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Abstract Objective The Swiss guidelines for driving with epilepsy require that electroencephalogram (EEG) findings must be compatible with the fitness to drive (FTD) without specifying any criteria. This nationwide survey investigated how Swiss neurologists implement this requirement in clinical practice. Methods An online survey, including 19 EEG examples and statements about the compatibility of the EEG with FTD, was distributed to all members of the Swiss Society of Clinical Neurophysiology and all Swiss neurological clinics with residency programs. Descriptive statistics and Fleiss' Kappa for inter‐rater agreement were performed. Results 102 participants (37% female, 45%

Objectives We aimed to examine the adherence of large language models (LLMs) to bacterial meningitis guidelines using a hypothetical medical case, highlighting their utility and limitations in healthcare.Methods A simulated clinical scenario of a patient with bacterial meningitis secondary to mastoiditis was presented in three independent sessions to seven publicly accessible LLMs (Bard, Bing, Claude-2, GTP-3.5, GTP-4, Llama, PaLM). Responses were evaluated for adherence to good clinical practice and two international meningitis guidelines.Results A central nervous system infection was identified in 90% of LLM sessions. All recommended imaging, while 81% suggested lumbar puncture. Blood cultures and specific mastoiditis work-up were proposed in only 62% and 38% sessions, respectively. Only 38% of sessions provided the correct empirical antibiotic treatment, while antiviral treatment and dexamethasone were advised in 33% and 24%, respectively. Misleading statements were generated in 52%. No significant correlation was found between LLMs’ text length and performance (r=0.29, p=0.20). Among all LLMs, GTP-4 demonstrated the best performance.Discussion Latest LLMs provide valuable advice on differential diagnosis and diagnostic procedures but significantly vary in treatment-specific information for bacterial meningitis when introduced to a realistic clinical scenario. Misleading statements were common, with performance differences attributed to each LLM’s unique algorithm rather than output length.Conclusions Users must be aware of such limitations and performance variability when considering LLMs as a support tool for medical decision-making. Further research is needed to refine these models' comprehension of complex medical scenarios and their ability to provide reliable information.

ObjectiveDoublecortin (DCX) and glypican-2 (GPC2) are neurodevelopmental proteins involved in the differentiation of neural stem/progenitor cells (NSPCs) to neurons, and are developmentally downregulated in neurons after birth. In this study, we investigated whether the concentrations of DCX and GPC2 in the cerebrospinal fluid (CSF) from human pediatric patients reflect this developmental process or are associated with cerebral damage or inflammatory markers.MethodsCSF was collected from pediatric patients requiring neurosurgical treatment. The concentrations of DCX, GPC2, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, and TNF-⍺) were measured using immunoassays.ResultsFrom March 2013 until October 2018, 63 CSF samples were collected from 38 pediatric patients (20 females; 17 patients with repeated measurements); the median term born-adjusted age was 3.27 years [Q1: 0.31, Q3: 7.72]. The median concentration of DCX was 329 pg/ml [Q1: 192.5, Q3: 1179.6] and that of GPC2 was 26 pg/ml [Q1: 13.25, Q3: 149.25]. DCX and GPC2 concentrations independently significantly associated with age, and their concentration declined with advancing age, reaching undetectable levels at 0.3 years for DCX, and plateauing at 1.5 years for GPC2. Both DCX and GPC2 associated with hydrocephalus, NSE, IL-1β, IL-2, IL-8, IL-13. No relationship was found between sex, acute infection, S100B, IL-4, IL-6, IL-10, IFN-γ, TNF-α and DCX or GPC2, respectively.ConclusionsConcentrations of DCX and GPC2 in the CSF from pediatric patients are developmentally downregulated, with the highest concentrations measured at the earliest adjusted age, and reflect a neurodevelopmental stage rather than a particular disease state.

BackgroundCerebral microbleeds (CMBs) may have a differential impact on clinical outcome in stroke patients with atrial fibrillation (AF) treated with different types of oral anticoagulation (OAC).MethodsObservational single-center study on AF-stroke-patients treated with OAC. Magnetic-resonance-imaging was performed to assess CMBs. Outcome measures consisted of recurrent ischemic stroke (IS), intracranial hemorrhage (ICH), death, and their combined analysis. Functional disability was assessed by mRS. Using adjusted logistic regression and Cox proportional-hazards models, we assessed the association of the presence of CMBs and OAC type (vitamin K antagonists [VKAs] vs. direct oral anticoagulants [DOACs]) with clinical outcome.ResultsOf 310 AF-stroke patients treated with OAC [DOACs: n = 234 (75%); VKAs: n = 76 (25%)], CMBs were present in 86 (28%) patients; of these, 66 (77%) received DOACs. In both groups, CMBs were associated with an increased risk for the composite outcome: VKAs: HR 3.654 [1.614; 8.277]; p = 0.002; DOACs: HR 2.230 [1.233; 4.034]; p = 0.008. Patients with CMBs had ~50% higher absolute rates of the composite outcome compared to the overall cohort, with a comparable ratio between treatment groups [VKAs 13/20(65%) vs. DOACs 19/66(29%); p < 0.01]. The VKA-group had a 2-fold higher IS [VKAs:4 (20%) vs. DOACs:6 (9%); p = 0.35] and a 10-fold higher ICH rate [VKAs: 3 (15%) vs. DOACs: 1 (1.5%); p = 0.038]. No significant interaction was observed between type of OAC and presence of CMBs. DOAC-patients showed a significantly better functional outcome (OR 0.40 [0.17; 0.94]; p = 0.04).ConclusionsIn AF-stroke patients treated with OAC, the presence of CMBs was associated with an unfavorable composite outcome for both VKAs and DOACs, with a higher risk for recurrent IS than for ICH. Strokes were numerically higher under VKAs and increased in the presence of CMBs.Clinical trial registrationhttp://www.clinicaltrials.gov, Unique identifier: NCT03826927.

Abstract Background Recent findings describe microglia as modulators of neurogenesis in the subventricular zone (SVZ). SVZ microglia in the adult rat are thought to adopt a neurotrophic phenotype after ischemic stroke. Early postnatal microglia are endogenously activated and may therefore exhibit an increased sensitivity to neonatal hypoxia-ischemia (HI). The goal of this study was to investigate the impact of cortico-striatal HI on the microglial phenotype, function, and gene expression in the early postnatal SVZ. Methods Postnatal day (P)7 rats underwent sham or right-hemispheric HI surgery. Microglia in the SVZ, the uninjured cortex, and corpus callosum were immunohistochemically analyzed at P10, P20, and P40. The transcriptome of microdissected SVZ and cortical microglia was analyzed at P10 and P20, and the effect of P10 SVZ microglia on neurosphere generation in vitro was studied. Results The microglial response to HI was region-specific. In the SVZ, a microglial accumulation, prolonged activation and phagocytosis was noted that was not observed in the cortex and corpus callosum. The transcriptome of SVZ microglia and cortical microglia were distinct, and after HI, SVZ microglia concurrently upregulated pro- and anti-inflammatory as well as neurotrophic genes. In vitro, microglia isolated from the SVZ supported neurosphere generation in a concentration-dependent manner. Conclusions Microglia are an inherent cellular component of the early postnatal SVZ and undergo developmental changes that are affected on many aspects by neonatal HI injury. Our results demonstrate that early postnatal SVZ microglia are sensitive to HI injury and display a long-lasting region-specific response including neurotrophic features.

Abstract Background To better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke. Methods The study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data. Results Placental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7–77.8) vs 27.7 (16.7–31.4) pg/ml (p

Background and Purpose Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis (IVT) or endovascular treatment (EVT). Methods This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban (September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were 100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage. Results Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range [IQR] 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100 ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment. Conclusions Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach.

Background: Neurofilament light chain (NfL) is a highly promising biomarker of neuroaxonal injury that has mainly been studied in adult neurodegenerative disease. Its involvement in neonatal disease remains largely unknown. Our aim was to establish NfL plasma concentrations in preterm and term infants in the first week of life.Methods: Plasma NfL was measured by single molecule array immunoassay in two neonatal cohorts: cohort 1 contained 203 term and preterm infants, median gestational age (GA) 37.9 weeks (interquartile range [IQR] 31.9–39.4), in whom venous and arterial umbilical cord blood was sampled at birth and venous blood at day of life (DOL) 3; cohort 2 contained 98 preterm infants, median GA 29.3 weeks (IQR 26.9–30.6), in whom venous blood was sampled at DOL 7.Results: Median NfL concentrations in venous blood increased significantly from birth (18.2 pg/mL [IQR 12.8–30.8, cohort 1]) to DOL 3 (50.9 pg/mL [41.3–100, cohort 1]) and DOL 7 (126 pg/mL [78.8–225, cohort 2]) (p < 0.001). In both cohorts NfL correlated inversely with birth weight (BW, Spearman's rho −0.403, p < 0.001, cohort 1; R −0.525, p < 0.001, cohort 2) and GA (R −0.271, p < 0.001, cohort 1; R −0.487, p < 0.001, cohort 2). Additional significant correlations were found for maternal age at delivery, preeclampsia, delivery mode, 5-min Apgar, duration of oxygen supplementation, sepsis, and brain damage (intraventricular hemorrhage or periventricular leukomalacia). Multivariable logistic regression analysis identified the independent predictors of NfL in cohort 1 as BW (beta = −0.297, p = 0.003), delivery mode (beta = 0.237, p = 0.001) and preeclampsia (beta = 0.183, p = 0.022) and in cohort 2 as BW (beta = −0.385, p = 0.001) and brain damage (beta = 0.222, p = 0.015).Conclusion: Neonatal NfL levels correlate inversely with maturity and BW, increase during the first days of life, and relate to brain injury factors such as intraventricular hemorrhage and periventricular leukomalacia, and also to vaginal delivery.

Abstract Background Preclinical studies indicate that the systemic application of C1-inhibitor, clinically used to treat hereditary angioedema, reduces secondary brain injury after ischemic stroke. This study assessed the effect of C1-inhibitor on secondary brain injury after hemorrhagic stroke. Methods We used an established striatal whole-blood injection mouse model to mimic intracerebral hemorrhage-related secondary brain injury. Based on the spatiotemporal dynamics in our model, we calculated the necessary sample size (n = 24) and determined the most sensitive time point to detect potential group differences (48 h) prior to the experiments. The experimental setup, tissue processing and image analysis adhered to our published protocol. We randomized mice into three groups: C1-inhibitor treatment, placebo, and sham. Histology was standardized by taking eight anatomically predefined slices across the entire lesion. Lesion size, vascular leakage, and inflammatory responses were assessed using automated thresholding and dextran/ICAM1/CD45 intensity mapping. Investigators were blinded to group allocation during the experiment, tissue processing, and image analysis. Results Whole blood injection resulted in significantly larger lesion size and more pronounced vascular leakage and cellular inflammation compared to the sham group. However, there was no difference in lesion size or inflammatory markers between the C1-inhibitor and placebo groups. In addition, there was no difference in the inflammatory response of the choroid plexus, which has been identified as a central organ orchestrating inflammation after intracerebral hemorrhage. Conclusion The protective effect of C1-inhibitor might be isolated to pathophysiological processes with a predominant thromboinflammatory component, as in ischemia-reperfusion, but less so in permanent ischemia or intracerebral hemorrhage.

Abstract Background Spontaneous supratentorial intracerebral hemorrhage is the deadliest form of stroke with mortality rates over 50%. Currently, no sufficiently effective treatment to improve both mortality and functional outcome rates exists. However, it seems that minimally invasive surgery, especially endoscopic surgery, might be beneficial in improving survival and functional outcome rates, yet large confirmatory studies thereof are lacking. The aim of this trial is to compare whether early minimally invasive endoscopic surgery leads to improved functional outcome rates compared to the best medical treatment. Methods This is a prospective, parallel-arm, outcome assessor blinded multicenter trial across Switzerland. Endoscopic surgery will be compared to the best medical treatment in a 1:1 randomization over a total time of 12 months. The primary outcome is defined as improved functional outcome (mRS

The administration of intravenous thrombolysis (IVT) for patients with acute ischemic stroke who have recently ingested direct oral anticoagulants (DOACs) presents a clinical challenge due to the perceived increased risk of intracranial hemorrhage (ICH). Traditional guidelines from the US and European authorities advise against IVT within 48 h of last DOAC ingestion, unless specific coagulation tests indicate safety. However, emerging observational studies suggest that IVT might be safe in selected patients. A US stroke registry study and a global multicenter cohort study both reported no significant increase in symptomatic ICH among patients on DOACs compared to those not on anticoagulants. A systematic review of all published observational studies further supported these findings, showing comparable bleeding rates and functional outcomes in DOAC-treated patients. Reversal agents like idarucizumab for dabigatran have demonstrated potential in facilitating safer IVT administration, though logistical and cost-related barriers limit their widespread use. The variability in global guidelines reflects differing approaches to risk assessment and resource availability, highlighting the need for individualized treatment decisions. In India, the increasing prevalence of atrial fibrillation and stroke as well as prescription of DOACs necessitate adapted guidelines that consider local health-care infrastructure. Despite the promising observational data, the lack of randomized controlled trials underscores the need for further research to establish robust evidence for IVT use in this context. Collaborative international efforts and inclusion of diverse patient populations in future studies will be crucial to refine treatment protocols and improve outcomes for stroke patients on DOACs.

BackgroundWhether minimally invasive endoscopic surgery (ES) improves survival and functional outcome in people with spontaneous supratentorial intracerebral hemorrhage (SSICH) is unknown.MethodsThis is a single-center pilot study performed between July 2021 to January 2023. Any supratentorial hematoma with a volume between 20 mL and 100 mL was endoscopically evacuated within 24 h after bleeding onset. Participants were followed-up for 6 months, assessing clinical and radiological outcomes. The primary feasibility outcome was satisfactory hematoma removal (

Background and Purpose We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. Methods In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0–4 and LVO who underwent EVT 6–24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0–2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2–4) and those without (mRS score 0–1). Results A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P

Background and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. Methods From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. Results Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95). Conclusion Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes. Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population. Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke. Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71–0.89; p

Abstract The impact of small vessel disease (SVD) on stroke outcome was investigated either separately for its single features in isolation or for SVD sum score measuring a qualitative (binary) assessment of SVD-lesions. We aimed to investigate which SVD feature independently impacts the most on stroke outcome and to compare the continuous versus binary SVD assessment that reflects pronouncement and presence correspondingly. Patients with a first-ever anterior circulation ischemic stroke were retrospectively investigated. We performed an ordered logistic regression analysis to predict stroke outcome (mRS 3 months, 0–6) using age, stroke severity, and pre-stroke disability as baseline input variables and adding SVD-features (lacunes, microbleeds, enlarged perivascular spaces, white matter hyperintensities) assessed either continuously (model 1) or binary (model 2). The data of 873 patients (age 67.9 ± 15.4, NIHSS 24 h 4.1 ± 4.8) was analyzed. In model 1 with continuous SVD-features, the number of microbleeds was the only independent predictor of stroke outcome in addition to clinical parameters (OR 1.21; 95% CI 1.07–1.37). In model 2 with the binary SVD assessment, only the presence of lacunes independently improved the prediction of stroke outcome (OR 1.48, 1.1–1.99). In a post hoc analysis, both the continuous number of microbleeds and the presence of lacunes were independent significant predictors. Thus, the number of microbleeds evaluated continuously and the presence of lacunes are associated with stroke outcome independent from age, stroke severity, pre-stroke disability and other SVD-features. Whereas the presence of lacunes is adequately represented in SVD sum score, the microbleeds assessment might require another cutoff and/or gradual scoring, when prediction of stroke outcome is needed.

Abstract Determining the optimal transportation for each stroke patient is critically important to achieve the best possible outcomes. In border regions the next comprehensive stroke center may be just across an international border, but bureaucratic and financial hurdles may prevent a simple transfer to the next stroke center. We hypothesized that in regions close to international borders, patients may benefit from an "open border, closed transfer scenario", meaning that patients in whom a large vessel occlusion (LVO) is detected in the primary stroke center will benefit from a transfer to the nearest stroke center offering endovascular thrombectomy—even if this may be across a national border. We used the Swiss-German–French trinational region as an example for a region with several international borders within close proximity to one another, and compared two feasible scenarios; (a) a “closed borders, open transfer” scenario, where the patient is transported to any center in the same country, (b) an “open border, closed transfer” scenario, where patients are always transported to the nearby primary stroke center first and then to the nearest comprehensive stroke center in either the same or a neighboring country and (c) and “open borders, open transfer” scenario. The outcome of interest was the predicted probability of acute ischemic stroke patients to achieve a good outcome using a conditional probability model which predicts the likelihood of excellent outcome (modified Rankin scale score of 0–1 at 90 days post-stroke) for patients with suspected LVO. Results were modeled in a virtual map from which the ideal transport concept emerged. For an exemplary LVO stroke patient in Germany, the probability of a good outcome was higher in an open border, closed transfer scenario than with closed borders, open transfer (33.1 vs. 30.1%). Moreover, time to EVT would decrease from 232 min in the first scenario to 169 min in an open border, closed transfer scenario. The catchment area of the University Hospital Basel was almost double the size in an open border, closed transfer scenario compared to closed borders (1674 km2 vs. 2897 km2) and would receive transfers from 3 primary stroke centers in other countries (2 in Germany and 1 in France). Stroke patients showed a higher likelihood of good outcome in the “open border” scenarios without transfer restrictions to a specific healthcare system. This probably has implications for stroke treatment in all border regions where EVT eligible stroke patients may benefit from transport to the closest EVT capable center whenever possible, regardless of whether this hospital is located in the same or a neighboring country/jurisdiction.

BackgroundThe “translational roadblock” between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution.MethodsTo verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later.ResultsOur preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%.ConclusionOur study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.

Abstract Aim Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA. Methods Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3rd Edition. The association of age with MA characteristics was assessed. Results The median age was 29 (IQR 28–52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P

BackgroundThis study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS).MethodsConsecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke.ResultsA total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th–75th percentiles 67–84 years versus 70 years, 25th–75th percentiles 60–80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01–2.19, value of p 0.044).ConclusionThis study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Background The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. We compared clinical and technical outcomes with first‐line stent retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international case–control study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion presenting within 24 hours of time last seen well from January 2015 to August 2022. The primary outcome was the first‐pass effect (FPE), defined as expanded Treatment in Cerebral Infarction (TICI) 2c/3 on the first pass. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. Results There were 326 patients who met inclusion criteria, 56.1% male, median age 75 (interquartile range 65–82) years, and median National Institutes of Health Stroke Scale score 8 (5–12). Occlusion segments were PCA‐P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. FPE was lower in patients treated with first‐line CA or combined technique compared with SR (CA versus SR: adjusted odds ratio 0.45 [0.19–1.06]; P=0.07; combined versus SR: adjusted odds ratio 0.35 [0.016–0.80]; P=0.01). There were lower odds of functional independence (modified Rankin scale score 0–2) in the first‐line CA versus SR alone group (adjusted odds ratio 0.52 [0.28–0.95]; P=0.04). FPE was associated with higher rates of favorable outcomes (modified Rankin scale score 0–2: 58% versus 43.4%; P=0.01; modified Rankin scale score 0–1: 36.6% versus 25.8%; P=0.05). Overall, symptomatic intracranial hemorrhage was present in 5.6% (18/326) and mortality in 10.9% (35/326) without difference between first‐line technique. Conclusion In patients with isolated PCA occlusion, SR was associated with a higher rate of FPE compared with CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90 days was more likely with first‐line SR compared with CA. FPE was associated with better 90‐day clinical outcomes.

Abstract Introduction In 2022 the DGN (Deutsche Gesellschaft für Neurologie) published an updated Transient Global Amnesia (TGA) guideline. TGA is characterized by a sudden onset of retrograde and anterograde amnesia for a period of one to a maximum of 24 h (with an average of 6 to 8 h). The incidence is estimated between 3 and 8 per 100,000 population/year. TGA is a disorder that occurs predominantly between 50 and 70 years. Recommendations The diagnosis of TGA should be made clinically. In case of an atypical clinical presentation or suspicion of a possible differential diagnosis, further diagnostics should be performed immediately. The detection of typical unilateral or bilateral punctate DWI/T2 lesions in the hippocampus (especially the CA1 region) in a proportion of patients proves TGA. The sensitivity of MRI is considered higher when performed between 24 and 72 h after onset. If additional DWI changes occur outside the hippocampus, a vascular etiology should be considered, and prompt sonographic and cardiac diagnostics should be performed EEG may help to differentiate TGA from rare amnestic epileptic attacks, especially in recurrent amnestic attacks. TGA in patients

Dissecting aneurysms in patients with spontaneous cervical artery dissections have, so far, been reported as “benign”, but more specific information is scarce. We aimed to elucidate (1) vascular risk factors, (2) local and ischemic symptoms, and (3) long-term prognosis compared to non-aneurysmal dissections. This case–control study included consecutive patients with spontaneous cervical artery dissection from three university hospitals in Switzerland and France, evaluated at baseline and at 3 months. In addition, further follow-ups were performed at the discretion of the treating physician. Dissecting aneurysms were diagnosed with duplex sonography, magnetic resonance angiography, and/or digital subtraction angiography. Of 1012 patients, 151 (14.9%) presented with 167 dissecting aneurysms at baseline (n = 103) or follow-up (n = 64). The median follow-up was 24.9 months (IQR: 6.8–60.8). Compared to patients without a dissecting aneurysm there were no significant differences in the vascular risk factors or local symptoms (91.4 vs. 89.8%). Ischemic strokes at baseline were less common (29.1% vs. 54.4%; OR: 0.41; 95% CI: 0.28–0.60) in patients with a dissecting aneurysm, even after correction for the degree of stenosis of the dissected arteries (OR: 0.53; 95% CI: 0.34–0.81). Patients with a dissecting aneurysm more often had a favorable clinical outcome (modified Rankin Scale Score of 0–1) at 3 months (80.6% vs. 54.5%). There was no significant difference in recurrent cerebrovascular events at 3 months or overall. The lower rate of ischemic strokes at baseline may reflect a different pathogenic mechanism, such as a smaller initial tear in the vessel wall or an increased vessel caliber from an early or primary intramural hematoma with a different shape.

Introduction The benefit of additional reperfusion attempts in patients with partial angiographic reperfusion (TICI2b) is unknown. The PROCEED model predicts subsequent favorable occurrence of complete reperfusion (i.e. delayed reperfusion [DR]) at 24 hours after initial incomplete angiographic reperfusion at the conclusion of thrombectomy. This study aims to externally validate the PROCEED model using pooled data from multiple international trials that systematically performed follow‐up perfusion imaging. Methods Individual patient data for external validation were obtained from the EXTEND‐IA, EXTEND‐IA TNK part 1 and 2 trials (clinicaltrials.gov, unique‐identifier: NCT01492725, NCT02388061 and NCT03340493). The model’s primary outcome of interest was the occurrence of DR, defined as the absence of any focal perfusion deficit on follow‐up CT or MRI perfusion imaging maps, despite initial incomplete angiographic reperfusion on the final thrombectomy angiography series. The updated model’s performance was evaluated with discrimination, calibration and clinical decision curves. Results We analyzed 267 patients for the external validation, with median age of 74 (IQR 64 – 80), 44.2% were female and 62% had DR. The externally validated model had good discrimination (C‐statistic 0.81, 95% CI 0.72 – 0.86) and was well calibrated (intercept 0.22, 95% CI 0.18‐0.33 and slope 0.96, 95% CI 0.81‐1.23). With threshold probability of R=12% (i.e. 88% chance of having DR), pursuing additional reperfusion attempts to pursue complete angiographic reperfusion in a patient with high‐likelihood of DR were seven times worse (Cost:Benefit Ratio 1:7, Figure 1) than no further endovascular maneuver. In terms of standardized net reduction, the PROCEED model could reduce one in five unnecessary interventions without missing an intervention for any patient who would eventually have DR. Across a wide range of threshold probabilities, the model outperformed the scenario of the typical decision‐making process in the angiography suite, based on the current treatment guidelines. Conclusion The externally validated model had good predictive accuracy and discrimination. Depending on the acceptable risk threshold, the model may compliment clinical judgment of the treating physicians and inform on natural progression of untreated incomplete reperfusion.

Introduction Clinical utility and diagnostic sensitivity of new‐generation flat‐panel computed tomography perfusion imaging (FPCTP) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCTP obtained directly after MT could provide additional potentially relevant information on tissue reperfusion status. Methods Qualitative, single‐center analysis of all consecutive acute stroke patients admitted between 06/2019 and 03/2021 who underwent MT and post‐interventional FPCTP (n=26). A core‐lab blinded to technical details and clinical data performed reperfusion grading on post‐interventional digital subtraction angiography (DSA) images and time‐sensitive FPCTP maps. All patients were classified according to agreement between DSA and FPCTP. Results In 10/26 patients FPCTP revealed new, potentially clinically relevant information. Core‐lab adjudicated dichotomized detection of hypoperfusion (present/absent) was concurring in 21/26 (81%) patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 (62%) patients, while in 5 (19%) patients with incomplete reperfusion, FPCTP showed additional hypoperfused areas missed on DSA. Of the remaining five patients subject to disagreement regarding the presence or absence of hypoperfusion, three showed complete reperfusion on DSA but hypoperfusion was noted on FPCTP, whereas two showed incomplete reperfusion on DSA without detectable hypoperfusion on FPCTP. FPCTP findings could have avoided Thrombolysis in Cerebral Infarction (TICI) overestimation in all false‐positive operator‐rated TICI3 cases. Conclusion In both core‐lab and real‐world operator assessment, FPCTP may provide additional clinically relevant information in a considerable percentage of patients undergoing MT. Hence, FPCTP may constitute a new standard for evaluating reperfusion efficacy and informed decision making in the angiography suite.

Introduction The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06], p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8

Background The RACECAT (Transfer to the Closest Local Stroke Center vs Direct Transfer to Endovascular Stroke Center of Acute Stroke Patients With Suspected Large Vessel Occlusion in the Catalan Territory) trial was the first randomized trial addressing the prehospital triage of acute stroke patients based on the distribution of thrombolysis centers and intervention centers in Catalonia, Spain. The study compared the drip‐and‐ship with the mothership paradigm in regions where a local thrombolysis center can be reached faster than the nearest intervention center (equipoise region). The present study aims to determine the population‐based applicability of the results of the RACECAT study to 4 stroke networks with a different degree of clustering of the intervention centers (clustered, dispersed). Methods and Results Stroke networks were compared with regard to transport time saved for thrombolysis (under the drip‐and‐ship approach) and transport time saved for endovascular therapy (under the mothership approach). Population‐based transport times were modeled with a local instance of an openrouteservice server using open data from OpenStreetMap.The fraction of the population in the equipoise region differed substantially between clustered networks (Catalonia, 63.4%; France North, 87.7%) and dispersed networks (Southwest Bavaria, 40.1%; Switzerland, 40.0%). Transport time savings for thrombolysis under the drip‐and‐ship approach were more marked in clustered networks (Catalonia, 29 minutes; France North, 27 minutes) than in dispersed networks (Southwest Bavaria and Switzerland, both 18 minutes). Conclusions Infrastructure differences between stroke networks may hamper the applicability of the results of the RACECAT study to other stroke networks with a different distribution of intervention centers. Stroke networks should assess the population densities and hospital type/distribution in the temporal domain before applying prehospital triage algorithms to their specific setting.

Background and aimParaneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer.MethodsActive cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression.ResultsAmong 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12–4.68), history of smoking (aOR 2.77, 95% CI 1.34–5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26–2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00–1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04–1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00–1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58–3.88) and occult cancer (aHR 3.08, 95% CI 1.30–7.32).ConclusionCancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population.

The prediction of stroke outcome is challenging due to the high inter-individual variability in stroke patients. We recently suggested the adaptation of the concept of brain reserve (BR) to improve the prediction of stroke outcome. This concept was initially developed alongside the one for the cognitive reserve for neurodegeneration and forms a valuable theoretical framework to capture high inter-individual variability in stroke patients. In the present work, we suggest and discuss (i) BR-proxies—quantitative brain characteristics at the time stroke occurs (e.g., brain volume, hippocampus volume), and (ii) proxies of brain pathology reducing BR (e.g., brain atrophy, severity of white matter hyperintensities), parameters easily available from a routine MRI examination that might improve the prediction of stroke outcome. Though the influence of these parameters on stroke outcome has been partly reported individually, their independent and combined impact is yet to be determined. Conceptually, BR is a continuous measure determining the amount of brain structure available to mitigate and compensate for stroke damage, thus reflecting individual differences in neural resources and a capacity to maintain performance and recover after stroke. We suggest that stroke outcome might be defined as an interaction between BR at the time stroke occurs and lesion load. BR in stroke can potentially be influenced, e.g., by modifying cardiovascular risk factors. In addition to the potential power of the BR concept in a mechanistic understanding of inter-individual variability in stroke outcome and establishing individualized therapeutic approaches, it might help to strengthen the synergy of preventive measures in stroke, neurodegeneration, and healthy aging.