Abstract Background and aims Mechanical thrombectomy (MT) is effective for acute Basilar artery occlusion(BAO), but the optimal technique for quick recanalization and improved outcomes remains unclear. We compared Stent retriever (SR), Contact aspiration (CA) and combined SR plus CA technique as first-line approach during mechanical thrombectomy for BAO. Methods We emulated a hypothetical trial comparing CA, SR and combined technique as first-line in patients with BAO, using data from the Italian Registry of Endovascular Treatment. The primary outcome was first-pass effect (FPE), defined as mTICI 2b-3 with 1 pass of MT. We used inverse probability weighting (IPW) adjusted for prespecified covariates to weight each individual’s contribution to the outcome. Results We included 960 patients with BAO treated with MT: 570 with CA, 268 with SR, and 122 with combined technique as first approach. After applying IPW, SR was associated with lower odds of FPE as compared to CA (aOR 0.48[95%CI 0.33-0.70]), no differences were found comparing SR versus combined technique neither CA versus combined technique. First-pass mTICI 3 was less frequent with SR as compared to CA (0.62[95%CI 0.43-0.90]). 90-day mRS 0-3 after FPE was more frequent with CA as compared to both SR (aOR 0.57[95%CI 0.38-0.85]) and combined technique (aOR 0.50[95%CI 0.28-0.89]). The results were consistent across all the subgroups (p for interaction>0.05). Conclusions In patients with BAO, CA was more effective than SR and was associated with better oucome compared to other techniques. Therefore, less traumatic approaches might be preferred as first-line in BAO. Conflict of interest E.N. is member of the medical and scientific advisory board of Cercare Medical and declares speaker's honoraria from Boehringer Ingelheim; A.C. has nothing to disclose; V.S. has nothing to disclose; G.P. has nothing to disclose; P.N. has nothing to disclose; M.D. has nothing to disclose; M.R. has nothing to disclose; D.T. declares consulting or advisory board fees or speaker’s honoraria from Alexion, ASTRA Zeneca, Boehringer, Medtronic and Pfizer. Figure 1 - belongs to Methods Figure 2 - belongs to Results

INTRODUCTION:Recent randomised trials have questioned the benefit of endovascular therapy (EVT) for MeVO stroke, but data from clinical practice are limited. This study aimed to assess the effectiveness and safety of EVT, with or without intravenous thrombolysis (IVT), vs IVT alone in MeVO stroke using registry-based real-world data. PATIENTS AND METHODS:This retrospective multicentre study included patients from 82 Italian centres in the Safe Implementation of Treatments in Stroke (SITS) registry (January 2020-December 2023). Adults with acute ischaemic stroke due to MeVO (ACA A1/A2, MCA M2/M3 or more distal or PCA P1/P2), treated with IVT or EVT ± IVT, and with available 90-day mRS scores were included. Patients with tandem occlusions were excluded. Propensity score matching (1:1) was used to balance baseline variables. Primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included in-hospital mortality, intracranial haemorrhage incidence and recanalisation status. RESULTS:Among 1375 total patients, 780 were included and matched (390 per group) by propensity score. Baseline characteristics were balanced. Functional independence at 90 days was achieved in 60.6% of EVT ± IVT patients vs 60.9% in the IVT-only group (odds ratio [OR] 0.99; 95% CI, 0.73-1.34; P = .939). When restricted to patients with baseline mRS < 2, functional independence rates remained comparable between groups, confirming the primary findings. In-hospital mortality was non-significantly lower in the EVT ± IVT group (5.4% vs 8.7%, P = .069). Symptomatic intracranial haemorrhage rates were comparable between groups, although overall haemorrhagic complications were higher with EVT (18.4% vs 11.2%, P < .0001). Stratified analyses by stroke severity and treatment timing showed consistent lack of benefit across all subgroups (all interaction P-values > .05). DISCUSSION:The absence of functional benefit from EVT observed in this real-world cohort is consistent with the results of the ESCAPE-MeVO and DISTAL randomized trials. Notably, the higher rate of any intracranial haemorrhage in the EVT group (18.4% vs 11.2%), driven primarily by minor haemorrhagic events, represents a clinically meaningful safety concern that must be weighed against the lack of demonstrated efficacy. A hypothesis-generating signal was observed in patients treated within 180 minutes (OR 2.16, 95% CI 1.06-4.38), warranting prospective investigation. The retrospective design and the limitations inherent to registry-based data, including incomplete procedural data and anatomical heterogeneity in MeVO classification, should be considered when interpreting these findings. CONCLUSIONS:Endovascular therapy did not improve long-term functional outcomes compared to IVT alone in MeVO stroke but was associated with higher haemorrhagic risk. These findings support a cautious approach to EVT in this setting, in line with recent trial evidence.

Abstract Background and aims National stroke registries provide high-quality real-world data, yet multinational analyses remain limited by data fragmentation, interoperability gaps, and regulatory constraints. The Federating European REgistries for Stroke (FERES) initiative was designed to enable large-scale European stroke research through privacy-preserving federated analytics. We report the methodological framework of FERES and its formal validation using a predefined clinical showcase. Methods FERES employs a GDPR-compliant federated architecture based on harmonization of national stroke registries to stroke-specific Common Data Elements (CDEs) and distributed analysis using a secure medical informatics platform. Validation was performed using a large harmonized stroke registry cohort, partitioned into independent nodes to emulate a multi-site federation. A predefined Minimal Analysis Subset (Figure 1) addressed a standard comparison between anterior and posterior circulation ischemic strokes. Identical analytical pipelines were executed centrally on pooled data and in federated mode. Agreement was assessed using absolute percentage error (APE) for descriptive metrics, concordance of hypothesis-test decisions, effect-size consistency, and agreement of regression coefficients in log-odds space. Results Federated execution reproduced centralized pooled-data analyses with numerical equivalence. For all descriptive metrics, APE for means, standard deviations, and proportions was effectively 0%, with exact matching counts. All predefined anterior–posterior circulation hypothesis tests showed complete decision concordance (all p<0.05). Effect sizes (Cohen’s d, rank-biserial correlation, Cramér’s V) and multivariable regression coefficients demonstrated only negligible differences across execution modes. No individual-level data were transferred. Conclusions FERES provides a validated, privacy-preserving federated framework that reproduces centralized stroke registry analyses. It enables scalable, multinational real-world evidence generation benchmarking and quality improvement in stroke care. Conflict of interest The FERES project received financial support by the European Academy of Neurology (EAN) and non-financial support from the European Stroke Organization (ESO). All authors : Nothing to disclose Figure 1 - belongs to Methods

Abstract Background and aims Perihematomal hypoperfusion has been considered a benign oligoemic state; however, emerging evidence suggests that it may represent an ischemic penumbra with potential progression to irreversible injury. This evolution may result from the combined effects of perfusion abnormalities and neuroinflammatory mediators of secondary brain injury. This study aims to characterize the pathophysiology of perihematomal hypoperfusion. The primary objective is to assess the association between acute-phase perfusion parameters and the development of ischemic lesions in the subacute phase. Secondary objectives are to evaluate the role of plasmatic mediators—including NADPH oxidase, an oxidative stress –related enzyme, and vasoactive molecules (endothelin-1 and nitric oxide)—in the development of perihematomal hypoperfusion and ischemic damage, and to assess their associations with hematoma and edema evolution and clinical outcomes. Imaging and plasmatic biomarkers may identify patients at increased risk of secondary injury. Methods We will enroll 124 patients with spontaneous ICH presenting to the Emergency Department of Umberto I Hospital, Rome, within 12 hours of symptom onset. CT perfusion/angiography will be performed, together with blood sampling for biomarkers analysis. Conventional (Tmax, rCBF/rCBV), microvascular and metabolic (OEF, CMRO2) perfusion parameters will be quantified in the perihematomal hypoperfusion area using Cercare Medical Neurosuite® software. A non-contrast CT at 24 hours will assess hematoma and edema volume evolution. MRI at 7 days will be performed to detect secondary ischemic lesions. Clinical outcome will be assessed by mRS at 3 months. Results The project is under review by the local ethics committee and will be initiated upon approval. Conflict of interest Paolo Amisano: recipient of the HippOnion–ISA AII 2025 Grant. Svetlana Lorenzano: nothing to disclose. Ettore Nicolini: advisory board member for CERCARE Medical and speaker honoraria from Boehringer Ingelheim. Antonio Ciacciarelli: speaker honoraria from the Angels Initiative. Marta Iacobucci: nothing to disclose. Danilo Toni: advisory board participation and speaker’s honoraria from Alexion, AstraZeneca, Boehringer Ingelheim, Medtronic, and Pfizer. Manuela De Michele: nothing to disclose.

Abstract Background and aims Leptomeningeal collateral (LMC) circulation helps preserve brain tissue during acute ischemic stroke (AIS), with poor collateral status predicting worse outcomes. This study assessed the association between asymmetric dimethylarginine (ADMA), LMCs, infarct volume, and oxidative stress in 101 AIS patients with large vessel occlusion within 6h or wake-up stroke. Methods LMC status was graded using the Menon score (poor, intermediate, or good) on CT angiography, and recanalization was assessed by the modified Thrombolysis in Cerebral Infarction score. Serum ADMA, NADPH oxidase 2 (NOX2), and nitric oxide (NO) levels were measured at admission (<6h, T0), 24h (T1), and 48h (T2). Results Among patients, 43.1% had good, 35.3% intermediate, 21.6% poor LMC status. Higher admission ADMA levels were significantly associated with poor LMC at T0 (p=0.028) and more severe neurological deficits at T1 and T2 (p=0.005, p=0.008). ADMA levels increased over time (p=0.046), and correlated with NOX2 at T1 (p<0.001). Rising NOX2 was associated with increased neutrophils (p=0.013) and decreased lymphocytes (p=0.006). Conclusions ADMA may impair endothelial function by reducing NO availability and enhancing NOX2-driven oxidative stress. These findings support a role for the ADMA-NO-NOX2 axis in limiting collateral circulation. Targeting this axis may represent a therapeutic strategy to improve outcomes in AIS. Conflict of interest Manuela De Michele: nothing to disclose

BACKGROUND:Acute ischemic stroke is a leading cause of death and disability. Despite strong evidence supporting reperfusion therapies and Stroke Unit care, access and quality of stroke services remain heterogeneous across Europe. Although national stroke registries provide valuable real-world data, fragmentation, limited interoperability, and data protection constraints have restricted multinational analyses and benchmarking. METHODS:The Federating European REgistries for Stroke (FERES) initiative establishes a GDPR-compliant federated framework for secondary use of stroke registry data. FERES harmonizes heterogeneous datasets through a stroke-specific Common Data Elements (CDE) model and performs analyses locally within each registry using the Medical Informatics Platform, sharing only aggregated, non-identifiable outputs. To validate the framework, a predefined showcase analysis comparing anterior versus posterior circulation acute ischemic stroke was executed in both centralized and federated modes using an identical harmonized dataset. RESULTS:FERES connected five national registries from Austria, Greece, Ireland, Italy, and Switzerland within a unified federated infrastructure. At the time of analysis, 149,772 patient events from two registries were accessible for federated querying, with three additional registries technically integrated and in advanced onboarding. The harmonized ontology comprised 945 standardized variables spanning the stroke care pathway. Federated execution reproduced centralized pooled-data results across descriptive statistics, hypothesis testing, effect sizes, and multivariable regression models with only minimal numerical discrepancies. CONCLUSIONS:FERES demonstrates that large-scale, multinational stroke research and benchmarking can be conducted in Europe using a privacy-preserving federated approach, providing a scalable foundation for cross-border real-world evidence generation and quality improvement.

BACKGROUND:Endovascular thrombectomy (EVT) is the standard of care for large-vessel occlusion stroke. Medium distal vessel occlusions (MDVO) account for 25-40% of acute ischemic stroke cases, but recanalization rates with intravenous thrombolysis (IVT) are often less than 50%. Recent randomized trials have failed to show better outcomes after EVT versus best medical management in MDVO stroke. The main research question of the study: Is the addition of EVT to IVT associated with benefits or harm when treating patients with MDVO stroke? METHODS:We performed a retrospective observational study of patients in the Safe Implementation of Treatments of Stroke International Stroke Treatment Registry (SITS-ISTR) 2016-2023, treated with IVT or IVT + EVT for occlusion of the anterior cerebral artery (ACA), posterior cerebral artery (PCA) or distal middle cerebral artery (MCA; M3 and more distal). Only patients with available occlusion data from computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) were included. Patients with M2 occlusions or those treated with EVT only were excluded. Outcomes were acute post-treatment hemorrhage, 3-month modified Rankin Scale (mRS) score, and death at 3 months. Propensity score matching was performed due to baseline imbalances (age, National Institutes of Health Stroke Scale [NIHSS], and occlusion site). RESULTS:Of 2198 included patients, 295 (13%) were treated with IVT + EVT, and 1903 (87%) received IVT alone. IVT + EVT patients were younger (73 vs. 75) and had higher median NIHSS: 10 (interquartile range [IQR]: 6-15) versus 8 (5-12), p < 0.001. More IVT + EVT patients were functionally independent (mRS 0-1) before stroke at 91.8% versus 83.0% (p < 0.001). For the IVT + EVT group, PCA occlusion was the most common (n = 179, 60.7%), and distal MCA (n = 1140, 59.9%) in the IVT group. After propensity score matching, IVT + EVT was associated with worse 3-month outcomes compared to IVT alone: mRS 0-1 (35.8% vs. 47.0%, p = 0.016, mRS 0-2 52.4% vs. 63.4%, p = 0.017, and death 21.4% vs. 11.8%, p = 0.005). Symptomatic intracerebral hemorrhage rates were higher in the IVT + EVT group according to European Collaborative Stroke Study II (ECASS II): 6.5% versus 2.4%, p = 0.043, but were similar according to National Institute of Neurological Disorders and Stroke (NINDS): 8.2% versus 4.2%, p = 0.095, and Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST): 0.6% versus 1.2%, p = 0.825. CONCLUSIONS:IVT + EVT for MDVO was associated with worse functional outcomes compared to IVT alone. Our results support recent publications but should be interpreted with caution due to the retrospective observational design, warranting further RCTs.

BACKGROUND:Collateral blood flow is a critical determinant of successful recanalization in acute ischemic stroke caused by large vessel occlusion. Head down tilt -15° (HDT15), similar to Trendelenburg positioning, is a simple, low-cost positional therapy that may augment cerebral collateral blood flow and penumbral survival. The aim of the study is to assess the safety, feasibility, and efficacy of HDT15 in improving cerebral collateral circulation and clinical outcomes in patients with large vessel occlusion-acute ischemic stroke treated with mechanical thrombectomy (MT). METHODS:The DOWN-SUITE trial (Head Down Tilt 15° to Increase Collateral Flow in Acute Ischemic Stroke) is a multicenter, randomized, open-label, phase 2a/b clinical trial with blinded outcome assessment, conducted across 7 Italian stroke centers. A total of 118 patients with acute ischemic stroke due to M1 segment middle cerebral artery occlusion will be randomized 1:1 in the emergency department to receive HDT15 or standard positioning (head-of-bed 0° to +30°) before and during MT. RESULTS:The primary end point is good collateral status (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grade 3-4), assessed on the first angiographic sequence during MT by a blinded imaging core laboratory. Secondary end points include feasibility (proportion maintaining HDT15, admission-to-MT time), safety (symptomatic intracranial hemorrhage, pneumonia, vomiting, neurological deterioration, vital signs), and efficacy (neurological improvement before MT, at 24 hours, and at 7 days or discharge, modified Rankin Scale score at 90 days). CONCLUSIONS:The DOWN-SUITE trial will provide evidence on the acute cerebrovascular effect of HDT15 in large vessel occlusion-acute ischemic stroke, potentially establishing a cost-effective, practice-changing intervention to improve collaterals for global stroke care. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06297863.

BACKGROUND AND OBJECTIVES:IV thrombolysis (IVT) is contraindicated in patients with acute ischemic stroke (AIS) while on dabigatran or other oral anticoagulant (OAC) treatment. Idarucizumab completely reverses the effect of dabigatran within minutes, without increasing the risk of thromboembolism. Limited data exist on IVT treatment after dabigatran reversal with idarucizumab. We aimed to investigate the safety and outcomes of IVT after dabigatran reversal in patients with AIS. METHODS:This is an observational study based on the Safe Implementation of Treatment in Stroke (SITS) International Stroke Thrombolysis Registry. Hospitals treating patients with AIS contributed data. The main outcome was safety as measured by any parenchymal hematoma (PH), symptomatic intracerebral hemorrhage (SICH) per SITS, and death within 3 months. The secondary outcome was functional independence defined as modified Rankin Scale scores of 0-2 at 3 months. Propensity score matching (PSM) was used to compare patients treated with dabigatran reversal to patients without prior OAC in primary analysis and for secondary analysis between patients treated with dabigatran reversal with idarucizumab to patients on dabigatran without reversal treatment. RESULTS:Among 258,589 IVT treated patients with AIS, 510 were on dabigatran and 156 received dabigatran reversal. Dabigatran reversal patients were older (75 vs 69 years, p < 0.01), had similar median baseline NIH Stroke Scale (9 vs 10, p = 0.47), and longer onset to IVT time (185 vs 150 minutes, p < 0.01) compared with patients without prior OAC treatment (n = 191,648). After PSM analysis where good balance was achieved, patients treated with dabigatran reversal before IVT had similar results in all outcomes as compared with patients treated with IVT without prior OAC (any PH: 3 vs 9%, p = 0.10; SICH: 1 vs 1%, p = 1.00; death: 25 vs 19%, p = 0.33, functional independence: 51 vs 52%, p = 0.95). Secondary analysis showed similar results for all outcomes before and after PSM. DISCUSSION:In our observational study with patients with AIS, IVT treatment after dabigatran reversal was safe and had similar outcomes to IVT treatment without previous OAC. Furthermore, comparison between dabigatran reversal vs no reversal also indicates that IVT is safe for patients on dabigatran without idarucizumab reversal, which is currently being investigated in clinical trials. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that IVT after idarucizumab reversal in patients with AIS who took dabigatran within 48 hours of onset of symptoms is safe and comparable with those of patients with AIS not on prior oral anticoagulation.

Background Endovascular therapy (EVT) is an established treatment for basilar artery occlusion (BAO) with severe deficits, but its benefit in patients with mild-to-moderate symptoms (National Institutes of Health Stroke Scale [NIHSS] <10) remains unclear due to limited randomized controlled trial (RCT) evidence. We performed a systematic review and meta-analysis to evaluate EVT efficacy and safety in this subgroup. Methods We searched PubMed, Embase, and the Cochrane Library for RCTs and observational studies published between January 1, 2014, and July 1, 2026, comparing EVT plus best medical treatment (BMT) versus BMT in BAO with NIHSS <10. The primary outcome was 90-day good functional status (modified Rankin Scale [mRS] 0–2). Secondary outcomes were favorable (mRS 0–3) and excellent (mRS 0–1) functional status. Safety outcomes included 90-day mortality, any intracerebral hemorrhage (ICH) and symptomatic ICH. Results Fifteen studies comprising 3981 patients (1812 EVT; 2169 BMT) were included. No significant differences were observed in good (OR = 1.51; 95% CI 0.89–2.54; p = 0.12) or favorable functional status (OR = 0.99; 95% CI 0.75–1.30; p = 0.92), while EVT increased the odds of excellent status (OR = 2.01; 95% CI 1.33–3.05; p < 0.001). Mortality (OR = 0.94; 95% CI 0.55–1.59), any ICH (OR = 1.23; 95% CI 0.69–2.19) and symptomatic ICH (OR = 0.98; 95% CI 0.61–1.57) were comparable. Conclusion Although no difference emerged for the primary outcome, EVT increased the likelihood of excellent recovery without compromising safety. These findings highlight the need for RCTs targeting this population.

BACKGROUND:Mechanical thrombectomy is the standard of care for acute ischemic stroke due to large vessel occlusion. Whether the mothership model or the drip-and-ship model provides superior outcomes remains unclear. This systematic review and meta-analysis aimed to compare functional and safety outcomes between these 2 models and assess the impact of onset-to-groin puncture delay on outcomes. METHODS:We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD420251034209). We searched PubMed, EMBASE, and Cochrane CENTRAL up to March 9, 2025. We included randomized trials, cohort studies enrolling patients with anterior circulation large vessel occlusion treated with mechanical thrombectomy. The primary outcome was 90-day functional independence (modified Rankin Scale score, 0-2). Secondary outcomes included excellent outcome (modified Rankin Scale score 0-1), successful recanalization, symptomatic intracranial hemorrhage, any intracranial hemorrhage, and 90-day mortality. Risk of bias was assessed using Risk of Bias in Non-randomized Studies of Interventions and Risk of Bias 2.0 tools. Meta-regression was performed to evaluate the effect of onset-to-groin puncture time differences on outcomes. RESULTS:Nineteen studies (16 485 patients) were included. The mothership model and drip-and-ship model showed no significant difference in achieving 90-day functional independence (odds ratio, 1.12 [95% CI, 0.94-1.32]). Meta-regression showed that longer delays to thrombectomy in the drip-and-ship model significantly reduced the odds of functional independence (P<0.001). A onset-to-groin time delay of approximately 43 minutes between the two models of care was identified as the threshold beyond which the mothership model conferred superior outcomes. CONCLUSIONS:Direct transport to a thrombectomy-capable center should be prioritized when secondary transfer is expected to delay treatment, as functional outcomes worsen significantly beyond this threshold.

BACKGROUND:Mechanical thrombectomy (MT) is effective for acute basilar artery occlusion (BAO), but the optimal technique for rapid recanalization and improved outcomes remains unclear. OBJECTIVE:We compared stent retriever (SR), contact aspiration (CA), and combined SR plus CA techniques as first-line approaches during MT for BAO. METHODS:We emulated a hypothetical trial comparing CA, SR, and combined technique as first-line in BAO patients. The primary outcome was first-pass effect (FPE), defined as modified Thrombolysis in Cerebral Infarction (mTICI) 3 with one pass of MT. Secondary outcomes included modified FPE (mFPE), functional outcome at 90 days, successful recanalization, and safety outcomes. We used inverse probability weighting (IPW) adjusted for prespecified covariates. RESULTS:The study included 960 BAO patients: 570 treated with CA, 268 with SR, and 122 with combined technique as the first approach. After applying IPW, SR was associated with lower odds of FPE (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.90) and of mFPE (aOR 0.48, 95% CI 0.33 to 0.70) compared with CA. No differences were found between the combined technique and either SR or CA. A 90-day modified Rankin Scale (mRS) 0-3 after mFPE was less frequent with SR (aOR 0.57, 95% CI 0.38 to 0.85) and with combined technique (aOR 0.50, 95% CI 0.28 to 0.89) compared with CA. Additionally, combined technique showed lower odds of mRS 0-1 at 90 days compared with CA (aOR 0.56, 95% CI 0.33 to 0.94). CONCLUSIONS:In BAO patients, CA was more effective than SR for complete and successful recanalization after first pass and resulted in better outcomes after mFPE as compared with other techniques. Less traumatic approaches might be preferred as first-line in BAO.

Abstract Background and aims Transient ischemic attack (TIA) confers a high early risk of subsequent ischemic stroke. Systemic inflammatory activation may contribute to this risk, but the prognostic value of inflammatory indices in TIAs remains unclear. We assessed their association with clinical outcomes and their role in refining ABCD2-based risk stratification. Methods We conducted a multicenter retrospective–prospective observational study including consecutive TIA patients admitted between January 2023 and August 2025. Systemic inflammatory indices (NLR, PLR, LMR, SII, SIRI) were derived from admission blood samples. Primary outcome was 90-day major adverse cardiovascular events (MACE); secondary outcomes included occurrence of stroke or TIA, ischemic stroke, and all-cause mortality up to 12 months. ROC analysis was used to develop a predictive model integrating inflammatory indices with the ABCD2 score (ABCD2-I). Results Among 291 patients included, 10% suffered from 90-day MACE. At multivariable analysis, increasing admission NLR independently predicted 90-day MACE (OR 1.70, 95%CI 1.12–2.58; p = 0.013). NLR was also associated with ischemic stroke or TIA (OR 1.48, 95%CI 1.02–2.13; p = 0.037), while ischemic stroke was independently associated with both NLR (OR 2.74, 95%CI 1.39–5.40; p = 0.003) and PLR (OR 1.01, 95%CI 1.00–1.02; p = 0.029). No inflammatory index predicted mortality. Integration of NLR into the ABCD2 score improved discrimination (AUC 0.605 vs 0.668), with an optimal cut-off of 4. Conclusions In TIA patients, systemic inflammatory burden independently predicts ischemic recurrence, and its integration into ABCD2 improves identification of high-risk patients beyond clinical models. Conflict of interest Marco Andrighetti: nothing to disclose.

Abstract Background and aims Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Whether the mothership model or the drip-and-ship model provides superior outcomes remains unclear. This systematic review and meta-analysis aimed to compare functional, procedural, and safety outcomes between these two models, and assess the impact of onset-to-groin puncture delay on outcomes. Methods We conducted a systematic review and meta-analysis following PRISMA guidelines, registered in PROSPERO (CRD420251034209). We searched PubMed, EMBASE, and Cochrane CENTRAL up to March 9, 2025. We included randomized trials and cohort studies enrolling patients with anterior circulation LVO treated with MT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] 0–2). Secondary outcomes included excellent outcome (mRS 0–1), successful recanalization, symptomatic intracranial hemorrhage, any intracranial hemorrhage, and 90-day mortality. Meta-regression was performed to evaluate the effect of onset-to-groin puncture time differences on outcomes. Results Nineteen studies (16,485 patients) were included. Meta-regression showed that longer delays to thrombectomy in the drip-and-ship model significantly reduced the odds of functional independence (p<0.001). A delay of approximately 43 minutes was identified as the threshold beyond which the mothership model conferred superior outcomes (figure ). No significant differences were found in rates of excellent outcome, successful reperfusion, symptomatic hemorrhage, any intracranial hemorrhage, or mortality. Conclusions When the drip-and-ship model introduces delays greater than 43 minutes, direct transport to comprehensive stroke centers (mothership) should be preferred to maximize clinical benefit. Conflict of interest nothing to disclose Figure 1 - belongs to Results

Abstract Background and aims Studies from the USA have reported lower access to reperfusion treatments (RTs) for Ischemic Stroke (IS) among racial/ethnic minorities; however, evidence from Italy is lacking. We aimed to assess the impact of race/ethnicity on RTS administration and onset-to-door time (ODT). Methods Consecutive adult patients with IS presenting to 14 Italian stroke centers between October 2024 and November 2025 were prospectively enrolled. Based on self-reported race/ethnicity, patients were classified as White or non-White. Outcomes were Intravenous Thrombolysis (IVT), Endovascular Treatment (EVT), and ODT. Associations between ODT and race/ethnicity were assessed using linear regression adjusted for demographics, comorbidities, baseline NIHSS, premorbid mRS, education level, mode of arrival, occupational status, language barriers, and cohabitation status. Logistic regressions adjusted for the same variables, plus large vessel occlusion, anticoagulant use, and ASPECTs were used to identify predictors of IVT and EVT. Results Overall, 2402 patients were enrolled in the study, of whom 2257 were Whites (94.0%). Overall, 830 patients (35.7%) received IVT and 648 (27.9%) EVT. Compared with White patients, non-White patients were younger (62.9±16.7 vs 74.1±13.9 years; p<0.001) and less frequently women (33.8% vs 47.2%, p=0.002). White category was not associated with IVT and EVT administration (aOR 0.70 95%CI (0.34-1.67), p=0.497 and aOR 2.50 95%CI (0.84-7.40), p=0.098, respectively) but was independently associated with shorter ODT (aβ -631.69 95%CI (-1100.34 - -163.03); p=0.008). Conclusions Our study suggests that racial/ethnic disparities in timely access to stroke care exist even in countries with universal healthcare systems, highlighting the need for public health interventions. Conflict of interest Nothing to disclose

Abstract Background and aims Systemic inflammatory indices have been associated with clinical outcomes in stroke. However, their relationship with the velocity of ischemic core expansion remains unclear. We investigated the association between systemic inflammatory markers and infarct growth rate (IGR) in patients with acute anterior large-vessel occlusion (LVO) ischemic stroke (IS). Methods We conducted a single-center retrospective observational study including consecutive patients admitted with acute anterior LVO IS, within 24 hours from known symptom onset, between January 2023 and August 2025. Ischemic core volume (CBF <30%) and IGR (core volume/onset-to-CT time) were calculated for each patient. Admission systemic inflammatory indices included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). The primary outcome was the fast ischemic core progression, defined as IGR ≥10 mL/h. Secondary outcomes included continuous associations with IGR and relationships with ischemic progression phenotypes (slow, intermediate, fast). Results Among 120 patients included, 77 (64.2%) were classified as fast progressors. Admission NLR was independently associated with rapid ischemic core progression (OR 2.13; 95%CI 1.22–3.70; p = 0.007). Ordinal regression analysis confirmed that higher NLR (OR 1.90; 95%CI 1.19–3.03; p = 0.006) and PLR (OR 1.02; 95%CI 1.01–1.03; p = 0.050) were independently associated with faster ischemic progression phenotypes. In contrast, no significant association was observed between continuous NLR values and IGR. Conclusions Elevated admission NLR independently predicts faster ischemic core progression in anterior circulation LVO stroke, highlighting a pathophysiological link between systemic inflammation and accelerated infarct evolution. Conflict of interest Marco Andrighetti: nothing to disclose.

Abstract Background and aims Cerebral perfusion parameters in acute ischemic stroke(AIS) could help in predicting response to acute treatments. This study aimed to assess temporal changes of perfusion parameters in routine clinical practice in treated patients with AIS and their impact on clinical outcome. Methods In this retrospective observational study, we included patients with AIS treated with IV thrombolysis and/or mechanical thrombectomy. All patients underwent multimodal CT at baseline and MRI within 24 hrs from symptom onset. We used an AI-based neuroimaging software. At the two timepoints, we measured volumes of total hypoperfusion (TH), ischemic core (IC), and mismatch/ischemic penumbra (M/IP). We evaluated impact of perfusion dynamics on clinical outcomes (modified Rankin score [mRS] and mortality at 3 months). Results Overall, 101 patients with AIS were included (women 40.6%, mean[±SD] age of 72.8[±13.3], median baseline NIHSS 8.50). 71.3% of patients had a perfusion parameter improvement/stability pattern with “Imaging/Clinical Post-treatment TIA” occurring in 22.8% of them. We observed a significant difference between median baseline volumes of TH (from 45.90 to 1.0 ml,p<0.001) and M/IP (from 38.80 to 0 ml,p<0.001) and those assessed in the post-treatment. IC reduction after treatment was found in a high proportion of patients(44.6%). We obtained similar results in the three treatment groups. IC and TH percentage changes were independent predictors of mRS and mortality at 3 months. Conclusions Our study demonstrated that IC as determined with the current neuroimaging tools and parameters could also include salvageable brain tissue areas. Conflict of interest Svetlana Lorenzano: nothing to disclose

Abstract Background and aims Early neurological improvement (ENI) at 24 hours is a robust predictor of favourable outcome after mechanical thrombectomy (MT). However, some patients fail to achieve functional independence despite ENI. We aimed to identify predictors of unfavourable outcome defined as a modified Rankin Scale (mRS) 3-6 in patients with stroke exhibiting ENI. Methods We analysed data from a national registry of endovascular treatment (2015-2022). Inclusion criteria were: anterior circulation stroke, MT and ENI (defined as NIHSS reduction of 4 points or NIHSS 0-1 at 24 hours). Patients with pre-stroke mRS>2 were excluded. The primary outcome was 90-day unfavourable functional outcome (mRS 3-6). Multivariable logistic regression was used to identify independent predictors. Results Of 10936 eligible patients, 6234 (57%) showed ENI. Among these, 1122 (18%) had an unfavourable outcome at 90 days. In multivariable analysis, independent predictors of poor outcome despite ENI included: Age >75 years (aOR 2.8, 95%CI 2.1-3.6), Diabetes Mellitus (aOR 1.6, 95%CI 1.3-1.9), Symptomatic Intracranial Haemorrhage (sICH) (aOR 4.5, 95%CI 2.8-7.1), and longer Last-Known-Well-to-Puncture time (aOR 1.1 per hour). Successful reperfusion with a modified Thrombolysis in Cerebral Infarction (mTICI) of 3 was protective against 90-day unfavourable outcome (aOR 0.6, 95%CI 0.5-0.8). Intravenous thrombolysis showed no interaction with 90-day outcome. Conclusions Nearly one in five patients with ENI failed to achieve functional independence. Advanced age, diabetes, sICH, and delayed treatment were strong predictors of futile early recovery. These findings suggest that 24-hour NIHSS improvement, while valuable, may not fully capture long-term disability in high-risk patients. Conflict of interest The authors report no disclosures