AimThe TACHIS study (from the ancient Greek adjective "tachýs" meaning rapid) aimed to evaluate eptinezumab effectiveness and tolerability in routine clinical practice, integrating patient-reported outcomes and use of International Headache Society (IHS)-endorsed categories of migraine control by treatment.BackgroundEptinezumab is the only intravenous anti-calcitonin gene related peptide (CGRP) monoclonal antibody (mAb) approved for migraine prevention. While its efficacy has been demonstrated in RCTs, real-world evidence in patients with prior preventive treatment failures is still limited.MethodsTACHIS is a prospective, multicenter, observational study conducted in Italy. Adults with episodic or chronic migraine initiating eptinezumab were followed for 24 weeks. Primary outcomes included change from baseline in monthly migraine days (MMDs) and ≥50% responder rate. Secondary outcomes included changes from baseline in acute medication use, Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) and IHS-defined residual burden categories. Logistic regression identified factors of response status.ResultsA total of 128 patients were included (82% female; 82% chronic migraine). MMDs decreased overall by 5.7 days (95% CI: -7.2 to -4.3) at week 12 and 6.9 (95% CI: -8.5 to -5.2) at week 24 (p < 0.001). A ≥ 50% response was achieved in 43.8% and 48.2% of patients at weeks 12 and 24, respectively. Over 40% of patients achieved optimal or modest migraine control. CGRP targeted therapy-naïve patients experienced significant greater benefit, though non-naïve patients also improved. Female sex and chronic migraine diagnosis were independently associated with response at 12 weeks. Adverse events were infrequent (4.7%) and mild, with no discontinuations due to safety concerns.ConclusionsEptinezumab demonstrated effectiveness and tolerability in a real-world population of patients with migraine and prior preventive treatment failures. The integration of migraine control metrics provides a comprehensive evaluation of therapeutic impact and supports eptinezumab use in routine care.Trial RegistrationThe TACHIS study was preregistered on clinicaltrial.gov, NCT06409845.

INTRODUCTION:Identification of factors associated with haematoma expansion (HE) in patients with primary intracerebral haemorrhage (ICH) is crucial for optimization of management and therapeutic strategies. We investigated whether such factors differed according to supratentorial ICH location, comparing deep versus lobar ICH. METHODS:Retrospective analysis of patients with primary ICH admitted at nine sites. HE was defined as growth ≥6 mL and/or ≥33% from baseline to follow-up imaging. We evaluated independent associations using multivariable logistic regression models adjusted for age, sex, baseline haematoma volume, anticoagulants and antiplatelets use and other relevant confounders identified in univariate analyses. RESULTS:A total of 1768 patients were included (mean age 70 years, 56% males) of whom 1020 (58%) had deep and 748 (42%) had lobar ICH; HE occurred in 531 (30%) patients (28% deep and 33% lobar ICH). Age and baseline haematoma volume were shared predictors of HE in lobar and deep ICH. Anticoagulant use (OR = 1.61;95%, 1.04-2.50) and lower Glasgow Come Scale (OR = 0.91;95%CI, 0.85-0.96) were associated with HE only in lobar ICH, whereas the associations between systolic blood pressure >140 mmHg (OR = 1.53;95%CI, 1.03-2.29) and presentation before 3 h from onset (OR = 1.40;95%CI, 1.02-1.92) and HE were observed only in patients with deep ICH. CONCLUSIONS:Some factors associated with HE were shared between deep and lobar ICH whereas others appeared to be location-specific. Our findings may reflect differences in the pathophysiology of HE according to ICH location and might improve the stratification of HE risk in clinical practice or randomized trials.

Magnetic resonance–guided focused ultrasound (MRgFUS) is an expanding therapy for tremor in Parkinson’s disease (PD). This study aimed to characterize trajectories of tremor and cognitive functions following MRgFUS treatment over 24 hours, 1 month, and 6 months, and to explore potential predictors of outcomes. This single-center, prospective, observational cohort study included PD patients undergoing MRgFUS over a 7-year period. Tremor severity was assessed using the Fahn–Tolosa–Marin Tremor Rating Scale (FTM) and the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III). Cognitive performance was evaluated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). 107 patients were included. Tremor severity showed a significant time effect (FTM and MDS-UPDRS-III: both p < 0.001), with a marked reduction at 24 hours followed by partial attenuation and stabilization over time, while remaining lower than baseline at 1 and 6 months (both p < 0.001). The 24-hour improvement was greater in patients with longer disease duration, who showed higher baseline severity (p < 0.001) and converged to cohort-level severity at post-treatment timepoints (all p ≥ 0.085). Cognitive status (MMSE and MoCA scores) remained stable throughout follow-up (all p ≥ 0.287). Levodopa equivalent daily dose (LEDD) significantly decreased from baseline to 6 months (F = 19.992, p < 0.001), suggesting a reduced need for dopaminergic treatment following tremor improvement. MRgFUS provided meaningful tremor improvement without negative effects on cognition. The significant LEDD reduction at 6 months supports a beneficial medication-sparing effect associated with tremor improvement.

Abstract Background and aims Breakthrough ischemic stroke during oral anticoagulation (OAC) for atrial fibrillation (AF) represents a major therapeutic challenge, especially in patients with cancer, who face competing risks of thrombosis and bleeding. This study investigated the impact of cancer on 90-day outcomes after ischemic stroke on OAC. Methods We analyzed patients with AF who experienced ischemic stroke while on continuous OAC enrolled in the international retrospective ASPERA-R study, comprising 35 stroke centers across 9 countries. Inverse probability weighting (IPW) was applied to adjust for baseline imbalances, and weighted Cox, ordinal logistic and generalized liner models were used to estimate adjusted 90-day risks for the primary (ischemic stroke or TIA), secondary (mRS shift, vascular/all-cause death), and safety (moderate-to-severe bleeding, intracranial hemorrhage, 24-h hemorrhagic transformation) outcomes. Results Among 1,649 included patients (mean age 78.0 ± 10.7 years; 45.8% male), 247 (15.0%) had cancer, of whom 87 (35.2%) active and 160 (64.8%) in remission. After IPW, patients with cancer had a higher 90-day risk of new ischemic stroke or TIA (8.2% vs 2.8%; aHR 2.56,95% CI 1.59–4.13;P < 0.001) and worse mRS score (aOR 1.29,95% CI 1.08-1.54;P = 0.005) than those without cancer. Active cancer conferred a > 4-fold higher risk of new ischemic stroke/TIA and nearly 3-fold of moderate-to-severe bleeding. Hematological malignancies carried higher risk for both new ischemic stroke/TIA and moderate-to-severe bleeding versus solid malignancies. Conclusion Cancer, particularly active and hematological malignancies, substantially worsens 90-day prognosis after breakthrough stroke on OAC for AF. Conflict of interest Prof Casolla declares speaker’s fees from ACTICOR Biotech and SANOFI-AVENTIS France. Prof Sacco reports compensation from Novartis for other services; compensation from Novo Nordisk for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Teva Pharmaceutical Industries for consultant services; compensation from Allergan for consultant services; employment by Università degli Studi dell’Aquila; compensation from Novartis for consultant services; compensation from Allergan for consultant services; compensation from PFIZER CANADA INC for consultant services; compensation from Abbott Canada for consultant services; compensation from H. Lundbeck A S for consultant services; compensation from AstraZeneca for consultant services; and. Figure 1 - belongs to Results

Abstract Background and aims Randomized trials support early initiation of direct oral anticoagulants (DOACs) after atrial fibrillation (AF)–related ischemic stroke. However, patients with breakthrough ischemic stroke occurring despite ongoing anticoagulation have been largely under-represented. We evaluated the comparative effectiveness and safety of early versus delayed DOAC resumption after breakthrough stroke. Methods We conducted a target-trial emulation comparing early versus delayed DOAC resumption after breakthrough stroke. Treatment strategies were prespecified using severity-adapted timing rules based on baseline NIHSS scores. To emulate random treatment assignment and address immortal time bias, a cloning–censoring–weighting approach with inverse probability weighting was applied. Primary outcomes were 90-day new ischemic events and moderate-to-severe bleeding. Risk ratios (RRs), absolute risk differences (RDs), and hazard ratios (HRs) were estimated using weighted regression and Cox models. Results We included 833 patients (median age 81 years); 336 were assigned to early and 497 to delayed DOAC initiation. At 90 days, early initiation was associated with a lower risk of new ischemic events (3.0% vs 6.6%; RR 0.44, 95% CI 0.21–0.90; RD −3.64%, 95% CI −6.40 to −0.87; HR 0.43, 95% CI 0.21–0.91). Moderate-to-severe bleeding was less frequent with early initiation. Early initiation was associated with lower all-cause and vascular mortality. Net Early Benefit Score integrating ischemic and bleeding risks was positive across all NIHSS strata. Conclusions In patients with breakthrough ischemic stroke, early DOAC initiation was associated with reduced recurrent ischemic events and mortality at 90 days without increased bleeding. These findings support early anticoagulation initiation in this population pending randomized trials. Conflict of interest NOTHING TO DISCLOSE

INTRODUCTION:Organised stroke care and reperfusion therapies are key components of modern stroke treatment. We assessed accessibility of organised stroke care and reperfusion therapies in Europe and explored its association with key organisational indicators. PATIENTS AND METHODS:Stroke Action Plan for Europe (SAP-E) Stroke Service Tracker data from 2023 reported by 47 European countries was assessed. Accessibility indicators included stroke unit (SU) admission proportions, intravenous thrombolysis (IVT) and EVT treatment proportions. Organisational indicators included the facility density of SU, IVT-capable centres and EVT-capable centres per capita (number of centres per 100,000 population), presence of national stroke plans and quality programmes. RESULTS:Across Europe, marked variations were observed in facility density of SU (0.21-0.48), IVT-capable centres (0.19-0.45) and EVT-capable centres (0.06-0.15). SU admission proportions ranked from 0.8% to 96.7%, IVT treatment proportions from 1.3% to 34.7% and EVT treatment proportions from 0.2% to 14.3%. Stroke unit admission proportions were associated with SU density (r = 0.42, P = .03). Density of reperfusion-capable centres showed a possible trending association with IVT treatment proportions (r = 0.34, P = .08), but no association with EVT treatment proportions (r = 0.22, P = .23). Neither the presence of a national stroke plan nor a quality programme were associated with accessibility of SU care, IVT or EVT. CONCLUSION:Large inequities in access to organised stroke care and reperfusion therapies persist across Europe. At the country level, national stroke plans and quality programmes have not yet translated into effect on accessibility indicators, suggesting that achieving effective implementation takes time or could primarily manifest as within-country improvements.

Optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute ICH remains uncertain. In light of new data published since the previous ESO guidelines, this update provides revised, evidence-based recommendations across 8 key clinical questions to support BP management in acute stroke. The guidelines were developed using the ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, including literature searches, systematic reviews and meta-analyses of relevant RCTs, assessment of evidence quality and formulation of specific recommendations. We advise against routine pre-hospital BP lowering in suspected stroke (moderate-certainty evidence). In AIS patients undergoing reperfusion therapy, we recommend maintaining BP < 185/110 mmHg before the bolus of intravenous thrombolysis and < 180/105 mmHg during and for 24 h after intravenous thrombolysis (low-certainty evidence) and/or mechanical thrombectomy (moderate-certainty evidence). We recommend against intensively lowering systolic BP < 140 mmHg in the first 24 h after successful mechanical thrombectomy (high-certainty evidence). Routine use of vasopressors to raise BP in AIS patients with neurological deterioration who are not treated with acute reperfusion therapies is discouraged (low-certainty evidence). In acute ICH, the net clinical benefit of intensive BP lowering remains uncertain; however, expert consensus supports early systolic BP reduction to < 140 mmHg in patients with small-to-moderate haematomas to limit haematoma expansion. Overall, the updated recommendations reaffirm the core principles of current clinical practice while providing more nuanced guidance for specific scenarios. However, the quality of evidence remains moderate to very low, limited by a lack of high-quality RCTs, methodological issues, inconsistent results and study heterogeneity. Consequently, most recommendations are weak and supported by expert consensus. These guidelines provide specific recommendations on BP thresholds and management strategies tailored to distinct acute stroke subgroups. They also highlight the ongoing uncertainty and emphasise the need for future RCTs to define optimal BP targets, timing, treatment strategies and ideal antihypertensive agents across different clinical contexts.

Background Stress hyperglycemia (SHG) is associated with worse clinical outcomes in minor ischemic stroke. Hemorrhagic transformation (HT) represents a potential mechanism mediating this association, but clear characterization of this relationship is lacking. We therefore aimed to investigate whether HT mediates the effect of SHG on functional outcomes in patients with minor stroke. Methods This was a prospective international cohort study (5 comprehensive stroke centers, Italy/United Kingdom). Individuals presenting with National Institutes of Health Stroke Scale ≤5, prestroke modified Rankin Scale ≤1, and without large vessel occlusion between January 2022 and December 2023 were included. SHG was assessed ≤24 hours using the glucose‐to‐glycated hemoglobin ratio. HT ≤7 days was classified in hemorrhagic infarction and parenchymal hematoma. Causal mediation was used to estimate SHG effect on modified Rankin Scale ≥2 at 3 months mediated by HT. Effect modification of age, diabetes, C‐reactive protein, and intravenous thrombolysis was explored. Results There were 1316 patients included (mean age 69.6±12.7 years, 837 men [63.6%]). Higher glucose‐to‐glycated hemoglobin ratio quartiles were associated with modified Rankin Scale ≥2 (adjusted odds ratio [OR], 1.72 [95% CI, 1.24–2.40]; P=0.001) and HT severity (adjusted OR, 2.32 [95% CI, 1.43–3.76]; P=0.001). A significant proportion (14.8%) of the SHG effect on mRS was mediated by HT (average causal mediation effect, 0.014 [95% CI, 0.003–0.030]; P=0.006). Effect modification was found for younger age (≈60 years old), higher C‐reactive protein (≈7 mg/L), and absence of diabetes, but not for intravenous thrombolysis use. Conclusions In patients with minor stroke, HT significantly mediated the effect of SHG on unfavorable outcome. The mediating effect of HT was greater in patients either ≈60 years old, without diabetes, or with high baseline C‐reactive protein levels. These initial results might inform patient selection for future interventional studies.

OBJECTIVES:The aim of this study was to describe the long-term effectiveness and treatment persistence of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) in migraine and to identify baseline factors associated with 2-year treatment continuation. METHODS:A prospective observational multicenter registry-based study of anti-CGRP MAbs was conducted. We analyzed changes in monthly headache days (MHDs) at 24 months (M24) compared with baseline in those who reached M24 (ON-group). We analyzed patterns of response at 4 time points (6, 12, 18, and 24 months). We defined sustained response (SR) as a ≥50% reduction in MHDs at ≥3 of 4 time points. We compared baseline characteristics of the ON-group with those of the discontinuation group because of lack of effectiveness (OFF-group). RESULTS:A total of 1,340 individuals reached M24 (ON-group: median age 48.0 [41.0-55.0] years; 81.7% female). The median MHD at baseline was 20.0 (13.0-28.0) days. At M24, 60.4% of patients demonstrated ≥50% reduction in MHDs (809/1,340). The proportion of participants achieving SR at M24 was 53.8% (142/264). When compared with the ON-group (n = 1,340), the OFF-group (n = 1,057) showed statistically significant higher baseline MHDs (ON: 20.0 [13.0-28.0] vs OFF: 25.0 [16.0-28.0]) and a greater proportion of patients with aura (ON: 16.2% vs OFF: 22.9%), depression (ON: 22.8% vs OFF: 37.9%), and obesity (ON: 7.2% vs OFF: 19.1%) (p < 0.001). DISCUSSION:Sustained reductions in MHDs to anti-CGRP treatment at 2 years was observed. Delayed treatment onset, migraine with aura, depression, and obesity may negatively affect treatment persistence. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that, in patients with migraine, treatment with anti-CGRP MAbs is associated with sustained reductions in MHDs over a 24-month period.

BackgroundIndividuals with difficult-to-treat migraine, including resistant migraine (ResM) and refractory migraine (RefM), might experience treatment delays, undergo unnecessary diagnostic tests and receive misdiagnoses, which might influence treatment outcomes. For this reason, we hypothesized that individuals with ResM and RefM might report more diagnostic tests and misdiagnoses in their medical history compared with those with non-resistant/non-refractory migraine (NRNRM).MethodsThis analysis used baseline, cross-sectional data from the REFINE study, a multicenter, prospective observational study conducted in 15 European tertiary headache centers. Adults with episodic or chronic migraine were classified into RefM, ResM, or NRNRM groups. Baseline data were analyzed to assess the frequency of previous diagnostic tests and misdiagnoses.ResultsOverall, 689 participants were included with a median age of 46 years (interquartile range 36-53); 570 participants (82.7%) were female; 355 (51.5%) had NRNRM, 261 (37.9%) ResM, and 73 (10.9%) RefM. Referring to diagnostic tests, 335 participants (48.7%) had one and 237 (34.4%) multiple brain magnetic resonance imaging scans. ResM and RefM participants underwent more diagnostic tests than NRNRM. Overall, 193 participants (28.0%) had at least one prior headache misdiagnosis, most commonly cervical spine disorders and sinusitis; misdiagnoses were more frequent in NRNRM and ResM than in RefM (31.1%, 28.5%, and 15.1%, respectively; p = 0.025). Misdiagnosis rates were not influenced by age, sex, disease duration, or comorbidities.ConclusionsDiagnostic tests use and misdiagnoses are highly prevalent in all the three groups of individuals with ResM, RefM, and NRNRM with some differences across the three groups that may depend on multiple factors. Our findings emphasize a need for better diagnostic accuracy and care pathway across the entire spectrum of migraine, to avoid unnecessary diagnostic tests and misdiagnoses.

Background: A substantial proportion of patients with chronic migraine (CM) with previous failures among oral standard-of-care migraine medications do not respond to monoclonal antibodies targeting the calcitonine gene related peptide pathway (CGRP-mAbs), leaving limited evidence-based options for subsequent preventive strategies. The present multicentre real-world study evaluated the effectiveness of onabotulinumtoxin-A (BoNT-A) in CM patients with previous CGRP-mAb failure and multiple prior oral preventive failures. Methods: This prospective, observational, non-randomized multicentre study enrolled patients with CM who had failed ≥3 classes of oral preventive treatments and ≥1 CGRP-mAb due to lack of efficacy or intolerance. Participants received BoNT-A according to the PREEMPT “follow-the-pain” paradigm every three months and were followed for 6 months. Co-primary outcomes were change in monthly headache days (MHD) after three and six months and ≥50% MHD responder rates at both time points. Results: Fifty-three patients were analysed (85% female, aged 48.5 ± 15.2 years, range 20–73). Compared to the baseline, at the third month and sixth month, MHD decreased from 22.83 (SD 6.74) to 15.38 (SD 7.91; p < 0.001) and 14.55 (SD 9.35; p < 0.001), respectively. The percentages of participants achieving the response status in MMD at the third month and sixth month were 30% and 45%, respectively. In the third and sixth months, 22 patients (41.5%) and 27 patients (50.9%), respectively, converted from chronic to episodic migraine, while the prevalence of medication-overuse headache decreased from 81.1% of patients at baseline to 45.3% and 43.4%, respectively. Migraine-related impact and disability scores improved over follow-up, alongside improvements in anxiety and depressive symptoms and in migraine-specific quality of life. Conclusions: The present findings support the use of BoNT-A in difficult-to-treat patients with CM following CGRP-mAb failure and provide further evidence that its therapeutic effects may rely on mechanisms that are at least partially distinct from, and potentially complementary to, those of CGRP-targeted therapies.

BACKGROUND AND PURPOSE:Randomized trials support early initiation of direct oral anticoagulants (DOACs) after atrial fibrillation (AF)-related ischemic stroke, but patients with breakthrough ischemic stroke occurring despite ongoing anticoagulation have been largely under-represented. We evaluated the effectiveness and safety of early versus delayed DOAC initiation after breakthrough ischemic stroke. METHODS:We performed a target trial emulation comparing early versus delayed DOAC initiation in patients with breakthrough ischemic stroke. Treatment strategies were prespecified using severity-adapted timing thresholds based on baseline National Institutes of Health Stroke Scale (NIHSS) scores. The study population was drawn from the retrospective arm of the international, multicenter Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulant (ASPERA) study and included patients with AF who experienced an ischemic stroke while receiving continuous anticoagulation. To emulate random assignment and avoid immortal time bias, a cloning-censoring-weighting approach with inverse probability weighting was applied. Primary outcomes were 90-day new ischemic events and moderate-to-severe bleeding. Risk ratios (RRs), absolute risk differences (RDs), and hazard ratios (HRs) were estimated using weighted regression and Cox models. RESULTS:Among 833 patients (median age = 81 years), 336 were assigned to early and 497 to delayed DOAC initiation. At 90 days, early initiation was associated with a lower risk of new ischemic events (RR = 0.44, 95% CI = 0.21-0.90; RD = -3.64%, 95% CI = -6.40 to -0.87; HR = 0.43, 95% CI = 0.21-0.91). Moderate-to-severe bleeding occurred less frequently with early initiation (RR = 0.10, 95% CI = 0.01-0.76). Early initiation was also associated with lower 90-day all-cause and vascular mortality. A Net Early Benefit Score integrating ischemic and bleeding risks was positive across all NIHSS strata. CONCLUSION:In patients with breakthrough ischemic stroke, early severity-adapted DOAC initiation was associated with lower risks of recurrent ischemic events and mortality at 90 days without an increase in major bleeding. These findings support early anticoagulation initiation in this high-risk population.

Abstract Background and aims The clinical utility of implantable cardiac monitors (ICMs) for atrial fibrillation (AF) detection following cryptogenic stroke or embolic stroke of undetermined source (ESUS) is well established. However, the optimal timing for ICM implantation to maximize diagnostic yield remains uncertain. We aim to systematically review the literature and conduct a meta-analysis to determine whether earlier ICM implantation after cryptogenic stroke or ESUS ischemic stroke improves detection rates and reduces the time to AF diagnosis. Methods A comprehensive search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception to June 2025. We included observational studies or randomized trials reporting ICM in patients with ESUS or cryptogenic stroke/TIA, providing data on AF detection rates and/or timing metrics (stroke-to-ICM interval, ICM-to-AF interval). The primary outcomes were pooled AF detection rate and mean time from ICM implantation to AF diagnosis. Timing of implantation was assessed as a continuous and categorical (early, intermediate, delayed) variable. Results Forty-seven studies (N = 6,918 patients) were included. Early ICM implantation (<31.5 days from index event) was associated with a higher AF detection rate compared to delayed implantation (30.0% vs. 23.7%; p = 0.0017), independent of monitoring duration (Figure 1). For each additional day of delay in ICM implantation, the time to AF diagnosis increased by an additional 0.32 days on average, even after accounting for monitoring duration (p = 0.0007). Conclusions These findings suggest that earlier ICM implantation enhances AF detection after ESUS or cryptogenic stroke and shortens diagnostic delay. Conflict of interest Nothing to disclose Figure 1 - belongs to Results

IntroductionCerebrovascular diseases are a major cause of morbidity/mortality worldwide, yet more than 30% of strokes remain of undetermined origin. Rare cerebrovascular diseases (rCVDs) contribute to this burden but are often underdiagnosed due to limited awareness, clinical heterogeneity, and fragmented diagnostic access. The ALIGNED project was established to address these gaps through a nationwide multidisciplinary network.MethodsALIGNED was aimed to improve clinical/molecular characterization of rCVDs through standardized data collection, assess level of care of rCVDs by an online/on-site survey and reduce the geographical gap across Italy, by a virtual model of rCVDs care. In the first phase we conducted a survey to evaluate the availability of diagnostic/therapeutic pathways. Preliminary molecular profiling (i.e., transcriptomic/proteomic analyses) has been carried out on middle-cerebral artery and plasma samples from Moyamoya angiopathy (MMA) patients.ResultsFourty-nine centers adhered to the project. Initially, we collected a cohort of 308 subjects with rCVDs: CADASIL (162), COL4A1/A2-related disease (9), Sneddon syndrome (25), Fabry disease (32), and MMA (80). Web-based survey and site visits provided a representative overview of national capabilities in rCVD diagnosis and care. Transcriptomic analysis showed a peculiar expression profile of angiogenesis growth factors/inhibitors in MMA cerebral vessels. Plasma proteomic profiles of MMA patients highlighted circulating proteins expressed in dysfunctional angiogenesis.DiscussionPreliminary data suggested a substantial variability in the quality of rCVDs management and in the availability of diagnostic tools across Italy. Thus, mapping Italian expertise and facilities emerged as a crucial target for pinpointing gaps, improving resource allocation, standardizing rCVD care to guarantee equitable access for patients.

Abstract Background and aims Intravenous thrombolysis (IVT) is the approved treatment for all ischemic stroke subtypes; however, its effectiveness in lacunar stroke remains uncertain. To explore this, we conducted an international survey to assess clinician perspectives on the management of suspected lacunar stroke. We examined treatment preferences across clinical scenarios, attitudes toward IVT and dual antiplatelet therapy (DAPT), and support for future randomized trials comparing these approaches. Methods We conducted a cross-sectional international survey with scenario-based questions and Likert-scale responses using REDCap. Descriptive statistics were used to analyze treatment preferences across subgroups. Results A total of 393 physicians participated, including 61.1% vascular neurologists and 38.9% non-stroke specialists. IVT was the preferred treatment across all scenarios (67.9%), with no major differences observed between specialties or between comprehensive stroke centers and other settings. DAPT was most frequently considered (40.7%) in a scenario involving a 61-year-old patient with vascular risk factors and a lacunar stroke presenting as sensorimotor hemiparesis predominantly affecting the right leg (National Institutes of Health Stroke Scale [NIHSS] 3); 74.9% of respondents felt this case was not well represented in current IVT guidelines. Willingness to enroll similar patients in a randomized trial comparing DAPT and IVT was high, ranging from 88.8% in the low NIHSS case to 79.5% in a more severe presentation (NIHSS 7) involving dementia and leukoencephalopathy. Conclusions Clinician preferences varied across lacunar stroke scenarios, particularly in lower NIHSS presentations, indicating clinical equipoise. These findings underscore the need for a randomized controlled trial comparing DAPT and IVT in patients with suspected lacunar stroke. Conflict of interest Jessika Gorzolka. nothing to disclose. Chantal Kaempf. nothing to disclose. Simona Sacco. nothing to disclose. Hui-Sheng Chen. nothing to disclose. Urs Fischer. nothing to disclose. Bruce Campbell. nothing to disclose. Diana Aguiar de Sousa. nothing to disclose. Volker Puetz. nothing to disclose. Goetz Thomalla. nothing to disclose. Bastian Cheng. nothing to disclose. Charlotte Cordonnier. nothing to disclose. Grégoire Boulouis. nothing to disclose. Espen Kristoffersen. nothing to disclose. Michael Hill. nothing to disclose. Luciano Sposato. nothing to disclose. Mai Duy Ton. nothing to disclose. Hiroshi Yamagami. nothing to disclose. Wei Hu. nothing to disclose. Mira Katan. nothing to disclose. Thanh N. Nguyen. nothing to disclose. Joachim Fladt. nothing to disclose.

Although guidelines for controlled trials have proposed a definition for a migraine day, substantial variability remains across clinical trials, highlighting the need for a universally adopted definition. Through three survey rounds using an eDelphi method, a panel of 18 headache experts evaluated clinical scenarios to achieve consensus on a standardized definition of a migraine day. The first two rounds provided clear-cut cases with the question whether a clinical scenario should be labelled as a migraine day and the third round proposed a migraine day definition. Consensus was predefined at 70

Background: Migraine in older adults represents an increasingly relevant yet underrecognized clinical challenge in aging societies, where multimorbidity, frailty, and polypharmacy complicate both diagnosis and management. Although traditionally considered a disorder of younger individuals, migraine frequently persists or presents after the age of 60 with atypical features, contributing to diagnostic uncertainty. Methods: This narrative review, conducted in accordance with the SANRA principles, aims to provide a comprehensive overview of the epidemiology, clinical presentation, pathophysiology, and management of migraine in older adults, with particular emphasis on age-related complexities, therapeutic challenges, and unmet clinical needs. Results: Migraine in this population often presents with atypical or misleading features, such as aura without headache, vestibular symptoms, or overlap with cerebrovascular conditions, leading to delayed or incorrect diagnoses. The burden of disease is substantial, affecting physical function, mobility, cognition, emotional well-being, and social participation, and is further amplified by comorbid conditions including cardiovascular and metabolic disorders, mood disturbances, and chronic pain syndromes. Aging-related neurobiological changes, such as impaired pain modulation, endothelial dysfunction, and neuroinflammation, may influence disease expression and treatment response. Therapeutic management is challenged by contraindications, increased susceptibility to adverse drug effects, and the complexity of polypharmacy, highlighting the importance of individualized and non-pharmacological approaches. Conclusions: Migraine in older adults is a significant but often overlooked contributor to disability and reduced quality of life. Improved recognition of its unique clinical features and age-specific vulnerabilities is essential to optimize patient-centered care. Future research should prioritize the inclusion of older populations and the development of tailored, safe, and effective management strategies.

INTRODUCTION:Endovascular therapy (EVT) has become an increasingly important part of acute stroke management. However, the lack of trained neurointerventionalists represents a key barrier in expanding availability of EVT in Europe. This project aimed to investigate the association between the number of neurointerventionalists and overall EVT rates. PATIENTS AND METHODS:A cross-sectional analysis was conducted using publicly available data from the Global Burden of Disease Report 2021 and the Stroke Action Plan for Europe (Stroke Service Tracker). Data on the number of neurointerventionalists across 35 European countries were surveyed through a structured survey distributed via the Resident and Research Fellow Section (RRFS) of the European Academy of Neurology (EAN). Correlation analyses were performed to estimate the association between neurointerventionalist density per served population, EVT rates and stroke-related mortality and morbidity. RESULTS:Survey response rate was 71% (25/35 countries). The proportion of acute ischaemic stroke patients treated with EVT ranged from 0.05% to 14.96% of people with ischaemic stroke, and the number of neurointerventionalists ranged from 9 to 137 per country and from 0.3 to 7.5 per million inhabitants. There was a positive correlation between the number of neurointerventionalists per population served and EVT rates (Spearman coefficient ρ = 0.507; 95% CI, 0.209-0.719). Greater availability of trained neurointerventionalists was moderately associated with lower national ischaemic-stroke mortality (ρ = -0.473; 95% CI, -0.746 to -0.065) and lower overall disability-adjusted life years (ρ = -0.444; 95% CI, -0.729 to -0.027). DISCUSSION AND CONCLUSION:The number of neurointerventionalists correlates positively with the annual volume of EVT across European countries; higher EVT rates were also associated with lower stroke-related mortality and disability; however, these associations are unadjusted for other important confounders and causality cannot be inferred. These data suggest an urgent need to increase neurointerventional capacity in Europe, for example, by expanding dedicated national training programmes and enhancing support from national and international professional societies.