Publications by authors named "Kevin N Sheth"

299 Publications

Bedside Monitoring of Hypoxic Ischemic Brain Injury Using Low-Field, Portable Brain Magnetic Resonance Imaging After Cardiac Arrest.

Resuscitation 2022 May 10. Epub 2022 May 10.

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

Background: Assessment of brain injury severity is critically important after survival from cardiac arrest (CA). Recent advances in low-field MRI technology have permitted the acquisition of clinically useful bedside brain imaging. Our objective was to deploy a novel approach for evaluating brain injury after CA in critically ill patients at high risk for adverse neurological outcome.

Methods: This retrospective, single center study involved review of all consecutive portable MRIs performed as part of clinical care for CA patients between September 2020 and January 2022. Portable MR images were retrospectively reviewed by a blinded board-certified neuroradiologist (S.P.). Fluid-inversion recovery (FLAIR) signal intensities were measured in select regions of interest.

Results: We performed 22 low-field MRI examinations in 19 patients resuscitated from CA (68.4% male, mean [standard deviation] age, 51.8 [13.1] years). Twelve patients (63.2%) had findings consistent with HIBI on conventional neuroimaging radiology report. Low-field MRI detected findings consistent with HIBI in all of these patients. Low-field MRI was acquired at a median (interquartile range) of 78 (40-136) hours post-arrest. Quantitatively, we measured FLAIR signal intensity in three regions of interest, which were higher amongst patients with confirmed HIBI. Low-field MRI was completed in all patients without disruption of intensive care unit equipment monitoring and no safety events occurred.

Conclusion: In a critically ill CA population in whom MR imaging is often not feasible, low-field MRI can be deployed at the bedside to identify HIBI. Low-field MRI provides an opportunity to evaluate the time-dependent nature of MRI findings in CA survivors.
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http://dx.doi.org/10.1016/j.resuscitation.2022.05.002DOI Listing
May 2022

CT angiographic radiomics signature for risk stratification in anterior large vessel occlusion stroke.

Neuroimage Clin 2022 7;34:103034. Epub 2022 May 7.

Section of Neuroradiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States. Electronic address:

Background And Purpose: As "time is brain" in acute stroke triage, the need for automated prognostication tools continues to increase, particularly in rapidly expanding tele-stroke settings. We aimed to create an automated prognostication tool for anterior circulation large vessel occlusion (LVO) stroke based on admission CTA radiomics.

Methods: We automatically extracted 1116 radiomics features from the anterior circulation territory on admission CTAs of 829 acute LVO stroke patients who underwent mechanical thrombectomy in two academic centers. We trained, optimized, validated, and compared different machine-learning models to predict favorable outcome (modified Rankin Scale ≤ 2) at discharge and 3-month follow-up using four different input sets: "Radiomics", "Radiomics + Treatment" (radiomics, post-thrombectomy reperfusion grade, and intravenous thrombolysis), "Clinical + Treatment" (baseline clinical variables and treatment), and "Combined" (radiomics, treatment, and baseline clinical variables).

Results: For discharge outcome prediction, models were optimized/trained on n = 494 and tested on an independent cohort of n = 100 patients from Yale. Receiver operating characteristic analysis of the independent cohort showed no significant difference between best-performing Combined input models (area under the curve, AUC = 0.77) versus Radiomics + Treatment (AUC = 0.78, p = 0.78), Radiomics (AUC = 0.78, p = 0.55), or Clinical + Treatment (AUC = 0.77, p = 0.87) models. For 3-month outcome prediction, models were optimized/trained on n = 373 and tested on an independent cohort from Yale (n = 72), and an external cohort from Geisinger Medical Center (n = 232). In the independent cohort, there was no significant difference between Combined input models (AUC = 0.76) versus Radiomics + Treatment (AUC = 0.72, p = 0.39), Radiomics (AUC = 0.72, p = 0.39), or Clinical + Treatment (AUC = 76, p = 0.90) models; however, in the external cohort, the Combined model (AUC = 0.74) outperformed Radiomics + Treatment (AUC = 0.66, p < 0.001) and Radiomics (AUC = 0.68, p = 0.005) models for 3-month prediction.

Conclusion: Machine-learning signatures of admission CTA radiomics can provide prognostic information in acute LVO stroke candidates for mechanical thrombectomy. Such objective and time-sensitive risk stratification can guide treatment decisions and facilitate tele-stroke assessment of patients. Particularly in the absence of reliable clinical information at the time of admission, models solely using radiomics features can provide a useful prognostication tool.
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http://dx.doi.org/10.1016/j.nicl.2022.103034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108990PMC
May 2022

Association of intraventricular fibrinolysis with clinical outcomes in ICH: an individual participant data meta-analysis.

Stroke 2022 May 6. Epub 2022 May 6.

Department of Neurology, Klinikum Dortmund, GERMANY.

In patients with intracerebral hemorrhage (ICH) the presence of intraventricular hemorrhage (IVH) constitutes an important therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. This individual participant data (IPD) meta-analysis pooled 1,501 patients from two randomized trials and seven observational studies enrolled during 2004 to 2015. We compared IVF vs standard of care (SoC, including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH and/or IVH. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS, range:0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS:0-3 vs mRS:4-6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random-effects- and doubly-robust-models to calculate odds-ratios (OR) and absolute treatment-effects (ATE). Comparing treatment of 596 with IVF to 905 with SoC resulted in an ATE to achieve the primary outcome of 9.3%[95%CI4.4-14.1]. IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common-OR:1.75[95%CI1.39-2.17], reduced mortality, OR:0.47[95%CI 0.35-0.64], without increased adverse events, absolute difference:1.0%[95%CI-2.7-4.8]. Exploratory analyses provided that early IVF-treatment (≤48 hours) after symptom onset was associated with an ATE:15.2%[95%CI8.6-21.8] to achieve the primary outcome. As compared to SoC, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage significantly improved functional outcome at 6 months. The treatment effect was linked to an early time-window<48h, specifying a target population for future trials.
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http://dx.doi.org/10.1161/STROKEAHA.121.038455DOI Listing
May 2022

Effect of Intensive Blood Pressure Control on Incident Stroke Risk in Patients With Mild Cognitive Impairment.

Stroke 2022 May 3:101161STROKEAHA122038818. Epub 2022 May 3.

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

Background: Patients with mild cognitive impairment may be at higher risk of incident stroke, but the effect of intensive blood pressure (BP) control on that risk has not been explored.

Methods: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) and included patients with a baseline Montreal Cognitive Assessment score of 19 to 25 and without a prior history of stroke. The primary outcome was incident stroke (ischemic and hemorrhagic) during follow-up. We report the unadjusted cumulative risk of our primary outcome by SPRINT randomization arm (intensive versus standard BP control) and also fit Cox models to the primary outcome and adjusted for patient age at randomization, race/ethnicity, sex, baseline BP, atrial fibrillation, diabetes, and smoking.

Results: We included 5091 patients (mean age 68.2, 44% female, 56.7% non-Hispanic White, and 50.2% randomized to intensive BP control), of which 95/5091 (1.9%) had an incident stroke during a mean of 3.8±0.9 years of follow-up. The risk of incident stroke in patients randomized to standard BP control was 57/2536 (2.3%) and to intensive BP control was 38/2555 (1.5%; =0.045). In the adjusted Cox model, the hazard ratio for incident stroke events with intensive BP control was 0.65 (95% CI, 0.43-0.98; =0.040).

Conclusions: Although the SPRINT trial failed to show a reduction in stroke with intensive BP control for all subjects, those with a Montreal Cognitive Assessment score consistent with mild cognitive impairment at baseline had an association between intensive BP control and lower risk of incident stroke. Future trials of primary prevention of stroke may benefit from enrichment using baseline vascular biomarkers of elevated risk, such as mild cognitive impairment.
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http://dx.doi.org/10.1161/STROKEAHA.122.038818DOI Listing
May 2022

White matter hyperintensity progression is associated with incident probable dementia or mild cognitive impairment.

Stroke Vasc Neurol 2022 Apr 29. Epub 2022 Apr 29.

Neurology, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA.

Background: White matter hyperintensity (WMH) on brain MRI is associated with developing dementia or mild cognitive impairment (MCI), but WMH progression over time has not been fully investigated as an independent risk factor.

Methods: We performed a post hoc analysis of the Systolic Blood Pressure Intervention Trial - Memory and Cognition in Decreased Hypertension (SPRINT MIND) trial. The primary outcome was incident probable dementia or MCI (dementia/MCI) before the follow-up MRI at 48 months from enrolment. The primary predictor was WMH progression, defined as the Z score difference between the follow-up and baseline WMH volumes. The secondary predictor was a binary WMH progression threshold (≥1.4 mL vs <1.4 mL).

Results: Among the 433 included patients, 33 (7.6%) developed dementia/MCI. There were 156 (36.0%) patients who met the WMH progression threshold of ≥1.4 mL, in whom the rate of dementia/MCI was 12.8% (20/156) vs 4.7% (13/277) of patients with <1.4 mL WMH progression (p=0.002). In multivariable logistic regression, the Z score of WMH progression was associated with dementia/MCI (OR 1.51, 95% CI 1.12 to 2.04, p=0.007) as was the WMH progression threshold of ≥1.4 mL (OR 2.89, 95% CI 1.23 to 6.81, p=0.015).

Conclusions: In this post hoc analysis of SPRINT MIND, WMH progression over 48 months was associated with the development of probable dementia or MCI.
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http://dx.doi.org/10.1136/svn-2021-001357DOI Listing
April 2022

Correlation Between Computed Tomography-Based Tissue Net Water Uptake and Volumetric Measures of Cerebral Edema After Reperfusion Therapy.

Stroke 2022 Apr 22:101161STROKEAHA121037073. Epub 2022 Apr 22.

Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (F.C.N., N.Y., G.S., S.M.D., B.C.V.C.).

Background: Cerebral edema after large hemispheric infarction is associated with poor functional outcome and mortality. Net water uptake (NWU) quantifies the degree of hypoattenuation on unenhanced-computed tomography (CT) and is increasingly used to measure cerebral edema in stroke research. Hemorrhagic transformation and parenchymal contrast staining after thrombectomy may confound NWU measurements. We investigated the correlation of NWU measured postthrombectomy with volumetric markers of cerebral edema and association with functional outcomes.

Methods: In a pooled individual patient level analysis of patients presenting with anterior circulation large hemispheric infarction (core 80-300 mL or Alberta Stroke Program Early CT Score ≤5) in the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set, cerebral edema was defined as the volumetric expansion of the ischemic hemisphere expressed as a ratio to the contralateral hemisphere(rHV). NWU and midline-shift were compared with rHV as the reference standard on 24-hour follow-up CT, adjusted for hemorrhagic transformation and the use of thrombectomy. Association between edema markers and day 90 functional outcomes (modified Rankin Scale) was assessed using ordinal logistic regression.

Results: Overall (n=144), there was no correlation between NWU and rHV (r=0.055, =0.51). In sub-group analyses, a weak correlation between NWU with rHV was observed after excluding patients with any degree of hemorrhagic transformation (r=0.211, =0.015), which further improved after excluding thrombectomy patients (r=0.453, =0.001). Midline-shift correlated strongly with rHV in all sub-group analyses (r>0.753, =0.001). Functional outcome at 90 days was negatively associated with rHV (adjusted common odds ratio, 0.46 [95% CI, 0.32-0.65]; <0.001) and midline-shift (adjusted common odds ratio, 0.85 [95% CI, 0.78-0.92]; <0.001) but not NWU (adjusted common odds ratio, 1.00 [95% CI, 0.97-1.03]; =0.84), adjusted for age, baseline National Institutes of Health Stroke Scale, and thrombectomy. Prognostic performance of NWU improved after excluding patients with hemorrhagic transformation and thrombectomy (adjusted odds ratio, 0.90 [95% CI, 0.80-1.02]; =0.10).

Conclusions: NWU correlated poorly with conventional markers of cerebral edema and was not associated with clinical outcome in the presence of hemorrhagic transformation and thrombectomy. Measuring NWU postthrombectomy requires validation before implementation into clinical research. At present, the use of NWU should be limited to baseline CT, or follow-up CT only in patients without hemorrhagic transformation or treatment with thrombectomy.
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http://dx.doi.org/10.1161/STROKEAHA.121.037073DOI Listing
April 2022

Portable, low-field magnetic resonance imaging enables highly accessible and dynamic bedside evaluation of ischemic stroke.

Sci Adv 2022 Apr 20;8(16):eabm3952. Epub 2022 Apr 20.

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

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.
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http://dx.doi.org/10.1126/sciadv.abm3952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020661PMC
April 2022

Looking into the future.

Authors:
Kevin N Sheth

Lancet Neurol 2022 05;21(5):415-416

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http://dx.doi.org/10.1016/S1474-4422(22)00122-3DOI Listing
May 2022

Brain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery.

Bioact Mater 2022 Oct 7;16:57-65. Epub 2022 Mar 7.

Department of Neurosurgery, USA.

Stroke is the leading cause of death and disability. Currently, there is no effective pharmacological treatment for this disease, which can be partially attributed to the inability to efficiently deliver therapeutics to the brain. Here we report the development of natural compound-derived nanoparticles (NPs), which function both as a potent therapeutic agent for stroke treatment and as an efficient carrier for drug delivery to the ischemic brain. First, we screened a collection of natural nanomaterials and identified betulinic acid (BA) as one of the most potent antioxidants for stroke treatment. Next, we engineered BA NPs for preferential drug release in acidic ischemic tissue through chemically converting BA to betulinic amine (BAM) and for targeted drug delivery through surface conjugation of AMD3100, a CXCR4 antagonist. The resulting AMD3100-conjugated BAM NPs, or A-BAM NPs, were then assessed as a therapeutic agent for stroke treatment and as a carrier for delivery of NA1, a neuroprotective peptide. We show that intravenous administration of A-BAM NPs effectively improved recovery from stroke and its efficacy was further enhanced when NA1 was encapsulated. Due to their multifunctionality and significant efficacy, we anticipate that A-BAM NPs have the potential to be translated both as a therapeutic agent and as a drug carrier to improve the treatment of stroke.
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http://dx.doi.org/10.1016/j.bioactmat.2022.02.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958421PMC
October 2022

Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial.

Stroke 2022 Apr 1:101161STROKEAHA121037974. Epub 2022 Apr 1.

Departments of Neurology and Neurosurgery, New York Medical College, Valhalla, NY (S.A.M.).

Background: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH.

Methods: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale).

Results: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, =0.001) and early neurological deterioration (31 versus 17%, =0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, <0.001) and 24 hours (14 versus 38mL, <0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, =0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; =0.01).

Conclusions: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.
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http://dx.doi.org/10.1161/STROKEAHA.121.037974DOI Listing
April 2022

Brain Targeting, Antioxidant Polymeric Nanoparticles for Stroke Drug Delivery and Therapy.

Small 2022 Mar 20:e2107126. Epub 2022 Mar 20.

Department of Biomedical Engineering, Yale University, New Haven, CT, 06510, USA.

Ischemic stroke is a leading cause of death and disability and remains without effective treatment options. Improved treatment of stroke requires efficient delivery of multimodal therapy to ischemic brain tissue with high specificity. Here, this article reports the development of multifunctional polymeric nanoparticles (NPs) for both stroke treatment and drug delivery. The NPs are synthesized using an reactive oxygen species (ROS)-reactive poly (2,2'-thiodiethylene 3,3'-thiodipropionate) (PTT) polymer and engineered for brain penetration through both thrombin-triggered shrinkability and AMD3100-mediated targeted delivery. It is found that the resulting AMD3100-conjugated, shrinkable PTT NPs, or ASPTT NPs, efficiently accumulate in the ischemic brain tissue after intravenous administration and function as antioxidant agents for effective stroke treatment. This work shows ASPTT NPs are capable of efficient encapsulation and delivery of glyburide to achieve anti-edema and antioxidant combination therapy, resulting in therapeutic benefits significantly greater than those by either the NPs or glyburide alone. Due to their high efficiency in brain penetration and excellent antioxidant bioactivity, ASPTT NPs have the potential to be utilized to deliver various therapeutic agents to the brain for effective stroke treatment.
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http://dx.doi.org/10.1002/smll.202107126DOI Listing
March 2022

Risk Factors Associated With Mortality and Neurologic Disability After Intracerebral Hemorrhage in a Racially and Ethnically Diverse Cohort.

JAMA Netw Open 2022 03 1;5(3):e221103. Epub 2022 Mar 1.

Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and most survivors experience significant disability.

Objective: To assess primary patient risk factors associated with mortality and neurologic disability 3 months after ICH in a large, racially and ethnically balanced cohort.

Design, Setting, And Participants: This cohort study included participants from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, which prospectively recruited 1000 non-Hispanic White, 1000 non-Hispanic Black, and 1000 Hispanic patients with spontaneous ICH to study the epidemiological characteristics and genomics associated with ICH. Participants included those with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Analyses were completed in November 2021.

Exposures: Patient demographic and clinical characteristics as well as hospital event and imaging variables were examined, with characteristics meeting P < .20 considered candidates for a multivariate model. Elements included in the ICH score were specifically analyzed.

Main Outcomes And Measures: Individual characteristics were screened for association with 3-month outcome of neurologic disability or mortality, as assessed by a modified Rankin Scale (mRS) score of 4 or greater vs 3 or less under a logistic regression model. A total of 25 characteristics were tested in the final model, which minimized the Akaike information criterion. Analyses were repeated removing individuals who had withdrawal of care.

Results: A total of 2568 patients (mean [SD] age, 62.4 [14.7] years; 1069 [41.6%] women and 1499 [58.4%] men) had a 3-month outcome determination available, including death. The final logistic model had a significantly higher area under the receiver operating characteristics curve (C = 0.88) compared with ICH score alone (C = 0.76; P < .001). Among characteristics associated with neurologic disability and mortality were larger log ICH volume (OR, 2.74; 95% CI, 2.36-3.19; P < .001), older age (OR per 1-year increase, 1.04; 95% CI, 1.02-1.05; P < .001), pre-ICH mRS score (OR, 1.62; 95% CI, 1.41-1.87; P < .001), lobar location (OR, 0.22; 95% CI, 0.16-0.30; P < .001), and presence of infection (OR, 1.85; 95% CI, 1.42-2.41; P < .001).

Conclusions And Relevance: The findings of this cohort study validate ICH score elements and suggest additional baseline and interim patient characteristics were associated with variation in 3-month outcome.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.1103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924717PMC
March 2022

Association Between Systemic Amyloidosis and Intracranial Hemorrhage.

Stroke 2022 03 3;53(3):e92-e93. Epub 2022 Feb 3.

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology (D.C., C.Z., N.P., A.E.M., B.B.N., M.E.F., H.K., S.B.M.), Weill Cornell Medicine, NY.

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http://dx.doi.org/10.1161/STROKEAHA.121.038451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885899PMC
March 2022

The authors reply.

Crit Care Med 2022 02;50(2):e215-e216

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

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http://dx.doi.org/10.1097/CCM.0000000000005388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842829PMC
February 2022

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

Stroke 2022 Jan 28:STROKEAHA121036706. Epub 2022 Jan 28.

Department of Neurology, Weill Cornell Medicine, NY (A.E.M., H.K.).

Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018.

Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge.

Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; , 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, <0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis.

Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.
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http://dx.doi.org/10.1161/STROKEAHA.121.036706DOI Listing
January 2022

Bedside detection of intracranial midline shift using portable magnetic resonance imaging.

Sci Rep 2022 01 7;12(1):67. Epub 2022 Jan 7.

Hyperfine, Inc, Guilford, CT, USA.

Neuroimaging is crucial for assessing mass effect in brain-injured patients. Transport to an imaging suite, however, is challenging for critically ill patients. We evaluated the use of a low magnetic field, portable MRI (pMRI) for assessing midline shift (MLS). In this observational study, 0.064 T pMRI exams were performed on stroke patients admitted to the neuroscience intensive care unit at Yale New Haven Hospital. Dichotomous (present or absent) and continuous MLS measurements were obtained on pMRI exams and locally available and accessible standard-of-care imaging exams (CT or MRI). We evaluated the agreement between pMRI and standard-of-care measurements. Additionally, we assessed the relationship between pMRI-based MLS and functional outcome (modified Rankin Scale). A total of 102 patients were included in the final study (48 ischemic stroke; 54 intracranial hemorrhage). There was significant concordance between pMRI and standard-of-care measurements (dichotomous, κ = 0.87; continuous, ICC = 0.94). Low-field pMRI identified MLS with a sensitivity of 0.93 and specificity of 0.96. Moreover, pMRI MLS assessments predicted poor clinical outcome at discharge (dichotomous: adjusted OR 7.98, 95% CI 2.07-40.04, p = 0.005; continuous: adjusted OR 1.59, 95% CI 1.11-2.49, p = 0.021). Low-field pMRI may serve as a valuable bedside tool for detecting mass effect.
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http://dx.doi.org/10.1038/s41598-021-03892-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742125PMC
January 2022

Methodology for Low-Field, Portable Magnetic Resonance Neuroimaging at the Bedside.

Front Neurol 2021 10;12:760321. Epub 2021 Dec 10.

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

Neuroimaging is a critical component of triage and treatment for patients who present with neuropathology. Magnetic resonance imaging and non-contrast computed tomography are the gold standard for diagnosis and prognostication of patients with acute brain injuries. However, these modalities require intra-hospital transport to strict, access-controlled environments, which puts critically ill patients at risk for complications and secondary injuries. A novel, portable MRI (pMRI) device that can be deployed at the patient's bedside provides a needed solution. In a dual-center investigation, Yale New Haven Hospital has obtained regular neuroimaging on patients using the pMRI as part of routine clinical care in the Emergency Department and Intensive Care Unit (ICU) since August of 2020. Massachusetts General Hospital has begun using pMRI in the Neuroscience Intensive Care Unit since January 2021. This technology has expanded the population of patients who can receive MRI imaging by increasing accessibility and timeliness for scan completion by eliminating the need for transport and increasing the potential for serial monitoring. Here we describe our methods for screening, coordinating, and executing pMRI exams and provide further detail on how to scan specific patient populations.
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http://dx.doi.org/10.3389/fneur.2021.760321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703196PMC
December 2021

Risk of Mortality After an Arterial Ischemic Event Among Intracerebral Hemorrhage Survivors.

Neurohospitalist 2022 Jan 25;12(1):19-23. Epub 2021 Jun 25.

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, NY, USA.

Background And Purpose: The impact of arterial ischemic events after intracerebral hemorrhage (ICH) on outcomes is unclear. This study aimed to evaluate the risk of death among ICH survivors with and without an incident arterial ischemic event.

Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries with a non-traumatic ICH from January 2008 to October 2015. Our exposure was an arterial ischemic event, a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was mortality. We used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for confounders as time-varying covariates.

Results: Among 8,804 Medicare beneficiaries with ICH, 2,371 (26.9%) had an arterial ischemic event. During a median follow-up time of 1.9 years (interquartile range, 0.7-3.9), ICH patients with an arterial ischemic event had a mortality rate of 21.7 (95% confidence interval [CI], 20.4-23.0) per 100 person-years compared to a rate of 15.0 (95% CI, 14.4-15.6) per 100 person-years in those without. In the marginal structural model, an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.6-1.9). In secondary analyses, the mortality risk was elevated after an ischemic stroke (HR, 1.7; 95% CI, 1.5-1.8), and MI (HR, 3.0; 95% CI, 2.4-3.8).

Conclusions: We found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI.
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http://dx.doi.org/10.1177/19418744211026709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689534PMC
January 2022

Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials.

Neurology 2022 03 22;98(10):e1013-e1020. Epub 2021 Dec 22.

From the Division of Neurocritical Care and Emergency Neurology (J.R.M.-B., A.M., C.Z., C.I., H.K., S.B.M.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Brain Injury Outcomes Center (Y.L., R.A., N.M., D.H.), Johns Hopkins University; Division of Neurosciences Critical Care (S.-M.C., P.J.P., W.C.Z.), Johns Hopkins University School of Medicine, Baltimore, MD; Vagelos College of Physicians and Surgeons (D.J.R.), Department of Neurology, Columbia University; Department of Radiology (A.G.), Clinical and Translational Neuroscience Unit (G.F., K.S.), Feil Family Brain and Mind Research Institute, and Department of Neurology (G.F., K.S.), Weill Cornell Medicine, New York, NY; Department of Neurology (A.S.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; Zeenat Qureshi Stroke Institutes (A.Q.) and Department of Neurology (A.Q.), University of Missouri, Columbia; Henry and Allison McCance Center for Brain Health (J.R.), Hemorrhagic Stroke Research Program (J.R.), J. Philip Kistler Stroke Research Center, and Department of Emergency Medicine (J.G.), Massachusetts General Hospital, Boston; and Department of Neurological Surgery (I.A.), University of Chicago School of Medicine, IL. Yunke Li is currently at The George Institute China at Peking University Health Sciences Center, Beijing, China.

Background And Objectives: To study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH).

Methods: We pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 (MISTIE III) trial. We included individuals with a brain MRI scan. Exposure was the presence of a CMB. The coprimary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbid conditions considered fixed effects and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number and hematoma characteristics.

Results: Of the 1,499 patients with ICH enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjusted models, presence of CMBs was associated with smaller ICH volume (β = -0.26, 95% confidence interval [CI] -0.44 to -0.08) and lower odds of hematoma expansion (odds ratio 0.65, 95% CI 0.40-0.95; = 0.04). The strength of association between CMBs and hematoma characteristics increased with increasing number of CMBs. The location of the CMBs and the severity of leukoaraiosis did not modify these results.

Discussion: In a pooled cohort of patients with ICH, our results are consistent with the hypothesis that more severe underlying small vessel disease, as represented by CMBs, leads to smaller baseline hematoma volumes and reduced hematoma expansion. Underlying cerebral small vessel disease may be of prognostic significance after ICH.

Trial Registration Information: ClinicalTrials.gov Identifier: NCT01176565 and NCT01827046.

Classification Of Evidence: This study provides Class II evidence that the presence of microbleeds on MRI is associated with a smaller ICH volume at presentation and a lower rate of hematoma expansion on follow-up imaging.
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http://dx.doi.org/10.1212/WNL.0000000000013247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967392PMC
March 2022

Passive Localization of the Central Sulcus during Sleep Based on Intracranial EEG.

Cereb Cortex 2021 Dec 18. Epub 2021 Dec 18.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.

We test the performance of a novel operator-independent EEG-based method for passive identification of the central sulcus (CS) and sensorimotor (SM) cortex. We studied seven patients with intractable epilepsy undergoing intracranial EEG (icEEG) monitoring, in whom CS localization was accomplished by standard methods. Our innovative approach takes advantage of intrinsic properties of the primary motor cortex (MC), which exhibits enhanced icEEG band-power and coherence across the CS. For each contact, we computed a composite power, coherence, and entropy values for activity in the high gamma band (80-115) Hz of 6-10 min of NREM sleep. Statistically transformed EEG data values that did not reach a threshold (th) were set to 0. We computed a metric M based on the transformed values and the mean Euclidian distance of each contact from contacts with Z-scores higher than 0. The last step was implemented to accentuate local network activity. The SM cortex exhibited higher EEG-band-power than non-SM cortex (P < 0.0002). There was no significant difference between the motor/premotor and sensory cortices (P < 0.47). CS was localized in all patients with 0.4 < th < 0.6. The primary hand and leg motor areas showed the highest metric values followed by the tongue motor area. Higher threshold values were specific (94%) for the anterior bank of the CS but not sensitive (42%). Intermediate threshold values achieved an acceptable trade-off (0.4: 89% specific and 70% sensitive).
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http://dx.doi.org/10.1093/cercor/bhab443DOI Listing
December 2021

Assessing the utility of low resolution brain imaging: treatment of infant hydrocephalus.

Neuroimage Clin 2021 23;32:102896. Epub 2021 Nov 23.

Center for Neural Engineering, Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, USA; Departments of Neurosurgery, and Physics, The Pennsylvania State University, University Park, PA, USA. Electronic address:

As low-field MRI technology is being disseminated into clinical settings around the world, it is important to assess the image quality required to properly diagnose and treat a given disease and evaluate the role of machine learning algorithms, such as deep learning, in the enhancement of lower quality images. In this post hoc analysis of an ongoing randomized clinical trial, we assessed the diagnostic utility of reduced-quality and deep learning enhanced images for hydrocephalus treatment planning. CT images of post-infectious infant hydrocephalus were degraded in terms of spatial resolution, noise, and contrast between brain and CSF and enhanced using deep learning algorithms. Both degraded and enhanced images were presented to three experienced pediatric neurosurgeons accustomed to working in low- to middle-income countries (LMIC) for assessment of clinical utility in treatment planning for hydrocephalus. In addition, enhanced images were presented alongside their ground-truth CT counterparts in order to assess whether reconstruction errors caused by the deep learning enhancement routine were acceptable to the evaluators. Results indicate that image resolution and contrast-to-noise ratio between brain and CSF predict the likelihood of an image being characterized as useful for hydrocephalus treatment planning. Deep learning enhancement substantially increases contrast-to-noise ratio improving the apparent likelihood of the image being useful; however, deep learning enhancement introduces structural errors which create a substantial risk of misleading clinical interpretation. We find that images with lower quality than is customarily acceptable can be useful for hydrocephalus treatment planning. Moreover, low quality images may be preferable to images enhanced with deep learning, since they do not introduce the risk of misleading information which could misguide treatment decisions. These findings advocate for new standards in assessing acceptable image quality for clinical use.
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http://dx.doi.org/10.1016/j.nicl.2021.102896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646178PMC
January 2022

Combining Transcranial Doppler and EEG Data to Predict Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

Neurology 2022 02 29;98(5):e459-e469. Epub 2021 Nov 29.

From the Department of Neurology (H.Y.C., E.J.G., L.J.H., H.P.Z., K.N.S., N.H.P., J.A.K.), Yale University, New Haven, CT; Department of Critical Care Medicine (J.E.), University of Pittsburgh Medical Center, PA; and Department of Neurology (S.F.Z., M.G., V.M.J., E.S.R., M.B.W.), Massachusetts General Hospital, Boston.

Background And Objectives: Delayed cerebral ischemia (DCI) is the leading complication of subarachnoid hemorrhage (SAH). Because DCI was traditionally thought to be caused by large vessel vasospasm, transcranial Doppler ultrasounds (TCDs) have been the standard of care. Continuous EEG has emerged as a promising complementary monitoring modality and predicts increased DCI risk. Our objective was to determine whether combining EEG and TCD data improves prediction of DCI after SAH. We hypothesize that integrating these diagnostic modalities improves DCI prediction.

Methods: We retrospectively assessed patients with moderate to severe SAH (2011-2015; Fisher 3-4 or Hunt-Hess 4-5) who had both prospective TCD and EEG acquisition during hospitalization. Middle cerebral artery (MCA) peak systolic velocities (PSVs) and the presence or absence of epileptiform abnormalities (EAs), defined as seizures, epileptiform discharges, and rhythmic/periodic activity, were recorded daily. Logistic regressions were used to identify significant covariates of EAs and TCD to predict DCI. Group-based trajectory modeling (GBTM) was used to account for changes over time by identifying distinct group trajectories of MCA PSV and EAs associated with DCI risk.

Results: We assessed 107 patients; DCI developed in 56 (51.9%). Univariate predictors of DCI are presence of high-MCA velocity (PSV ≥200 cm/s, sensitivity 27%, specificity 89%) and EAs (sensitivity 66%, specificity 62%) on or before day 3. Two univariate GBTM trajectories of EAs predicted DCI (sensitivity 64%, specificity 62.75%). Logistic regression and GBTM models using both TCD and EEG monitoring performed better. The best logistic regression and GBTM models used both TCD and EEG data, Hunt-Hess score at admission, and aneurysm treatment as predictors of DCI (logistic regression: sensitivity 90%, specificity 70%; GBTM: sensitivity 89%, specificity 67%).

Discussion: EEG and TCD biomarkers combined provide the best prediction of DCI. The conjunction of clinical variables with the timing of EAs and high MCA velocities improved model performance. These results suggest that TCD and cEEG are promising complementary monitoring modalities for DCI prediction. Our model has potential to serve as a decision support tool in SAH management.

Classification Of Evidence: This study provides Class II evidence that combined TCD and EEG monitoring can identify delayed cerebral ischemia after SAH.
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http://dx.doi.org/10.1212/WNL.0000000000013126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826465PMC
February 2022

Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets.

J Stroke Cerebrovasc Dis 2022 Feb 23;31(2):106219. Epub 2021 Nov 23.

Department of Neurology, Yale University School of Medicine, 15 York Street, New Haven, CT 06510, USA. Electronic address:

Objectives: Self-reported Black (SRB) Americans are approximately twice as likely to have a stroke as self-reported White (SRW) Americans. While social determinants of health and vascular risk factors account for some of the disparity, half the increased risk remains unexplained and may be related to unmeasured real-world factors of the racialized experience.

Materials: and Methods In this cohort study, we compared SRB and SRW participants in the Systolic Blood Pressure Intervention Trial (SPRINT) to the same groups in the observational Atherosclerosis Risk in Communities (ARIC) study to evaluate if clinical trial participation mitigates disparities in stroke risk. We set the ARIC baseline at visit 4 and excluded participants with prior stroke to create an ARIC cohort similar in age to SPRINT participants. The study outcome was incident primary stroke. We report hazard ratios from Cox models and inverse-probability weighted Cox models with propensity score matching on participant age, sex, diabetes, atrial fibrillation, and smoking.

Results: We included 10,094 patients from ARIC and 8,869 from SPRINT, of which 26.1% were SRB. The risk of stroke between SRW participants in SPRINT versus ARIC was not significantly different (IPW-Weighted HR 0.78 [0.52-1.19]). SRB ARIC participants were twice as likely to have a stroke as SRW ARIC participants (IPW-Weighted HR = 1.96 [1.41-2.71]). However, SRB SPRINT participants did not have higher stroke risk compared to SRW SPRINT or ARIC participants (IPW-Weighted HR 0.99 [0.68--1.77] and 0.95 [.57-1.59], respectively). SRB SPRINT participants in the intensive BP control group had a lower risk of stroke compared to SRB ARIC participants (IPW-Weighted HR = 0.39 [0.20-0.75]).

Conclusions: SRB race, compared to SRW race, is associated with an increase in primary stroke risk in the ARIC study but not in the SPRINT trial. The absence of the racial disparity in stroke incidence in SPRINT indicates that aspects of the disparity are modifiable. Population-based interventions that test this hypothesis deserve further attention.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106219DOI Listing
February 2022

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

Stroke 2022 04 16;53(4):1216-1225. Epub 2021 Nov 16.

Department of Neurosurgery (A.M.M.), Vanderbilt University Medical Center, Nashville, TN.

Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes.

Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death.

Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], <0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; =0.04). No significant association was found between trajectory group and hemorrhagic transformation.

Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.
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http://dx.doi.org/10.1161/STROKEAHA.121.034408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960326PMC
April 2022

Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review.

Int J Mol Sci 2021 Nov 2;22(21). Epub 2021 Nov 2.

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Sulfonylurea receptor 1 (SUR1) is a member of the adenosine triphosphate (ATP)-binding cassette (ABC) protein superfamily, encoded by Abcc8, and is recognized as a key mediator of central nervous system (CNS) cellular swelling via the transient receptor potential melastatin 4 (TRPM4) channel. Discovered approximately 20 years ago, this channel is normally absent in the CNS but is transcriptionally upregulated after CNS injury. A comprehensive review on the pathophysiology and role of SUR1 in the CNS was published in 2012. Since then, the breadth and depth of understanding of the involvement of this channel in secondary injury has undergone exponential growth: SUR1-TRPM4 inhibition has been shown to decrease cerebral edema and hemorrhage progression in multiple preclinical models as well as in early clinical studies across a range of CNS diseases including ischemic stroke, traumatic brain injury, cardiac arrest, subarachnoid hemorrhage, spinal cord injury, intracerebral hemorrhage, multiple sclerosis, encephalitis, neuromalignancies, pain, liver failure, status epilepticus, retinopathies and HIV-associated neurocognitive disorder. Given these substantial developments, combined with the timeliness of ongoing clinical trials of SUR1 inhibition, now, another decade later, we review advances pertaining to SUR1-TRPM4 pathobiology in this spectrum of CNS disease-providing an overview of the journey from patch-clamp experiments to phase III trials.
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http://dx.doi.org/10.3390/ijms222111899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584331PMC
November 2021

Effect of Primary Prophylactic Antiseizure Medication for Seizure Prevention Following Intracerebral Hemorrhage in the ERICH Study.

J Stroke Cerebrovasc Dis 2022 Jan 26;31(1):106143. Epub 2021 Oct 26.

Department of Neurology, MedStar Georgetown University Hospital, Washington, DC, USA.

Objectives: Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic antiseizure medications (ASMs) as a means of preventing post-stroke seizures, particularly following lobar ICH. However, evidence for ASM efficacy in preventing seizures and reducing disability is lacking given limited randomized trials. Herein, we report analysis from a large prospective observational study that evaluates the effect of primary prophylactic ASM administration on seizure occurrence and disability following ICH.

Materials And Methods: Primary analysis was performed on 1630 patients with ICH enrolled in the ERICH study. A propensity score for administration of prophylactic ASM was developed and patients were matched by the closest propensity score (difference < 0.1). McNemar's test was used to compare occurrence of in-hospital seizure and disability, defined by modified Rankin Score (mRS) ≥ 3 at 3 months post ICH.

Results: Of the 815 matched pairs of patients treated with primary prophylactic ASM, there was no significant difference in seizure occurrence (p = 0.4631) or disability (p = 0.4653). Subset analysis of 280 matched pairs of patients with primary lobar ICH similarly revealed no significant difference in seizure occurrence (p = 0.1011) or disability (p = 1.00) between prophylactically treated and untreated patients.

Conclusions: Although current guidelines do not recommend primary prophylactic ASM following ICH, clinical use remains widespread. Data from the ERICH study did not find an association between administering primary prophylactic ASM and preventing seizures or reducing disability following ICH, thus providing evidence to influence clinical practice and patient care.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106143DOI Listing
January 2022
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