Dawn M Meyer

Can comprehensive stroke centers erase the 'weekend effect'?

Background: Prior epidemiological work has shown higher mortality in ischemic stroke patients admitted on weekends, which has been termed the ‘weekend effect’. Our aim was to assess stroke patient outcomes in order to determine the significance of the ‘weekend effect’ at 2 comprehensive stroke centers. Methods: Consecutive stroke patients were identified using prospective databases. Patients were categorized into 4 groups: intracerebral hemorrhage (ICH group), ischemic strokes not treated with IV t-PA (intravenous tissue plasminogen activator; IS group), acute ischemic strokes treated with IV t-PA (AIS-TPA group), and transient ischemic attack (TIA group). Weekend admission was defined as the period from Friday, 17:01, to Monday, 08:59. Patients treated beyond the 3-hour window, receiving intra-arterial therapy, or enrolled in nonobservational clinical trials were excluded. Patient demographics, NIHSS scores, and admission glucose levels were examined. Adverse events, poor functional outcome (modified Rankin scale, mRS, 3–6), and mortality were compared. Results: A total of 2,211 patients were included (1,407 site 1, 804 site 2). Thirty-six percent (800/2,211) arrived on a weekend. No significant differences were found in the ICH, IS, AIS-TPA, or TIA groups with respect to the rate of symptomatic ICH, mRS on discharge, discharge disposition, 90-day mRS, or 90-day mortality when comparing weekend and weekday groups. Using multivariate logistic regression to adjust for site, age, admission NIHSS, and blood glucose, weekend admission was not a significant independent predictive factor for in-hospital mortality in all strokes (OR = 1.10, 95% CI 0.74–1.63, p = 0.631). Conclusions: Our results suggest that comprehensive stroke centers (CSC) may ameliorate the ‘weekend effect’ in stroke patients. These results may be due to 24/7 availability of stroke specialists, advanced neuroimaging, or ongoing training and surveillance of specialized nursing care available at CSC. While encouraging, these results require confirmation in prospective studies.

LOAD: a pilot study of the safety of loading of aspirin and clopidogrel in acute ischemic stroke and transient ischemic attack.

BACKGROUND Most patients with ischemic stroke present to the emergency department beyond the approved 3-hour time window for thrombolytic or other revascularization therapies. Clopidogrel and aspirin loading is commonly used to prevent deterioration in other acute vascular occlusive events. This pilot study examined the safety of antiplatelet loading in acute ischemic stroke and transient ischemic attack. METHODS Forty patients with stroke or transient ischemic attack symptoms, not eligible for revascularization, received a single dose of 375 mg of clopidogrel and 325 mg of aspirin within 36 hours of stroke onset. All patients were admitted to a comprehensive stroke department and monitored for neurologic deterioration (2-point increase on National Institutes of Health stroke scale [NIHSS] score) and bleeding complications until hospital day 7 or discharge. NIHSS was performed at 24 hours postadmission and on hospital day 7 or discharge, whichever came first. RESULTS A total of 40 patients were loaded with 375 mg of clopidogrel and 325 mg of aspirin (mean 12 hours 32 minutes). Mean admission NIHSS score was 6. There were no cases of systemic hemorrhage or mortality. A single symptomatic intracranial hemorrhage (2.5%) was detected 43 hours posttreatment. When compared with matched control subjects, loaded patients were no more likely to experience hemorrhage and significantly less likely to experience neurologic deterioration (odds ratio 17.2; P < .002). CONCLUSIONS Loading with 375 mg of clopidogrel and 325 mg of aspirin appears to be safe when administered up to 36 hours after stroke and transient ischemic attack onset in this pilot study. Neurologic deterioration may be decreased and warrants further study.

Comprehensive stroke centers and the 'weekend effect': the SPOTRIAS experience.

Background and Purpose: Previous studies have found mortality among ischemic stroke patients to be higher on weekends. We sought to evaluate whether weekend admission was associated with worse outcomes in a large comprehensive stroke center (CSC) cohort. Methods: Consecutive ischemic stroke patients presenting within 6 h of symptom onset were identified using the 8 CSC SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) database. Patients who received intra-arterial therapy or who were enrolled in a nonobservational clinical trial were excluded. All patients meeting the inclusion criteria were then divided into two groups: weekday admissions or weekend admissions. Weekend admission was defined as Friday 17:01 to Monday 08:59. The remainder were classified as weekday admissions. Multivariate logistic regression was used, adjusting for age, stroke severity on admission [according to the National Institutes of Health Stroke Scale (NIHSS)] and admission glucose, in order to compare the outcomes of the weekend versus the weekday groups. Results: Eight thousand five hundred and eighty-one subjects from the combined SPOTRIAS database were screened from 2002 to 2009; 2,090 (24.4%) of these met the inclusion criteria. There was no significant difference in tissue plasminogen activator treatment rates between the weekday and weekend groups (58.5 vs. 60.4%, p = 0.397). Weekend admission was not a significant independent predictor of inhospital mortality (8.4 vs. 9.9%, p = 0.056), length of stay (4 vs. 5 days, p = 0.442), favorable discharge disposition (38.0 vs. 42.2%, p = 0.122), favorable functional outcome at discharge (41.6 vs. 43.4%, p = 0.805), favorable 90-day functional outcome (54.2 vs. 46.9%, p = 0.301), or 90-day mortality (18.2 vs. 19.8%, p = 0.680) when adjusting for age, NIHSS and admission glucose. Conclusions: In this large cohort of ischemic stroke patients treated at CSCs, we did not observe the ‘weekend effect.’ This may be due to access to stroke specialists 24 h a day on 365 days a year, nurses with stroke experience and the organized system for delivering care that is available at CSCs. These results suggest that EMS protocol should be reexamined regarding the preferential delivery of weekend stroke victims to hospitals that provide all levels of reperfusion therapy. This further highlights the importance of organized stroke care.

Diffusion-weighted Imaging–Fluid Attenuated Inversion Recovery Mismatch in Nocturnal Stroke Patients with Unknown Time of Onset

BACKGROUND More than a quarter of patients with ischemic stroke (IS) are excluded from thrombolysis because of an unknown time of symptom onset. Recent evidence suggests that a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset. METHODS We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI scan within 6 hours from stroke onset (control A) and 19 patients who had an MRI scan between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software. RESULTS The DWI-FLAIR mismatch was different among groups (unknown 43.7%; control A 63.6%; control B 10.5%; Fisher-Freeman-Halton test; P = .001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown 0.05 ± 0.12; control A 0.17 ± 0.15; control B 0.04 ± 0.06; Kruskal-Wallis test; P < .0001). Post-hoc pairwise comparisons revealed that FLAIR/DWI ratio from the unknown group was significantly different from the control B group (P = .0045) but not different from the control A group. DWI volumes were not different among the 3 groups. CONCLUSIONS A large proportion of patients with nocturnal IS and an unknown time of stroke initiation have a DWI-FLAIR mismatch, suggesting a recent onset of stroke.

Defining mild stroke: outcomes analysis of treated and untreated mild stroke patients.

Introduction Mild deficit is a relative contraindication to administration of IV rtPA for acute ischemic stroke. However, what constitutes “mild” deficit is vague. Prior studies showed patients with mild strokes have substantial disability rates at hospital discharge and at 90 days. We investigated whether the application of a new definition altered the rates of disability overall, and assessed the effects of thrombolysis. Methods This analysis included all adult acute ischemic stroke patients from a prospective registry of consecutive patients (UCSD SPOTRIAS database, 2003-2014) with 90-day mRS score available who were defined as “mild” using either: NIHSS 0-5 or a TREAT Task Force definition (NIHSS 0-5 and non-disabling based on pre-specified syndromes). Dichotomized 90-day mRS were compared between treated and untreated patients using the two definitions. Results Of 802 ischemic stroke patients with mRS scores available, 184 had baseline mRS(0) and met TREAT criteria; 45(24.5%) were rtPA-treated. Among treated patients, 35.6% had 90-day mRS(2-6), versus 28.8% in the untreated group, a non-significant difference after adjusting for baseline NIHSS (p=0.47). None of the 45 treated patients had symptomatic hemorrhage. Outcomes were similar using the simpler NIHSS 0-5 definition. Conclusions About one-third of mild stroke patients were not functionally independent at 90 days, irrespective of treatment or mild definition applied, calling into question the treatment efficacy of IV rtPA for mild strokes as well as what constitutes an appropriate definition of “mild”. Randomized studies are necessary to determine rtPA treatment efficacy in mild stroke patients.

Is the ICH score a valid predictor of mortality in intracerebral hemorrhage

Purpose:The intracerebral hemorrhage (ICH) score utilizes a 0‐ to 6‐point scoring system to predict 30‐day mortality in ICH patients. The purpose of this analysis was to (a) validate the ICH score in an international, heterogeneous population of ICH patients; and (b) assess the usefulness of a 72‐h ICH score. Data sources:Analyses were based on data from 399 patients in the Novo Nordisk trial F7ICH‐1371. The ICH scores ability to predict mortality was determined by calculating the sensitivity, specificity, and positive predictive value (PPV). Conclusions:Both the baseline and 72‐h ICH score had high specificity but low sensitivity resulting in an overall PPV of 57%–76%. Specificity of the ICH score was higher in the baseline ICH score (95%) as compared to the 72‐h score (89%). Sensitivity of the ICH score was higher in the 72‐h ICH score (75%) as compared to the baseline score (36%). Implications for practice:The baseline ICH score provides reasonable PPV while the 72‐h score provides higher sensitivity. ICH scores obtained at baseline and/or 72 h are valid and may help practitioners to more accurately predict 30‐day mortality in ICH patients.

Antiplatelet Loading Improves Behavioral Outcome in a Rabbit Model of Stroke

Background and Purpose— No approved acute therapy exists for thousands of patients with ischemic stroke who present ineligible for thrombolytics. The purpose of this proof-of-concept study was to evaluate the efficacy of acute antiplatelet loading on stroke outcome in the rabbit small clot embolic model. Methods— Sixty male New Zealand white rabbits were embolized via small clots into the middle cerebral artery. Two hours later, animals were treated with (1) aspirin (5 mg/kg; n=20); (2) usual dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 10 mg/kg; n=20); or (3) high-dose dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 30 mg/kg; n=20). The coprimary outcomes were as follows: (1) platelet inhibition and (2) behavioral outcome as measured by the P50 (milligrams of clot that leads to neurological dysfunction in 50% of animals in a group). Results— There was a significant difference in 3-hour arachidonic acid and ADP (P<0.011); 6-hour collagen and ADP (P<0.01, P<0.01); and 24-hour collagen, arachidonic acid, and ADP (P=0.02, P<0.01, P<0.01) platelet inhibition. The behavioral outcome was significantly better in the usual dual antiplatelet loading versus aspirin group (P=0.02). Conclusions— This study suggests that usual dual antiplatelet loading is clinically beneficial in a validated model of acute stroke. Study of usual dual antiplatelet loading in acute stroke is warranted to provide treatment to stroke victims ineligible for current therapies.

Dose-finding study of phototherapy on stroke outcome in a rabbit model of ischemic stroke.

GOAL While transcranial laser therapy (TLT) has been shown to improve clinical outcome in a preclinical model of ischemic stroke, optimal timing and dosing has yet to be tested adequately. The purpose of this study was to assess clinical stroke outcome in the Rabbit Small Clot Embolic Model (RSCEM) with dose escalating TLT. METHODS We utilized the rabbit small clot embolic stroke model (RSCEM) using dose-escalating regimens. Behavioral analysis was conducted at 24h post-embolization, allowing for the determination of the effective stroke dose (ES50) or clot amount (mg) that produces neurological deficits in 50% of a group of rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the ES50 compared with the control group. FINDINGS A significant behavioral benefit was seen at triple TLT of 111mW treatment of 2min at 2h post-embolization (6.47±1.06, n=17; p=0.03), compared with the previously used regimen (3.09±0.51, n=15). CONCLUSION TLT results in significant behavioral improvement when administered 2h post-embolization. Studies are warranted to evaluate this therapy in combination with thrombolysis.

Visual Determination of Conjugate Eye Deviation on Computed Tomography Scan Predicts Diagnosis of Stroke Code Patients

BACKGROUND Head computed tomography (CT) is critical for stroke code evaluations and often happens prior to completion of the neurological exam. Eye deviation on neuroimaging (DeyeCOM sign) has utility for predicting stroke diagnosis and correlates with National Institutes of Health Stroke Scale (NIHSS) gaze score. We further assessed the utility of the DeyeCOM sign, without complex caliper-based eye deviation calculations, but simply with a visual determination method. METHODS Patients with initial head CT and final diagnosis from an institutional review board-approved consecutive prospective registry of stroke codes at the University of California, San Diego, were included. Five stroke specialists and 1 neuroradiologist reviewed each CT. DeyeCOM+ patients were compared to DeyeCOM- patients (baseline characteristics, diagnosis, and NIHSS gaze score). Kappa statistics compared stroke specialists to neuroradiologist reads, and visual determination to caliper measurement of DeyeCOM sign. RESULTS Of 181 patients, 46 were DeyeCOM+. Ischemic stroke was more commonly diagnosed in DeyeCOM+ patients compared to other diagnoses (P = .039). DeyeCOM+ patients were more likely to have an NIHSS gaze score of 1 or higher (P = .006). The NIHSS score of DeyeCOM+ stroke versus DeyeCOM- stroke patients was 8.3 ± 6.0 versus 6.7 ± 8.0 (P = .065). Functional outcomes were similar (P = .59). Stroke specialists had excellent agreement with the neuroradiologist (Κ = .89). Visual inspection had excellent agreement with the caliper method (Κ = .88). CONCLUSIONS Using a time-sensitive visual determination of gaze deviation on imaging was predictive of ischemic stroke diagnosis and presence of NIHSS gaze score, and was consistent with the more complex caliper method. This study furthers the clinical utility of the DeyeCOM sign for predicting ischemic strokes.

The Sustained DeyeCOM Sign as a Predictor of Large Vessel Occlusions and Stroke Mimics

INTRODUCTION Rapid imaging in acute stroke is critical and often occurs before full examination. Early, reliable examination findings clarify diagnosis and improve treatment times. The DeyeCOM sign has been described as a predictor of ischemic stroke. In this study, we evaluate a sustained DeyeCOM sign on serial computed tomography scans in prediction of large vessel occlusion. METHODS Between April and June 2017, we retrospectively reviewed 46 patients with acute stroke from the University of California, San Diego Stroke Registry, who had both computed tomography and computed tomography angiography as part of their acute work-up. A DeyeCOM(+) sign was defined as a conjugate gaze deviation on imaging of at least 15°. DeyeCOM(++) was defined as sustained gaze deviation on both scans. RESULTS Three groups of patients were observed: DeyeCOM(++), nonsustained gaze deviation, and no gaze deviation (DeyeCOM(--)). All patients in the DeyeCOM(++) (8 of 8, 100%) had large vessel occlusion. Of those with nonsustained gaze deviation, 2 of 7 (29%) had large vessel occlusion. No patients in the DeyeCOM(--) (0 of 31, 100%) had large vessel occlusion. The specificity and sensitivity of DeyeCOM(++) for large vessel occlusion was 100% (confidence interval [CI] .90-1.0) and 80% (CI .44-.97). The specificity and sensitivity of DeyeCOM(--) for absence of large vessel occlusion was 100% (CI .69-1.0) and 86% (CI .70-.95). CONCLUSIONS DeyeCOM(++) had 100% specificity for large vessel occlusion, whereas DeyeCOM(--) had a 100% specificity for absence of large vessel occlusion. Sustained DeyeCOM, whether positive or negative, is a strong predictor of ultimate diagnosis that could lead to quicker endovascular treatment times.