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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). 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. Sex differences in history, presentation, adequate reperfusion (TICI 2b-3), and 90-day good outcome [delta modified Rankin Scale (mRS) ≤ 2 from pre-stroke] were examined. Multivariable logistic regression analyses were performed to assess sex-specific associations with outcomes. Three hundred and eighty-one consecutive ELVO patients were identified. Women (N = 193) were older (75 vs 64 years, p

Background and purposeDepression 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.MethodsAll Medicare fee-for-service beneficiaries aged 65 or older hospitalised for ischaemic stroke in participating Get With The Guidelines-Stroke hospitals between April and December 2014 were eligible for this analysis. Outcome measures included days alive and not in a healthcare institution (home time), all-cause mortality and readmission within 1-year postdischarge. Propensity score (PS)-adjusted logistic regression models were used to evaluate the associations between AD use and each outcome measure. We also compared outcomes in patients prescribed selective serotonin reuptake inhibitors (SSRIs) AD versus those prescribed non-SSRI ADs.ResultsOf 21 805 AD naïve patients included in this analysis, 1835 (8.4%) were started on an AD at discharge. Patients started on an AD had higher rates of depression and prior ischaemic stroke, presented with higher admission National Institutes of Health Stroke Scale score and were less likely to be discharged home. Similarly, patients started on an SSRI had lower rates of discharge to home. Adjusting for stroke severity, patients started on an AD had worse all-cause mortality, all-cause readmission, major adverse cardiac events, readmission for depression and decreased home-time. However, AD use was also associated with an increased risk for the sepsis, a falsification endpoint, suggesting the presence of residual confounding.ConclusionsPatients with ischaemic stroke initiated on AD therapy are at increased risk of poor clinical outcomes and readmission even after PS adjustment, suggesting that poststroke depression requiring medication is a poor prognostic sign. Further research is needed to explore the reasons why depression is associated with worse outcome, and whether AD treatment modifies this risk or not.

BackgroundPersons with pre-existing disabilities represent over one-third of acute stroke presentations, but account for a far smaller proportion of those receiving endovascular thrombectomy (EVT) and thrombolysis. This is despite existing ethical, economic, legal, and social directives to maximize equity for this vulnerable population. We sought to determine associations between baseline modified Rankin Scale (mRS) and outcomes after EVT.MethodsIndividuals who underwent EVT were identified from a prospectively maintained database. Demographics, medical history, presentations, treatments, and outcomes were recorded. Baseline disability was defined as baseline mRS≥2. Accumulated disability was defined as the delta between baseline mRS and absolute 90-day mRS.ResultsOf 381 individuals, 49 had baseline disability (five with mRS=4, 23 mRS=3, 21 mRS=2). Those with baseline disability were older (81 vs 68 years, PConclusionsWhile baseline mRS was associated with absolute 90-day disability, there was no association with accumulated disability or other outcomes. Patients with baseline disability should not be routinely excluded from EVT based on baseline mRS alone.

Effective treatment options for patients with life-threatening neurological disorders are limited. To address this unmet need, high-impact translational research is essential for the advancement and development of novel therapeutic approaches in neurocritical care. “The Neurotherapeutics Symposium 2019—Neurological Emergencies” conference, held in Rochester, New York, in June 2019, was designed to accelerate translation of neurocritical care research via transdisciplinary team science and diversity enhancement. Diversity excellence in the neuroscience workforce brings innovative and creative perspectives, and team science broadens the scientific approach by incorporating views from multiple stakeholders. Both are essential components needed to address complex scientific questions. Under represented minorities and women were involved in the organization of the conference and accounted for 30–40% of speakers, moderators, and attendees. Participants represented a diverse group of stakeholders committed to translational research. Topics discussed at the conference included acute ischemic and hemorrhagic strokes, neurogenic respiratory dysregulation, seizures and status epilepticus, brain telemetry, neuroprognostication, disorders of consciousness, and multimodal monitoring. In these proceedings, we summarize the topics covered at the conference and suggest the groundwork for future high-yield research in neurologic emergencies.

Since approval by the United States Food and Drug Administration in 1996, alteplase utilization rates for acute ischemic stroke have increased. Despite its efficacy for improving stroke outcomes, however, the majority of ischemic stroke patients still do not receive alteplase. To address this issue, different methods for improving access to alteplase have been tested with varying degrees of success.This article gives an overview of the recent approaches pursued to improve access to alteplase for acute ischemic stroke patients. Utilization of stroke systems of care, quality metrics, and quality-improvement initiatives to improve alteplase treatment rates are discussed. The implementation of Telestroke networks to improve access and timely evaluation by a stroke specialist are also reviewed. Lastly, this review discusses the use of neuroimaging techniques to identify alteplase candidates in stroke of unknown symptom onset or beyond the 4.5-h treatment window.Expanding access to alteplase therapy for acute ischemic stroke is a multi-faceted approach. Specific considerations based on region, population, and health-care resources should be considered for each strategy. Neuroimaging approaches to identify alteplase-eligible patients beyond the 4.5-h treatment window are a recent development in acute stroke care that holds promise for increasing alteplase treatment rates.

OBJECTIVE:To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). PATIENTS AND METHODS:This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission. RESULTS:Utilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm3) was associated with age (β -0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β -0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β -0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. CONCLUSION:Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.

Objective: 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. Methods: 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 via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health. NIH-NINDS (MRI-GENIE: R01NS086905 - PI NR; K23NS064052, R01NS082285 - NR; SiGN: U01 NS069208 - JR, SK; R01NS059775, R01NS063925, R01NS082285, P50NS051343, R01NS086905, U01 NS069208 - OW); NIH NIBIB (NAC P41EB015902 PG, U01NS030678 Kissela, Kleindorfer; EB015325 OW); ISGS (R01NS423733 P.I. JM, Swedish Heart and Lung Foundation, Lund University, Region Skåne, the Freemasons Lodge of Instruction Eos Lund, Skåne University Hospital, the Foundation of Färs &Frosta (One of Sparbanken Skånes ownership Foundations), and the Swedish Stroke Association - AL, Swedish Research Council and the Swedish Heart and Lung Foundation, the Swedish State under the ALF agreement CJ, Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (Funding for Research in Health PI051737, PI10/02064, PI12/01238 and PI15/00451 JJ-C), Fondos FEDER/EDRF Red de Investigación Cardiovascular (RD12/0042/0020 JJ-C), Fundació la Marató TV3 (76/C/2011 - JJ-C) and Recercaixa13 (JJ086116 JJ-C), Wistron Corporation (PG); The European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 753896 - MS; RL is a senior clinical investigator of FWO Flanders; MB was supported by the ISITE-ULNE Fundation, the Société Française de Neuroradiologie, the Société Française de Radiologie, the Thérèse and René Planiol Fundation; ME was supported by the American Academy of Neurology and MGH Executive Council on Research; TT was supported by the Helsinki University Central Hospital, Sigrid Juselius Foundation, Sahlgrenska University Hospital, and University of Gothenburg. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article of the decision to submit it for publication.

ObjectiveNeuroimaging 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.MethodsWe analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).ResultsRadiomic features were predictive of WMH burden (R2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1–6 < 0.001, p-valueCV7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.ConclusionRadiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients’ brain health.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy–mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy–mild cognitive impairment and non-cerebral amyloid angiopathy–mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy–mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy–mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy–mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

The aim of the current study was to explore the whole‐brain dynamic functional connectivity patterns in acute ischemic stroke (AIS) patients and their relation to short and long‐term stroke severity. We investigated resting‐state functional MRI‐based dynamic functional connectivity of 41 AIS patients two to five days after symptom onset. Re‐occurring dynamic connectivity configurations were obtained using a sliding window approach and k‐means clustering. We evaluated differences in dynamic patterns between three NIHSS‐stroke severity defined groups (mildly, moderately, and severely affected patients). Furthermore, we built Bayesian hierarchical models to evaluate the predictive capacity of dynamic connectivity and examine the interrelation with clinical measures, such as white matter hyperintensity lesions. Finally, we established correlation analyses between dynamic connectivity and AIS severity as well as 90‐day neurological recovery (ΔNIHSS). We identified three distinct dynamic connectivity configurations acutely post‐stroke. More severely affected patients spent significantly more time in a configuration that was characterized by particularly strong connectivity and isolated processing of functional brain domains (three‐level ANOVA: p, By employing dynamic functional connectivity analyses, Bonkhoff et al. demonstrate that severe acute ischemic stroke is linked to transiently increased isolated information processing in multiple functional domains. Additionally, they show that dynamic connectivity involving default mode network components significantly correlates with recovery in the first three months poststroke.

Objectives Despite the proven efficacy of endovascular thrombectomy (EVT) for large vessel occlusion stroke, over half treated remain functionally disabled or die. Infarct topography may have implications for prognostication, patient selection, and the development of tissue-specific neuroprotective agents. We sought to quantify white matter injury in anterior circulation acute infarcts post-EVT to understand its significance and identify its determinants. Materials and Methods Demographics, history, presentations, and outcomes for consecutive patients treated with EVT were recorded in a prospectively maintained database at a single center. Acute infarct masks were coregistered to standard space. Standard atlases of white matter, cortex, and basal ganglia were used to determine region-specific infarct volumes. Results 167 individuals were identified with median age 69 years and 53% women. 85% achieved adequate reperfusion (TICI 2b-3) after EVT; 43% achieved 90-day functional independence (mRS 0-2). Median infarct volumes were 45cc (IQR 18-122) for total, 17cc (6-49) for white matter, 21cc (4-53) for cortex, and 5cc (1-8) for basal ganglia. The odds of 90-day mRS 0-2 were reduced in patients with larger white matter infarct volume (cc, OR=0.89, 95%CI=0.81-0.96), independent of cortex infarct volume, basal ganglia infarct volume, age, NIHSS, and TICI 2b-3 reperfusion. Reperfusion-to-MRI time was associated with white matter infarct volume (hr, β=0.119, p=0.017), but not cortical or basal ganglia infarct volume. Conclusions These data quantitatively describe region-specific infarct volumes after EVT and suggest the clinical relevance of white matter infarct volume as a predictor of long-term outcomes. Further study is warranted to examine delayed white matter infarction and the significance of specific white matter tracts.

Background and purpose Endovascular thrombectomy (EVT) has revolutionized large vessel occlusion stroke care. However, not all patients with good endovascular results achieve good outcomes. We sought to understand the clinical significance of magnetic resonance imaging defined infarct growth despite adequate reperfusion and identify associated clinical and radiographic variables. Methods History, presentation, treatments, and outcomes for consecutive EVT patients at a referral center were collected. Adequate reperfusion was defined as thrombolysis in cerebral infarction (TICI) score 2b-3. Region-specific infarct volumes in white matter, cortex, and basal ganglia were determined on diffusion-weighted imaging. Infarct growth was defined as post-EVT minus pre-EVT volume. Good outcome was defined as 90-day modified Rankin Scale ≤2. Results Forty-four patients with adequate reperfusion were identified with median age 72 years; 64% were women. Each region showed infarct growth: white matter (median pre-EVT 7 cubic centimeters [cc], post-EVT 16 cc), cortex (4 cc, 15 cc), basal ganglia (2 cc, 4 cc), total (20 cc, 39 cc). In multivariable regression, total infarct growth independently decreased the odds of good outcome (odds ratio = .946, 95% CI = .897, .998). Further multivariable analyses for determinants of infarct growth identified female sex was associated with less total growth (β = -.294, P = .042), TICI 3 was associated with less white matter growth (β = -.277, P = .048) and cortical growth (β = -.335, P = .017), and both female sex (β = -.332, P = .015) and coronary disease (β = -.337, P = .015) were associated with less cortical growth. Conclusions Infarct growth occurred despite adequate reperfusion, disproportionately in the cortex, and independently decreased the odds of good outcome. Infarct growth occurred while patients were hospitalized and may represent a therapeutic target. Potential determinants of region-specific infarct growth were identified that require confirmation in larger studies.

The purpose of this article is to review the current approaches using neuroimaging techniques to expand eligibility for intravenous thrombolytic therapy in acute ischemic stroke patients with stroke of unknown symptom onset. In recent years, several randomized, placebo-controlled trials have shown neuroimaging-guided approaches to be feasible in determining eligibility for alteplase beyond 4.5 h from last known well, and efficacious for reducing disability. DWI-FLAIR mismatch on MRI is an effective tool to identify stroke lesions less than 4.5 h in onset in patients with stroke of unknown symptom onset. Additionally, an automated perfusion-based approach, assessing for a disproportionate amount of salvageable tissue, is effective in identifying patients likely to benefit from late window alteplase treatment. In patients with stroke of unknown symptom onset, an individualized approach using neuroimaging to determine time of stroke onset or presence of salvageable brain tissue is feasible in the acute setting and associated with improved long-term outcomes.

Background:Telestroke provides access to vascular neurology expertise for hospitals lacking stroke coverage, and its use has risen rapidly in the past decade. We aim to characterize consultations, spoke behavior, and the relationship between spoke telestroke utilization (number of telestroke consults per year) and spoke alteplase treatment metrics in an academic telestroke network.Methods and Results:We analyzed prospectively collected data on all telestroke consults from 2003 to 2018. Trends in network performance and spoke characteristics were analyzed using generalized estimating equations and Kendall τβ nonparametric tests as appropriate. Unadjusted and adjusted linear regression models determined associations between telestroke utilization and treatment metrics. The network included 2 hubs and 43 spokes with 12 803 consults performed during the study period. Network growth overall was +1.8 spokes per year, and median duration of spoke participation was 7.9 years. The numbers of consults and alteplase-treated patients increased annually, even after adjusting for the number of spokes in the network (PPP=0.02), number of patients treated with alteplase was an additional 1.7 (PP=0.03).Conclusions:Telestroke network size and utilization increased over time. Increased use of teleconsults was associated with increased and timely use of alteplase. Over time, the delivery of timely emergency care has improved significantly among emergency departments participating in this telestroke network. Replication of these findings in other networks is warranted.

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Registration is a core component of many imaging pipelines. In case of clinical scans, with lower resolution and sometimes substantial motion artifacts, registration can produce poor results. Visual assessment of registration quality in large clinical datasets is inefficient. In this work, we propose to automatically assess the quality of registration to an atlas in clinical FLAIR MRI scans of the brain. The method consists of automatically segmenting the ventricles of a given scan using a neural network, and comparing the segmentation to the atlas ventricles propagated to image space. We used the proposed method to improve clinical image registration to a general atlas by computing multiple registrations - one directly to the general atlas and others via different age-specific atlases - and then selecting the registration that yielded the highest ventricle overlap. Finally, as an example application of the complete pipeline, a voxelwise map of white matter hyperintensity burden was computed using only the scans with registration quality above a predefined threshold. Methods were evaluated in a single-site dataset of more than 1000 scans, as well as a multi-center dataset comprising 142 clinical scans from 12 sites. The automated ventricle segmentation reached a Dice coefficient with manual annotations of 0.89 in the single-site dataset, and 0.83 in the multi-center dataset. Registration via age-specific atlases could improve ventricle overlap compared to a direct registration to the general atlas (Dice similarity coefficient increase up to 0.15). Experiments also showed that selecting scans with the registration quality assessment method could improve the quality of average maps of white matter hyperintensity burden, instead of using all scans for the computation of the white matter hyperintensity map. In this work, we demonstrated the utility of an automated tool for assessing image registration quality in clinical scans. This image quality assessment step could ultimately assist in the translation of automated neuroimaging pipelines to the clinic.

White matter hyperintensities of presumed vascular origin (WMH) are a prevalent form of cerebral small-vessel disease and an important risk factor for post-stroke cognitive dysfunction. Despite this prevalence, it is not well understood how WMH contributes to post-stroke cognitive dysfunction. Preliminary findings suggest that increasing WMH volume is associated with total hippocampal volume in chronic stroke patients. The hippocampus, however, is a complex structure with distinct subfields that have varying roles in the function of the hippocampal circuitry and unique anatomical projections to different brain regions. For these reasons, an investigation into the relationship between WMH and hippocampal subfield volume may further delineate how WMH predispose to post-stroke cognitive dysfunction. In a prospective study of acute ischemic stroke patients with moderate/severe WMH burden, we assessed the relationship between quantitative WMH burden and hippocampal subfield volumes. Patients underwent a 3T MRI brain within 2–5 days of stroke onset. Total WMH volume was calculated in a semi-automated manner. Mean cortical thickness and hippocampal volumes were measured in the contralesional hemisphere. Total and subfield hippocampal volumes were measured using an automated, high-resolution, ex vivo computational atlas. Linear regression analyses were performed for predictors of total and subfield hippocampal volumes. Forty patients with acute ischemic stroke and moderate/severe white matter hyperintensity burden were included in this analysis. Median WMH volume was 9.0 cm3. Adjusting for intracranial volume and stroke laterality, age (β = −3.7, P < 0.001), hypertension (β = −44.7, P = 0.04), WMH volume (β = −0.89, P = 0.049), and mean cortical thickness (β = 286.2, P = 0.006) were associated with total hippocampal volume. In multivariable analysis, age (β = −3.3, P < 0.001) and cortical thickness (β = 205.2, P = 0.028) remained independently associated with total hippocampal volume. In linear regression for predictors of hippocampal subfield volume, increasing WMH volume was associated with decreased hippocampal-amygdala transition area volume (β = −0.04, P = 0.001). These finding suggest that in ischemic stroke patients, increased WMH burden is associated with selective hippocampal subfield degeneration in the hippocampal-amygdala transition area.

BackgroundSelective serotonin reuptake inhibitors (SSRIs) have been implicated in contributing to recovery after acute ischaemic stroke. In particular, poststroke initiation of an SSRI has been demonstrated to improve motor recovery. The role of prestroke SSRI use on functional outcomes and stroke recovery is less clear. We aimed to examine the effect of prestroke SSRI use on metrics of hospitalisation and functional recovery.MethodsWe included 4968 consecutive patients from January 2006 to June 2015 in our local Get With The Guidelines-Stroke registry in whom a preadmission drug list could be extracted from an administrative research data registry. Univariate and multivariate analyses were performed to identify predictors of functional outcomes.ResultsOn univariate analysis, among 4698 ischaemic strokes (740 SSRI users and 3948 non-users), SSRI use before acute ischaemic stroke did not impact the National Institutes of Health Stroke Scale (NIHSS) admission score, length of stay or rate of symptomatic haemorrhage. Patients using SSRIs prior to their stroke were more likely to present with weakness (57% vs 47.3%; PConclusionsSSRI use preceding an acute ischaemic stroke is associated with lower rates of discharge to home despite no significant increase in length of stay or NIHSS score.

We present the case of a 63-year-old woman with a glioblastoma multiforme on immunosuppressive steroid doses who developed lethargy and fever. We review the differential diagnosis and emphasize the importance of reframing the case when the clinical course differs from expectation. Once the diagnosis is evident, we discuss the incidence and clinical course in different patient populations.

Acute ischemic stroke represents a major cause of long-term adult disability. Accurate prognostication of post-stroke functional outcomes is invaluable in guiding patient care, targeting early rehabilitation efforts, selecting patients for clinical research, and conveying realistic expectations to families. The involvement of specific brain regions by acute ischemia can alter post-stroke recovery potential. Understanding the influences of infarct topography on neurologic outcomes holds significant promise in prognosis of functional recovery. In this review, we discuss the recent evidence of the contribution of infarct location to patient management decisions and functional outcomes after acute ischemic stroke.

Background and Purpose— We evaluated deep learning algorithms’ segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods— Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms’ performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated. Results— The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (ρ=0.92; P 3 (0.9–16.6 cm 3 ). Patients with small artery occlusion stroke subtype had smaller lesion volumes ( P Conclusions— Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.

Background and purposeFunctional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor long-term functional outcomes after ischaemic stroke. The aim of the study is to characterise sex-specific differences in microvascular integrity in individuals with acute ischaemic stroke.MethodsA retrospective analysis of subjects with acute ischaemic stroke and brain MRI with diffusion-weighted (DWI) and dynamic-susceptibility contrast-enhanced (DSC) perfusion-weighted imaging obtained within 9 hours of last known well was performed. In the hemisphere contralateral to the acute infarct, normal-appearing white matter (NAWM) microvascular integrity was measured using the K2 coefficient and apparent diffusion coefficient (ADC) values. Regression analyses for predictors of K2 coefficient, DWI volume and good outcome (90-day modified Rankin scale (mRS) score Results105 men and 79 women met inclusion criteria for analysis. Despite no difference in age, women had increased NAWM K2 coefficient (1027.4 vs 692.7×10–6/s; p=0.006). In women, atrial fibrillation (β=583.6; p=0.04) and increasing NAWM ADC (β=4.4; p=0.02) were associated with increased NAWM K2 coefficient. In multivariable regression analysis, the K2 coefficient was an independent predictor of DWI volume in women (β=0.007; p=0.01) but not men.ConclusionsIn women with acute ischaemic stroke, increased NAWM K2 coefficient is associated with increased infarct volume and chronic white matter structural integrity. Prospective studies investigating sex-specific differences in white matter microvascular integrity are needed.

PurposeWhite matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke (AIS).Materials and MethodsWe created a novel age-appropriate high-resolution brain template and anatomically delineated the cerebral vascular territories. We used WMH masks derived from the clinical T2 FLAIR MRI scans and spatial normalization of the template to discriminate between WMH volume within each subject’s anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories. Linear regression modeling including age, sex, common vascular risk factors, and TOAST stroke subtypes was used to assess for spatial specificity of WMH volume (WMHv) in a cohort of 882 AIS patients.ResultsMean age of this cohort was 65.23±14.79 years, 61.7% were male, 63.6% were hypertensive, 35.8% never smoked. Mean WMHv was 11.58c +/-13.49 cc. There were significant differences in territory-specific, relative to global, WMH burden. In contrast to PCA territory, age (0.018±0.002, pConclusionsOur data establish the spatial specificity of WMH distribution in relation to vascular territory and risk factor exposure in AIS patients and offer new insights into the underlying pathology.

Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffusion tensor imaging within 12 h and at day 3–5 post stroke. Early neurological outcomes were measured as the change in NIH Stroke Scale score from admission to day 3–5 post stroke. Target mismatch profile, percent mismatch lost, infarct growth, and rates of good perfusion were measured to assess ischemic tissue outcomes. NAWM mean diffusivity was significantly lower in the group with early neurological improvement (ENI, 0.79 vs. 0.82 × 10−3, mm2/s; P = 0.02). In multivariable logistic regression, NAWM mean diffusivity was an independent radiographic predictor of ENI (β = − 17.6, P = 0.037). Median infarct growth was 118% (IQR 26.8–221.9%) despite good reperfusion being observed in 65.6% of the cohort. NAWM and WMH diffusivity metrics were not associated with target mismatch profile, percent mismatch lost, or infarct growth. Our results suggest that, in AIS patients, white matter structural integrity is associated with poor early neurological outcomes independent of ischemic tissue outcomes.

Despite the proven efficacy of intravenous alteplase or endovascular thrombectomy for the treatment of patients with acute ischemic stroke, only a minority receive these treatments. This low treatment rate is due in large part to delay in hospital arrival or uncertainty as to the exact time of onset of ischemic stroke, which renders patients outside the current guideline-recommended window of eligibility for receiving these therapeutics. However, recent pivotal clinical trials of late window thrombectomy now force us to rethink the value of a simplistic chronological formulation that “time is brain.” We must recognize a more nuanced concept that the rate of tissue death as a function of time is not invariant, that still salvageable tissue at risk of infarction may be present up to 24 hour after last known well, and that those patients may strongly benefit from reperfusion. Multiple studies have sought to address this clinical dilemma using neuroimaging methods to identify a radiographic time-stamp of stroke onset or evidence of salvageable ischemic tissue and thereby increase the number of patients eligible for reperfusion therapies. In this review, we provide a critical analysis of the current state of neuroimaging techniques to select patients with unwitnessed stroke for revascularization therapies and speculate on the future direction of this clinically relevant area of stroke research.

The geographic proximity to a primary stroke center is highly variable and region dependent.1 Telestroke represents 1 approach in the treatment of stroke that holds promise to overcome the barrier of patient access to expert stroke care in areas underserved by neurologists and to increase utilization of efficacious thrombolytic therapies.2,3 At our institution, we have witnessed multiple fellows who graduate from our Vascular Neurology and Neurocritical Care Fellowships apply the principles acquired during their training to develop and implement a telestroke program at the institution where they join as junior faculty. Newly minted vascular neurologists may find the following approaches helpful. The start-up and implementation of a new telestroke program can seem daunting. One of the first steps should be to obtain support from hospital leadership for building your program in the form of resources and financial support given the relatively high start-up cost. As a foundation, endorsement of the initiative should be acquired from the hospital departments that are most deeply invested in offering such a program including the Departments of Neurology, Radiology, and Neurosurgery, and less often Anesthesia, Emergency Medicine, or others. When negotiating hospital support it may be useful to emphasize that the start-up costs can be offset by fee-for-service contracts with the spokes, revenue from transfers of patients who require a higher level of care, and yearly cost savings within the network. Additional funding can also be obtained in the form of grants at the federal (eg, USDA or NIH), state, or foundation levels to supplement the budget. Once approval and interest have been identified, the communication of the goals and objectives of the telestroke program with the hospital president or their designee is essential for ensuring alignment with the hospital’s broader initiatives. Obtaining the support of these individuals will be especially …

Background: Advanced diffusion imaging approaches that model intracellular and extracellular diffusion components such as neurite orientation dispersion and density imaging (NODDI) may provide additional insight into evolution of acute ischemic stroke (AIS) injury over standard diffusion tensor imaging approaches (DTI). Methods: NODDI was acquired at discharge in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Follow-up (FU) infarct volumes were drawn on discharge FLAIR. MD, AD, RD, FA, MK, AK, RK, OD and ND values were compared (1-way ANOVA) in infarct core (abnormal acute DWI), Growth (normal acute DWI, abnormal FU) and normal contralateral gray matter (nGM) and white matter (nWM). Results: Patient characteristics were: mean±SD age 69±10 y, median [IQR] initial NIH SS score 6 [3-11], time-to-acute MRI 7.3±5.3 h, time-to-FU MRI 2.8±1.2 days, acute DWI lesion 3.1 [0.5-18.8] cm 3 , FU lesion 8.1 [1.2-45.4] cm 3 and 61% men. Figure A shows examples of maps from a single subject. Core and growth values differed significantly (P Discussion: Increased OD is expected with tissue infarction due to loss of structural integrity. In contrast, increased ND in the subacute time-frame is paradoxical. One possible mechanism could be that hyperacute ischemia-induced cellular swelling increases tortuosity of water diffusion paths, imposing direction-dependent restrictions upon diffusion, increasing intracellular and extracellular diffusion.

Prediction of functional outcome after stroke based on initial presentation remains an open challenge, suggesting that an important aspect is missing from these prediction models. There exists the notion of a protective mechanism called brain reserve, which may be utilized to understand variations in disease outcome. In this work, we expand the concept of brain reserve (effective reserve) to improve prediction models of functional outcome after acute ischemic stroke (AIS). Consecutive AIS patients with acute brain magnetic resonance imaging (, European Commission. Framework Programme for Research and Innovation. Marie Sklodowska-Curie Actions (Grant 753896), National Institute of Neurological and Communicative Disorders and Stroke (Grant K23NS064052), National Institute of Neurological and Communicative Disorders and Stroke (Grant R01NS082285), National Institute of Neurological and Communicative Disorders and Stroke (Grant R01NS086905)

Background and Purpose— Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. Methods— We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. Results— Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P =0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P =0.04), and lower rate of tobacco use (21.1% versus 35.9%; P =0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score P =0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. Conclusions— Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism.

Leukoaraiosis, a radiographic marker of cerebral small vessel disease detected on T2-weighted brain magnetic resonance imaging (MRI) as white matter hyperintensity (WMH), is a key contributor to the risk and severity of acute cerebral ischemia. Prior investigations have emphasized the pathophysiology of WMH development and progression; however, more recently, an association between WMH burden and functional outcomes after stroke has emerged. There is growing evidence that WMH represents macroscopic injury to the white matter and that the extent of WMH burden on MRI influences functional recovery in multiple domains following acute ischemic stroke (AIS). In this review, we discuss the current understanding of WMH pathogenesis and its impact on AIS and functional recovery.

Objective:To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS).Methods:Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses.Results:Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1–8), and median normalized WMHv was 6.19 cm3 (IQR 3.0–12.6 cm3). Admission stroke severity (β = 0.16, p < 0.0001) and small vessel stroke subtype (β = −1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (β = −9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv.Conclusions:FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.

BACKGROUND: The extent to which omega-3 fatty acid status is related to risk for death from any cause and for incident cardiovascular disease (CVD) remains controversial. OBJECTIVE: To examine these associations in the Framingham Heart Study. DESIGN: Prospective and observational. SETTING: Framingham Heart Study Offspring cohort. MEASUREMENTS: The exposure marker was red blood cell levels of eicosapentaenoic and docosahexaenoic acids (the Omega-3 Index) measured at baseline. Outcomes included mortality (total, CVD, cancer, and other) and total CVD events in participants free of CVD at baseline. Follow-up was for a median of 7.3 years. Cox proportional hazards models were adjusted for 18 variables (demographic, clinical status, therapeutic, and CVD risk factors). RESULTS: Among the 2500 participants (mean age 66 years, 54% women), there were 350 deaths (58 from CVD, 146 from cancer, 128 from other known causes, and 18 from unknown causes). There were 245 CVD events. In multivariable-adjusted analyses, a higher Omega-3 Index was associated with significantly lower risks (P-values for trends across quintiles) for total mortality (P = .02), for non-CVD and non-cancer mortality (P = .009), and for total CVD events (P = .008). Those in the highest (>6.8%) compared to those in the lowest Omega-3 Index quintiles (

ObjectiveTo determine whether the rich-club organization, essential for information transport in the human connectome, is an important biomarker of functional outcome after acute ischemic stroke (AIS).MethodsConsecutive AIS patients (N=344) with acute brain magnetic resonance imaging (MRI) (ResultsOf 344 patients (median age 65, inter-quartile range 54-76 years) with a median DWI lesion volume (DWIv) of 3cc, 64% were male. We established that an increase in number of rich-club regions affected by a stroke increases the odds of poor stroke outcome, measured by NIHSS (OR: 1.77, 95%CI 1.41-2.21) and mRS (OR: 1.38, 95%CI 1.11-1.73). Additionally, we demonstrated that the OR exceeds traditional markers, such as DWIv (ORNIHSS 1.08, 95%CI 1.06-1.11; ORmRs 1.05, 95%CI 1.03-1.07) and age (ORNIHSS 1.03, 95%CI 1.01-1.05; ORmRs 1.05, 95%CI 1.03-1.07).ConclusionIn this proof-of-concept study, the number of rich-club nodes affected by a stroke lesion presents a translational biomarker of stroke outcome, which can be readily assessed using standard clinical AIS imaging protocols and considered in functional outcome prediction models beyond traditional factors.