Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Direct Versus Indirect Revascularization for Moyamoya: a Large Multicenter Study.

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Comparative Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Patients with ASPECTS 2-3 vs. 4-5.

BACKGROUND: The influence of Alberta Stroke Program Early CT Score (ASPECTS) on outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients with low ASPECTS remains unknown. In this study, we compared the outcomes of AIS patients treated with MT for large vessel occlusion (LVO) categorized by ASPECTS value. METHODS: We conducted a retrospective analysis involving 305 patients with AIS caused by LVO, defined as the occlusion of the internal carotid artery and/or the M1 segments of the middle cerebral artery, stratified into two groups: ASPECTS 2-3 and 4-5. The primary outcome was favorable outcome defined as a 90-day modified Rankin Scale (mRS) score of 0-3. Secondary outcomes were 90-day mRS 0-2, 90-day mortality, any intracerebral hemorrhage (ICH), and symptomatic ICH (sICH). We performed multivariable logistic regression analysis to evaluate the impact of ASPECTS 2-3 vs. 4-5 on outcomes. RESULTS: Fifty-nine patients (19.3%) had ASPECTS 2-3 and 246 (80.7%) had ASPECTS 4-5. Favorable outcomes showed no significant difference between the two groups (adjusted odds ratio [aOR]= 1.13, 95% confidence interval [CI]: 0.52-2.41, p=0.80). There were also no significant differences in 90-day mRS 0-2 (aOR= 1.65, 95% CI: 0.66-3.99, p=0.30), 90-day mortality (aOR= 1.14, 95% CI: 0.58-2.20, p=0.70), any ICH (aOR= 0.54, 95% CI: 0.28-1.00, p=0.06), and sICH (aOR= 0.70, 95% CI: 0.27-1.63, p = 0.40) between the groups. CONCLUSIONS: AIS patients with LVO undergoing MT with ASPECTS 2-3 had similar outcomes compared to ASPECTS 4-5.

Higher Hospital Frailty Risk Score Is Associated With Increased Risk of Stroke: Observational and Genetic Analyses.

BACKGROUND: Frailty is a prevalent state associated with several aging-related traits and conditions. The relationship between frailty and stroke remains understudied. Here we aim to investigate whether the hospital frailty risk score (HFRS) is associated with the risk of stroke and determine whether a significant association between genetically determined frailty and stroke exists. DESIGN: Observational study using data from All of Us research program and Mendelian Randomization analyses. METHODS: Participants from All of Us with available electronic health records were selected for analysis. All of Us began national enrollment in 2018 and is expected to continue for at least 10 years. All of Us is recruiting members of groups that have traditionally been underrepresented in research. All participants provided informed consent at the time of enrollment, and the date of consent was recorded for each participant. Incident stroke was defined as stroke event happening on or after the date of consent to the All of Us study HFRS was measured with a 3-year look-back period before the date of consent for stroke risk. The HFRS was stratified into 4 categories: no-frailty (HFRS=0), low (HFRS ≥1 and <5), intermediate (≥5 and <15), and high (HFRS ≥15). Last, we implemented Mendelian Randomization analyses to evaluate whether genetically determined frailty is associated with stroke risk. RESULTS: Two hundred fifty-three thousand two hundred twenty-six participants were at risk of stroke. In multivariable analyses, frailty status was significantly associated with risk of any (ischemic or hemorrhagic) stroke following a dose-response way: not-frail versus low HFRS (HR, 4.9 [CI, 3.5-6.8]; P<0.001), not-frail versus intermediate HFRS (HR, 11.4 [CI, 8.3-15.7]; P<0.001) and not-frail versus high HFRS (HR, 42.8 [CI, 31.2-58.6]; P<0.001). We found similar associations when evaluating ischemic and hemorrhagic stroke separately (P value for all comparisons <0.05). Mendelian Randomization confirmed this association by indicating that genetically determined frailty was independently associated with risk of any stroke (OR, 1.45 [95% CI, 1.15-1.84]; P=0.002). CONCLUSIONS: Frailty, based on the HFRS was associated with higher risk of any stroke. Mendelian Randomization analyses confirmed this association providing evidence to support a causal relationship.

Detection of Intracerebral Hemorrhage Using Low-Field, Portable Magnetic Resonance Imaging in Patients With Stroke.

BACKGROUND: Neuroimaging is essential for detecting spontaneous, nontraumatic intracerebral hemorrhage (ICH). Recent data suggest ICH can be characterized using low-field magnetic resonance imaging (MRI). Our primary objective was to investigate the sensitivity and specificity of ICH on a 0.064T portable MRI (pMRI) scanner using a methodology that provided clinical information to inform rater interpretations. As a secondary aim, we investigated whether the incorporation of a deep learning (DL) reconstruction algorithm affected ICH detection. METHODS: The pMRI device was deployed at Yale New Haven Hospital to examine patients presenting with stroke symptoms from October 26, 2020 to February 21, 2022. Three raters independently evaluated pMRI examinations. Raters were provided the images alongside the patient's clinical information to simulate real-world context of use. Ground truth was the closest conventional computed tomography or 1.5/3T MRI. Sensitivity and specificity results were grouped by DL and non-DL software to investigate the effects of software advances. RESULTS: A total of 189 exams (38 ICH, 89 acute ischemic stroke, 8 subarachnoid hemorrhage, 3 primary intraventricular hemorrhage, 51 no intracranial abnormality) were evaluated. Exams were correctly classified as positive or negative for ICH in 185 of 189 cases (97.9% overall accuracy). ICH was correctly detected in 35 of 38 cases (92.1% sensitivity). Ischemic stroke and no intracranial abnormality cases were correctly identified as blood-negative in 139 of 140 cases (99.3% specificity). Non-DL scans had a sensitivity and specificity for ICH of 77.8% and 97.1%, respectively. DL scans had a sensitivity and specificity for ICH of 96.6% and 99.3%, respectively. CONCLUSIONS: These results demonstrate improvements in ICH detection accuracy on pMRI that may be attributed to the integration of clinical information in rater review and the incorporation of a DL-based algorithm. The use of pMRI holds promise in providing diagnostic neuroimaging for patients with ICH.

Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.

We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.

Deep Learning Applications for Acute Stroke Management.

Brain imaging is essential to the clinical care of patients with stroke, a leading cause of disability and death worldwide. Whereas advanced neuroimaging techniques offer opportunities for aiding acute stroke management, several factors, including time delays, inter-clinician variability, and lack of systemic conglomeration of clinical information, hinder their maximal utility. Recent advances in deep machine learning (DL) offer new strategies for harnessing computational medical image analysis to inform decision making in acute stroke. We examine the current state of the field for DL models in stroke triage. First, we provide a brief, clinical practice-focused primer on DL. Next, we examine real-world examples of DL applications in pixel-wise labeling, volumetric lesion segmentation, stroke detection, and prediction of tissue fate postintervention. We evaluate recent deployments of deep neural networks and their ability to automatically select relevant clinical features for acute decision making, reduce inter-rater variability, and boost reliability in rapid neuroimaging assessments, and integrate neuroimaging with electronic medical record (EMR) data in order to support clinicians in routine and triage stroke management. Ultimately, we aim to provide a framework for critically evaluating existing automated approaches, thus equipping clinicians with the ability to understand and potentially apply DL approaches in order to address challenges in clinical practice. ANN NEUROL 2022;92:574-587.

The Impact of Dual Antiplatelet Therapy Duration on Unruptured Aneurysm Occlusion After Flow Diversion: A Multicenter Study.

OBJECTIVE: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion. METHODS: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. RESULTS: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76). CONCLUSIONS: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications.

Endovascular Treatment of Acute Ischemic Stroke With the Penumbra System in Routine Practice: COMPLETE Registry Results.

BACKGROUND AND PURPOSE: The purpose of the COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device) registry was to evaluate the generalizability of the safety and efficacy of the Penumbra System (Penumbra, Inc, Alameda) in a real-world setting. METHODS: COMPLETE was a global, prospective, postmarket, multicenter registry. Patients with large vessel occlusion-acute ischemic stroke who underwent mechanical thrombectomy using the Penumbra System with or without the 3D Revascularization Device as frontline approach were enrolled at 42 centers (29 United States, 13 Europe) from July 2018 to October 2019. Primary efficacy end points were successful postprocedure angiographic revascularization (modified Thrombolysis in Cerebral Infarction ≥2b) and 90-day functional outcome (modified Rankin Scale score 0-2). The primary safety end point was 90-day all-cause mortality. An imaging core lab determined modified Thrombolysis in Cerebral Infarction scores, Alberta Stroke Program Early CT Scores, clot location, and occurrence of intracranial hemorrhage at 24 hours. Independent medical reviewers adjudicated safety end points. RESULTS: Six hundred fifty patients were enrolled (median age 70 years, 54.0% female, 49.2% given intravenous recombinant tissue-type plasminogen activator before thrombectomy). Rate of modified Thrombolysis in Cerebral Infarction 2b to 3 postprocedure was 87.8% (95% CI, 85.3%-90.4%). First pass and postprocedure rates of modified Thrombolysis in Cerebral Infarction 2c to 3 were 41.5% and 66.2%, respectively. At 90 days, 55.8% (95% CI, 51.9%-59.7%) had modified Rankin Scale score 0 to 2, and all-cause mortality was 15.5% (95% CI, 12.8%-18.3%). CONCLUSIONS: Using Penumbra System for frontline mechanical thrombectomy treatment of patients with large vessel occlusion-acute ischemic stroke in a real-world setting was associated with angiographic, clinical, and safety outcomes that were comparable to prior randomized clinical trials with stringent site and operator selection criteria. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03464565.

Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Hospital Revisits for Post-Ischemic Stroke Epilepsy after Acute Stroke Interventions.

OBJECTIVES: Improvements in acute stroke care have led to an increase in ischemic stroke survivors, who are at risk for development of post-ischemic stroke epilepsy (PISE). The impact of therapies such as thrombectomy and thrombolysis on risk of hospital revisits for PISE is unclear. We utilized administrative data to investigate the association between stroke treatment and PISE-related visits. MATERIALS AND METHODS: Using claims data from California, New York, and Florida, we performed a retrospective analysis of adult survivors of acute ischemic strokes. Patients with history of epilepsy, trauma, infections, or tumors were excluded. Included patients were followed for a primary outcome of revisits for seizures or epilepsy. Cox proportional hazards regression was used to identify covariates associated with PISE. RESULTS: In 595,545 included patients (median age 74 [IQR 21], 52% female), the 6-year cumulative rate of PISE-related revisit was 2.20% (95% CI 2.16-2.24). In multivariable models adjusting for demographics, comorbidities, and indicators of stroke severity, IV-tPA (HR 1.42, 95% CI 1.31-1.54, p<0.001) but not MT (HR 1.62, 95% CI 0.90-1.50, p=0.2) was associated with PISE-related revisit. Patients who underwent decompressive craniectomy experienced a 2-fold increase in odds for returning with PISE (HR 2.35, 95% CI 1.69-3.26, p<0.001). In-hospital seizures (HR 4.06, 95% CI 3.76-4.39, p<0.001) also elevated risk for PISE. SIGNIFICANCE: We demonstrate that ischemic stroke survivors who received IV-tPA, underwent decompressive craniectomy, or experienced acute seizures were at increased risk PISE-related revisit. Close attention should be paid to these patients with increased potential for long-term development of and re-hospitalization for PISE.

Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH). METHODS: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes. RESULTS: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (ß, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (ß 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (ß 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome. CONCLUSIONS: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.

Genetically Determined Smoking Behavior and Risk of Nontraumatic Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Animal and observational studies indicate that smoking is a risk factor for aneurysm formation and rupture, leading to nontraumatic subarachnoid hemorrhage (SAH). However, a definitive causal relationship between smoking and the risk of SAH has not been established. Using Mendelian randomization (MR) analyses, we tested the hypothesis that smoking is causally linked to the risk of SAH. METHODS: We conducted a 1-sample MR study using data from the UK Biobank, a large cohort study that enrolled over 500 000 Britons aged 40 to 69 from 2006 to 2010. Participants of European descent were included. SAH cases were ascertained using a combination of self-reported, electronic medical record, and death registry data. As the instrument, we built a polygenic risk score using independent genetic variants known to associate (P<5×10-8) with smoking behavior. This polygenic risk score represents the genetic susceptibility to smoking initiation. The primary MR analysis utilized the ratio method. Secondary MR analyses included the inverse variance weighted and weighted median methods. RESULTS: A total of 408 609 study participants were evaluated (mean age, 57 [SD 8], female sex, 220 937 [54%]). Among these, 132 566 (32%) ever smoked regularly, and 904 (0.22%) had a SAH. Each additional SD of the smoking polygenic risk score was associated with 21% increased risk of smoking (odds ratio [OR], 1.21 [95% CI, 1.20-1.21]; P<0.001) and a 10% increased risk of SAH (OR, 1.10 [95% CI, 1.03-1.17]; P=0.006). In the primary MR analysis, genetic susceptibility to smoking was associated with a 63% increase in the risk of SAH (OR, 1.63 [95% CI, 1.15-2.31]; P=0.006). Secondary analyses using the inverse variance weighted method (OR, 1.57 [95% CI, 1.13-2.17]; P=0.007) and the weighted median method (OR, 1.74 [95% CI, 1.06-2.86]; P=0.03) yielded similar results. There was no significant pleiotropy (MR-Egger intercept P=0.39; MR Pleiotropy Residual Sum and Outlier global test P=0.69). CONCLUSIONS: These findings provide evidence for a causal link between smoking and the risk of SAH.

Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients.

[Figure: see text].

Effect of Hispanic Status in Mechanical Thrombectomy Outcomes After Ischemic Stroke: Insights From STAR.

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race. Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days. Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72­84), compared with 63 years (54­74) for NHB, and 71 years (60­80) for NHW patients (P<0.001). Hispanic patients had a higher incidence of diabetes (41%; P<0.001) and hypertension (82%; P<0.001) compared with NHW and NHB patients. Median procedure time was shorter in Hispanics (36 minutes) compared to NHB (39 minutes) and NHW (44 minutes) patients (P<0.001). In multivariate analysis, Hispanic patients were less likely to have favorable outcome (odds ratio, 0.502 [95% CI, 0.263­0.959]), controlling for other significant predictors (age, admission National Institutes Health Stroke Scale, onset to groin time, number of attempts, procedure time). Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.

Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN: Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING: Two randomized clinical trials and one multiethnic observational study. PATIENTS: Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.

Intracerebral Hemorrhage with Intraventricular Extension Associated with Loss of Consciousness at Symptom Onset.

BACKGROUND: In patients with spontaneous intracerebral hemorrhage (ICH), pre-hospital markers of disease severity might be useful to potentially triage patients to undergo early interventions. OBJECTIVE: Here, we tested whether loss of consciousness (LOC) at the onset of ICH is associated with intraventricular hemorrhage (IVH) on brain computed tomography (CT). METHODS: Among 3000 ICH cases from ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage study, NS069763), we included patients with complete ICH/IVH volumetric CT measurements and excluded those with seizures at ICH onset. Trained investigators extracted data from medical charts. Mental status at symptom onset (categorized as alert/oriented, alert/confused, drowsy/somnolent, coma/unresponsive/posturing) and 3-month disability (modified Rankin score, mRS) were assessed through standardized interviews of participants or dedicated proxies. We used logistic regression and mediation analysis to assess relationships between LOC, IVH, and unfavorable outcome (mRS 4-6). RESULTS: Two thousand seven hundred and twenty-four patients met inclusion criteria. Median admission Glasgow Coma Score was 15 (interquartile range 11-15). 46% had IVH on admission or follow-up CT. Patients with LOC (mental status: coma/unresponsive, n = 352) compared to those without LOC (all other mental status, n = 2372) were younger (60 vs. 62 years, p = 0.005) and had greater IVH frequency (77 vs. 41%, p < 0.001), greater peak ICH volumes (28 vs. 11 ml, p < 0.001), greater admission systolic blood pressure (200 vs. 184 mmHg, p < 0.001), and greater admission serum glucose (158 vs. 127 mg/dl, p < 0.001). LOC was independently associated with IVH presence (odds ratio, OR, 2.6, CI 1.9-3.5) and with unfavorable outcome (OR 3.05, CI 1.96-4.75). The association between LOC and outcome was significantly mediated by IVH (beta = 0.24, bootstrapped CI 0.17-0.32). CONCLUSION: LOC at ICH onset may be a useful pre-hospital marker to identify patients at risk of having or developing IVH.

Failure Mode and Effect Analysis: Engineering Safer Neurocritical Care Transitions.

BACKGROUND/OBJECTIVE: Inter-hospital patient transfers for neurocritical care are increasingly common due to increased regionalization for acute care, including stroke and intracerebral hemorrhage. This process of transfer is uniquely vulnerable to errors and risk given numerous handoffs involving multiple providers, from several disciplines, located at different institutions. We present failure mode and effect analysis (FMEA) as a systems engineering methodology that can be applied to neurocritical care transitions to reduce failures in communication and improve patient safety. Specifically, we describe our local implementation of FMEA to improve the safety of inter-hospital transfer for patients with intracerebral and subarachnoid hemorrhage as evidence of success. METHODS: We describe the conceptual basis for and specific use-case example for each formal step of the FMEA process. We assembled a multi-disciplinary team, developed a process map of all components required for successful transfer, and identified "failure modes" or errors that hinder completion of each subprocess. A risk or hazard analysis was conducted for each failure mode, and ones of highest impact on patient safety and outcomes were identified and prioritized for implementation. Interventions were then developed and implemented into an action plan to redesign the process. Importantly, a comprehensive evaluation method was established to monitor outcomes and reimplement interventions to provide for continual improvement. RESULTS: This intervention was associated with significant reductions in emergency department (ED) throughput (ED length of stay from 300 to 149 min, (p < .01), and improvements in inter-disciplinary communication (increase from pre-intervention (10%) to post- (64%) of inter-hospital transfers where the neurological intensive care unit and ED attendings discussed care for the patient prior to their arrival). CONCLUSIONS: Application of the FMEA approach yielded meaningful and sustained process change for patients with neurocritical care needs. Utilization of FMEA as a change instrument for quality improvement is a powerful tool for programs looking to improve timely communication, resource utilization, and ultimately patient safety.