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The objective of this article is to summarize the state of the literature surrounding the use of ketamine as a neuroprotective agent following cardiac arrest.Five electronic databases were used to search for studies related to the use of ketamine for neuroprotection following cardiac arrest. This search was performed once in May 2020, and an updated search was conducted in May 2021 and March 2022.All searches combined retrieved 181 results; no clinical trials were identified. As such, the authors were limited to writing a scoping review of the literature rather than a systematic review.The current state of the literature describes the mechanism of action of ketamine as a neuroprotective agent through its action as an NMDA antagonist. There is evidence of its efficacy as a neuroprotective agent in preclinical models of cardiac arrest. Current published clinical work supports the use of ketamine ameliorating neurologic outcomes in other conditions such as epilepsy, traumatic brain injury, and depression. The current state of the literature is reflective of the notion that the use of ketamine following cardiac arrest may result in improved neurologic outcomes. Future research directions should focus on the use of ketamine as a possible clinical intervention following cardiac arrest.

BackgroundThe Alteplase compared to Tenecteplase (AcT) randomized controlled trial (RCT) showed that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known, however the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase.MethodsPatients included were from AcT, a pragmatic, registry linked, phase 3 RCT comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4·5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin scale(mRS) 0-1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality rates. Mixed effects logistic regression was used to assess a)the association of stroke symptom onset to needle time (ONT), b)door (hospital arrival) to needle time(DNT) with outcomes and c)if these associations were modified by type of thrombolytic administered (tenecteplase vs. alteplase), after adjusting for age, sex, baseline stroke severity and site of intracranial occlusion.ResultsOf the 1538 patients included in this analysis, 1146(74.5%)[591: tenecteplase, 555 alteplase] presented within 3 hours vs. 392 (25.5%)[196: TNK, 196 alteplase] who presented within 3-4.5 hours of symptom onset. Baseline patient characteristics in the 0-3 hour versus 3-4.5-hour time window were similar, except patients in the 3-to-4.5-hour window had lower median baseline NIHSS (10 vs 7 respectively) and lower proportion of patients with large vessel occlusion on baseline CT Angiography (26.9% vs 18.7% respectively). Type of thrombolytic agent (tenecteplase vs. alteplase) did not modify the association between ONT(pinteraction= 0.161) or DNT(pinteraction= 0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-min reduction in ONT was associated with a 1.8% increase while every 10 min reduction in DNT was associated with a 0.2% increase in the probability of achieving 90-day mRS 0-1 respectively.ConclusionThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.Key points:QuestionIn patients with acute ischemic stroke, does the effect of time to thrombolysis on clinical outcomes differ with tenecteplase vs. alteplase administration?FindingsIn this analysis from the alteplase compared to tenecteplase (AcT) trial, a pragmatic, registry linked, phase 3 randomized controlled trial, each 30-min reduction in stroke onset to thrombolysis start time was associated with a 1.8% increase in the probability of achieving excellent functional outcome, which means that for every 30-minute reduction in onset to needle time two more of a 100 people achieved an excellent outcome. This effect was not modified by type of thrombolytic used (alteplase versus tenecteplase)MeaningThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.

Our study considered the problem of classifying routine clinical EEG. We incorporated NLP tools into the workflow for time series classification. We transformed EEG signals into strings of symbols. We then applied byte-pair encoding (BPE) to split the new text into combinations of symbols or tokens, each associated with different patterns of changes in EEG amplitude. We validated the proposed workflow under the framework of predicting patients' biological age.

Background Intravenous thrombolysis with alteplase is widely used in patients with acute ischemic stroke presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared with alteplase. This study investigates whether intravenous tenecteplase is noninferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial (AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke]) with blinded end point assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, maximum dose 25 mg) is noninferior to intravenous alteplase (0.9 mg/kg body weight; maximum dose, 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a noninferiority margin of 5%, assuming incidence of the 90‐day modified Rankin Scale score of 0 to 1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate Results The blinded primary end point is the proportion of subjects achieving a 90‐day modified Rankin Scale score of 0 to 1. Key safety outcomes include 24‐hour symptomatic intracerebral hemorrhage and 90‐day all‐cause mortality. All serious adverse events within a 24‐hour period will be reported and coded using the Medical Dictionary for Regulatory Activities. Outcomes are collected either centrally (primary, key secondary, and safety end points) or through ongoing Canadian stroke registries. The primary analysis is a simple unadjusted comparison of proportions. Conclusions Results from the trial will provide real‐world evidence of the effectiveness of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke presenting early after stroke onset.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Background : Intravenous thrombolysis with alteplase is widely used in acute ischemic stroke patients presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared to alteplase. This study investigates whether intravenous tenecteplase is non‐inferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods : This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial with blinded endpoint assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non‐inferior to intravenous alteplase (0.9 mg/kg body weight, max dose 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a non‐inferiority margin of 5%, assuming incidence of 90‐day mRS 0–1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate < 5%. Results : The blinded primary endpoint is the proportion of subjects achieving a 90‐day mRS (modified Rankin scale) of 0–1. Key safety outcomes include 24‐hour symptomatic intracerebral hemorrhage and 90‐day all‐cause mortality. All serious adverse events within 24‐hour period will be reported and coded using MedDRA. Outcomes are collected either centrally (primary, key secondary and safety endpoints) or through ongoing Canadian stroke registries. The primary analysis is a simple unadjusted comparison of proportions. Conclusion : Results from the trial will provide real‐world evidence of the effectiveness of intravenous tenecteplase vs. alteplase in patients with acute ischemic stroke presenting early after stroke onset. Clinical Trial Registration: NCT03889249 https://clinicaltrials.gov/ct2/show/NCT03889249 This article is protected by copyright. All rights reserved

Severe internal carotid stenosis, if left untreated, can pose serious risks for ischemic stroke and cognitive impairments. The effects of revascularization on any aspects of cognition, however, are not well understood, as conflicting results are reported, which have mainly been centered on paper-based cognitive analyses. Here, we summarized and evaluated the publications to date of functional MRI (fMRI) studies that examined the mechanisms of functional brain activation and connectivity as a way to reflect cognitive effects of revascularization on patients with carotid stenosis.A PubMed and Google Scholar (covering the relevant literature until November 1, 2021) search yielded eight original studies of the research line, including seven resting-state and one task-based fMRI reports.Findings demonstrated treatment-related alterations in fMRI signal intensity and symmetry level, regional fMRI activation pattern, and functional brain network connectivity. The functional brain changes were associated largely with improvement in cognitive function assessed using standard cognitive test scores.These findings support the contribution of fMRI to the understanding of brain functional activation and connectivity changes revealing cognitive effects of revascularization in the management of severe carotid stenosis. The review also highlighted the importance of reproducibility through enhancing experimental designs and cognitive task applications with future research for potential clinical translation.

Background: Hemorrhagic transformation after acute ischemic stroke is a dreaded and severe complication of thrombolysis and thrombectomy. However, its detection on post-thrombectomy conventional non-contrast computed tomography (CT) scan can be complicated by the frequent (and sometimes concomitant) presence of contrast, resulting in changes in management.Aims: Our objective was to assess the inter- and intra-rater reliability for the detection of blood and/or contrast on day-1 post-thrombectomy CT scans.Methods: A total of 18 raters across 3 different specialties independently examined 30 post-thrombectomy CT scans selected from the Aspiration vs. STEnt-Retriever (ASTER) trial. They were asked to judge the presence of blood and contrast. Thirty days later, the same 18 raters again independently judged the 30 scans, in randomized order. Agreement was measured with Fleiss' and Cohen's K statistics.Results: Overall agreement on blood and/ or contrast presence was only fair, k = 0.291 (95% CI = 0.273–0.309). There were 0 scans with consensus among the 18 readers on the presence of blood and/or contrast. However, intra-rater global agreement across all 18 physicians was relatively high, with a median kappa value of 0.675. This intra-rater consistency was seen across all specialties, regardless of level of training.Conclusion: Physician judgment for the presence of blood and/or contrast on day-1 post-thrombectomy non-contrast CT scan shows limited inter-observer reliability. Advanced imaging modalities may then be warranted for challenging clinical cases.

This project aimed to develop and evaluate a fast and fully-automated deep-learning method applying convolutional neural networks with deep supervision (CNN-DS) for accurate hematoma segmentation and volume quantification in computed tomography (CT) scans. Non-contrast whole-head CT scans of 55 patients with hemorrhagic stroke were used. Individual scans were standardized to 64 axial slices of 128 × 128 voxels. Each voxel was annotated independently by experienced raters, generating a binary label of hematoma versus normal brain tissue based on majority voting. The dataset was split randomly into training (n = 45) and testing (n = 10) subsets. A CNN-DS model was built applying the training data and examined using the testing data. Performance of the CNN-DS solution was compared with three previously established methods. The CNN-DS achieved a Dice coefficient score of 0.84 ± 0.06 and recall of 0.83 ± 0.07, higher than patch-wise U-Net ( 1412 s) and slice-based U-Net (> 12 s). Comparable interrater agreement rates were observed between “method-human” vs. “human–human” (Cohen’s kappa coefficients > 0.82). The fully automated CNN-DS approach demonstrated expert-level accuracy in fast segmentation and quantification of hematoma, substantially improving over previous methods. Further research is warranted to test the CNN-DS solution as a software tool in clinical settings for effective stroke management.

Advances in MRI technology have significantly contributed to our ability to understand the process of brain ageing, allowing us to track and assess changes that occur during normal ageing and neurological conditions. This paper focuses on reviewing structural changes of the ageing brain that are commonly seen using MRI, summarizing the pathophysiology, prevalence, and neuroanatomical distribution of changes including atrophy, lacunes, white matter lesions, and dilated perivascular spaces. We also review the clinically accessible methodology for assessing these MRI-based changes, covering visual rating scales, as well computer-aided and fully automated methods. Subsequently, we consider novel assessment methods designed to evaluate changes across the whole brain, and finally discuss new directions in this field of research.

Introduction Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors’ quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Methods and analysis Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. Ethics and dissemination The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging scientists, computing scientists and clinical professionals in neurology and neuroradiology and includes patient representatives. Research outputs will be disseminated following knowledge translation plans towards improving stroke patient care. Significant findings will be published in scientific journals. Anticipated deliverables include computer solutions for improved clinical assessment of haematoma using NCCT.

Giant cell arteritis, which most commonly affects the temporal arteries, may involve intrarenal vessels and may be associated with a variety of renal lesions, including necrotizing arteritis, necrotizing glomerulonephritis, granulomatous glomerulonephritis, and membranous glomerulopathy. Isolated giant cell arteritis of the kidney is a rare cause of renal failure. We report a case of a previously healthy 54-year-old white woman who presented with nonoliguric renal failure and a 4-week history of persistent low-grade fever associated with diffuse mild myalgias. She had no history of previous renal or neurologic disease and denied any headaches or visual disturbances. Antinuclear antibody and antineutrophilic cytoplasmic antibody were negative. Renal biopsy revealed noncaseating granulomatous infiltration of arterial and arteriolar walls, a patchy mononuclear cell interstitial infiltrate, and no significant glomerular changes. Treatment with prednisone resulted in dramatic improvement of renal function.