Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke.

OBJECTIVE: To determine the association between sex and functional outcomes after thrombolytic treatment for acute ischemic stroke in the context of a clinical trial. METHODS: We analyzed predictors of outcome among patients treated with recombinant tissue plasminogen activator (rtPA) in the Glycine Antagonist in Neuroprotection for Patients with Acute Stroke Americas trial, a multicenter, randomized, double-blind, placebo-controlled study of a putative neuroprotectant. RESULTS: Among 1,367 trial patients, 333 (24%) were treated with rtPA within 3 hours. The proportion of patients achieving good functional outcomes at 3 months differed by sex (47.5% of men vs 30.3% of women had Barthel Index [BI] > or = 95; 32.2% of men vs 23.4% of women had modified Rankin Score [mRS] < or = 1). NIH Stroke Score was similar by sex. Men were more likely to have good functional outcomes after adjusting for relevant covariates: for BI > or = 95, adjusted odds ratio (OR) 3.28 (1.74 to 6.17); for mRS < or = 1, adjusted OR 2.12 (1.11 to 4.03). Survival was worse among men: adjusted OR 0.45 (0.20 to 1.01). Other predictors of functional outcomes included age, stroke side, severity, complications, and infections. CONCLUSIONS: Among tissue plasminogen activator-treated patients in this clinical trial population, men were approximately three times as likely to have good functional outcomes, despite elevated mortality. Thrombolysis for stroke may not reverse the tendency for women to have worse functional outcomes after stroke.

Correlation of aphasia and/or neglect with cortical infarction in a subpopulation of RANTTAS.

Classically in neurology, aphasia and neglect were accepted as reliable markers of cortical lesions. The actual prognostic values of aphasia and neglect have yet to be formally tested. This analysis sought to determine the predictive accuracy of aphasia and/or neglect in acute stroke for cortical infarction. Data from the RANTTAS investigation of tirilazad mesylate in stroke patients were reanalyzed, comparing acute National Institutes of Health Stroke Scale (NIHSS) measures of aphasia and neglect to lesion location on day 7-10 CT scans. Correlations between the presence of aphasia and/or neglect and the presence of a cortical lesion were only in the moderate range, and positive predictive values were far from perfect, as would be expected. 'Subcortical' aphasia or neglect was more likely in large, subcortical lesions. Aphasia and neglect, as determined in the acute setting by the NIHSS, are only moderately associated with cortical infarct identified on follow-up CT scans. If selective neuroprotection is envisioned for acute stroke patients, more accurate markers of cortical infarction may be needed.

Antiplatelet therapy in secondary stroke prevention.

This article focuses on recent data about the safety and effectiveness of antiplatelet therapies for secondary stroke prevention. Highlights include a discussion of changes in the professional labeling for aspirin and the results of a low- versus high-dose aspirin trial (Aspirin after Carotid Endarterectomy trial). Safety issues regarding aspirin also are considered. Other topics include a review of recent data on thrombotic thrombocytopenic purpura (TTP) associated with ticlopidine and a brief update on clopidogrel. A summary of discussions related to the European Stroke Prevention Study 2 data and Food and Drug Administration consideration of combination dipyridamole/aspirin therapy are presented.

A predictive risk model for outcomes of ischemic stroke.

BACKGROUND AND PURPOSE: The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome. The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone. The purpose of this study was to determine the multivariable relationship between infarct volume, 6 clinical variables, and 3-month outcomes in ischemic stroke patients. METHODS: Included in the study were 256 eligible patients from the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS). Six clinical variables and 1-week infarct volume were the prespecified predictor variables. The National Institutes of Health Stroke Scale, Barthel Index, and Glasgow Outcome Scale were the outcomes. Multivariable logistic regression techniques were used to develop the model equations, and bootstrap techniques were used for internal validation. Predictive performance of the models was assessed for discrimination with receiver operator characteristic (ROC) curves and for calibration with calibration curves. RESULTS: The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves. The areas under the ROC curves were statistically greater (P<0.001) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability. CONCLUSIONS: Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients. Demonstration of this relationship with acute clinical variables and 1-week infarct information supports future attempts to predict 3-month outcome with all acute variables.

Antiplatelet agents, carotid endarterectomy, and perioperative complications.

Neurosurgeons are frequently involved in choosing an antiplatelet therapy for their patients in the perioperative period. New data obtained from the Aspirin and Carotid Endarterectomy (ACE) Trial suggest that low-dose aspirin is superior to high-dose aspirin therapy in reducing rates of perioperative stroke and death. The ACE-related data are reviewed, and the authors provide an update on current Food and Drug Administration-approved antiplatelet therapies for secondary stroke prevention, as well as a summary of antiplatelet therapies being developed.

Update on therapies for acute ischemic stroke.

Acute ischemic stroke is now considered a neurological emergency for which there are new therapies. Neurosurgeons and neurologists need to remain apprised of advances in this field. The authors discuss approved and emerging therapies for patients suffering from acute ischemic stroke, based on a review of recent publications. Currently, intravenous tissue-type plasminogen activator is the only Food and Drug Administration-approved therapy for acute ischemic stroke. Intraarterial delivery of thrombolytics is a promising treatment and may be effective in selected patients. Other therapies for acute cerebral ischemia are intriguing but still in the investigational stages.

Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators.

BACKGROUND AND PURPOSE: Reduction in infarct volume is the standard measure of therapeutic success in animal stroke models. Reduction in infarct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit, disability, and global clinical scales. However, few studies have investigated correlations between infarct volume and clinical end points in acute ischemic stroke patients. METHODS: CT scans at days 6 to 11 were acquired prospectively in 191 fully eligible patients enrolled in the Randomized Trial of Tirilazad Mesylate in Patients With Acute Stroke (RANTTAS). Patients were enrolled within 6 hours of onset of stroke in any vessel distribution. Infarct volume was measured by operator-assisted computerized planimetry. RESULTS: One hundred thirty-two patients had visible new supratentorial infarcts, with median infarct volume of 28.0 cm3 (interquartile range, 9.0 to 93.0 cm3). Fifty-nine patients had no visible new infarct. Correlations with standard 3-month outcome scales and mortality were as follows: Barthel Index, r=0.43; Glasgow Outcome Scale, r=0.53; National Institutes of Health Stroke Scale, r=0.54; mortality, r=0.31. For visible infarcts alone, correlations were as follows: BI, r=0.46; GOS, r=0.59; NIHSS, r=0.56; mortality, r=0.32. CONCLUSIONS: Subacute CT infarct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales. The modesty of this linkage constrains the use of infarct volume as a surrogate end point in ischemic stroke clinical trials.

Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators.

BACKGROUND AND PURPOSE: Medical and neurological complications after acute ischemic stroke may adversely impact outcome and in some cases may be preventable. Limited data exist regarding the frequency of such complications occurring in the first days after the ictus and the relationship of these complications to outcome. Our objective was to identify the types, severity, and frequency of medical and neurological complications following acute ischemic stroke and to determine their role in mortality and functional outcome. METHODS: Rates of serious (life-threatening) and nonserious medical and neurological complications and mortality were derived from the placebo limb of the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) database (n=279). Complications were correlated with clinical outcome using logistic regression techniques. RESULTS: Of all patients, 95% had at least one complication. The most common serious medical complication was pneumonia (5%), and the most common serious neurological complication was new cerebral infarction or extension of the admission infarction (5%). The 3-month mortality was 14%; 51% of these deaths were attributed primarily to medical complications. Outcome was significantly worse in patients with serious medical complications, after adjustment for baseline imbalances, as measured by the Barthel Index (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.5 to 15.1) and by the Glasgow Outcome Scale (OR, 11.6; 95% CI, 4.3 to 30.9). After death was discounted, serious medical complications were associated with severe disability at 3 months as determined by the Glasgow Outcome Scale (OR, 4.4; 95% CI, 1.3 to 14.8). CONCLUSIONS: Medical complications that follow ischemic stroke not only influence mortality but may influence functional outcome.

Emergency imaging of the acute stroke patient.

Patients presenting with suspected acute stroke require rapid diagnosis and treatment. Neuroimaging is critical in determining acute-stroke type and thus appropriate management. A review of various neuroimaging techniques and their role in the evaluation of both acute ischemic stroke and acute hemorrhagic stroke is provided.