Myzoon Ali

Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes.

Background: Hematoma expansion (HE) is a surrogate marker in intracerebral hemorrhage (ICH) trials. However, the amount of HE necessary to produce poor outcomes in an individual is unclear; there is no agreement on a clinically meaningful definition of HE. We compared commonly used definitions of HE in their ability to predict poor outcome as defined by various cutpoints on the modified Rankin Scale (mRS). Methods: In this cohort study, we analyzed 531 patients with ICH from the Virtual International Stroke Trials Archive. Primary outcome was mRS at 90 days, dichotomized into 0–3 vs 4–6. Secondary outcomes included other mRS cutpoints and mRS “shift analysis.” Sensitivity, specificity, and predictive values for commonly used HE definitions were calculated. Results: Between 13% and 32% of patients met the commonly used HE definitions. All definitions independently predicted poor outcome; positive predictive values increased with higher growth cutoffs but at the expense of lower sensitivities. All HE definitions showed higher specificity than sensitivity. Absolute growth cutoffs were more predictive than relative cutoffs when mRS 5–6 or 6 was defined as “poor outcome.” Conclusion: HE robustly predicts poor outcome regardless of the growth definition or the outcome definition. The highest positive predictive values are obtained when using an absolute growth definition to predict more severe outcomes. Given that only a minority of patients may have clinically relevant HE, hemostatic ICH trials may need to enroll a large number of patients, or select for a population that is more likely to have HE.

The Virtual International Stroke Trials Archive

Background and Purpose— Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods— Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results— Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on >15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69±12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions— This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning.

Relationship Between Hyperacute Blood Pressure and Outcome After Ischemic Stroke Data From the VISTA Collaboration

Background and Purpose— High blood pressure (BP) is associated independently with poor outcome after acute ischemic stroke, although in most analyses “baseline” BP was measured 24 hours or more postictus, and not during the hyperacute period. Methods— Analyses included 1722 patients in hyperacute trials (recruitment <8 hours) from the Virtual Stroke International Stroke Trial Archive (VISTA) Collaboration. Data on BP at enrolment and after 1, 2, 16, 24, 48, and 72 hours, neurological impairment at 7 days (NIHSS), and functional outcome at 90 days (modified Rankin scale) were assessed using logistic regression models, adjusted for confounding variables; results are for 10-mm Hg change in BP. Results— Mean time to enrolment was 3.7 hours (range 1.0 to 7.9). High systolic BP (SBP) was significantly associated with increased neurological impairment (odds ratio, OR 1.06, 95% confidence interval, 95% CI 1.01 to 1.12), and poor functional outcome; odds ratios for both increased with later BP measurements made at up to 24 hours poststroke. Smaller (versus larger) declines in SBP over the first 24 hours were significantly associated with poor NIHSS scores (OR 1.16, 95% CI 1.05 to 1.27) and functional outcome (OR 1.23, 95% CI 1.13 to 1.34). A large variability in SBP was also associated with poor functional outcome. Conclusions— High SBP and large variability in SBP in the hyperacute stages of ischemic stroke are associated with increased neurological impairment and poor functional outcome, as are small falls in SBP over the first 24 hours.

Interconversion of the National Institutes of Health Stroke Scale and Scandinavian Stroke Scale in acute stroke

INTRODUCTION The National Institutes of Health Stroke Scale (NIHSS) and Scandinavian Stroke Scale (SSS) are both validated measures of neurologic impairment and have been used in many acute stroke trials. Methods for interconverting SSS and NIHSS are needed. METHODS Conversion equations were developed using linear regression (both unadjusted, and adjusted for age and sex) using a random 50% of the data at both baseline and 90 days. The remaining 50% of data were used to test the accuracy of the models produced. RESULTS Data from 5 acute stroke trials (2004 patients) were included. Fitted models at baseline were NIHSS = 25.68 - 0.43 * SSS (R(2) = 0.57, prediction error [PE] -0.2, P = .20), and SSS = 50.37 - 1.63 * NIHSS (R(2) = 0.59, PE 0.2, P = .35). The 90-day models were NIHSS = 22.99 - 0.39 * SSS (R(2) = 0.82, PE -0.3, P = .001), and SSS = 56.68 - 2.20 * NIHSS (R(2) = 0.80, PE -0.4, P = .08). Adjustment did not materially improve the R(2) values. CONCLUSION Total scores for NIHSS and SSS may be interconverted with good precision; the mathematic conversion equations may prove useful in clinical practice and in comparison of data from observational studies and randomized trials.

Small intracerebral haemorrhages are associated with less haematoma expansion and better outcomes.

Background and purpose Haematoma expansion following intracerebral haemorrhage is a major determinant of early neurological worsening and poor clinical outcome. This has created interest in improving patient selection for therapies targeting haematoma expansion. Based on prior observations, we hypothesised that intracerebral haemorrhage volumes under 10 ml would be less likely to expand. We additionally sought to define a baseline haematoma volume below which significant growth was not observed. Methods Patient data were obtained from the Virtual International Stroke Trials Archive. Patients with intracerebral haemorrhage presented within six-hours of symptom onset had baseline clinical, radiological and laboratory data, and computed tomographic scan at 72 h and three-month follow-up. The predictor of interest was baseline haematoma volume. Primary outcomes were absolute and relative haematoma growth. Secondary outcomes were early neurological worsening, good functional outcome, and 90-day mortality. Results The final dataset consisted of 496 patients. Baseline haematoma volumes under 10 ml were associated with much lower odds of absolute expansion compared to larger haematomas. Smaller haematomas were associated with significantly decreased odds of early neurological worsening and three-month mortality, and increased odds of good functional outcome. The smallest haematoma to double in size was 3·97 ml. Among the 34 subjects with very small haematomas (<3 ml), none had early neurological worsening and most had good three-month outcome (73·5%, mRS≤3). Conclusions This study provides observational evidence that very small haematomas are unlikely to expand, by commonly used absolute growth definitions, and may represent a subgroup of patients with intracerebral haemorrhage destined towards good clinical outcomes.

Stroke Outcome in Clinical Trial Patients Deriving From Different Countries

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<0.05), whereas those enrolled in Germany had the worst functional outcome at 90 days (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.

Delayed Detection of Atrial Fibrillation after Ischemic Stroke

BACKGROUND Detection of atrial fibrillation (AF) after ischemic stroke is important because anticoagulation is indicated to reduce the risk of recurrent stroke. However, no consensus exists about the optimum method for detecting underlying paroxysmal AF not apparent on presentation with stroke. The aim of this study was to characterize the rate, timing, and predictors of delayed detection of AF after stroke. METHODS The Virtual International Stroke Trials Archive provided data from 3464 patients in the placebo arms of 4 clinical trials of therapies for acute ischemic stroke. Patients who had AF by history or on the baseline electrocardiogram were excluded. Electrocardiograms were obtained routinely and as clinically indicated. The time to detection of AF was evaluated using Kaplan-Meier survival statistics. Cox proportional hazards analysis was used to evaluate risk factors for AF. RESULTS Among 2504 qualifying patients, AF was detected in 174 (6.9%; 95% confidence interval [CI] 6.0%-8.0%). In 68% of patients, AF was detected more than 48 hours after presentation. Detection of AF was associated with increasing age (hazard ratio [HR] 1.6/decade; 95% CI 1.4-1.9; P < .005), female sex (HR 1.7; CI 1.2-2.4; P < .005), congestive heart failure (HR 1.9; CI 1.1-3.4; P = .02), and the absence of hypertension (HR 1.6; CI 1.1-2.2; P = .01). CONCLUSIONS Delayed detection of AF was common in this large cohort of patients carefully monitored after ischemic stroke. Current methods of screening may fail to detect underlying paroxysmal AF in a substantial proportion of patients.

Association Between Disability Measures and Healthcare Costs After Initial Treatment for Acute Stroke

Background and Purpose— The distribution of 3-month modified Rankin scale (mRS) scores has been used as an outcome measure in acute stroke trials. We hypothesized that hospitalization and institutional care home stays within the first 90 days after stroke should be closely related to 90-day mRS, that each higher mRS category will reflect incremental cost, and that resource use may be less clearly linked to the National Institutes of Health Stroke Scale (NIHSS) or Barthel index. Methods— We examined resource use data from the GAIN International trial comparing 90-day mRS with total length of stay in hospital or other institutions during the first 90 days. We repeated analyses using NIHSS and Barthel index scores. Relationships were examined by analysis of variance (ANOVA) with Bonferroni contrasts of adjacent score categories. Estimated costs were based on published Scottish figures. Results— We had full data from 1717 patients. Length of stay was strongly associated with final mRS (P<0.0001). Each mRS increment from 0 to 1–2 to 3–4 was significant (mean length of stay: 17, 25, 44, 58, 79 days; P<0.0005). Ninety-five percent confidence limits for estimated costs (£) rose incrementally: 2493 to 3412, 3369 to 4479, 5784 to 7008, 7300 to 8512, 10 095 to 11 141, 11 772 to 13 560, and 2623 to 3321 for mRS 0 to 5 and dead, respectively. Weaker relationships existed with Barthel and NIHSS. Conclusions— Each mRS category reflects different average length of hospital and institutional stay. Associated costs are meaningfully different across the full range of mRS outcomes. Analysis of the full distribution of mRS scores is appropriate for interpretation of treatment effects after acute stroke and more informative than Barthel or NIHSS end points.

Standardized measurement of sensorimotor recovery in stroke trials: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable

Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.

Recovery From Poststroke Visual Impairment Evidence From a Clinical Trials Resource

Introduction. Limited evidence suggests that visual impairments may influence outcome after stroke. The degree of recovery from these impairments is poorly characterized. Objectives. To describe recovery and to determine whether visual impairments influence functional outcome and quality of life. Methods. We extracted demographic and outcome data from the Virtual International Stroke Trials Archive (VISTA). We examined horizontal eye movement disorders and hemianopia using the Best Gaze and Visual domains of the National Institutes of Health Stroke Scale (NIHSS) and described recovery at 30 and 90 days. Proportional odds modelling was used to examine the association between impairments at baseline, modified Rankin Scale (mRS), and European Quality of Life Score (EQ-5D) at 90 days. Results. Visual impairments were reported in 7,204/11,900 (60.5%) patients at baseline. Complete recovery occurred in 1,398/3,285 (42.6%) and 3,243/7,204 (45.0%) patients by 30 and 90 days respectively. The burden of persistent visual impairment in survivors was 1,135/4,028 (28.2%) at 30 days and 1,915/9,338 (20.5%) at 90 days. Partial gaze palsy (P < .0001; OR = 0.81; 95% CI = 0.74-0.87), forced deviation (P < .0001; OR = 0.48; 95% CI = 0.43-0.53), and complete homonymous hemianopia (P < .0001; OR = 0.67; 95% CI = 0.62-0.73) at baseline were associated with poor mRS at 90 days. Conclusions. The rate of recovery was greater in the first month after stroke, suggesting a potential time frame for interventions. The associations between visual impairments and poor mRS suggest that these impairments should be considered in multidisciplinary assessments and interventions.