Publications by authors named "Guido J Falcone"

110 Publications

Similar admission NIHSS may represent larger tissue-at-risk in patients with right-sided versus left-sided large vessel occlusion.

J Neurointerv Surg 2021 Oct 13. Epub 2021 Oct 13.

Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, USA

Background: We investigated the effects of the side of large vessel occlusion (LVO) on post-thrombectomy infarct volume and clinical outcome with regard to admission National Institutes of Health Stroke Scale (NIHSS) score.

Methods: We retrospectively identified patients with anterior LVO who received endovascular thrombectomy and follow-up MRI. Applying voxel-wise general linear models and multivariate analysis, we assessed the effects of occlusion side, admission NIHSS, and post-thrombectomy reperfusion (modified Thrombolysis in Cerebral Infarction, mTICI) on final infarct distribution and volume as well as discharge modified Rankin Scale (mRS) score.

Results: We included 469 patients, 254 with left-sided and 215 with right-sided LVO. Admission NIHSS was higher in those with left-sided LVO (median (IQR) 16 (10-22)) than in those with right-sided LVO (14 (8-16), p>0.001). In voxel-wise analysis, worse post-thrombectomy reperfusion, lower admission NIHSS score, and poor discharge outcome were associated with right-hemispheric infarct lesions. In multivariate analysis, right-sided LVO was an independent predictor of larger final infarct volume (p=0.003). There was a significant three-way interaction between admission stroke severity (based on NIHSS), LVO side, and mTICI with regard to final infarct volume (p=0.041). Specifically, in patients with moderate stroke (NIHSS 6-15), incomplete reperfusion (mTICI 0-2b) was associated with larger final infarct volume (p<0.001) and worse discharge outcome (p=0.02) in right-sided compared with left-sided LVO.

Conclusions: When adjusted for admission NIHSS, worse post-thrombectomy reperfusion is associated with larger infarct volume and worse discharge outcome in right-sided versus left-sided LVO. This may represent larger tissue-at-risk in patients with right-sided LVO when applying admission NIHSS as a clinical biomarker for penumbra.
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http://dx.doi.org/10.1136/neurintsurg-2021-017785DOI Listing
October 2021

The coronal plane maximum diameter of deep intracerebral hemorrhage predicts functional outcome more accurately than hematoma volume.

Int J Stroke 2021 Oct 13:17474930211050749. Epub 2021 Oct 13.

Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.

Background: Among prognostic imaging variables, the hematoma volume on admission computed tomography (CT) has long been considered the strongest predictor of outcome and mortality in intracerebral hemorrhage.

Aims: To examine whether different features of hematoma shape are associated with functional outcome in deep intracerebral hemorrhage.

Methods: We analyzed 790 patients from the ATACH-2 trial, and 14 shape features were quantified. We calculated Spearman's Rho to assess the correlation between shape features and three-month modified Rankin scale (mRS) score, and the area under the receiver operating characteristic curve (AUC) to quantify the association between shape features and poor outcome defined as mRS>2 as well as mRS > 3.

Results: Among 14 shape features, the maximum intracerebral hemorrhage diameter in the coronal plane was the strongest predictor of functional outcome, with a maximum coronal diameter >∼3.5 cm indicating higher three-month mRS scores. The maximum coronal diameter versus hematoma volume yielded a Rho of 0.40 versus 0.35 ( = 0.006), an AUC of 0.71 versus 0.68 ( = 0.004), and an AUC of 0.71 versus 0.69 ( = 0.029). In multiple regression analysis adjusted for known outcome predictors, the maximum coronal diameter was independently associated with three-month mRS (p < 0.001).

Conclusions: A coronal-plane maximum diameter measurement offers greater prognostic value in deep intracerebral hemorrhage than hematoma volume. This simple shape metric may expedite assessment of admission head CTs, offer a potential biomarker for hematoma size eligibility criteria in clinical trials, and may substitute volume in prognostic intracerebral hemorrhage scoring systems.
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http://dx.doi.org/10.1177/17474930211050749DOI Listing
October 2021

Association of lichen planus with cardiovascular disease: A combined analysis of the UK Biobank and All of Us Study.

J Am Acad Dermatol 2021 Sep 22. Epub 2021 Sep 22.

Department of Neurology, Yale School of Medicine, New Haven, Connecticut. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.09.030DOI Listing
September 2021

Mendelian Randomization in Stroke: A Powerful Approach to Causal Inference and Drug Target Validation.

Front Genet 2021 12;12:683082. Epub 2021 Aug 12.

Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT, United States.

Stroke is a leading cause of death and disability worldwide. However, our understanding of its underlying biology and the number of available treatment options remain limited. Mendelian randomization (MR) offers a powerful approach to identify novel biological pathways and therapeutic targets for this disease. Around ~100 MR studies have been conducted so far to explore, confirm, and quantify causal relationships between several exposures and risk of stroke. In this review, we summarize the current evidence arising from these studies, including those investigating ischemic stroke, hemorrhagic stroke, or both. We highlight the different types of exposures that are currently under study, ranging from well-known cardiovascular risk factors to less established inflammation-related mechanisms. Finally, we provide an overview of future avenues of research and novel approaches, including drug target validation MR, which is poised to have a substantial impact on drug development and drug repurposing.
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http://dx.doi.org/10.3389/fgene.2021.683082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387928PMC
August 2021

Portable, bedside, low-field magnetic resonance imaging for evaluation of intracerebral hemorrhage.

Nat Commun 2021 08 25;12(1):5119. Epub 2021 Aug 25.

Department of Radiology, Yale University School of Medicine, New Haven, CT, USA.

Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5-3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68-0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90-0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings.
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http://dx.doi.org/10.1038/s41467-021-25441-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387402PMC
August 2021

Cardiovascular Health Disparities in Racial and Other Underrepresented Groups: Initial Results From the All of Us Research Program.

J Am Heart Assoc 2021 Sep 25;10(17):e021724. Epub 2021 Aug 25.

Department of Neurology Yale School of Medicine New Haven CT.

Background All of Us is a novel research program that aims to accelerate research in populations traditionally underrepresented in biomedical research. Our objective was to evaluate the burden of cardiovascular disease (CVD) in broadly defined underrepresented groups. Methods and Results We evaluated the latest data release of All of Us. We conducted a cross-sectional analysis combining survey and electronic health record data to estimate the prevalence of CVD upon enrollment in underrepresented groups defined by race, ethnicity, age (>75 years), disability (not able to carry out everyday physical activities), sexual orientation and gender identity lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+), income (annual household income <$35 000 US dollars) and education (less than a high school degree). We used multivariate logistic regression to estimate the adjusted odds ratio (OR) and product terms to test for interaction. The latest All of Us data release includes 315 297 participants. Of these, 230 577 (73%) had information on CVD and 17 958 had CVD (overall prevalence, 7.8%; 95% CI, 7.7-7.9). Multivariate analyses adjusted by hypertension, hyperlipidemia, type 2 diabetes mellitus, body mass index, and smoking indicated that, compared with White participants, Black participants had a higher adjusted odds of CVD (OR, 1.21; 95% CI, 1.16-1.27). Higher adjusted odds of CVD were also observed in underrepresented groups defined by other factors, including age >75 years (OR, 1.90; 95% CI, 1.81-1.99), disability (OR, 1.60; 95% CI, 1.53-1.68), and income <$35 000 US dollars (OR, 1.22; 95% CI, 1.17-1.27). Sex significantly modified the odds of CVD in several of the evaluated groups. Conclusions Among participants enrolled in All of Us, underrepresented groups defined based on race, ethnicity and other factors have a disproportionately high burden of CVD. The All of Us research program constitutes a powerful platform to accelerate research focused on individuals in underrepresented groups.
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http://dx.doi.org/10.1161/JAHA.121.021724DOI Listing
September 2021

Powassan Meningoencephalitis: A Case Report Highlighting Diagnosis and Management.

Cureus 2021 Jul 23;13(7):e16592. Epub 2021 Jul 23.

Neurology, Yale School of Medicine, New Haven, USA.

Powassan virus (POWV), a rare flavivirus that may be transmitted by a tick bite, causes rare but severe cases of encephalitis, meningitis, and meningoencephalitis in humans. We present the case of a 62-year-old man with prior Lyme disease and reactive arthritis who presented to the hospital with symptoms of fever, headache, and fatigue. The patient developed rapid deterioration of mental status including profound expressive aphasia and required intubation and high-dose steroids. Cerebrospinal fluid (CSF) serologies were found to be positive for the POWV.
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http://dx.doi.org/10.7759/cureus.16592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378285PMC
July 2021

Admission computed tomography radiomic signatures outperform hematoma volume in predicting baseline clinical severity and functional outcome in the ATACH-2 trial intracerebral hemorrhage population.

Eur J Neurol 2021 09 18;28(9):2989-3000. Epub 2021 Jul 18.

Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.

Background And Purpose: Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT).

Methods: We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n = 895) were randomly allocated to discovery (n = 448) and independent validation (n = 447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume.

Results: In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p = 0.008), admission NIHSS (0.69 vs. 0.57, p < 0.001), and 3-month mRS scores (0.44 vs. 0.32, p < 0.001). Similarly, in independent validation, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.43 vs. 0.41, p = 0.02), NIHSS (0.64 vs. 0.56, p < 0.001), and 3-month mRS scores (0.43 vs. 0.33, p < 0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts.

Conclusions: Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density, and shape on baseline CT can provide imaging correlates for clinical presentation and 3-month outcome. These findings couldtrigger a paradigm shift where imaging biomarkers may improve current modelsfor prognostication, risk-stratification, and treatment triage of ICH patients.
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http://dx.doi.org/10.1111/ene.15000DOI Listing
September 2021

Stroke Disparities Among Nonracial Minorities in the All of Us Research Program.

Stroke 2021 Aug 18;52(8):e488-e490. Epub 2021 Jun 18.

Department of Neurology, Yale School of Medicine, New Haven, CT.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316290PMC
August 2021

Intracerebral Hemorrhage in Patients With COVID-19: An Analysis From the COVID-19 Cardiovascular Disease Registry.

Stroke 2021 07 4;52(7):e321-e323. Epub 2021 Jun 4.

Department of Neurology, Yale School of Medicine, New Haven, CT (A.C.L., L.H.S., G.J.F., K.N.S.).

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238884PMC
July 2021

Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage.

Curr Opin Lipidol 2021 08;32(4):244-248

Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.

Purpose Of Review: The role of lipids in spontaneous, nontraumatic intracerebral haemorrhage (ICH) remains controversial, as some studies suggest that lower levels of total and LDL cholesterol could increase the risk of this disease. Because of their random assortment during meiosis, genetic variants known to associate with lipid levels can be used as instruments to evaluate this relationship from a causal perspective. The purpose of this review is to summarize the existing literature related to genetically determined LDL cholesterol levels and risk of ICH.

Recent Findings: A number of studies have demonstrated that lower LDL levels are associated with a higher risk of ICH and a higher burden of neuroimaging markers of cerebral small vessel disease, such as microbleeds and white matter hyperintensity volume. As for genetically elevated lipid levels, several studies confirmed an inverse association between LDL levels and ICH. However, a number of observational studies and large meta-analyses of clinical trials of statins have failed to show such association.

Summary: Observational studies and clinical trials of statins have yielded inconsistent results regarding a possible link between LDL levels and the risk of ICH. Genetic studies focused on genetically elevated LDL levels and risk of ICH have, for the most, found an inverse association.
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http://dx.doi.org/10.1097/MOL.0000000000000761DOI Listing
August 2021

Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage.

Stroke 2021 May 8;52(5):1835-1838. Epub 2021 Apr 8.

Department of Neurology (G.J.F., K.N.V., A.C.L., L.H.S., K.N.S.), Yale University, New Haven, CT.

Background And Purpose: To determine whether obstructive sleep apnea (OSA) is associated with intracerebral hemorrhage (ICH) risk, we assessed premorbid OSA exposure of patients with nontraumatic ICH and matched controls.

Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage is a multicenter, case-control study evaluating risk factors for ICH that recruited 3000 cases with ICH and 3000 controls. OSA status was ascertained using the Berlin Questionnaire as a surrogate for premorbid OSA. We performed logistic regression analyses to evaluate the association between OSA and ICH.

Results: Two thousand and sixty-four (71%) cases and 1516 (52%) controls were classified as having OSA by the Berlin Questionnaire. Cases with OSA were significantly more likely to be male and have hypertension, heart disease, hyperlipidemia, and higher body mass index compared with those without OSA. OSA was more common among cases compared with controls (71% versus 52%, odds ratio, 2.28 [95% CI, 2.05-2.55]). In a multivariable logistic regression model, OSA was associated with increased risk for ICH (odds ratio, 1.47 [95% CI, 1.29-1.67]).

Conclusions: OSA is a risk factor for ICH.
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http://dx.doi.org/10.1161/STROKEAHA.120.033342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085039PMC
May 2021

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

Stroke 2021 May 8;52(5):1733-1740. Epub 2021 Mar 8.

Department of Neurology (A.C.L., L.R.K., K.N.V., L.H.S., G.J.F., K.N.S.), Yale University School of Medicine, New Haven, CT.

Background And Objectives: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH).

Methods: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes.

Results: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; =0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, =0.002), with a stronger association seen in lobar (β, 12.51 [95% CI, 6.47-18.55], <0.001) versus nonlobar (β 5.32 [95% CI, 3.36-7.28], <0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (β 1.22 [95% CI, 0.15-2.29], =0.03). Treatment group was not associated with IL-6 levels or outcome.

Conclusions: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.
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http://dx.doi.org/10.1161/STROKEAHA.120.032888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085132PMC
May 2021

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

Crit Care Med 2021 05;49(5):828-837

Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT.

Objectives: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage.

Design: Individual patient data meta-analysis of three studies of intracerebral hemorrhage.

Setting: Two randomized clinical trials and one multiethnic observational study.

Patients: Patients with spontaneous, nontraumatic intracerebral hemorrhage.

Interventions: None.

Measurements And Main Results: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion.

Conclusions: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.
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http://dx.doi.org/10.1097/CCM.0000000000004891DOI Listing
May 2021

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

Neurocrit Care 2021 Jan 21. Epub 2021 Jan 21.

Department of Neurology, Yale School of Medicine, 15 York Street, LLCI 10th floor, Room 1003C, P.O. Box 208018, New Haven, CT, 06520, USA.

Background: In patients with spontaneous intracerebral hemorrhage (ICH), pre-hospital markers of disease severity might be useful to potentially triage patients to undergo early interventions.

Objective: Here, we tested whether loss of consciousness (LOC) at the onset of ICH is associated with intraventricular hemorrhage (IVH) on brain computed tomography (CT).

Methods: Among 3000 ICH cases from ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage study, NS069763), we included patients with complete ICH/IVH volumetric CT measurements and excluded those with seizures at ICH onset. Trained investigators extracted data from medical charts. Mental status at symptom onset (categorized as alert/oriented, alert/confused, drowsy/somnolent, coma/unresponsive/posturing) and 3-month disability (modified Rankin score, mRS) were assessed through standardized interviews of participants or dedicated proxies. We used logistic regression and mediation analysis to assess relationships between LOC, IVH, and unfavorable outcome (mRS 4-6).

Results: Two thousand seven hundred and twenty-four patients met inclusion criteria. Median admission Glasgow Coma Score was 15 (interquartile range 11-15). 46% had IVH on admission or follow-up CT. Patients with LOC (mental status: coma/unresponsive, n = 352) compared to those without LOC (all other mental status, n = 2372) were younger (60 vs. 62 years, p = 0.005) and had greater IVH frequency (77 vs. 41%, p < 0.001), greater peak ICH volumes (28 vs. 11 ml, p < 0.001), greater admission systolic blood pressure (200 vs. 184 mmHg, p < 0.001), and greater admission serum glucose (158 vs. 127 mg/dl, p < 0.001). LOC was independently associated with IVH presence (odds ratio, OR, 2.6, CI 1.9-3.5) and with unfavorable outcome (OR 3.05, CI 1.96-4.75). The association between LOC and outcome was significantly mediated by IVH (beta = 0.24, bootstrapped CI 0.17-0.32).

Conclusion: LOC at ICH onset may be a useful pre-hospital marker to identify patients at risk of having or developing IVH.
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http://dx.doi.org/10.1007/s12028-020-01180-2DOI Listing
January 2021

Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage and Risk of Stroke: A MISTIE III and ATACH-2 Analysis.

Stroke 2021 Jan 20;52(2):595-602. Epub 2021 Jan 20.

Division of Neurosciences Critical Care, Johns Hopkins University School of Medicine, Baltimore, MD (S.-M.C., L.R.-L., W.C.Z.).

Background And Purpose: Punctate ischemic lesions noted on diffusion-weighted imaging (DWI) are associated with poor functional outcomes after intracerebral hemorrhage (ICH). Whether these lesions increase long-term risk of stroke is poorly understood.

Methods: We pooled individual patient data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3). We included subjects with a magnetic resonance imaging scan. The exposure was a DWI lesion. The primary outcome was any stroke, defined as a composite of ischemic stroke or recurrent ICH, whereas secondary outcomes were incident ischemic stroke and recurrent ICH. Using multivariate Cox regression analysis, we evaluated the risk of stroke.

Results: Of 505 patients with ICH with magnetic resonance imaging, 466 were included. DWI lesions were noted in 214 (45.9%) subjects, and 34 incident strokes (20 ischemic stroke and 14 recurrent ICH) were observed during a median follow-up of 324 days (interquartile range, 91-374). Presence of a DWI lesion was associated with a 6.9% (95% CI, 2.2-11.6) absolute increase in risk of all stroke (hazard ratio, 2.6 [95% CI, 1.2-5.7]). Covariate adjustment with Cox regression models also demonstrated this increased risk. In the secondary analyses, there was an increased risk of ischemic stroke (hazard ratio, 3.5 [95% CI, 1.1-11.0]) but not recurrent ICH (hazard ratio, 1.7 [95% CI, 0.6-5.1]).

Conclusions: In a heterogeneous cohort of patients with ICH, presence of a DWI lesion was associated with a 2.5-fold heightened risk of stroke among ICH survivors. This elevated risk persisted for ischemic stroke but not for recurrent ICH.
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http://dx.doi.org/10.1161/STROKEAHA.120.031628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340082PMC
January 2021

Genetically Determined Smoking Behavior and Risk of Nontraumatic Subarachnoid Hemorrhage.

Stroke 2021 Jan 14;52(2):582-587. Epub 2021 Jan 14.

Division of Neurocritical Care and Emergency Neurology, Department of Neurology (J.N.A., N.S., C.P.B., K.V., R.B.N., K.N.S., G.J.F.), Yale School of Medicine, New Haven, CT.

Background And Purpose: Animal and observational studies indicate that smoking is a risk factor for aneurysm formation and rupture, leading to nontraumatic subarachnoid hemorrhage (SAH). However, a definitive causal relationship between smoking and the risk of SAH has not been established. Using Mendelian randomization (MR) analyses, we tested the hypothesis that smoking is causally linked to the risk of SAH.

Methods: We conducted a 1-sample MR study using data from the UK Biobank, a large cohort study that enrolled over 500 000 Britons aged 40 to 69 from 2006 to 2010. Participants of European descent were included. SAH cases were ascertained using a combination of self-reported, electronic medical record, and death registry data. As the instrument, we built a polygenic risk score using independent genetic variants known to associate (<5) with smoking behavior. This polygenic risk score represents the genetic susceptibility to smoking initiation. The primary MR analysis utilized the ratio method. Secondary MR analyses included the inverse variance weighted and weighted median methods.

Results: A total of 408 609 study participants were evaluated (mean age, 57 [SD 8], female sex, 220 937 [54%]). Among these, 132 566 (32%) ever smoked regularly, and 904 (0.22%) had a SAH. Each additional SD of the smoking polygenic risk score was associated with 21% increased risk of smoking (odds ratio [OR], 1.21 [95% CI, 1.20-1.21]; <0.001) and a 10% increased risk of SAH (OR, 1.10 [95% CI, 1.03-1.17]; =0.006). In the primary MR analysis, genetic susceptibility to smoking was associated with a 63% increase in the risk of SAH (OR, 1.63 [95% CI, 1.15-2.31]; =0.006). Secondary analyses using the inverse variance weighted method (OR, 1.57 [95% CI, 1.13-2.17]; =0.007) and the weighted median method (OR, 1.74 [95% CI, 1.06-2.86]; =0.03) yielded similar results. There was no significant pleiotropy (MR-Egger intercept =0.39; MR Pleiotropy Residual Sum and Outlier global test =0.69).

Conclusions: These findings provide evidence for a causal link between smoking and the risk of SAH.
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http://dx.doi.org/10.1161/STROKEAHA.120.031622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856108PMC
January 2021

Vessel wall MRI in ruptured cranial dural arteriovenous fistulas.

Interv Neuroradiol 2021 Aug 11;27(4):553-557. Epub 2021 Jan 11.

Department of Neurosurgery, Yale University School of Medicine, New Haven, USA.

Intracranial high-resolution vessel wall MRI (VW-MRI) is an imaging paradigm that is useful in site-of-rupture identification in patients presenting with spontaneous subarachnoid hemorrhage and multiple intracranial aneurysms. Only a handful of case reports describe its potential utility in the evaluation of more complex brain vascular malformations. We report for the first time three patients with ruptured cranial dural arteriovenous fistulas (dAVFs) that were evaluated with high-resolution VW-MRI. The presumed site-of-rupture was identified based on contiguity of a venous ectasia with adjacent blood products and thick, concentric wall enhancement. This preliminary experience suggests a role for high-resolution VW-MRI in the evaluation of ruptured cranial dAVFs, in particular, site-of-rupture identification. It also supports an emerging hypothesis that all spontaneously ruptured, macrovascular lesions demonstrate avid vessel wall enhancement.
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http://dx.doi.org/10.1177/1591019920988205DOI Listing
August 2021

Andexanet Alfa Versus 4-Factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage.

Neurocrit Care 2021 08 6;35(1):255-261. Epub 2021 Jan 6.

Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale School of Medicine, 15 York Street, LLCI 1004D, Box 208018, New Haven, CT, 06520, USA.

Background/objective: There are limited data on the risks and benefits of using andexanet alfa (AA) in comparison with four-factor prothrombin complex concentrate (4F-PCC) to reverse factor Xa inhibitors (FXi) associated intracranial hemorrhage (ICH). We sought to describe our experience with AA or 4F-PCC in patients with oral FXi-related traumatic and spontaneous ICH.

Methods: We conducted a retrospective review of consecutive adult patients with FXi-related ICH who received AA or 4F-PCC. FXi-related ICH cases included traumatic and spontaneous intracranial hemorrhages. Our primary analysis evaluated ICH stability on head computed tomography scan (CT), defined as a similar amount of blood from the initial scan at the onset of ICH to subsequent scans, at 6-h and 24-h post-administration of AA or 4F-PCC. For the subset of spontaneous intraparenchymal hemorrhages, volume was measured at 6-h and 24-h post-reversal. In secondary analyses, we evaluated good functional outcome at discharge, defined as a Modified Rankin Score of less than 3, and the incidence of thrombotic events after AA or 4F-PCC adminstration, during hospitalization.

Results: A total of 44 patients (16 traumatic and 28 spontaneous ICH) with median age of 79 years [72-86], 36% females, with a FXi-related ICH, were included in this study. The majority of spontaneous ICHs were intraparenchymal 19 (68%). Twenty-eight patients (64%) received AA and 16 patients (36%) received 4F-PCC. There was no difference between AA and 4F-PCC in terms of CT stability at 6 h (21 [78%] vs 10 [71%], p = 0.71) and 24 h (15 [88%] vs 6 [60%], p = 0.15). In a subgroup of patients with spontaneous intraparenchymal hemorrhage, there was no difference in the degree of achieved hemostasis based on hematoma volume between AA and 4F-PCC at 6 h (9.3 mL [6.9-26.4] vs 10 mL [9.4-22.1], adjusted p = 0. 997) and 24-h (9.2 mL [6.1-18.8] vs 9.9 [9.4-21.1], adjusted p = 1). The number of patients with good outcome based on mRS on discharge were 10 (36%) and 6 (38%) in the AA and 4F-PCC groups, respectively (adjusted p = 0.81). The incidence of thromboembolic events was similar in the AA and 4F-PCC groups (2 [7%] vs 0, p = 0.53).

Conclusion: In this limited sample of patients, we found no difference in neuroimaging stability, functional outcome and thrombotic events when comparing AA and 4F-PCC in patients with FXi-related ICH. Since our analysis is likely underpowered, a multi-center collaborative network devoted to this question is warranted.
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http://dx.doi.org/10.1007/s12028-020-01161-5DOI Listing
August 2021

Statin treatment and cerebral microbleeds: A systematic review and meta-analysis.

J Neurol Sci 2021 01 8;420:117224. Epub 2020 Nov 8.

Division of Neurology, McMaster University / Population Health Research Institute, Hamilton, ON, Canada.

Although statins have been associated with increased risk of spontaneous intracerebral hemorrhage, their relationship with cerebral microbleeds (CMBs) formation is poorly understood. We systematically reviewed previously published studies reporting on the association between CMBs presence and current statin use. We performed a systematic search in MEDLINE and SCOPUS databases on October 24, 2019 to identify all cohorts from randomized-controlled clinical trials or observational studies reporting on CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Random effects model was used to calculate the pooled estimates. We included 7 studies (n = 3734 participants): unselected general population [n = 1965], ischemic stroke [n = 849], hemorrhagic stroke [n = 252] and patients with hypertension over the age of 60 [n = 668]. Statin use was not associated with CMBs presence in either unadjusted (OR = 1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR = 1.09, 95%CI: 0.64-1.86). Statin use was more strongly related to lobar CMB presence (OR = 2.01, 95%CI: 1.48-2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR = 2.26, 95%CI: 0.86-5.91). Except for the analysis on the unadjusted probability of lobar CMBs presence, considerable heterogeneity was present in all other analyses (I > 60%). Our findings suggest that statin treatment seems not to be associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.
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http://dx.doi.org/10.1016/j.jns.2020.117224DOI Listing
January 2021

Plasma neurofilament light predicts mortality in patients with stroke.

Sci Transl Med 2020 11;12(569)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

Given the heterogeneity of stroke brain injury, there is a clear need for a biomarker that determines the degree of neuroaxonal injury across stroke types. We evaluated whether blood neurofilament light (NFL) would fulfill this purpose for patients with acute cerebral infarction (ACI; = 227), aneurysmal subarachnoid hemorrhage (aSAH; = 58), or nontraumatic intracerebral hemorrhage (ICH; = 29). We additionally validated our findings in two independent cohorts of patients with ICH ( = 96 and = 54) given the scarcity of blood biomarker studies for this deadliest stroke type. Compared to healthy individuals ( = 79 and = 48 for the discovery and validation cohorts, respectively), NFL was higher for all stroke types. NFL associated with radiographic markers of brain tissue damage. It correlated with the extent of early ischemic injury in patients with ACI, hemorrhage severity in patients with aSAH, and intracranial hemorrhage volume in patients with ICH. In all patients, NFL independently correlated with scores from the NIH Stroke Scale, the modified Rankin Scale, and the Mini-Mental State Examination at blood draw, which respectively assess neurological, functional, and cognitive status. Furthermore, higher NFL concentrations independently associated with 3- or 6-month functional disability and higher all-cause mortality. These data support NFL as a uniform method to estimate neuroaxonal injury and forecast mortality regardless of stroke mechanism. As a prognostic biomarker, blood NFL has the potential to assist with planning supportive and rehabilitation services and improving clinical trial efficiency for stroke therapeutics and devices.
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http://dx.doi.org/10.1126/scitranslmed.aay1913DOI Listing
November 2020

Prior antiplatelet therapy and haematoma expansion after primary intracerebral haemorrhage: an individual patient-level analysis of CLEAR III, MISTIE III and VISTA-ICH.

J Neurol Neurosurg Psychiatry 2020 Oct 26. Epub 2020 Oct 26.

Departments of Neurology, Neurosurgery, and Anesthesiology Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Objective: To evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.

Methods: We pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.

Results: Among 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, -0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.

Conclusions: In a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.
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http://dx.doi.org/10.1136/jnnp-2020-323458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071838PMC
October 2020

Cause of death in spontaneous intracerebral hemorrhage survivors: Multistate longitudinal study.

Neurology 2020 11 11;95(20):e2736-e2745. Epub 2020 Sep 11.

From the Divisions of Neurocritical Care and Emergency Neurology (L.R.K., A.C.L., J.N.A., K.V., G.J.F., K.N.S.) and Stroke and Vascular Neurology (L.H.S.), Department of Neurology, and Department of Neurosurgery (C.C.M.), Yale School of Medicine, New Haven, CT; and Clinical and Translational Neuroscience Unit (S.B.M., H.K.), Department of Neurology, Weill Cornell Medicine, New York, NY.

Objective: To determine the leading causes of death in intracerebral hemorrhage (ICH) survivors, we used administrative data from 3 large US states to identify adult survivors of a first-time spontaneous ICH and track all hospital readmissions resulting in death.

Methods: We performed a longitudinal analysis of prospectively collected claims data from hospitalizations in California (2005-2011), New York (2005-2014), and Florida (2005-2014). Adult residents admitted with a nontraumatic ICH who survived to discharge were included. Patients were followed for a primary outcome of any readmission resulting in death. The cause of death was defined as the primary diagnosis assigned at discharge. Multivariable Cox proportional hazards and multinomial logistic regression were used to determine factors associated with the risk for and cause of death.

Results: Of 72,432 ICH survivors (mean age 68 years [SD 16], 48% female), 12,753 (18%) died during a median follow-up period of 4.0 years (interquartile range 2.3-6.3). The leading causes of death were infection (34%), recurrent intracranial hemorrhage (14%), cardiac disease (8%), respiratory failure (8%), and ischemic stroke (5%). Death in patients with atrial fibrillation (AF) was more likely to be caused by ischemic stroke (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.9-2.9, < 0.001) and less likely to be caused by recurrent intracranial hemorrhage (OR 0.7, 95% CI 0.6-0.8, < 0.001) compared to patients without AF.

Conclusions: Infection is the leading cause of death in all ICH survivors. Survivors with AF were at increased risk for death from ischemic stroke. These findings will help prioritize interventions aimed to improve long-term survival and recovery in ICH survivors.
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http://dx.doi.org/10.1212/WNL.0000000000010736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734723PMC
November 2020

Association of race and ethnicity to incident epilepsy, or epileptogenesis, after subdural hematoma.

Neurology 2020 11 9;95(21):e2890-e2899. Epub 2020 Sep 9.

From the Division of Neurocritical Care and Emergency Neurology (S.C.B., L.K., E.J.G., J.A.K., G.J.F., K.N.S.), Department of Neurology, and Department of Neurosurgery (S.B.O.), Yale School of Medicine, New Haven, CT; David Geffen School of Medicine at UCLA (Z.A.K.), Los Angeles, CA; Department of Neurology (H.K., S.M.), Weill Cornell Medicine; and Department of Neurology (J.A.F.), New York University School of Medicine, New York.

Objective: To determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy.

Methods: We performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy.

Results: We identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28-1.64, < 0.001). Status epilepticus during the index SDH admission, although infrequent (n = 94 [0.3%]), was associated with a nearly 4-fold risk of epilepsy (HR 3.75, 95% CI 2.80-5.03, < 0.001). Alcohol use, drug use, smoking, renal disease, and markers of injury severity (i.e., intubation, surgical intervention, length of stay, disposition other than home) were also associated with epilepsy (all < 0.05).

Conclusions: We found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.
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http://dx.doi.org/10.1212/WNL.0000000000010742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734738PMC
November 2020

Assessment of Brain Injury Using Portable, Low-Field Magnetic Resonance Imaging at the Bedside of Critically Ill Patients.

JAMA Neurol 2020 Sep 8. Epub 2020 Sep 8.

Division of Neurocritical Care, Department of Neurology, Massachusetts General Hospital, Boston.

Importance: Neuroimaging is a key step in the clinical evaluation of brain injury. Conventional magnetic resonance imaging (MRI) systems operate at high-strength magnetic fields (1.5-3 T) that require strict, access-controlled environments. Limited access to timely neuroimaging remains a key structural barrier to effectively monitor the occurrence and progression of neurological injury in intensive care settings. Recent advances in low-field MRI technology have allowed for the acquisition of clinically meaningful imaging outside of radiology suites and in the presence of ferromagnetic materials at the bedside.

Objective: To perform an assessment of brain injury in critically ill patients in intensive care unit settings, using a portable, low-field MRI device at the bedside.

Design, Setting, And Participants: This was a prospective, single-center cohort study of 50 patients admitted to the neuroscience or coronavirus disease 2019 (COVID-19) intensive care units at Yale New Haven Hospital in New Haven, Connecticut, from October 30, 2019, to May 20, 2020. Patients were eligible if they presented with neurological injury or alteration, no contraindications for conventional MRI, and a body habitus not exceeding the scanner's 30-cm vertical opening. Diagnosis of COVID-19 was determined by positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction nasopharyngeal swab result.

Exposures: Portable MRI in an intensive care unit room.

Main Outcomes And Measures: Demographic, clinical, radiological, and treatment data were collected and analyzed. Brain imaging findings are described.

Results: Point-of-care MRI examinations were performed on 50 patients (16 women [32%]; mean [SD] age, 59 [12] years [range, 20-89 years]). Patients presented with ischemic stroke (n = 9), hemorrhagic stroke (n = 12), subarachnoid hemorrhage (n = 2), traumatic brain injury (n = 3), brain tumor (n = 4), and COVID-19 with altered mental status (n = 20). Examinations were acquired at a median of 5 (range, 0-37) days after intensive care unit admission. Diagnostic-grade T1-weighted, T2-weighted, T2 fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences were obtained for 37, 48, 45, and 32 patients, respectively. Neuroimaging findings were detected in 29 of 30 patients who did not have COVID-19 (97%), and 8 of 20 patients with COVID-19 (40%) demonstrated abnormalities. There were no adverse events or complications during deployment of the portable MRI or scanning in an intensive care unit room.

Conclusions And Relevance: This single-center series of patients with critical illness in an intensive care setting demonstrated the feasibility of low-field, portable MRI. These findings demonstrate the potential role of portable MRI to obtain neuroimaging in complex clinical care settings.
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http://dx.doi.org/10.1001/jamaneurol.2020.3263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489395PMC
September 2020

Direct carotid puncture for mechanical thrombectomy in acute ischemic stroke patients with prohibitive vascular access.

J Neurosurg 2020 Aug 14:1-11. Epub 2020 Aug 14.

2Neurology, Yale University School of Medicine, New Haven, Connecticut.

Objective: While the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access.

Methods: The authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression.

Results: Of 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age [± SD] 82 ± 11 years, mean National Institutes of Health Stroke Scale [NIHSS] score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non-flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non-flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (-4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02-24.5; p = 0.048).

Conclusions: DCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.
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http://dx.doi.org/10.3171/2020.5.JNS192737DOI Listing
August 2020

Effects of Collateral Status on Infarct Distribution Following Endovascular Therapy in Large Vessel Occlusion Stroke.

Stroke 2020 09 12;51(9):e193-e202. Epub 2020 Aug 12.

Department of Radiology and Biomedical Imaging, Division of Neurocritical Care and Emergency Neurology, Department of Neurology (S.M.S., C.K.N., K.U.P., S.K., A.S., G.J.F., K.N.S., N.H.P.), Yale University School of Medicine, New Haven, CT.

Background And Purpose: We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel occlusion ischemic stroke.

Methods: Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2.

Results: Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0-2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI (<0.001) and collateral status (<0.001) were among independent predictors of final infarct volumes. However, mTICI (<0.001), but not collateral status (=0.058), predicted favorable outcome at discharge.

Conclusions: In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success-but not collateral status-was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.
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http://dx.doi.org/10.1161/STROKEAHA.120.029892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484023PMC
September 2020

Stroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic.

Stroke 2020 09 31;51(9):2664-2673. Epub 2020 Jul 31.

Department of Neurology (A.S.J., P.C., I.M., R.M., M.E., Q.Z., K.N., K.V., M.A., N.P., G.J.F., P.L., N.Z., R.N., H.A., D.N., C.L., D.Y.H., J.S., S.S., K.N.S., L.H.S., R.S.), Yale University School of Medicine, New Haven, CT.

Background: Anecdotal reports suggest fewer patients with stroke symptoms are presenting to hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We quantify trends in stroke code calls and treatments at 3 Connecticut hospitals during the local emergence of COVID-19 and examine patient characteristics and stroke process measures at a Comprehensive Stroke Center (CSC) before and during the pandemic.

Methods: Stroke code activity was analyzed from January 1 to April 28, 2020, and corresponding dates in 2019. Piecewise linear regression and spline models identified when stroke codes in 2020 began to decline and when they fell below 2019 levels. Patient-level data were analyzed in February versus March and April 2020 at the CSC to identify differences in patient characteristics during the pandemic.

Results: A total of 822 stroke codes were activated at 3 hospitals from January 1 to April 28, 2020. The number of stroke codes/wk decreased by 12.8/wk from February 18 to March 16 (=0.0360) with nadir of 39.6% of expected stroke codes called from March 10 to 16 (30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019). There was no commensurate increase in within-network telestroke utilization. Compared with before the pandemic (n=167), pandemic-epoch stroke code patients at the CSC (n=211) were more likely to have histories of hypertension, dyslipidemia, coronary artery disease, and substance abuse; no or public health insurance; lower median household income; and to live in the CSC city (<0.05). There was no difference in age, sex, race/ethnicity, stroke severity, time to presentation, door-to-needle/door-to-reperfusion times, or discharge modified Rankin Scale.

Conclusions: Hospital presentation for stroke-like symptoms decreased during the COVID-19 pandemic, without differences in stroke severity or early outcomes. Individuals living outside of the CSC city were less likely to present for stroke codes at the CSC during the pandemic. Public health initiatives to increase awareness of presenting for non-COVID-19 medical emergencies such as stroke during the pandemic are critical.
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http://dx.doi.org/10.1161/STR.0000000000000347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446978PMC
September 2020

A Pooled Analysis of Diffusion-Weighted Imaging Lesions in Patients With Acute Intracerebral Hemorrhage.

JAMA Neurol 2020 11;77(11):1390-1397

Division of Neurosciences Critical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: The etiology and significance of diffusion-weighted imaging (DWI) lesions in patients with acute intracerebral hemorrhage (ICH) remain unclear.

Objective: To evaluate which factors are associated with DWI lesions, whether associated factors differ by ICH location, and whether DWI lesions are associated with functional outcomes.

Design, Setting, And Participants: This analysis pooled individual patient data from 3 randomized clinical trials (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage trial, and Intracerebral Hemorrhage Deferoxamine phase 2 trial) and 1 multicenter prospective study (Ethnic/Racial Variations of Intracerebral Hemorrhage). Patients were enrolled from August 1, 2010, to September 30, 2018. Of the 4782 patients, 1788 who underwent magnetic resonance imaging scans of the brain were included. Data were analyzed from July 1 to December 31, 2019.

Main Outcomes And Measures: The primary outcome consisted of factors associated with DWI lesions. Secondary outcomes were poor functional outcome, defined as a modified Rankin score (mRS) of 4 to 6, and mortality, both assessed at 3 months. Mixed-effects logistic regression was used to evaluate the association between exposures and outcomes. Subgroup analyses stratified by hematoma location were performed.

Results: After exclusion of 36 patients with missing data on DWI lesions, 1752 patients were included in the analysis (1019 men [58.2%]; mean [SD] age, 60.8 [13.3] years). Diffusion-weighted imaging lesions occurred in 549 patients (31.3%). In mixed-effects regression models, factors associated with DWI lesions included younger age (odds ratio [OR] per year, 0.98; 95% CI, 0.97-0.99), black race (OR, 1.64; 95% CI, 1.17-2.30), admission systolic blood pressure (OR per 10-mm Hg increase, 1.13; 95% CI, 1.08-1.18), baseline hematoma volume (OR per 10-mL increase, 1.12; 95% CI, 1.02-1.22), cerebral microbleeds (OR, 1.85; 95% CI, 1.39-2.46), and leukoaraiosis (OR, 1.59; 95% CI, 1.67-2.17). Diffusion-weighted imaging lesions were independently associated with poor mRS (OR, 1.50; 95% CI, 1.13-2.00), but not with mortality (OR, 1.11; 95% CI, 0.72-1.71). In subgroup analyses, similar factors were associated with DWI lesions in lobar and deep ICH. Diffusion-weighted imaging lesions were associated with poor mRS in deep but not lobar ICH.

Conclusions And Relevance: In a large, heterogeneous cohort of prospectively identified patients with ICH, results were consistent with the hypothesis that DWI lesions represent acute sequelae of chronic cerebral small vessel disease, particularly hypertensive vasculopathy. Diffusion-weighted imaging lesions portend a worse prognosis after ICH, mainly deep hemorrhages.
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http://dx.doi.org/10.1001/jamaneurol.2020.2349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372494PMC
November 2020

Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage.

Stroke 2020 07 10;51(7):2153-2160. Epub 2020 Jun 10.

Department of Neurology (A.B., S.U., A.R.-T., A.C., M.P., C.K., K.S., Z.D., S.M.G., A.V., M.E.G., C.D.A., J.R.), Massachusetts General Hospital, Boston.

Background And Purpose: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the () gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest.

Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and genotype predict ICH recurrence. We then developed and validated a combined -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis.

Results: Cortical superficial siderosis, cerebral microbleed, and ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all <0.05). Combining genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH.

Conclusions: Combining MRI and genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.
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http://dx.doi.org/10.1161/STROKEAHA.120.028310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311289PMC
July 2020
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