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ObjectiveThe widespread adoption of endovascular therapy (EVT) for emergent large vessel occlusion has led to increased nationwide demand for neurointerventionalists, heightened interest among neurology residents to pursue neurointervention as a career, and increased importance of neurointervention exposure for all neurologists who care for patients with acute ischemic stroke. Exposure to neurointervention and its career path are not well-defined for neurology trainees.MethodsThe Society for Vascular and Interventional Neurology (SVIN) Education Committee conducted a multicenter electronic survey directed towards neurology residents and vascular neurology (VN), neurocritical care (NCC), and neurointervention fellows in June 2018. A total of 250 programs were invited to participate; 76 trainees completed the survey.ResultsRespondents self-identified as 22% postgraduate year (PGY)2, 40% PGY3/4, 30% VN fellows, and 8% neurointervention or NCC fellows. Eighty-seven percent of trainees had more than 2 months exposure to VN during residency, 41% to NCC, and only 3% to neurointervention. Sixty-eight percent of respondents had no exposure to neurointervention during residency. Whereas 72% believed that a background in neurology was good preparation for neurointervention, only 41% agreed that fellowship training pathway in neurointervention is well-structured for neurology residents when compared to other subspecialties.ConclusionIn this survey, respondents identified lack of exposure to neurointervention and a well-defined training pathway as obstacles towards pursuing neurointervention as a career. These obstacles must be addressed for the continued development of neurointervention as a subspecialty of neurology.

Background Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial. Methods We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days. Results From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from ‘fair’ to ‘very good’ and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination. Conclusions Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power. Trial registration Protocol available at reviewregistry540. Electronic supplementary material The online version of this article (10.1186/s13063-019-3222-x) contains supplementary material, which is available to authorized users.

Background and aim The availability and access of hospital administrative data [coding for Charlson comorbidity index (CCI)] in large data form has resulted in a surge of interest in using this information to predict mortality from stroke. The aims of this study were to determine the minimum clinical data set to be included in models for predicting disability after ischemic stroke adjusting for CCI and clinical variables and to evaluate the impact of CCI on prediction of outcome. Method We leverage anonymized clinical trial data in the Virtual International Stroke Trials Archive. This repository contains prospective data on stroke severity and outcome. The inclusion criteria were patients with available stroke severity score such as National Institutes of Health Stroke Scale (NIHSS), imaging data, and outcome disability score such as 90-day Rankin Scale. We calculate CCI based on comorbidity data in this data set. For logistic regression, we used these calibration statistics: Nagelkerke generalised R2 and Brier score; and for discrimination we used: area under the receiver operating characteristics curve (AUC) and integrated discrimination improvement (IDI). The IDI was used to evaluate improvement in disability prediction above baseline model containing age, sex, and CCI. Results The clinical data among 5,206 patients (55% males) were as follows: mean age 69 ± 13 years, CCI 4.2 ± 0.8, and median NIHSS of 12 (IQR 8, 17) on admission and 9 (IQR 5, 15) at 24 h. In Model 2, adding admission NIHSS to the baseline model improved AUC from 0.67 (95% CI 0.65–0.68) to 0.79 (95% CI 0.78–0.81). In Model 3, adding 24-h NIHSS to the baseline model resulted in substantial improvement in AUC to 0.90 (95% CI 0.89–0.91) and increased IDI by 0.23 (95% CI 0.22–0.24). Adding the variable recombinant tissue plasminogen activator did not result in a further change in AUC or IDI to this regression model. In Model 3, the variable NIHSS at 24 h explains 87.3% of the variance of Model 3, follow by age (8.5%), comorbidity (3.7%), and male sex (0.5%). Conclusion Our results suggest that prediction of disability after ischemic stroke should at least include 24-h NIHSS and age. The variable CCI is less important for prediction of disability in this data set.

Background Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood–brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J). Aims The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4–24, age 18–85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients. Methods Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0–1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging. Conclusion Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions but not extended ischemic brain damage can be safely and effectively treated up to nine-hours after onset.

You have just encountered a possible stroke patient. You ask yourself: what should I do first? How do I know it is a stroke? Is it too late to reverse the damage? How do I do the right things in the right order? This book will help you answer these critical questions. It provides practical advice on the care of stroke patients in a range of acute settings. The content is arranged in chronological order, covering the things to consider in assessing and treating the patient in the emergency department, the stroke unit and then on transfer to a rehabilitation facility. All types of stroke are covered. This new edition provides updated information from recently completed clinical trials and added information on endovascular therapy, hemicraniectomy for severe stroke, DVT prophylaxis and stroke prevention. A comprehensive set of appendices contain useful reference information including dosing algorithms, conversion factors and stroke scales.

Background and Purpose— Intra-arterial recanalization therapy (IAT) is increasingly used for acute stroke. Despite high rates of recanalization, the outcome is variable. We attempted to identify predictors of outcome that will enable better patient selection for IAT. Methods— All patients who underwent IAT at the University of Texas Houston Stroke Center were reviewed. Poor outcome was defined as modified Rankin Scale score 4 to 6 on hospital discharge. Findings were validated in an independent data set of 175 patients from the University of California at Los Angeles Stroke Center. Results— One hundred ninety patients were identified. Mean age was 62 years and median baseline National Institutes of Health Stroke Scale score was 0.18. Recanalization rate was 75%, symptomatic hemorrhage rate was 6%, and poor outcome rate was 66%. Variables associated with poor outcome were: age, baseline National Institutes of Health Stroke Scale, admission glucose, diabetes, heart disease, previous stroke, and the absence of mismatch on the pretreatment MRI. Logistic regression identified 3 variables independently associated with poor outcome: age ( P =0.049; OR, 1.028), National Institutes of Health Stroke Scale ( P =0.013; OR, 1.084), and admission glucose ( P =0.031; OR, 1.011). Using these data, we devised the Houston IAT score: 1 point for age >75 years; 1 for National Institutes of Health Stroke Scale score >18, and 1 point for glucose >150 mg/dL (range, 0 to 3 mg/dL). The percentage of poor outcome by Houston IAT score was: score of 0, 44%; 1, 67%; 2, 97%; and 3, 100%. Recanalization rates were similar across the scores ( P =0.4). Applying Houston IAT to the external cohort showed comparable trends in outcome and nearly identical rates in the Houston IAT therapy 3 tier. Conclusions— The Houston IAT score estimates the chances of poor outcome after IAT, even with recanalization. It may be useful in comparing cohorts of patients and when assessing the results of clinical trials.

Background and Purpose— Stroke incidence and outcome vary widely within and across geographical locations. We examined whether differences in index stroke severity, stroke risk factors, mortality, and stroke outcome across geographical locations remain after adjusting for case mix. Methods— We analyzed 3284 patients from the Virtual International Stroke Trials Archive (VISTA). We used logistic regression to examine the incidence of mild index stroke, functional, and neurological outcomes after accounting for age, medical history, year of trial recruitment, and initial stroke severity in the functional and neurological outcome analyses. We examined mortality between geographical regions using a Cox proportional hazards model, accounting for age, initial stroke severity, medical history, and year of trial recruitment. Results— Patients enrolled in the USA and Canada had the most severe index strokes. Those recruited in Austria and Switzerland had the best functional and neurological outcomes at 90 days ( P P =0.013). Patients enrolled in Austria, Switzerland, Belgium, Netherlands, Finland, Germany, Greece, Israel, Spain, and Portugal had a significantly better survival rate when compared with those enrolled in USA and Canada. Patients enrolled in trials after 1998 had more severe index strokes, with no significant difference in outcome compared with those enrolled before 1998. Conclusion— We identified regional variations in index stroke severity, outcome, and mortality for patients enrolled in ischemic stroke clinical trials over the past 13 years that were not fully explained by case mix. Index stroke severity was greater in patients enrolled after 1998, with no significant improvement in outcomes compared to those enrolled before 1998.

Background: The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute ischemic stroke is related to clot lysis and arterial recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. However, human data on this combination are limited. Design: We report an update of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose escalation, safety, and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 h. After standard dose intravenous rtPA administration, a 100-μg/kg bolus of argatroban followed by infusion of 1 μg/kg per min for 48 h was adjusted to a target partial thromboplastin time of 1.75 times baseline. Results: Twenty patients with middle cerebral artery occlusions (including 13 men) have been enrolled, with a mean ± SD age of 61 ± 13 years. Baseline median National Institute of Health Stroke Scale score was 12.5 (range, 3–25). The mean ± SD time from symptom onset to argatroban bolus administration was 177 ± 56 min. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 2 patients and there was 1 death. Recanalization was complete in 7 patients and partial in another 7, and reocclusion occurred in 4 within 2 h of rtPA bolus administration. Conclusion: The combination of low-dose argatroban and intravenous rtPA may be safe, and produce faster and more complete recanalization, but a larger cohort of patients is required to confirm this pilot study.

Background The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute stroke is linked to clot lysis and artery recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. There are no human data on this combination. Design We report the first phase of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose-escalation, safety and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 hours. After standard-dose intravenous rtPA administration, a 100-μg/kg bolus of argatroban followed by infusion of 1 μg/kg per minute for 48 hours was adjusted to a target partial thromboplastin time of 1.75 times that of the control group. Results Fifteen patients (including 10 men) were enrolled, with a mean ± SD age of 61 ± 13 years. All patients had middle cerebral artery occlusions. Baseline median National Institute of Health Stroke Scale score was 14 (range, 4-25). The mean ± SD time from symptom onset to argatroban bolus administration was 172 ± 53 minutes. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 1 patient and there was 1 death. Recanalization was complete in 6 patients and partial in another 4, and reocclusion occurred in 3 within 2 hours of rtPA bolus administration. Conclusion The safety of low-dose argatroban combined with intravenous rtPA may be within acceptable limits, and its efficacy for producing fast and complete recanalization is promising, but a larger cohort of patients is required to confirm these preliminary observations. Trial Registration clinicaltrials.gov Identifier:NCT00268762