Abstract Background and aims In acute ischaemic stroke (AIS), central autonomic dysfunction is common and has been linked to increased cardiovascular mortality. However, a reliable and easily applicable biomarker for post-stroke dysautonomia is lacking. We investigated whether pupillomotor dysfunction is associated with functional outcomes following AIS. Methods APEX was a prospective observational study including patients with AIS treated at a tertiary stroke centre in Germany (06/2023-05/2025). Patients were enrolled within 72 hours of stroke onset and underwent automated pupillography at baseline and day 3, comprehensive cardiovascular phenotyping, and assessment of functional outcome (mRS) at 90 days. Adjusted probabilities were derived from ordinal logistic regression models adjusting for age, ASPECTS, baseline NIHSS, BMI, prior stroke, atrial fibrillation, diabetes, hypercholesterolemia, nicotine and alcohol use, coronary heart disease, beta-blocker therapy, and antithrombotic medication. Results The study population comprised 100 AIS patients (median age 76 years [IQR 69–83], 47% female). Each one-standard-deviation increase in maximal pupillary latency was associated with a 64% higher odds of being in a worse mRS category at 90 days (adjusted OR 1.64, 95% CI 1.02–2.63; p=0.042). Adjusted probabilities of poor functional outcome (90-day mRS≥3) increased stepwise across quartiles of maximal pupillary latency (Figure). No change in pupillomotor function was observed between day 1 and day 3 (p=ns), and no association with new-onset atrial fibrillation or autonomic symptoms at 90 days was found (p=ns). Conclusions Early pupillomotor dysfunction is independently associated with worse functional outcome after AIS. Automated pupillography may provide a non-invasive marker to improve early risk stratification after stroke. Conflict of interest Daniela Schöne: nothing to disclose, Lara Kretzschmar: nothing to disclose, Martin Arndt: nothing to disclose, Annahita Sedghi: nothing to disclose, Lydia Plitzko: nothing to disclose, Isabella Püschel: nothing to disclose, Kristian Barlinn: nothing to disclose, Hagen B Huttner: nothing to disclose, Timo Siepmann: nothing to disclose Figure 1 - belongs to Conclusions

Background Post-stroke spasticity (PSS) is a frequent and disabling complication after stroke. Real-world data on the implementation of guideline-recommended antispastic treatment within structured follow-up programs are limited. Methods In this prospective cohort study, patients with persistent motor deficits after stroke were followed within a structured post-stroke care program. Spasticity was assessed using the Modified Ashworth Scale (MAS) at predefined follow-up intervals (3 and 12 months after stroke onset). Clinically relevant spasticity was defined as MAS ≥ 2 in at least one joint. Antispastic treatments, including botulinum toxin type A (BoNT-A), were recorded. The implementation gap for BoNT-A was defined as the proportion of patients with a treatment recommendation who had not initiated therapy. Results Using a cumulative 12-month MAS-based definition among patients with persistent paresis and available follow-up assessments, clinically relevant spasticity was observed in 40/55 patients (72.7%, 95%CI 59-83.9), while 51/55 patients (92.7%, 95%CI 82.4–97.9) showed any increase in muscle tone (MAS > 0). Clinically relevant spasticity was present in 34/53 patients at 3 months (64.2%, 95%CI 49.8–76.9) and in 26/46 patients at 12 months (56.5%, 95%CI 41.1–71.1). Among patients with clinically relevant spasticity, BoNT-A treatment was recommended in 11.8% at 3 months and 26.9% at 12 months, while no patient with a documented recommendation had initiated therapy. Conclusions PSS occurs early and affects a substantial proportion of patients with persistent motor deficits after stroke. Despite structured follow-up and systematic screening, implementation of guideline-recommended BoNT-A therapy remained absent in patients with documented treatment recommendations, indicating substantial barriers to evidence-based outpatient spasticity care.

While therapeutic coma is an established escalation strategy in generalized convulsive status epilepticus, evidence for benefit in non-convulsive status epilepticus (NCSE) is limited and treatment-related complications may affect outcome. We performed a retrospective cohort study of patients with NCSE treated at a tertiary hospital. Patients were classified according to receipt of therapeutic coma, defined as continuous intravenous and/or inhalational anesthetic administration for seizure control. The primary outcome was the occurrence of predefined clinically relevant in-hospital medical complications, including pneumonia, sepsis, cardiac arrhythmias, acute renal failure, renal replacement therapy, venous thromboembolism and cardiopulmonary resuscitation. Secondary outcomes included in-hospital mortality, ICU length of stay and successful termination of NCSE. Confounding by indication was addressed using inverse probability of treatment weighting (IPTW) based on propensity scores. Among 283 patients with NCSE, 111 (39.2

BACKGROUND:Neurocardiac autonomic impairment with reduced heart rate variability (HRV) has been linked to SARS-CoV-2 infection and may persist in patients with post-COVID-19 syndrome. We synthesised meta-analytic data on HRV in post-COVID-19 syndrome. METHODS:Our systematic review and meta-analysis were guided by PRISMA standards. We used MEDLINE, Embase and Web of Science to identify non-randomised studies of HRV in patients with post-COVID-19 syndrome, conducted more than 3 months after infection and compared with healthy controls. The search covered the period from 01/2020 to 09/2023. We pooled data on the following HRV parameters: standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (rMSSD) and low-frequency to high-frequency ratio (LF/HF ratio). We applied a random effects model to account for heterogeneity. Risk of bias was assessed. RESULTS:From 856 initially identified records, we included 11 studies with a total of 1162 participants (593 post-COVID-19 patients and 565 healthy controls). We observed a trend toward lower HRV in post-COVID patients compared to controls, with small to medium effects for SDNN (SMD: 0.26, 95% CI: -0.03 to 0.56, p = 0.09), rMSSD (SMD: 0.11, 95% CI: -0.15 to 0.36, p = 0.41) and LF/HF ratio (SMD: -0.271, 95% CI: -0.61 to 0.07, p = 0.12). Moderate to high statistical heterogeneity of the effects was observed (I2 = 83% for SDNN and 78% for rMSSD) and nine of 11 studies had a high risk of bias. CONCLUSION:This meta-analysis suggests a possible association between post-COVID condition and alterations in neurocardiac autonomic function.

Background/Objectives: The American Heart Association Life's Essential 8 (LE8) is a tool proposed to categorize overall cardiovascular health (CVH), ranging from 0 to 100 and classifies CVH as low (<50), moderate (50-79) or high (≥80), based on the following health behaviors (diet, physical activity, nicotine exposure and sleep) and health factors (body mass index-BMI, lipid levels, glycemic profile and blood pressure). Although used in the general population, it is not part of the health assessment routine in the workplace. We assessed CVH of healthcare workers using an LE8-based score through a mobile application. Methods: Cross-sectional pilot study with adults working at a tertiary hospital in Brazil. We used an app for self-reporting LE8 metrics. Additionally, data on age, sex, and mental health (10-item Perceived Stress Scale, PSS-10) were collected. Results: Sixty-five adults (58.5% female; mean age 36 ± 9.01 years) were included. The mean LE8 overall score was 69.39 ± 12.63. The proportion of participants in the low, moderate and high cardiovascular health categories were 6.2%, 69.2% and 24.6%, respectively. Diet quality (34.76 ± 24.3) and physical activity (45.38 ± 40.58) were in the "low cardiovascular health" category. "Health behaviors" had a significantly lower mean score than "health factors" (58.90 ± 20.53 vs. 79.88 ± 15.55, p < 0.001). The mean PSS-10 score was 19.01 ± 7.49, indicating moderate perceived stress. Overall LE8 and PSS-10 scores were not significantly correlated (rs = -0,0.17; p = 0.161). There was no significant difference in the mean overall LE8 score in the linear regression model adjusting for age, sex and perceived stress. Conclusions: Among employees of a Brazilian tertiary hospital, the adapted LE8 score indicated overall moderate CVH. Health behaviors-particularly diet quality and physical activity-were the main vulnerable areas. Implementation of an LE8-based assessment in the workplace may be useful for targeted prevention strategies in Brazil. Future larger and longitudinal studies are warranted to confirm these findings.

Abstract Background and aims Early re-stenosis or re-occlusion after endovascular therapy (EVT) for middle cerebral artery (MCA) occlusion in intracranial atherosclerotic disease worsens outcomes. We investigated the association between periprocedural tirofiban and post-interventional steno-occlusion assessed by transcranial duplex sonography. Methods We retrospectively analyzed patients with proximal MCA occlusion due to angiographically-confirmed intracranial stenosis treated at a tertiary stroke center (10/2018-11/2025). EVT was performed with or without intracranial stenting; tirofiban was administered at the treating interventionalist’s discretion. Transcranial color-coded duplex sonography (TCCS) was performed within 48 hours after final angiographic run. Post-interventional stenosis was classified as no/moderate and severe/occlusive. Post-interventional intracerebral hemorrhage (ICH, defined as PH1/PH2) was assessed within 24 hours; favorable functional outcome at 3 months was defined as mRS 0-2. Results Of 75 patients, 27 were excluded due to insufficient acoustic windows, leaving 48 patients for analysis; 29 (60.4%) received tirofiban. Intracranial stenting was performed in 36 patients (75%). Post-interventional stenosis or occlusion occurred in 32 patients (66.7%). Tirofiban was not associated with reduced odds of severe post-interventional stenosis or occlusion in the overall cohort (aOR 0.86, 95%CI 0.24–3.05; p=0.82) or in stented patients (aOR 0.63, 95%CI 0.12–3.22; p=0.57). Post-interventional ICH occurred in 17.9% with tirofiban and 0% without (p=0.072). Favorable outcome at 90 days was observed in 22.2% with tirofiban and 44.4% without (p=0.188). Conclusions TCCS-detected steno-occlusion after EVT for MCA occlusion was common. Periprocedural tirofiban was not associated with reduced steno-occlusion, hemorrhage risk or favorable functional outcome. Conflict of interest Daniela Schöne: nothing to disclose, Jan Emmerich: nothing to disclose, Daniel P. Kaiser: nothing to disclose, Volker Puetz: nothing to disclose, Timo Siepmann: nothing to disclose, Johannes Gerber: nothing to disclose, Hagen B. Huttner: nothing to disclose, Kristian Barlinn: nothing to disclose

Background and Purpose: Bridging intravenous thrombolysis (IVT) for anterior circulation large vessel occlusion (acLVO) stroke may alter clot architecture and influence thrombectomy performance, but effects may differ by clot origin. We investigated the association between IVT and time-to-recanalization during thrombectomy by stroke etiology. Methods: We conducted a time-to-event analysis of consecutive patients with acLVO from our prospective thrombectomy registry who were treated at a tertiary stroke center in Germany between January 2017 and January 2023. We assessed the association between bridging IVT and groin-to-recanalization time by stroke etiology (cardioembolic vs non-cardioembolic) using multivariable stratified Cox regression analysis adjusted for demographic, cardiovascular and stroke-related characteristics. Results: Of 1702 patients screened, 798 (413 female [51.8%], median age 77 years [66-84, IQR]) underwent thrombectomy for acLVO and were included. Of these, 395 (49.5%) received IVT and 680 (85.2%) achieved successful reperfusion. In non-cardioembolic stroke, bridging IVT was associated with a 40% higher likelihood of achieving successful reperfusion at any time point during thrombectomy compared with direct thrombectomy (adjusted HR 1.40; 95%CI [1.08, 1.81]; p=0.01; Figure 1A). In contrast, among cardioembolic stroke patients, IVT was linked to a 43% lower likelihood of successful reperfusion when distal thrombus migration was detected on repeated imaging (adjusted HR 0.57; 95%CI [0.33, 0.96]; p=0.03; Figure 1B). Conclusions: Bridging IVT accelerated reperfusion during thrombectomy in non-cardioembolic acLVO but was associated with delayed reperfusion in cardioembolic stroke with distal thrombus migration. Clot origin may be an important determinant of response to IVT before thrombectomy.

Abstract Background and aims Most telestroke models focus on the hyperacute phase and acute stroke therapies, while post-acute management is less frequently covered. Assisted reality (AR) technologies enable real-time audiovisual transmission from the examiner’s perspective, making them suitable for routine ward rounds. The aim of this study is to explore the feasibility of AR-based remote supervision of stroke unit ward rounds. Methods This is a prospective, controlled pilot study conducted at a tertiary stroke unit, designed to simulate a peripheral hospital setting without continuous on-site stroke expertise. Acute stroke patients admitted within 24 hours of symptom onset are included. Over a 12-week study period, two ward rounds per week are randomized 1:1 to AR-supported remote supervision or standard on-site senior supervision. On intervention days, residents conduct ward rounds wearing an AR headset and are connected to a senior stroke neurologist, who can guide examination steps and participate in clinical decision-making, including NIHSS assessment. On control days, ward rounds are conducted by an on-site senior stroke neurologist. The primary endpoint is feasibility, defined as successful AR-supported supervision without major technical failure. Secondary endpoints include system usability, perceived decision support, educational value, time metrics and interrater reliability of NIHSS assessments. NIHSS is additionally assessed by an independent rater blinded to study allocation. Results Study completion is expected in April 2026. Conclusions STROKE-AR will provide prospective data on the feasibility and reliability of AR-supported telemedical stroke unit ward rounds and may help to define the role of AR technologies in routine stroke care. Conflict of interest Daniela Schöne: nothing to disclose, Annahita Sedghi: nothing to disclose, Martin Arndt: nothing to disclose, Marie Nicklas: nothing to disclose, Norma J. Diel: nothing to disclose, Hagen B. Huttner: nothing to disclose, Timo Siepmann: nothing to disclose, Kristian Barlinn: nothing to disclose Figure 1 - belongs to Conclusions

Abstract Background and aims Acute stroke care requires rapid decision-making under significant time pressure. In many emergency departments, initial assessment is performed by residents, particularly during off-hours, with senior neurologists providing supervision by telephone. This setting may increase uncertainty and workload for residents and affect decision-making quality. Assisted reality (AR) technologies allow real-time audiovisual transmission from examiner’s perspective and enable visual remote supervision. The aim of SAFE-AR is to provide prospective data on the feasibility and potential clinical value of AR-based remote supervision in acute stroke care. Findings may help to define the role of AR technologies in supporting clinical decision-making and resident training in time-critical stroke care and inform the design of larger outcome-focused studies. Methods This is a prospective single-center controlled pilot study with day-wise randomization to AR-supported supervision or standard care. Patients with suspected acute stroke and symptom onset <24 hours are included. On intervention days, residents wear an AR headset during initial assessment when deemed necessary by resident, supervising senior neurologist, or both. On control days, supervision is provided by telephone only. Clinical decision-making follows routine standard-of-care algorithms in both study arms. Primary endpoint is feasibility, defined as successful AR-supported supervision without major technical failure. Secondary endpoints include system usability (system usability scale), perceived safety and decision support, educational value and stroke process metrics. Results Recruitment is ongoing. Study completion is expected in May 2026. Conflict of interest "Norma J. Diel: nothing to disclose", "Eyad Altarsha: nothing to disclose", "Simon Winzer: nothing to disclose", "Patrick Schramm: nothing to disclose", "Daniela Schoene: nothing to disclose", "Timo Siepmann: nothing to disclose", " Hagen B. Huttner: nothing to disclose", "Kristian Barlinn: nothing to disclose"

ABSTRACT Objective Intravenous thrombolysis (IVT) before thrombectomy for ischemic stroke may alter clot structure and procedural performance. We investigated how IVT relates to thrombectomy metrics across stroke etiologies. Methods We performed a time‐to‐event analysis of consecutive patients with anterior circulation large vessel occlusion (acLVO) stroke from a prospective thrombectomy registry at a German tertiary stroke center (January 2017–January 2023). The associations between IVT and groin‐to‐recanalization time and number of aspiration attempts were assessed using multivariable stratified Cox regression adjusted for demographic, cardiovascular, and stroke‐related variables. Results Of 1702 patients screened, 798 (413 female [51.8%], median age 77 years [66, 84; IQR]) underwent thrombectomy. IVT was administered to 395 (49.5%) patients, and successful reperfusion (mTICI ≥ 2b) was achieved in 680 (85.2%) patients. In non‐cardioembolic stroke, IVT facilitated clot removal, yielding a 40% higher likelihood of successful reperfusion at any time point compared with direct thrombectomy (aHR 1.40; 95% CI [1.08, 1.81]; p = 0.01) and a 36% reduction of aspiration attempts (IRR = 0.64, 95% CI [0.50–0.84], p = 0.001). In cardioembolic stroke, IVT did not alter the incidence of successful reperfusion during thrombectomy (aHR 1.13; 95% CI [0.92, 1.39]; p = 0.26) or the number of aspiration attempts (combined IRR ≈ 1.00, 95% CI [0.82–1.22]) but was associated with a 43% lower likelihood of successful reperfusion throughout the intervention if distal thrombus migration occurred (aHR 0.57; 95% CI [0.33, 0.96]; p = 0.03). Interpretation IVT was associated with faster reperfusion during thrombectomy in non‐cardioembolic acLVO, whereas in cardioembolic stroke with distal clot migration it was associated with delayed reperfusion.

Abstract Background and aims Endovascular thrombectomy restores cerebral perfusion but may cause hemorrhagic reperfusion injury. We investigated whether chronic hyperglycemia, reflected by elevated HbA1c, increases this risk. Methods We performed a post hoc analysis of a prospective registry of consecutive adults treated with endovascular thrombectomy for anterior circulation large vessel occlusion between 1/2017 and 1/2023 at a tertiary stroke center serving as the hub of a regional telemedicine network with 13 referring hospitals in Germany. Patients were categorized by HbA1c (normal, prediabetes, diabetes). Intracranial hemorrhage was classified using the Heidelberg Bleeding Classification. Causal effects were estimated using double-robust inverse probability weighted regression with adjustment for demographic, clinical, imaging, and procedural confounders. Dose-response relationships and robustness were assessed using continuous HbA1c models and sensitivity analyses. Results Among 983 patients, intracranial hemorrhage occurred in 35.5% (hemorrhagic infarction 24.9%, parenchymal hematoma 7.4%). After weighting with excellent covariate balance, diabetic HbA1c levels (≥6.5%) were associated with a significantly higher risk of hemorrhagic reperfusion injury compared with normal HbA1c (<5.7%) (Average Treatment Effect 14.7%, 95% CI 3.9–25.6%, p=0.008), corresponding to an absolute risk increase from 32.9% to 47.6% (Number-Needed-to-Harm=6). Dose-response analyses demonstrated a progressive rise in hemorrhage risk at HbA1c values above the diabetes threshold (Figure 1). These findings were consistent across sensitivity analyses using alternative HbA1c cut points, propensity score matching, and adjusted regression models. Conclusions Elevated HbA1c is associated with a dose-dependent increase in intracranial hemorrhage after thrombectomy, identifying chronic hyperglycemia as a clinically relevant and potentially modifiable risk factor of cerebral reperfusion injury. Conflict of interest "Norma J. Diel: nothing to disclose", "Martin Arndt: nothing to disclose", " Isabella Püschel: nothing to disclose", "Erik Simon: nothing to disclose", "Kristian Barlinn: nothing to disclose", "Daniel P. O. Kaiser: nothing to disclose", "Hagen B. Huttner: nothing to disclose", "Annahita Sedghi: nothing to disclose", "Timo Siepmann: nothing to disclose" Figure 1 - belongs to Results

Background: Diagnostic discrimination between ischemic stroke (IS) and hemorrhagic stroke (HS) is required for successful intervention with time-critical acute treatments. The available data on blood-based RNA biomarkers and discrimination between IS and HS are limited. This systematic review aimed to examine and summarize the existing literature on potentially useful blood-based RNA biomarkers that may aid in preclinical acute diagnosis. Methods: We systematically reviewed the literature on the ability of blood-based RNA biomarkers to discriminate between IS and HS according to PRISMA guidelines. We searched PubMed, EMBASE, The Cochrane Library, and The Web of Science for eligible randomized controlled trials, observational studies, and case-control studies published in the English language without time limitation. The risk of bias was evaluated using the Newcastle-Ottawa Scale. Results: We included eight studies with a total of 728 patients (436 with IS and 292 with HS) in our review. The study quality was good in five and fair in three investigations. No meta-analysis was performed due to high heterogeneity in methods and study endpoints. Reported biomarkers include miRNA-124-3p, miRNA-16, miRNA-340-5p, lncRNA XIST (X-inactive specific transcript), PFKFB3 mRNA (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase), tRNA derivatives, tRNA fragments, extracellular miRNAs, transcriptome changes, and MCEMP1 gene expression. Assessment techniques varied widely across studies, ranging from RNA sequencing to qPCR, microarray, human transcriptome array, and ELISA. MicroRNA-124-3p, miRNA-340-5p, lncRNA XIST, PFKFB3 mRNA, and MCEMP1 gene expression differed significantly between IS and HS. In one study, principal component analysis and unsupervised learning demonstrated the utility of hierarchical clustering of differentially expressed exons to discriminate between HS and IS. Conclusions: This review demonstrates the utility of single RNA-based targets and clusters that may have diagnostic value in distinguishing IS from HS. However, the current body of evidence is limited by considerable methodological heterogeneity between studies. Registration: This systematic review was prospectively registered on PROSPERO on 21 April 2023 (CRD42023411203).

Importance:Telestroke networks provide coverage of neurological expertise in rural areas. While most teleneurological consultations focus on acute stroke care in emergency departments, neurological expertise remains crucial in the subacute phase. However, teleneurological ward rounds have not yet been systematically investigated for feasibility and quality. Objective:To assess noninferiority of teleneurological ward rounds compared with conventional on-site ward rounds during subacute inpatient stroke care, focusing on adherence to guideline-based quality indicators. Design, Setting, and Participants:This prospective, multicenter, nonrandomized, noninferiority study was conducted at 15 primary care hospitals within 4 German telestroke networks from October 2022 to December 2024. Adults (18 years or older) hospitalized with suspected acute ischemic or hemorrhagic stroke or transient ischemic attack were eligible. A total of 1908 patients were screened. These data were analyzed from January 2025 to May 2025. Exposures:Patients received both a teleneurological and an on-site neurological ward round. Teleneurological ward rounds were performed by network neurologists via video consultation; on-site consultations were performed by local neurologists. Documentation from both consultations was evaluated by blinded external neurovascular experts. Main Outcomes and Measures:The primary outcome was complete fulfillment of 6 predefined, guideline-based quality domains: etiological classification, neurological examination, risk assessment, diagnostic recommendations, secondary prevention, and recommended aftercare. Noninferiority was defined as a maximum difference in proportions of correct assessments of 5 percentage points. Secondary outcomes included correctness of individual domains and expert quality ratings on a visual analoge scale. Results:A total of 518 patients were enrolled (median age, 71 years; 222 female [44%] and 296 male [56%]) and 501 were included in the final analysis. Complete adherence to all quality criteria was achieved in 92% (95% CI, 90%-94%) of teleneurological ward rounds compared with 54% (95% CI, 49%-58%) of on-site ward rounds (absolute difference, 38 percentage points; 90% CI, 34-42). Superiority of teleneurological ward rounds was consistent across all quality domains with the most pronounced differences observed for secondary prevention (absolute difference, 21% percentage points; 90% CI, 17-24). Conclusions and relevance:Teleneurological ward rounds in subacute stroke care were noninferior and even superior when compared with on-site consultations, with respect to guideline adherence across all quality domains. These findings support the integration of telemedicine into routine inpatient stroke care, particularly in regions with limited access to neurological expertise.

Abstract Background and aims We hypothesized that higher HDL-C levels provide neuroprotection and mitigate hemorrhagic reperfusion injury in patients undergoing thrombectomy for anterior circulation large vessel occlusion (acLVO). Methods The prospective SHIELD-EVT registry study evaluated patients treated with thrombectomy for acLVO at 15 German centers between 1/2017 and 1/2025. We utilized inverse probability weighted regression and ordered logistic shift analysis to assess the impact of HDL-C levels on imaging-defined hemorrhagic injury (intracerebral or subarachnoid bleeding per Heidelberg classification) and 90-day functional outcomes. Results In our cohort of 7085 thrombectomy patients (51.9% women; median age, 76 years [IQR, 65–83], median HDL-C 43.4 mg/dL [IQR, 35-53]), those in the lowest HDL-C quintile (4-33 mg/dL) had a 32.9% risk of hemorrhagic reperfusion injury. Compared with this group, hemorrhage risk decreased by 6.2% in quintile 2 (34-40 mg/dL; P=0.02), by 6.0% in quintile 3 (40-47 mg/dL; P=0.04), by 6.2% in quintile 4 (47-56 mg/dL; P=0.03), and by 5.9% in quintile 5 (56-205 mg/dL; P=0.04). The dose response plot showed a threshold effect above 33 mg/dL with sustained protection across normal-to-high HDL ranges. (Figure A) We observed a significant shift in the overall distribution of 90-day mRS scores in favor of a HDL-C level above the median (adjusted OR 0.61; 95CI% [0.55; 0.69]; p<0.001). (Figure B) Conclusions Higher HDL-C levels above a 33 mg/dL threshold are independently associated with a significant reduction in hemorrhagic reperfusion injury and superior 90-day functional recovery following thrombectomy for acLVO. Conflict of interest Figure 1 - belongs to Conclusions

Abstract Background and aims Hyperglycemia has been suggested as a risk factor for haemorrhagic reperfusion injury after endovascular thrombectomy (EVT) in large vessel occlusion (LVO) stroke. However, the specific glucose thresholds impacting clinical outcomes remain unclear. We investigated the dose-response relationship between admission glucose and intracranial hemorrhage (ICH) in a large, real-world cohort. Methods We analysed data from our prospective thrombectomy registry of LVO patients treated from 01/2017 to 01/01/2023 at a German tertiary stroke centre. We evaluated the association between blood glucose levels at admission and risk of ICH as classified by the Heidelberg Bleeding Classification. Blood glucose levels were categorized in quintiles to account for nonlinearity. Causal effects were estimated applying inverse probability weighted regression analysis with adjustment for relevant demographic, clinical, laboratory (including hemoglobin A1c), and imaging characteristics. Results In our cohort of 1080 LVO patients (544 female [50.4%], median age 77 years [67-84, IQR]), haemorrhagic reperfusion injury occurred in 423 patients (39.2%). We identified a U-shaped relationship between admission glucose and ICH risk (Figure). Compared to an optimal blood glucose range (5.96-6.73mmol/L, ICH rate 33.3%), both low glucose (3.96-5.95mmol/L, average treatment effect (ATE) 14.5%, 95%CI[3,1%-25,8%], p=0.01) and high glucose levels (9.10-23.18mmol/L, ATE 13.1%, 95%CI[1,8%-24,5%], p=0.02) were independently associated with increased ICH risk. Conclusions Strict maintenance of normoglycemia prior to EVT—avoiding both hypo- and hyperglycemia—represents a promising strategy to reduce reperfusion injury; notably, this effect is independent of long-term glycemic control, underscoring the importance of glucose management during the hyperacute phase of stroke. Conflict of interest Annahita Sedghi: nothing to disclose, Norma Diel: nothing to disclose, Martin Arndt, Isabella Püschel: nothing to disclose, Kristian Barlinn: nothing to disclose, Daniel Kaiser: nothing to disclose, Timo Siepmann: nothing to disclose Figure 1 - belongs to Conclusions

Abstract Background and aims Cardiovascular autonomic dysfunction is a frequent complication following acute ischemic stroke (AIS), leading to microcirculatory disturbances. However, its specific impact on paretic limbs and its role in functional recovery remain poorly understood. We characterized cutaneous microcirculation after AIS and hypothesized that microcirculatory impairment is more pronounced in paretic extremities. Methods LUMOS was a prospective observational study (12/2022–12/2023) of AIS survivors at a German tertiary stroke center. Cutaneous microcirculation (mean perfusion units, PU) was assessed bilaterally at three forearm sites using Laser Doppler Imaging (LDI) at admission (t1) and on day three (t2). Functional outcome (mRS) was assessed at 90 days. Generalized linear mixed models (GLMM) were used for analysis, with model fit determined by the Akaike information criterion. Results In our cohort of 66 AIS patients (median age 74 years [IQR 64–84]), mean cutaneous blood flow was significantly lower in paretic extremities compared to non-paretic limbs (81.90 ± [SD] PU vs. 86.12 ± 26.23 PU; p=0.02). Perfusion decreased significantly over time in paretic and non-paretic extremities (t1: 88.49 ± 27.08 PU vs. t2: 79.32 ± 28.84 PU; p=0.002) (Figure). However, early microcirculatory impairment did not predict 90-day functional outcome (p > 0.05). Conclusions Cutaneous micocirculation deteriorated in both, paretic and non-paretic extremities in AIS survivors, suggesting systemic dysautonomia beyond the effect of local immobilization. LDI-based assessment of cutaneous microcirculation may be a viable bedside tool for autonomic function monitoring in these patients but its long-term prognostic value warrants further investigation. Conflict of interest Isabella Püschel: nothing to disclose. Aileen Dürr: nothing to disclose. Eyad Altarsha: nothing to disclose. Norma Diel: nothing to disclose. Erik Simon: nothing to disclose. Kristian Barlinn: nothing to disclose. Hagen B. Huttner: nothing to disclose. Timo Siepmann: nothing to disclose. Figure 1 - belongs to Results

Abstract Background and aims Bow-Hunter syndrome is a rare cause of ischemic stroke due to compression of the vertebral artery (VA) during head rotation. We describe an unusual “Inverse Bow Hunter” variant. Methods A 50-year-old male with recurrent embolic posterior circulation strokes presented to our tertiary stroke center. Prior CT revealed proliferative osseous changes of the left superior articular process of C6, causing narrowing of the ipsilateral transverse foramen and focal stenosis of the left VA (V2 segment). We performed dynamic digital subtraction angiography (DSA) and duplex sonography of positional hemodynamics. Results DSA in a neutral head position confirmed stenosis of the left V2 segment with absent antegrade flow and collateral filling of distal VA segments via the ascending cervical artery. Dynamic imaging revealed that maximal leftward head rotation resulted in markedly reduced VA flow, whereas maximal rightward rotation successfully restored antegrade flow. Duplex sonography corroborated these findings, demonstrating reduced flow in the neutral position, normalization during leftward rotation, and a stenotic flow pattern during rightward rotation. Subsequent MRI identified new silent embolic cerebellar infarcts. Following a multidisciplinary discussion of therapeutic options, the patient was maintained on antiplatelet therapy, and surgical resection of the compressive osseous structure was scheduled. Conclusions This case illustrates a rare “Inverse Bow Hunter” variant with flow arrest in neutral head position and relief during head rotation, where hemodynamic changes may lead to thromboembolic strokes. Dynamic imaging in rotated head positions may hence be helpful in the workup of suspected vertebral artery stenosis. Conflict of interest Martin Arndt: nothing to disclose; Pawel Krukowski: nothing to disclose. Timo Siepmann: nothing to disclose. Hagen B. Huttner: nothing to disclose. Ilker Eyüpoglu: nothing to disclose. Daniel P.O. Kaiser: nothing to disclose.

Layering hyperintensity in the gallbladder is frequently observed on T1-weighted (T1w) magnetic resonance imaging (MRI), but its association with hepatobiliary disorders is not well understood. This study aimed to evaluate the prevalence of T1w layering in the gallbladder and its correlation with ultrasound (US) findings and patient characteristics in a cohort with significant liver disease. A single-center study from 2015 to 2022 included patients who underwent MRI and abdominal US within one week. Exclusion criteria were poor imaging quality and prior cholecystectomy. MRI findings were correlated with US and analyzed against patient characteristics. Among 415 patients (mean age 58.3 ± 14.8 years; mean BMI 28.0 ± 4.5 kg/m²), 67

Background: Direct oral anticoagulants (DOAC) are associated with an increased risk of hematoma expansion (HE) in spontaneous intracerebral hemorrhage (ICH). However, the critical DOAC level influencing this risk remains unclear. This study investigates the impact of DOAC levels on the risk of HE in patients with DOAC-associated ICH. Methods: We conducted a retrospective analysis of patients with DOAC-associated ICH who had DOAC-calibrated anti-Xa or -IIa activity levels measured upon admission. Patients were categorized based on a clinically established cutoff for subtherapeutic DOAC levels (<30 ng/ml). Hematoma expansion was defined as a ≥35% increase in hematoma volume between admission and 24-72 hour follow-up CT scans, with symptomatic HE defined as a concurrent ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS). Multivariable logistic regression models were used to assess the association between DOAC levels and HE, adjusting for baseline ICH volume, onset-to-imaging time, systolic blood pressure, and the use of reversal agents. Results: Among 2147 ICH patients admitted between January 2012 and November 2023, 88 had DOAC-associated ICH with available DOAC levels (apixaban, n=36; rivaroxaban, n=30; edoxaban, n=17; dabigatran, n=4). No significant differences were observed in baseline (24.3±27.5 vs. 19.5±16.6 ml; p=0.6) or follow-up ICH volumes (30.6±36.4 vs. 36.4±14.6 ml; p=0.6) between patients with high versus low DOAC levels. Rates of HE (15.4% vs. 22.2%; p=0.6) and symptomatic HE (7.7% vs. 11.1%; p=0.5) were also similar across groups. DOAC levels below the cutoff did not predict HE (adjusted OR 0.7, 95% CI 0.1-4.5; p=0.7). These findings remained consistent when applying a <50 ng/ml DOAC cutoff and in the subgroup of patients not receiving reversal therapy. Conclusions: Our study suggests that DOAC levels, as defined by the current cutoffs, do not significantly predict hematoma expansion in patients with DOAC-associated ICH. Further research in multicenter cohorts is necessary to better delineate the relationship between specific DOAC levels and the risk of HE.

BACKGROUND:Early differentiation between acute ischemic stroke (AIS) and stroke mimics remains challenging in emergency setting. Molecular biomarkers such as matrix metalloproteinase-9 (MMP-9) may aid in improving diagnostic accuracy. METHODS:A systematic literature search was conducted according to PRISMA guidelines across PubMed, EMBASE, Cochrane Library, and Web of Science. Studies assessing MMP-9 concentrations within 24 hours of symptom onset in AIS patients versus stroke mimics or healthy/matched controls ≥18 years were included. Random-effects meta-analyses were used to estimate pooled mean differences (MD) in MMP-9 levels between groups. Heterogeneity was assessed using I² and Cochran's Q. RESULTS:Twenty-seven studies were included, with 16 (2,661 AIS patients, 1,283 all controls) meeting criteria for meta-analysis. Mean MMP-9 concentrations were significantly higher in AIS patients compared to all controls combined (MD: 93.9 ng/mL; 95%CI: 25.0-162.8; p=0.01, I²=96%, Cochran's Q: p<0.001). Subgroup analyses confirmed elevated levels in AIS patients versus healthy/matched controls (MD: 110.6 ng/mL; 95%CI:13.8-207.4; p=0.029) and versus stroke mimics (MD: 66.61 ng/mL; 95%CI: -6.2-139.4; p=0.01). Heterogeneity remained consistently high across comparisons (I² ≥ 95%; p<0.05). CONCLUSION:MMP-9 levels appear significantly elevated in AIS patients compared to both stroke mimics and healthy controls/matched controls, supporting its potential as a diagnostic biomarker in the acute setting. However, substantial inter-study heterogeneity limits generalizability, and standardized studies are needed to validate their clinical applicability. (PROSPERO: CRD42024611953) FUNDING: We acknowledge support from the German Research Foundation, the Medical Faculty Carl Gustav Carus, and the SLUB, as well as the Open Access Publication Funds of the TU Dresden. The funding bodies had no impact on any aspect of the study or the content of the manuscript.