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OBJECTIVE Spontaneous angiogram-negative nonperimesencephalic subarachnoid hemorrhage (an-NPSAH) can represent a diagnostic and management dilemma. The authors sought to determine radiographic predictors of aneurysmal etiology based on admission noncontrast head CT scans. METHODS The authors performed a retrospective cohort study of prospectively collected data from consecutive patients who were admitted for spontaneous subarachnoid hemorrhage (SAH) with suspected aneurysmal etiology to an academic center from 2016 to 2021. They compared blood thickness in the basal cisterns and sylvian fissures and modified Graeb scores on admission head CT scans between the two groups and subsequently developed a predictive model to identify aneurysmal etiology. RESULTS Of 259 included patients (mean age 56 years [SD 12.7 years]; 55% female), 209 had aneurysmal SAH (aSAH) and 50 had an-NPSAH. The median modified Graeb scores were similar for aSAH and an-NPSAH (6 [IQR 2–10] vs 3.5 [IQR 0–8.5], p = 0.33). The mean blood thickness was greater in the sylvian fissure (p = 0.010) and interhemispheric cisterns (p = 0.002), and there was a greater median degree of extension of blood in the sylvian fissures (p = 0.001) in aSAH than in an-NPSAH patients, but the mean blood thickness was less in the prepontine cistern (p = 0.014). The authors’ scoring model was constructed based on differences in radiographic features. Receiver operating characteristic curve analysis showed acceptable accuracy in predicting aneurysmal etiology (area under the curve 0.71, 95% CI 0.62–0.79). CONCLUSIONS There are differences in radiographic features on admission head CT between an-NPSAH and aSAH patients. The authors’ proposed risk stratification model may be considered for further development and use in clinical practice in the future.

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Background and ObjectivesProlonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence.MethodsWe searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT).ResultsWe included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54–6.03; RR 2.16, 95% CI 1.66–2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57–2.70; RR 2.01, 95% CI 1.43–2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15–0.59), but not in RCTs (RR 0.72, 95% CI 0.49–1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders.DiscussionPCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

Background: There are known associations between sex-specific reproductive health factors such as reproductive lifespan and stroke risk. The relation of endogenous sex hormones, specifically sex hormone binding globulin (SHBG), to stroke risk remains uncertain, however, despite some data showing an inverse association between SHBG and stroke. We conducted a pilot case-control study to evaluate SHBG as a stroke risk factor, to report SHBG levels in the period immediately after acute ischemic stroke (AIS), and to demonstrate the feasibility of collecting data on sex hormones and reproductive history in this study population. Methods: In STOP STROKE, postmenopausal women were enrolled from a single large healthcare system in the northeast between July 2020 and May 2022. Case participants were postmenopausal women ≥50 years old newly admitted with AIS to a large stroke center; controls were postmenopausal women without a history of stroke recruited from an outpatient clinic in the same healthcare system. Among others, exclusion criteria included use of menopausal hormone therapy within 10 years, prior stroke, surgical menopause, and history of hormone-related cancers. We ascertained data on stroke risk factors and collected blood samples between 24 and 72 hours after stroke onset or at the time of enrollment for controls. Serum SHBG was measured using enzyme-linked immunosorbent assays. Following descriptive analyses, age- and BMI-adjusted SHBG levels were compared between cases and controls using multiple linear regression. Multiple logistic regression was then performed to assess associations between SHBG, clinical risk factors, and the outcome of AIS, with covariates chosen a priori based on prior literature. Results: In total, 32 cases and 30 controls were enrolled; median age was 69.0 years (IQR 64.5-82.0) for cases vs. 62.0 (IQR (59.0-68.0) for controls. The mean SHBG of AIS cases was 68.8 (SD 36.1) nmol/L compared to 56.6 (SD 30.0) nmol/L among controls (p=0.16). In models adjusted for age and body mass index (BMI), SHBG was similar between cases and controls (beta = 3.0, 95%CI -15.0 - 21.1, p=0.74). Adjusted for age, BMI, history of hypertension, history of diabetes, and age at menarche and menopause, there was a positive association between SHBG and AIS (OR 1.04, 95%CI 1.004-1.071, p=0.03). Conclusions: Our pilot study demonstrates the feasibility of enrolling newly admitted AIS patients and controls among postmenopausal women in the catchment area of our comprehensive stroke center. To understand initial findings of a positive association between SHBG and AIS, work is ongoing to measure estrogens and androgens at study baseline and all hormones in follow-up specimens (3-6 months post stroke).

Background: While optimizing medical treatment contributed to the low recurrence risk seen in SAMMPRIS medical arm, other factors such as delayed enrollment may have contributed to this low event rate. In this study, we aim to determine the 30-day recurrence risk in a real-world setting in patients with symptomatic intracranial atherosclerosis. Methods: We used a stroke registry of a comprehensive stroke center to identify hospitalized patients with acute ischemic stroke in the setting of symptomatic intracranial atherosclerosis of the ICA, M1, vertebral, or basilar with 50-99% luminal narrowing. We excluded patients with a clear indication for anticoagulation and those who received endovascular treatment. The outcome was recurrent stroke attributed to the affected artery within 30-days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. Results: Among 131 symptomatic 50-99% intracranial stenosis hospitalizations over 3 years, 66 patients met the inclusion criteria. The mean age was 71.9 years and 51.5% were men; 75.8% were treated with best medical management (dual antiplatelet therapy/high intensity stain therapy). Over 30-day follow-up, 21.2 % had recurrent stroke, 57.1% (8/14) occurred within first 7 days. The recurrence risk was similar to another real world ICAD cohort, and higher than that seen in SAMMPRIS (Figure). While maximal medical treatment was the only factor associated with a lower rate of recurrence (OR 0.32 95% CI 0.09-1.12, p = 0.075), the recurrence rate in patients treated with maximal medical therapy (16.0%, 95% CI 8.1-29.3%) and those SAMMPRIS eligible (17.6%, 95% CI 7.9-34.9%) remained elevated. Conclusions: In patients with symptomatic ICAS, the real-world recurrence is higher than that seen in clinical trials, despite optimally using the same medical treatment strategies. This may suggest that the low risk of recurrence achieved in clinical trials may not apply to real world practice.

Introduction: Stroke secondary to intracranial atherosclerosis (ICAD) results in three distinct infarct patterns: (a) border zone infarcts (BZI) due to impaired distal perfusion (b) territorial infarcts due to distal plaque/thrombus embolization, and (c) perforator infarcts due to plaque progression. Previous studies indicate higher stroke recurrence in ICAD patients with BZI. Methods: This registered systematic review (CRD42021265230) comprised Medline and Web of Science search from inception to March 2022 for keywords (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Border zone OR Infarct Pattern) to identify papers and conference abstracts reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAD. Sensitivity analyses were performed for studies including any BZI vs isolated BZI and those excluding posterior circulation strokes. The study outcome included neurological deterioration and/or stroke recurrence. For all outcome events, corresponding risk ratios (RR) and 95% confidence intervals (CI) were calculated. Risk of bias assessments will be presented. Results: Literature search yielded 4478 studies,11 met inclusion criteria (n=1315 patients, 354 with BZI, weighted proportions summarized in figure). The meta-analysis of these studies with moderate heterogeneity (I 2 =38.7%) demonstrated that RR of outcomes in BZI group compared to non-BZI group was 2.10 (95% CI 1.52-2.90). Limiting analysis to studies including any BZI, RR (and 95% CI) was 2.32 (1.58-3.40), and 3.25 (2.09-5.07) for studies only including anterior circulation strokes with low heterogeneity for both (I 2 =0%). A non-significantly high outcome rate was seen with isolated BZI (RR 2.29, 95% CI 0.94-5.62) but with moderate heterogeneity across studies (I 2 =70.25%). Conclusion: We demonstrate the presence of BZI secondary to symptomatic ICAD can be imaging biomarker to predict neurological deterioration and/or stroke recurrence.

Introduction: Up to 25% of strokes are recognized upon awakening. Recent studies have demonstrated that a “tissue clock” rather than a time clock can be used to identify patients who may benefit from intravenous thrombolytics (IVT) beyond 4.5 hours from last known well (LKW). Consistent access to hyperacute MRI limits many centers from treating wake-up stroke patients. We created a formal protocol of clinical and imaging criteria to standardize evaluation and management of wake-up strokes. Methods: This retrospective, observational study reviewed consecutive patients admitted to our Comprehensive Stroke Center who qualified for the wake-up protocol between February 2022 and June 2022. The implemented protocol, based on clinical trials’ inclusion criteria, is comprised of the following: 1) arrival within 12 hours from LKW and within 4.5 hours from symptom discovery; 2) high suspicion for acute ischemic stroke; 3) no contraindication to MRI; 4) NIHSS of at least 4; 5) baseline mRS 0-3; 6) no absolute contraindications to IVT. For patients meeting above inclusion criteria, emergent MRI with perfusion was performed. Diffusion-FLAIR mismatch (signal intensity ratio) and diffusion-perfusion mismatch were reviewed to determine thrombolysis eligibility by a trained neuroradiologist or vascular neurologist. Results: Ten patients qualified for the wake-up protocol in the first five months of protocol implementation. Median NIHSS was 7, median LKW to arrival time was 8 hours, and median door to MRI time was 72.5 minutes. A final diagnosis of ischemic stroke was made in 80% of these cases. Overall, 50% were eligible for IVT based on our criteria, and 30% received thrombolysis. Median door to needle time was 92 minutes (range 75-117). There were no symptomatic intracranial hemorrhages. All patients treated with IVT were discharged home with no to minimal residual deficits with mRS 0-1 and median NIHSS at discharge of 2 (range 0-4). Conclusion: A formal protocol for wake-up stroke management allowed a streamlined approach to expand the number of IVT-eligible cases. Continued efforts are needed to improve door to needle times in such cases and to follow clinical courses of treated patients.

Background: Elevated systolic blood pressure (SBP) has been linked to pre-procedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the relationship between blood pressure parameters including mean arterial pressure (MAP) with rebleeding both prior to and during aneurysm securement remains unclear. This study seeks to determine the association between BP parameters and rebleeding events and outcomes in patients with aSAH. Design/Methods: We performed a retrospective analysis of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center between July 2016 and March 2021. All BP parameters, which were recorded on an hourly basis from admission, were reviewed. Per our institutional protocol, the SBP target is Results: The cohort included 295 patients (mean age 57 years [SD 13.4], 61% female, 87% received endovascular treatments, 13% surgical clipping). Two or more consecutive SBP values >140 were seen in 41% and >160 in 15% of patients. Rebleeding prior or during securing aneurysms including intra-procedural bleeding occurred in 53 patients (18%). There was no association between either maximum recorded SBP (169.7 mmHg [36.2] vs. 166.9 [32.7], p=0.57) or MAP (121 mmHg [22.9] vs. 117.8 [22.9], p=0.42) and rebleeding. However, maximum recorded MAP was associated with poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.006-1.02, p=0.039). Conclusions: Elevated MAP peri-securement of a ruptured cerebral aneurysm can be associated with poor outcome. Multicenter prospective studies should further examine the association between MAP cut offs and outcomes to be considered in guidelines.

Introduction: Percutaneous gastrostomy tubes are frequently required for patients with strokes due to dysphagia, malnutrition, and intestinal dysmotility. Though generally well tolerated, delayed detection of complications following percutaneous gastrostomy tube insertion (including dislodgement, infection and bleeding) can lead to increased morbidity and mortality. Methods: At a single academic tertiary hospital, a standardized protocol was instituted (September 2021) to enhance early detection and prevention of feeding tube complications on the neurology service, consisting predominantly of stroke patients. The protocol comprised of: 1) consistent documentation of feeding tube insertion by proceduralists, 2) universal abdominal binder application, 3) nursing driven delirium screening, 4) post procedural nursing assessment for high-risk feeding tube site changes, and 5) an escalation algorithm to address early complications. We compared rates of complications pre- (July 2020 - August 2021, 13 months) and post- (September 2021 - June 2022, 10 months) protocol implementation. Results: A total of 103 gastrostomy tube insertions were reviewed (64 pre and 39 post protocol implementation). Overall complication rates decreased from 12.5% (N = 8 of 64; 3 dislodgements, 3 infections, 2 insertion site bleeding) to 2.5% (N = 1 of 39; 1 dislodgment) following the intervention. Mortality from complications decreased from 1.6% to 0%. Conclusion: Complication rates of percutaneous gastrostomy tube placement may be reduced through implementation of standardized protocols on inpatient stroke patients. Further studies are warranted to assess its long-term effects and viability in other specialty services.

Introduction: It is well established that reduced door-to-needle (DTN) time leads to improved outcomes in acute ischemic stroke. Rhode Island Hospital is a Comprehensive Stroke Center focused on improving outcomes by seeking novel methods to improve the DTN to below the institutional goal of a median of < 30 minutes. Methods: We sought to reduce DTN time by the following methods: 1) Addition of an electronic DTN Timer appearing in the Electronic Medical Record (EMR) to improve situational awareness of elapsed time in Code Strokes in real time (Figure). 2) Creation of a multidisciplinary Thrombolysis Focus Group to analyze data and improve processes. 3) Increased awareness of metric exclusion criteria and ease of processes for providers to document exclusions. 4) Concurrent review of each thrombolysis case with direct provider feedback and opportunity to appropriately document and clarify delays. 5) Creation of a thrombolysis Time-Out process. Results: The median DTN for the pre-implementation period of January 2020 to August 2021 was 40.3 minutes compared to 35.8 min for the post-implantation period of September 2021 to June 2022. Additionally, the percent of thrombolysis cases meeting the institutional goal of under 30 minutes improved from 22.6% to 29.8% percent (Figure) and when exclusions were applied, this percentage improved from 29.8% to 49.4% (Figure). Conclusion: Novel measures to reduce the DTN time in acute stroke thrombolysis can positively impact both the door-to-needle time and percent of cases under the institutional DTN time goal. Figure 1.

Introduction: Cervical artery dissection (CAD) is a common cause of stroke in the young and carries a high risk of early recurrence. We aim to compare the characteristics of patients from a real-world cohort to those from prior randomized controlled trials. Methods: We pooled data from consecutive patients with a diagnosis of spontaneous CAD treated at a comprehensive stroke center who were followed for at least 90 days. We excluded patients with traumatic dissection and those with primary intracranial hemorrhage in the setting of trauma or dissection. We compared the baseline characteristics and stroke recurrence rates in our cohort to the TREAT-CAD (2021) and CADISS (2019) trials. We report recurrence rates in patients treated with single antiplatelet (SAPT), dual antiplatelet (DAPT), and anticoagulation (AC). Results: 80 patients with CAD met our inclusion criteria. Our study sample characteristics differ from TREAT-CAD and CADISS, with our cohort more likely to have hypertension and diabetes but less likely to have a smoking history. The rate of recurrent stroke at 90 days was numerically higher in our patient cohort (6.3%) compared to TREAT-CAD (3.6%) and CADISS (1.6%). The rates of recurrent stroke were 8.6% (3/35) with SAPT, 4.2% (1/24) with DAPT, and 5% (1/20) with AC strategies. Conclusions: Characteristics of a real-world CAD population differ from those enrolled in clinical trials with an overall higher rate of recurrent stroke but comparable rates among patients treated with DAPT and AC. The ongoing STOP-CAD study will compare DAPT to AC with a substantially larger number of patients, with an estimated projection of at least 3000 patients in a multi-center international cohort.

Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97–1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56–0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37–1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40–7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08–6.21), p = 0.032), p for interaction = 0.613. Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.

Purpose To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. Materials and methods We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring 24 h after presentation (“later-onset”). Results Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5–7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1–8.2]), and troponin (OR 3.0 [95% CI 1.2–7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. Conclusions Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.

Background An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. Methods We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0–3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. Results We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586–0.755) compared with each component alone. Conclusions WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

Anemia has been linked to delayed cerebral ischemia (DCI) and worse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the association of hemoglobin (Hb) trend and outcomes is not well studied. We investigated predictors of Hb trend and its association with outcomes in patients with aSAH. Our hypothesis was that a negative Hb trend is associated with poorer outcomes independent of Hb values.We conducted a retrospective study of a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center (2016-2021). We tested the association of Hb trend and values with measures including DCI and poor functional outcome defined as modified Rankin scale 4-6 at 3 months after discharge. Multiple linear regression analysis was used to identify factors associated with Hb difference from admission to discharge.We included 310 patients with confirmed aneurysmal etiology (mean age 57 years, SD13.6; 62 % female). Greater Hb decrement from admission to discharge was independently associated with higher likelihood of both DCI (OR 1.28 per 1 g/dl decrease in Hb, 95 % CI 1.08-1.47; p = 0.003) and poor functional outcome (OR 1.27 per 1 g/dl decrease in Hb, 1.03-1.53; p = 0.026) independent of any absolute Hb values. Predictors of Hb decrement from admission to discharge were hospital length of stay, Hunt and Hess grades, female sex and age.Greater Hb decrement can be associated with higher likelihood of DCI and poor functional outcome in aSAH. More evidence is needed to use Hb trend to guide transfusion threshold in aSAH patients.

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients.We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD).The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome.Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Background Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. Methods We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. Results Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) Conclusions Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.

IntroductionPredictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors.MethodsThe Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH.ResultsOut of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%–99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92).ConclusionIn patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

Background and Purpose— The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods— We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score−24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score−24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95–100 and modified Rankin Scale score of 0–1), good 3-month functional outcome (modified Rankin Scale score of 0–2), and 3-month infarct volume. Results— There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P =0.045) but not median delta NIHSS (3 versus 2; P =0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month Barthel Index (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.75), excellent 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.74; ROC admission , 0.78), and good 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.78). Conclusions— In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

ObjectiveCardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes.MethodsA cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA.ResultsA total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119).ConclusionsLA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

For more than a year, the SARS-CoV-2 pandemic has had a devastating effect on global health. High-, low-, and middle-income countries are struggling to cope with the spread of newer mutant strains of the virus. Delivery of acute stroke care remains a priority despite the pandemic. In order to maintain the time-dependent processes required to optimize delivery of intravenous thrombolysis and endovascular therapy, most countries have reorganized infrastructure to optimize human resources and critical services. Low-and-middle income countries (LMIC) have strained medical resources at baseline and often face challenges in the delivery of stroke systems of care (SSOC). This position statement aims to produce pragmatic recommendations on methods to preserve the existing SSOC during COVID-19 in LMIC and propose best stroke practices that may be low cost but high impact and commonly shared across the world.

This scientific statement describes a path to optimizing care for patients who experience an in-hospital stroke. Although these patients are in a monitored environment, their evaluation and treatment are often delayed compared with patients presenting to the emergency department, contributing to higher rates of morbidity and mortality. Reducing delays and optimizing treatment for patients with in-hospital stroke could improve outcomes. This scientific statement calls for the development of hospital systems of care and targeted quality improvement for in-hospital stroke. We propose 5 core elements to optimize in-hospital stroke care: 1. Deliver stroke training to all hospital staff, including how to activate in-hospital stroke alerts. 2. Create rapid response teams with dedicated stroke training and immediate access to neurological expertise. 3. Standardize the evaluation of patients with potential in-hospital stroke with physical assessment and imaging. 4. Address barriers to treatment potentially, including interfacility transfer to advanced stroke treatment. 5. Establish an in-hospital stroke quality oversight program delivering data-driven performance feedback and driving targeted quality improvement efforts. Additional research is needed to better understand how to reduce the incidence, morbidity, and mortality of in-hospital stroke.

Introduction: The faster IV Alteplase and mechanical thrombectomy is initiated in acute ischemic stroke, the better the outcome. Delays can significantly impact times to treatment. A mechanism to communicate time targets to code stroke teams can play an important role in providing knowledge about time sensitive metrics. The utilization of the ASA Stroke Time Tracker tool was created to improve communication in a timely manner to stroke teams providing acute treatment. The emphasis is on the education of time targets to improve door to treatment times. Hypothesis: To explore whether the use of the American Stroke Association Time Tracker tool as a communication instrument is associated with improved DTN and DTD times in both direct and transfer patients. Methods: In March 2020 the application of the ASA time tracker tool was introduced. A retrospective review revealed that DTN times improved from 58.7% to 71.6 % for those receiving t-PA within 45 minutes or less during the period the tool was in use. To explore whether timely feedback using the Time Tracker tool was associated with improved DTD times, mechanical thrombectomy data including DTD was collected and communicated to stroke care teams in April 2021. Compilation of time sensitive metrics in the evaluation of DTN times continued through Q2 2021. A retrospective analysis was conducted. Results: For those who received IV Alteplase, the percentage of patients treated within 30 minutes continued to improve, 21.1% (Q3 2020) vs. 35.7% (Q2 2021). The percentage of patients treated within 45 minutes also improved from 71.8% (Q3 2020) to 80.0% (Q2 2021). In patients who received endovascular therapy during Quarter 3 2020, 56.1% met the advanced therapy AHA Elite Plus criteria of DTD within 60 minutes (transfer patients) OR within 90 minutes (direct admit). This improved to 73.1% patients in Quarter 2 2021, during the use of the tool. Conclusions: There is an association between use of the ASA Time Tracker tool and improved DTN and DTD times. Further study should include continued use of the tool to confirm an association between direct communication with Code Stroke teams and improved treatment times.

Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.

Introduction: Approximately 30% of ischemic strokes are cryptogenic and 40-50% of these patients have a patent foramen ovale (PFO) detected during work up. While the risk of ischemic stroke attributed to PFO is 0.5-1% per year, the proportion of disabling ischemic strokes in the setting of PFO is unknown. In this study, we aim to determine differences in rates and predictors of poor outcome in patients with stroke and PFO compared to those without PFO. Methods: This retrospective, observational cohort study included consecutive patients aged 18-60 admitted to our comprehensive stroke center with a diagnosis of ischemic stroke over a two-year period. modified Rankin Score (mRS) was collected at 90-days according to institutional protocol. Poor functional outcome was defined as mRS of 2-6. We compared baseline characteristics of ischemic stroke patients with PFO to those without PFO, and then determined associations with poor outcome using multivariable logistic regression that adjusted for age and stroke severity. We performed similar analyses in the subgroup of patients with cryptogenic stroke. Results: Out of 321 patients with ischemic stroke (mean age 49; 42% women), 146 had cryptogenic stroke - embolic stroke of undetermined source subtype (CS-ESUS). Baseline characteristics, demographics, and stroke severity did not differ between those with PFO when compared to those without PFO both across the entire cohort and in the subgroup of CS-ESUS. Among patients with cs-ESUS with PFO, 48% (10/21) had poor functional outcome, and the rates did not significantly differ based on ROPE score (p = 0.362). In our binary logistic regression model adjusting for age and NIHSS score, the rate of poor functional outcome in patients with CS-ESUS did not significantly differ based on presence vs. absence of PFO (OR 1.10 95% CI 0.39-3.09, p = 0.859). Conclusions: Our study suggests that a significant portion (almost 1 in 2) of cryptogenic strokes in patients with a PFO were disabling at 90 days and disability rates did not significantly differ as a function of PFO attributability of their ischemic stroke. Further studies are needed to identify patients with high-risk PFOs that may especially predispose to disabling strokes and to determine optimal primary stroke prevention strategies.

Background: Randomized trials have shown that dual antiplatelet therapy (DAPT) reduces the risk of subsequent ischemic stroke in patients with minor stroke or high-risk TIA (MS-TIA). However, the 90 day risk remains elevated at 5-8%. In this exploratory study, we aimed to identify predictors of subsequent ischemic stroke in patients with MS-TIA treated with DAPT. Methods: This is a post-hoc analysis of the POINT trial that randomized patients with MS-TIA to DAPT versus aspirin monotherapy. For this analysis, we included only patients treated with DAPT and performed univariate and adjusted Cox-regression analyses to determine predictors of subsequent ischemic stroke. We also performed receiver operating analysis to determine predictive accuracy. P Results: Among 2,398 MS-TIA patients treated with DAPT, 109 (4.5%) had ischemic stroke during the 90 day follow up interval. In Cox-regression analyses, predictors of subsequent ischemic stroke were admission glucose level per 10 mg/dL increase (adjusted HR 1.04 95% CI 1.03-1.06, p < 0.001), admission blood pressure per 10 mm Hg increase (aHR 1.10 95% CI 1.03-1.17, p = 0.006) and presence of infarct on index imaging (adjusted HR 2.04 95% CI 1.40-2.98, p Conclusion: Patients with MS-TIA who have hyperglycemia or hypertension on admission are at a relatively high risk of subsequent ischemic stroke despite DAPT. Future studies are needed to validate our findings and explore whether targeted treatment of these factors can affect short term stroke risk.

Background: Cannabinoids are hypothesized to cause cardiovascular disease including stroke; this is potentially due to dysregulation of endogenous lipid mediator endocannabinoids and their G-protein coupled receptors. Our aim is to investigate cannabinoid use in patients with acute ischemic stroke and determine associations between stroke subtype and functional outcome at 90-days. Methods: This is a retrospective, observational, cohort study of consecutive patients admitted with acute ischemic stroke to our Comprehensive Stroke Center. We included patients 60 years or younger who had a drug screen performed during their acute stroke hospitalization. We compared demographic factors, stroke subtype, and 90-day functional outcomes between the two groups (Cannabinoid positive vs. Cannabinoid negative). Stroke subtype was determined based on TOAST criteria, ESUS criteria and good outcome was defined as mRS 0-1 at 90-days. Results: We identified 256 patients who met inclusion criteria. Mean age was 50 years, 61% were men and 20% were cannabinoid positive. Cannabinoid positive patients were younger (47.0 ± 10.7 vs. 50.5 ± 8.5, p = 0.032) and more likely to test positive for cocaine (17.3% vs. 3.9%, p = 0.002). Gender and vascular risk factors including smoking were similar between cannabinoid positive and negative patients. Cannabinoid positive patients were more likely to have a stroke related to large artery atherosclerosis (23.0% vs. 10.3%, p = 0.020). In an adjusted binary regression analysis, cannabinoid use was associated with non-significantly lower odds of good outcome (OR 0.61 95% CI 0.31 -1.23, p = 0.1). Conclusions: Cannabinoid use is associated with atherosclerotic stroke subtypes and a non-significantly reduced likelihood of good functional recovery. Larger studies are needed to further test these associations.

Background: Patients with symptomatic intracranial stenosis (ICAS) face elevated risks of recurrent cerebrovascular events (RCE) despite optimal medical therapy. Borderzone infarcts (BZI) indirectly correlate with impaired distal perfusion, a known mechanism of recurrence. Studies assessing associations between borderzone infarcts and recurrence rates are observational and have relatively small sample size. We therefore performed a meta-analysis of published studies investigating this association. Methods: We performed a Medline and Web of Science search using the key words (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Borderzone OR Infarct Pattern) to identify studies reporting associations between index infarct pattern and RCE, defined as recurrent ischemic stroke or neurological deterioration, or new infarct on follow up neuroimaging in patients with symptomatic ICAS. We included relevant papers and scientific abstracts with more than 20 patients included. For all outcome events we calculated the corresponding risk ratios (RRs) and 95% confidence intervals (95% CI). Results: We identified 178 studies using Web of Science and 384 studies using Medline with only 6 studies (591 patients) meeting our inclusion criteria (2 prospective and 4 retrospective). The weighted proportion of patients with BZI was 32.5% (28.7%-36.4%). During a follow-up period of 7-950 days, 33.1% (26.3%-40.5%) of patients with BZI had RCE and 63.6% (30.8%-89.1%) had new infarction on a 6-8 week follow up brain MRI. In meta-analysis, BZI was associated with increased rates of RCE (RR 2.40 95% CI 1.71-3.37) and new infarct(s) on follow up brain MRI (RR 2.55 95% CI 1.31-4.94). The findings were unchanged when the analysis was limited to 90-day RCE risks only (RR 2.22 95% 1.49-3.29). Conclusions: BZI are associated with over 2-fold increased risk of RCE and recurrent infarct in patients with symptomatic ICAS. Prospective studies are needed to validate these findings.

Disturbances in serum sodium levels are common following aneurysmal subarachnoid hemorrhage (aSAH) and may lead to increased morbidity, mortality, and poor functional outcomes. This study aims to examine the relationship between abnormal sodium levels following aSAH and patient outcomes. A retrospective cohort study of consecutive patients with aSAH who were admitted to an academic referral center between 2015 and 2021 was performed. Dysnatremia was categorized as either mild or moderate-severe and patients were sorted accordingly. Multivariable logistic regression was used to test the association of any dysnatremia and outcomes, including modified Rankin Scale (mRS) at 3 months after discharge, vasospasm (based on transcranial Doppler criteria), delayed cerebral ischemia (DCI) and refractory hydrocephalus requiring ventriculoperitoneal shunt. Multiple linear regression was used to test the association of hospital length of stay and dysnatremia (categorical variables). We included 320 patients (mean age 57.8 years (SD 14.3), 61% female, 70% white). Hyponatremia was seen in 58% for a median of 3 days [IQR 1-6], with moderate-severe hyponatremia occurring in 5%. Hypernatremia was observed in 49% for a median of 5 days [IQR 2-8], 56% of whom had moderate-severe hypernatremia. Of 156 hypernatremic patients, 80% were treated with hypertonic saline for cerebral edema. Hypernatremia was independently associated with a higher odds of vasospasm (OR 1.75, 95% CI 1.02-303, p =0.04) when adjusted for Hunt and Hess grades, cerebral edema and modified Fisher scales. There was no independent association between any dysnatremia and mRS, DCI or refractory hydrocephalus. Hospital length of stay was longer in patients with hypernatremia (8.11 more hospital days, 95% CI 5.4-10.8; p

Introduction: Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication of acute ischemic stroke (AIS). We performed a nationwide analysis to evaluate rate and risk factors for VTE readmission in patients with AIS. Methods: Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included adult patients with a principal discharge diagnosis of AIS from 2016 to 2018. AIS, pulmonary embolism, deep vein thrombosis and other diagnosis were identified based on standard ICD-10 CM codes. Patients who had VTE diagnosis during the index admission were excluded. We determined 90-day VTE readmission rates and trends in patients with a principal diagnosis of AIS stratified by 30-day epochs. We then constructed a stepwise binary logistic regression model to determine odds ratios (OR) of demographic and clinical factors associated with VTE readmission rates. Results: Of the 1,023,478 patients with AIS, 8378 (0.82%) had VTE during readmission and 2906 (0.28%) had VTE as principal diagnosis for readmission within 90 days of discharge. Among them, more than half (4557, 54.39% and 1581, 54.40%, respectively) of patients were readmitted within 30 days of discharge. The rate of VTE readmission decreased further away from index event (P < 0.001). In the Cox regression model, obesity (OR 1.48, 95% CI 1.24-1.76, P < 0.001), plegia of at least one limb (OR 1.24, 95% CI 1.08-1.43, P = 0.003), longer hospital length of stay (OR 1.02, 95% CI 1.01-1.02, P < 0.001), higher NIHSS (OR 1.04, 95% CI 1.03-1.05, P < 0.001) were associated with VTE readmission. Conversely, VTE readmission rates were lower in patients with a history of atrial fibrillation/flutter (OR 0.72, 95% CI 0.62-0.84, P < 0.001). Conclusion: Patients with obesity, paralysis, higher NIHSS score, or prolonged hospital length of stay are at higher risk for VTE readmission. AF strokes are less likely to have DVT/PE, perhaps due to anticoagulant use in such patients. Studies are needed to determine whether early mobilization and mechanical and/or chemical prophylaxis reduces VTE risk in high-risk patients.

Introduction: Antiplatelet agents are commonly used after endovascular repair of ruptured aneurysms in patients with subarachnoid hemorrhage (SAH). Recent evidence suggests post-treatment antiplatelets may reduce risk of delayed cerebral ischemia (DCI) and worse outcome. We sought to determine potential risks and benefits of antiplatelets in our patients’ population Methods: This is a retrospective cohort study of consecutive patients with aneurysmal SAH who were admitted to an academic referral center from 2016 to 2021. We used multivariable logistic regression analysis, propensity score matching and multiple linear regression to test the association of antiplatelets use and functional outcome (modified Rankin Scale at 3 months), DCI, any intracranial hemorrhagic complications including EVD tract hemorrhage and ICU length of stay (continuous variable). Results: Of the confirmed aneurysmal SAH patients (n=315), mean age was 57 years (SD 13.6) and majority of patients were female (62%) and white (70%). Thirty-nine percent of patients received antiplatelets (26% single agent; 13% dual agents) with no differences in demographics. Of the patients in the cohort, 85% received endovascular treatments (including 59% coil, 12% pipeline and stent assisted coil, 14 other endovascular treatments) and 15% underwent surgical clipping. Antiplatelets were used more in aneurysms originating from posterior circulation compared to anterior circulation (54% vs 35%, p=0.012). There was no difference in functional outcome (modified Rankin Scale at 3 months), DCI, or any intracranial hemorrhagic complications including EVD tract hemorrhage. ICU length of stay was longer in patients who received antiplatelets (3.32 additional days, 95% CI 0.4-6.3; p=0.02) and this association was independent of Hunt and Hess grades, modified Fisher scales, aneurysm treatment modality, age, comorbidities, and hospital complications. Conclusion: Use of antiplatelets may not reduce risk of DCI and worse outcome but can be associated with longer ICU length of stay. Further studies are required to identify appropriate candidates who may benefit from antiplatelets.

Background and Purpose: Cryptogenic stroke accounts for 30% of ischemic stroke and in such patients, cardiac monitoring leads to increased detection of AF, increased utilization of anticoagulation, and decreased risk of recurrent stroke. We aim to identify differences in inpatient utilization of implantable cardiac monitors (ICMs) in patients with ischemic stroke. Methods: This is an analysis of the National Inpatient Sample. We included all ischemic stroke hospitalizations nation-wide between Jan 1 st 2016 and Dec 31 st 2018. We excluded patients with history of atrial fibrillation or atrial flutter. We compared survey weighted baseline demographics and characteristics between patients who received an inpatient ICM versus those who didn’t using logistic regression models. Results: We identified a weighted total 1,069,395 patients who met the inclusion criteria; 2.2% received an inpatient ICM. In multivariable analyses, factors associated with decreased odds of inpatient ICM placement including Black race (OR 0.76 95% CI 0.68 - 0.84, p < 0.001), residence in a micropolitan area (OR 0.79 95% CI 0.67 - 0.94, p = 0.008), hospital region [Midwest (OR 0.74 95% CI 0.61 - 0.90, p = 0.002), South (OR 0.68 95% CI 0.57 - 0.81, p < 0.001), and West (OR 0.37 95% CI 0.29 - 0.45, p < 0.001)], hospital bed size [small (OR 0.38 95% CI 0.39-0.46, p < 0.001) and medium hospital bed size (OR 0.73 95% CI 0.63 - 0.84, p < 0.001)], insurance status [Medicaid (OR 0.86 95% CI 0.76 - 0.98, p = 0.02) and self-pay (OR 0.51 95% CI 0.41 - 0.62, p < 0.001)], and non-teaching hospital (OR 0.52 95% CI 0.47 - 0.60, p < 0.001). Conclusions: There are important differences in inpatient ICM placement in patients with ischemic stroke highlighting disparities in inpatient care for patients hospitalized with ischemic stroke. More studies are needed to validate our findings.