Nils Wahlgren - Academia.edu (original) (raw)
Papers by Nils Wahlgren
Cochrane Database of Systematic Reviews, 2007
Experimental animal research shows that treatment with amphetamines improves recovery after focal... more Experimental animal research shows that treatment with amphetamines improves recovery after focal cerebral ischaemia. If the effect were similar in humans, amphetamine treatment could have a major impact on recovery from stroke. The objective of this review was to assess the effects of amphetamine treatment in patients with stroke. We searched the Cochrane Stroke Group Trials Register (last searched November 2002). In addition, we searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4 2002), MEDLINE (1966-September 2002), EMBASE (1980-November 2002), and Science Citation Index (1992-December 2002). The reference lists of all relevant articles and reviews were checked, and we contacted researchers in the field to identify further published and unpublished studies. Randomized unconfounded trials comparing amphetamine with placebo. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Seven studies involving 172 patients were included. The quality of the trials varied but was generally high. Based on two trials (85 patients) there was no evidence that amphetamine treatment reduced death or dependence (Peto's odds ratio, [Peto OR] 1.54; 95% Confidence Interval [CI] 0.64 to 3.73). In these two trials, there were imbalances at baseline, with more serious strokes allocated to amphetamine. This imbalance may account for the trend for more deaths at the end of follow-up among amphetamine allocated patients (Peto OR 3.33; 95% CI 0.99 to 11.24). Based on 4 studies (95 patients) there was evidence of a better relative change in motor function according to the Fugl-Meyer motor scale (Weighted Mean Difference, [WMD] -8.17 points; 95% CI -13.58 to -2.76) and based on 1 study (21 patients) there was evidence of a better change in language function as assessed by the Porch Index of Communicative Ability score (WMD -7.51 points; 95% CI -14.42 to -0.60) in amphetamine allocated patients. At present, too few patients have been studied to draw any definite conclusions about the effects of amphetamine treatment on recovery from stroke. The suggested benefits on motor and language function, and the non-significant trend towards increased risk of death, could be related to imbalances in prognostic variables or other bias in studies. Further research in this area is therefore justified.
Stroke, 2014
Background and Purpose— Little is known about the effect of thrombolysis in patients with preexis... more Background and Purpose— 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. Methods— 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. Results— 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 symptomat...
Stroke, 2010
Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral he... more Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke. Methods— We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale ≥4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale ≥4 plus any ICH]), functional outcome at 3 months and mortality. Results— A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogre...
Stroke, 2010
Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral he... more Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke. Methods— We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale ≥4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale ≥4 plus any ICH]), functional outcome at 3 months and mortality. Results— A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogre...
Stroke, 2003
Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, bu... more Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia. Methods— Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke. Results— Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo ( P ≤0.01). There was no difference bet...
Stroke, 2003
Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, bu... more Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia. Methods— Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke. Results— Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo ( P ≤0.01). There was no difference bet...
Stroke, 2011
Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CA... more Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. Methods— We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. Results— We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stro...
Stroke, 2011
Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CA... more Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. Methods— We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. Results— We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stro...
Stroke, 2009
Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has dem... more Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods— In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical effi...
Stroke, 2009
Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has dem... more Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods— In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical effi...
Neuroradiology, 2014
Introduction We present our results from the first 6 years with mechanical thrombectomy in the tr... more Introduction We present our results from the first 6 years with mechanical thrombectomy in the treatment of ischemic stroke. Methods Every patient treated with mechanical thrombectomy for acute ischemic stroke from September 2005 to December 2011 was consecutively included in this retrospective analysis. Baseline and outcome data were retrieved from computerized records at the hospital. National Institute of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score were used as outcome parameters. Favorable outcome was defined as a mRS score of 0-2, corresponding to independence in activities of daily living. We also evaluated revascularization and severe adverse events, with focus on symptomatic intracranial hemorrhage. Results Good functional outcome (mRS 0-2) was achieved in 50 % (120/240) of all patients. For patients with no neurological deficit prior to stroke onset (i.e., mRS=0 before stroke), the proportion with good functional outcome was 54 %. Symptomatic hemorrhages occurred in 4.6 % of the cases (5.7 % in the anterior circulation). Conclusion In summary, our results supports that mechanical thrombectomy is a safe and effective method to restore blood flow in selected patients suffering from an acute ischemic stroke.
The Lancet, 2007
Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MO... more Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was to assess the safety and effi cacy of intravenous alteplase as thrombolytic therapy within the fi rst 3 h of onset of acute ischaemic stroke. Under European Union regulations, SITS-MOST was required to assess the safety profi le of alteplase in clinical practice by comparison with results in randomised controlled trials. Methods 6483 patients were recruited from 285 centres (50% with little previous experience in stroke thrombolysis) in 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of ≥4) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months. We compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane defi nition, and functional outcome at 3 months with relevant pooled results from randomised controlled trials. Findings Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled randomised controlled trials. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage (per the SITS-MOST protocol) was 1•7% (107/6444; 95% CI 1•4-2•0); at 7 days, the proportion with the same condition as per the Cochrane defi nition was 7•3% (468/6438; 6•7-7•9) compared with 8•6% (40/465; 6•3-11•6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11•3% (701/6218; 10•5-12•1) compared with 17•3% (83/479; 14•1-21•1) in the pooled randomised controlled trials. Interpretation These data confi rm that intravenous alteplase is safe and eff ective in routine clinical use when used within 3 h of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The fi ndings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.
The Lancet, 2007
Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MO... more Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was to assess the safety and effi cacy of intravenous alteplase as thrombolytic therapy within the fi rst 3 h of onset of acute ischaemic stroke. Under European Union regulations, SITS-MOST was required to assess the safety profi le of alteplase in clinical practice by comparison with results in randomised controlled trials. Methods 6483 patients were recruited from 285 centres (50% with little previous experience in stroke thrombolysis) in 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of ≥4) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months. We compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane defi nition, and functional outcome at 3 months with relevant pooled results from randomised controlled trials. Findings Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled randomised controlled trials. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage (per the SITS-MOST protocol) was 1•7% (107/6444; 95% CI 1•4-2•0); at 7 days, the proportion with the same condition as per the Cochrane defi nition was 7•3% (468/6438; 6•7-7•9) compared with 8•6% (40/465; 6•3-11•6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11•3% (701/6218; 10•5-12•1) compared with 17•3% (83/479; 14•1-21•1) in the pooled randomised controlled trials. Interpretation These data confi rm that intravenous alteplase is safe and eff ective in routine clinical use when used within 3 h of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The fi ndings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.
Circulation. Cardiovascular quality and outcomes, 2015
Intravenous thrombolysis (IVT) for acute ischemic stroke is subject to label and guideline contra... more Intravenous thrombolysis (IVT) for acute ischemic stroke is subject to label and guideline contraindications. Updated European guidelines in 2008/2009 recommended IVT in selected patients aged >80 years and stroke onset-to-treatment time 3 to 4.5 hours, which the label still prohibited. Our aim was to compare contraindication nonadherence before and after the guideline update. Data on IVT-treated patients with stroke at 232 European hospitals participating in the Safe Implementation of Treatments in Stroke registry during both periods 2006 to 2007 (n=6354) and 2010 to 2011 (n=12 046). After the 2008/2009 guideline update, the proportion of patients nonadherent to label increased from 23.6% to 51.1% (P<0.001). Specifically, nonadherence to onset-to-treatment time >3 hours increased from 8.2% to 27.9% and IVT in patients aged >80 years from 8.9% to 17.2% (both P<0.001). Nonadherence also increased to the contraindications severe stroke (National Institutes of Health Str...
International journal of stroke : official journal of the International Stroke Society, Jan 4, 2015
The Totaled Health Risks in Vascular Events (THRIVE) score is a previously validated ischemic str... more The Totaled Health Risks in Vascular Events (THRIVE) score is a previously validated ischemic stroke outcome prediction tool. Although simplified scoring systems like the THRIVE score facilitate ease-of-use, when computers or devices are available at the point of care, a more accurate and patient-specific estimation of outcome probability should be possible by computing the logistic equation with patient-specific continuous variables. We used data from 12 207 subjects from the Virtual International Stroke Trials Archive and the Safe Implementation of Thrombolysis in Stroke - Monitoring Study to develop and validate the performance of a model-derived estimation of outcome probability, the THRIVE-c calculation. Models were built with logistic regression using the underlying predictors from the THRIVE score: age, National Institutes of Health Stroke Scale score, and the Chronic Disease Scale (presence of hypertension, diabetes mellitus, or atrial fibrillation). Receiver operator charac...
![Research paper thumbnail of [Activities in a neurologic acute department. Retrospective study of a 3-month period in 1974 at Karolinska Hospital]](https://attachments.academia-assets.com/88258632/thumbnails/1.jpg)
](Läkartidningen, Jan 5, 1977
International journal of stroke : official journal of the International Stroke Society, 2012
Analysis of reliable registry data can direct future research to influence clinical care. Data fr... more Analysis of reliable registry data can direct future research to influence clinical care. Data from the Virtual International Stroke Trials Archive have been used to test hypotheses and inform trial design. We sought to expand Virtual International Stroke Trials Archive into a broader stroke resource with new opportunities for research and international collaboration. Using procedures initially developed for an acute stroke trial archive, we invited trialists to lodge data on rehabilitation, secondary prevention, intracerebral haemorrhage, imaging, and observational stroke studies. We have extended Virtual International Stroke Trials Archive into six subsections: Virtual International Stroke Trials Archive-Acute (n = 28 190 patients' data), Virtual International Stroke Trials Archive-Rehab (n = 10 194), Virtual International Stroke Trials Archive-intracerebral haemorrhage (n = 1829), Virtual International Stroke Trials Archive-Prevention, Virtual International Stroke Trials Arch...
Cochrane Database of Systematic Reviews, 2007
Experimental animal research shows that treatment with amphetamines improves recovery after focal... more Experimental animal research shows that treatment with amphetamines improves recovery after focal cerebral ischaemia. If the effect were similar in humans, amphetamine treatment could have a major impact on recovery from stroke. The objective of this review was to assess the effects of amphetamine treatment in patients with stroke. We searched the Cochrane Stroke Group Trials Register (last searched November 2002). In addition, we searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4 2002), MEDLINE (1966-September 2002), EMBASE (1980-November 2002), and Science Citation Index (1992-December 2002). The reference lists of all relevant articles and reviews were checked, and we contacted researchers in the field to identify further published and unpublished studies. Randomized unconfounded trials comparing amphetamine with placebo. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Seven studies involving 172 patients were included. The quality of the trials varied but was generally high. Based on two trials (85 patients) there was no evidence that amphetamine treatment reduced death or dependence (Peto&amp;#39;s odds ratio, [Peto OR] 1.54; 95% Confidence Interval [CI] 0.64 to 3.73). In these two trials, there were imbalances at baseline, with more serious strokes allocated to amphetamine. This imbalance may account for the trend for more deaths at the end of follow-up among amphetamine allocated patients (Peto OR 3.33; 95% CI 0.99 to 11.24). Based on 4 studies (95 patients) there was evidence of a better relative change in motor function according to the Fugl-Meyer motor scale (Weighted Mean Difference, [WMD] -8.17 points; 95% CI -13.58 to -2.76) and based on 1 study (21 patients) there was evidence of a better change in language function as assessed by the Porch Index of Communicative Ability score (WMD -7.51 points; 95% CI -14.42 to -0.60) in amphetamine allocated patients. At present, too few patients have been studied to draw any definite conclusions about the effects of amphetamine treatment on recovery from stroke. The suggested benefits on motor and language function, and the non-significant trend towards increased risk of death, could be related to imbalances in prognostic variables or other bias in studies. Further research in this area is therefore justified.
Stroke, 2014
Background and Purpose— Little is known about the effect of thrombolysis in patients with preexis... more Background and Purpose— 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. Methods— 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. Results— 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 symptomat...
Stroke, 2010
Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral he... more Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke. Methods— We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale ≥4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale ≥4 plus any ICH]), functional outcome at 3 months and mortality. Results— A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogre...
Stroke, 2010
Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral he... more Background and Purpose— Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke. Methods— We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale ≥4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale ≥4 plus any ICH]), functional outcome at 3 months and mortality. Results— A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogre...
Stroke, 2003
Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, bu... more Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia. Methods— Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke. Results— Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo ( P ≤0.01). There was no difference bet...
Stroke, 2003
Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, bu... more Background and Purpose— Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia. Methods— Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke. Results— Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo ( P ≤0.01). There was no difference bet...
Stroke, 2011
Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CA... more Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. Methods— We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. Results— We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stro...
Stroke, 2011
Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CA... more Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. Methods— We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. Results— We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stro...
Stroke, 2009
Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has dem... more Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods— In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical effi...
Stroke, 2009
Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has dem... more Background and Purpose— Microplasmin is a recombinant truncated form of human plasmin. It has demonstrated efficacy in experimental animal models of stroke and tolerability in healthy volunteers. We tested the tolerability of microplasmin in patients with acute ischemic stroke. Methods— In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical effi...
Neuroradiology, 2014
Introduction We present our results from the first 6 years with mechanical thrombectomy in the tr... more Introduction We present our results from the first 6 years with mechanical thrombectomy in the treatment of ischemic stroke. Methods Every patient treated with mechanical thrombectomy for acute ischemic stroke from September 2005 to December 2011 was consecutively included in this retrospective analysis. Baseline and outcome data were retrieved from computerized records at the hospital. National Institute of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score were used as outcome parameters. Favorable outcome was defined as a mRS score of 0-2, corresponding to independence in activities of daily living. We also evaluated revascularization and severe adverse events, with focus on symptomatic intracranial hemorrhage. Results Good functional outcome (mRS 0-2) was achieved in 50 % (120/240) of all patients. For patients with no neurological deficit prior to stroke onset (i.e., mRS=0 before stroke), the proportion with good functional outcome was 54 %. Symptomatic hemorrhages occurred in 4.6 % of the cases (5.7 % in the anterior circulation). Conclusion In summary, our results supports that mechanical thrombectomy is a safe and effective method to restore blood flow in selected patients suffering from an acute ischemic stroke.
The Lancet, 2007
Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MO... more Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was to assess the safety and effi cacy of intravenous alteplase as thrombolytic therapy within the fi rst 3 h of onset of acute ischaemic stroke. Under European Union regulations, SITS-MOST was required to assess the safety profi le of alteplase in clinical practice by comparison with results in randomised controlled trials. Methods 6483 patients were recruited from 285 centres (50% with little previous experience in stroke thrombolysis) in 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of ≥4) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months. We compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane defi nition, and functional outcome at 3 months with relevant pooled results from randomised controlled trials. Findings Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled randomised controlled trials. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage (per the SITS-MOST protocol) was 1•7% (107/6444; 95% CI 1•4-2•0); at 7 days, the proportion with the same condition as per the Cochrane defi nition was 7•3% (468/6438; 6•7-7•9) compared with 8•6% (40/465; 6•3-11•6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11•3% (701/6218; 10•5-12•1) compared with 17•3% (83/479; 14•1-21•1) in the pooled randomised controlled trials. Interpretation These data confi rm that intravenous alteplase is safe and eff ective in routine clinical use when used within 3 h of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The fi ndings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.
The Lancet, 2007
Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MO... more Background The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was to assess the safety and effi cacy of intravenous alteplase as thrombolytic therapy within the fi rst 3 h of onset of acute ischaemic stroke. Under European Union regulations, SITS-MOST was required to assess the safety profi le of alteplase in clinical practice by comparison with results in randomised controlled trials. Methods 6483 patients were recruited from 285 centres (50% with little previous experience in stroke thrombolysis) in 14 countries between 2002 and 2006 for this prospective, open, monitored, observational study. Primary outcomes were symptomatic (a deterioration in National Institutes of Health stroke scale score of ≥4) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months. We compared mortality, the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane defi nition, and functional outcome at 3 months with relevant pooled results from randomised controlled trials. Findings Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled randomised controlled trials. At 24 h, the proportion of patients with symptomatic intracerebral haemorrhage (per the SITS-MOST protocol) was 1•7% (107/6444; 95% CI 1•4-2•0); at 7 days, the proportion with the same condition as per the Cochrane defi nition was 7•3% (468/6438; 6•7-7•9) compared with 8•6% (40/465; 6•3-11•6) in the pooled randomised controlled trials. The mortality rate at 3 months in SITS-MOST was 11•3% (701/6218; 10•5-12•1) compared with 17•3% (83/479; 14•1-21•1) in the pooled randomised controlled trials. Interpretation These data confi rm that intravenous alteplase is safe and eff ective in routine clinical use when used within 3 h of stroke onset, even by centres with little previous experience of thrombolytic therapy for acute stroke. The fi ndings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres.
Circulation. Cardiovascular quality and outcomes, 2015
Intravenous thrombolysis (IVT) for acute ischemic stroke is subject to label and guideline contra... more Intravenous thrombolysis (IVT) for acute ischemic stroke is subject to label and guideline contraindications. Updated European guidelines in 2008/2009 recommended IVT in selected patients aged >80 years and stroke onset-to-treatment time 3 to 4.5 hours, which the label still prohibited. Our aim was to compare contraindication nonadherence before and after the guideline update. Data on IVT-treated patients with stroke at 232 European hospitals participating in the Safe Implementation of Treatments in Stroke registry during both periods 2006 to 2007 (n=6354) and 2010 to 2011 (n=12 046). After the 2008/2009 guideline update, the proportion of patients nonadherent to label increased from 23.6% to 51.1% (P<0.001). Specifically, nonadherence to onset-to-treatment time >3 hours increased from 8.2% to 27.9% and IVT in patients aged >80 years from 8.9% to 17.2% (both P<0.001). Nonadherence also increased to the contraindications severe stroke (National Institutes of Health Str...
International journal of stroke : official journal of the International Stroke Society, Jan 4, 2015
The Totaled Health Risks in Vascular Events (THRIVE) score is a previously validated ischemic str... more The Totaled Health Risks in Vascular Events (THRIVE) score is a previously validated ischemic stroke outcome prediction tool. Although simplified scoring systems like the THRIVE score facilitate ease-of-use, when computers or devices are available at the point of care, a more accurate and patient-specific estimation of outcome probability should be possible by computing the logistic equation with patient-specific continuous variables. We used data from 12 207 subjects from the Virtual International Stroke Trials Archive and the Safe Implementation of Thrombolysis in Stroke - Monitoring Study to develop and validate the performance of a model-derived estimation of outcome probability, the THRIVE-c calculation. Models were built with logistic regression using the underlying predictors from the THRIVE score: age, National Institutes of Health Stroke Scale score, and the Chronic Disease Scale (presence of hypertension, diabetes mellitus, or atrial fibrillation). Receiver operator charac...
Läkartidningen, Jan 5, 1977
International journal of stroke : official journal of the International Stroke Society, 2012
Analysis of reliable registry data can direct future research to influence clinical care. Data fr... more Analysis of reliable registry data can direct future research to influence clinical care. Data from the Virtual International Stroke Trials Archive have been used to test hypotheses and inform trial design. We sought to expand Virtual International Stroke Trials Archive into a broader stroke resource with new opportunities for research and international collaboration. Using procedures initially developed for an acute stroke trial archive, we invited trialists to lodge data on rehabilitation, secondary prevention, intracerebral haemorrhage, imaging, and observational stroke studies. We have extended Virtual International Stroke Trials Archive into six subsections: Virtual International Stroke Trials Archive-Acute (n = 28 190 patients' data), Virtual International Stroke Trials Archive-Rehab (n = 10 194), Virtual International Stroke Trials Archive-intracerebral haemorrhage (n = 1829), Virtual International Stroke Trials Archive-Prevention, Virtual International Stroke Trials Arch...