Medicine and Health Sciences Commons^™

Genetic Complexities Of Cerebral Small Vessel Disease, Blood Pressure, And Dementia, Muralidharan Sargurupremraj, Chia-Ling Phuah, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain.

OBJECTIVE: To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases.

DESIGN, SETTING, AND PARTICIPANTS: This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was …

Inhibiting Metabotropic Glutamate Receptor 5 After Stroke Restores Brain Function And Connectivity, Jakob Hakon, Miriana J Quattromani, Carin Sjölund, Daniela Talhada, Byungchan Kim, Slavianka Moyanova, Federica Mastroiacovo, Luisa Di Menna, Roger Olsson, Elisabet Englund, Ferdinando Nicoletti, Karsten Ruscher, Adam Q Bauer, Tadeusz Wieloch

2020-Current year OA Pubs

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Recombinant Human Perlecan Dv And Its Lg3 Subdomain Are Neuroprotective And Acutely Functionally Restorative In Severe Experimental Ischemic Stroke, Ifechukwude Joachim Biose, Ibolya Rutkai, Bryan Clossen, Gary Gage, Kenneth Schechtman, H Davis Adkisson 4th, Gregory J Bix

2020-Current year OA Pubs

Despite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that  ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2β1 and α5β1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDV

Was Covid-19 Associated With Worsening Inequities In Stroke Treatment And Outcomes?, Laurent G Glance, Curtis G Benesch, Karen E Joynt Maddox, Matthew T Bender, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Jacob W Nadler, Christopher Galton, Andrew W Dick

2020-Current year OA Pubs

Background COVID-19 stressed hospitals and may have disproportionately affected the stroke outcomes and treatment of Black and Hispanic individuals. Methods and Results This retrospective study used 100% Medicare Provider Analysis and Review file data from between 2016 and 2020. We used interrupted time series analyses to examine whether the COVID-19 pandemic exacerbated disparities in stroke outcomes and reperfusion therapy. Among 1 142 560 hospitalizations for acute ischemic strokes, 90 912 (8.0%) were Hispanic individuals; 162 752 (14.2%) were non-Hispanic Black individuals; and 888 896 (77.8%) were non-Hispanic White individuals. The adjusted odds of mortality increased by 51% (adjusted odds ratio …

Brain Abscess And Stroke In Children And Adults With Hereditary Hemorrhagic Telangiectasia: Analysis Of A Large National Claims Database, Andrew J. White, Itay Marmor, Kate M. Peacock, Katelin B. Nickel, Jessica Zavadil, Margaret A. Olsen

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT.

METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using

RESULTS: …

Changing Trends In Demographics, Risk Factors, And Clinical Features Of Patients With Infective Endocarditis-Related Stroke, 2005-2015, Mohamed Ridha, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: There is a rising incidence of infective endocarditis-related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.

METHODS: This is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and …

Predicting Later Categories Of Upper Limb Activity From Earlier Clinical Assessments Following Stroke: An Exploratory Analysis, Jessica Barth, Keith R Lohse, Marghuretta D Bland, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Accelerometers allow for direct measurement of upper limb (UL) activity. Recently, multi-dimensional categories of UL performance have been formed to provide a more complete measure of UL use in daily life. Prediction of motor outcomes after stroke have tremendous clinical utility and a next step is to explore what factors might predict someone's subsequent UL performance category.

PURPOSE: To explore how different machine learning techniques can be used to understand how clinical measures and participant demographics captured early after stroke are associated with the subsequent UL performance categories.

METHODS: This study analyzed data from two time points from a …

Machine Learning Approximations To Predict Epigenetic Age Acceleration In Stroke Patients, Isabel Fernández-Pérez, Joan Jiménez-Balado, Uxue Lazcano, Eva Giralt-Steinhauer, Lucía Rey Álvarez, Elisa Cuadrado-Godia, Ana Rodríguez-Campello, Adrià Macias-Gómez, Antoni Suárez-Pérez, Anna Revert-Barberá, Isabel Estragués-Gázquez, Carolina Soriano-Tarraga, Jaume Roquer, Angel Ois, Jordi Jiménez-Conde

2020-Current year OA Pubs

Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A. We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, …

Cognition And Education Benefits Of Increased Hemoglobin And Blood Oxygenation In Children With Sickle Cell Disease, Joanna P. Macewan, Allison A. King, Andy Nguyen, Anuj Mubayi, Irene Agodoa, Kim Smith-Whitley

2020-Current year OA Pubs

BACKGROUND: Among individuals with sickle cell disease (SCD), decreased hemoglobin is associated with lower oxygen saturation (SpO2) and increased risk of stroke, both of which are associated with lower intelligence quotient (IQ) scores. Thus, increasing hemoglobin and SpO2 in individuals with SCD may increase IQ and educational attainment.

METHODS: A cohort simulation model was built to determine academic performance and educational attainment based on cognitive function (measured by IQ) of a pediatric SCD cohort randomly assigned to treatment and control groups. The model contained two key stages: childhood (<10 years) and adolescence (≥10 years). In stage 1, increased hemoglobin and increased SpO2 (assigned to the treatment group) were determinants of higher IQ, prevention of IQ deterioration over time. Increased hemoglobin was also a determinant of decreased stroke risk. In stage 2, improvement in adolescent IQ as a result of treatment was a determinant of academic performance.

RESULTS: In a simulated cohort of 2000 children and adolescents with …

Association Of Noncontrast Computed Tomography And Perfusion Modalities With Outcomes In Patients Undergoing Late-Window Stroke Thrombectomy, Guilherme B F Porto, Joshua Osbun, Et Al.

2020-Current year OA Pubs

IMPORTANCE: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy.

OBJECTIVE: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI).

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel …

Altered Methylation Pattern In Exoc4 Is Associated With Stroke Outcome: An Epigenome-Wide Association Study, Natalia Cullell, Carolina Soriano-Tárraga, Et Al.

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: The neurological course after stroke is highly variable and is determined by demographic, clinical and genetic factors. However, other heritable factors such as epigenetic DNA methylation could play a role in neurological changes after stroke.

METHODS: We performed a three-stage epigenome-wide association study to evaluate DNA methylation associated with the difference between the National Institutes of Health Stroke Scale (NIHSS) at baseline and at discharge (ΔNIHSS) in ischaemic stroke patients. DNA methylation data in the Discovery (n = 643) and Replication (n = 62) Cohorts were interrogated with the 450 K and EPIC BeadChip. Nominal CpG sites …

Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li

2020-Current year OA Pubs

Hydraulic fracturing or fracking has led to a rapid growth of oil and gas production in the United States, but the impact of fracking on public health is an important but underresearched topic. We designed a methodology to study spatiotemporal correlations between the risk of fracking and stroke mortality. An annualized loss expectancy (ALE) model is applied to quantify the risk of fracking. The geographically and temporally weighted regression (GTWR) model is used to analyze spatiotemporal correlations of stroke mortality, fracking ALE, and nine other socioeconomic- and health-related factors. The analysis shows that fracking ALE is moderately correlated with stroke …

Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta

2020-Current year OA Pubs

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.

Post-Stroke Reorganization Of Transient Brain Activity Characterizes Deficits And Recovery Of Cognitive Functions, Elvira Pirondini, Nawal Kinany, Cécile Le Sueur, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Dimitri Van De Ville

2020-Current year OA Pubs

Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to …

Surgery For Pituitary Tumor Apoplexy Is Associated With Rapid Headache And Cranial Nerve Improvement, Kevin A Cross, Rupen Desai, Ananth Vellimana, Yupeng Liu, Keith Rich, Gregory Zipfel, Ralph Dacey, Michael Chicoine, Cristine Klatt-Cromwell, Jonathan Mcjunkin, Patrik Pipkorn, John S Schneider, Julie Silverstein, Albert H Kim

2020-Current year OA Pubs

Pituitary tumor apoplexy (PTA) classically comprises sudden-onset headache, loss of vision, ophthalmoparesis, and decreased consciousness. It typically results from hemorrhage and/or infarction within a pituitary adenoma. Presentation is heterologous, and optimal management is debated. The time course of recovery of cranial nerve deficits (CNDs) and headaches is not well established. In this study, a retrospective series of consecutive patients with PTA managed at a single academic institution over a 22-year period is presented. Headaches at the time of surgery were more severe in the early and subacute surgical cohort and improved significantly within 72 h postoperatively (

Homotopic Contralesional Excitation Suppresses Spontaneous Circuit Repair And Global Network Reconnections Following Ischemic Stroke, Annie R Bice, Qingli Xiao, Justin Kong, Ping Yan, Zachary Pollack Rosenthal, Andrew W Kraft, Karen P Smith, Tadeusz Wieloch, Jin-Moo Lee, Joseph P Culver, Adam Q Bauer

2020-Current year OA Pubs

Understanding circuit-level manipulations that affect the brain's capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems- and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received …

Rate Of Infarct-Edema Growth On Ct Predicts Need For Surgical Intervention And Clinical Outcome In Patients With Cerebellar Infarction, Yan Wang, Michael M Binkley, Min Qiao, Amanda Pardon, Salah Keyrouz, Rajat Dhar, Andria L Ford

2020-Current year OA Pubs

BACKGROUND: Up to 20% of patients with cerebellar infarcts will develop malignant edema and deteriorate clinically. Radiologic measures, such as initial infarct size, aid in identifying individuals at risk. Studies of anterior circulation stroke suggest that mapping early edema formation improves the ability to predict deterioration; however, the kinetics of edema in the posterior fossa have not been well characterized. We hypothesized that faster edema growth within the first hours after acute cerebellar stroke would be an indicator for individuals requiring surgical intervention and those with worse neurological outcomes.

METHODS: Consecutive patients admitted to the neurological intensive care unit with …

International Stroke Genetics Consortium Recommendations For Studies Of Genetics Of Stroke Outcome And Recovery, Arne G Lindgren, Jin-Moo Lee, Et Al

2020-Current year OA Pubs

Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable …

Risk Of Intracranial Haemorrhage And Ischaemic Stroke After Convexity Subarachnoid Haemorrhage In Cerebral Amyloid Angiopathy: International Individual Patient Data Pooled Analysis, Isabel Charlotte Hostettler, Diane Aum, Gregory Joseph Zipfel, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA).

METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences.

RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each …

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Edge-Centric Analysis Of Stroke Patients: An Alternative Approach For Biomarkers Of Lesion Recovery, Sebastian Idesis, Joshua Faskowitz, Richard F Betzel, Maurizio Corbetta, Olaf Sporns, Gustavo Deco

2020-Current year OA Pubs

Most neuroimaging studies of post-stroke recovery rely on analyses derived from standard node-centric functional connectivity to map the distributed effects in stroke patients. Here, given the importance of nonlocal and diffuse damage, we use an edge-centric approach to functional connectivity in order to provide an alternative description of the effects of this disorder. These techniques allow for the rendering of metrics such as normalized entropy, which describes the diversity of edge communities at each node. Moreover, the approach enables the identification of high amplitude co-fluctuations in fMRI time series. We found that normalized entropy is associated with stroke lesion severity …

Relationships Between Accelerometry And General Compensatory Movements Of The Upper Limb After Stroke, Jessica Barth, Joeseph W Klaesner, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Standardized assessments are used in rehabilitation clinics after stroke to measure restoration versus compensatory movements of the upper limb. Accelerometry is an emerging tool that can bridge the gap between in- and out-of-clinic assessments of the upper limb, but is limited in that it currently does not capture the quality of a person's movement, an important concept to assess compensation versus restoration. The purpose of this analysis was to characterize how accelerometer variables may reflect upper limb compensatory movement patterns after stroke.

METHODS: This study was a secondary analysis of an existing data set from a Phase II, single-blind, …

Utstein Recommendation For Emergency Stroke Care, A. Rudd, P. Panagos, Et Al

2020-Current year OA Pubs

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient.

AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients.

METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain …