Search Results for: Tumore prostata, test della saliva piu’ attendibile del PSA

Stroke, Volume 56, Issue Suppl_1, Page ATP93-ATP93, February 1, 2025. Introduction:Cognitive and language trajectory has been extensively studied following ischemic stroke, with large epidemiological studies showingon averagea decline in naming and cognition acutely followed by continued decline over time. We tested the hypothesis that average decline reflects a marked decline in patients who show progressive brain atrophy (even in the uninfarcted hemisphere), but improvement in other patients without progressive atrophy. We quantified atrophy in the right (non-infarcted) hemisphere in each individual over time, and examined its relationship to naming change over time.Methods:Participants (n=71) in a longitudinal study of language and MRI over the first year after left hemisphere ischemic stroke were included if they completed an MRI and the Boston Naming Test (BNT) acutely and chronically (either 6m or 12m post-stroke). Stroke volumes were extracted from acute imaging, and atrophy was measured by comparing baseline scans to chronic scans for each individual. Pearson correlations between atrophy and change in BNT score were identified for each hemisphere.Results:Left hemisphere stroke volume correlated with increased left hemisphere atrophy (likely reflecting Wallerian degeneration) (r=0.50, p=0.0001), but not with right hemisphere atrophy (Figure 1). Naming improvedmorewith less right hemisphere atrophy, but the correlation was statistically significant only when 3 outliers were removed (r= 0.56; p=0.0057; Figure 2). Conversely, naming tended to improvelesswith less left hemisphere atrophy (NS; Figure 3), likely reflecting smaller strokes, with less room for improvement.Conclusions:As right hemisphere atrophy is not significantly influenced by left hemisphere stroke volume, progressive decline in naming over the first year after stroke in a subset of patients with progressive right hemisphere atrophy likely points to a separate degenerative process. The subset of patients who show minimal right hemisphere atrophy show improvement, rather than continued decline, in naming over the first year after stroke.

Stroke, Volume 56, Issue Suppl_1, Page AWP224-AWP224, February 1, 2025. Background:The astroglial protein GFAP (glial fibrillary acidic protein) is a promising biomarker candidate for prehospital differentiation between intracerebral hemorrhage (ICH) and ischemic stroke. GFAP is rapidly released into plasma from disrupted astrocytes in expanding ICH, but increases more slowly following ischemic cell necrosis. Besides hematoma volume, factors associated with GFAP release in acute ICH have not been explored. It has been noted in previous studies that a certain proportion of ICH patients did not show elevated GFAP levels, leading to a reduced sensitivity of the test. The aim of this study was to analyze GFAP release kinetics according to ICH location and the time span between symptom onset and blood sampling.Methods:Consecutive ICH patients admitted within 6 hours of symptom onset were derived from a prospective biomarker study in acute stroke. All blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) point of care device. We determined both ICH volume and hematoma location from the first available brain scan after admission in a standardized way.Results:We analyzed 74 ICH patients (mean age 73.5 ± 12.4 years). The median [IQR] time span from symptom onset to blood sampling was 144.0 minutes [113.3] and the mean ICH volume was 35.7 ± 38.8 mL. A strong correlation between hematoma volume and GFAP plasma levels was observed (Spearman rho 0.697; p

Stroke, Volume 56, Issue Suppl_1, Page AWP220-AWP220, February 1, 2025. Background:Several studies have shown that tranexamic acid (TXA), an anti-fibrinolytic agent, may reduce hematoma expansion (HE) in intracerebral hemorrhage (ICH), but its therapeutic time window is unclear. We analyzed the efficacy and safety of TXA based on its time of administration after hemorrhage onset.Methods:We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) published up to July 27, 2024 comparing TXA with placebo in ICH. We excluded trials that used TXA for longer than 3 days which causes delayed vasospasm, increasing the risk of cerebral ischemia. The primary outcomes were HE, 24-hour hemorrhagic volume change, 90-day mortality and poor functional outcome. We grouped the trials into 2 hours, 8 hours or 24 hours of TXA administration after hemorrhage onset. We pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) using Rstudio. Heterogeneity was examined with the I2 test.Results:We included 12 studies with 3,567 patients. Most of the studies used 1 g TXA in patients with Glasgow Coma Scale score ranging from 13-15. TXA reduced HE risk (OR 0.85; 95% CI 0.73 to 0.98; p= 0.03; I2= 0%). This reduction was observed in studies that administered TXA within 8 hours of ICH onset (OR 0.82; 95% CI 0.70 to 0.97; p= 0.02; I2= 0%). TXA slightly reduced 24-hour hemorrhagic volume (MD -1.30 mL; 95% CI -2.51; -0.09; p= 0.04; I2= 47%). This reduction was mainly seen in patients who were administered TXA within 8 hours of hemorrhage onset (MD -1.86 mL; 95% CI -3.15 to -0.58; p< 0.01; I2= 35%). There were no significant differences in poor functional outcome (OR 0.87; 95% CI 0.67 to 1.15; p= 0.34; I2= 24%), 90-day mortality (OR 1.00; 95% CI 0.84 to 1.19; p= 0.96; I2= 0%), major thromboembolic events (OR 1.22; 95% CI 0.82 to 1.82; p= 0.33; I2= 0%), neurosurgical intervention (OR 0.94; 95% CI 0.61-1.45; p= 0.78; I2= 0%) or length of hospital stay (MD -0.49 days; 95% CI -3.27 to 2.29; p= 0.73; I2= 0%).Conclusion:TXA reduced the risk of HE and slightly reduced 24-hour hemorrhagic volume in patients with ICH within 8 hours. Larger RCTs stratifying administration timing are required to establish these findings.

Stroke, Volume 56, Issue Suppl_1, Page AWP218-AWP218, February 1, 2025. Background:Identifying patients likely to have significant hematoma expansion (HE) has been a challenge in clinical trials of intracerebral hemorrhage (ICH). Non-contrast CT (NCCT) markers of HE have been described. Time from symptom onset to CT affects the predictive value of these markers, with limited data in the ultra-early time period (33% or >6ml from baseline. Regression analyses were adjusted for treatment group and baseline hematoma volume.Results:There were 246 patients included in this analysis (median age 67 years, 38.8% female, median time from onset to imaging 75 min [IQR 59-88 min], 50.4% tranexamic acid), of whom 105 (42.7%) had HE on 24-hour imaging. Inter-rater agreement was excellent for all NCCT markers (kappa score >0.8). Most patients (85.7%) had ≥1 marker of HE. The most frequent marker was the swirl sign (74.3%) and the least frequent was the blend sign (7.3%) (Table 1). HE occurred more often in patients with any marker at baseline (45.5% vs 25.6%, p=0.03). The blend sign (15.2% vs 1.4%, p

Stroke, Volume 56, Issue Suppl_1, Page AWP401-AWP401, February 1, 2025. Introduction:Aging is accompanied by a gradual increase in inflammation, oxidative stress and immune system dysfunction. Our previous work with heterochronic parabiosis, in which the circulatory systems of young and aged mice are shared, provided insights into how systemic factors influence brain aging. Notably, our findings revealed that aged blood induces a reactive oxygen species-induced senescence pathway in the young brain, while young blood activates a selenium network pathway in the aged brain. Wehypothesizethat selenium deficiency increases oxidative stress and ROS-induced senescence in microglia, thereby contributing to neuroinflammation and cognitive decline.Methods:We fed aged (16-month) C57BL/6 male mice either a selenium deficient or control diet (n = 9-10/grp) for 3 months. Cognition and motor activity were assessed at 1- and 3-months with the novel object recognition test (NORT) and open field (OF). Brain and spleen were harvested after 3 months for flow cytometric (FC) analysis and immunohistochemistry (IHC). Additionally, we explored the potential therapeutic effects of selenium supplementation on senescence markers in primary microglial cell cultures, which were assessed by qPCR and stained for senescence activity (beta-galactosidase).Results:After one month, selenium deficient mice had significantly impaired locomotor activity in the OF (p=.0010) and an increase in cognitive impairment in the NORT (p=.0792). Surprisingly, these deficits normalized to levels seen in the control group after 3 months of selenium deficient diet, raising the possibility of an adaptive or compensatory redox signaling mechanism in the aged brain. FC analysis at 3 months revealed only mild alterations in microglia, brain endothelial cells, and splenic neutrophils, consistent with the behavioral outcomes.In vitroexperiments demonstrated that treatment with selenomethionine (p=.0134) and selenium nanoparticles (p=.0176) alleviated senescence-associated phenotypes in microglia post-H2O2 stimulation.Conclusion:We have established an important role for dietary selenium in healthy brain aging and novel evidence for a delayed compensatory redox mechanism to mitigate the detrimental effects of chronic selenium deficiency in aged mice. By elucidating the role of dietary selenium in brain aging, this study aims to identify novel therapeutic targets for preventing or delaying the cognitive decline associated with aging.

Stroke, Volume 56, Issue Suppl_1, Page A120-A120, February 1, 2025. Background:Decompressive hemicraniectomy (DHC) and mechanical thrombectomy (MT) are critical interventions for acute ischemic stroke. This study examined trends in their use from 2016 to 2021, the relationship between them, and associated patient demographics and outcomes.Methods:National inpatient Sample (NIS) (n=798,712) was analyzed. Trends in DHC and MT per year were analyzed using the Cochran-Armitage test for trend to assess changes in DHC use over time and assessed overall and stratified by MT status. Logistic regression evaluated the association between year, MT, and their interaction with DHC odds. Patient demographics and outcomes were also examined.Results:Overall, DHC use increased significantly from 2016 to 2021 with a non-linear trend (chi2(4)=86.69, p

Stroke, Volume 56, Issue Suppl_1, Page ATP36-ATP36, February 1, 2025. Stroke, the leading cause of adult disability, necessitates new therapeutic strategies informed by a deeper understanding of brain repair mechanisms. This pilot study investigates the role of parvalbumin inhibitory interneurons (PV-INs) in post-stroke recovery using wide-field optical imaging (WFOI) and optogenetics. PV-INs, the largest subclass of GABAergic interneurons, are crucial in regulating cortical excitability and mediating activity-dependent plasticity. However, their specific function in stroke recovery remains unclear.Here we use 5 aged mice expressing Channelrhodopsin (ChR2) in PV-INs and the red-shifted genetically encoded calcium indicator, jRGECO1a, driven by the Thy1 promoter to allow for simultaneous optogenetic targeting of PV-INs and mesoscopic imaging of excitatory activity. Photothrombosis was induced in the left primary somatosensory forepaw cortex and subsequent optogenetic photostimulation of PV-INs, calcium, and hemodynamic imaging was conducted pre- and post-stroke to map PV-IN circuitry and assess changes in cortical activity.Preliminary results revealed significant disruptions in homotopic resting-state functional connectivity and cortical activity one-week post-stroke. Power maps indicated reduced activity in the somatosensory, hindpaw, and parietal cortices, with electrical forepaw stimulation showing decreased activity in both left and right primary somatosensory forepaw regions. Contralesional excitation increased in the retrosplenial and parietal cortices during forepaw stimulation. Further, optogenetic stimulation of PV-INs pre-stroke showed increased inhibition, while post-stroke stimulation resulted in less ipsilesional inhibition and more global excitation. Behavioral assessments using the cylinder rearing test indicated a 26% decrease in right forepaw use post-stroke, aligning with imaging findings.Ongoing studies aim to extend these observations by including a larger cohort of aged mice and a cohort of young mice at 1-, 4-, and 8- weeks post-stroke to examine age-related differences in PV-IN-mediated plasticity during stroke recovery. These studies will elucidate the critical contributions of PV-INs to post-stroke plasticity and recovery, potentially guiding new therapeutic approaches for stroke rehabilitation.

Stroke, Volume 56, Issue Suppl_1, Page A128-A128, February 1, 2025. Introduction:Acute infection transiently increases risk for childhood arterial ischemic stroke (AIS). We hypothesize that this paradox of a common exposure linked to a rare outcome could be explained by either (1)unusual infections—uncommon pathogens or combinations of pathogens—or (2) anunusual host responseto infection. While previous studies relied solely on clinical history and targeted laboratory testing as measures of infection, we leveraged metagenomic next-generation sequencing (mNGS) as an unbiased measure of infection to test the first hypothesis.Methods:The Vascular effects of Infection in Pediatric Stroke II(VIPS II) study is a North American and Australian prospective cohort study which enrolled children (28 days – 18 years old) with AIS at 22 sites over a 5-year period. We collected data on preceding infection via parental interview and chart abstraction at time of admission. We performed mNGS of serum and throat swabs collected within 72 hours of stroke ictus. To assess for the background spectrum of pathogens, we enrolled and performed mNGS on unmatched stroke-free well controls (WC) and ill controls (IC).Results:Between 2017 and 2022, VIPS II enrolled 205 cases, 95 WC, and 47 IC(Table 1). Both serum and throat swab mNGS data was available for 190/205 cases, 91/95 WC, and 27/47 IC. Parents reported clinical infection in the 4 weeks prior to stroke in 47/190 (25%) cases. Chart abstraction identified hospital diagnoses of pre-stroke infection in 69/190 (35%) cases. Typical childhood viral pathogens were identified by mNGS in 26/190 (14%) cases, 9/91 WC (10%), and 9/27 (33%) IC; multiple pathogens in a single patient were rare(Table 2).Clinical infection (parental history or chart abstraction) was present in 18/26 (69%) cases with infection detected on mNGS. Overall, infection preceding or coincident with stroke was identified by parental interview, chart abstraction, or mNGS in 46% of cases.Conclusions:Almost half of cases had evidence of infection prior to or coincident with AIS, supporting prior literature. Unbiased pathogen detection with mNGS, performed for the first time in children with AIS, detected a variety of common childhood infections in both cases and controls, suggesting that the paradoxical relationship between infection and AIS is not explained by unusual or multiple pathogens. The alternative hypothesis regarding an unusual host immune response to infection in the pathogenicity in AIS should be further explored.

Stroke, Volume 56, Issue Suppl_1, Page A127-A127, February 1, 2025. Introduction:Advanced Practice Providers (APP) are being integrated into more medical sub-specialties and opportunities may exist to increase the acuity of the patients they serve. We evaluated whether utilizing an APP in the emergency room affected timing and safety of IV thrombolytic therapy.Methods:Single center academic hospital retrospective analysis on acute ischemic stroke patients given thrombolytic therapy in the emergency department between January 2022 and June 2024. Patients treated greater than 4.5 hours of symptom onset and those with non-disabling symptoms upon emergency room arrival were excluded. Primary outcome: door to needle (DTN) time of the APP versus neurology residents using quantile (median) regression adjusted for age, NIHSS and delays for treating hypertension. Secondary outcome evaluated symptomatic intracranial hemorrhage (sICH) post thrombolysis comparing APP versus neurology residents using Fisher’s exact test. To evaluate for potential time confounds due to the APP’s working schedule, a subgroup analysis compared patients treated by neurology residents during APP scheduled work times to APP off hours using quantile (median) regression adjusted for aforementioned cofounding variables.Results:There were 278 patients given thrombolytic therapy in the emergency room and after exclusions 271 patients were included in the study and all analyses. The APP had a lower median DTN time than the neurology residents, 32 minutes versus 54 minutes. After adjusting for confounding variables the APP treated patients 18.98 [95% CI 5.11, 32.85] minutes quicker than neurology residents, p=0.008. Rates of sICH were similar between the APP and neurology residents, 0(0%) versus 5(1.9%), p >0.99. Neurology resident DTN times remained consistent when covering APP shift and outside of APP scheduled hours, adjusted median difference in door to needle time, 2.50[95% CI -11.43,16.44], p=0.72.Conclusion:The utilization of an APP who specializes in treating ischemic stroke patients with thrombolytic therapy provides safe and fast administration. APPs may be used to respond to emergency room stroke alerts to determine eligibility and administration of thrombolytic therapy.

Stroke, Volume 56, Issue Suppl_1, Page AWP205-AWP205, February 1, 2025. Background:The bovine aortic arch is a vascular variant in which the left common carotid artery originates from the brachiocephalic trunk rather than directly from the aortic arch. The bovine anatomical variation may alter the blood flow dynamics, potentially contributing to the formation and progression of carotid plaques. In this study, we evaluated the association of the bovine aortic arch and the severity of carotid stenosis.Methods:In this retrospective study, we included patients with carotid artery disease undergoing carotid endarterectomy (CEA) and pre-surgical computed tomography angiography (CTA). CTAs were reviewed to assess the carotid stenosis and the anatomy of the aortic arch. The left carotid artery was classified as normal if it originated from the aortic arch and as bovine if it originated from the brachiocephalic trunk(Figure 1). Unlimited propensity score matching was performed to balance baseline characteristics between patients with bovine and normal anatomies. The Mann-Whitney U test was applied to compare carotid stenosis between bovine and normal arteries.Results:A total of 203 patients (bovine:23, normal:180) were initially enrolled. Using propensity score matching, 20 patients with bovine anatomy were matched to 45 patients with normal anatomy(Figure 2). Among the 65 patients included, 47 (74.6%) were male, with a median age of 70 [IQR:65.0-76.0] years. Left-sided carotid artery disease was more prevalent in the bovine compared to normal group (N=12, 66.7% vs. N=16, 36.4%; p=0.030). Additionally, the severity of carotid stenosis in CEA-treated side was higher in patients with bovine arch compared to normal controls (82.5% [76.2-88.7] vs. 70.0% [50.0-95.0]; p=0.030)(Figure 3).Conclusions:The association of a bovine aortic arch with more severe carotid stenosis suggests that this anatomical variant may be a marker for increased cerebrovascular risk.

Stroke, Volume 56, Issue Suppl_1, Page ATP31-ATP31, February 1, 2025. Diabetes increases the risk of Vascular Contributions to Cognitive Impairment&Dementia (VCID) and stroke further amplifies this effect. Diabetes also dysregulates the Endothelin (ET) system. Elevated brain ET-1 levels correlate with tissue perfusion status and disease severity in patients with ADRD. There is emerging evidence that ETB receptor agonism improves outcomes in patients with cerebral ischemic stroke, but long-term effects, especially in diabetes, are unknown. Therefore, we hypothesized that intranasal treatment with ETA antagonist or ETB agonist will improve sensorimotor/cognitive outcomes in diabetic animals after ischemic stroke.Methods:We used a post-stroke cognitive impairment (PSCI) model of VCID. Male rats underwent 60-min middle cerebral artery occlusion surgery (MCAO) 8 weeks after diabetes onset. Rats that met the preset inclusion criteria (adhesive removal time > 35 sec. and either a modified Bederson score 10% on Day 3) were randomized to ETA antagonist BQ-123 (3 µg/100 µl PBS), ETB agonist Sovateltide (5 µg/kg), or vehicle intranasal treatment for 3 days per week until 8 weeks post-stroke (n=6-8). Sensorimotor and cognitive outcomes were monitored for 8 weeks.Results (Table 1):Behavior indices from the novel object recognition (NOR) test and Y-Maze test showed that diabetic rats developed cognitive deficits even in the sham group. Sovateltide improved both recognition memory and working spatial memory after stroke. BQ-123 partially prevented the decline in recognition memory. Animals treated with BQ-123 showed an improvement in depressive symptoms after stroke.Conclusions:These results suggest that intranasal stimulation of brain ETB receptors or ETA receptor inhibition can prevent the development of progressive cognitive decline after stroke. While further studies are required to better understand how the brain ET system impacts stroke recovery in diabetes, our findings provide novel insights into potential neuroprotective therapies for VCID.

Stroke, Volume 56, Issue Suppl_1, Page ATP37-ATP37, February 1, 2025. Introduction:Prefrontal cortex (PFC) has long been thought to be involved in dual-tasking, and is also found to be associated with areas involved in motor control (supplementary motor area (SMA), premotor cortex). Functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging technology, allows measurement of cortical activity during dual-tasking. This study aimed to compare cognitive-motor interference and brain activity between people with subcortical stroke and their healthy counterparts.Methods:People with subcortical chronic stroke and their healthy counterparts (N=25/group; aged ≥ 50 years old, Montreal Cognitive Assessment score ≥ 22 points, Mini Balance Evaluation Systems Test score ≥16 points) were included. Each participant performed tasks in random order including: (1) single-task maintaining balance in standing position under vibration disturbance, (2) single-task serial-7-subtractions/clock test (while standing), and (3) dual-task maintaining balance in standing position in conjunction with a serial-7-subtractions/clock test. Participants were instructed to maintain balance as fast as they could safely while generating as many correct answers as possible during dual-task balance maintenance. Oxyhemoglobin (HbO) changes in bilateral PFC and SMA were measured with 46 channels of a continuous-wave system in fNIRS (ETG-4000, Hitachi). Path length of center of gravity was monitored by DynSTABLE system for postural sway. For both HbO and postural sway, dual-task cost was calculated as (dual-task performance-single-task performance) × 100%) / (single-task performance).Results:People with subcortical stroke had greater dual-task cost for postural sway during dual-task serial-7-subtractions than their healthy counterparts (P

Stroke, Volume 56, Issue Suppl_1, Page ATP18-ATP18, February 1, 2025. Background and Objectives:Central retinal artery occlusion (CRAO) is a rare form of acute ischemic stroke that causes severe visual loss, which is a relatively rare emergency but devastating eye condition. There is currently no guideline-endorsed treatment for CRAO. Data on hyperbaric oxygen therapy (HBOT) for CRAO is minimal. We aim to investigate the benefit of HBOT in patients with CRAO compared to conservative management.Methods:We conducted a retrospective single-center study that recruited patients with diagnosed non-arteritic CRAO from January 2019 to May 2024. HBOT was offered to CRAO patients who presented to the emergency room within 24 hours from symptom onset. Eight patients underwent a full course of HBOT (twice a day for five days with a total of 10 HBO treatments). Twelve CRAO patients received partial HBOT (from 1 to 7 treatments); HBOT was discontinued per patients’ request, either due to anxiety or no noted visual improvement. Twenty-seven CRAO patients did not undergo HBOT due to being outside of the treatment window or HBOT was declined by patients. The primary outcome was visual improvement at the time of discharge. Student’s T-test and Chi-square test were used to compare the change in LogMAR best-corrected visual acuity (BCVA) in patients before and after HBOT.Results:There was no statistical difference among the three groups in patient demographic and clinical characteristics (vascular risk factors). In the HBOT group, patients who received an entire course of HBOT (twice a day for five days) revealed significant visual improvement at discharge evaluation with LogMAR BCVA compared to the partial HBOT and the control group (Table 1). Only one patient developed an episode of seizure while receiving HBOT; no complications occurred in the rest of the patients.Conclusions:HBOT improves visual outcomes in CRAO patients who receive a full course of therapy. The benefit from HBOT does not appear to improve the visual outcome of patients who receive partial HBOT or no treatment. Our result suggests that HBOT is safe and should be offered to CRAO patients who present to the hospital within 24 hours of symptom onset as part of the standard of care. A large-scale prospective study is surely needed to validate our retrospective result.

Stroke, Volume 56, Issue Suppl_1, Page ATP88-ATP88, February 1, 2025. Background:Patients experiencing a hyperacute stroke and requiring transfer to higher level hospitals commonly incur transfer delays for which causative factors have not previously been quantified. We developed the valid and reliable SWIFT instrument to capture contributors to transfer delays.Methods:An exhaustive literature review was completed, and qualitative focus group interviews were conducted with clinicians experienced in managing transfers for acute stroke patients. Key contributors were identified (previously published) and used to develop quantitative measures covering the transfer process as well as Likert scale items examining perceptions of the quality of the transfer experience. Following analysis by Bartlett’s Test of Sphericity, construct validity was assessed using exploratory factor analysis; internal consistency and reliability were estimated using Cronbach’s alpha.Results:Data were collected on patient transfers from PSCs to CSCs occurring across the USA. Internal structure was analyzed on 78 cases that met all inclusion criteria. Bartlett’s test of Sphericity was significant (x2= 728.469,df= 276, p < 0.001), indicating presence of relationships among variables analyzed, supporting factor analysis. Three factors emerged accounting for 47% of the total variance:System Responsiveness;Transfer Competence&Confidence;Transfer Facilitators&Constraints. The overall instrument Cronbach’s alpha was .703, indicating acceptable internal consistency.Conclusions:The SWIFT instrument demonstrates acceptable psychometric quality for use as a standard measure to quantify stroke transfer performance metrics. Measurement of transfer performance metrics using SWIFT on a large national sample will significantly improve knowledge of factors that slow door-in-door-out times, enabling interventions targeting improvement.

Stroke, Ahead of Print. Background:Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is the most prevalent monogenic inherited cause of cerebral small-vessel disease. Despite its prevalence, there is currently no proven therapy to prevent or reverse the progression of the disease.Methods:This study aimed to characterize the functional integrity of long white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum added on, utilizing optical resting-state functional connectivity imaging alongside behavioral examinations. Additionally, we examined the efficacy of tocotrienol, a neuroprotective derivative of vitamin E derived from palm oil, which has shown promise in preventing white matter disease progression in clinical trials involving patients with small vessel disease.Results:At baseline, resting-state inter and intrahemispheric functional connectivity was significantly lower in Notch3R169C than in Notch3WT (p=0.004), and the grid walk test revealed a higher number of foot faults in the Notch3R169C group compared to Notch3WT. Sex did not interact with the genotype on the primary outcomes. Introducing a lesion in the corpus callosum compromised functional connectivity and behavior outcomes in both genotypes to a similar extent; lesion volumes did not differ between the genotypes. Tocotrienol treatment did not show any protective effect on any endpoint.Conclusion:These data show impaired resting-state functional connectivity and increased foot faults in the Notch3R169C mutant model of CADASIL. Future work will aim to test therapeutic or preventive interventions in CADASIL mutants using these measures.

Stroke, Volume 56, Issue Suppl_1, Page ATP54-ATP54, February 1, 2025. Background:Comprehensive Stroke Center assigned annual education using self-learning [SL] via an online learning system [OLS] with post-test upon completion. Education for all staff included BE FAST to remember stroke symptoms and immediate actions to take when recognized for in-hospital stroke alert activation [IH-SA-A]. “BE FAST Fridays” [BFF] were implemented May 2024 and voluntary in-person, one-on-one education [1:1E] was conducted every Friday to assess current knowledge, review BE FAST and actions to take for IH-SA-A. The teach-back method was used to assess overall understanding. Flyers and day-of-event overhead announcements were shared for staff awareness. Event was held in the hospital front lobby for visibility. Breakfast and stroke t-shirts were provided after completing 1:1E. Designated “BE FAST Office Hours” [BFOH] were implemented June 2024 to allow for ongoing 1:1E.PURPOSEEvaluate the impact of SL via an OLS and 1:1E conducted through BFF and BFOH on IH-SA-A.Method:Retrospective review of 1,202 education records in 2024 was conducted to determine total 1:1E participation. Participants were grouped as re-education [1:1E after SL] and initial education/new staff [1:1E only] for analysis. Retrospective review of 54 IH-SA-A was conducted to determine those that occurred before 1:1E [PRE] Jan 2022-April 2024 and after 1:1E [POST] May-July 2024. POST IH-SA-A were evaluated for 1) positive brain imaging [PBI]; 2) transfer to higher level of care [THLC]; 3) thrombolytic administration [TA]; and 4) mechanical thrombectomy [MT]. All groups were divided into hospital departments [HD] for analysis.Results:Total participants 655, included 76% 1:1E after SL and 24% 1:1E only. Highest number of participants and 1:1E after SL were PACU/Adult Units [P/A], Women’s Services [WS], and Other Staff [OS]. Highest number of 1:1E only were P/A and OS. IH-SA-A increased from monthly average of 1.57 PRE to 3.33 POST with increases in all HD. Largest increase was in Stroke Unit and P/A. WS had 1 IH-SA-A POST after having 0 PRE. Outcomes of POST IH-SA-A included 50% PBI, 63% THLC, and 10% MT.Conclusion:Education using 1:1E format provided enhanced individualized experiences that resulted in increased BE FAST recognition leading to increased IH-SA-A. While SL provides flexibility for completion and ease of tracking, staff are more likely to benefit from 1:1E that encourages active listening/discussion, allows for questions, and provides targeted feedback.