Carlos Molina | Universidad Central de Venezuela (original) (raw)

Papers by Carlos Molina

Research paper thumbnail of Prediction of Early Neurological Deterioration Using Diffusion- and Perfusion-Weighted Imaging in Hyperacute Middle Cerebral Artery Ischemic Stroke

Stroke, 2002

Background and Purpose— Early neurological deterioration (END) occurs in approximately one third ... more Background and Purpose— Early neurological deterioration (END) occurs in approximately one third of all ischemic stroke patients and is associated with a poor outcome. Our study sought to assess the value of ultra-early MRI in the prediction of END in stroke patients. Methods— Between August 1999 and November 2001, 38 stroke patients with a proven middle cerebral artery (MCA) or intracranial internal carotid artery (ICA) occlusion on MR angiography underwent perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) within 6 hours after onset, and 30 fulfilled all inclusion criteria. Control DWI and MR angiography were performed between days 3 and 5. Cranial CT was performed to rule out hemorrhagic transformation. Vascular risk factors, temperature, blood pressure, glycemia, and blood count were assessed on admission. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 6, 12, 24, and 48 hours. At the same time points, transcranial Do...

Research paper thumbnail of Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial

International journal of stroke : official journal of the International Stroke Society, Jan 29, 2015

We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ... more We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ultrasound using an operator-independent headframe to recombinant tissue-plasminogen-activator for the treatment of acute ischemic stroke. Combined lysis of thrombus with ultrasound and systemic tissue-plasminogen-activator for emergent revascularization in acute ischemic stroke is a randomized, double-blind, placebo-controlled clinical trial that will enroll subjects with the following main inclusion criteria: less than 4·5 hours from symptom onset (three-hours in US and Canada), age 18-80 years, baseline National Institutes of Health Stroke Scale score ≥ 10, and premorbid modified-Rankin-score of 0-1, eligibility for full dose recombinant tissue-plasminogen-activator. Subjects will receive two-hours of 2-MHz pulsed wave transcranial ultrasound (target group) or sham ultrasound (control group). The projected sample size is approximately 824 subjects. The primary endpoint, based on inten...

Research paper thumbnail of Impact of Time to Treatment on Tissue-Type Plasminogen Activator-Induced Recanalization in Acute Ischemic Stroke

Stroke, 2014

Background and Purpose— Although tissue-type plasminogen activator (tPA) efficacy depends on time... more Background and Purpose— Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke. Methods— Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point. Results— Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >...

Research paper thumbnail of Age-adjusted infarct volume threshold for good outcome after endovascular treatment

Journal of NeuroInterventional Surgery, 2013

Background and purpose Infarct volume and age are strong predictors of outcome in patients with s... more Background and purpose Infarct volume and age are strong predictors of outcome in patients with stroke. We aimed to determine the impact of infarct volume on outcome according to age. Methods Consecutive patients with acute stroke with documented internal carotid artery/middle cerebral artery occlusion who underwent endovascular procedures were studied. Patients were categorized in three age groups: <70 years (G1), 70-79 years (G2), ≥80 years (G3). The Alberta Stroke Program Early CT score (ASPECTS) was graded on initial CT. Time of successful recanalization (Thrombolysis In Cerebral Infarct (TICI) ≥2b)and good outcome at 3 months (modified Rankin Scale score ≤2) were recorded. Infarct volume was measured on the 24 h control CT. Results A total of 214 patients were studied (G1: 68; G2: 74; G3: 72). For all patients the mean infarct volume was 94.7±127 mL; 35.6% had a good outcome. We observed larger infarct volumes in patients with a bad outcome in each age group (G1: 22 vs 182 mL, p<0.01/G2: 22 vs 164 mL, p<0.01/G3: 7.6 vs 132 mL, p<0.01). However, the target cutoff infarct volume that better predicted a good outcome decreased as age

Research paper thumbnail of Lower concentrations of thrombin-antithrombin complex (TAT) correlate to higher recanalisation rates among ischaemic stroke patients treated with t-PA

Thrombosis and Haemostasis, 2009

SummaryAn elevated concentration of the thrombin-antithrombin complex (TAT) has been associated w... more SummaryAn elevated concentration of the thrombin-antithrombin complex (TAT) has been associated with high mortality rates and poor outcome in ischaemic stroke patients treated with tissue plasminogen activator (t-PA). Moreover, antithrombin drugs have been tested in combination with t-PA in the acute phase of ischaemic stroke to increase treatment efficacy. We aimed to study whether poor outcome associated with TAT among ischaemic stroke patients treated with t-PA could be due to the effects of this complex on recanalisation rates of the middle cerebral artery (MCA) and on haemorrhagic transformation. The TAT levels of 89 patients having a proximal MCA occlusion were measured by ELISA, and the patients were then treated with t-PA. Complete recanalisation was diagnosed by transcranial Doppler (TCD) at 1, 2 and 6 hours post-t-PA infusion and haemorrhagic transformation was identified by computed tomography (CT). Lower levels of TAT were associated with better recanalisation rates at a...

Research paper thumbnail of Baseline National Institutes of Health Stroke Scale–Adjusted Time Window for Intravenous Tissue-Type Plasminogen Activator in Acute Ischemic Stroke

Stroke, 2014

Background and Purpose— The effect of tissue-type plasminogen activator on functional outcome dec... more Background and Purpose— The effect of tissue-type plasminogen activator on functional outcome decreases progressively over time. However, given the differential pattern of arterial occlusion, stroke severity, and speed of ischemic lesion growth among candidates for reperfusion, the time window should be adjusted accordingly. We aimed to identify the impact of time-to-treatment according to stroke severity on functional outcome in patients with acute ischemic stroke. Methods— We included 581 consecutive patients treated with alteplase according to the European Summary of Product Characteristics criteria. Patients were categorized according to National Institutes of Health Stroke Scale (NIHSS) severity in mild NIHSS (≤8), moderate NIHSS (9–15), and severe stroke NIHSS (≥16). We sequentially analyzed time-to-treatment to achieve favorable outcome (modified Rankin Scale ≤2 at 3 months). Results— Overall, 19.8% had mild, 30.3% had moderate, and 49.9% had severe stroke. Favorable outcome ...

Research paper thumbnail of Speed of tPA-Induced Clot Lysis Predicts DWI Lesion Evolution in Acute Stroke

Stroke, 2007

Background and Purpose— We sought to evaluate the impact of the speed of recanalization on the ev... more Background and Purpose— We sought to evaluate the impact of the speed of recanalization on the evolution of diffusion- weighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). Methods— We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (<1 minute), stepwise (1 to 29 minutes), or slow (>30 minutes). Results— During transcranial Doppler monitoring, 13 (12.3%) patients recanalized suddenly, 32 (30.2%) recanalized in a stepwise manner, and 18 (17%) recanalized slowly. Baseline clinical...

Research paper thumbnail of Impact of Admission Hyperglycemia on Stroke Outcome After Thrombolysis: Risk Stratification in Relation to Time to Reperfusion

Stroke, 2004

Background and Purpose-We evaluated the impact of admission hyperglycemia (HG) on stroke outcome ... more Background and Purpose-We evaluated the impact of admission hyperglycemia (HG) on stroke outcome in relation to the timing of reperfusion in patients treated with tissue plasminogen activator (tPA). Methods-We studied 138 consecutive stroke patients with a documented middle cerebral artery (MCA) occlusion treated with intravenous tPA Ͻ3 hours of stroke onset. Serum glucose was determined at baseline before tPA administration. HG was defined as a glucose level Ͼ140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hour. Transcranial Doppler monitoring of recanalization was conducted during the first 12 hour of stroke onset. mRS was used to assess outcome at 3 months. Results-Median baseline NIHSS score was 17 points. At baseline, 42 (37.3%) patients were hyperglycemic and 96 (62.7%) normoglycemic. Reperfusion was achieved Ͻ3 hours of stroke onset in 32 (23%) patients, between 3 to 6 hours in 49 (36%), 6 to 12 hours in 15 (12%), and in 32 (23%) the MCA remained occluded at 12 hours. A logistic regression model revealed that baseline NIHSS score Ͼ16 points (odds ratio [OR], 3.32; 95% CI, 2.18 to 24.7; Pϭ0.032) and admission glucose level Ͼ140 mg/dL (OR, 5.65; 95% CI, 1.97 to 16.18; Pϭ0.002) independently predicted poor outcome (modified Rankin scale, 3 to 6) at 3 months. After adjusting by age, stroke severity, site of MCA occlusion, and degree of recanalization, the contribution of HG for poor outcome was higher as shorter the time to reperfusion. The highest odds for poor outcome related to HG corresponded to patients who recanalized Ͻ3 hour (OR, 3.1; 95% CI, 1.8 to 14.3; Pϭ0.002), as compared with those who recanalized between 3 and 6 hours (OR, 2.1; 95% CI, 1.1 to 16; Pϭ0.034) and between 6 to 12 hours (OR, 1.1; 95% CI, 0.7 to 21; Pϭ0.43). Moreover, baseline glucose level was negatively correlated (rϭϪ0.45; Pϭ0.001) with the degree of improvement in the NIHSS score at 24 hours after early (Ͻ3 hours) but not after delayed (Ͼ3 hours) or no recanalization. Conclusion-The impact of admission HG on stroke outcome varies depending on the time to tPA-induced reperfusion. The detrimental effect of acute HG is higher after early than after delayed or no reperfusion. Ultra-early glycemic control before reperfusion may improve the efficacy of thrombolytic therapy.

Research paper thumbnail of Time Course of Tissue Plasminogen Activator-Induced Recanalization in Acute Cardioembolic Stroke: A Case-Control Study

Stroke, 2001

Background and Purpose — The relationship between arterial recanalization, infarct size, and outc... more Background and Purpose — The relationship between arterial recanalization, infarct size, and outcome in patients treated with intravenous thrombolytics remains unclear. Therefore, we aimed to determine the time course of recombinant tissue plasminogen activator (rtPA)-induced recanalization in patients with cardioembolic stroke treated <3 hours from symptom onset and to investigate the relationship between arterial recanalization, infarct volume, and outcome. Methods — We prospectively studied 72 patients with an acute cardioembolic stroke in the middle cerebral artery territory: 24 treated with rtPA at <3 hours and 48 matched controls. Serial transcranial Doppler examinations were performed on admission and at 6,12, 24, and 48 hours. Infarct volume was measured by use of CT at day 5 to 7. Modified Rankin Scale score was used to assess outcome at 3 months. Results — Rate of 6-hour recanalization was higher ( P <0.001) in the rtPA group (66%) than in the control group (15%)....

Research paper thumbnail of Timing of Recanalization After Microbubble-Enhanced Intravenous Thrombolysis in Basilar Artery Occlusion

Stroke, 2007

Background and Purpose— Information about early recanalization of basilar artery occlusion after ... more Background and Purpose— Information about early recanalization of basilar artery occlusion after systemic tissue plasminogen activator remains unknown. We aimed to determine the timing of recanalization in basilar artery occlusion treated with systemic thrombolysis, microbubbles, and continuous transcranial Doppler monitoring. Methods— We studied 20 patients with <12 hours basilar artery occlusion treated with intravenous tissue plasminogen activator, 2 hours continuous ultrasound, and 3 boluses of microbubbles. Transcranial Doppler assessed recanalization at different time points. Outcome was assessed using the National Institutes of Health Stroke Scale and modified Rankin scale. Patients were considered to be independent if modified Rankin scale score was <3 at 90 days. Results— Median admission National Institutes of Health Stroke Scale was 18.5 (interquartile range 16 to 26.5) and median time to treatment was 180 minutes (range, 80 to 720 minutes). Rate of complete recanal...

Research paper thumbnail of Plasma VAP-1/SSAO Activity Predicts Intracranial Hemorrhages and Adverse Neurological Outcome After Tissue Plasminogen Activator Treatment in Stroke

Stroke, 2010

Background and Purpose— Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enz... more Background and Purpose— Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme involved in recruitment of lymphocytes and neutrophils through its semicarbazide-sensitive amine oxidase (SSAO) activity. We aimed to study plasma VAP-1/SSAO activity in relation to the risk for intracranial bleeding complications in patients with stroke treated with tissue plasminogen activator (tPA), the greatest safety concern with this treatment. Methods— In 141 patients with ischemic stroke, we measured VAP-1/SSAO activity in plasma taken before tPA administration. Hemorrhagic events were classified according to brain CT criteria and functional outcomes evaluated using the National Institutes of Health Stroke Scale. We also assessed the potential therapeutic effect of blocking VAP-1/SSAO activity in a rat embolic stroke model treated with tPA. Results— We saw significantly higher levels of plasma VAP-1/SSAO activity in patients who subsequently experienced hemorrhagic transforma...

Research paper thumbnail of Is it Time to Reassess the SITS-MOST Criteria for Thrombolysis?: A Comparison of Patients With and Without SITS-MOST Exclusion Criteria

Stroke, 2009

Background and Purpose— The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-... more Background and Purpose— The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) established guidelines to increase safety in acute stroke thrombolysis, but precluding treatment in an important proportion of patients. We aimed to assess safety/efficacy of thrombolysis in patients with SITS-MOST exclusion criteria. Methods— 369 nonlacunar tPA-treated patients were studied. Patients were classified as SITS-MOST (SM) or non–SITS-MOST (NSM) according to SITS-MOST–criteria fulfilling. Clinical evaluation was assessed by NIHSS and functional outcome by mRS at 3 months (functional independency=mRS ≤2). Results— Baseline NIHSS was 17. 169 (45.8%) patients were SM and 200 (54.1%) NSM. Recanalization (47.6%/50.3%, P =0.36), 24-hour-improvement (55.6%/49.5%, P =0.114), and SICH were similar (4.8%/5.1%, P =0.554). At discharge, clinical improvement in SM-group was higher (66.7%/55.7%, P =0.024). NSM tended to higher mortality (10.5%/16.1%, P =0.084) and lower functional in...

Research paper thumbnail of Clinical Deterioration After Intravenous Recombinant Tissue Plasminogen Activator Treatment: A Multicenter Transcranial Doppler Study

Stroke, 2006

Background and Purpose— Patients may experience clinical deterioration (CD) after treatment with ... more Background and Purpose— Patients may experience clinical deterioration (CD) after treatment with intravenous recombinant tissue plasminogen activator (rt-PA). We evaluated the ability of flow findings on transcranial Doppler to predict CD and outcomes on modified Rankin Scale. Methods— Patients with acute stroke received intravenous rt-PA within 3 hours of symptom onset at four academic centers. CD was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score by 4 points or more within 24 hours. Poor long-term outcome was defined by modified Rankin Scale ≥2 at 3 months. Transcranial Doppler findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion, or complete recanalization. Multiple regression analysis was used to identify transcranial Doppler flow as a predictor for CD after controlling for age, sex, baseline NIHSS, hypertension, and glucose. Results— A total of 374 patients re...

Research paper thumbnail of Timing of Spontaneous Recanalization and Risk of Hemorrhagic Transformation in Acute Cardioembolic Stroke

Stroke, 2001

Background and Purpose —The relationship between reperfusion and hemorrhagic transformation (HT) ... more Background and Purpose —The relationship between reperfusion and hemorrhagic transformation (HT) remains uncertain. Therefore, we aimed to clarify the relationship between the time course of recanalization and the risk of HT in patients with cardioembolic stroke studied within 6 hours of symptom onset. Methods —Fifty-three patients with atrial fibrillation and nonlacunar stroke in the middle cerebral artery (MCA) territory admitted within the first 6 hours after symptom onset were prospectively studied. Serial TCD examinations were performed on admission and at 6, 12, 24, and 48 hours. CT was performed within 6 hours after stroke onset and again at 36 to 48 hours. Results —Proximal and distal MCA occlusions were detected in 32 patients (60.4%) and 18 patients (34%), respectively. Early spontaneous recanalization occurring within 6 hours was identified in 10 patients (18.8%). Delayed recanalization (>6 hours) occurred in 28 patients (52.8%). HT on CT scan was detected in 17 patien...

Research paper thumbnail of Safety and Efficacy of Ultrasound-Enhanced Thrombolysis

Stroke, 2009

Background and Purpose— Ultrasound-enhanced thrombolysis is a promising new approach to facilitat... more Background and Purpose— Ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3 different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care (intravenous tPA). Subjects and Methods— Through Medline, Embase, and Cochrane database search, we identified and abstracted all studies of ultrasound-enhanced thrombolysis in acute cerebral ischemia. Principal investigators were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage (sICH) and recanalization rates were compared between tPA, tPA+TCD±microspheres (μS), tPA+TCCD±μS, and tPA+low-frequency u...

Research paper thumbnail of Effects of Admission Hyperglycemia on Stroke Outcome in Reperfused Tissue Plasminogen Activator–Treated Patients

Stroke, 2003

Background and Purpose— We sought to investigate the impact of hyperglycemia before reperfusion o... more Background and Purpose— We sought to investigate the impact of hyperglycemia before reperfusion on long-term outcome in patients treated with intravenous tissue plasminogen activator (tPA). Methods— Of 268 consecutive patients with a nonlacunar middle cerebral artery (MCA) stroke evaluated at <3 hours after onset, 73 (27.2%) received intravenous tPA. Serum glucose was determined at baseline before tPA administration. Hyperglycemia was defined as a glucose level >140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours. Transcranial Doppler monitoring of recanalization and reocclusion was conducted during the first 24 hours. Total infarct volume was measured on CT at day 5 to 7. Modified Rankin Scale was used to assess outcome at 3 months. Results— Median NIHSS score was 17. At baseline, 31 patients (42.5%) were hyperglycemic and 42 (57.5%) normoglycemic. Early reperfusion (<6 hours) occurred in 43 patients (58.9%). Admissio...

Research paper thumbnail of Thrombolysis-Related Hemorrhagic Infarction: A Marker of Early Reperfusion, Reduced Infarct Size, and Improved Outcome in Patients With Proximal Middle Cerebral Artery Occlusion

Stroke, 2002

Background and Purpose — The role of early and delayed recanalization after thrombolysis in the d... more Background and Purpose — The role of early and delayed recanalization after thrombolysis in the development of hemorrhagic transformation (HT) subtypes remains uncertain. We sought to explore the association between the timing of recanalization and HT risk in patients with proximal middle cerebral artery (MCA) occlusion treated with intravenous recombinant tissue plasminogen activator (rtPA) <3 hours of stroke onset and to investigate the relationship between HT subtypes, infarct volume, and outcome. Methods — Thirty-two patients with acute stroke caused by proximal MCA occlusion treated with rtPA <3 hours of symptom onset were prospectively studied. Serial transcranial Doppler examinations were performed on admission and at 6, 12, 24, and 48 hours. Presence and type of HT were assessed on CT at 36 to 48 hours. Modified Rankin scale was used to assess outcome at 3 months. Results — Early and delayed recanalization was identified in 17 patients (53.1%) and 8 patients (25%), res...

Research paper thumbnail of Safety Profile of Tissue Plasminogen Activator Treatment Among Stroke Patients Carrying a Common Polymorphism (C-1562T) in the Promoter Region of the Matrix Metalloproteinase-9 Gene

Stroke, 2003

Background and Purpose— Matrix metalloproteinase-9 (MMP-9) expression, related to blood-brain bar... more Background and Purpose— Matrix metalloproteinase-9 (MMP-9) expression, related to blood-brain barrier disruption, has been implicated in the appearance of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment in stroke patients. Because an in vitro functional polymorphism of the promoter region of MMP-9 gene (C-1562T) has been described, we hypothesize that patients carrying this mutation might have higher MMP-9 levels and greater susceptibility to developing HT when receiving tPA. Methods— We studied strokes involving the middle cerebral artery territory of 61 patients who received tPA <3 hours after stroke onset. Blood samples were obtained before tPA administration. Plasmatic MMP-9 determinations were performed (enzyme-linked immunosorbent assay, ng/mL), and C-1562T genotype was determined by polymerase chain reaction. Healthy age-matched control subjects were used to study allele distribution (n=59). Hemorrhagic events were classified according to...

Research paper thumbnail of Fas System Activation in Perihematomal Areas After Spontaneous Intracerebral Hemorrhage

Stroke, 2008

Background and Purpose— Apoptosis has been implicated as the prominent form of cell death in the ... more Background and Purpose— Apoptosis has been implicated as the prominent form of cell death in the brain perihematomal region in animal models and in autopsy or postsurgical human studies. Both the Fas system and caspase activation play a central role in apoptotic pathways. The aims of this study were to investigate soluble Fas (s-Fas) plasma levels after acute intracerebral hemorrhage (ICH), to determine its influence on clinical and radiologic features, and to assess Fas receptor and Fas ligand (Fas-L) protein expression in human ICH brain tissue. Methods— s-Fas plasma levels were determined on admission in 78 consecutive ICH patients and serially in a subgroup of 21 of them, at the time of neurologic assessment, by means of ELISA. ICH and perihematomal edema volumes were determined at baseline and on follow-up computed tomography scans, and ICH and perihematomal edema growth was calculated. The presence of Fas receptor and Fas-L was assessed in different brain tissue samples by imm...

Research paper thumbnail of Temporal Profile of Recanalization After Intravenous Tissue Plasminogen Activator: Selecting Patients for Rescue Reperfusion Techniques

Stroke, 2006

Background and Purpose— Intravenous thrombolysis in stroke achieves arterial recanalization in &5... more Background and Purpose— Intravenous thrombolysis in stroke achieves arterial recanalization in &50% of cases. Determining temporal profile of recanalization may address patient selection and potential benefits of further rescue reperfusion techniques. Methods— We studied 179 consecutive intravenous tissue plasminogen activator (t-PA)–treated patients with intracranial artery occlusion. Continuous transcranial Doppler assessed recanalization (none-partial-complete) at 60 minutes (early), 120 minutes (delayed) after t-PA bolus, and 6 hours (late) from symptom onset. Outcomes were determined: National Institutes of Health Stroke Scale (NIHSS; 48-hour NIHSS) and 3-month modified Rankin Scale (mRS). Results— On admission, 68% of patients presented proximal middle cerebral artery occlusion, median NIHSS 17. Early recanalization was complete for 30 patients (17%), partial for 50 (28%), and none for 99 (55%). Delayed recanalization was complete for 56 patients (31%), partial for 39 (22%), a...

Research paper thumbnail of Prediction of Early Neurological Deterioration Using Diffusion- and Perfusion-Weighted Imaging in Hyperacute Middle Cerebral Artery Ischemic Stroke

Stroke, 2002

Background and Purpose— Early neurological deterioration (END) occurs in approximately one third ... more Background and Purpose— Early neurological deterioration (END) occurs in approximately one third of all ischemic stroke patients and is associated with a poor outcome. Our study sought to assess the value of ultra-early MRI in the prediction of END in stroke patients. Methods— Between August 1999 and November 2001, 38 stroke patients with a proven middle cerebral artery (MCA) or intracranial internal carotid artery (ICA) occlusion on MR angiography underwent perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) within 6 hours after onset, and 30 fulfilled all inclusion criteria. Control DWI and MR angiography were performed between days 3 and 5. Cranial CT was performed to rule out hemorrhagic transformation. Vascular risk factors, temperature, blood pressure, glycemia, and blood count were assessed on admission. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 6, 12, 24, and 48 hours. At the same time points, transcranial Do...

Research paper thumbnail of Combined lysis of thrombus with ultrasound and systemic tissue plasminogen activator for emergent revascularization in acute ischemic stroke (CLOTBUST-ER): design and methodology of a multinational phase 3 trial

International journal of stroke : official journal of the International Stroke Society, Jan 29, 2015

We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ... more We designed a Phase 3 clinical trial to determine the safety and efficacy of adding transcranial ultrasound using an operator-independent headframe to recombinant tissue-plasminogen-activator for the treatment of acute ischemic stroke. Combined lysis of thrombus with ultrasound and systemic tissue-plasminogen-activator for emergent revascularization in acute ischemic stroke is a randomized, double-blind, placebo-controlled clinical trial that will enroll subjects with the following main inclusion criteria: less than 4·5 hours from symptom onset (three-hours in US and Canada), age 18-80 years, baseline National Institutes of Health Stroke Scale score ≥ 10, and premorbid modified-Rankin-score of 0-1, eligibility for full dose recombinant tissue-plasminogen-activator. Subjects will receive two-hours of 2-MHz pulsed wave transcranial ultrasound (target group) or sham ultrasound (control group). The projected sample size is approximately 824 subjects. The primary endpoint, based on inten...

Research paper thumbnail of Impact of Time to Treatment on Tissue-Type Plasminogen Activator-Induced Recanalization in Acute Ischemic Stroke

Stroke, 2014

Background and Purpose— Although tissue-type plasminogen activator (tPA) efficacy depends on time... more Background and Purpose— Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke. Methods— Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point. Results— Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >...

Research paper thumbnail of Age-adjusted infarct volume threshold for good outcome after endovascular treatment

Journal of NeuroInterventional Surgery, 2013

Background and purpose Infarct volume and age are strong predictors of outcome in patients with s... more Background and purpose Infarct volume and age are strong predictors of outcome in patients with stroke. We aimed to determine the impact of infarct volume on outcome according to age. Methods Consecutive patients with acute stroke with documented internal carotid artery/middle cerebral artery occlusion who underwent endovascular procedures were studied. Patients were categorized in three age groups: <70 years (G1), 70-79 years (G2), ≥80 years (G3). The Alberta Stroke Program Early CT score (ASPECTS) was graded on initial CT. Time of successful recanalization (Thrombolysis In Cerebral Infarct (TICI) ≥2b)and good outcome at 3 months (modified Rankin Scale score ≤2) were recorded. Infarct volume was measured on the 24 h control CT. Results A total of 214 patients were studied (G1: 68; G2: 74; G3: 72). For all patients the mean infarct volume was 94.7±127 mL; 35.6% had a good outcome. We observed larger infarct volumes in patients with a bad outcome in each age group (G1: 22 vs 182 mL, p<0.01/G2: 22 vs 164 mL, p<0.01/G3: 7.6 vs 132 mL, p<0.01). However, the target cutoff infarct volume that better predicted a good outcome decreased as age

Research paper thumbnail of Lower concentrations of thrombin-antithrombin complex (TAT) correlate to higher recanalisation rates among ischaemic stroke patients treated with t-PA

Thrombosis and Haemostasis, 2009

SummaryAn elevated concentration of the thrombin-antithrombin complex (TAT) has been associated w... more SummaryAn elevated concentration of the thrombin-antithrombin complex (TAT) has been associated with high mortality rates and poor outcome in ischaemic stroke patients treated with tissue plasminogen activator (t-PA). Moreover, antithrombin drugs have been tested in combination with t-PA in the acute phase of ischaemic stroke to increase treatment efficacy. We aimed to study whether poor outcome associated with TAT among ischaemic stroke patients treated with t-PA could be due to the effects of this complex on recanalisation rates of the middle cerebral artery (MCA) and on haemorrhagic transformation. The TAT levels of 89 patients having a proximal MCA occlusion were measured by ELISA, and the patients were then treated with t-PA. Complete recanalisation was diagnosed by transcranial Doppler (TCD) at 1, 2 and 6 hours post-t-PA infusion and haemorrhagic transformation was identified by computed tomography (CT). Lower levels of TAT were associated with better recanalisation rates at a...

Research paper thumbnail of Baseline National Institutes of Health Stroke Scale–Adjusted Time Window for Intravenous Tissue-Type Plasminogen Activator in Acute Ischemic Stroke

Stroke, 2014

Background and Purpose— The effect of tissue-type plasminogen activator on functional outcome dec... more Background and Purpose— The effect of tissue-type plasminogen activator on functional outcome decreases progressively over time. However, given the differential pattern of arterial occlusion, stroke severity, and speed of ischemic lesion growth among candidates for reperfusion, the time window should be adjusted accordingly. We aimed to identify the impact of time-to-treatment according to stroke severity on functional outcome in patients with acute ischemic stroke. Methods— We included 581 consecutive patients treated with alteplase according to the European Summary of Product Characteristics criteria. Patients were categorized according to National Institutes of Health Stroke Scale (NIHSS) severity in mild NIHSS (≤8), moderate NIHSS (9–15), and severe stroke NIHSS (≥16). We sequentially analyzed time-to-treatment to achieve favorable outcome (modified Rankin Scale ≤2 at 3 months). Results— Overall, 19.8% had mild, 30.3% had moderate, and 49.9% had severe stroke. Favorable outcome ...

Research paper thumbnail of Speed of tPA-Induced Clot Lysis Predicts DWI Lesion Evolution in Acute Stroke

Stroke, 2007

Background and Purpose— We sought to evaluate the impact of the speed of recanalization on the ev... more Background and Purpose— We sought to evaluate the impact of the speed of recanalization on the evolution of diffusion- weighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). Methods— We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (<1 minute), stepwise (1 to 29 minutes), or slow (>30 minutes). Results— During transcranial Doppler monitoring, 13 (12.3%) patients recanalized suddenly, 32 (30.2%) recanalized in a stepwise manner, and 18 (17%) recanalized slowly. Baseline clinical...

Research paper thumbnail of Impact of Admission Hyperglycemia on Stroke Outcome After Thrombolysis: Risk Stratification in Relation to Time to Reperfusion

Stroke, 2004

Background and Purpose-We evaluated the impact of admission hyperglycemia (HG) on stroke outcome ... more Background and Purpose-We evaluated the impact of admission hyperglycemia (HG) on stroke outcome in relation to the timing of reperfusion in patients treated with tissue plasminogen activator (tPA). Methods-We studied 138 consecutive stroke patients with a documented middle cerebral artery (MCA) occlusion treated with intravenous tPA Ͻ3 hours of stroke onset. Serum glucose was determined at baseline before tPA administration. HG was defined as a glucose level Ͼ140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hour. Transcranial Doppler monitoring of recanalization was conducted during the first 12 hour of stroke onset. mRS was used to assess outcome at 3 months. Results-Median baseline NIHSS score was 17 points. At baseline, 42 (37.3%) patients were hyperglycemic and 96 (62.7%) normoglycemic. Reperfusion was achieved Ͻ3 hours of stroke onset in 32 (23%) patients, between 3 to 6 hours in 49 (36%), 6 to 12 hours in 15 (12%), and in 32 (23%) the MCA remained occluded at 12 hours. A logistic regression model revealed that baseline NIHSS score Ͼ16 points (odds ratio [OR], 3.32; 95% CI, 2.18 to 24.7; Pϭ0.032) and admission glucose level Ͼ140 mg/dL (OR, 5.65; 95% CI, 1.97 to 16.18; Pϭ0.002) independently predicted poor outcome (modified Rankin scale, 3 to 6) at 3 months. After adjusting by age, stroke severity, site of MCA occlusion, and degree of recanalization, the contribution of HG for poor outcome was higher as shorter the time to reperfusion. The highest odds for poor outcome related to HG corresponded to patients who recanalized Ͻ3 hour (OR, 3.1; 95% CI, 1.8 to 14.3; Pϭ0.002), as compared with those who recanalized between 3 and 6 hours (OR, 2.1; 95% CI, 1.1 to 16; Pϭ0.034) and between 6 to 12 hours (OR, 1.1; 95% CI, 0.7 to 21; Pϭ0.43). Moreover, baseline glucose level was negatively correlated (rϭϪ0.45; Pϭ0.001) with the degree of improvement in the NIHSS score at 24 hours after early (Ͻ3 hours) but not after delayed (Ͼ3 hours) or no recanalization. Conclusion-The impact of admission HG on stroke outcome varies depending on the time to tPA-induced reperfusion. The detrimental effect of acute HG is higher after early than after delayed or no reperfusion. Ultra-early glycemic control before reperfusion may improve the efficacy of thrombolytic therapy.

Research paper thumbnail of Time Course of Tissue Plasminogen Activator-Induced Recanalization in Acute Cardioembolic Stroke: A Case-Control Study

Stroke, 2001

Background and Purpose — The relationship between arterial recanalization, infarct size, and outc... more Background and Purpose — The relationship between arterial recanalization, infarct size, and outcome in patients treated with intravenous thrombolytics remains unclear. Therefore, we aimed to determine the time course of recombinant tissue plasminogen activator (rtPA)-induced recanalization in patients with cardioembolic stroke treated <3 hours from symptom onset and to investigate the relationship between arterial recanalization, infarct volume, and outcome. Methods — We prospectively studied 72 patients with an acute cardioembolic stroke in the middle cerebral artery territory: 24 treated with rtPA at <3 hours and 48 matched controls. Serial transcranial Doppler examinations were performed on admission and at 6,12, 24, and 48 hours. Infarct volume was measured by use of CT at day 5 to 7. Modified Rankin Scale score was used to assess outcome at 3 months. Results — Rate of 6-hour recanalization was higher ( P <0.001) in the rtPA group (66%) than in the control group (15%)....

Research paper thumbnail of Timing of Recanalization After Microbubble-Enhanced Intravenous Thrombolysis in Basilar Artery Occlusion

Stroke, 2007

Background and Purpose— Information about early recanalization of basilar artery occlusion after ... more Background and Purpose— Information about early recanalization of basilar artery occlusion after systemic tissue plasminogen activator remains unknown. We aimed to determine the timing of recanalization in basilar artery occlusion treated with systemic thrombolysis, microbubbles, and continuous transcranial Doppler monitoring. Methods— We studied 20 patients with <12 hours basilar artery occlusion treated with intravenous tissue plasminogen activator, 2 hours continuous ultrasound, and 3 boluses of microbubbles. Transcranial Doppler assessed recanalization at different time points. Outcome was assessed using the National Institutes of Health Stroke Scale and modified Rankin scale. Patients were considered to be independent if modified Rankin scale score was <3 at 90 days. Results— Median admission National Institutes of Health Stroke Scale was 18.5 (interquartile range 16 to 26.5) and median time to treatment was 180 minutes (range, 80 to 720 minutes). Rate of complete recanal...

Research paper thumbnail of Plasma VAP-1/SSAO Activity Predicts Intracranial Hemorrhages and Adverse Neurological Outcome After Tissue Plasminogen Activator Treatment in Stroke

Stroke, 2010

Background and Purpose— Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enz... more Background and Purpose— Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme involved in recruitment of lymphocytes and neutrophils through its semicarbazide-sensitive amine oxidase (SSAO) activity. We aimed to study plasma VAP-1/SSAO activity in relation to the risk for intracranial bleeding complications in patients with stroke treated with tissue plasminogen activator (tPA), the greatest safety concern with this treatment. Methods— In 141 patients with ischemic stroke, we measured VAP-1/SSAO activity in plasma taken before tPA administration. Hemorrhagic events were classified according to brain CT criteria and functional outcomes evaluated using the National Institutes of Health Stroke Scale. We also assessed the potential therapeutic effect of blocking VAP-1/SSAO activity in a rat embolic stroke model treated with tPA. Results— We saw significantly higher levels of plasma VAP-1/SSAO activity in patients who subsequently experienced hemorrhagic transforma...

Research paper thumbnail of Is it Time to Reassess the SITS-MOST Criteria for Thrombolysis?: A Comparison of Patients With and Without SITS-MOST Exclusion Criteria

Stroke, 2009

Background and Purpose— The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-... more Background and Purpose— The Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) established guidelines to increase safety in acute stroke thrombolysis, but precluding treatment in an important proportion of patients. We aimed to assess safety/efficacy of thrombolysis in patients with SITS-MOST exclusion criteria. Methods— 369 nonlacunar tPA-treated patients were studied. Patients were classified as SITS-MOST (SM) or non–SITS-MOST (NSM) according to SITS-MOST–criteria fulfilling. Clinical evaluation was assessed by NIHSS and functional outcome by mRS at 3 months (functional independency=mRS ≤2). Results— Baseline NIHSS was 17. 169 (45.8%) patients were SM and 200 (54.1%) NSM. Recanalization (47.6%/50.3%, P =0.36), 24-hour-improvement (55.6%/49.5%, P =0.114), and SICH were similar (4.8%/5.1%, P =0.554). At discharge, clinical improvement in SM-group was higher (66.7%/55.7%, P =0.024). NSM tended to higher mortality (10.5%/16.1%, P =0.084) and lower functional in...

Research paper thumbnail of Clinical Deterioration After Intravenous Recombinant Tissue Plasminogen Activator Treatment: A Multicenter Transcranial Doppler Study

Stroke, 2006

Background and Purpose— Patients may experience clinical deterioration (CD) after treatment with ... more Background and Purpose— Patients may experience clinical deterioration (CD) after treatment with intravenous recombinant tissue plasminogen activator (rt-PA). We evaluated the ability of flow findings on transcranial Doppler to predict CD and outcomes on modified Rankin Scale. Methods— Patients with acute stroke received intravenous rt-PA within 3 hours of symptom onset at four academic centers. CD was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score by 4 points or more within 24 hours. Poor long-term outcome was defined by modified Rankin Scale ≥2 at 3 months. Transcranial Doppler findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion, or complete recanalization. Multiple regression analysis was used to identify transcranial Doppler flow as a predictor for CD after controlling for age, sex, baseline NIHSS, hypertension, and glucose. Results— A total of 374 patients re...

Research paper thumbnail of Timing of Spontaneous Recanalization and Risk of Hemorrhagic Transformation in Acute Cardioembolic Stroke

Stroke, 2001

Background and Purpose —The relationship between reperfusion and hemorrhagic transformation (HT) ... more Background and Purpose —The relationship between reperfusion and hemorrhagic transformation (HT) remains uncertain. Therefore, we aimed to clarify the relationship between the time course of recanalization and the risk of HT in patients with cardioembolic stroke studied within 6 hours of symptom onset. Methods —Fifty-three patients with atrial fibrillation and nonlacunar stroke in the middle cerebral artery (MCA) territory admitted within the first 6 hours after symptom onset were prospectively studied. Serial TCD examinations were performed on admission and at 6, 12, 24, and 48 hours. CT was performed within 6 hours after stroke onset and again at 36 to 48 hours. Results —Proximal and distal MCA occlusions were detected in 32 patients (60.4%) and 18 patients (34%), respectively. Early spontaneous recanalization occurring within 6 hours was identified in 10 patients (18.8%). Delayed recanalization (>6 hours) occurred in 28 patients (52.8%). HT on CT scan was detected in 17 patien...

Research paper thumbnail of Safety and Efficacy of Ultrasound-Enhanced Thrombolysis

Stroke, 2009

Background and Purpose— Ultrasound-enhanced thrombolysis is a promising new approach to facilitat... more Background and Purpose— Ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3 different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care (intravenous tPA). Subjects and Methods— Through Medline, Embase, and Cochrane database search, we identified and abstracted all studies of ultrasound-enhanced thrombolysis in acute cerebral ischemia. Principal investigators were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage (sICH) and recanalization rates were compared between tPA, tPA+TCD±microspheres (μS), tPA+TCCD±μS, and tPA+low-frequency u...

Research paper thumbnail of Effects of Admission Hyperglycemia on Stroke Outcome in Reperfused Tissue Plasminogen Activator–Treated Patients

Stroke, 2003

Background and Purpose— We sought to investigate the impact of hyperglycemia before reperfusion o... more Background and Purpose— We sought to investigate the impact of hyperglycemia before reperfusion on long-term outcome in patients treated with intravenous tissue plasminogen activator (tPA). Methods— Of 268 consecutive patients with a nonlacunar middle cerebral artery (MCA) stroke evaluated at <3 hours after onset, 73 (27.2%) received intravenous tPA. Serum glucose was determined at baseline before tPA administration. Hyperglycemia was defined as a glucose level >140 mg/dL. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours. Transcranial Doppler monitoring of recanalization and reocclusion was conducted during the first 24 hours. Total infarct volume was measured on CT at day 5 to 7. Modified Rankin Scale was used to assess outcome at 3 months. Results— Median NIHSS score was 17. At baseline, 31 patients (42.5%) were hyperglycemic and 42 (57.5%) normoglycemic. Early reperfusion (<6 hours) occurred in 43 patients (58.9%). Admissio...

Research paper thumbnail of Thrombolysis-Related Hemorrhagic Infarction: A Marker of Early Reperfusion, Reduced Infarct Size, and Improved Outcome in Patients With Proximal Middle Cerebral Artery Occlusion

Stroke, 2002

Background and Purpose — The role of early and delayed recanalization after thrombolysis in the d... more Background and Purpose — The role of early and delayed recanalization after thrombolysis in the development of hemorrhagic transformation (HT) subtypes remains uncertain. We sought to explore the association between the timing of recanalization and HT risk in patients with proximal middle cerebral artery (MCA) occlusion treated with intravenous recombinant tissue plasminogen activator (rtPA) <3 hours of stroke onset and to investigate the relationship between HT subtypes, infarct volume, and outcome. Methods — Thirty-two patients with acute stroke caused by proximal MCA occlusion treated with rtPA <3 hours of symptom onset were prospectively studied. Serial transcranial Doppler examinations were performed on admission and at 6, 12, 24, and 48 hours. Presence and type of HT were assessed on CT at 36 to 48 hours. Modified Rankin scale was used to assess outcome at 3 months. Results — Early and delayed recanalization was identified in 17 patients (53.1%) and 8 patients (25%), res...

Research paper thumbnail of Safety Profile of Tissue Plasminogen Activator Treatment Among Stroke Patients Carrying a Common Polymorphism (C-1562T) in the Promoter Region of the Matrix Metalloproteinase-9 Gene

Stroke, 2003

Background and Purpose— Matrix metalloproteinase-9 (MMP-9) expression, related to blood-brain bar... more Background and Purpose— Matrix metalloproteinase-9 (MMP-9) expression, related to blood-brain barrier disruption, has been implicated in the appearance of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) treatment in stroke patients. Because an in vitro functional polymorphism of the promoter region of MMP-9 gene (C-1562T) has been described, we hypothesize that patients carrying this mutation might have higher MMP-9 levels and greater susceptibility to developing HT when receiving tPA. Methods— We studied strokes involving the middle cerebral artery territory of 61 patients who received tPA <3 hours after stroke onset. Blood samples were obtained before tPA administration. Plasmatic MMP-9 determinations were performed (enzyme-linked immunosorbent assay, ng/mL), and C-1562T genotype was determined by polymerase chain reaction. Healthy age-matched control subjects were used to study allele distribution (n=59). Hemorrhagic events were classified according to...

Research paper thumbnail of Fas System Activation in Perihematomal Areas After Spontaneous Intracerebral Hemorrhage

Stroke, 2008

Background and Purpose— Apoptosis has been implicated as the prominent form of cell death in the ... more Background and Purpose— Apoptosis has been implicated as the prominent form of cell death in the brain perihematomal region in animal models and in autopsy or postsurgical human studies. Both the Fas system and caspase activation play a central role in apoptotic pathways. The aims of this study were to investigate soluble Fas (s-Fas) plasma levels after acute intracerebral hemorrhage (ICH), to determine its influence on clinical and radiologic features, and to assess Fas receptor and Fas ligand (Fas-L) protein expression in human ICH brain tissue. Methods— s-Fas plasma levels were determined on admission in 78 consecutive ICH patients and serially in a subgroup of 21 of them, at the time of neurologic assessment, by means of ELISA. ICH and perihematomal edema volumes were determined at baseline and on follow-up computed tomography scans, and ICH and perihematomal edema growth was calculated. The presence of Fas receptor and Fas-L was assessed in different brain tissue samples by imm...

Research paper thumbnail of Temporal Profile of Recanalization After Intravenous Tissue Plasminogen Activator: Selecting Patients for Rescue Reperfusion Techniques

Stroke, 2006

Background and Purpose— Intravenous thrombolysis in stroke achieves arterial recanalization in &5... more Background and Purpose— Intravenous thrombolysis in stroke achieves arterial recanalization in &50% of cases. Determining temporal profile of recanalization may address patient selection and potential benefits of further rescue reperfusion techniques. Methods— We studied 179 consecutive intravenous tissue plasminogen activator (t-PA)–treated patients with intracranial artery occlusion. Continuous transcranial Doppler assessed recanalization (none-partial-complete) at 60 minutes (early), 120 minutes (delayed) after t-PA bolus, and 6 hours (late) from symptom onset. Outcomes were determined: National Institutes of Health Stroke Scale (NIHSS; 48-hour NIHSS) and 3-month modified Rankin Scale (mRS). Results— On admission, 68% of patients presented proximal middle cerebral artery occlusion, median NIHSS 17. Early recanalization was complete for 30 patients (17%), partial for 50 (28%), and none for 99 (55%). Delayed recanalization was complete for 56 patients (31%), partial for 39 (22%), a...