Publications by authors named "Mark R Etherton"

Objectives: To determine the relationship between patient-reported outcome measures (PROMs) and volumetric imaging markers in acute ischemic stroke (AIS).

Patients And Methods: Patients presenting at Massachusetts General Hospital between February 14, 2017 and February 5, 2020 with a confirmed AIS by MRI were eligible and underwent a telephone interview including PROM-10 questionnaires 3-15 months after stroke. White matter hyperintensity (V) and brain volumes (V) were automatically determined using admission clinical MRI.

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Background And Objectives: Accumulating evidence suggests that gray matter atrophy, often considered a marker of Alzheimer disease (AD), can also result from cerebral small vessel disease (CSVD). Cerebral amyloid angiopathy (CAA) is a form of sporadic CSVD, diagnosed through neuroimaging criteria, that often co-occurs with AD pathology and leads to cognitive impairment. We sought to identify the role of hippocampal integrity in the development of cognitive impairment in a cohort of patients with possible and probable CAA.

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A leading cause of white matter (WM) injury in older individuals is cerebral small vessel disease (SVD). Cerebral SVD is the most prevalent vascular contributor to cognitive impairment and dementia. Therapeutic progress for cerebral SVD and other WM disorders depends on the development and validation of neuroimaging markers suitable as outcome measures in future interventional trials.

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Background: Ischemic stroke (IS) is a leading cause of long-term disability with sex-specific differences in outcomes. Identifying the influential factors that contribute to sex-specific disparities in stroke outcomes, therefore, holds potential to develop individualized interventions for reducing long-term disability. Further, investigating the association between sex and Patient-Reported Outcome Measures (PROMs) provides additional information on the individual impact and heterogeneity of IS.

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Purpose Of Review: To review the current evidence and ongoing clinical trials evaluating the efficacy and safety of tenecteplase (TNK), an alternative tissue plasminogen activator (tPA), in the acute management of arterial ischemic stroke (AIS). To date, alteplase is the only tPA approved by the United States FDA for use in AIS.

Recent Findings: There have been multiple phase two and three trials investigating the safety and efficacy of TNK in AIS.

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Introduction: For patients with large vessel occlusion (LVO) stroke, time to treatment with endovascular thrombectomy (EVT) is crucial to prevent infarction and improve outcomes. We sought to evaluate the hub arrival-to-puncture times and outcomes for transferred patients accepted directly to the angio-suite (LVO2OR) versus those accepted through the emergency department (ED) in a hub-and-spoke telestroke network.

Methods: Consecutive patients transferred for EVT with spoke CTA-confirmed LVO, spoke ASPECTS >6, and LKW-to-hub arrival <6 hours were identified.

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Article Synopsis
  • The study examines the relationship between neuroimaging-derived brain age estimates and post-stroke outcomes, hypothesizing that older brain age correlates with cardiovascular risk factors and poorer recovery.
  • T2-FLAIR images from over 4,000 stroke patients were analyzed to derive a Relative Brain Age (RBA), which indicates how aged a patient's brain appears compared to their chronological age.
  • The findings showed that higher RBA was linked to a history of conditions like hypertension and diabetes, and significantly affected functional outcomes after stroke, especially in patients with minor strokes.
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This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions.

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Background: Peak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD).

Purpose: Investigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA).

Materials And Methods: We analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center.

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Background And Objectives: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

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Background: Access to endovascular thrombectomy (EVT) is relatively limited. Hub-and-spoke networks seek to transfer appropriate large vessel occlusion (LVO) candidates to EVT-capable hubs. However, some patients are ineligible upon hub arrival, and factors that drive transfer inefficiencies are not well described.

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Background Purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.

Materials And Methods: Analyses relied upon imaging and clinical data from the international MRI-GENIE study.

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Article Synopsis
  • The study investigates the link between high white matter hyperintensity (WMH) levels and stroke severity/functionality, focusing on specific brain lesion patterns.
  • Data from 928 acute ischemic stroke patients were analyzed using MR imaging and statistical modeling to determine how different brain regions affected stroke outcomes.
  • Findings suggest that certain brain lesions, especially in the left hemisphere, have a greater impact on stroke severity and unfavorable recovery when WMH burden is high.
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For over two decades, telestroke has been utilized as a means for improving acute access to a stroke specialist when this expertise is otherwise unavailable. During this time, telestroke use has increased and improvements in care metrics have been widely reported. Several telestroke model variations are utilized; each has different workflow implications.

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Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment.

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Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation.

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Background And Objectives: The care of patients with large vessel occlusion (LVO) stroke has been revolutionized by endovascular thrombectomy (EVT). While EVT has a large effect size, most patients treated with EVT remain disabled or die within 90 days. A better understanding of outcomes may influence EVT selection criteria, novel therapies, and prognostication.

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Article Synopsis
  • The study explores the connection between global white matter microstructural integrity, measured by peak width of skeletonized mean diffusivity (PSMD), and the outcomes of ischemic stroke, focusing on data from 300 patients.
  • It highlights that factors like age, white matter hyperintensity volume, and pre-stroke disability are linked to higher PSMD, and that increased PSMD correlates with poorer functional outcomes post-stroke.
  • The findings suggest that PSMD can be used as a potential marker to predict stroke recovery, especially how age affects functional outcomes through its impact on white matter integrity.
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To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden modeling of expected WMH burden based on the VRF profile of each individual patient.

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Background And Purpose: Ischemic diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch may be useful in guiding acute stroke treatment decisions given its relationship to onset time and parenchymal viability; however, it relies on subjective grading. Radiomics is an emerging image quantification methodology that may objectively represent continuous image characteristics. We propose a novel radiomics approach to characterize DWI-FLAIR mismatch.

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Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

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Article Synopsis
  • Acute ischemic stroke presents differently in men and women, with women experiencing more severe symptoms compared to men.
  • Researchers developed a specialized Bayesian modeling framework to analyze lesion patterns from stroke patients, revealing that extensive brain lesions impact severity differently by sex.
  • The study emphasizes that for women, particularly severe strokes are linked to specific brain regions, indicating the need for tailored approaches in treating acute ischemic stroke based on sex differences.
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Introduction: Sex-specific differences in ischemic stroke outcomes are prevalent. We sought to investigate sex differences in the determinants of reperfusion and functional outcomes after endovascular thrombectomy (EVT) for emergent large vessel occlusion ischemic stroke (ELVO).

Methods: Patients presenting to a single referral center with an anterior circulation ELVO that underwent EVT from 2011 to 2019 were included in this retrospective analysis.

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Background And Purpose: Depression is common after stroke and is often treated with antidepressant medications (AD). ADs have also been hypothesised to improve stroke recovery, although recent randomised trials were neutral. We investigated the patterns of in-hospital AD initiation after ischaemic stroke and association with clinical and readmission outcomes.

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