = 7) or IVT (n = 2) and to review the literature., Methods: Retrospective analysis of clinical and neuroradiological findings; literature review from 1980 to present., Main Outcome Measure: Modified Rankin Scale (mRS) score., Results: Of 7 patients treated with LIT, 3 had good outcomes (mRS score of 0-2) and 4 had bad outcomes (mRS score of 3-6) at 3 months. The 2 patients who had received IVT recovered to mRS scores of 0 and 3. Twenty-one patients were identified in the literature. Overall (N = 30), in the IVT group (n = 19), the outcome was good in 8 patients (42%) and bad in 11 (58%); in the LIT group (n = 11), 6 patients (55%) had a good outcome and 5 (45%) had a bad outcome. Overall, 47% (14/30) of the patients (IVT and LIT groups) had a good outcome. Total mortality was 13% (4/30). There were no secondary complications due to extension of wall hematoma or angiography. One symptomatic hemorrhage occurred., Conclusions: Thrombolysis is feasible in acute stroke caused by CAD. Local complications from extension of wall hematoma did not occur. Further prospective studies are needed to determine the safety and efficacy of thrombolysis in the special circumstance of acute stroke caused by CAD.

Diffusion-weighted MRI (DWI) is becoming important for diagnosis and investigation of acute cerebral ischaemia. It has been reported that apparent diffusion coefficient (ADC) maps could be an indicator of reperfusion. Our aim was to use echo-planar technology to investigate this phenomenon. We report 19 patients treated by local intra-arterial thrombolysis for middle cerebral artery stroke within 6 h of the onset of symptoms, in whom we performed follow-up DWI. ADC were found to be higher in the patients with angiographically proven reperfusion.

Background and Purpose: Occlusion of the central retinal artery (CRAO) causes a sudden decrease of monocular vision. Because early restoration of blood flow may improve outcome, we attempted to treat CRAO with selective intra-arterial fibrinolysis., Methods: Intra-arterial fibrinolysis was performed within 6 hours after symptom onset in 17 patients with thromboembolic CRAO. Symptoms were painless, acute and severe decrease of vision. Urokinase (100 000 to 900 000 IU) was given through a microcatheter into the ophthalmic artery over 10 to 90 minutes. For comparison, the history and visual outcome of 15 control patients who did not receive fibrinolytics were evaluated. In both groups some of the patients underwent paracentesis and/or received carboanhydrase inhibitors., Results: Patients who underwent fibrinolysis fared better than control patients (P=0.01). Three patients (17.6%) recovered completely after fibrinolysis and regained visual acuity of 20/20 (n=2) to 25/20 (n=1). Two additional patients (11.8%) showed a marked improvement to a visual acuity of 20/30. In 6 patients (35. 3%) vision improved slightly. They were able to count fingers, detect hand movements, or perceive light. In 6 patients (35.3%), fibrinolytic treatment was without effect. Among control patients, 1 patient (6.7%) showed partial, 4 patients (26.7%) minimal, and 10 (66.7%) no improvement of vision., Conclusions: A complete or marked improvement of visual acuity was achieved in one third of intra-arterial fibrinolysis patients but in none of the control patients. Intra-arterial fibrinolysis seems to have the potential to "lighten" the spontaneously poor outcome of CRAO.

Background and Purpose: We performed a retrospective analysis of the prognostic factors in patients treated with local intra-arterial thrombolysis (LIT). The purpose of this study was to evaluate the safety and efficacy of LIT using urokinase in patients with acute ischemic stroke of the anterior or posterior circulation and to determine the influence of clinical and radiological parameters on outcome., Methods: Forty-three patients were treated with LIT using urokinase (median dose, 0.75x10(6) IU). The median National Institutes of Health Stroke Scale (NIHSS) score at hospital admission was 18 (range, 9 to 36). Nine patients had occlusions of the internal carotid artery (ICA), 23 of the middle cerebral artery (MCA), 1 of the anterior cerebral artery, and 10 of the basilar artery (BA). Outcome was assessed after 3 months and classified as good for Rankin Scale (RS) scores of 0 to 3 and poor for RS scores of 4 or 5 and death., Results: Nine patients (21%) recovered to RS scores 0 or 1, 17 (40%) to scores of 2 or 3, and 7 (16%) to scores of 4 or 5. Ten patients (23%) died. Outcome was good in 17 patients (80%) with MCA occlusions, in 3 patients (33%) with ICA, and in 5 patients (50%) with BA occlusions. Good outcome was associated with an initial NIHSS score of <20 (P<0.001), improvement by 4 or more points on NIHSS score within 24 hours (P=0.001), and vessel recanalization (P=0.02). Recanalization was more likely if LIT was started within 4 hours (P=0.01). Symptomatic cerebral hemorrhage occurred in 2 patients (4.7%)., Conclusions: LIT was most efficacious in patients with MCA and BA occlusions when the initial NIHSS score was less than 20 and when treated within 4 hours. It is of limited value in patients with distal ICA occlusions.