Abstract Background and aims Complications after aneurysmal subarachnoid hemorrhage (aSAH) remain only partially understood. This study aimed to identify predictors of seizures and to explore their association with EBI, DCI, and mortality. Methods We retrospectively analyzed patients with aSAH admitted to the ICU of Bufalini Hospital between 2019 and 2025. Demographic, clinical, EEG, and radiological variables were collected. Univariable and multivariable logistic regression analyses were conducted to identify independent predictors of seizures, while secondary analyses explored factors associated with EBI, DCI, and mortality. Results Among 195 included patients, NCSE or overall seizures occurred in 12.8%. Patients with seizures had longer ICU stays (20.0 ± 11.0 vs 10.8 ± 8.7 days, p<0.001), more hydrocephalus (75.0% vs 40.4%, p=0.001), higher rates of DVE (89.3% vs 55.4%, p=0.001), and more vasospasm (57.1% vs 26.5%, p=0.002). In multivariable analysis, vasospasm remained the only independent predictor (OR 3.30, 95% CI 1.15–9.72, p=0.028). EBI was associated with higher Hunt–Hess and modified Fisher scores, early complications (rebleeding, fever, hyponatremia), and moderate vasospasm, whereas DCI correlated with hypertension, CTA/TCD vasospasm, perfusion deficits, and clinical deterioration. Mortality was linked to baseline severity (WFNS, IVH, raised ICP) but not to seizure occurrence. Conclusions Vasospasm emerged as the main determinant of overall seizures after aSAH, suggesting that vasospasm should not only be treated to prevent DCI but also recognized as a marker of cortical excitability and potential ictogenesis. Multimodal monitoring integrating cEEG, TCD, CTA/CTP, and ICP measurements may help detect and interrupt the vicious cycle between hypoperfusion and seizure activity. Conflict of interest Claudia Faini: nothing to disclose; Carlo Bergamini: nothing to disclose; Andrea Salcuni: nothing to disclose; Luca Bastia; nothing to disclose; Mattia Carnelli: nothing to disclose; Manlio Meca; nothing to disclose; Luca Gobbi: nothing to disclose; Francesca Gatti: nothing to disclose; Elvis Lafe: nothing to disclose; Marcello D'Andrea: nothing to disclose; Marco Longoni; nothing to disclose; Vanni Agnoletti: nothing to disclose; Luigino Tosatto: nothing to disclose; Maria Ruggiero: nothing to disclose; Yerma Bartolini: nothing to disclose; Michele Romoli: nothing to disclose.

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 Early neurological deterioration (END) may occur despite angiographically successful mechanical thrombectomy (MT). Flat-panel detector CT (FPDCT) allows immediate post-procedural detection of distal embolization and reperfusion-related injury. We investigated whether FPDCT markers identify patients at increased risk of END beyond conventional angiographic grading. Methods In this prospective multicentre observational study, consecutive patients with anterior circulation stroke treated with MT at two comprehensive stroke centres were included. Post-procedural FPDCT was used to assess the presence of the distal occlusion tracker (DOT) sign. The primary outcome was END. Secondary outcomes included functional outcome, 24-hour ASPECTS and haemorrhagic complications. Associations between the DOT sign and clinical-radiological variables, including Thrombolysis in Cerebral Infarction recanalization score (TICI), were evaluated through univariate and multivariate logistic regression. Results Among 374 patients, the DOT sign was present in 31%.DOT-positive patients had higher rates of END compared with DOT-negative patients (25.0%vs12.8%, P = 0.003).The DOT sign was associated with lower rates of successful reperfusion (TICI≥2b:79.3%vs91.1%,P < 0.001) and higher prevalence of cortical hyperattenuation on FPDCT.In multivariate analysis, the DOT sign independently predicted END (adjusted OR2.07,95%,CI1.03–4.15), together with cardioembolic etiology, baseline NIHSS, lower FPDCT ASPECTS and unsuccessful reperfusion. DOT-based adjudication led to reclassification of approximately half of angiographic TICI3 cases to lower reperfusion grades. Conclusions The DOT sign is a practical post- thrombectomy imaging marker helping in the prediction of END. Integrating the DOT sign assessment may help in the stratification of tissues at risk and risk of END, adding to the selection of patients for adjunctive intra-arterial medications. Conflict of interest Valentina Tudisco: nothing to disclose; Michele Romoli: nothing to disclose; Francesca Giannini: nothing to disclose; Davide Vicari: nothing to disclose; Federica N. Sepe: nothing to disclose; Fabrizio Giammello: nothing to disclose; Marco Longoni: nothing to disclose; Antonio Toscano: nothing to disclose; Maria Ruggiero: nothing to disclose.

Abstract Background and aims Despite adequate anticoagulation, patients with atrial fibrillation (AF) still experience a 13% annual risk of recurrent stroke. We investigated in a multicentre prospective study whether a strategy based on DOAC prescribed according to plasma levels was superior to standard DOAC prescription in the prevention of recurrent stroke. Methods This study enrolled consecutive patients admitted with stroke while on DOAC for AF from 2024 to 2026 (currently) at 9 comprehensive stroke centres. Anticoagulation was restarted after stroke according to current guidelines, with DOAC chosen by the clinician. Three centers (RN, CE, BA) transitioned to a dosing strategy, measuring peak-trough DOAC plasma level after anticoagulation restart, switching DOAC until reaching therapeutic plasma levels (tailored group). The remaining centers maintained a standard of care policy, with prescription of DOAC without plasma level dosage. Recurrence of ischemic stroke, hemorrhagic stroke, TIA and major cardiovascular events were adjudicated by at 3 and 12-months through hot and cold pursuit. Results Overall 510 consecutive patients with stroke while on DOACs were consecutively included across all centers, 65 in the tailored group and 445 in the standard of care group. Mean age was 78 years, 50.5% male. No differences in terms of clinical features, cardiovascular risk factors and hyperacute treatment were found across groups. The 3-month recurrent stroke rate was 4.2% in tailored group and 5.9% in the standard of care group. Conclusions We expect to reach 85 patients in tailored group in Feb2026, finalizing the analysis for recurrent ischemic stroke and ICH in April 2026. Conflict of interest

Background A relevant proportion of patients experience early neurological deterioration (END) despite technically successful recanalisation for acute ischaemic stroke. We prospectively assessed the distal occlusion tracker (DOT) sign, detectable on flat-panel detector CT (FPDCT) immediately after mechanical thrombectomy (MT), to identify distal embolisation or incomplete microvascular reperfusion associated with END. Methods Our prospective multicentre observational study included consecutive patients with anterior circulation stroke treated with MT between January 2022 and December 2023 at two large comprehensive stroke centres. Post-procedural FPDCT was used to assess the presence of the DOT sign. The primary outcome was END. Secondary outcomes included 3 month functional outcome, 24 hour Alberta Stroke Program Early CT Score (ASPECTS) and haemorrhagic complications. Associations between the DOT sign and clinical-radiological variables, including Thrombolysis in Cerebral Infarction recanalization score (TICI), were evaluated through univariate and multivariate logistic regression. Results The DOT sign was present in 31% of cases and was associated with higher rates of END (25% vs 12.8%, p=0.003), lower recanalisation success (79.3% vs 91.1%, p<0.001) and greater prevalence of cortical hyperattenuation. On multivariate analysis, independent predictors of END included the DOT sign (aOR=2.07, p=0.040), cardioembolic aetiology, baseline National Institutes of Health Stroke Scale, FPDCT ASPECTS and unsuccessful reperfusion. The DOT sign led to reclassification of half of TICI 3 cases to lower grades. No significant difference in symptomatic intracranial haemorrhage was observed between groups. Conclusions The DOT sign is a practical post-thrombectomy imaging marker helping in the prediction of END. Integrating the DOT sign assessment may help in the stratification of tissues at risk and risk of END, adding to the selection of patients for adjunctive intra-arterial medications.

Abstract Background and aims A substantial proportion of patients exhibit biological non-responsiveness to commonly used antiplatelet agents, which is associated with a markedly increased risk of early recurrence. The TAILOR trial aims to evaluate whether a tailored, platelet function–guided antiplatelet strategy improves short-term outcomes compared with usual care in patients with non-cardioembolic ischaemic stroke. Methods TAILOR is a phase IV, multicentre, pragmatic, open-label, gender-stratified, randomised controlled trial with blinded endpoint adjudication. Patients with recent non-cardioembolic ischaemic stroke requiring secondary prevention with antiplatelet therapy will be randomised 1:1 to either usual care or a tailored strategy guided by platelet aggregation testing. Following a 7–10-day run-in period, platelet function is assessed, and antiplatelet therapy is modified in the tailored arm in case of non-responsiveness. Participants are followed for 3 months. The primary endpoint is the 3-month cumulative incidence of a composite of recurrent ischaemic stroke, myocardial infarction, or cardiovascular death. Recruitment is planned to start in early 2026, with enrolment over 24 months across three Italian stroke centres. Results The trial is powered to detect a clinically meaningful reduction in the primary composite endpoint, assuming a decrease from 9% under usual care to 5% with tailored therapy. Interim safety and feasibility analyses are scheduled during recruitment. Study duration is 36 months. Final results are expected within six months after completion. Conclusions TAILOR will provide robust evidence on the effectiveness of a precision-medicine approach to antiplatelet secondary prevention after ischaemic stroke, with potential to reduce early cardiovascular events. Conflict of interest Andrea Zini: funding reveived by AIFA (Italian drug agency). Matteo Paolucci: nothing to disclose; Stefano Forlivesi: nothing to disclose; Giacomo Urbinati: nothing to disclose; Mauro Gentile: nothing to disclose; Francesca Rosafio: nothing to disclose; Laura Vandelli: nothing to disclose; Michele Romoli: nothing to disclose; Marco Longoni: nothing to disclose; Guido Bigliardi: nothing to disclose.

The optimal revascularization treatment in patients with acute ischemic stroke (AIS) and isolated extracranial artery occlusion remains uncertain. We aimed to compare outcomes between endovascular treatment (EVT) and intravenous thrombolysis (IVT) alone in patients with AIS and isolated extracranial artery occlusion without concomitant ipsilateral large intracranial occlusion treated ≤ 4.5 h of onset. We retrospectively analyzed prospectively collected data from two multicenter registries (IRETAS for EVT and SITS-ISTR for IVT). Primary efficacy endpoints were 3-month modified Rankin Scale (mRS) score 0–1 and 0–2. Primary safety endpoints were symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Multivariable logistic regression was used to adjust for imbalances in demographics, clinical variables, stroke etiology data, and procedure data. A total of 793 patients were included in the study (EVT, n = 358; IVT alone, n = 389; control angiography, n = 46), of whom 633 with extracranial internal carotid artery (ICA) occlusion and 160 with extracranial vertebral artery (VA) occlusion. In the isolated extracranial ICA or VA occlusions, EVT was associated with lower rates of mRS 0–1 (aOR: 0.45, 95

Knowledge on the prevalence and clinical effects of Lewy body (LB) pathology in patients with rapidly progressive dementia (RPD) has been limited by the lack of a pathology-specific marker. The introduction of the alpha-synuclein (α-syn) seed amplification assay (SAA) has recently provided the first accurate in vivo biomarker of LB pathology. Based on data from limited neuropathological cohorts, we hypothesised that LB pathology is frequent in non-prion RPD and often clinically unrecognised. We studied 171 consecutively referred clinically well-characterised patients with RPD, defined as those reaching the stage of major neurocognitive disorder within one year of symptom onset. Patients diagnosed with Creutzfeldt-Jakob disease or a treatable form of RPD were excluded. Records on specific clinical features were retrospectively reviewed. We tested all patients with a validated α-syn CSF SAA to evaluate the prevalence and clinical correlates of LB pathology. Moreover, CSF biomarkers of Alzheimer’s disease (AD) pathology were measured in all cases. In the cohort, 39.2

BACKGROUND:Nearly half of the patients who received endovascular thrombectomy (EVT) for large vessel occlusion experience poor functional outcomes. Reliable tools for early post-procedural prognostication are needed. We aimed to assess and compare the performance of existing, pragmatic post-EVT prognostic scores in a large national multicenter cohort. METHODS:We conducted a systematic literature search to identify pragmatic post-thrombectomy prognostic scores predicting 90-day functional outcomes. Models relying on advanced imaging, small derivation samples, or machine learning were excluded. We analyzed data from the IRETAS registry-a prospective, multicenter Italian cohort of stroke patients treated with EVT. Inclusion criteria were pre-stroke modified Rankin Scale (mRS) ⩽ 2 and available 90-day mRS. The primary outcome was good functional outcome (mRS ⩽ 2). Prognostic performance was assessed using c-statistics in the samples where each individual score was measurable. Scores were compared using DeLong tests in the subset of patients for whom all scores were measurable. RESULTS:Three scores were identified: HERMES-24, BET, and SNARL. Among 22,768 patients in the registry, 18,408 (89.1%) had a measurable HERMES-24 score, 13,593 (59.7%) had a measurable BET score, and 19,007 (83.5%) had a measurable SNARL score. Median age was 75 years (IQR 65-82), and 11,528 (50.6%) were female. In the subset in which each test was measurable, HERMES-24 showed the best performance for predicting mRS ⩽ 2 (c-statistic = 0.889), followed by BET (c-statistic = 0.794) and SNARL (c-statistic = 0.762) (p < 0.001). In the subset of 12,233 patients for whom all three prognostic scores were calculable, a head-to-head comparison confirmed the superior performance of the HERMES-24 model: HERMES-24 score versus BET score (c-statistic difference = 0.098 [95% CI = 0.092-0.105]; p < 0.001) and HERMES-24 score versus SNARL score (c-statistic difference = 0.124 [95% CI = 0.116-0.132]; p < 0.001). CONCLUSIONS:In this large, multicenter, national cohort, the post-EVT HERMES-24 score-which accounts only for age and 24-h NIHSS-demonstrated the highest prognostic performance among existing, pragmatic post-EVT scores. Its simplicity and robust performance support its routine adoption in clinical practice.

BACKGROUND:In the early time window, direct mechanical thrombectomy (MT) is not non-inferior to combined treatment with intravenous thrombolysis (IVT) for patients with large vessel occlusion (LVO) stroke, while its non-inferiority in the extended time window remains uncertain. This study assessed whether direct MT is non-inferior to IVT + MT beyond 4.5 h or at wake-up. METHODS:We emulated a non-inferiority trial, comparing direct MT vs. IVT + MT, including patients with anterior circulation LVO between 4.5 and 24 h from symptom onset or at wake-up, without contraindications to IVT and with target perfusion mismatch. We used inverse probability weighting (IPW) adjusted for pre-specified covariates. The primary outcome was 90-day mRS 0-2, with non-inferiority defined by a lower 95% CI boundary of the Risk Difference (RD) ≥ -1.3%. RESULTS:Among 347 patients, 212 received direct MT and 135 received IVT + MT. After IPW, patients treated with direct MT and IVT + MT had a similar likelihood of achieving a 90-day mRS of 0-2 (adjRD -2.90 [95% CI -6.64 to 0.84]) with the lower boundary of the RD 95% CI crossing the non-inferiority margin. Additionally, direct MT was associated with a shift toward a higher score on the 90-day mRS (adjusted Common OR 1.59 [95% CI 1.05-2.39]), not confirmed after IPW, and with lower odds of successful recanalization (adjOR 0.38 [95% CI 0.18-0.78]). Rates of 90-day mRS 0-1, sICH, and mortality were similar between groups. CONCLUSIONS:In our target trial emulation, direct MT was not non-inferior to IVT + MT treatment beyond 4.5 h from symptom onset or at wake-up, with IVT before MT yielding higher successful recanalization rates.

INTRODUCTION:We aim to evaluate the association between door-to-needle time (DTN) and outcomes in a population of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) + mechanical thrombectomy (MT) in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). MATERIALS AND METHODS:Patients with AIS secondary to middle cerebral artery or intracranial internal carotid artery occlusion with known times of symptoms onset, directly presenting to an MT-capable center, were included in the analysis. According to pre-defined DTN cut-off values (⩽30, ⩽45, and ⩽60 min), we evaluated the association between DTN and outcomes by multivariate logistic regression analyses. Effectiveness outcomes were 3-month functional independence, 3-month excellent outcome and successful reperfusion. Safety outcomes were any intracranial hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 3-month mortality. RESULTS:About 1602 patients were included in our analysis. After logistic regression analysis, a DTN ⩽ 60 min was significantly associated with 3-month functional independence (OR 1.36; 95% CI 1.02-1.82). DTNs ⩽ 30, ⩽45, and ⩽60 min were significantly associated with successful reperfusion (OR 2.66; 95% CI 1.6-4.43; OR 1.68; 95%CI 1.25-2.26; OR 1.57; 95% CI 1.21-2.05; respectively). A DTN ⩽ 60 min was also significantly associated with lower rate of any ICH (OR 0.61; 95% CI 0.43-0.86). DTNs ⩽ 30, ⩽45, and ⩽60 min were significantly associated with lower 3-month mortality (OR 0.24; 95% CI 0.08-0.67; OR 0.45; 95% CI 0.29-0.72; OR 0.58; 95% CI 0.39-0.84; respectively). CONCLUSIONS:In patients with AIS treated with IVT + MT, a shorter DTN is associated with better outcomes if IVT is initiated within 1 h of hospital admission.

Introduction Infarct growth rate (IGR) is highly heterogeneous among ischemic stroke patients, reflecting a spectrum of progressor phenotypes with clinical implications. We aim to compare different imaging approaches to investigate stroke progressors phenotypes and their clinical implications in patients undergoing thrombectomy. Methods Data are from the prospective Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). Patients with M1/M2 occlusion and known symptom onset were included. Progressor phenotypes were defined using (1) NCCT-based definitions (ASPECTS points decay per hour < 0.25 pts/h=slow progressor, 0.25-0.50 pts/h=intermediate, and > 0.50 pts/h=fast); and (2) CTP-based definitions (CTP-estimated core divided by time of onset < 5 mL/h=slow progressors, 5-10mL/h=intermediate, and > 10 mL/h=fast). The primary outcome was 90-day good functional outcome (modified Rankin Scale [mRS] = 0-2). Associations were assessed with logistic regression analyses adjusted for age, sex, NIHSS, TICI score, thrombolysis, and imaging-to-recanalization time. Results Of 26799 patients screened, 8322 (31.1%) were included (NCCT group: 8076; CTP group: 897 patients). NCCT-based progressor phenotype was associated with lower odds of good outcome (aOR 0.82 [95%CI = 0.72-0.92] per each progressor phenotype increase). ASPECTS decay per hour was associated with lower odds of good outcome (acOR 0.94 [95%CI = 0.89-0.99]). No significant association was observed for either CTP-based progressor phenotype or CTP-based IGR (mL/h). Similar findings were observed for secondary outcomes. Conclusions In this large, real-world cohort of stroke patients, NCCT-based IGR was associated with functional outcomes, whereas CTP-based IGR was not. This highlights the need to refine and identify more accurate markers of infarct growth within perfusion imaging.

Background and ObjectivesThe management of anterior circulation tandem lesion stroke remains controversial, given its under-representation in randomized thrombectomy trials and uncertainty regarding optimal extracranial carotid intervention. We aimed to determine whether emergent carotid stenting (eCAS) during endovascular thrombectomy (EVT) for anterior circulation tandem lesions improves 90-day functional outcomes compared with a no-stenting strategy.MethodsWe conducted an international multicenter longitudinal retrospective cohort study (CERES-TANDEM, NCT06965036) of consecutive adults treated at 49 comprehensive stroke centers in Europe, North America, and Singapore for anterior circulation acute ischemic stroke due to tandem lesions from January 1, 2018, to December 31, 2024. Exclusion criteria were primary hemorrhagic stroke, absence of intracranial occlusion, presentation >24 hours from symptom onset, and age younger than 18 years. We compared 90-day modified Rankin Scale (mRS) scores between participants receiving eCAS and those receiving no stenting during EVT. The primary estimand was mRS shift, analyzed by stabilized inverse probability of treatment weighting (IPTW)-weighted ordinal regression. Additional estimands were direct-effect estimand adjusting for successful recanalization (defined as Thrombolysis in Cerebral Infarction grade 2b or higher) and symptomatic intracranial hemorrhage (sICH) (estimand 2) and stratum estimand restricting to never-crossers (estimand 3).ResultsOf 4,053 patients (mean age 70 years, 65.5% female), 2,522 underwent eCAS and 1,531 received no stenting. After IPTW, eCAS was associated with an improved 90-day functional outcome (common odds ratio (OR) 1.31; 95% CI 1.17-1.47;p < 0.001) and higher odds of mRS score 0-1 (OR 1.27; 95% CI 1.08-1.50; p = 0.005) and mRS score 0-2 (OR 1.30; 95% CI 1.13-1.51; p < 0.001), without a significant increase in sICH (OR 1.21; 95% CI 0.93-1.56; p = 0.15). Findings were consistent in direct-effect (common OR 1.17; 95% CI 1.04-1.31; p = 0.008) and stratum (common OR 1.37; 95% CI 1.21-1.55; p < 0.001) estimands. There was no interaction for intracranial occlusion site, IV thrombolysis, sedation technique, EVT approach, or access site. Sensitivity analysis including recanalization in IPTW-weighted estimand 1 framework confirmed the association of eCAS with improved 90-day functional outcomes (common OR 1.14, 95% CI1.02-1.27, p = 0.008).DiscussionIn this large real-world cohort, eCAS during EVT for anterior circulation tandem lesions was associated with superior 90-day functional recovery without increased hemorrhagic risk. These findings support consideration of eCAS in clinical practice and warrant confirmation in randomized trials.Trial Registration InformationRegistered in clinicaltrials.gov, NCT06965036.Classification of EvidenceThis study provides Class II evidence that in patients with stroke due to anterior circulation tandem lesions, eCAS during EVT improves 90-day functional outcomes compared with EVT alone.

Background: Recent randomized trials have questioned the benefit of endovascular therapy (EVT) for medium vessel occlusion (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), versus IVT alone in MeVO stroke using registry-based real-world data. Methods: This retrospective multicenter study included patients from 76 Italian centers in the SITS registry (January 2020-December 2023). Adults with acute ischemic 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 modified Rankin Scale (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 hemorrhage incidence, and recanalization 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 57.7% of EVT±IVT patients versus 59.2% in the IVT-only group (OR 0.939, 95% CI 0.706-1.248, p=0.663). In-hospital mortality was non significantly lower in the EVT±IVT group (5.4% vs 8.7%, p=0.069). Symptomatic intracranial hemorrhage rates were comparable between groups, although overall hemorrhagic complications were higher with EVT (18.4% vs 11.2%, p<0.0001). Successful recanalization occurred in 81.0% of EVT cases. Stratified analyses by stroke severity and treatment timing showed consistent lack of benefit across all subgroups (all interaction p-values >0.05). Conclusions: EVT did not improve long-term functional outcomes compared to IVT alone in MeVO stroke but was associated with higher hemorrhagic risk. These findings support a cautious approach to EVT in this setting, in line with recent trial evidence. ### Competing Interest Statement AZ declares consulting and speaker fees from Bayer, Boehringer-Ingelheim, Alexion, Daiichi Sankyo, Pfizer, PIAM, Amgen, fees for Advisory Board from Boehringer-Ingelheim, Daiichi Sankyo, Bayer and Astra Zeneca, not related to this study. ### Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The coordinating center (Fondazione IRCCS San Gerardo dei Tintori, Monza) determined that this study is exempt from full review as it involves secondary analysis of de-identified data from the SITS registry. Participating sites confirmed that no additional local approval was required for use of de-identified registry data, per local regulations. Informed consent was [waived/not required] due to use of de-identified data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data are available from the SITS registry but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the SITS registry.

Introduction: Cervical artery dissection (CAD) accounts for nearly 2% of all ischemic strokes but up to 25% of ischemic strokes in young adults. Dissection is likely precipitated by the interplay between risk factors (migraine, low body mass index), environmental triggers (cervical trauma or infection), and genetic connective tissue abnormalities (e.g. Ehlers-Danlos or Marfan’s disease). In this study, we delineate the prevalence of triggers and risk factors in a multicenter cohort of cervical artery dissection. Methods: This is a post-hoc analysis of the Antithrombotic for Stroke Prevention in Cervical Artery Dissection Study (STOP-CAD). We recorded information using the admission data on risk factors (migraine), triggers (upper respiratory infection, COVID-19, and minor cervical injury), and whether the patient had a known connective tissue disorder (CTD). We determined the prevalence of risk factors, triggers, and presence of CTD in patients with cervical artery dissection as well as the interplay between these factors in the pathogenesis of CAD. Results: We identified 4023 patients with CAD, the mean age was 47 years and 45% were women. A history of migraines was present in 16.6% (668) patients. At least one environmental trigger was present in 26.3% of patients (1061 patients), with minor cervical injury being the most common (22.2%, 892 patients), then upper respiratory infections (6.2%, 251 patients), and COVID-19 (1.2%, 49 patients). Among cervical injury, the most common was chiropractic manipulation (5.7%, 228 patients). Only 2% (83 patients) were known to have a CTD with Fibromuscular Dysplasia being the most common (0.6%, 23 patients). Among the entire STOP-CAD cohort, only 5 patients (0.1%) had evidence of at least one trigger, risk factor, or a known connection tissue disease. On the other hand, 61% of patients (2441 patients) had none of the three recorded. Conclusion: In patients with CAD, the absence of any risk factor, trigger, or known CTD is common and should not lead to dismissing a dissection diagnosis in patients with symptoms concerning for CAD.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons, with 90

The benefits and safety of mechanical thrombectomy (MT) in patients with prestroke disability, classified as modified Rankin Scale (mRS) score of 3 to 4, and anterior circulation stroke remain uncertain. This study aims to evaluate these factors using data from the Italian Registry of Endovascular Treatment in Acute Stroke. We analyzed data collected between 2015 and 2021, comparing functional outcomes (mRS), symptomatic intracerebral hemorrhage, and recanalization rates (Thrombolysis in Cerebral Infarction) at 90 days post-MT in patients with prestroke mRS score of 3 to 4 versus 0 to 2. A good outcome was defined as no change in the mRS score from baseline. Subgroup analysis was stratified by age. A total of 11.411 (96%) patients with prestroke mRS score of 0 to 2 and 477 (4%) patients with prestroke mRS score of 3 to 4 were included. Compared with patients with a baseline mRS score 0 to 2, those with mRS score 3 to 4 were older (82 versus 75 years; P<0.001) and predominantly female (71.7% versus 53%; P<0.001). The maintenance of the same mRS score after MT was observed in 100 (23.3%) patients with prestroke mRS score 3 to 4, compared with 2332 (22.1%) patients with mRS score 0 to 2 (P=0.556). Mortality was significantly higher in the mRS score 3 to 4 group (n=159 [37.1%] versus n=1939 [18.4%]; P<0.001). Successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) was lower in the mRS score 3 to 4 group (n=333 [71.6%] versus n=8706 [77.7%]; P=0.002), while no significant differences in symptomatic intracerebral hemorrhage were found. The benefit of MT was maintained in patients aged 80 to 85 and over 85 years with prestroke mRS score 3 to 4, although mortality remained higher. Our data suggest that prestroke disability does not imply less chance of returning to prestroke conditions after MT, even in octogenarians, despite higher mortality and lower recanalization rate. More data are warranted to better understand the benefit of MT in this subgroup of patients.

Neurological disorders rank within the leading causes of disability and premature death in Europe and Italy, and their prevalence is expected to rise due to the aging population. In Italy, the current approach to neurological care is primarily centered in hospitals. However, an effective community-based neurology care system would ensure that patients receive appropriate care in the right setting, from the right healthcare professional, and at the right time. This "precision" approach would also alleviate the burden on acute neurology facilities. To address the growing demand for neurological care services, experts from the Italian Society of Neurology (SIN) have launched a nationwide initiative aimed at supporting a transformative program in local health and care systems, enabling them to better meet the needs of neurological patients. This document presents a set of consensus recommendations for redesigning neurological care in Italy, with the objective of aligning services with the health requirements of neurological patients and establishing an integrated model for managing neurological disorders.

Type 2 diabetes mellitus (T2DM) as a comorbidity in amyotrophic lateral sclerosis (ALS) has sparked interest for its potential impact on disease expression and prognosis. In this retrospective cohort study, we investigated the prevalence and clinical correlates of T2DM in a large cohort of patients from the ALS registry of a Northern Italy region, Emilia Romagna, established in 2009. Out of 1756 ALS patients enrolled up to 2021, 145 were affected by T2DM (diALS). Patients with diALS were older than those without T2DM (ndALS) (71.56 vs. 65.76 years, p < 0.001), had a higher body mass index (25.63 vs. 24.23, p < 0.001), but experienced greater weight loss at diagnosis (6.87% vs. 5.44%, p < 0.007). Respiratory onset (6.2% vs. 2.6%, p = 0.013) and respiratory phenotype (4.2% vs. 1.4%, p = 0.04) were more frequent among diALS. Coherently, diALS presented a lower forced vital capacity (74.9% vs. 87.9%, p ≤ 0.001) and more frequently adopted Non-Invasive Ventilation (NIV) (50.35% vs. 37.61%, p = 0.003), with significant influence on time to NIV (HR 1.71, 95% CI 1.07-2.74, p = 0.024). Exploring genetic background, among all the genes examined C9ORF72 emerged as underrepresented among diALS (7.64% in ndALS vs. 0% in diALS, p = 0.039). In conclusion, we confirmed a more severe respiratory dysfunction in diALS, suggesting a specific frailty in respiratory muscles, together with some peculiar clinical features consistent with the previous literature data, such as a later onset. The lower prevalence of C9ORF72 expansion in this population may hint towards a specific role of the gene in metabolism and inflammation, granting more space to non-genetic causes, warranting further studies for confirmation.