Person:

Schwamm, Lee

Background: We tested the hypothesis that in patients with occlusion of the terminal internal carotid artery and/or the proximal middle cerebral artery, a diffusion abnormality of 70 ml or less is accompanied by a diffusion/perfusion mismatch of at least 100%. Methods: Sixty-eight consecutive patients with terminal ICA and/or proximal MCA occlusions and who underwent diffusion/perfusion MRI within 24 hours of stroke onset were retrospectively identified. DWI and mean transit time (MTT) volumes were measured. Prospectively, 48 consecutive patients were identified with the same inclusion criteria. DWI and time to peak (TTP) lesion volumes were measured. A large mismatch volume was defined as an MTT or TTP abnormality at least twice the DWI lesion volume. Results: In the retrospective study, 49 of 68 patients had a DWI lesion volume ≤ 70 ml (mean 20.2 ml; SEM 2.9 ml). A DWI/MTT mismatch of > 100% was observed in all 49 patients (P < .0001). In the prospective study, there were 35/48 patients with DWI volumes ≤ 70 ml (mean 18.7 ml; SEM 3.0 ml). A mismatch > 100% was present in all 35 (P < .0001). Conclusions: Acute stroke patients with major anterior circulation artery occlusion are exceedingly likely to have a major diffusion/perfusion mismatch if the diffusion lesion volume is 70 ml or less. This suggests that physiology-based patient assessments may be made using only vessel imaging and diffusion MRI as a simple alternative to perfusion imaging.

Objective: To study the perception of informed consent among various raters for thrombolysis in acute ischemic stroke patients receiving intravenous tissue plasminogen activator (IV-tPA). Methods: Twenty randomly selected videotaped telestroke consultations of acute stroke patients administered IV-tPA were retrospectively reviewed. Adequacy of informed consent was reviewed by five raters: a neurologist and emergency physician who routinely treat stroke, a medical risk management paralegal, a bioethicist, and a lay person. Raters assessed the quality of the informed consent presentation by the treating physician and the degree of understanding demonstrated by the patient/family authorizing consent. Factors associated with adequacy of consent were analyzed. Results: Consent was rated as adequately understood by the patient-family in 78.6% cases. Agreement between all five raters with regard to the patient-family understanding of consent was poor and also between the subgroups of non-physician and physician (all k < 0.20). Similarly, the quality of the physician consent process was poor for agreement between all five raters (k = 0.07) or between the subgroup of the three non-physician raters (k = −0.06) and fair between the two physician raters (k = 0.24). The legal reviewer and the bioethicist rated the physician consent process as being of lower quality than did the two physicians and the layperson. Conclusion: Despite high variability in the perception of informed consent among raters in this time-sensitive clinical situation, almost 80% of patients were rated by all reviewers as having adequate understanding of risks and benefits of tPA. This suggests the need for a standardized but brief tPA consent process that includes patient/family demonstration of understanding.

Objective: To investigate whether centralisation of acute stroke services in two metropolitan areas of England was associated with changes in mortality and length of hospital stay. Design: Analysis of difference-in-differences between regions with patient level data from the hospital episode statistics database linked to mortality data supplied by the Office for National Statistics. Setting: Acute stroke services in Greater Manchester and London, England. Participants: 258 915 patients with stroke living in urban areas and admitted to hospital in January 2008 to March 2012. Interventions “Hub and spoke” model for acute stroke care. In London hyperacute care was provided to all patients with stroke. In Greater Manchester hyperacute care was provided to patients presenting within four hours of developing symptoms of stroke. Main outcome measures Mortality from any cause and at any place at 3, 30, and 90 days after hospital admission; length of hospital stay. Results: In London there was a significant decline in risk adjusted mortality at 3, 30, and 90 days after admission. At 90 days the absolute reduction was −1.1% (95% confidence interval −2.1 to −0.1; relative reduction 5%), indicating 168 fewer deaths (95% confidence interval 19 to 316) during the 21 month period after reconfiguration in London. In both areas there was a significant decline in risk adjusted length of hospital stay: −2.0 days in Greater Manchester (95% confidence interval −2.8 to −1.2; 9%) and −1.4 days in London (−2.3 to −0.5; 7%). Reductions in mortality and length of hospital stay were largely seen among patients with ischaemic stroke. Conclusions: A centralised model of acute stroke care, in which hyperacute care is provided to all patients with stroke across an entire metropolitan area, can reduce mortality and length of hospital stay.

Background: Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery (ICA) or proximal middle cerebral artery (MCA) or both account for about one-third of ischemic strokes with mostly poor outcomes. These strokes are treatable by IV-tPA and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with DWI at known times after stroke onset in patients with documented ICA/MCA occlusions. Methods: Retrospectively, we included 47 consecutive patients with documented ICA/MCA occlusions who underwent DWI within 30h of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data was reviewed in those who underwent perfusion imaging. Results: Acute infarct volumes ranged from 0.41-318.3ml. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were less than 25% the territory at risk (<70ml) whether they were imaged < or >8h after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Conclusions: Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30h. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows.

Background: Compared to those who never smoked, a paradoxical effect of smoking on reducing mortality in patients admitted with myocardial ischemia has been reported. We sought to determine if this effect was present in patients hospitalized with ischemic stroke. Methods and Results: Using the local Get with the Guidelines‐Stroke registry, we analyzed 4305 consecutively admitted ischemic stroke patients (March 2002–December 2011). The sample was divided into smokers versus nonsmokers. The main outcome of interest was the overall inpatient mortality. Compared to nonsmokers, tobacco smokers were younger, more frequently male and presented with fewer stroke risk factors such as hypertension, hyperlipidemia, diabetes, coronary artery disease, and atrial fibrillation. Smokers also had a lower average NIH Stroke Scale (NIHSS) and fewer received tissue plasminogen activator (tPA). Patients in both groups had similar adherence to early antithrombotics, dysphagia screening prior to oral intake, and deep vein thrombosis (DVT) prophylaxis. Smoking was associated with lower all‐cause in‐hospital mortality (6.6% versus 12.4%; unadjusted OR 0.46; CI [0.34 to 0.63]; P<0.001). In multivariable analysis, adjusted for age, gender, ethnicity, hypertension, diabetes mellitus, hyperlipidemia, CAD, atrial fibrillation, NIHSS, and tPA, smoking remained independently associated with lower mortality (adjusted OR 0.64; CI [0.42 to 0.96]; P=0.03). Conclusions: Similar to myocardial ischemia, smoking was independently associated with lower inpatient mortality in acute ischemic stroke. This effect may be due to tobacco‐induced changes in cerebrovascular vasoreactivity, or may be due in part to residual confounding. Larger, multicenter studies are needed to confirm the finding and the effect on 30‐day and 1‐year mortality.

Objective To examine the association between warfarin treatment and longitudinal outcomes after ischemic stroke in patients with atrial fibrillation in community practice. Design: Observational study. Setting: Hospitals (n=1487) participating in the Get With The Guidelines (GWTG)-Stroke program in the United States, from 2009 to 2011. Participants: 12 552 warfarin naive atrial fibrillation patients admitted to hospital for ischemic stroke and treated with warfarin compared with no oral anticoagulant at discharge, linked to Medicare claims for longitudinal outcomes. Main outcome measures Major adverse cardiovascular events (MACE) and home time, a patient centered outcomes measure defined as the total number of days free from institutional care after discharge. A propensity score inverse probability weighting method was used to account for all differences in observed characteristics between treatment groups. Results: Among 12 552 survivors of stroke, 11 039 (88%) were treated with warfarin at discharge. Warfarin treated patients were slightly younger and less likely to have a history of previous stroke or coronary artery disease but had similar severity of stroke as measured by the National Institutes of Health Stroke Scale. Relative to those not treated, patients treated with warfarin had more days at home (as opposed to institutional care) during the two years after discharge (adjusted home time difference 47.6 days, 99% confidence interval 26.9 to 68.2). Patients discharged on warfarin treatment also had a reduced risk of MACE (adjusted hazard ratio 0.87, 99% confidence interval 0.78 to 0.98), all cause mortality (0.72, 0.63 to 0.84), and recurrent ischemic stroke (0.63, 0.48 to 0.83). These differences were consistent among clinically relevant subgroups by age, sex, stroke severity, and history of previous coronary artery disease and stroke. Conclusions: Among ischemic stroke patients with atrial fibrillation, warfarin treatment was associated with improved long term clinical outcomes and more days at home. Clinical trial registration Clinical trials NCT02146274.

Background and Purpose— Value-based health care aims to bring together patients and health systems to maximize the ratio of quality over cost. To enable assessment of healthcare value in stroke management, an international standard set of patient-centered stroke outcome measures was defined for use in a variety of healthcare settings. Methods— A modified Delphi process was implemented with an international expert panel representing patients, advocates, and clinical specialists in stroke outcomes, stroke registers, global health, epidemiology, and rehabilitation to reach consensus on the preferred outcome measures, included populations, and baseline risk adjustment variables. Results— Patients presenting to a hospital with ischemic stroke or intracerebral hemorrhage were selected as the target population for these recommendations, with the inclusion of transient ischemic attacks optional. Outcome categories recommended for assessment were survival and disease control, acute complications, and patient-reported outcomes. Patient-reported outcomes proposed for assessment at 90 days were pain, mood, feeding, selfcare, mobility, communication, cognitive functioning, social participation, ability to return to usual activities, and health-related quality of life, with mobility, feeding, selfcare, and communication also collected at discharge. One instrument was able to collect most patient-reported subdomains (9/16, 56%). Minimum data collection for risk adjustment included patient demographics, premorbid functioning, stroke type and severity, vascular and systemic risk factors, and specific treatment/care-related factors. Conclusions— A consensus stroke measure Standard Set was developed as a simple, pragmatic method to increase the value of stroke care. The set should be validated in practice when used for monitoring and comparisons across different care settings.

Background: Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results: We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England–based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver‐operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM‐Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM‐Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions: SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision‐support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time‐critical telestroke evaluations.

Background: Relatively little is known about the quality of care and outcomes for hospitalized ischemic stroke patients with chronic kidney disease (CKD). We examined quality of care and in‐hospital prognoses among patients with CKD in the Get With The Guidelines–Stroke (GWTG‐Stroke) program Methods and Results: We analyzed 679 827 patients hospitalized with ischemic stroke from 1564 US centers participating in the GWTG‐Stroke program between January 2009 and December 2012. Use of 7 predefined ischemic stroke performance measures, composite “defect‐free” care compliance, and in‐hospital mortality were examined based on glomerular filtration rate (GFR) categorized as a dichotomous (+CKD as <60) or rank‐ordered variable: normal (≥90), mild (≥60 to <90), moderate (≥30 to <60), severe (≥15 to <30), and kidney failure (<15 or dialysis). There were 236 662 (35%) ischemic stroke patients with CKD. Patients with severe renal dysfunction or failure were significantly less likely to receive guideline‐based therapies. Compared with patients with normal kidney function (≥90), those with CKD (adjusted OR 0.91 [95% CI: 0.89 to 0.92]), moderate dysfunction (adjusted OR 0.94 [95% CI: 0.92 to 0.97]), severe dysfunction (adjusted OR 0.80 [95% CI: 0.77 to 0.84]), or failure (adjusted OR 0.72 [95% CI: 0.68 to 0.0.76]), were less likely to receive 100% defect‐free care measure compliance. Inpatient mortality was higher for patients with CKD (adjusted odds ratio 1.44 [95% CI: 1.40 to 1.47]), and progressively rose with more severe renal dysfunction. Conclusions: Despite higher in‐hospital mortality rates, ischemic stroke patients with CKD, especially those with greater severity of renal dysfunction, were less likely to receive important guideline‐recommended therapies.

Background and Purpose— Patients with acute ischemic stroke are at increased risk of developing parenchymal hemorrhage (PH), particularly in the setting of reperfusion therapies. We have developed a predictive model to examine the risk of PH using combined magnetic resonance perfusion and diffusion parameters, including cerebral blood volume (CBV), apparent diffusion coefficient, and microvascular permeability (K2). Methods— Voxel-based values of CBV, K2, and apparent diffusion coefficient from the ischemic core were obtained using pretreatment magnetic resonance imaging data from patients enrolled in the MR RESCUE clinical trial (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy). The associations between PH and extreme values of imaging parameters were assessed in univariate and multivariate analyses. Receiver-operating characteristic curve analysis was performed to determine the optimal parameter(s) and threshold for predicting PH. Results— In 83 patients included in this analysis, 20 developed PH. Univariate analysis showed significantly lower 10th percentile CBV and 10th percentile apparent diffusion coefficient values and significantly higher 90th percentile K2 values within the infarction core of patients with PH. Using classification tree analysis, the 10th percentile CBV at threshold of 0.47 and 90th percentile K2 at threshold of 0.28 resulted in overall predictive accuracy of 88.7%, sensitivity of 90.0%, and specificity of 87.3%, which was superior to any individual or combination of other classifiers. Conclusions— Our results suggest that combined 10th percentile CBV and 90th percentile K2 is an independent predictor of PH in patients with acute ischemic stroke with diagnostic accuracy superior to individual classifiers alone. This approach may allow risk stratification for patients undergoing reperfusion therapies. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT00389467.