Carolyn A. Cronin

Higher volume endovascular stroke centers have faster times to treatment, higher reperfusion rates and higher rates of good clinical outcomes

Background and purpose Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches. Methods A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care. Results A total of 442 consecutive patients of mean age 66±14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p<0.008). Conclusions Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.

Advanced modality imaging evaluation in acute ischemic stroke may lead to delayed endovascular reperfusion therapy without improvement in clinical outcomes

Purpose Advanced neuroimaging techniques may improve patient selection for endovascular stroke treatment but may also delay time to reperfusion. We studied the effect of advanced modality imaging with CT perfusion (CTP) or MRI compared with non-contrast CT (NCT) in a multicenter cohort. Materials and methods This is a retrospective study of 10 stroke centers who select patients for endovascular treatment using institutional protocols. Approval was obtained from each institutions review board as only de-identified information was used. We collected demographic and radiographic data, selected time intervals, and outcome data. ANOVA was used to compare the groups (NCT vs CTP vs MRI). Binary logistic regression analysis was performed to determine factors associated with a good clinical outcome. Results 556 patients were analyzed. Mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 18 (IQR 14–22). NCT was used in 286 (51%) patients, CTP in 190 (34%) patients, and MRI in 80 (14%) patients. NCT patients had significantly lower median times to groin puncture (61 min, IQR (40–117)) compared with CTP (114 min, IQR (81–152)) or MRI (124 min, IQR (87–165)). There were no differences in clinical outcomes, hemorrhage rates, or final infarct volumes among the groups. Conclusions The current retrospective study shows that multimodal imaging may be associated with delays in treatment without reducing hemorrhage rates or improving clinical outcomes. This exploratory analysis suggests that prospective randomised studies are warranted to support the hypothesis that advanced modality imaging is superior to NCT in improving clinical outcomes.

INTRAVENOUS TISSUE PLASMINOGEN ACTIVATOR FOR STROKE: A REVIEW OF THE ECASS III RESULTS IN RELATION TO PRIOR CLINICAL TRIALS

BACKGROUND Intravenous tissue plasminogen activator (IV tPA) is currently approved by the Food and Drug Administration for use in acute ischemic stroke patients up to 3 h from symptom onset, based primarily on the National Institute of Neurological Disorders and Stroke tPA trials published in 1995. The most recent trial published with IV tPA in stroke (European Cooperative Acute Stroke Study [ECASS] III) studied patients between 3 and 4.5 h from symptom onset and found a benefit to treatment in the rate of favorable outcome when compared to placebo, with no difference in mortality. OBJECTIVES To examine the patient selection criteria and primary outcomes in ECASS III as compared to prior clinical trials and the current practice in the United States to determine how these new data could be applied to clinical practice. DISCUSSION With the exception of the longer time from symptom onset to treatment, ECASS III used more restrictive patient selection criteria than is the current practice in the United States to determine patient eligibility for IV tPA. CONCLUSIONS Based on the combined data from all trials, the benefits of thrombolysis with IV tPA for acute ischemic stroke outweigh the risks of treatment for selected patients up to 4.5 h from symptom onset. It is already known that thrombolysis is not beneficial for all stroke patients and strict criteria should be applied before treatment. As time from symptom onset increases, the need for careful patient selection likely also increases.

Door‐to‐Puncture: A Practical Metric for Capturing and Enhancing System Processes Associated With Endovascular Stroke Care, Preliminary Results From the Rapid Reperfusion Registry

Background In 2011, the Brain Attack Coalition proposed door‐to‐treatment times of 2 hours as a benchmark for patients undergoing intra‐arterial therapy (IAT). We designed the Rapid Reperfusion Registry to capture the percentage of stroke patients who meet the target and its impact on outcomes. Methods and Results This is a retrospective analysis of anterior circulation patients treated with IAT within 9 hours of symptom onset. Data was collected from December 31, 2011 to December 31, 2012 at 2 centers and from July 1, 2012 to December 31, 2012 at 7 centers. Short “Door‐to‐Puncture” (D2P) time was hypothesized to be associated with good patient outcomes. A total of 478 patients with a mean age of 68±14 years and median National Institutes of Health Stroke Scale (NIHSS) of 18 (IQR 14 to 21) were analyzed. The median times for IAT delivery were 234 minutes (IQR 163 to 304) for “last known normal‐to‐groin puncture” time (LKN‐to‐GP) and 112 minutes (IQR 68 to 176) for D2P time. The overall good outcome rate was 39.7% for the entire cohort. In a multivariable model adjusting for age, NIHSS, hypertension, diabetes, reperfusion status, and symptomatic hemorrhage, both short LKN‐to‐GP (OR 0.996; 95% CI [0.993 to 0.998]; P<0.001) and short D2P times (OR 0.993, 95% CI [0.990 to 0.996]; P<0.001) were associated with good outcomes. Only 52% of all patients in the registry achieved the targeted D2P time of 2 hours. Conclusions The time interval of D2P presents a clinically relevant time frame by which system processes can be targeted to streamline the delivery of IAT care nationally. At present, there is much opportunity to enhance outcomes through reducing D2P.

Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-Hour Exclusions and Association With Outcome: Data From Get With The Guidelines-Stroke

Background and Purpose— The American Heart Association/American Stroke Association guidelines recommend intravenous tissue-type plasminogen activator (tPA) treatment 3 to 4.5 hours from symptom onset according to criteria used in the Third European Cooperative Acute Stroke Study (ECASS III). However, ECASS III excluded certain patient groups in addition to the standard exclusions used for 0 to 3 hours in the United States: age >80 years, history of stroke and diabetes mellitus, oral anticoagulant treatment, and National Institutes of Health Stroke Scale >25. We investigated adherence to these additional exclusion criteria for patients treated 3 to 4.5 hours from onset and their association with outcome. Methods— We analyzed data from Get With The Guidelines-Stroke on 32 019 patients with ischemic stroke from 1464 hospitals who were treated with tPA ⩽4.5 hours from onset from January 2009 to January 2012, excluding patients transferred from another hospital. The percent of patients meeting versus not meeting each exclusion criterion were compared between treatment time windows. Results— Overall, 1544 of 4910 (31.5%) patients treated with tPA >3 to 4.5 hours had at least 1 of the additional exclusions, the most common was age >80 years. With the exception of prior stroke and diabetes mellitus, the percent of tPA–treated patients with each exclusion criterion was significantly lower at >3 to 4.5 hours compared with 0 to 3 hours. For each additional exclusion criterion, there was no increased risk of symptomatic intracranial hemorrhage or worse hospital outcome for patients treated >3 to 4.5 hours compared with 0 to 3 hours, after adjusting for baseline differences. Conclusions— Patients with ECASS III–specific exclusion criteria for the >3 to 4.5 hours window are frequently treated with tPA. The presence of the additional exclusion criteria was not associated with worse outcomes in the >3 to 4.5 hours window compared with the 0 to 3 hours window.

No Increased Risk of Symptomatic Intracerebral Hemorrhage After Thrombolysis in Patients With European Cooperative Acute Stroke Study (ECASS) Exclusion Criteria

Background and Purpose— The European Cooperative Acute Stroke Study (ECASS) III trial used additional exclusion criteria not present in current guidelines for thrombolytic therapy in the United States (age >80 years; National Institutes of Health Stroke Scale >25, combination of previous stroke and diabetes, aggressive measures required to control blood pressure [intravenous infusion], and oral anticoagulant treatment). We tested the hypothesis that thrombolysis is not safe in patients with 1 of the additional exclusion criteria. Methods— All patients treated with intravenous tissue-type plasminogen activator for acute stroke at our center between June 2006 and June 2010 were identified (n=191), and stratified based on presence of each of the exclusion criteria. Primary outcomes were rate of symptomatic intracerebral hemorrhage and in-hospital mortality. Additionally, patients with and without symptomatic intracerebral hemorrhage were analyzed for differences in baseline characteristics. Results— No exclusion criterion was associated with increased risk of symptomatic intracerebral hemorrhage. Symptomatic intracerebral hemorrhage was associated with atrial fibrillation (5 of 9 [55%], versus 35 of 182 [19.2%]; P=0.021), larger final infarct volume (mean 173 mL3 versus 42 mL3; P=0.0002), and elevated glucose (mean 166 mg/dL versus 127 mg/dL; P=0.038). There was higher mortality in patients >80 years (5 of 31 [16%] versus 6 of 160 [4%]; P=0.0186) and those with National Institutes of Health Stroke Scale >25 (2 of 5 [40%] versus 7 of 159 [4.4%]; P=0.025). Conclusions— In our cohort, none of the more stringent exclusion criteria from ECASS III were associated with increased risk of symptomatic intracerebral hemorrhage. Prospective randomized studies are needed clarify the safety and efficacy of tissue-type plasminogen activator in these patients through all treatment time windows.

Cocaine Use and Risk of Ischemic Stroke in Young Adults

Background and Purpose— Although case reports have long identified a temporal association between cocaine use and ischemic stroke (IS), few epidemiological studies have examined the association of cocaine use with IS in young adults, by timing, route, and frequency of use. Methods— A population-based case–control study design with 1090 cases and 1154 controls was used to investigate the relationship of cocaine use and young-onset IS. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between cocaine use and IS with and without adjustment for potential confounders. Results— Ever use of cocaine was not associated with stroke with 28% of cases and 26% of controls reporting ever use. In contrast, acute cocaine use in the previous 24 hours was strongly associated with increased risk of stroke (age–sex–race adjusted odds ratio, 6.4; 95% confidence interval, 2.2–18.6). Among acute users, the smoking route had an adjusted odds ratio of 7.9 (95% confidence interval, 1.8–35.0), whereas the inhalation route had an adjusted odds ratio of 3.5 (95% confidence interval, 0.7–16.9). After additional adjustment for current alcohol, smoking use, and hypertension, the odds ratio for acute cocaine use by any route was 5.7 (95% confidence interval, 1.7–19.7). Of the 26 patients with cocaine use within 24 hours of their stroke, 14 reported use within 6 hours of their event. Conclusions— Our data are consistent with a causal association between acute cocaine use and risk of early-onset IS.

Altered Taste and Stroke: A Case Report and Literature Review

Abstract Patients with altered taste perception following stroke are at risk for malnutrition and associated complications that may impede recovery and adversely affect quality of life. Such deficits often induce and exacerbate depressive symptomatology, which can further hamper recovery. It is important for clinicians and rehabilitation specialists to monitor stroke patients for altered taste perception so that this issue can be addressed. The authors present the case of a patient who experienced an isolated ischemic infarct affecting a primary cortical taste area. This case is unusual in that the isolated injury allowed the patient to remain relatively intact cognitively and functionally, and thus able to accurately describe her taste-related deficits. The case is further used to describe the relevant neurological taste pathways and review potential taste-related therapies.

Posttreatment Variables Improve Outcome Prediction after Intra-Arterial Therapy for Acute Ischemic Stroke

Background: There are multiple clinical and radiographic factors that influence outcomes after endovascular reperfusion therapy (ERT) in acute ischemic stroke (AIS). We sought to derive and validate an outcome prediction score for AIS patients undergoing ERT based on readily available pretreatment and posttreatment factors. Methods: The derivation cohort included 511 patients with anterior circulation AIS treated with ERT at 10 centers between September 2009 and July 2011. The prospective validation cohort included 223 patients with anterior circulation AIS treated in the North American Solitaire Acute Stroke registry. Multivariable logistic regression identified predictors of good outcome (modified Rankin score ≤2 at 3 months) in the derivation cohort; model β coefficients were used to assign points and calculate a risk score. Discrimination was tested using C statistics with 95% confidence intervals (CIs) in the derivation and validation cohorts. Calibration was assessed using the Hosmer-Lemeshow test and plots of observed to expected outcomes. We assessed the net reclassification improvement for the derived score compared to the Totaled Health Risks in Vascular Events (THRIVE) score. Subgroup analysis in patients with pretreatment Alberta Stroke Program Early CT Score (ASPECTS) and posttreatment final infarct volume measurements was also performed to identify whether these radiographic predictors improved the model compared to simpler models. Results: Good outcome was noted in 186 (36.4%) and 100 patients (44.8%) in the derivation and validation cohorts, respectively. Combining readily available pretreatment and posttreatment variables, we created a score (acronym: SNARL) based on the following parameters: symptomatic hemorrhage [2 points: none, hemorrhagic infarction (HI)1-2 or parenchymal hematoma (PH) type 1; 0 points: PH2], baseline National Institutes of Health Stroke Scale score (3 points: 0-10; 1 point: 11-20; 0 points: >20), age (2 points: <60 years; 1 point: 60-79 years; 0 points: >79 years), reperfusion (3 points: Thrombolysis In Cerebral Ischemia score 2b or 3) and location of clot (1 point: M2; 0 points: M1 or internal carotid artery). The SNARL score demonstrated good discrimination in the derivation (C statistic 0.79, 95% CI 0.75-0.83) and validation cohorts (C statistic 0.74, 95% CI 0.68-0.81) and was superior to the THRIVE score (derivation cohort: C statistic 0.65, 95% CI 0.60-0.70; validation cohort: C-statistic 0.59, 95% CI 0.52-0.67; p < 0.01 in both cohorts) but was inferior to a score that included age, ASPECTS, reperfusion status and final infarct volume (C statistic 0.86, 95% CI 0.82-0.91; p = 0.04). Compared with the THRIVE score, the SNARL score resulted in a net reclassification improvement of 34.8%. Conclusions: Among AIS patients treated with ERT, pretreatment scores such as the THRIVE score provide only fair prognostic information. Inclusion of posttreatment variables such as reperfusion and symptomatic hemorrhage greatly influences outcome and results in improved outcome prediction.

Occipital Bone Abnormality Causing Recurrent Posterior Circulation Strokes

We report the case of a young man with recurrent posterior circulation strokes over the course of 6 years. Standard stroke evaluation was unremarkable until careful review of catheter angiogram and CT angiogram images revealed a bony protuberance from the occiput impinging on the left vertebral artery. Local vessel injury with thrombosis and distal embolization is the presumed etiology of the recurrent infarcts. Surgical removal of this developmental anomaly was accomplished, with no subsequent neurological events.