Importance:Despite high recanalization rates with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion, functional outcomes remain suboptimal. The benefit of adjunctive intra-arterial thrombolysis after successful thrombectomy is uncertain. Objective:To assess whether adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion. Design, Setting, and Participants:Randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain from December 11, 2023, through November 26, 2025. A total of 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 were randomized. Interventions:Thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg) infused over 15 minutes (n = 221) or thrombectomy alone (n = 219). Main Outcomes and Measures:The primary outcome was an excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0 or 1. There were 6 secondary outcomes, including residual hypoperfusion on follow-up computed tomography perfusion. The safety outcomes included symptomatic intracranial hemorrhage and death. Results:Of 3786 patients treated with thrombectomy, 2776 (73%) fulfilled angiographic criteria and 440 (12%) were randomized. There were 433 patients who were treated as randomized (median age, 76 [IQR, 75-78] years; 51% female). At 90 days, 57.5% of patients (123/214) in the thrombectomy plus intra-arterial alteplase group had a modified Rankin Scale score of 0 or 1 vs 42.5% of patients (93/219) in the thrombectomy alone group (adjusted risk difference, 15.0% [95% CI, 5.7% to 24.3%]; P = .002). Of 6 secondary outcomes, 4 showed no significant between-group differences. Residual hypoperfusion occurred in 28.6% (55/192) of patients in the thrombectomy plus intra-arterial alteplase group vs 50.5% (96/190) of patients in the thrombectomy alone group (adjusted risk difference, -22.0% [95% CI, -31.5% to -12.4%]; P < .001) and symptomatic intracranial hemorrhage occurred in 1.4% (3/214) vs 0.5% (1/219), respectively (adjusted odds ratio, 3.10 [95% CI, 0.32 to 30.0]; P = .33). Mortality at 90 days was 12.1% (26/214) in the thrombectomy plus intra-arterial alteplase group vs 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9% [95% CI, 0.5% to 11.3%]; P = .03). Conclusions and Relevance:Among patients with acute ischemic stroke and successful thrombectomy, adjunctive intra-arterial alteplase increased the proportion achieving excellent functional outcome at 90 days without a significant increase in symptomatic intracranial hemorrhage. Higher mortality in the thrombectomy plus intra-arterial alteplase group warrants further study. Trial Registration:ClinicalTrials.gov Identifier: NCT05797792.

Importance Despite high recanalization rates with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion, functional outcomes remain suboptimal. The benefit of adjunctive intra-arterial thrombolysis after successful thrombectomy is uncertain. Objective To assess whether adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion. Design, Setting, and Participants Randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain from December 11, 2023, through November 26, 2025. A total of 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 were randomized. Interventions Thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg) infused over 15 minutes (n = 221) or thrombectomy alone (n = 219). Main Outcomes and Measures The primary outcome was an excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0 or 1. There were 6 secondary outcomes, including residual hypoperfusion on follow-up computed tomography perfusion. The safety outcomes included symptomatic intracranial hemorrhage and death. Results Of 3786 patients treated with thrombectomy, 2776 (73%) fulfilled angiographic criteria and 440 (12%) were randomized. There were 433 patients who were treated as randomized (median age, 76 [IQR, 75-78] years; 51% female). At 90 days, 57.5% of patients (123/214) in the thrombectomy plus intra-arterial alteplase group had a modified Rankin Scale score of 0 or 1 vs 42.5% of patients (93/219) in the thrombectomy alone group (adjusted risk difference, 15.0% [95% CI, 5.7% to 24.3%]; P = .002). Of 6 secondary outcomes, 4 showed no significant between-group differences. Residual hypoperfusion occurred in 28.6% (55/192) of patients in the thrombectomy plus intra-arterial alteplase group vs 50.5% (96/190) of patients in the thrombectomy alone group (adjusted risk difference, –22.0% [95% CI, −31.5% to −12.4%]; P < .001) and symptomatic intracranial hemorrhage occurred in 1.4% (3/214) vs 0.5% (1/219), respectively (adjusted odds ratio, 3.10 [95% CI, 0.32 to 30.0]; P = .33). Mortality at 90 days was 12.1% (26/214) in the thrombectomy plus intra-arterial alteplase group vs 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9% [95% CI, 0.5% to 11.3%]; P = .03). Conclusions and Relevance Among patients with acute ischemic stroke and successful thrombectomy, adjunctive intra-arterial alteplase increased the proportion achieving excellent functional outcome at 90 days without a significant increase in symptomatic intracranial hemorrhage. Higher mortality in the thrombectomy plus intra-arterial alteplase group warrants further study. Trial Registration ClinicalTrials.gov Identifier: NCT05797792

Abstract Background and aims Malignant cerebral infarction (MCI) is a life-threatening complication of large vessel occlusion (LVO). Baseline CT-perfusion (CTP) thresholds and ASPECTS predict MCI, but their performance may depend on time-to-imaging and reperfusion success. We evaluated whether these factors influence the predictive accuracy of baseline markers (ASPECTS, relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF]) for MCI. Methods We retrospectively analyzed 249 patients with severe anterior circulation LVO and multimodal CT at admission. Patients were stratified into four groups by time-to-CTP (Early <3h vs. Late ≥3h) and reperfusion status (Successful, mTICI 2b–3 vs. Unsuccessful). MCI was defined by both clinical and radiological criteria. Predictive performance of ASPECTS, rCBV, and rCBF core volumes across thresholds (0–100% of contralateral values) was assessed using ROC area, sensitivity, specificity, positive predictive value (PPV), and F1-score. Results MCI occurred in 62/249 patients (25%). Time and reperfusion showed a strong interaction (p<0.001): rates were 12% (Early+Successful), 32% (Early+Unsuccessful), 14% (Late+Successful), and 46% (Late+Unsuccessful). In the Early+Unsuccessful group, rCBV<40% had higher predictive capacity than ASPECTS or rCBF. In the Late+Unsuccessful group, all three parameters reached high predictive values. In both reperfused subgroups, PPV for all baseline parameters dropped to 20–35% despite sensitivity >90%. Conclusions Baseline imaging prediction of MCI is strongly time- and reperfusion-dependent. rCBV is the most robust early marker of malignant evolution when reperfusion fails, whereas successful reperfusion essentially invalidates predictions derived from baseline cores. Conflict of interest Name of author: nothing to disclose

INTRODUCTION Sleep disruption, particularly loss of slow-wave sleep (SWS), is common in Alzheimer's disease (AD), but its neurobiological underpinnings remain unclear. We investigated whether locus coeruleus (LC) integrity relates to SWS across the AD continuum and whether sex and perivascular spaces (PVSs) modify these associations. METHODS In a cohort (11 controls, 30 mild cognitive impairment, 17 AD dementia) we combined overnight polysomnography with LC-sensitive magnetic resonance imaging of the LC, basal ganglia and centrum semiovale PVS ratings, and cerebrospinal fluid noradrenaline. Multivariable linear regression adjusted for demographics, disease stage, and medication use. RESULTS Higher LC integrity was associated with greater slow-wave activity and slow oscillation power, with stronger effects in females. Basal ganglia PVS burden was related to lower SWS spectral power, whereas noradrenaline levels were not associated with sleep. DISCUSSION LC integrity, sex, and PVS burden show associations with SWS alterations in aging and AD, supporting restorative sleep as a potential therapeutic target.

Abstract Background and aims Circulating biomarkers reflecting inflammation and endothelial dysfunction have been proposed as indicators of cerebral small vessel disease. Still, their relevance during the hyperacute phase of ischemic stroke, not only in small vessel disease, remains uncertain. In this study we examine whether circulating biomarker profiles measured on admission differ between in patients with recent small subcortical infarcts (RSSI) and small cortical or cortico-subcortical stroke (non-RSSI), and whether they have prognostic value beyond conventional predictors. Methods Retrospective analysis of 168 patients with acute ischemic stroke treated with intravenous thrombolysis within 4.5 hours of onset. Patients were classified by magnetic resonance imaging as RSSI (n=84) or non-RSSI (n=84). Admission blood levels of interleukin-1β, interleukin-6, matrix metalloproteinase-9, vascular cell adhesion molecule-1, neurofilament light chain, C-reactive protein, and leukocyte count ratios were measured. Associations with 3-month functional outcomes (modified Rankin Scale) were evaluated using multivariable regression. Results RSSI patients were younger (66 vs. 74 years, p <0.001) and had smaller infarcts (median 0.68 vs. 2.55 mL, p<0.001). Neurofilament light chain (OR 2.07, p<0.001) and vascular cell adhesion molecule-1 (OR 1.84, p=0.034) predicted poorer outcomes in adjusted models. The prognostic value of C-reactive protein, matrix metalloproteinase-9, and VCAM-1 was more substantial in RSSI than in non-RSSI patients. Conclusions In RSSI, markers of inflammation and endothelial dysfunction improved outcome prediction, suggesting a role for microvascular pathology in recovery. The integration of biomarker profiling into early stroke assessment might help identify patients who could benefit from adjunctive therapies targeting microvascular dysfunction. Conflict of interest Dario Ramis: nothing to disclose.

Circulating biomarkers reflecting inflammation and endothelial dysfunction have been proposed as indicators of cerebral small vessel disease; however, their relevance during the hyperacute phase of ischemic stroke remains uncertain. We aimed to determine whether circulating biomarkers measured on admission differ between small ischemic stroke subtypes and whether they provide prognostic information beyond conventional predictors. We conducted a retrospective analysis of 168 patients with acute ischemic stroke treated with intravenous thrombolysis within 4.5 h of onset, classified by MRI as having recent small subcortical infarcts (RSSI; n = 84) or small cortical or cortico-subcortical infarcts (non-RSSI; n = 84). We measured admission blood levels of interleukin-1β, interleukin-6, matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), neurofilament light chain (NfL), C-reactive protein (CRP), and leukocyte ratios, and evaluated their associations with 3‑month functional outcomes using the modified Rankin Scale. Our findings showed that RSSI patients were younger (66 vs. 74 years, p < 0.001) and had smaller infarcts (0.68 vs. 2.55 mL, p < 0.001). Higher NfL (OR 2.07, p < 0.001) and VCAM‑1 levels (OR 1.84, p = 0.034) were associated with poorer outcomes. Notably, the prognostic contribution of CRP, MMP‑9, and VCAM‑1 was more pronounced in patients with RSSI. These findings suggest that circulating biomarkers may offer additional prognostic value, with patterns varying across small ischemic stroke subtypes, though their clinical utility warrants further investigation.

Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers. We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume. All patients (mean age 70 years, 36

Background: Vascular risk factors (VRFs) are known to influence cerebral small vessel disease (cSVD) burden and progression. However, their specific impact on the presence and distribution of each cSVD imaging marker (white matter hyperintensity [WMH], perivascular spaces [PVSs], lacunes, and cerebral microbleeds [CMBs]) and their spatial distribution remains unclear. Methods: We conducted a retrospective analysis of 93 patients with lacunar stroke with a standardized investigational magnetic resonance imaging protocol using a 3T scanner. WMH and PVSs were segmented semi-automatically, and lacunes and CMBs were manually segmented. We assessed the univariable associations of four common VRFs (hypertension, hyperlipidemia, diabetes, and smoking) with the load of each cSVD marker. Then, we assessed the independent associations of these VRFs in multivariable regression models adjusted for age and sex. Spatial lesion patterns were explored with regional volumetric comparisons using Pearson’s coefficient analysis, which was adjusted for multiple comparisons, and by visually examining heatmap lesion distributions. Results: Hypertension was the VRF that exhibited stronger associations with the cSVD markers in the univariable analysis. In the multivariable analysis, only lacunes (p = 0.009) and PVSs in the basal ganglia (p = 0.014) and white matter (p = 0.016) were still associated with hypertension. In the regional analysis, hypertension showed a higher WMH load in deep structures and white matter, particularly in the posterior periventricular regions. In patients with hyperlipidemia, WMH was preferentially found in hippocampal regions. Conclusions: Hypertension was confirmed to be the VRF with the most impact on cSVD load, especially for lacunes and PVSs, while the lesion topography was variable for each VRF. These findings shed light on the complexity of cSVD expression in relation to factors detrimental to vascular health.

Background: Horizontal conjugate eye deviation (HCED) is typically associated with supratentorial strokes affecting the frontal eye fields and associated pathways. However, a rare form of HCED, ocular ipsipulsion, is caused by a lateral medullary lesion. The presumed mechanism involves disruption of decussating olivocerebellar fibers, leading to an imbalance in vestibular nuclei activity.Purpose: To report a case of isolated ocular ipsipulsion as a diagnostic clue to central vertigo.Research Design: Case report.Study Sample: An 82-year-old man with a right lateral medullary infarction.Data Collection: Neurological examination and brain magnetic resonance imaging (MRI) were performed. Ocular findings were documented through bedside observation and video recording.Results: The patient presented with acute vertigo and HCED consistent with ocular ipsipulsion, without other neurological signs. On brain MRI a right lateral medullary infarction was observed.Conclusions: This oculomotor dysfunction can be the only clue in the neurological examination to suspect a central vertigo. Clinicians should be aware of this sign and include its assessment in the bedside evaluation of acute vertigo in the emergency setting if a central cause is suspected.

BACKGROUND AND PURPOSE:The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary vein (DMV) integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct. MATERIALS AND METHODS:We gathered demographic, clinical, and 3T MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluated the venular integrity by using 2 visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures by using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score. RESULTS:In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter, and DTI along the perivascular spaces, were associated with 1 or both venular scores. In multivariate analysis, free water (OR, 1.33, 95% CI, 1.03-1.73), mean diffusivity (OR, 4.56, 95% CI, 1.32-15.81), fractional anisotropy (OR, 0.77, 95% CI, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (OR, 2.39, 95% CI, 1.06-5.39; OR 0.78, 95% CI, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (OR, 0.48, 95% CI, 0.25-0.94), fractional anisotropy with and without free water correction (OR, 0.82, 95% CI, 0.86-0.99; OR, 0.83, 95% CI, 0.7-0.99, respectively) remained robust for vein count. CONCLUSIONS:In patients with a recent small subcortical infarct, disruption of the DMVs, increased extracellular water, and white matter injury appear to be associated.

Purpose: Cerebral small vessel disease (cSVD) is a highly prevalent disorder leading to physical, cognitive and functional decline. We report key barriers in the management of individuals with cSVD, the potential benefit of cSVD-dedicated health services, and evidence from existing models of care for adults with cSVD. Methods: We examined information from a scientific seminar developed between seven experts in cSVD during the eighth European Stroke Organisation Conference that discussed the optimal health care for adults with cSVD and what health services dedicated to cSVD should include. Findings: Barriers in cSVD care include unrecognised symptoms and modifiable risk factors, heterogeneity of clinical presentations, inefficient inter/intra-clinical services communication/organisation, and uncertainties regarding what assessments/treatments should be routinely done, when and by whom. However, existing health services and research studies suggest models of care in cSVD. Multi-step approaches can be used for identification and aetiological workup in individuals with cSVD, including basic and selected advanced evaluations, for example, monogenic cSVD testing. Although current guidelines for management of cSVD illlustrate limitations, there are recommendations on risk factors and lifestyle considerations, as well as pharmacological and non-pharmacological interventions for people with cSVD. Discussion and conclusion: Existing healthcare models do not provide optimal care for individuals with cSVD. Lack of awareness of heterogeneous clinical presentations and uncertainty in threshold of cSVD ‘burden’ for referral to specialist multidisciplinary services, are key challenges for health services to overcome. Creating cSVD-dedicated services may prevent underdiagnosing and achieve standardised holistic management to improve outcomes in people with cSVD. However, adequate prevention and early management should be offered at all levels of care.

BACKGROUND:Evidence from randomized clinical trials shows that mechanical thrombectomy (MT) enhances functional outcomes in patients with large core ischemic stroke. OBJECTIVE:To evaluate trends in the use of revascularization therapies, particularly MT, and their impact on functional outcomes in patients with large core ischemic stroke in routine clinical settings. METHODS:Observational data from the Stroke Code Registry of Catalonia (CICAT, 2016-2024) were analyzed. Patients with anterior circulation ischemic stroke and Alberta Stroke Program Early CT Score (ASPECTS) <6, whether treated with reperfusion therapies or not, were included. Statistical analyses included trend analysis and multivariable logistic regression to identify predictors of favorable outcomes (modified Rankin Scale score 0-3 at 90 days) and mortality. RESULTS:Among 599 patients, MT use increased significantly from 22% pre-2022 to 36% post-2022. This increase was associated with improved functional outcomes, with favorable outcomes rising from 29% to 43% post-2022. MT was a significant independent predictor of favorable outcomes (OR 3.4, 95% CI 2.1 to 5.5) and reduced mortality (OR 0.46, 95% CI 0.32 to 0.68). Intravenous thrombolysis also improved outcomes (OR 2.1, 95% CI 1.3 to 3.5). The benefit of MT was consistent across ASPECTS subgroups (0-2 and 3-5). Mediation analysis indicated that 88% of improvement could be attributed to increased MT use. CONCLUSIONS:Increased MT use significantly improved outcomes for patients with large core ischemic stroke, particularly after 2022. Benefits were observed across subgroups, including those with very low ASPECTS. These findings support broadening MT access and suggest the need to update treatment guidelines to consider patients with large ischemic cores, aiming to optimize outcomes in routine clinical practice.

Malignant cerebral infarction (MCI) is rare but often fatal. Early identification helps guide monitoring and decompressive surgery. This study evaluated whether serum biomarkers add predictive value beyond clinical and imaging data in severe stroke patients with anterior circulation large vessel occlusion (LVO). In this prospective study, 73 acute severe LVO stroke patients underwent whole-brain CT perfusion (CTP) with rCBV-based core measurement at admission and follow-up MRI at 24 ± 12 h for infarct and edema volume assessment. Serum biomarkers (s100b, NSE, VEGF, ICAM1) were sampled a median of 20.5 h after baseline imaging. Logistic regression models predicted MCI using baseline variables (NIHSS, ASPECTS, rCBV < 30%), adding treatment data (rtPA, mTICI, NIHSS posttreatment), and adding serum biomarkers. Performance was assessed by AUC, accuracy, F1, and cross-validated R2. MCI occurred in 18/73 (24%) patients. Baseline models showed an AUC of 0.72; adding treatment improved the AUC to 0.88. Biomarkers slightly increased the AUC (0.90) but did not improve F1. Higher s100b was associated with more severe injury but did not enhance the prediction of MCI. Models with baseline imaging and treatment best explained infarct (R2 ≈ 0.27) and edema (R2 ≈ 0.58). In conclusion, admission severity, CTP, and early treatment response are the main predictors of MCI and aid early risk stratification of patients. Despite their pathophysiologic relevance, serum biomarkers do not add substantial predictive value.

BACKGROUND AND OBJECTIVES:Factors associated with cerebral small vessel disease (SVD) progression, including incident infarcts, are unclear. We aimed to determine the frequency of incident infarcts over 1 year after minor stroke and their relation to baseline SVD burden, vascular risks, and recurrent stroke and cognitive outcomes. METHODS:We recruited patients with lacunar or nondisabling cortical stroke. After diagnostic imaging, we repeated structural MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on diffusion-weighted imaging or FLAIR. We used logistic regression to determine associations of baseline vascular risks, SVD score, and index stroke subtype with subsequent incident infarcts. We assessed cognitive and functional outcomes at 1 year using Montreal Cognitive Assessment (MoCA) and modified Rankin scale (mRS), adjusting for baseline age, mRS, MoCA, premorbid intelligence, and SVD score. RESULTS:We recruited 229 participants, mean age 65.9 (SD 11.1). Over half of all participants, 131 of 229 (57.2%) had had an index lacunar stroke. From baseline to 1-year MRI, we detected 117 incident infarcts in n = 57/229 (24.8%) participants. Incident infarcts were mainly of the small subcortical (86/117 [73.5%] in n = 38/57 [66.7%]) vs cortical infarct subtype (n = 19/57 [33.3%]). N = 39/57 participants had incident infarcts at 1 visit; 18 of 57 at 2 or more visits; and 19 of 57 participants had multiple infarcts at a single visit. Only 7 of 117 incident infarcts corresponded temporally to clinical stroke syndromes. The baseline SVD score was the strongest predictor of incident infarcts (adjusted odds ratio [OR] 1.87, 95% CI 1.39-2.58), while mean arterial pressure was not associated. All participants with incident infarcts were prescribed an antiplatelet or anticoagulant. Lower 1-year MoCA was associated with lower baseline MoCA (β 0.47, 95% CI 0.33-0.61), lower premorbid intelligence, and older age. Higher 1-year mRS was associated with higher baseline mRS only (OR 5.57 [3.52-9.10]). Neither outcome was associated with incident infarcts. DISCUSSION:In the year after stroke in a population enriched for lacunar stroke, incident infarcts occurred in one-quarter and were associated with worse baseline SVD. Most incident infarcts detected on imaging did not correspond to clinical stroke/transient ischemic attack. Worse 1-year cognition and function were not associated with incident infarcts.

Background and ObjectivesFactors associated with cerebral small vessel disease (SVD) progression, including incident infarcts, are unclear. We aimed to determine the frequency of incident infarcts over 1 year after minor stroke and their relation to baseline SVD burden, vascular risks, and recurrent stroke and cognitive outcomes.MethodsWe recruited patients with lacunar or nondisabling cortical stroke. After diagnostic imaging, we repeated structural MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on diffusion-weighted imaging or FLAIR. We used logistic regression to determine associations of baseline vascular risks, SVD score, and index stroke subtype with subsequent incident infarcts. We assessed cognitive and functional outcomes at 1 year using Montreal Cognitive Assessment (MoCA) and modified Rankin scale (mRS), adjusting for baseline age, mRS, MoCA, premorbid intelligence, and SVD score.ResultsWe recruited 229 participants, mean age 65.9 (SD 11.1). Over half of all participants, 131 of 229 (57.2%) had had an index lacunar stroke. From baseline to 1-year MRI, we detected 117 incident infarcts in n = 57/229 (24.8%) participants. Incident infarcts were mainly of the small subcortical (86/117 [73.5%] in n = 38/57 [66.7%]) vs cortical infarct subtype (n = 19/57 [33.3%]). N = 39/57 participants had incident infarcts at 1 visit; 18 of 57 at 2 or more visits; and 19 of 57 participants had multiple infarcts at a single visit. Only 7 of 117 incident infarcts corresponded temporally to clinical stroke syndromes. The baseline SVD score was the strongest predictor of incident infarcts (adjusted odds ratio [OR] 1.87, 95% CI 1.39-2.58), while mean arterial pressure was not associated. All participants with incident infarcts were prescribed an antiplatelet or anticoagulant. Lower 1-year MoCA was associated with lower baseline MoCA (beta 0.47, 95% CI 0.33-0.61), lower premorbid intelligence, and older age. Higher 1-year mRS was associated with higher baseline mRS only (OR 5.57 [3.52-9.10]). Neither outcome was associated with incident infarcts.DiscussionIn the year after stroke in a population enriched for lacunar stroke, incident infarcts occurred in one-quarter and were associated with worse baseline SVD. Most incident infarcts detected on imaging did not correspond to clinical stroke/transient ischemic attack. Worse 1-year cognition and function were not associated with incident infarcts.

Background and Purpose: Perivascular spaces (PVS) are usually enlarged in small vessel disease (SVD). However, the significance of PVS patterns in different locations is uncertain. Hence, we analyzed the distribution of PVS in patients with a recent small subcortical infarct (RSSI) and their correlation with clinical and imaging factors. Materials and Methods: In a cohort of 71 patients with an RSSI with complete clinical data, including the Pittsburgh Sleep Quality Index (PSQI), we segmented PVS in white matter (WM-PVS), basal ganglia (BG-PVS), and brainstems (BS-PVS) on 3T-MRI T2-weighted sequences, obtaining fractional volumes (%), and calculated the WM/BG-PVS ratio. We analyzed the Pearson’s correlation coefficients between PVS regional loads. We used normalized PVS measures to assess the associations with clinical and MRI-SVD features (white matter hyperintensities (WMHs), number of lacunes, and microbleeds) in univariable and multivariable linear regressions adjusted for age, sex, and hypertension. Results: In our cohort (mean age 70 years; 27% female), the Pearson’s correlation coefficients between WM-PVS/BG-PVS, WM-PVS/BS-PVS, and BG-PVS/BS-PVS were 0.67, 0.61, and 0.59 (all p < 0.001). In the adjusted models, BG-PVS were associated with lacunes (p = 0.034), WMHs (p = 0.006), and microbleeds (p = 0.017); WM-PVS with lacunes (p = 0.003); while BS-PVS showed no associations. The WM/BG-PVS ratio was associated with lacunes (p = 0.018) and the PSQI (p = 0.046). Conclusions: PVS burdens in different regions are highly correlated in patients with RSSI but with different SVD patterns. Sleep quality impairment might affect waste removal mechanisms differently in the WM and BG regions.

Introduction: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. Materials and Methods: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. Results: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden’s index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F-score 0.71, Youden’s index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F-score 0.62, Youden’s index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. Discussion and conclusion: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.

Background and Objectives The time taken to achieve blood pressure (BP) control could be pivotal in the benefits of reducing BP in acute intracerebral hemorrhage (ICH). We aimed to assess the relationship between the rapid achievement and sustained maintenance of an intensive systolic BP (SBP) target with radiologic, clinical, and functional outcomes. Methods Rapid, Intensive, and Sustained BP lowering in Acute ICH (RAINS) was a multicenter, prospective, observational cohort study of adult patients with ICH <6 hours and SBP >= 150 mm Hg at 4 Comprehensive Stroke Centers during a 4.5-year period. Patients underwent baseline and 24-hour CT scans and 24-hour noninvasive BP monitoring. BP was managed under a rapid (target achievement <= 60 minutes), intensive (target SBP <140 mm Hg), and sustained (target stability for 24 hours) BP protocol. SBP target achievement <= 60 minutes and 24-hour SBP variability were recorded. Outcomes included hematoma expansion (>6 mL or >33%) at 24 hours (primary outcome), early neurologic deterioration (END, 24-hour increase in NIH Stroke Scale score >= 4), and 90-day ordinal modified Rankin scale (mRS) score. Analyses were adjusted by age, sex, anticoagulation, onset-to-imaging time, ICH volume, and intraventricular extension. Results We included 312 patients (mean age 70.2 +/- 13.3 years, 202 [64.7%] male). Hematoma expansion occurred in 70/274 (25.6%) patients, END in 58/291 (19.9%), and the median 90-day mRS score was 4 (interquartile range, 2-5). SBP target achievement <= 60 minutes (178/312 [57.1%]) associated with a lower risk of hematoma expansion (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.23-0.77), lower END rate (aOR 0.43, 95% CI 0.23-0.80), and lower 90-day mRS scores (aOR 0.48, 95% CI 0.32-0.74). The mean 24-hour SBP variability was 21.0 +/- 7.6 mm Hg. Higher 24-hour SBP variability was not related to expansion (aOR 0.99, 95% CI 0.95-1.04) but associated with higher END rate (aOR 1.15, 95% CI 1.09-1.21) and 90-day mRS scores (aOR 1.06, 95% CI 1.04-1.10). Discussion Among patients with acute ICH, achieving an intensive SBP target within 60 minutes was associated with lower hematoma expansion risk. Rapid SBP reduction and stable sustention within 24 hours were related to improved clinical and functional outcomes. These findings warrant the design of randomized clinical trials examining the impact of effectively achieving rapid, intensive, and sustained BP control on hematoma expansion. Classification of Evidence This study provides Class III evidence that in adults with spontaneous ICH and initial SBP >= 150 mm Hg, lowering SBP to <140 mm Hg within the first hour and maintaining this for 24 hours is associated with decreased hematoma expansion.

Introduction Factors associated with incident infarcts after stroke are unclear. We aimed to determine whether subsequent incident infarcts continue to develop one year post-stroke and how incident infarcts relate to baseline imaging features, vascular risks, and cognitive outcomes. Methods We recruited patients with non-disabling stroke. After diagnostic MRI, we repeated MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on DWI or FLAIR. We used logistic regression to determine associations with incident infarcts, including baseline vascular risks, SVD score, and index stroke subtype. We quantified 7-level ordinal cognitive outcome status at one year, using MoCA/telephone MoCA and modified Rankin Scale.[1,2] We used ordinal regression to determine whether cognitive outcomes associated with incident infarcts and baseline age, mRS, MoCA, and WMH volume. Results We recruited 229 participants, mean age 65.9 (SD 11.1) years; 77/229 (33.6%) female; 130/229 (56.8%) index lacunar stroke. From baseline to one-year MRI, we detected 117 incident infarcts in n=57/229 participants at 80 visits. Most were small subcortical infarcts: 86/117 (73.5%) infarcts in n=38/57 (66%). N=39 participants had incident infarcts at one visit; n=14 at two visits; n=3 at three visits, and n=1 at four visits. Nineteen participants had multiple incident infarcts at a single visit. Baseline summary SVD score was the strongest predictor of incident infarcts (aOR 1.74, 95%CI 1.29-2.41, Figure 1). At one year, 10/218 (4.6%) participants met criteria for single-domain and 62/218 (28.4%) for multi-domain neurocognitive disorder; 15/218 (6.8%) for mild dementia; 2/218 (0.9%) for moderate dementia; none severe; 3/229 (1.3%) had died. Participants’ odds of impaired one-year cognition increased for every one-unit increment in baseline mRS (aOR=2.03 [1.30-3.10]) and decreased for every one-unit increment in baseline MoCA (aOR=0.78 [0.71-0.85]). For participants with incident small subcortical infarcts, the odds of impaired cognition were 23% higher than for incident cortical infarcts, though not statistically significant (aOR 1.23 [0.55-2.1])(Figure 2). Discussion In a mild stroke population, incident infarcts, mostly small subcortical, occur in one quarter and associate with worse baseline SVD. Minor neurocognitive disorder occurs in one third and associates with baseline mRS, MoCA, and trends towards incident small subcortical rather than cortical infarcts.

Background The optimal strategy for transferring patients to specialized acute stroke care remains controversial. This substudy of the Effect of Direct Transportation to Thrombectomy‐Capable Center vs Local Stroke Center on Neurological Outcomes in Patients with suspected Large‐Vessel Occlusion Stroke in Nonurban Areas (RACECAT) trial aims to investigate the impact of local hospital characteristics and performance on the optimal transport strategy and stroke outcomes. Methods This was a secondary post hoc analysis of the RACECAT trial, evaluating factors potentially associated with functional outcomes among patients initially evaluated at a local stroke center (Local‐SC) versus a thrombectomy‐capable center. The primary outcome was the shift in the 90‐day modified Rankin Scale score in the target population of the RACECAT trial. Door‐to‐needle time, level of care of the Local‐SC (telestroke versus primary stroke center), the specialty of the physician involved with therapeutic decisions, and Local‐SC case volume were assessed for subgroup analyses. Results Of the 1367 patients included in the analysis, 903 had acute ischemic strokes (modified intention to treat). The 90‐day modified Rankin Scale score was associated with door‐to‐needle time in the entire modified intention‐to‐treat cohort ( P = 0.026) and in patients initially evaluated in a Local‐SC ( P = 0.063), and with local hospital level of care (telestroke versus primary stroke center; P = 0.10). There was a trend favoring direct transport to thrombectomy‐capable center for patients whose assigned Local‐SC was a telestroke center (adjusted odds ratio [OR], 1.47 [95% CI, 0.93–2.33] versus 0.94 [95% CI, 0.71–1.24]; P interaction = 0.08) or had door‐to‐needle time over the global median (adjusted OR, 1.52 [95% CI, 0.97–2.40] versus 0.94 [95% CI, 0.71–1.25]; P interaction = 0.06). In patients with confirmed large‐vessel occlusion, the benefit of direct transport to thrombectomy‐capable centers when the Local‐SC was a telestroke center ( P interaction = 0.04) or had longer door‐to‐needle time ( P interaction = 0.07) was more evident. Conclusions Direct transport to thrombectomy‐capable centers may be preferable in areas primarily covered by telestroke or Local‐SCs with poorer performance, especially in patients with large‐vessel occlusion. These findings can contribute to refining prehospital triage strategies and optimizing stroke systems of care.