2024 AHA/ASA Performance and Quality Measures for Spontaneous Intracerebral Hemorrhage: A Report From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released a revised spontaneous intracerebral hemorrhage guideline in 2022. A working group of stroke experts reviewed this guideline and identified a subset of recommendations that were deemed suitable for creating performance measures. These 15 performance measures encompass a wide spectrum of intracerebral hemorrhage patient care, from prehospital to posthospital settings, highlighting the importance of timely interventions. The measures also include 5 quality measures and address potential challenges in data collection, with the aim of future improvements.

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024.

StrokeClassifier: ischemic stroke etiology classification by ensemble consensus modeling using electronic health records.

Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists' review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists' diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier's diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

Prediction of Large Vessel Occlusion Stroke Using Clinical Registries for Research.

OBJECTIVES: A reliable method of predicting large vessel occlusion (LVO) stroke in data sets without neuroimaging could be retrospectively applied to expand research efforts. METHODS: We conducted a retrospective, cross-sectional cohort analysis of the Get With The Guidelines (GWTG)-Stroke registry. We included adult patients with a final diagnosis of ischemic stroke from 2016 to 2021 who had brain and vascular imaging and excluded those with missing data or posterior circulation stroke. RESULTS: We included 416,022 patients of which 125,381 (30.1%) had LVO. The mean age was 71 years, and 48.2% were female. The area under the receiver operating curve (AUC) for the final model, including age, sex, hypertension, dyslipidemia, atrial fibrillation, diabetes, TOAST stroke mechanism, and NIH Stroke Scale (NIHSS), was 0.79 (95% CI 0.79-0.80). Without TOAST mechanism, the AUC was 0.74. The specificity did not exceed 0.5 using different cut points for the NIHSS. DISCUSSION: We found that 30% of adult acute ischemic stroke patients in GWTG-Stroke have LVO and that the combination of clinical covariates and NIHSS is only moderately predictive of LVO status. These results are consistent with previous studies and suggest it may not be possible to retrospectively predict LVO with high accuracy in data sets without vascular neuroimaging.

Use of a dedicated open transcarotid access system for neurovascular disease.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an increasingly popular technique for the management of extracranial carotid stenosis. Its off-label use in the treatment of intracranial neurovascular disease is poorly described. Our objective is to describe the use of a dedicated open transcarotid access system for the treatment of neurovascular pathologies other than extracranial carotid stenosis. METHODS: We conducted a retrospective review of a prospectively maintained database of consecutive patients who underwent treatment of neurovascular disease at a single academic center using the ENROUTE Transcarotid Arterial Sheath. Demographics, procedural characteristics, and patient outcomes were reported. RESULTS: Twenty patients were included in the study between September 2017 and March 2023. The following pathologies were treated: intracranial atherosclerotic disease (ICAD, nine patients), complex cervico-petrous carotid disease (five patients), intracranial aneurysms (three patients), and large vessel occlusion-acute ischemic stroke (three patients). Eighteen of the 20 cases were performed with active carotid flow reversal. All cases were successfully completed. There were no access-related complications. One periprocedural complication was incurred: a microguidewire perforation during an exchange maneuver for the treatment of ICAD. CONCLUSION: An open transcarotid approach using a dedicated transcarotid system may offer a safe alternative access strategy for the endovascular treatment of complex neurovascular pathologies when a traditional transfemoral or transradial approach is contraindicated or failed.

Impact of sleep quality and physical activity on blood pressure variability.

Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, we examined sleep quality and physical activity over one year, operationalized as mean daily step count and number of sleep interruptions, both transformed into tertiles. The primary study outcome was high BPV, defined as the top tertile of systolic blood pressure standard deviation. Our cohort comprised 29,375 individuals (mean age = 58.6 years) with 127.8±90.1 mean days of measurements. After adjusting for age, gender, country, body mass index, measurement days, mean blood pressure, and total time in bed, the odds ratio of having high BPV for those in the top tertile of sleep interruptions (poor sleep) was 1.37 (95% CI, 1.28-1.47) and 1.44 (95% CI, 1.35-1.54) for those in the lowest tertile of step count (physically inactive). Combining these exposures revealed a significant excess relative risk of 0.20 (95% CI, 0.04-0.35, p = 0.012), confirming their super-additive effect. Comparing individuals with the worst exposure status (lowest step count and highest sleep interruptions, n = 2,690) to those with the most optimal status (highest step count and lowest sleep interruptions, n = 3,531) yielded an odds ratio of 2.01 (95% CI, 1.80-2.25) for high BPV. Our findings demonstrate that poor sleep quality and physical inactivity are associated with increased BPV both independently and super-additively.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Secondary Prevention in Patients With Stroke Versus Myocardial Infarction: Analysis of 2 National Cohorts.

BACKGROUND: The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in comparison to participants with MI. METHODS AND RESULTS: In cross-sectional analyses within the UK Biobank and All of Us Research Program, involving 14 760 (9193 strokes, 5567 MIs) and 7315 (2948 strokes, 4367 MIs) participants, respectively, we evaluated cardiovascular prevention profiles assessing low-density lipoprotein (<100 mg/dL), blood pressure (systolic, <140 mm Hg; and diastolic, <90 mm Hg), statin and antiplatelet use, and a cardiovascular prevention score that required meeting at least 3 of these criteria. The results revealed that, within the UK Biobank, patients with stroke had significantly lower odds of meeting all the preventive criteria compared with patients with MI: low-density lipoprotein control (odds ratio [OR], 0.73 [95% CI, 0.68-0.78]; P<0.001), blood pressure control (OR, 0.63 [95% CI, 0.59-0.68]; P<0.001), statin use (OR, 0.45 [95% CI, 0.42-0.48]; P<0.001), antiplatelet therapy use (OR, 0.30 [95% CI, 0.27-0.32]; P<0.001), and cardiovascular prevention score (OR, 0.42 [95% CI, 0.39-0.45]; P<0.001). Similar patterns were observed in the All of Us Research Program, with significant differences across all comparisons (P<0.05), and further analysis suggested that the odds of having a good cardiovascular prevention score were influenced by race and ethnicity as well as neighborhood deprivation levels (interaction P<0.05 in both cases). CONCLUSIONS: In 2 independent national cohorts, patients with stroke showed poorer cardiovascular prevention profiles and lower adherence to guideline-directed therapies compared with patients with MI. These findings underscore the need to explore the reasons behind the underuse of secondary prevention in vulnerable stroke survivors.

Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019.

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures: In this study, no particular exposure was specifically targeted. Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021.

BACKGROUND: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. METHODS: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. RESULTS: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). CONCLUSION: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Burden of Neurologic Health Care and Incident Neurologic Diagnoses in the Year After COVID-19 or Influenza Hospitalization.

BACKGROUND AND OBJECTIVE: Following the outbreak of viral infections from the severe acute respiratory syndrome coronavirus 2 virus in 2019 (coronavirus disease 2019 [COVID-19]), reports emerged of long-term neurologic sequelae in survivors. To better understand the burden of neurologic health care and incident neurologic diagnoses in the year after COVID-19 vs influenza, we performed an analysis of patient-level data from a large collection of electronic health records (EMR). METHODS: We acquired deidentified data from TriNetX, a global health research network providing access to EMR data. We included individuals aged 18 years or older during index event, defined as hospital-based care for COVID-19 (from April 1, 2020, until November 15, 2021) or influenza (from 2016 to 2019). The study outcomes were subsequent health care encounters over the following year for 6 neurologic diagnoses including migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia. We also created a composite of the 6 diagnoses as an incident event, which we call "incident neurologic diagnoses." We performed a 1:1 complete case nearest-neighbor propensity score match on age, sex, race/ethnicity, marital status, US census region patient residence, preindex years of available data, and Elixhauser comorbidity score. We fit time-to-event models and reported hazard ratios for COVID-19 vs influenza infection. RESULTS: After propensity score matching, we had a balanced cohort of 77,272 individuals with COVID-19 and 77,272 individuals with influenza. The mean age was 51.0 ± 19.7 years, 57.7% were female, and 41.5% were White. Compared with patients with influenza, patients with COVID-19 had a lower risk of subsequent care for migraine (HR 0.645, 95% CI 0.604-0.687), epilepsy (HR 0.783, 95% CI 0.727-0.843), neuropathies (HR 0.567, 95% CI 0.532-0.604), movement disorders (HR 0.644, 95% CI 0.598-0.693), stroke (HR 0.904, 95% CI 0.845-0.967), or dementia (HR 0.931, 95% CI 0.870-0.996). Postinfection incident neurologic diagnoses were observed in 2.79% of the COVID-19 cohort vs 4.91% of the influenza cohort (HR 0.618, 95% CI 0.582-0.657). DISCUSSION: Compared with a matched cohort of adults with a hospitalization or emergency department visit for influenza infection, those with COVID-19 had significantly fewer health care encounters for 6 major neurologic diagnoses over a year of follow-up. Furthermore, we found that COVID-19 infection was associated with a lower risk of an incident neurologic diagnosis in the year after infection.

Impact of Procedure Time on First Pass Effect in Mechanical Thrombectomy for Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT). METHODS: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation. RESULTS: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable. CONCLUSION: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

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.

Uncertainty-aware deep-learning model for prediction of supratentorial hematoma expansion from admission non-contrast head computed tomography scan.

Hematoma expansion (HE) is a modifiable risk factor and a potential treatment target in patients with intracerebral hemorrhage (ICH). We aimed to train and validate deep-learning models for high-confidence prediction of supratentorial ICH expansion, based on admission non-contrast head Computed Tomography (CT). Applying Monte Carlo dropout and entropy of deep-learning model predictions, we estimated the model uncertainty and identified patients at high risk of HE with high confidence. Using the receiver operating characteristics area under the curve (AUC), we compared the deep-learning model prediction performance with multivariable models based on visual markers of HE determined by expert reviewers. We randomly split a multicentric dataset of patients (4-to-1) into training/cross-validation (n = 634) versus test (n = 159) cohorts. We trained and tested separate models for prediction of ≥6 mL and ≥3 mL ICH expansion. The deep-learning models achieved an AUC = 0.81 for high-confidence prediction of HE≥6 mL and AUC = 0.80 for prediction of HE≥3 mL, which were higher than visual maker models AUC = 0.69 for HE≥6 mL (p = 0.036) and AUC = 0.68 for HE≥3 mL (p = 0.043). Our results show that fully automated deep-learning models can identify patients at risk of supratentorial ICH expansion based on admission non-contrast head CT, with high confidence, and more accurately than benchmark visual markers.

Time-Dependent Changes in Hematoma Expansion Rate after Supratentorial Intracerebral Hemorrhage and Its Relationship with Neurological Deterioration and Functional Outcome.

BACKGROUND: Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT. METHODS: We included 567 consecutive patients with supratentorial ICH and baseline head CT within 24 h of onset. ND was defined as a ≥4-point increase on the NIH stroke scale (NIHSS) or a ≥2-point drop on the Glasgow coma scale. Poor outcome was defined as a modified Rankin score of 4 to 6 at 3-month follow-up. RESULTS: The rate of HE was higher among those scanned within 3 h (124/304, 40.8%) versus 3 to 24 h post-ICH onset (53/263, 20.2%) (p < 0.001). However, HE was an independent predictor of ND (p < 0.001), poor outcome (p = 0.010), and mortality (p = 0.003) among those scanned within 3 h, as well as those scanned 3-24 h post-ICH (p = 0.043, p = 0.037, and p = 0.004, respectively). Also, in a subset of 180/567 (31.7%) patients presenting with mild symptoms (NIHSS ≤ 5), hematoma growth was an independent predictor of ND (p = 0.026), poor outcome (p = 0.037), and mortality (p = 0.027). CONCLUSION: Despite decreasing rates over time after ICH onset, HE remains an independent predictor of ND, functional outcome, and mortality among those presenting >3 h after onset or with mild symptoms.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

APOE ε4 and Intracerebral Hemorrhage in Patients With Brain Arteriovenous Malformation.

Importance: Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH. Objective: To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM. Design, Setting, and Participants: This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status. Main Outcomes and Measures: For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression. Results: The discovery phase included 253 UK Biobank participants with known AVM (mean [SD] age, 56.6 [8.0] years, 119 [47.0%] female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean [SD] age, 57.1 [15.9] years; 106 [66.7%] female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03). Conclusions and Relevance: The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.

Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Stroke genetic research has made substantial progress in the past decade. Its recovery application, however, remains behind, in part due to its reliance on the modified Rankin Scale (mRS) score as a measure of poststroke outcome. The mRS does not map well to biological processes because numerous psychosocial factors drive much of what the mRS captures. Second, the mRS contains multiple disparate biological events into a single measure further limiting its use for biological discovery. This led us to investigate the effect of distinct stroke recovery phenotypes on genetic variation associations with Genome-Wide Association Studies (GWASs) by repurposing the NIH Stroke Scale (NIHSS) and its subscores. METHODS: In the Vitamin Intervention for Stroke Prevention cohort, we estimated changes in cognition, motor, and global impairments over 2 years using specific measures. We included genotyped participants with a total NIHSS score greater than zero at randomization and excluded those with recurrent stroke during the trial. A GWAS linear mixed-effects model predicted score changes, with participant as a random effect, and included initial score, age, sex, treatment group, and the first 5 ancestry principal components. RESULTS: In total, 1,270 participants (64% male) were included with a median NIHSS score of 2 (interquartile range [IQR] 1-3) and median age 68 (IQR 59-75) years. At randomization, 20% had cognitive deficits (NIHSS Cog-4 score >0) and 70% had ≥1 motor deficits (impairment score >1). At 2 years, these percentages improved to 7.2% with cognitive deficits and 30% with motor deficits. GWAS identified novel suggestive gene-impairment associations (p < 5e-6) for cognition (CAMK2D, EVX2, LINC0143, PTPRM, SGMS1, and SMAD2), motor (ACBD6, KDM4B, MARK4, PTPRS, ROBO1, and ROBO2), and global (MSR1 and ROBO2) impairments. DISCUSSION: Defining domain-specific stroke recovery phenotypes and using longitudinal clinical trial designs can help detect novel genes associated with chronic recovery. These data support the use of granular endpoints to identify genetic associations related to stroke recovery.

Association of Poor Oral Health With Neuroimaging Markers of White Matter Injury in Middle-Aged Participants in the UK Biobank.

BACKGROUND AND OBJECTIVES: Poor oral health is a modifiable risk factor that is associated with clinically observed cardiovascular disease. However, the relationship between oral and brain health is not well understood. We tested the hypothesis that poor oral health is associated with worse neuroimaging brain health profiles in middle-aged persons without stroke or dementia. METHODS: We performed a 2-stage cross-sectional neuroimaging study using UK Biobank data. First, we tested for association between self-reported poor oral health and MRI neuroimaging markers of brain health. Second, we used Mendelian randomization (MR) analyses to test for association between genetically determined poor oral health and the same neuroimaging markers. Poor oral health was defined as the presence of dentures or loose teeth. As instruments for the MR analysis, we used 116 independent DNA sequence variants linked to increased composite risk of dentures or teeth that are decayed, missing, or filled. Neuroimaging markers of brain health included white matter hyperintensity (WMH) volume and aggregate measures of fractional anisotropy (FA) and mean diffusivity (MD), 2 metrics indicative of white matter tract disintegrity obtained through diffusion tensor imaging across 48 brain regions. RESULTS: We included 40,175 persons (mean age 55 years, female sex 53%) enrolled from 2006 to 2010, who underwent a dedicated research brain MRI between 2014 and 2016. Among participants, 5,470 (14%) had poor oral health. Poor oral health was associated with a 9% increase in WMH volume (ß = 0.09, SD = 0.014, p < 0.001), 10% change in aggregate FA score (ß = 0.10, SD = 0.013, p < 0.001), and 5% change in aggregate MD score (ß = 0.05, SD = 0.013, p < 0.001). Genetically determined poor oral health was associated with a 30% increase in WMH volume (ß = 0.30, SD = 0.06, p < 0.001), 43% change in aggregate FA score (ß = 0.43, SD = 0.06, p < 0.001), and 10% change in aggregate MD score (ß = 0.10, SD = 0.03, p < 0.01). DISCUSSION: Among middle age Britons without stroke or dementia, poor oral health was associated with worse neuroimaging brain health profiles. Genetic analyses confirmed these associations, supporting a potentially causal association. Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health.