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Background and Aims: The association between white matter abnormalities (WMA) and cognitive decline previously reported in poststroke patients has been mainly documented using visual scales. However, automated segmentation of WMA provides a precise determination of the volume of WMA. Nonetheless, it is rarely used in the stroke population and its potential advantage over visual scales is still unsettled. The objective of this study was to examine whether automated segmentation of WMA provides a better account than the visual Fazekas and Wahlund scales of the decline in executive functions and processing speed in stroke patients., Methods: The analyses were conducted on the 358 patients of the GRECogVASC cohort with an MRI performed at six months poststroke in the Amiens center. WMA were visually analyzed using the Fazekas (subcortical abnormalities) and Wahlund scales. Segmentation was performed using LST (3.0.3). Following preliminary studies to determine the optimal segmentation threshold, we examined the relationship between cognitive status and WMA volume computed at each threshold using receiver operating characteristic (ROC) curves. Finally, we assessed the ability of both Fazekas and Wahlund visual scores and WMA volume to account for cognitive scores by using a bivariate Pearson correlation analysis, comparing correlation coefficients with the Fisher transformation and repeating correlation analysis after adjustment for the lesion volume., Results: Increasing the threshold led to an underestimation of WMA (P=0.0001) (significant for a threshold ≥0.2) and an improvement in correct rejection of signal changes in the stroke cavity (P=0.02) (significant for a threshold ≤0.5), susceptibility artifacts (P=0.002) (significant for a threshold ≤0.6), and corticospinal degeneration (P=0.03) (significant for a threshold ≤0.5). WMA volume decreased with increasing threshold (P=0.0001). Areas under the curve (AUC) did not differ according to the threshold (processing speed: P=0.85, executive cognitive functions: P=0.7). Correlation coefficients between cognitive scores and WMA were higher for WMA volume than the Fazekas (processing speed: Z=-3.442, P=0.001; executive functions: Z=-2.751, P=0.006) and Wahlund scores (processing speed: Z=-3.615, P=0.0001; executive functions: Z=-2.769, P=0.006). Adjustment for lesion volume did not alter the correlations with WMA volume (processing speed: r=-0.327 [95%CI: -0.416; -0.223], P=0.0001; executive functions: r=-0.262 [95%CI: -0.363; -0.150], P=0.0001)., Conclusion: This study shows that WMA volume assessed by automated segmentation provides a better account of cognitive disorders than visual analysis. This should favor its wider use to refine imaging determinants of poststroke cognitive disorders., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: The few voxel-wise lesion-symptom mapping (VLSM) studies aimed at identifying the anatomy of executive function are limited by the absence of a model and by small populations. Using Trail Making Test (TMT) and verbal fluency and a model of their architectures, our objective was to identify the key structures underlying two major executive processes, set-shifting and strategic word search., Methods: We applied a validated VLSM analysis to harmonized cognitive and imaging data from 2009 ischemic stroke patients as a part of the Meta VCI Map consortium. All contrast analyses used an adjusted threshold with 2000 Freedman-Lane permutations (p ≤ 0.05)., Results: The TMT parts A and B were associated with structures involved in visual-spatial processing, the motor system, the frontal lobes, and their subcortical connections. Set-shifting depended on the left dorsomedial frontal region. Both semantic and phonemic fluency tests depended on verbal output abilities and processing speed with similar slopes in different languages. The strategic search process depended on Broca's area, F2 and related tracts, temporal and deep regions. Lastly, the lesion map of set-shifting did not overlap with those of strategic word search processes., Interpretation: Our results identify the anatomical substrates of two main executive processes, revealing that they represent only a specific subpart of previously reported structures. Finally, our results indicate that executive functions depend on several specific, anatomically separable executive processes mainly operating in various parts of the frontal lobes., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cerebrovascular accidents (CVAs) in dogs are diagnosed using magnetic resonance imaging (MRI). This modality is sometimes unavailable, and CVAs can resemble other lesions on MRI. D-dimer concentration and thromboelastography (TEG) are utilized in human medicine in addition to diagnostic imaging to support diagnosis of CVAs, but their use in veterinary patients has not been assessed., Objective: Assess utility of blood D-dimer concentration and TEG in supporting the imaging diagnosis of CVAs in dogs., Animals: Sixty-eight client-owned dogs with neurologic signs that had brain MRI and D-dimer concentration or TEG performed., Methods: Multicenter, retrospective study. The incidence of abnormal D-dimer concentration or TEG was compared between patients with MRI evidence of CVA and a control population. Analysis methods included Fisher's exact test or Chi-squared test for association and comparison of independent proportions., Results: Neither D-dimer concentration nor TEG was significantly associated with a CVA (P = .38 and .2, respectively). D-dimer testing was performed in a low-risk population and showed low sensitivity (30.8%; 95% confidence interval [CI], 10%-61%) and high specificity (86.4%; 95% CI, 64%-96%) for CVA diagnosis. Thromboelastography was performed in a high-risk population and showed moderate sensitivity (64.3%; 95% CI, 44%-81%) and specificity (66.7%; 95% CI, 24%-94%) for CVA diagnosis. Abnormal D-dimer concentration or TEG were not helpful in differentiating hemorrhagic from ischemic stroke (P = .43 and .41, respectively)., Conclusions: Although blood D-dimer concentration or TEG alone are not diagnostic of CVAs in dogs, a positive D-dimer result supports additional testing for CVA., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Significant advances have been made in our understanding of the endolysosomal cycle. Disruption of this cycle leads to cell death. The objective of this study aims to investigate the role of disrupted endolysosomal cycle in brain ischemia-reperfusion injury., Methods: A total of 57 mice were randomly assigned into four experimental groups: (i) wildtype (wt) sham control; (ii) wt middle cerebral artery occlusion (MCAO); (iii) cathepsin B (CTSB) knockout (KO) sham control; and (iv) CTSB KO MCAO. Mice were subjected either to 0 min (sham) or 40 min of MCAO, followed by reperfusion for 1 or 7 days. Physical and behavioral examinations were conducted in the 7-day reperfusion group for 7 consecutive days after MCAO. Confocal microscopy was used to assess the levels, redistributions, and co-localizations of key endolysosomal cycle-related proteins. Histopathology was examined by light microscopy., Results: Confocal microscopy revealed a significant accumulation of CTSB in post-ischemic penumbral neurons relative to those in the sham group. In addition, N-ethylmaleimide sensitive factor ATPase (NSF) was irreversibly depleted in these neurons. Furthermore, CTSB-immunostained structures were enlarged and diffusely distributed in both the cytoplasm and extracellular space, indicating the release of CTSB from post-ischemic neurons. Compared to wt mice, CTSB KO mice showed a significant decrease in hippocampal injury area, a significant increase in the number of survival neurons in the striatal core area, and a significant improvement in physical and functional performance in post-MCAO mice., Conclusion: Brain ischemia leads to a cascade of events leading to inactivation of NSF, disruption of the endolysosomal cycle, endolysosomal structural buildup and damage, and the release of CTSB, eventually resulting in brain ischemia reperfusion injury. CTSB KO in mice protected the brain from ischemia-reperfusion injury., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans., Methods: We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00-22:59) and nighttime (23:00-06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status., Results: Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2-9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4-3.5; P <0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate ( P <0.05)., Conclusions: Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow., Competing Interests: Disclosures Dr Henon received speaker fees from Sanofi Aventis. Dr Heit reports consulting fees from Medtronic and MicroVention, and he is a member of the medical and scientific advisory board for iSchemaView. Dr Olivot reports consultant services for Acticor, Abbvie, Boehringer-Ingelheim, Pfizer, Bristol-Myers Squibb, and Medtronic. Dr Albers reports stock holdings in iSchemaView; compensation from Biogen, iSchemaView, and Genentech for consultant services. The other authors report no conflicts.

Purpose: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows., Methods: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study., Results: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately., Conclusion: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Volumetric accuracy of using computed tomography perfusion (CTP) to estimate the post-treatment infarct in stroke patients with successful recanalization after mechanical thrombectomy (MT) has been studied a lot, however the spatial accuracy and its influence factors has not been fully investigated., Methods: This retrospective study reviewed the data from consecutive anterior large vessel occlusion (LVO) patients who had baseline CTP, successful recanalization after MT, and post-treatment diffusion-weighed imaging (DWI). Ischemic core on baseline CTP was estimated using relative cerebral blood flood (CBF) of < 30%. The infarct area was outlined manually on post-treatment DWI, and registered to CTP. Spatial agreement was assessed using the Dice similarity coefficient (DSC) and average Hausdorff distance. According to the median DSC, the study population was dichotomized into high and low Dice groups. Univariable and multivariable regression analyses were used to determine the factors independently associated with the spatial agreement., Results: In 72 included patients, the median DSC was 0.26, and the median average Hausdorff distance was 1.77 mm. High Dice group showed significantly higher median ischemic core volume on baseline CTP (33.90 mL vs 3.40 mL, P < 0.001), lower proportion of moderate or severe leukoaraiosis [27.78% vs 52.78%, P = 0.031], and higher median infarct volume on follow-up DWI (51.17 mL vs 9.42 mL, P < 0.001) than low Dice group. Ischemic core volume on baseline CTP was found to be independently associated with the spatial agreement (OR, 1.092; P < 0.001)., Conclusions: CTP could help to spatially locate the post-treatment infarct in anterior LVO patients who achieving successful recanalization after MT. Ischemic core volume on baseline CTP was independently associated with the spatial agreement., (© 2023. The Author(s).)

Objectives: Cerebral perfusion imaging may be used to identify the ischemic core in acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation; however, perfusion parameters that predict the ischemic core in AIS patients with a basilar artery occlusion (BAO) are poorly described. We determined which cerebral perfusion parameters best predict the ischemic core after successful endovascular thrombectomy (EVT) in BAO patients., Materials and Methods: We performed multicenter retrospective study of BAO patients with perfusion imaging before EVT and a DWI after successful EVT. The ischemic core was defined as regions on CTP, which were co-registered to the final DWI infarct. Various time-to-maximum (Tmax) and cerebral blood flow (CBF) thresholds were compared to final infarct volume to determine the best predictor of the final infarct., Results: 28 patients were included in the analysis for this study. Tmax >8s (r 2 : 0.56; median absolute error, 16.0 mL) and Tmax >10s (r 2 : 0.73; median absolute error, 11.3 mL) showed the strongest agreement between the pre-EVT CTP study and the final DWI. CBF <38% (r 2 : 0.76; median absolute error, 8.2 mL) and CBF <34% (r 2 : 0.76; median absolute error, 9.1 mL) also correlated well with final infarct volume on DWI., Conclusions: Pre-EVT CT perfusion imaging is useful to predict the final ischemic infarct volume in BAO patients. Tmax >8s and Tmax >10s were the strongest predictors of the post-EVT final infarct volume., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly., Methods: Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged <75 and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale [mRS] at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated., Results: A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged <75 years in the EVT arm (median 10.7 mL versus 23.9 mL, P <0.001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV <50 mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35-4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved., Conclusions: Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.

Background: Vertebral artery dissection (VAD) is a treatable cause of vertebrobasilar ischemic stroke and can be spontaneous or more commonly traumatic. Craniovertebral junction (CVJ) anomalies are a rare and often overlooked cause of VAD., Objective: The objective of this study was to study cases where CVJ anomaly presented as posterior circulation infarct and to conduct a relevant literature review., Materials and Methods: The medical records of seven patients who were managed for posterior circulation infarct associated with CVJ anomaly at our center from January 2009 through August 2013 were reviewed. PubMed and MEDLINE databases were also searched for similar cases, and the published case reports/series were reviewed., Results: Seven patients met our inclusion criteria and were included in the study. The mean age was 17.4 years (range: 10-35 years). All the patients were males. The most common symptoms were headache, vomiting, and gait ataxia. Slurring of speech was seen in one patient. One patient had repeated episodes of gait ataxia with left-sided weakness with complete recovery in between the episodes. One patient presented in unconscious state. Four patients complained of vertigo. The median duration of symptoms was 7 days (range: 3 days-12 months)., Conclusions: CVJ anomalies can present as posterior circulation infarct. One must evaluate all patients with posterior circulation stroke, especially young patients, for possible CVJ anomalies. Dynamic lateral cervical spine X-ray is an important tool to diagnose AAD. CVJ anomalies represent a treatable cause of VAD., Competing Interests: None

There are many neuro-imaging studies on the presence of brain lesions in the preterm infant, using cranial ultrasound (cUS) and/or term equivalent age MRI (TEA-MRI). These studies however tend to focus on germinal matrix-intraventricular hemorrhage (GMH-IVH) and white matter injury. Data about perinatal arterial ischemic stroke (PAIS) or cerebral sinovenous thrombosis (CSVT) in the preterm infant are very limited. In fact, several large cohort studies on neuro-imaging in preterm infants do not even mention neonatal stroke. 1-4 Most studies about PAIS exclude preterm infants. 5 The aim of this review was to provide an update on neonatal stroke in the preterm infant, with a focus on neuro-imaging findings., Competing Interests: Declaration of Competing Interest The authors have no potential conflicts to disclose, (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The awareness of the "Cerebellar Cognitive Affective Syndrome" (CCAS) as a clinical entity is emerging. The CCAS is characterized by impaired executive functions, linguistic skills, visuospatial cognition and personality change. Here we report a 56-year-old, male teacher who developed acute psychomotor retardation, low energy level, infrequent speech, and mild cognitive decline. Two months before admission, he was initially diagnosed as depression, and later misdiagnosed as encephalitis, which misled him to receive high-dose intravenous steroids and antimicrobial drugs. The Brain MRI revealed multiple posterior cerebellar infarcts predominantly at the lobules VII and VIII. The standard neuropsychological tests were unremarkable; however, the CCAS Scale confirmed the diagnosis. The treatment of depression and secondary prevention of stroke was conducted. In cases that present with features of cognitive and affective disorders but with mild voluntary motor or without typical cerebellar features, the role of posterior cerebellar and vermian pathologies should be considered. The CCAS Scale is an appropriate screening tool to detect these patients and provides a framework for evidence-based treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A singleton fetus was referred to fetal magnetic resonance imaging (MRI) at 25 weeks due to mild ventriculomegaly and an abnormal fetal echocardiogram showing cardiomegaly, right ventricular hypertrophy and tricuspid insufficiency. Patchy areas of ischemic infarction, extensive subacute and chronic hemorrhage not respecting vascular territories, encephaloclastic cysts and closed lip schizencephaly were identified. Cataract was detected postnatally. The anomalies were caused by a pathogenic mutation (c.353 G>A; p.G118D) in the COL4A1 gene. The phenotype seen in this case, i.e. small vessel cerebral disease with or without ocular anomalies caused by COL4A1 mutations, is likely an underrecognized cause of perinatal stroke. The pattern of abnormalities reported herein should prompt strong consideration for diagnosis and molecular testing.

Introduction: The coronavirus disease (COVID-19) pandemic has changed routine clinical practice worldwide with major impacts on the provision of care and treatment for stroke patients., Methods: This retrospective observational study included all patients admitted to the Royal Stoke University Hospital in Stoke-on-Trent, UK, with a stroke or transient ischaemic attack between March 15th and April 14th, 2020 (COVID). Patient demographics, characteristics of the stroke, treatment details and logistics were compared with patients admitted in the corresponding weeks in the year before (2019)., Results: There was a 39.5% (n = 101 vs n = 167) reduction in admissions in the COVID cohort compared with 2019 with more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) 7 vs 4, p = 0.02), and fewer strokes with no visible acute pathology (21.8 vs 37.1%, p = 0.01) on computed tomography. There was no statistically significant difference in the rates of thrombolysis (10.9 vs 13.2%, p = 0.72) and/or thrombectomy (5.9 vs 4.8%, p = 0.90) and no statistically significant difference in time from stroke onset to arrival at hospital (734 vs 576 min, p = 0.34), door-to-needle time for thrombolysis (54 vs 64 min, p = 0.43) and door-to-thrombectomy time (181 vs 445 min, p = 0.72). Thirty-day mortality was not significantly higher in the COVID year (10.9 vs 8.9%, p = 0.77). None of the 7 stroke patients infected with COVID-19 died., Conclusions: During the COVID-19 pandemic, the number of stroke admissions fell, and stroke severity increased. There was no statistically significant change in the delivery of thrombolysis and mechanical thrombectomy and no increase in mortality.

Purpose: Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[ 18 F]fluoro-D-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice., Procedures: The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99m Tc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins., Results: The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice., Conclusions: Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.

Background: Childhood stroke is rare, and diagnosis is frequently delayed. The use of pediatric stroke teams has the potential to decrease time to neurology evaluation and imaging, hastening appropriate diagnosis and treatment for acute neurologic presentations in children., Methods: We performed a retrospective analysis of our institutional pediatric stroke or "brain attack" team (pedsBAT) activations from October 2014 to July 2017. Clinical characteristics and timing parameters were compared between pedsBAT activations in the inpatient vs emergency department (ED) / outpatient settings as well as between pediatric and adult BAT activations in the same time period., Results: We identified 120 pedsBAT activations (75% in the ED/outpatient setting) during the study time period. Inpatient pedsBAT activations were more likely than outpatient activations to have heart disease as a risk factor for ischemic stroke and presented more frequently with altered mental status, but there were no differences in the proportion of cerebrovascular diagnoses or timing parameters between the 2 groups. When compared with adult BAT activations, outpatient pedsBAT activations had a longer time from symptom discovery to arrival at the ED, and inpatient pedsBAT activations had longer time from symptom discovery to BAT activation., Conclusions: Compared with adults, the interval leading up to stroke team activation was longer in children, suggesting delays in symptom recognition. Future interventions should be aimed at reducing these delays in presentation to care and stroke alert activation in pediatric patients.

Ischemic stroke causes immediate cell death within the infarct core, whereas cells in the surrounding penumbra region are damaged but can be salvaged. Rapid restoration of blood flow can rescue these cells in the first few hours post-stroke. It remains unclear how long cells within the penumbra region can survive. To address this, we compared the acute cellular response within the ischemic core versus the penumbra region following an Endothelin-1-induced focal ischemic stroke in mice. We used vascular labelling to distinguish the three regions of blood perfusion: the non-perfused core; the hypo-perfused penumbra; and the perfused region. Within 4 hr post-stroke ~80% of neurons died in the non-perfused core, while 40% of neurons died in the hypo-perfused region. From 4 to 24 hr post-stroke, surviving neurons within the hypo-perfused region underwent extensive dendritic and axonal degeneration. Breakdown of the blood brain barrier, microglia activation, monocyte/neutrophil infiltration and astrogliosis, however, was not observed until 24 hr post-stroke. The cellular response within the hypo-perfused region was distinct from the non-perfused core. The core was comprised primarily of infiltrating peripheral monocytes and leukocytes, whereas the hypo-perfused region contained activated microglia and astrocytes. This study shows that small, localized ischemic strokes exhibit altered breakdown of the BBB in comparison with larger strokes. Furthermore, the massive degeneration of neuronal processes within the penumbra region suggests that the timeline to salvage surviving neurons is limited. In summary, the findings from this study reinforce the urgent need for therapeutic strategies targeting the acute hours post-stroke., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Pituitary adenomas are rare in children, and often present with symptoms of headache, nausea or emesis, visual disturbance, or hormonal hypersecretion. With large tumors, mass effect from the lesion can lead to severe endocrinopathy and compression of intracranial neurovascular structures. In this case report, we describe an unusual presentation of an ischemic stroke in the territory of the right middle cerebral artery resulting from a prolactin-secreting macroadenoma. The patient's primary symptoms were headache, left facial droop, and left hemibody weakness. She was successfully managed with cabergoline, a dopamine agonist, with a reduction in the size of the tumor and normalization of serum prolactin levels. She remained clinically stable throughout her hospitalization, and was safely discharged without surgical intervention. In her recent 2-year follow-up, her tumor and prolactin levels were stable and she had dramatic improvements in her left-sided muscle strength.

Automated wireless sensing of force dynamics during a visuomotor control task was used to rapidly assess residual motor function during finger pinch (right and left hand) and lower lip compression in a cohort of seven adult males with chronic, unilateral middle cerebral artery (MCA) stroke with infarct confirmed by anatomic magnetic resonance imaging (MRI). A matched cohort of 25 neurotypical adult males served as controls. Dependent variables were extracted from digitized records of 'ramp-and-hold' isometric contractions to target levels (0.25, 0.5, 1, and 2 Newtons) presented in a randomized block design; and included force reaction time, peak force, and dF/dt max associated with force recruitment, and end-point accuracy and variability metrics during the contraction hold-phase (mean, SD, criterion percentage 'on-target'). Maximum voluntary contraction force (MVCF) was also assessed to establish the force operating range. Results based on linear mixed modeling (LMM, adjusted for age and handedness) revealed significant patterns of dissolution in fine force regulation among MCA stroke participants, especially for the contralesional thumb-index finger followed by the ipsilesional digits, and the lower lip. For example, the contralesional thumb-index finger manifest increased reaction time, and greater overshoot in peak force during recruitment compared to controls. Impaired force regulation among MCA stroke participants during the contraction hold-phase was associated with significant increases in force SD, and dramatic reduction in the ability to regulate force output within prescribed target force window (±5% of target). Impaired force regulation during contraction hold-phase was greatest in the contralesional hand muscle group, followed by significant dissolution in ipsilateral digits, with smaller effects found for lower lip. These changes in fine force dynamics were accompanied by large reductions in the MVCF with the LMM marginal means for contralesional and ipsilesional pinch forces at just 34.77% (15.93 N vs. 45.82 N) and 66.45% (27.23 N vs. 40.98 N) of control performance, respectively. Biomechanical measures of fine force and MVCF performance in adult stroke survivors provide valuable information on the profile of residual motor function which can help inform clinical treatment strategies and quantitatively monitor the efficacy of rehabilitation or neuroprotection strategies.

Multimodal magnetic resonance imaging (MRI) has emerged as a promising tool for diagnosing ischemic stroke and for determining treatment strategies in the acute phase. The detection and quantification of the penumbra and the infarct core regions aid the assessment of the potential risks and benefits of thrombolysis by providing information on salvageable tissue or ischemic lesion age. In this study, we proposed a fully automated and real-time algorithm to compute parameter maps of perfusion-weighted images (PWIs) and to identify an infarct core from diffusion-weighted images (DWIs). DWI and PWI were obtained using a 1.5 Tesla MRI scanner for 15 patients with acute ischemic stroke. Parameter maps of PWI were computed using restricted gamma-variate curve fitting and Fourier-based deconvolution. The ischemic penumbra was identified using time-to-maximum (T max ) > 6 s as the mutual optimal threshold, while the infarct core was segmented using an adaptive thresholding on DWI. When the penumbra on PWI was compared with that generated using commercial software Pearson's linear correlation coefficient between penumbra volumes was 0.601 (p = 0.030), and the Dice coefficient was 0.51 ± 0.15. The infarct core on DWI was compared with the manually segmented gold standard. Dice coefficient between the manually drawn and automated segmented infarct cores was 0.62 ± 0.18. The processing times for PWI and DWI were 222.9 ± 16.4 and 53.4 ± 4.8 s, respectively. In conclusion, we demonstrate a fully automated and real-time algorithm to segment the penumbra and the infarct core regions based on PWI and DWI.

Background and Purpose: CT Perfusion technique (CTP) is a quantitative, easily performed, accepted and reliable method for detection of ischemic brain changes. Based on calculated parameters, the size of ischemic penumbra and irreversibly damaged infarct core can be determined which helps guide treatment decisions. However, due to the dynamic nature of the CTP study, it is dose intensive. This study determines the consequences of retrospectively reducing the number of scans in the dynamic acquisition by half on the volume of the automatically calculated infarct core (non-viable tissue) and penumbra (tissue at risk) volumes. Our hypothesis was that equivalent volumetric information could be obtained at a substantial dose savings., Materials and Methods: Fifty one consecutive patients with occlusion of M1 and/or M2 segment of the middle cerebral artery and ischemic stroke proven by follow-up MRI were included. CTP scans were first analyzed in a standard fashion and automatically generated volumes measured in milliliters were recorded in a database. A second analysis was conducted after removing every second data acquisition from the sequential CTP scans. Automatic volume measurements were repeated, recorded and compared to the initial values obtained using the full dataset., Results: The two CTP protocols were statistically equivalent pertaining to automatic infarct core volume calculation but a case-by-case analysis revealed substantial overestimation in some cases., Conclusion: Reduction of radiation exposure in CTP without objective loss of accuracy of automatically calculated infarct core volume is feasible but might lead to clinically relevant infarct core overestimation in individual cases., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Acute stroke is a leading cause of morbidity and mortality in the United States. Acute ischemic strokes have been classified according to The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, and this system aids in proper management. Nearly every patient who presents to a hospital with acute stroke symptoms has some form of emergent imaging. As such, imaging plays an important role in early diagnosis and management. This article reviews the imaging patterns of acute strokes, and how the infarct pattern and imaging characteristics can suggest an underlying cause., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ischemic stroke provokes a neuroinflammatory response and simultaneously promotes release of epinephrine and norepinephrine by the sympathetic nervous system. This increased sympathetic outflow can act on β2-adrenergic receptors expressed by immune cells such as brain-resident microglia and monocyte-derived macrophages (MDMs), but the effect on post-stroke neuroinflammation is unknown. Thus, we investigated how changes in β2-adrenergic signaling after stroke onset influence the microglia/MDM stroke response, and the specific importance of microglia/MDM β2-adrenergic receptors to post-stroke neuroinflammation., Methods: To investigate the effects of β2-adrenergic receptor manipulation on post-stroke neuroinflammation, we administered the β2-adrenergic receptor agonist clenbuterol to mice 3 h after the onset of photothrombotic stroke. We immunostained to quantify microglia/MDM numbers and proliferation and to assess morphology and activation 3 days later. We assessed stroke outcomes by measuring infarct volume and functional motor recovery and analyzed gene expression levels of neuroinflammatory molecules. Finally, we evaluated changes in cytokine expression and microglia/MDM response in brains of mice with selective knockout of the β2-adrenergic receptor from microglia and monocyte-lineage cells., Results: We report that clenbuterol treatment after stroke onset causes enlarged microglia/MDMs and impairs their proliferation, resulting in reduced numbers of these cells in the peri-infarct cortex by 1.7-fold at 3 days after stroke. These changes in microglia/MDMs were associated with increased infarct volume in clenbuterol-treated animals. In mice that had the β2-adrenergic receptor specifically knocked out of microglia/MDMs, there was no change in morphology or numbers of these cells after stroke. However, knockdown of β2-adrenergic receptors in microglia and MDMs resulted in increased expression of TNFα and IL-10 in peri-infarct tissue, while stimulation of β2-adrenergic receptors with clenbuterol had the opposite effect, suppressing TNFα and IL-10 expression., Conclusions: We identified β2-adrenergic receptor signaling as an important regulator of the neuroimmune response after ischemic stroke. Increased β2-adrenergic signaling after stroke onset generally suppressed the microglia/MDM response, reducing upregulation of both pro- and anti-inflammatory cytokines, and increasing stroke size. In contrast, diminished β2-adrenergic signaling in microglia/MDMs augmented both pro- and anti-inflammatory cytokine expression after stroke. The β2-adrenergic receptor may therefore present a therapeutic target for improving the post-stroke neuroinflammatory and repair process.

Obesity is associated with worse neurological outcomes following overt ischemic strokes. The majority of strokes however, are covert, small strokes that often evade detection. How obesity impacts the cellular response to covert strokes is unclear. Here, we used a diet-induced obesity model by feeding mice a high fat diet (HFD) and examining its impact on the behavioral and cellular responses to either an Endothelin-1-induced focal ischemic stroke or a saline injection (control). Specifically, we examined cells in regions with different levels of blood perfusion: the non-perfused core, the hypo-perfused surround and the perfused region around the infarct. We show that HFD selectively exacerbated the response to stroke but not to saline injections. Stroke affected the composition of microglia/macrophages, astrocytes and neurons within each region of perfusion. In the non-perfused core, the majority of cells were Iba-1+ microglia and macrophages. HFD resulted in a greater infiltration of CD68+ macrophages into the infarct core while CD68+ /TMEM119+ microglia were reduced. Furthermore, there was a trend towards an increased spread of the astrogliosis scar from the infarct border in the HFD condition. Within the hypo-perfused region, significantly fewer neurons survived in HFD-fed mice than Chow-fed mice, suggesting that neurons in the HFD condition have an increased vulnerability. In summary, diet-induced obesity exacerbates covert-like stroke injuries by worsening the cellular responses in the varying levels of perfusion across the infarct., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the differences among grades of recanalization on outcomes of endovascular treatment for acute anterior large vessel occlusion with small infarct core beyond the 6-hour time window., Methods: Patients beyond the 6-hour time window with Alberta Stroke Program Early Computed Tomography Score >7 were retrospectively enrolled from the endovascular treatment for acute anterior circulation ischemic stroke (ACTUAL) registry. They were divided into 3 groups according to the degree of recanalization: modified treatment in cerebral infarction (mTICI) 0-2a, 2b, and 3. We compared the differences of outcomes among groups on modified Rankin Scale score at 90 days, symptomatic intracerebral hemorrhage within 72 hours, and mortality., Results: A total of 101 patients were enrolled. Median time from onset to groin puncture was 415 minutes (interquartile range: 387-497 minutes). Favorable functional outcomes were significantly better in patients with successful recanalization than in patients with failed recanalization (mTICI 0-2a, 22.7% [5/22]; mTICI 2b, 48.0% [12/25]; and mTICI 3, 61.1% [33/54]; trend P = 0.01). Complete recanalization (mTICI 3) (odds ratio, 5.34; 95% confidence interval, 1.71-16.66; P = 0.004) was associated with good functional outcome. Mortality was different among groups at 90 days (mTICI 0-2a, 36.4% [8/22]; mTICI 2b, 0, [0/25]; P = 0.001; mTICI 0-2a, 36.4% [8/22]; mTICI 3, 9.3% [5/54]; P = 0.008; and mTICI 2b, 0, [0/25]; mTICI 3, 9.3% [5/54]; P = 0.173). There were no significant differences of symptomatic intracranial hemorrhage among groups (mTICI 0-2a, 22.7% [5/22]; mTICI 2b, 12.0% [3/25]; and mTICI 3, 9.3% [5/54]; P = 0.28)., Conclusions: For acute anterior circulation stroke patients, who were beyond the 6-hour time window, yet with small ischemic core, complete recanalization following endovascular treatment may play the most important role on clinical outcome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background/aims: Post-stroke neurocognitive disorders (post-stroke NCD) have been reported with a very variable prevalence., Methods: Based on a systematic literature search, hospital-based studies published between January 1990 and September 2015 were selected when they reported the prevalence of total, mild, and major post-stroke NCD diagnosed by using specified criteria. Factors affecting prevalence were assessed using meta-regression analysis., Results: Among the 7,440 references evaluated, 16 hospital-based studies were selected, corresponding to a total of 3,087 patients. The overall prevalence of total post-stroke NCD was 53.4% (95% CI: 46.9-59.8): 36.4% for mild post-stroke NCD (95% CI: 29-43.8) and 16.5% (95% CI: 12.1-20.8) for major post-stroke NCD. The overall prevalence was mainly influenced by the threshold score used for categorization (p = 0.0001) and, in the subgroup of studies using a conservative threshold (i.e., ≤7th percentile), by the recurrent stroke rate (p = 0.0005). The prevalence of major post-stroke NCD was mainly influenced by age (p = 0.003)., Conclusion: More than half of stroke survivors experience post-stroke NCD, corresponding to mild post-stroke NCD in two-thirds of cases and major post-stroke NCD in one-third of cases. Harmonization of stroke assessment and cognitive score thresholds is urgently needed to allow more accurate estimation of post-stroke NCD prevalence, especially mild post-stroke NCD., (© 2018 S. Karger AG, Basel.)

Pediatric arterial ischemic stroke (AIS) is an uncommon but important cause of neurologic morbidity in neonates and children, with consequences including hemiparesis, intellectual disabilities, and epilepsy. The causes of pediatric AIS are unique to those typically associated with stroke in adults. Familiarity with the risk factors for AIS in children will help with efficient diagnosis, which is unfortunately frequently delayed. Here we review the epidemiology and risk factors for AIS in neonates and children. We also outline consensus-based practices in the evaluation and management of pediatric AIS. Finally we discuss the outcomes observed in this population. While much has been learned in recent decades, many uncertainties sill persist in regard to pediatric AIS. The ongoing development of specialized centers and investigators dedicated to pediatric stroke will continue to answer such questions and improve our ability to effectively care for these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Imaging is paramount to the diagnosis and management of ischemic stroke, offering a battery of structural and functional probes of cerebrovascular physiology. The technical underpinnings of stroke imaging continue to evolve, bringing the neuroscience community increasingly closer to high-resolution, tissue-level biomarkers of brain perfusion, metabolism, and viability. The rapid expansion of neuroimaging in this domain has met with controversies, and in many respects, a lack of generalizable conclusions regarding optimized use in cerebrovascular disease. This review aims to provide the reader with the depth and scope of both established and emerging techniques, and an overview of prevailing viewpoints regarding neuroimaging in acute ischemic stroke., (Copyright © 2017 by the Congress of Neurological Surgeons.)

Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: In dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010-2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed., Results: Twenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1-10 days of hospitalisation., Conclusions: Dogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the first week following the ischaemic stroke.

Background: Stroke is the second most common cause of death worldwide. Only one treatment for acute ischemic stroke is currently available, thrombolysis with rt-PA, but it is limited in its use. Many efforts have been invested in order to find additive treatments, without success. A multitude of reasons for the translational problems from mouse experimental stroke to clinical trials probably exists, including infarct size estimations around the peak time of edema formation. Furthermore, edema is a more prominent feature of stroke in mice than in humans, because of the tendency to produce larger infarcts with more substantial edema., Purpose: This paper will give an overview of previous studies of experimental mouse stroke, and correlate survival time to peak time of edema formation. Furthermore, investigations of whether the included studies corrected the infarct measurements for edema and a comparison of correction methods will be discussed., Method: Relevant terms were searched in the National Library of Medicine PubMed database. A method for classification of infarct measurement methods was made using a naming convention., Conclusion: Our study shows that infarct size estimations are often performed around the peak time of edema, with a median of 24h. Most studies do consider edema formation, however, there is no consensus on what method to use to correct for edema. Furthermore, investigations into neuroprotective drugs should use longer survival times to ensure completion of the investigated process. Our findings indicate a need for more research in this area, and establishment of common correction methodology., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Knowledge of the typical lesion topography and volumetry is important for clinical stroke diagnosis as well as for anatomo-behavioral lesion mapping analyses. Here we used modern lesion analysis techniques to examine the naturally occurring lesion patterns caused by ischemic and by hemorrhagic infarcts in a large, representative acute stroke patient sample. Acute MR and CT imaging of 439 consecutively admitted right-hemispheric stroke patients from a well-defined catchment area suffering from ischemia (n = 367) or hemorrhage (n = 72) were normalized and mapped in reference to stereotaxic anatomical atlases. For ischemic infarcts, highest frequencies of stroke were observed in the insula, putamen, operculum and superior temporal cortex, as well as the inferior and superior occipito-frontal fascicles, superior longitudinal fascicle, uncinate fascicle, and the acoustic radiation. The maximum overlay of hemorrhages was located more posteriorly and more medially, involving posterior areas of the insula, Heschl's gyrus, and putamen. Lesion size was largest in frontal and anterior areas and lowest in subcortical and posterior areas. The large and unbiased sample of stroke patients used in the present study accumulated the different sub-patterns to identify the global topographic and volumetric pattern of right hemisphere stroke in humans.

Diagnosing behavioral variant frontotemporal dementia (bvFTD) in patients with prior history of stroke or with silent brain infarcts on neuroimaging studies can be challenging. Vascular changes in patients with bvFTD are not unusual, but bvFTD tends to be ruled out in the presence of cerebrovascular disease. We aimed to identify the clinical, cognitive, and risk factor profile of bvFTD with coexistent cerebrovascular disease (V-bvFTD). We compared demographic data, clinical diagnoses, vascular risk factors, functional status, and normalized neuropsychological z-scores between patients with V-bvFTD versus bvFTD without concomitant cerebrovascular disease (NV-bvFTD) from the National Alzheimer's Coordinating Centre database. We included 391 neuropathologically-diagnosed cases of frontotemporal lobe degeneration. We excluded patients that were diagnosed with aphasic variants of frontotemporal dementia before death. Patients with V-bvFTD (n = 62) were older at the time of onset of cognitive decline (71.6 vs. 62.5 years, p < 0.001) and death (78.7 vs. 69.6, p < 0.001), more likely to be hypertensive (75.8% vs. 45.7%, p = 0.002) and to have a history of stroke (21.2% vs. 6.1%, p = 0.007) than those with NV-bvFTD (n = 329). V-bvFTD was often underdiagnosed, affected elderly patients, and had a similar cognitive profile as NV-bvFTD despite the presence of brain infarcts. In the whole cohort, we observed enhanced cognitive performance with increasing age quintiles despite larger proportions of cerebrovascular disease pathology, likely meaning that frontotemporal lobe degeneration-related primary neurodegeneration exerts a stronger impact on cognition than cerebrovascular disease. Coexisting cerebrovascular disease should not preclude the diagnosis of bvFTD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Neuroimaging plays a key role in the initial work-up of patients with symptoms of acute stroke. Understanding the advantages and limitations of available CT and MR imaging techniques and how to use them optimally in the emergency setting is crucial for accurately making the diagnosis of acute stroke and for rapidly determining appropriate treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Levels of cerebral amyloid, presumably β-amyloid (Abeta), toxicity and the incidence of cortical and subcortical ischemia increases with age. However, little is known about the severe pathological condition and dementia that occur as a result of the comorbid occurrence of this vascular risk factor and Abeta toxicity. Clinical studies have indicated that small ischemic lesions in the striatum are particularly important in generating dementia in combination with minor amyloid lesions. These cognitive deficits are highly likely to be caused by changes in the cortex. In this study, we examined the viability and morphological changes in microglial and neuronal cells, gap junction proteins (connexin43) and neuritic/axonal retraction (Fer Kinase) in the striatum and cerebral cortex using a comorbid rat model of striatal injections of endothelin-1 (ET1) and Abeta toxicity. The results demonstrated ventricular enlargement, striatal atrophy, substantial increases in β-amyloid, ramified microglia and increases in neuritic retraction in the combined models of stroke and Abeta toxicity. Changes in connexin43 occurred equally in both groups of Abeta-treated rats, with and without focal ischemia. Although previous behavioral tests demonstrated impairment in memory and learning, the visual discrimination radial maze task did not show significant difference, suggesting the cognitive impairment in these models is not related to damage to the dorsolateral striatum. These results suggest an insight into the relationship between cortical/striatal atrophy, pathology and functional impairment., (© 2014 International Society of Neuropathology.)

Diabetes worsens functional outcome and is associated with greater hemorrhagic transformation (HT) after ischemic stroke. We have shown that diabetic Goto-Kakizaki (GK) rats develop greater HT and neurological deficit despite smaller infarcts after transient middle cerebral artery occlusion (MCAO) with the suture model. However, the impact of (1) the duration of ischemia/reperfusion (I/R); (2) the method of ischemia; and (3) acute glycemic control on neurovascular injury and functional outcome in diabetic stroke remained unanswered. Wistar and GK rats were subjected to variable MCAO by suture or embolus occlusion. A group of GK rats were treated with insulin or metformin before stroke with suture occlusion. In all groups, infarct size, edema, HT occurrence and severity, and functional outcome were measured. Infarct size at 24h was smaller in GK rats with both suture and embolic MCAO, but expanded with longer reperfusion period. Edema and HT were increased in GK rats after 90min and 3h occlusion with the suture model, but not in the embolic MCAO. Neurological deficit was greater in diabetic rats. These findings suggest that diabetes accelerates the development of HT and amplifies vascular damage in the suture model where blood flow is rapidly reestablished. Acute metformin treatment worsened the infarct size, HT, and behavior outcome, whereas insulin treatment showed a protective effect. These results suggest that the impact of ischemia/reperfusion on neurovascular injury and functional outcome especially in disease models needs to be fully characterized using different models of stroke to model the human condition., (© 2013 Published by Elsevier B.V.)

Introduction: Patients with a large vessel occlusion (LVO) stroke who are transferred to a comprehensive stroke center (CSC) for endovascular thrombectomy (EVT) often experience infarct growth. We aimed to investigate the clinical predictors of fast infarct growth and its effect on clinical outcomes. Methods: We retrospectively collected EVT data of patients with LVO transferred to our center between March 14, 2019, and June 28, 2022. The absolute rate of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) decay was defined as (ASPECTS primary CT − ASPECTS repeat CT)/elapsed hours. The ratio of relative ASPECTS deterioration was defined as (ASPECTS primary CT − ASPECTS repeat CT)/ASPECTS primary CT. In the primary analysis, the study population was dichotomized into absolute slow progressors and absolute fast progressors using the median absolute rate of ASPECTS decay. Secondary analysis was also conducted using the median relative ASPECTS deterioration ratio, and the study population was categorized into relative fast progressors and relative slow progressors. Favorable outcome was defined as a 90-day modified Rankin Scale (mRS) score ≤ 2. Results: We included 309 patients: median age 72 years (IQR 65–77); median National Institutes of Health Stroke Scale (NIHSS) 14 (IQR 11–18). The median absolute rate of ASPECTS decay was 0.42 points/hour and the median relative ASPECTS deterioration ratio was 11.1%. Overall, fast infarct growth was independently associated with worse 90-day outcome (absolute rate of ASPECTS decay: OR = 3.395; 95% CI 1.844–6.250; P < 0.001; relative ASPECTS deterioration ratio: OR = 3.754; 95% CI 2.050–6.873; P < 0.001). In multivariable analysis, fast infarct growth was independently associated with high admission NIHSS, proximal occlusions, and poor collateral status, while intravenous thrombolysis before transfer was negative with fast inter-hospital infarct growth. Conclusions: For patients with LVO stroke who are transferred from a PSC to CSC for EVT, the infarct growth rate is highly variable and is strongly associated with 90-day outcomes. Initiation of intravenous bridging therapy before transfer may limit the infarct growth during inter-hospital transfer. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease is a common cause of death and the general histopathologist will often be responsible for the post mortem examination of stroke-related death. The pathological findings vary depending on the type of stroke, its location and aetiology. The underlying pathology is variable and includes atherosclerosis, cardiogenic embolism and small vessel disease alongside many rarer causes. The adequate post mortem examination of stroke is essential to usefully inform clinical teams, coronial services and relatives and requires proper preparation, familiarity with the range of underlying pathological processes, careful gross examination and judicious use of histology. [ABSTRACT FROM AUTHOR]

BackgroundSignificant advances have been made in our understanding of the endolysosomal cycle. Disruption of this cycle leads to cell death. The objective of this study aims to investigate the role of disrupted endolysosomal cycle in brain ischemia-reperfusion injury.MethodsA total of 57 mice were randomly assigned into four experimental groups: (i) wildtype (wt) sham control; (ii) wt middle cerebral artery occlusion (MCAO); (iii) cathepsin B (CTSB) knockout (KO) sham control; and (iv) CTSB KO MCAO. Mice were subjected either to 0 min (sham) or 40 min of MCAO, followed by reperfusion for 1 or 7 days. Physical and behavioral examinations were conducted in the 7-day reperfusion group for 7 consecutive days after MCAO. Confocal microscopy was used to assess the levels, redistributions, and co-localizations of key endolysosomal cycle-related proteins. Histopathology was examined by light microscopy.ResultsConfocal microscopy revealed a significant accumulation of CTSB in post-ischemic penumbral neurons relative to those in the sham group. In addition, N-ethylmaleimide sensitive factor ATPase (NSF) was irreversibly depleted in these neurons. Furthermore, CTSB-immunostained structures were enlarged and diffusely distributed in both the cytoplasm and extracellular space, indicating the release of CTSB from post-ischemic neurons. Compared to wt mice, CTSB KO mice showed a significant decrease in hippocampal injury area, a significant increase in the number of survival neurons in the striatal core area, and a significant improvement in physical and functional performance in post-MCAO mice.ConclusionBrain ischemia leads to a cascade of events leading to inactivation of NSF, disruption of the endolysosomal cycle, endolysosomal structural buildup and damage, and the release of CTSB, eventually resulting in brain ischemia reperfusion injury. CTSB KO in mice protected the brain from ischemia-reperfusion injury.

Objectives: Cerebellar infarction is an ischemic or hemorrhagic type episode involving the three main cerebellar arteries. An infarction in each of these arteries causes different but common symptoms, requiring a particularly important contribution of physiotherapy to its treatment. This overview aimed to investigate the effectiveness of physiotherapy programs on the symptoms of patients with cerebellar infarction. Methods: A literature search was performed using eight databases and the keywords, including physiotherapy, physical therapy, rehabilitation, therapeutic exercise, exercise, cerebellar infarct, cerebellar infarction, and cerebellar blockage. The selection process of the final studies was carried out after setting inclusion and exclusion criteria and separately by two reviewers. Results: Out of 1477 initial records, six studies met the inclusion criteria for this overview. Interventions focused on a balance training program and walking training, as opposed to a treadmill training program, seem to improve symptoms in these patients. Also, task-oriented approach was a promising method of rehabilitation. Discussion: Physiotherapy has a beneficial effect on the symptoms of patients with cerebellar infarction and should be considered for the overall recovery of the patient. However, future research is needed due to the small number of studies and to find therapeutically proven forms of intervention. Coresponding author: Georgios Marios Kyriakatis, E-mail: georgemarioskiriakatis2000@gmail.com You can also search for this author in: PubMed, Google Scholar

Abstract Background Capsular warning syndrome (CWS) is a rare clinical syndrome characterised by recurrent and transient episodes of focal neurological deficits with high risk of infarction. The exact physiological mechanism of CWS remains unclear but is most commonly believed to be a result of haemodynamic insufficiency in diseased, small penetrating vessels. There are no defined treatment guidelines or established effective therapy. Case presentation We describe the case of a 65-year-old man who presented to the emergency department with recurrent episodes of dysarthria coupled with right facial droop and right-sided weakness. Symptoms recurred a total of ten times within a span of 3 h. He had new onset atrial fibrillation. An initial cerebral angiogram showed mild intracranial atherosclerotic disease with no proximal large vessel occlusion or acute infarct. Magnetic resonance imaging 1 h later demonstrated an infarct in the left corona radiata. Conclusions This case illustrates an uncommon etiology of CWS. We will also discuss the lack of consensus in treatment options for CWS to mitigate a complete stroke.

Background: Left atrial volume index (LAVI) is one marker of atrial myopathy, which is increasingly being recognized as a cause of cardioembolic stroke even in the absence of atrial fibrillation. Cardiac embolism is associated with larger strokes than other stroke mechanisms. The purpose of this study was to examine the association between LAVI and total brain infarct volume in patients with ischemic stroke. Methods: This was a retrospective study of 545 patients prospectively enrolled in the Cornell ActuE Stroke Academic Registry (CAESAR), which includes all acute ischemic stroke patients admitted to our hospital since 2011. LAVI measurements were obtained from our echocardiography image store system (Xclera, Philips Healthcare). Brain infarcts on diffusion-weighted images (DWI) were manually segmented and infarct volume was obtained on 3D Slicer. We used multiple linear regressionmodels adjusted for age, sex, race, and vascular comorbidities including atrial fibrillation. Results: Among 2,945 CAESAR patients, 545 patients had both total infarct volume and LAVI measured. We found an association between LAVI and log-transformed total brain infarct volume in both unadjusted (β = 0.018; p = 0.002) and adjusted (β = 0.024; p = 0.001) models. Conclusion: We found that larger left atrial volume was associated with larger brain infarcts. This association was independent of known cardioembolic risk factors such as atrial fibrillation and heart failure. These findings support the concept that atrial myopathy may be a source of cardiac embolism even in the absence of traditionally recognized mechanisms such as atrial fibrillation. [ABSTRACT FROM AUTHOR]