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Nerinetide is a neuroprotectant effective in preclinical models of acute ischaemic stroke when administered within 3 h of onset. However, the clinical evaluation of neuroprotectants in this short timeframe is challenging. We sought to establish the feasibility, safety, and effectiveness of nerinetide when given before hospital arrival within 3 h of symptom onset of suspected stroke. In this multicentre, randomised, double-blind, placebo-controlled study, paramedics enrolled participants aged 40–95 years within 3 h of suspected severe stroke onset, who were previously independent, and were being taken to one of seven stroke centres in Ontario or British Columbia, Canada. The primary hypothesis was that the administration of nerinetide would result in a higher rate of good functional outcomes. Participants were randomly assigned 1:1 to intravenous nerinetide (2·6 mg/kg) or placebo, each in visually identical vials. Paramedics, hospital care providers, and outcome evaluators were masked to treatment assignment. The primary outcome was good functional outcome on a sliding dichotomy of the modified Rankin Scale at 90 days. Participants were assessed on day 4, 30, and 90 by the stroke center research team, in person or over the telephone. Outcomes, adjusted for age and stroke severity, were evaluated in the modified intention-to-treat (mITT) population, and in the target population of those with acute ischaemic stroke. The safety population included all participants who received the study drug. This study is registered with ClinicalTrials.gov (NCT02315443), and trial enrolment has concluded. Between March 26, 2015, and March 27, 2023, 532 participants received nerinetide (n=265) or placebo (n=267). The mITT population of suspected stroke (n=507; 254 nerinetide and 253 placebo) included 321 (63%) with acute ischaemic stroke, 93 (18%) with intracranial haemorrhage, 44 (9%) with transient ischaemic attack, and 49 (10%) with stroke-mimicking conditions. Treatment began a median of 64 min (IQR 47–100) from symptom onset. Participants randomly assigned to nerinetide had more severe strokes compared with those receiving placebo (median National Institutes of Health Stroke Scale (NIHSS) 12, IQR 5–19 vs 10, 4–18 in mITT, and 14, 7–19 vs 10, 4–18 in the acute ischaemic stroke subgroup). Overall, 145 (57%) of 254 participants in the nerinetide group and 147 (58%) of 253 in the placebo group had the primary outcome of a favourable functional outcome using the prespecified sliding dichotomy at 90 days (adjusted odds ratio 1·05, 95% CI 0·73–1·51; adjusted risk ratio 1·04, 95% CI 0·85–1·25). In the 302 patients with ischaemic stroke, the favourable functional outcome adjusted for arrival NIHSS and age favoured nerinetide (odds ratio 1·53, 0·93–2·52 and risk ratio 1·21, 0·97–1·52). In those given reperfusion therapies (thrombolysis or endovascular thrombectomy, or both) nerinetide was associated with improved favourable functional outcomes (adjusted odds ratio 1·84, 1·03–3·28; adjusted risk ratio 1·29, 1·01–1·65). There was no apparent benefit in haemorrhagic stroke or acute ischaemic stroke without reperfusion. There were no safety concerns. Prehospital nerinetide did not improve neurological functional outcomes in all patients with suspected ischaemic stroke in the mITT population. Nerinetide might benefit patients with acute ischaemic stroke who are selected for reperfusion therapies within 3 h of symptom onset. This finding should be confirmed in a future trial. Brain Canada and NoNO.

BackgroundSurveys are increasingly used in neurointervention to gauge physicians’ and patients’ attitudes, practice patterns, and ‘real-world’ treatment strategies, particularly in conditions for which few, or no evidence-based, recommendations exist. While survey-based studies can provide valuable insights into real-world problems and management strategies, there is an inherent risk of bias.ObjectiveTo assess key themes, sample characteristics, response metrics, and report frequencies of quality indicators of neurointerventional surveys.MethodsA systematic review compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was performed. The PubMed database was searched for neurointerventional surveys published between 2000 and 2023. Survey topics, design, respondent characteristics, and survey quality criteria suggested by the Consensus-Based Checklist for Reporting of Survey Studies (CROSS) were assessed and described using descriptive statistics. Response rates and numbers of participants were further assessed for their dependence on sample characteristics and survey methodologies.ResultsA total of 122 surveys were included in this analysis. The number of surveys published each year increased steeply between 2000 (n=1) and 2023 (n=14). The most common survey topics were stroke (51/122, 41.8%) and aneurysm treatment (49/122, 40.2%). The median response rate was 58.5% (IQR=30.4–86.3), with a median number of respondents of 79 (IQR=50–201). Sixty-eight of 122 (55.7%) surveys published the questionnaire used for data collection. Only a subset of studies reported response rates (n=89, 73%), data collection time period (n=91, 74.6%), and strategies to prevent duplicate responses (n=57, 46.7%).ConclusionSurveys are increasingly used by neurointerventional researchers, particularly to assess real-world practice patterns in endovascular stroke and aneurysm treatment. Adapting best-practice guidelines like the CROSS checklist might improve homogeneity and quality in neurointerventional survey research.

Objective To determine the inter-reader reliability and diagnostic performance of classification and severity scales of Neuropathy Score Reporting And Data System (NS-RADS) among readers of differing experience levels after limited teaching of the scoring system. Methods This is a multi-institutional, cross-sectional, retrospective study of MRI cases of proven peripheral neuropathy (PN) conditions. Thirty-two radiology readers with varying experience levels were recruited from different institutions. Each reader attended and received a structured presentation that described the NS-RADS classification system containing examples and reviewed published articles on this subject. The readers were then asked to perform NS-RADS scoring with recording of category, subcategory, and most likely diagnosis. Inter-reader agreements were evaluated by Conger’s kappa and diagnostic accuracy was calculated for each reader as percent correct diagnosis. A linear mixed model was used to estimate and compare accuracy between trainees and attendings. Results Across all readers, agreement was good for NS-RADS category and moderate for subcategory. Inter-reader agreement of trainees was comparable to attendings (0.65 vs 0.65). Reader accuracy for attendings was 75% (95% CI 73%, 77%), slightly higher than for trainees (71% (69%, 72%), p = 0.0006) for nerves and comparable for muscles (attendings, 87.5% (95% CI 86.1–88.8%) and trainees, 86.6% (95% CI 85.2–87.9%), p = 0.4). NS-RADS accuracy was also higher than average accuracy for the most plausible diagnosis for attending radiologists at 67% (95% CI 63%, 71%) and for trainees at 65% (95% CI 60%, 69%) ( p = 0.036). Conclusion Non-expert radiologists interpreted PN conditions with good accuracy and moderate-to-good inter-reader reliability using the NS-RADS scoring system. Clinical relevance statement The Neuropathy Score Reporting And Data System (NS-RADS) is an accurate and reliable MRI-based image scoring system for practical use for the diagnosis and grading of severity of peripheral neuromuscular disorders by both experienced and general radiologists. Key Points • The Neuropathy Score Reporting And Data System (NS-RADS) can be used effectively by non-expert radiologists to categorize peripheral neuropathy. • Across 32 different experience-level readers, the agreement was good for NS-RADS category and moderate for NS-RADS subcategory. • NS-RADS accuracy was higher than the average accuracy for the most plausible diagnosis for both attending radiologists and trainees (at 75%, 71% and 65%, 65%, respectively).

BackgroundBetter reperfusion status results in smaller infarct volumes and better outcomes after thrombectomy. However, if large tissue volumes are already infarcted at baseline, reperfusion might also increase the risk of intracranial hemorrhage. This study aims to investigate the interaction between reperfusion status, baseline ischemic changes, and intracranial hemorrhage following thrombectomy.MethodsRetrospective analysis of the ESCAPE-NA1 randomized trial. Unadjusted and adjusted logistic regression models were used to estimate the associations of Alberta Stroke Program Early CT Score (ASPECTS) and expanded Treatment In Cerebral Infarction (eTICI) score on post-treatment hemorrhage. Treatment effect modification was assessed by including multiplicative interaction terms (ASPECTS*eTICI) in these models.ResultsA total of 1077 patients were included. Median age was 70.8 (IQR 60.7–79.7) and 543 (50.4%) were female. Any intracranial hemorrhage on 24-hour follow-up imaging occurred in 368/1077 (34.2%) patients. There was evidence of modification of the effect of final angiogram eTICI score on any intracranial hemorrhage by baseline ASPECTS (P=0.008). Marginal probabilities showed increased hemorrhage risk for patients with low ASPECTS with increasing final eTICI scores. This association was reversed in patients with small baseline ischemic changes and successful reperfusion. There was no association with symptomatic intracranial hemorrhage or parenchymal hematoma.ConclusionThe association of post-thrombectomy reperfusion status and post-treatment hemorrhage may be modified by the extent of baseline ischemia. Reperfusion is associated with reduced risk of hemorrhage in patients with small baseline infarcts, but increased hemorrhage risk in patients with extensive ischemic changes at baseline. However, no significant association was found with symptomatic intracranial hemorrhage or parenchymal hematoma.Trial registration numberNCT02930018.

Hintergrund und Ziele: Bei bakteriellen Hirnabszessen handelt es sich um eine zwar seltene Erkrankung, die jedoch auch zur heutigen Zeit noch immer mit einer hohen Letalität einhergeht. Die Pathogenese eines Hirnabszesses kann auf mehreren Ursachen beruhen. Kommt es beispielsweise bei einem Schädel-Hirn-Trauma zu einer Fraktur der Schädelkalotte, so kann sich ein Hirnabszess durch direkte Kontamination ausbilden. Das gleiche gilt für neurochirurgische Eingriffe am offenen Gehirn. In diesen beiden Fällen entstehen häufiger epidurale als intrazerebrale Abszesse. Eine weitere Möglichkeit der Entstehung wäre als Aussaat eines lokalen Fokus in einem der Schädelhöhle benachbarten Pneumatisationsraum, beispielsweise bei einem desolaten Zahnstatus, einer Mastoiditis oder Sinusitis. Auf hämatogenem Wege können Hirnabszesse im Rahmen einer Bakteriämie oder Sepsis entstehen. Nicht selten liegt bei den Betroffenen eine verminderte Immunabwehrsituation, wie z.B. AIDS (Acquired Immune Deficiency Syndrome) nach einer HIV (Human Immunedeficiency Virus) -Infektion oder eine medikamentöse Immunsuppression bei Zustand nach Organtransplantation vor. Von einer Infektion können alle Bevölkerungsschichten und alle Altersgruppen betroffen sein. Die klassische Symptom-Trias besteht aus Kopfschmerzen, begleitet von Fieber, sowie oftmals einem fokalen neurologischen Defizit. Kontrastmittelgestützte computertomographische oder magnetresonanztomographische Untersuchungen helfen, die Diagnose zu stellen. In den meisten Fällen ist eine neurochirurgische Intervention notwendig. Zum einen therapeutisch, um den durch den Abszess entstandenen Hirndruck zu senken und eine Einklemmung mit Druckschädigung von Teilen des Gehirns zu verhindern und zum anderen diagnostisch für die Gewinnung einer mikrobiologischen Probe zur Identifizierung der auslösenden Erreger. Im Anschluss daran folgt eine empirische antibiotische Therapie und meist ein langwieriger Aufenthalt auf einer Intensivstation, sodass die Gesamttherapiedauer meistes zwischen 6-8 Wochen liegt. Während der initialen Behandlung versucht man, das Erregerspektrum zu ermitteln, um auf eine gezielte Therapie umzustellen. Da in der heutigen Zeit viele Patienten bereits antibiotisch vorbehandelt sind, treten hierbei bereits die ersten Schwierigkeiten auf. Oftmals gelingt eine kulturelle Anzucht der Erreger nicht, weil das Keimwachstum durch wirksame Antibiotikaspiegel gehemmt ist. Eine Alternative zur Kultur stellt die PCR (polymerase chain reaction) basierte Sanger-Sequenzierung dar. Hierfür benötigt man lediglich die DNS, beziehungsweise im speziellen Fall der bakteriellen Infektion die 16S rDNS. Anhand der Basensequenzen lassen sich die unterschiedlichen Bakterien differenzieren. Doch auch hier gibt es insbesondere dann diagnostische Einschränkungen, wenn es sich um eine polymikrobielle Infektion handelt, bei welcher die klassische Sequenzierung kein eindeutiges Ergebnis liefern kann. Abhilfe schaffen in solchen Fällen die Methoden der nächsten Generation der Sequenzierung („Next Generation Sequencing“) im Sinne einer synchronen Sequenzierung von multiplen DNS-Strängen. Dies gelang bereits in einer Vielzahl von polymikrobiellen Infektion, darunter auch in einigen wenigen Studien bei Hirnabszessen. Ziel dieser Arbeit ist es, die Ergebnisse von vorangegangenen Studien zu verifizieren und die Aussagekraft der Methode zu verbessern. Zusätzlich zu Hirnabszessproben wurden auch Materialien von Patienten mit einer Meningitis-Infektion untersucht, da man hier meist von einem einzelnen pathogenen Erreger ausgeht. Dies soll helfen, zwischen falsch positiven und richtig positiven Signalen zu unterscheiden und damit die Anfälligkeit dieser Sequenzierungsmethode für Fehler und Kontaminationen zu ermitteln.Methoden:Es wurden 79 Proben von Patienten mit Meningitis- und Hirnabszess-Infektionen aus den Jahren 2010 bis 2016 am mikrobiologischen Institut in Erlangen untersucht. Im Rahmen der diagnostischen Aufarbeitung erfolgte neben einer konventionellen mikrobiologischen Anzucht und Färbung nach Gram auch in vielen Fällen eine Sanger-Sequenzierung.

The trend towards faster acquisition protocols in whole-body positron emission tomography/magnetic resonance (PET/MR) arises the question of whether short PET data acquisition protocols in a whole-body multi-station context allow for reduced PET acquisition times while providing adequate PET image quality and accurate quantification parameters. The study goal is to investigate how reducing PET acquisition times affects PET image quality and quantification in whole-body PET/MR in patients with oncologic findings. Fifty-one patients with different oncologic findings underwent a clinical whole-body 18F-Fluorodeoxyglucose PET/MR examination. PET data was reconstructed with 4, 3, 2, and 1 min/bed time intervals for each patient to simulate the effect of reduced PET acquisition times. The 4-minute PET reconstructions served as reference standard. All whole-body PET data sets were analyzed regarding image quality, lesion detectability, PET quantification and standardized uptake values. A total of 91 lesions were detected in the 4-minute PET reconstructions. The same number of congruent lesions was also noticed in the 3 and 2 minutes-per-bed (mpb) reconstructed images. A total of 2 lesions in 2 patients was not detected in the 1 minute PET data reconstructions due to poor image quality. Image noise in the blood pool increased from 22.2% (4 mpb) to 42.1% (1 mpb). Signal-to-noise ratio declined with shorter timeframes from 13.1 (4 mpb) to 9.3 (1 mpb). SUVmean and SUVmax showed no significant changes between 4 and 1 mpb reconstructed timeframes. Reconstruction of PET data with different time intervals has shown that 2 minutes acquisition time per bed position instead of 4 minutes is sufficient to provide accurate lesion detection and adequate image quality in a clinical setting, despite the trends to lower image quality with shorter PET acquisition times. This provides latitude for potential reduction of PET acquisition times in fast PET/MR whole-body examinations.

An exponential increase in the availability of information over the last two decades has asked for novel theoretical frameworks to examine how students optimally learn under these new learning conditions, given the limitations of human processing ability. In this special issue and in the current editorial introduction, [the authors] argue that such a novel theoretical framework should integrate (aspects of) cognitive load theory and self-regulated learning theory. [The authors] describe the effort monitoring and regulation (EMR) framework, which outlines how monitoring and regulation of effort are neglected but essential aspects of self-regulated learning. Moreover, the EMR framework emphasizes the importance of optimizing cognitive load during self-regulated learning by reducing the unnecessary load on the primary task or distributing load optimally between the primary learning task and metacognitive aspects of the learning task. Three directions for future research that derive from the EMR framework and that are discussed in this editorial introduction are: (1) How do students monitor effort? (2) How do students regulate effort? and (3) How do we optimize cognitive load during self-regulated learning tasks (during and after the primary task)? Finally, the contributions to the current special issue are introduced. (Orig.).

Electroencephalography (EEG) is a widely used technology for recording brain activity in brain-computer interface (BCI) research, where understanding the encoding-decoding relationship between stimuli and neural responses is a fundamental challenge. Recently, there is a growing interest in encoding-decoding natural stimuli in a single-trial setting, as opposed to traditional BCI literature where multi-trial presentations of synthetic stimuli are commonplace. While EEG responses to natural speech have been extensively studied, such stimulus-following EEG responses to natural video footage remain underexplored. We collect a new EEG dataset with subjects passively viewing a film clip and extract a few video features that have been found to be temporally correlated with EEG signals. However, our analysis reveals that these correlations are mainly driven by shot cuts in the video. To avoid the confounds related to shot cuts, we construct another EEG dataset with natural single-shot videos as stimuli and propose a new set of object-based features. We demonstrate that previous video features lack robustness in capturing the coupling with EEG signals in the absence of shot cuts, and that the proposed object-based features exhibit significantly higher correlations. Furthermore, we show that the correlations obtained with these proposed features are not dominantly driven by eye movements. Additionally, we quantitatively verify the superiority of the proposed features in a match-mismatch (MM) task. Finally, we evaluate to what extent these proposed features explain the variance in coherent stimulus responses across subjects. This work provides valuable insights into feature design for video-EEG analysis and paves the way for applications such as visual attention decoding.