Association of Anticoagulant Use With Hemorrhage Location and Etiology in Incident Spontaneous Intracerebral Hemorrhage.

BACKGROUND: It is unknown whether hypertensive microangiopathy or cerebral amyloid angiopathy (CAA) predisposes more to anticoagulant-associated intracerebral hemorrhage (AA-ICH). The purpose of our study was to determine whether AA-ICH is associated with lobar location and probable CAA. METHODS: This was a cross-sectional analysis of patients with first-ever spontaneous ICH admitted to a tertiary hospital in Boston, between 2008 and 2023. Univariable and multivariable logistic regression were used to investigate the association between anticoagulation use and both lobar hemorrhage location and probable CAA on magnetic resonance imaging (MRI) by Boston Criteria 2.0 or computed tomography by Simplified Edinburgh Criteria. RESULTS: A total of 1104 patients (mean [SD] age, 73 [12]; 499 females [45.0%]) were included. Of the 1104 patients, 268 (24.3%) had AA-ICH: 148 (55.2%) with vitamin K antagonists and 107 (39.9%) with direct oral anticoagulants. Brain MRI was performed in 695 (63.0%) patients. The proportion of patients with lobar hemorrhage was not different between those with and without AA-ICH (121/268 [45.1%] versus 424/836 [50.7%]; odds ratio [OR], 0.80 [95% CI, 0.61-1.05]; P=0.113). Patients with AA-ICH were less likely to have probable CAA on MRI (17/146 [11.6%] versus 127/549 [23.1%]; OR, 0.44 [95% CI, 0.25-0.75]; P=0.002) and probable CAA on MRI or computed tomography if MRI not performed (27/268 [10.0%] versus 200/836 [23.9%]; OR, 0.36 [95% CI, 0.23-0.55]; P<0.001). Among patients with AA-ICH, there were no differences in the proportion with lobar hemorrhage (63/148 [42.6%] versus 46/107 [43.0%]; OR, 1.02 [95% CI, 0.62-1.68]; P=0.946) or probable CAA on MRI (10/72 [13.9%] versus 7/69 [10.1%]; OR, 0.70 [95% CI, 0.25-1.96]; P=0.495) between vitamin K antagonists and direct oral anticoagulant users. CONCLUSIONS: AA-ICH was not associated with lobar hemorrhage location but was associated with reduced odds of probable CAA. These results suggest that hypertensive microangiopathy may predispose more toward incident AA-ICH than CAA and emphasize the importance of blood pressure control among anticoagulant users. These findings require replication in additional cohorts.

Clinical Characteristics, Functional Outcome, and Socioeconomic Impact of Ischemic Stroke among Young Egyptian Adults.

BACKGROUND: Stroke in young patients results in disproportionately high societal cost given the productive life-years lost. Little is known about stroke in young Egyptian patients. We aimed to analyze clinicodemographic characteristics, functional outcome, and socioeconomic impact of ischemic stroke among young Egyptian adults. METHODS: This is a prospective, observational cohort study of consecutively recruited patients with acute ischemic stroke (AIS), 18-50 years, between September 2022 and September 2023 at a tertiary stroke center in the south of Egypt. We recorded baseline demographic and cardiovascular risk factors, stroke severity, stroke subtype according to the TOAST classification, intravenous thrombolysis, employment, and ambulation status pre- and post-stroke, post-stroke complications, and 90-day functional outcome measured by the modified Rankin Scale (mRS). RESULTS: Our cohort comprised 210 patients, 38.0 (±7.8) years, 89 (42%) females. Mean NIHSS score was 11.2 (±4.8); in-hospital case fatality was 9% (19 patients). Dyslipidemia (n = 105, 50%), smoking (n = 105, 50%), and hypertension (n = 67, 32%) were the most prevalent cardiovascular risk factors. At 90 days, 58 (29%) patients had a 90-day mRS 0-1 and 53 (26%) met criteria for depression diagnosis. Sixty-nine of the 116 employed individuals (59%) remained out of work after 90 days of stroke, 61 of whom were single earners in their household. 36/60 (60%) thrombolysis-eligible patients received it; an additional 98 otherwise thrombolysis-eligible patients presented >4.5 h from symptom onset. Patients receiving IV thrombolysis were significantly more likely to have resumed full-time work at 90 days (32% vs. 11%, p = 0.006) but with no significant difference in 90-day mRS. CONCLUSIONS: Young adult AIS patients in Egypt experience high rates of post-stroke depression and face challenges in their ability to work and provide for their families. Since most patients have treatable cardiovascular risk factors and only about two-thirds of eligible patients receive thrombolysis, reinforcing primary prevention, education about early stroke signs, and benefits of acute can improve outcomes and have significant potential societal benefit.

Cognitive Outcome after Acute Spontaneous Intracerebral Hemorrhage: Analysis of the iDEF Randomized Trial.

INTRODUCTION: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. METHODS: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. RESULTS: 291 were available for analysis under the trial's modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8-18). The median baseline ICH volume was 12.9 IQR (6.4-26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. CONCLUSIONS: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Rationale and Design of the Statins Use in Intracerebral Hemorrhage Patients (SATURN) Trial.

INTRODUCTION: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials (RCTs) addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCE) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes and quality of life. METHODS: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment. A planned total of 1456 patients with lobar ICH will be recruited from 140 sites in the United States, Canada and Spain. Patients presenting within seven days of a spontaneous lobar ICH that occurred while taking a statin, will be randomized (1:1) to continuation (control) vs. discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a two-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. CONCLUSION: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from statins.

Etiology of Primary Cerebellar Intracerebral Hemorrhage Based on Topographic Localization.

BACKGROUND: Cerebellar intracerebral hemorrhage (cICH) is often attributed to hypertension or cerebral amyloid angiopathy (CAA). However, deciphering the exact etiology can be challenging. A recent study reported a topographical etiologic relationship with superficial cICH secondary to CAA. We aimed to reexamine this relationship between topography and etiology in a separate cohort of patients and using the most recent Boston criteria version 2.0. METHODS: We performed a retrospective analysis of consecutive patients with primary cICH admitted to a tertiary academic center between 2000 and 2022. cICH location on brain computed tomography/magnetic resonance imaging scan(s) was divided into strictly superficial (cortex, surrounding white matter, vermis) versus deep (cerebellar nuclei, deep white matter, peduncular region) or mixed (both regions). Magnetic resonance imaging was rated for markers of cerebral small vessel disease. We assigned possible/probable versus absent CAA using Boston criteria 2.0. RESULTS: We included 197 patients; 106 (53.8%) were females, median age was 74 (63-82) years. Fifty-six (28%) patients had superficial cICH and 141 (72%) deep/mixed cICH. Magnetic resonance imaging was available for 112 (57%) patients (30 [26.8%] with superficial and 82 [73.2%] with deep/mixed cICH). Patients with superficial cICH were more likely to have possible/probable CAA (48.3% versus 8.6%; odds ratio [OR], 11.43 [95% CI, 3.26-40.05]; P<0.001), strictly lobar cerebral microbleeds (51.7% versus 6.2%; OR, 14.18 [95% CI, 3.98-50.50]; P<0.001), and cortical superficial siderosis (13.8% versus 1.2%; OR, 7.70 [95% CI, 0.73-80.49]; P=0.08). Patients with deep/mixed cICH were more likely to have deep/mixed cerebral microbleeds (59.2% versus 3.4%; OR, 41.39 [95% CI, 5.01-341.68]; P=0.001), lacunes (54.9% versus 17.2%; OR, 6.14 [95% CI, 1.89-19.91]; P=0.002), severe basal ganglia enlarged perivascular spaces (36.6% versus 7.1%; OR, 7.63 [95% CI, 1.58-36.73]; P=0.01), hypertension (84.4% versus 62.5%; OR, 3.43 [95% CI, 1.61 to -7.30]; P=0.001), and higher admission systolic blood pressure (172 [146-200] versus 146 [124-158] mm Hg, P<0.001). CONCLUSIONS: Our results suggest that superficial cICH is strongly associated with CAA whereas deep/mixed cICH is strongly associated with hypertensive arteriopathy.

Variation in Ischemic Stroke Payments in the USA: A Medicare Beneficiary Study.

INTRODUCTION: The growing cost of stroke care has created the need for outcome-oriented and cost-saving payment models. Identifying imbalances in the current reimbursement model is an essential step toward designing impactful value-based reimbursement strategies. This study describes the variation in reimbursement fees for ischemic stroke management across the USA. METHODS: This Medicare Fee-For-Service claims study examines USA beneficiaries who suffered an ischemic stroke from 2021Q1 to 2022Q2 identified using the Medicare-Severity Diagnosis-Related Groups (MS-DRGs). Demographic national and regional US data were extracted from the Census Bureau. The MS-DRG codes were grouped into four categories according to treatment modality and clinical complexity. Our primary outcome of interest was payments made across individual USA and US geographic regions, assessed by computing the mean incremental payment in cases of comparable complexity. Differences between states for each MS-DRG were statistically evaluated using a linear regression model of the logarithmic transformed payments. RESULTS: 227,273 ischemic stroke cases were included in our analysis. Significant variations were observed among all DRGs defined by medical complexity, treatment modality, and states (p < 0.001). Differences in mean payment per case with the same MS-DRG vary by as high as 500% among individual states. Although higher payment rates were observed in MS-DRG codes with major comorbidities or complexity (MCC), the variation was more expressive for codes without MCC. It was not possible to identify a standard mean incremental fee at a state level. At a regional level, the Northeast registered the highest fees, followed by the West, Midwest, and South, which correlate with poverty rates and median household income in the regions. CONCLUSIONS: The payment variability observed across USA suggests that the current reimbursement system needs to be aligned with stroke treatment costs. Future studies may go one step further to evaluate accurate stroke management costs to guide policymakers in introducing health policies that promote better care for stroke patients.

The role of hyperglycemia in the outcome of intracerebral hemorrhage: A causative analysis.

BACKGROUND: Hyperglycemia in the acute phase of intracerebral hemorrhage (ICH) has been associated with poor functional outcomes, however all interventions to lower glucose have yielded neutral or negative results. We attempt an explanation of the causal role of hyperglycemia in ΙCH outcome using generalized structural equation modeling. MATERIALS AND METHODS: Consecutive primary ICH patients admitted to an academic hospital between 2007 and 2018 were identified. Patients with missing baseline or follow up CT scans and without 90 day follow up status were excluded. We constructed a causal model accounting for pre-defined markers of ICH severity to evaluate the association between mean 72 h glucose and 90 day functional outcome measured by modified Rankin Scale, dichotomized as favorable ≤2 or unfavorable >2. RESULTS: Primary analyses included 410 patients (70.4 ± 13.8years, 43 % female). Mean 72 h glucose was 137.5 ± 33.4mg/dl and 102 (25 %) patients were diabetic. On univariable analysis, higher glucose levels were negatively correlated with favorable outcome (p < 0.0001). However in the structural equation model, this relationship was significantly attenuated (p = 0.06) after accounting for the causal effect of diabetes (p < 0.0001), hematoma volume (p < 0.0001), intraventricular extension (p = 0.01) and Glasgow coma scale (p = 0.001) on glucose levels. On secondary analyses stratifying by diagnosis of diabetes, higher glucose levels were negatively correlated with favorable outcome in patients without diabetes (p = 0.04), but not in patients with diabetes (p = 0.35). CONCLUSIONS: Hyperglycemia may be a downstream effect of other markers of ICH severity, particularly among patients without diabetes, suggesting a possible explanation for the limited evidence of glucose lowering interventions in outcome.

An updated systematic review and meta-analysis investigating perihematomal edema and clinical outcome after intracerebral hemorrhage.

OBJECTIVES: The relationship between perihematomal edema (PHE) and intracerebral hemorrhage (ICH) outcomes is uncertain. Given newly published studies, we updated a previous systematic review and meta-analysis assessing the prognostic impact of PHE on ICH outcomes. MATERIALS AND METHODS: Databases were searched through September 2022 using pre-defined keywords. Included studies used regression to examine the association between PHE and functional outcome (assessed by modified Rankin Scale [mRS]) and mortality. The study quality was assessed using the Newcastle-Ottawa Scale. The overall pooled effect, and secondary analyses exploring different subgroups were obtained by entering the log transformed odds ratios and their confidence intervals into a DerSimonian-Laird random effects meta-analysis. RESULTS: Twenty-eight studies (n=8655) were included. The pooled effect size for overall outcome (mRS and mortality) was 1.05 (95% CI 1.03, 1.07; p<0.00). In secondary analyses, PHE volume and growth effect sizes were 1.03 (CI 1.01, 1.05) and 1.12 (CI 1.06, 1.19), respectively. Results of subgroup analyses assessing absolute PHE volume and growth at different time points were: baseline volume 1.02 (CI 0.98, 1.06), 72-hour volume 1.07 (CI 0.99, 1.16), growth at 24 hours 1.30 (CI 0.96, 1.74) and growth at 72 hours 1.10 (CI 1.04, 1.17). Heterogeneity across studies was substantial. CONCLUSIONS: This meta-analysis indicates that PHE growth, especially within the first 24 hours after ictus, has a stronger impact on functional outcome and mortality than PHE volume. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Relationship between prior statin therapy and radiological features and clinical outcomes of intracerebral hemorrhage.

OBJECTIVES: A post-hoc analysis of the ICH Deferoxamine (i-DEF) trial was performed to examine any associations pre-ICH statin use may have with ICH volume, PHE volume, and clinical outcomes. MATERIALS AND METHODS: Baseline characteristics were assessed. Various ICH and PHE parameters were measured via a quantitative, semi-automated method at baseline and follow-up CT scans 72-96 h later. A multivariable logistic regression model was created, adjusting for the variables that were significantly different on univariable analyses (p < 0.05), to assess any associations between pre-ICH statin use and measures of ICH and PHE, as well as good clinical outcome (mRS ≤2), at 90 and 180 days. RESULTS: 262 of 291 i-DEF participants had complete data available for analysis. 69 (26.3 %) used statins prior to ICH onset. Pre-ICH statin users had higher prevalences of hypertension, diabetes, and prior ischemic stroke; higher concomitant use of antihypertensives and antiplatelets; and higher blood glucose level at baseline. On univariable analyses, pre-ICH statin users had smaller baseline ICH volume and PHE volume on repeat scan, as well as smaller changes in relative PHE (rPHE) volume and edema extension distance (EED) between the baseline and repeat scans. In the multivariable analysis, none of the ICH and PHE measures or good clinical outcome was significantly associated with pre-ICH statin use. CONCLUSION: Pre-ICH statin use was not associated with measures of ICH or PHE, their growth, or clinical outcomes. These findings do not lend support to either overall protective or deleterious effects from statin use before or after ICH.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

The Prognostic Roles of Perihematomal Edema and Ventricular Size in Patients with Intracerebral Hemorrhage.

BACKGROUND: Conflicting data exist regarding the association of perihematomal edema (PHE) with outcomes after intracerebral hemorrhage (ICH). We performed a post hoc analysis of the ICH Deferoxamine trial to examine whether an early change in ventricular size (VS), as a composite measure of PHE growth and mass effect, intraventricular hemorrhage, and hydrocephalus, is a more accurate predictor of outcome than PHE measures alone. METHODS: Computerized tomography scans were performed at baseline and after 72-96 h. We evaluated measures of PHE and change in VS as predictors of outcome, assessed by a dichotomized modified Rankin Scale score (0-2 versus 3-6), primarily at 90 days and secondarily at 30 days. A multivariable logistic regression model was fitted for each predictor, with adjustment for the same confounders. RESULTS: A total of 248 participants were included after we excluded those requiring external ventricular drains. On univariate analyses, older age, female sex, lower Glasgow Coma Scale score and baseline temperature, greater ICH volume, absolute PHE volume, edema extension distance at presentation, lesser changes in relative PHE volume and edema extension distance, and an increase in VS were associated with poor outcome. In multivariable analyses, only the increase in VS was associated with lower odds of modified Rankin Scale scores 0-2 at 90 days (odds ratio 0.927, 95% confidence interval 0.866-0.970, p = 0.001) and 30 days (odds ratio 0.931, 95% confidence interval 0.888-0.975, p = 0.003). CONCLUSIONS: Within the context of a randomized controlled trial with standardized imaging and functional assessments, we did not find significant associations between measures of PHE and outcome but documented an independent association between early increase in VS and lower odds of good clinical outcome.

Perihematomal Edema and Clinical Outcome After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

BACKGROUND: Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH. METHODS: We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle-Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect. RESULTS: Twenty studies (n = 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02-1.08; p < 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90-1.14), functional outcome (1.04; 95% CI 1.02-1.07), both 90-day (1.06; 95% CI 1.02-1.11), and in-hospital assessments (1.04; 95% CI 1.00-1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01-1.07) and 1.14 (95% CI 1.04-1.25), respectively. Heterogeneity across studies was substantial except for PHE growth. CONCLUSIONS: This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Digital Peripheral Arterial Tonometry and Cardiovascular Disease Events: The Framingham Heart Study.

Background and Purpose: Novel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants. Methods: Using a fingertip PAT device, we assessed pulse amplitude in Framingham Offspring and Third Generation participants (n=3865; mean age, 55±14 years; 52% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia. The PAT ratio (relative hyperemia index) was calculated as the post-to-pre occlusion pulse signal ratio in the occluded arm, relative to the same ratio in the control (nonoccluded) arm, and corrected for baseline vascular tone. Baseline pulse amplitude and PAT ratio during hyperemia are measures of pressure pulsatility and microvascular function in the finger, respectively. We used Cox proportional hazards regression to relate PAT measures in the fingertip to incident CVD events. Results: During follow-up (median, 9.2 years; range, 0.04­10.0 years), 270 participants (7%) experienced new-onset CVD events (n=270). In multivariable models adjusted for cardiovascular risk factors, baseline pulse amplitude (hazard ratio [HR] per 1 SD, 1.04 [95% CI, 0.90­1.21]; P=0.57) and PAT ratio (HR, 0.95 [95% CI, 0.84­1.08]; P=0.43) were not significantly related to incident composite CVD events, including myocardial infarction or heart failure. However, higher PAT ratio (HR, 0.76 [95% CI, 0.61­0.94]; P=0.013), but not baseline pulse amplitude (HR, 1.15 [95% CI, 0.89­1.49]; P=0.29), was related to lower risk for incident stroke. In a sensitivity analysis by stroke subtype, higher PAT ratio was related to lower risk of incident ischemic stroke events (HR, 0.68 [95% CI, 0.53­0.86]; P=0.001). Conclusions: Novel digital PAT measures may represent a marker of stroke risk in the community.

Incidence of Transient Ischemic Attack and Association With Long-term Risk of Stroke.

Importance: Accurate estimation of the association between transient ischemic attack (TIA) and risk of subsequent stroke can help to improve preventive efforts and limit the burden of stroke in the population. Objective: To determine population-based incidence of TIA and the timing and long-term trends of stroke risk after TIA. Design, Setting, and Participants: Retrospective cohort study (Framingham Heart Study) of prospectively collected data of 14 059 participants with no history of TIA or stroke at baseline, followed up from 1948-December 31, 2017. A sample of TIA-free participants was matched to participants with first incident TIA on age and sex (ratio, 5:1). Exposures: Calendar time (TIA incidence calculation, time-trends analyses), TIA (matched longitudinal cohort). Main Outcomes and Measures: The main outcomes were TIA incidence rates; proportion of stroke occurring after TIA in the short term (7, 30, and 90 days) vs the long term (>1-10 years); stroke after TIA vs stroke among matched control participants without TIA; and time trends of stroke risk at 90 days after TIA assessed in 3 epochs: 1954-1985, 1986-1999, and 2000-2017. Results: Among 14 059 participants during 66 years of follow-up (366 209 person-years), 435 experienced TIA (229 women; mean age, 73.47 [SD, 11.48] years and 206 men; mean age, 70.10 [SD, 10.64] years) and were matched to 2175 control participants without TIA. The estimated incidence rate of TIA was 1.19/1000 person-years. Over a median of 8.86 years of follow-up after TIA, 130 participants (29.5%) had a stroke; 28 strokes (21.5%) occurred within 7 days, 40 (30.8%) occurred within 30 days, 51 (39.2%) occurred within 90 days, and 63 (48.5%) occurred more than 1 year after the index TIA; median time to stroke was 1.64 (interquartile range, 0.07-6.6) years. The age- and sex-adjusted cumulative 10-year hazard of incident stroke for patients with TIA (130 strokes among 435 cases) was 0.46 (95% CI, 0.39-0.55) and for matched control participants without TIA (165 strokes among 2175) was 0.09 (95% CI, 0.08-0.11); fully adjusted hazard ratio [HR], 4.37 (95% CI, 3.30-5.71; P < .001). Compared with the 90-day stroke risk after TIA in 1948-1985 (16.7%; 26 strokes among 155 patients with TIA), the risk between 1986-1999 was 11.1% (18 strokes among 162 patients) and between 2000-2017 was 5.9% (7 strokes among 118 patients). Compared with the first epoch, the HR for 90-day risk of stroke in the second epoch was 0.60 (95% CI, 0.33-1.12) and in the third epoch was 0.32 (95% CI, 0.14-0.75) (P = .005 for trend). Conclusions and Relevance: In this population-based cohort study from 1948-2017, the estimated crude TIA incidence was 1.19/1000 person-years, the risk of stroke was significantly greater after TIA compared with matched control participants who did not have TIA, and the risk of stroke after TIA was significantly lower in the most recent epoch from 2000-2017 compared with an earlier period from 1948-1985.

Intravenous Magnesium Sulfate in Acute Stroke.

Background and Purpose- Acute stroke treatment is challenging, and stroke remains a major cause of death and disability. The purpose of this meta-analysis is to investigate the effects of postacute stroke intravenous administration of the neuroprotectant magnesium sulfate (MgSO4) on global outcome, functional outcome, and mortality 90 days poststroke (ischemic and nonischemic). Methods- We searched in Pubmed, Science Direct, CENTRAL, and ClinicalTrials.gov, up to November 11, 2017, and we conducted a systematic review and meta-analysis of randomized controlled trials. We synthesized results by using random-effects model, weighted mean differences, standardized mean differences, and odds ratios. Results- Seven randomized controlled trials (4347 patients) met our criteria. Compared with placebo, treatment did not improve functional outcome defined as Barthel Index >60 (odds ratio =1.05; 95% CI, 0.92-1.19) and >95 (odds ratio =0.95; 95% CI, 0.76-1.20), 90 days poststroke. It also did not improve global outcome measured with modified Rankin Scale (standardized mean difference =-0.01; 95% CI, -0.12 to 0.10), 90 days poststroke. In an additional subgroup meta-analysis that exclusively included ischemic stroke patients, intravenous MgSO4 resulted in lower modified Rankin Scale score (improved global outcome; weighted mean difference =-0.96; 95% CI, -1.34 to -0.58; I2=0%], 90 days poststroke. Finally, mortality stayed unaltered (odds ratio =1.10; 95% CI, 0.94-1.29). Conclusions- The findings of our meta-analysis showed that intravenous MgSO4 generally did not improve global/functional outcomes and mortality at 90 days after stroke (combined ischemic stroke and nonischemic stroke). The finding of favorable neurological outcome, selectively in ischemic stroke patients, should be viewed with extreme caution given the limited number of patients included in this subgroup meta-analysis.

Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

Clinical Outcomes and Neuroimaging Profiles in Nondisabled Patients With Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods- Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related ICH divided into 2 groups according to the type of anticoagulant: NOAC versus VKA. We recorded baseline ICH volume, significant hematoma expansion (absolute [12.5 mL] or relative [>33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results- Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5-37.6] versus 19.5 [6.6-52.0] mL; P=0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P=0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P=0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:-0.415 [95% CI, -0.780 to -0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22-0.85) in multivariable-adjusted models. Conclusions- Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices.

Endotracheal Intubation and In-Hospital Mortality after Intracerebral Hemorrhage.

BACKGROUND: Many patients with acute intracerebral hemorrhages (ICHs) undergo endotracheal intubation with subsequent mechanical ventilation (MV) for "airway protection" with the intent to prevent aspiration, pneumonias, and its related mortality. Conversely, these procedures may independently promote pneumonia, laryngeal trauma, dysphagia, and adversely affect patient outcomes. The net benefit of intubation and MV in this patient cohort has not been systematically investigated. METHODS: We conducted a large single-center observational cohort study to examine the independent association between endotracheal intubation and MV, hospital-acquired pneumonia (HAP), and in-hospital mortality (HM) in patients with ICH. All consecutive patients admitted with a primary diagnosis of a spontaneous ICH to a tertiary care hospital in Boston, Massachusetts, from June 2000 through January 2014, who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Patients with pneumonia on admission, or those having brain or lung neoplasms were excluded. Our exposure of interest was endotracheal intubation and MV during hospitalization; our primary outcomes were incidence of HAP and HM, ascertained using International Classification of Diseases-9 and administrative discharge disposition codes, respectively, in patients who underwent endotracheal intubation and MV versus those who did not. Multivariable logistic regression was used to control for confounders. RESULTS: Of the 2,386 hospital admissions screened, 1,384 patients fulfilled study criteria and were included in the final analysis. A total of 507 (36.6%) patients were intubated. Overall 133 (26.23%) patients in the intubated group developed HAP versus 41 (4.67%) patients in the non-intubated group (p < 0.0001); 195 (38.5%) intubated patients died during hospitalization compared to 48 (5.5%) non-intubated patients (p < 0.0001). After confounder adjustments, OR for HAP and HM, were 4.23 (95% CI 2.48-7.22; p < 0.0001) and 4.32 (95% CI 2.5-7.49; p < 0.0001) with c-statistics of 0.79 and 0.89, in the intubated versus non-intubated patients, respectively. CONCLUSION: In this large hospital-based cohort of patients presenting with an acute spontaneous ICH, endotracheal intubation and MV were associated with increased odds of HAP and HM. These findings urge further examination of the practice of intubation in prospective studies.