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... 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relevant articles and reviews were checked, and we contacted researchers in the field to identify further published and unpublished studies.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.
Research Interests:
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... 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...
Research Interests: Medicine, Comorbidity, Stroke, Humans, Female, and 15 moreMale, Confidence intervals, Brain Ischemia, Registries, Clinical Sciences, Aged, Middle Aged, Odds ratio, Prognosis, Neurosciences, Logistic Models, Disabled Persons, Disability Evaluation, Thrombolysis, and Cardiovascular medicine and haematology
Research Interests:
Research Interests:
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... 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...
Research Interests: Adolescent, Humans, Female, Brain Ischemia, Incidence, and 15 moreAspirin, Implementation, Clinical Sciences, Aged, Adult, Antiplatelets, Antiplatelet Therapy, Double Blind, Hemorrhage, Drug Incompatibility, Cerebral Hemorrhage, Acute Ischemic Stroke, Acute Disease, alteplase, and Cardiovascular medicine and haematology
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... 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...
Research Interests: Adolescent, Humans, Female, Brain Ischemia, Incidence, and 15 moreAspirin, Implementation, Clinical Sciences, Aged, Adult, Antiplatelets, Antiplatelet Therapy, Double Blind, Hemorrhage, Drug Incompatibility, Cerebral Hemorrhage, Acute Ischemic Stroke, Acute Disease, alteplase, and Cardiovascular medicine and haematology
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... 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...
Research Interests: Consciousness, Medicine, Prospective studies, Humans, Placebo, and 15 moreBlood Pressure, Female, Male, Heart rate, Brain Ischemia, Body Temperature, Clinical Sciences, Aged, Middle Aged, Drug evaluation, Acute Ischemic Stroke, Neurosciences, Dextroamphetamine, Acute Disease, and Cardiovascular medicine and haematology
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... 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...
Research Interests: Consciousness, Medicine, Prospective studies, Humans, Placebo, and 15 moreBlood Pressure, Female, Male, Heart rate, Brain Ischemia, Body Temperature, Clinical Sciences, Aged, Middle Aged, Drug evaluation, Acute Ischemic Stroke, Neurosciences, Dextroamphetamine, Acute Disease, and Cardiovascular medicine and haematology
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... 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...
Research Interests:
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... 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...
Research Interests:
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... 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...
Research Interests: Brain Imaging, Clinical Trial, Magnetic Resonance Imaging, Treatment Outcome, Medicine, and 14 moreStroke, Humans, Female, Male, Diffusion weighted imaging, Placebos, Brain Ischemia, Clinical Sciences, Aged, Middle Aged, Acute Ischemic Stroke, Neurosciences, Acute Disease, and Cardiovascular medicine and haematology
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... 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...
Research Interests: Brain Imaging, Clinical Trial, Magnetic Resonance Imaging, Treatment Outcome, Medicine, and 14 moreStroke, Humans, Female, Male, Diffusion weighted imaging, Placebos, Brain Ischemia, Clinical Sciences, Aged, Middle Aged, Acute Ischemic Stroke, Neurosciences, Acute Disease, and Cardiovascular medicine and haematology
Research Interests:
Research Interests:
Research Interests: European Union, Medicine, Clinical Practice, Stroke, Humans, and 15 moreEurope, Female, Male, Randomised Controlled Trial, Lancet, Aged, Middle Aged, Observational Study, Ischaemic Stroke, Mortality rate, Randomized Controlled Trials as Topic, The Lancet, Medical and Health Sciences, functional outcome, and Intracranial hemorrhages
Research Interests: European Union, Medicine, Clinical Practice, Stroke, Humans, and 15 moreEurope, Female, Male, Randomised Controlled Trial, Lancet, Aged, Middle Aged, Observational Study, Ischaemic Stroke, Mortality rate, Randomized Controlled Trials as Topic, The Lancet, Medical and Health Sciences, functional outcome, and Intracranial hemorrhages
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... 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...
Research Interests:
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... 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 Interests: Medicine, Probability, Multivariate Analysis, Stroke, Humans, and 15 moreFemale, Male, Brain Ischemia, ROC Curve, Clinical Sciences, Computer User Interface Design, Aged, Middle Aged, Prognosis, Neurosciences, Logistic Models, Area Under Curve, Cohort Studies, Random Allocation, and Severity of Illness Index
Research Interests:
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... 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...
Research Interests:
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... 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;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.
Research Interests:
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... 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...
Research Interests: Medicine, Comorbidity, Stroke, Humans, Female, and 15 moreMale, Confidence intervals, Brain Ischemia, Registries, Clinical Sciences, Aged, Middle Aged, Odds ratio, Prognosis, Neurosciences, Logistic Models, Disabled Persons, Disability Evaluation, Thrombolysis, and Cardiovascular medicine and haematology
Research Interests:
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... 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...
Research Interests: Adolescent, Humans, Female, Brain Ischemia, Incidence, and 15 moreAspirin, Implementation, Clinical Sciences, Aged, Adult, Antiplatelets, Antiplatelet Therapy, Double Blind, Hemorrhage, Drug Incompatibility, Cerebral Hemorrhage, Acute Ischemic Stroke, Acute Disease, alteplase, and Cardiovascular medicine and haematology
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... 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...
Research Interests: Consciousness, Medicine, Prospective studies, Humans, Placebo, and 15 moreBlood Pressure, Female, Male, Heart rate, Brain Ischemia, Body Temperature, Clinical Sciences, Aged, Middle Aged, Drug evaluation, Acute Ischemic Stroke, Neurosciences, Dextroamphetamine, Acute Disease, and Cardiovascular medicine and haematology
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... 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...
Research Interests:
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... 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...
Research Interests: Brain Imaging, Clinical Trial, Magnetic Resonance Imaging, Treatment Outcome, Medicine, and 14 moreStroke, Humans, Female, Male, Diffusion weighted imaging, Placebos, Brain Ischemia, Clinical Sciences, Aged, Middle Aged, Acute Ischemic Stroke, Neurosciences, Acute Disease, and Cardiovascular medicine and haematology
Research Interests:
Research Interests: European Union, Medicine, Clinical Practice, Stroke, Humans, and 15 moreEurope, Female, Male, Randomised Controlled Trial, Lancet, Aged, Middle Aged, Observational Study, Ischaemic Stroke, Mortality rate, Randomized Controlled Trials as Topic, The Lancet, Medical and Health Sciences, functional outcome, and Intracranial hemorrhages
Research Interests: European Union, Public Health, Medicine, Multivariate Analysis, Prospective studies, and 15 moreHumans, Europe, Female, Male, Randomised Controlled Trial, Meta Analysis, Lancet, Aged, Middle Aged, Observational Study, Cerebral Hemorrhage, Ischaemic Stroke, Recovery of Function, Outcome measure, and Medical and Health Sciences
Research Interests: European Union, Public Health, Medicine, Multivariate Analysis, Prospective studies, and 15 moreHumans, Europe, Female, Male, Randomised Controlled Trial, Meta Analysis, Lancet, Aged, Middle Aged, Observational Study, Cerebral Hemorrhage, Ischaemic Stroke, Recovery of Function, Outcome measure, and Medical and Health Sciences
Research Interests: European Union, Public Health, Medicine, Multivariate Analysis, Prospective studies, and 15 moreHumans, Europe, Female, Male, Randomised Controlled Trial, Meta Analysis, Lancet, Aged, Middle Aged, Observational Study, Cerebral Hemorrhage, Ischaemic Stroke, Recovery of Function, Outcome measure, and Medical and Health Sciences
There is convincing evidence from animal models of stroke that ischemia leads to an increase in the extracellular concentrations of excitatory amino acids (EAAs), especially glutamate. This accumulation of glutamate, which can reach up to... more
There is convincing evidence from animal models of stroke that ischemia leads to an increase in the extracellular concentrations of excitatory amino acids (EAAs), especially glutamate. This accumulation of glutamate, which can reach up to 80 times normal at the centre of an ischemic lesion, is believed to be an important factor for the premature death of neurons that would otherwise survive the ischemic conditions and recover when flow is restored. In the technique of microdialysis, a small probe is inserted into the brain tissue. Fluid passing through the probe is separated from the brain parenchyma by a semipermeable membrane, through which substances released into the brain can diffuse. Analysis of the dialysate allows the nature and time course of release of substances, such as glutamate, to be determined. This technique has been used in patients undergoing resection of cerebral tumors, surgery for epilepsy, head trauma, subarachnoid hemorrhage, and cerebral infarction. Clamping or ligating the blood supply to the lobe about to be excised leads to a rapid accumulation in the dialysate of, among other substances, glutamate. Similar findings have been obtained during lobar resection for the treatment of severe epilepsy. Accumulations of glutamate to approximately 100 times the basal concentration have been found. There are also a few reports of microdialysis being performed in patients undergoing lobectomy after severe strokes or extracranial-intracranial bypass surgery. Again, high concentrations of glutamate have been reported. Another approach is to examine the blood and cerebrospinal fluid (CSF) for traces of EAAs. High concentrations of glutamate have been found in the blood and CSF within 24 hours of the onset of stroke. In animal models, plasma concentrations of glutamate begin to rise some 4 to 6 hours after middle cerebral artery (MCA) occlusions, reaching a peak at about 8 to 24 hours. Similarly, when glutamate is injected into the CSF of rats, there is a lag of approximately 4 hours before the concentration of glutamate in the blood rises. Therefore, it may be possible to detect the ongoing release of glutamate into the brain as a result of cerebral ischemia, which may aid in the selection of the most appropriate treatment. The results of microdialysis and plasma EAA analyses suggest that excitotoxic damage can occur over many hours. This implies that effective neuroprotectant strategies could provide clinical benefits over similarly prolonged periods.
Research Interests:
The SITS (Safe Implementation of Thrombolysis in Stroke)-EAST project was launched in 2007 to support evidence-based stroke treatments, including thrombolytic treatments (TLTs), in Central and Eastern Europe. The aim of this study was to... more
The SITS (Safe Implementation of Thrombolysis in Stroke)-EAST project was launched in 2007 to support evidence-based stroke treatments, including thrombolytic treatments (TLTs), in Central and Eastern Europe. The aim of this study was to detail the topography, efficacy, and specific characteristics of stroke centers in the Czech Republic (CZ), the country with the highest rate of TLT. The nationwide study was performed between September and November 2007 through a questionnaire sent to all centers registered in SITS. The questionnaire contained 25 questions addressing how centers met recommendations for primary and comprehensive stroke centers in 2006. Center characteristics predicting the number of TLTs were identified by multiple regression analysis. Altogether, data were obtained from 42 centers (88% response rate) with the following characteristics [median (min-max)]: catchment area population 150,000 (90,000-750,000); number of strokes/year 420 (150-1,589); number of TLTs 7.5 (2-45); number of physicians specialized in stroke 3 (1-7). Centers treated 4.3% of the patients with ischemic strokes with tissue plasminogen activator. A stroke unit was present in 32 (78%) departments. Rescue interventional therapies were performed in 11 (26%). Financial problems restricted TLT in 14 (35%) centers. Fourteen factors were associated with the number of TLTs in univariate regression analysis, but in multiple regression analysis, only the catchment area population (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3 physicians specialized in stroke (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and the presence of an acute interventional program (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.006) remained significant. This study provides the fundamental stroke treatment network data that are essential for certification and further SITS-EAST TLT expansion.
Research Interests: Neurology, Eastern Europe, Medicine, Linear models, Czech Republic, and 15 moreMultivariate Analysis, Stroke, Population, Humans, Physicians, Regression Analysis, Brain Ischemia, Ischemic Stroke, Clinical Sciences, Questionnaires, Time Factors, Multiple regression analysis, Neurosciences, Thrombolytic Therapy, and hospital units
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Background The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's... more
Background The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's discretion. Aim Our aim was to evaluate safety and effectiveness of intravenous alteplase in patients not fully adhering to the drug license compared with those treated strictly according to the license in Central and Eastern Europe. Methods We analyzed the data contributed to Safe Implementation of Thrombolysis in Stroke registry from nine countries between February 2003 and February 2010. Statistical analysis included multivariate logistic regression. Results Of 5594 consecutive patients, 1919 patients (34·3%) not fully adhered to the license. The most frequent deviations were: time-to-treatment >3 h (13·1%), use of intravenous antihypertensives (8·3%), age >80 years (7·3%), oral anticoagulation (4·2%), a previous stroke with concomitant diabetes...
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Background Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe... more
Background Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe Implementation of Thrombolysis in Stroke-Non-European Union World was required to assess the safety of alteplase in an Asian population by comparison with results from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study and pooled results from randomized controlled trials. Aims and/or hypothesis To evaluate the efficacy and safety of intravenous alteplase (0·9 mg/kg) as thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an Asian population. Methods The 591 patients included were treated at 48 centers in four countries (South Korea, China, India, and Singapore) between 2006 and 2008. Primary outcomes were symptomatic (deterioration in National Institutes of Health Stroke Scale score ≥4 or death within the fir...
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Background/Aim: The cause of elevated blood pressure (BP) in acute stroke is unknown. Stress is often suggested as a main contributing factor. We aimed to investigate the relationship between BP and stress in patients with acute stroke.... more
Background/Aim: The cause of elevated blood pressure (BP) in acute stroke is unknown. Stress is often suggested as a main contributing factor. We aimed to investigate the relationship between BP and stress in patients with acute stroke. Methods: 58 patients with clinical symptoms of stroke were recruited prospectively after exclusion of haemorrhage by CT scan within 14 h and 15 min (mean) after symptom onset (range 2 h and 45 min–23 h and 40 min). The mean age of the patients was 66 years (range 39–86 years), and the mean National Institute of Health Stroke Scale score was 7 (range 1–26). BP and pulse rate were recorded by non-invasive automatic monitoring hourly for 24 h. Stress was evaluated by testing the level of salivary cortisol. Four samples of saliva were obtained at inclusion, on the evening of the inclusion day (20.00–22.00 h), on the morning of the next day (7.00–9.00 h) and on the afternoon of the inclusion day/next day (15.00–17.00 h) within 24 h after inclusion in the ...
Research Interests: Cardiology, Cortisol, Humans, Hypertension, Blood Pressure, and 15 moreCircadian Rhythm, Female, Cerebrovascular diseases, Brain Ischemia, Ct Scan, Clinical Sciences, Aged, Adult, Biological markers, Cerebrovascular, Glucocorticoids, Diastole, hydrocortisone, Antihypertensive agents, and Geometric mean
Neurologic functions improve in most patients days and weeks after onset of a stroke. This can not be explained by recovery of the early salvageable ischemia zone. The most likely mechanism is relearning, a process in which healthy brain... more
Neurologic functions improve in most patients days and weeks after onset of a stroke. This can not be explained by recovery of the early salvageable ischemia zone. The most likely mechanism is relearning, a process in which healthy brain takes over functions lost with the infarct. Experimental studies indicate that this recovery can be modulated by pharmacological agents. NMDA antagonists and GABA agonists found to reduce infarct size in stroke models may have a harmful effect on relearning and neurologic recovery. This should be considered when clinical trial protocols are designed.
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Research Interests: Education, Evidence Based Medicine, Global Health, Health Education, Drug development, and 15 moreDatabases, Executive Function, Continuing Medical Education, Brain, Clinical research, Biomedical Research, Cerebrovascular Disease, Chronic Disease, Animals, Cerebrovascular diseases, Factual, Clinical Sciences, Cooperative Behavior, guidelines as topic, and Cardiovascular medicine and haematology
... Acute Treatment of Ischaemic Stroke Danilo Toni, Angel Chamorro, Markku Kaste, Kennedy Lees,Nils Gunnar Wahlgren, Werner Hacke ... Corbett D, Thornhill J: Temperature modulation (hypothermic and hyperthermic conditions) and its... more
... Acute Treatment of Ischaemic Stroke Danilo Toni, Angel Chamorro, Markku Kaste, Kennedy Lees,Nils Gunnar Wahlgren, Werner Hacke ... Corbett D, Thornhill J: Temperature modulation (hypothermic and hyperthermic conditions) and its influence on histological and behavioral ...
Research Interests: Humans, Anoxia, Hyperglycemia, Hypertension, Blood Pressure, and 15 morePulmonary Embolism, Pneumonia, Cerebrovascular diseases, Brain Ischemia, Case Management, Clinical Sciences, Fever, Risk Factors, Cerebrovascular, Intracranial Hypertension, Ischaemic Stroke, Neurosciences, Brain Edema, Combined Modality Therapy, and Acute Disease
There are many neuroprotectants currently under evaluation for the treatment of acute ischaemic stroke, but encouraging clinical trials have been rare. Neuroprotective drugs interfere with various stages of the ischaemic cascade leading... more
There are many neuroprotectants currently under evaluation for the treatment of acute ischaemic stroke, but encouraging clinical trials have been rare. Neuroprotective drugs interfere with various stages of the ischaemic cascade leading to irreversible tissue damage, and are not thought to affect bleeding. While trials of sodium/calcium channel modifiers have been problematic, there are hopes that the phenytoin derivative fos-phenytoin
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Outcome studies in cardiovascular diseases such as hypertension are often based in a number of countries recruiting from multiple centres. This can lead to difficulties in end-point evaluation and classification. The INSIGHT study... more
Outcome studies in cardiovascular diseases such as hypertension are often based in a number of countries recruiting from multiple centres. This can lead to difficulties in end-point evaluation and classification. The INSIGHT study provided the unique opportunity to examine the role and usefulness of a Critical Event Committee (CEC) established to examine all events occurring in a cohort of 6321 patients and classifying them according to pre-determined criteria. More than 28% of investigator-coded primary events and more than 41% of secondary events were re-classified by the CEC. Particularly difficult diagnoses included myocardial infarction, angina and heart failure, and the database finally analysed was substantially altered after CEC Committee evaluation. Post hoc analysis of the INSIGHT database demonstrated that the primary events compared would have been reduced from 6.3% vs 5.8% of those randomized on nifedipine vs co-amilozide to 5.1% vs 4.7%--an overall reduction of 72 events of 382, a fall of 18.8%. We conclude that a CEC should be a crucial component of any large outcome study and that if all events are subjected to scrutiny, the quality of the database is greatly enhanced.
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Background and Purpose— Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the... more
Background and Purpose— Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences. Methods— Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel. Results— During 2008, 942 pa...