Factors Associated With Anxiety After Hemorrhagic Stroke.

OBJECTIVE: A significant number of patients develop anxiety after stroke. The objective of this study was to identify risk factors for anxiety after hemorrhagic stroke that may facilitate diagnosis and treatment. METHODS: Patients admitted between January 2015 and February 2021 with nontraumatic hemorrhagic stroke (intracerebral [ICH] or subarachnoid [SAH] hemorrhage) were assessed telephonically 3 and 12 months after stroke with the Quality of Life in Neurological Disorders Anxiety Short Form to evaluate the relationships between poststroke anxiety (T score >50) and preclinical social and neuropsychiatric history, systemic and neurological illness severity, and in-hospital complications. RESULTS: Of 71 patients who completed the 3-month assessment, 28 (39%) had anxiety. There was a difference in Glasgow Coma Scale (GCS) scores on admission between patients with anxiety (median=14, interquartile range [IQR]=12-15) and those without anxiety (median=15, IQR=14-15) (p=0.034), and the incidence of anxiety was higher among patients with ICH (50%) than among those with SAH (20%) (p=0.021). Among patients with ICH, anxiety was associated with larger median ICH volume (25 cc [IQR=8-46] versus 8 cc [IQR=3-13], p=0.021) and higher median ICH score (2 [IQR=1-3] versus 1 [IQR=0-1], p=0.037). On multivariable analysis with GCS score, hemorrhage type, and neuropsychiatric history, only hemorrhage type remained significant (odds ratio=3.77, 95% CI=1.19-12.05, p=0.024). Of the 39 patients who completed the 12-month assessment, 12 (31%) had anxiety, and there was a difference in mean National Institutes of Health Stroke Scale scores between patients with (5 [IQR=3-12]) and without (2 [IQR=0-4]) anxiety (p=0.045). There was fair agreement (κ=0.38) between the presence of anxiety at 3 and 12 months. CONCLUSIONS: Hemorrhage characteristics and factors assessed with neurological examination on admission are associated with the development of poststroke anxiety.

Relationship Between Hemorrhage Type and Development of Emotional and Behavioral Dyscontrol After Hemorrhagic Stroke.

OBJECTIVE: Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke are heavily weighted toward ischemic stroke. This study was designed to compare risk of EBD following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and to identify risk factors for EBD following hemorrhagic stroke. METHODS: The authors conducted a prospective cohort study of patients hospitalized for nontraumatic hemorrhagic stroke between 2015 and 2021. Patients or legally authorized representatives completed the Quality of Life in Neurological Disorders (Neuro-QOL) EBD short-form inventory 3 months after hospitalization. Univariable and multivariable analyses identified risk factors for EBD after hemorrhagic stroke. RESULTS: The incidence of EBD was 21% (N=15 of 72 patients) at 3 months after hemorrhagic stroke. Patients with ICH were more likely to develop EBD; 93% of patients with EBD (N=14 of 15) had ICH compared with 56% of patients without EBD (N=32 of 57). The median Glasgow Coma Scale (GCS) score at hospital admission was lower among patients who developed EBD (13 vs. 15 among those without EBD). Similarly, admission scores on the National Institutes of Health Stroke Scale (NIHSS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were higher among patients with EBD (median NIHSS score: 7 vs. 2; median APACHE II score: 17 vs. 11). Multivariable analyses identified hemorrhage type (ICH) and poor admission GCS score as predictors of EBD 3 months after hemorrhagic stroke. CONCLUSIONS: Patients with ICH and a low GCS score at admission are at increased risk of developing EBD 3 months after hemorrhagic stroke and may benefit from early intervention.

Optimal medical therapy is lacking in patients undergoing intervention for symptomatic carotid artery stenosis and protects against larger areas of cerebral infarction.

OBJECTIVES: Carotid interventions are indicated for both patients with symptomatic and a subset of patients with severe asymptomatic carotid artery stenosis (CAS). Symptomatic CAS accounts for up to 12%-25% of overall carotid interventions, but predictors of symptomatic presentation remain poorly defined. The aim of this study was to identify factors associated with symptomatic CAS in our patient population. METHODS: Between January 2015 and February 2022, an institutional retrospective cohort study of prospectively collected data on patients undergoing interventions for CAS was performed. Procedures included carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TF-CAS). Demographic data, comorbidities, procedural details, and anatomic features from various imaging modalities were collected. Comparisons were made between symptomatic (symptoms within the prior 6 months) and asymptomatic patients. RESULTS: During the study period, 279 patients who underwent intervention for symptomatic CAS were paired with a randomly selected cohort of 300 patients who underwent intervention for asymptomatic CAS from a total patient cohort of 1143 patients undergoing interventions for asymptomatic CAS. Demographic data did not differ between groups. Patients with symptomatic CAS more frequently had prior TIA/stroke (>6 months remote to the current event), but less frequently had coronary artery disease or chronic kidney disease and were less likely to receive adequate medical management including antihypertensive agents, lipid-lowering agents, and anti-platelet therapy. On multivariate analysis, remote prior TIA/stroke and lack of anti-platelet therapy remained significant. Among symptomatic patients presenting with stroke, lack of anti-platelet therapy was associated with an overall larger area of parenchymal involvement. No difference was observed with single versus dual anti-platelet therapy. Furthermore, symptomatic patients were more likely to have ulcerated plaques (30.9% vs 18%, p < .001), and symptomatic patients with ulcerated plaques more frequently had less than 50% compared to moderate/severe CAS. Nine patients who presented with symptoms had mild CAS and underwent intervention. CONCLUSIONS: Symptomatic CAS was associated with a history of remote prior symptoms and lack of anti-platelet therapy at time of presentation. Furthermore, symptomatic patients not on anti-platelet agents were more likely to have a greater area of parenchymal involvement when presenting with stroke and symptomatic patients with ulcerated plaques were more likely to have mild CAS, suggesting the role of plaque instability in symptomatic presentation. These findings underscore the importance of appropriate medical management and adherence in all patients with CAS and perhaps a role for more frequent surveillance in those with potentially unstable plaque morphology.

Characteristics associated with 30-day post-stroke readmission within an academic urban hospital network.

OBJECTIVES: Hospital readmissions are associated with poor health outcomes including illness severity and medical complications. The objective of this study was to identify characteristics associated with 30-day post-stroke readmission in an academic urban hospital network. MATERIALS AND METHODS: We collected data on patients admitted with stroke from 2017 through 2022 who were readmitted within 30 days of discharge and compared them to a subset of non-readmitted stroke patients. Chart review was used to collect demographics, characteristics of the stroke, co-morbid conditions, in-hospital complications, and post-discharge care. Univariate analyses followed by regression analysis were used to assess characteristics associated with post-stroke readmission. RESULTS: We identified 4743 patients with stroke (18 % hemorrhagic, mean age 70.1 (standard deviation (SD) 17.2), 47.3 % female) discharged from the stroke services, of whom 282 (5.9 %) patients were readmitted within 30 days of index hospitalization. Univariate analyses identified 18 significantly different features between admitted and readmitted patients. Regression analysis revealed characteristics associated with readmission included private insurance (odds ratio (OR) 0.4, confidence interval (CI) 0.3-0.6, p < 0.001), comorbid peripheral vascular disease (PVD) (OR 2.7, CI 1.3-5.5, p = 0.009), malignancy (OR 1.6, CI 1.0-2.6, p = 0.04), seizure (OR 3.4, CI 1.4-8.2, p = 0.007), thrombolytic administration (OR 0.4, CI 0.2-0.7, p = 0.003), undergoing thrombectomy (OR 5.4, CI 2.9-10.1, p < 0.001), and higher discharge modified Rankin Scale score (OR 1.2, CI 1.0-1.3, p = 0.047). CONCLUSIONS: Our data demonstrate that thrombectomy, high discharge Rankin score, comorbid malignancy, seizure or PVD, and lack of thrombolytic administration or private insurance predict readmission.

Negative disease-related stigma 3-months after hemorrhagic stroke is related to functional outcome and female sex.

OBJECTIVES: The objective of this study was to determine factors associated with negative disease-related stigma after hemorrhagic stroke. MATERIALS AND METHODS: Patients with non-traumatic hemorrhage (ICH or SAH) admitted between January 2015 and February 2021 were assessed by telephone 3-months after discharge using the Quality of Life in Neurological Disorders (Neuro-QoL) Negative Disease-Related Stigma Short Form inventory. We evaluated the relationship between disease-related stigma (T-score >50) and pre-stroke demographics, admission data, and poor functional outcome (3-month mRS score 3-5 and Barthel Index <100). RESULTS: We included 89 patients (56 ICH and 33 SAH). The median age was 63 (IQR 50-69), 43 % were female, and 67 % graduated college. Admission median GCS score was 15 (IQR 13-15) and APACHE II score was 12 (IQR 9-17). 31 % had disease-related stigma. On univariate analysis, disease-related stigma was associated with female sex, non-completion of college, GCS score, APACHE II score, and 3-month mRS score (all p < 0.05). On multivariate analysis, disease-related stigma was associated with female sex (OR = 3.72, 95 % CI = 1.23-11.25, p = 0.02) and 3-month Barthel Index <100 (OR = 3.46, 95 % CI = 1.13-10.64, p = 0.03) on one model, and female sex (OR = 3.75, 95 % CI = 1.21-11.58, p = 0.02) and 3-month mRS score 3-5 (OR = 4.23, 95 % CI = 1.21-14.75, p = 0.02) on a second model. CONCLUSION: Functional outcome and female sex are associated with disease-related stigma 3-months after hemorrhagic stroke. Because stigma may negatively affect recovery, there is a need to understand the relationship between these factors to mitigate stroke-related stigma.

Acetazolamide-augmented BOLD MRI to Assess Whole-Brain Cerebrovascular Reactivity in Chronic Steno-occlusive Disease Using Principal Component Analysis.

Background Exhaustion of cerebrovascular reactivity (CVR) portends increased stroke risk. Acetazolamide-augmented blood oxygenation level-dependent (BOLD) MRI has been used to estimate CVR, but low signal-to-noise conditions relegate its use to terminal CVR (CVRend) measurements that neglect dynamic features of CVR. Purpose To demonstrate comprehensive characterization of acetazolamide-augmented BOLD MRI response in chronic steno-occlusive disease using a computational framework to precondition signal time courses for dynamic whole-brain CVR analysis. Materials and Methods This study focused on retrospective analysis of consecutive patients with unilateral chronic steno-occlusive disease who underwent acetazolamide-augmented BOLD imaging for recurrent minor stroke or transient ischemic attack at an academic medical center between May 2017 and October 2020. A custom principal component analysis-based denoising pipeline was used to correct spatially varying non-signal-bearing contributions obtained by a local principal component analysis of the MRI time series. Standard voxelwise CVRend maps representing terminal responses were produced and compared with maximal CVR (CVRmax) as isolated from binned (per-repetition time) denoised BOLD time course. A linear mixed-effects model was used to compare CVRmax and CVRend in healthy and diseased hemispheres. Results A total of 23 patients (median age, 51 years; IQR, 42-61, 13 men) who underwent 32 BOLD examinations were included. Processed MRI data showed twofold improvement in signal-to-noise ratio, allowing improved isolation of dynamic characteristics in signal time course for sliding window CVRmax analysis to the level of each BOLD repetition time (approximately 2 seconds). Mean CVRmax was significantly higher than mean CVRend in diseased (5.2% vs 3.8%, P < .01) and healthy (5.5% vs 4.0%, P < .01) hemispheres. Several distinct time-signal signatures were observed, including nonresponsive; delayed/blunted; brisk; and occasionally nonmonotonic time courses with paradoxical features in normal and abnormal tissues (ie, steal and reverse-steal patterns). Conclusion A principal component analysis-based computational framework for analysis of acetazolamide-augmented BOLD imaging can be used to measure unsustained CVRmax through twofold improvements in signal-to-noise ratio. © RSNA, 2023 Supplemental material is available for this article.

Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima.

BACKGROUND: Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend ). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. PURPOSE: To investigate CCD in CVRmax from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVRend estimation. STUDY TYPE: Retrospective. POPULATION: A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. FIELD STRENGTH/SEQUENCE: A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. ASSESSMENT: A custom denoising pipeline was used to generate BOLD-CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. STATISTICAL TESTS: Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P ≤ 0.05. RESULTS: CCD-related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r = 0.728) as compared to CVRmax (r = 0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r = 0.739) than for CVRend (r = 0.705). DATA CONCLUSION: CCD-related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 3.

Central Retinal Artery Visualization with Cone-Beam CT Angiography.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

Pre-admission antithrombotic use is associated with 3-month mRS score after thrombectomy for acute ischemic stroke.

In patients who undergo thrombectomy for acute ischemic stroke, the relationship between pre-admission antithrombotic (anticoagulation or antiplatelet) use and both radiographic and functional outcome is not well understood. We sought to explore the relationship between pre-admission antithrombotic use in patients who underwent thrombectomy for acute ischemic stroke at two medical centers in New York City between December 2018 and November 2020. Analyses were performed using analysis of variance and Pearson's chi-squared tests. Of 234 patients in the analysis cohort, 65 (28%) were on anticoagulation, 64 (27%) were on antiplatelet, and 105 (45%) with no antithrombotic use pre-admission. 3-month Modified Rankin Scale (mRS) score of 3-6 was associated with pre-admission antithrombotic use (71% anticoagulation vs. 77% antiplatelet vs. 56% no antithrombotic, p = 0.04). There was no relationship between pre-admission antithrombotic use and Thrombolysis in Cerebral Iinfarction (TICI) score, post-procedure Alberta Stroke Program Early CT Score (ASPECTS) score, rate of hemorrhagic conversion, length of hospital admission, discharge NIH Stroke Scale (NIHSS), discharge mRS score, or mortality. When initial NIHSS score, post-procedure ASPECTS score, and age at admission were included in multivariate analysis, pre-admission antithrombotic use was still significantly associated with a 3-month mRS score of 3-6 (OR 2.36, 95% CI 1.03-5.54, p = 0.04). In this cohort of patients with acute ischemic stroke who underwent thrombectomy, pre-admission antithrombotic use was associated with 3-month mRS score, but no other measures of radiographic or functional outcome. Further research is needed on the relationship between use of specific anticoagulation or antiplatelet agents and outcome after acute ischemic stroke, but moreover, improve stroke prevention.

Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage.

BACKGROUND: The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS: We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS: We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS: The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

Tachycardia is associated with mortality and functional outcome after thrombectomy for acute ischemic stroke.

BACKGROUND: The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS: We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS: Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS: Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.

Psychological Outcome after Hemorrhagic Stroke is Related to Functional Status.

BACKGROUND: To identify opportunities to improve morbidity after hemorrhagic stroke, it is imperative to understand factors that are related to psychological outcome. DESIGN/METHODS: We prospectively identified patients with non-traumatic hemorrhagic stroke (intracerebral or subarachnoid hemorrhage) between January 2015 and February 2021 who were alive 3-months after discharge and telephonically assessed 1) psychological outcome using the Quality of Life in Neurological Disorders anxiety, depression, emotional and behavioral dyscontrol, fatigue and sleep disturbance inventories and 2) functional outcome using the modified Rankin Scale (mRS) and Barthel Index. We also identified discharge destination for all patients. We then evaluated the relationship between abnormal psychological outcomes (T-score >50) and discharge destination other than home, poor 3-month mRS score defined as 3-5 and poor 3-month Barthel Index defined as <100. RESULTS: 73 patients were included; 41 (56%) had an abnormal psychological outcome on at least one inventory. There were 41 (56%) patients discharged to a destination other than home, 44 (63%) with poor mRS score and 28 (39%) with poor Barthel Index. Anxiety, depression, emotional and behavioral dyscontrol and sleep disturbance were all associated with a destination other than home, poor mRS score, and poor Barthel Index (all p<0.05). Fatigue was related to poor mRS score and poor Barthel Index (p=0.005 and p=0.006, respectively). CONCLUSION: Multiple psychological outcomes 3-months after hemorrhagic stroke are related to functional status. Interventions to improve psychological outcome and reduce morbidity in patients with poor functional status should be explored by the interdisciplinary team.

Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

[Figure: see text].

New Focus on Endovascular Therapy for Ischemic Stroke.

BACKGROUND: Over the past 2 decades, a growing number of large-scale clinical trials have helped expand the toolkit for emergency management of acute ischemic stroke. This article is intended to be an up-to-date resource to aid nonstroke specialist neurology providers and ophthalmologists in identifying situations and patient populations in which urgent stroke evaluation should be completed with options for emergent reperfusion therapy considered. EVIDENCE ACQUISITION: The literature forming the foundation of the guidelines for early management of patients with acute ischemic stroke was reviewed, annotated, and summarized. RESULTS: Data from both initial and follow-up trials investigating the benefits and indications for use of intravenous thrombolysis and endovascular intervention for stroke are reviewed systematically, with an emphasis on new updates to qualifying patient populations and time periods for treatment. CONCLUSIONS: Recent studies underscore the conclusion that timely reperfusion in acute ischemic stroke is the most effective available treatment and that there are a growing number of new scenarios and patients for which interventions maybe applied.

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System.

BACKGROUND AND PURPOSE: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage.

OBJECTIVES: Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear. MATERIALS AND METHODS: We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis. RESULTS: Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02). CONCLUSION: SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.

Risk of Ischemic Stroke in Patients With Atrial Fibrillation After Extracranial Hemorrhage.

BACKGROUND AND PURPOSE: Anticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH). METHODS: We conducted a retrospective study using the California State Inpatient Database including all nonfederal hospital admissions in California from 2005 to 2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke before or at the time of ECH diagnosis. We calculated adjusted hazard ratios for ischemic stroke during follow-up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and comorbidities. In subgroup analyses, subjects were stratified by primary ECH diagnosis, severity/type of ECH, age, CHA2DS2-VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer. RESULTS: We identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years. CONCLUSIONS: Patients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.

SARS-CoV-2 and Stroke in a New York Healthcare System.

BACKGROUND AND PURPOSE: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

Redefined Measure of Early Neurological Improvement Shows Treatment Benefit of Alteplase Over Placebo.

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

Cerebral Venous Sinus Thrombosis in the COVID-19 Pandemic.

BACKGROUND: Recent studies have noted concern for increased thromboembolic events in the setting of Coronavirus Disease 2019 (COVID-19). Cerebral venous sinus thrombosis (CVST) is a form of thromboembolism that has been observed as a neuro-ophthalmologic complication of COVID-19. METHODS: Review of the scientific literature. RESULTS: In this article, we report an overview of CVST epidemiology, clinical presentation, diagnostics, disease pathophysiology, and management in the setting of COVID-19. CONCLUSION: CVST is an uncommon thromboembolic event with variable phenotypes and multiple etiologies. Neurologic complications can be severe, including significant visual deficits and death. Current observations suggest that the risk of CVST may be profoundly impacted by this novel COVID-19 pandemic, thus prompting increased attention to disease presentation, pathogenesis, and management.