Search Results for: Sviluppo di un test meno invasivo per la malattia infiammatoria intestinale

Stroke, Volume 56, Issue Suppl_1, Page ATP373-ATP373, February 1, 2025. Objectives:Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is a leading monogenic cause of cerebral small-vessel disease. This study aimed to evaluate the functional integrity of long white matter tracts in CADASIL transgenic mice and assess the potential of tocotrienol (T3) as a therapeutic agent.Methods:Optical resting-state functional connectivity imaging and behavioral examinations were employed to characterize white matter tracts in CADASIL transgenic mice, both with and without focal white matter lesions in the corpus callosum. Functional connectivity and behavioral outcomes were compared between Notch3R169Cand Notch3WTmice. The efficacy of T3, a neuroprotective vitamin E derivative, was also evaluated based on findings from previous clinical trials in small vessel disease.Results:After performing stepwise elimination using the Akaike Information Criterion (AIC), the diet variable was removed from the model and we pooled the data in the two diet arms for subsequent analyses of interhemispheric homotopic connectivity. At baseline, resting-state interhemispheric functional connectivity was significantly reduced in Notch3R169Cmice compared to Notch3WTmice (p=0.004). No significant differences between genotypes were observed on day 1 and day 7 post-lesion. Behavioral analysis using the grid walk test revealed an increased number of foot faults in Notch3R169Cmice at baseline, with similar increases observed in both genotypes one week after lesion induction. Lesion volumes on day 7 did not differ between genotypes.Conclusions:The Notch3R169CCADASIL model demonstrated impaired resting-state functional connectivity and increased foot faults, indicating significant functional and behavioral deficits. Future research will focus on evaluating therapeutic and preventive interventions in CADASIL models using these parameters.

Stroke, Volume 56, Issue Suppl_1, Page ADP4-ADP4, February 1, 2025. Introduction:Intravenous thrombolysis with alteplase (tPA) or tenecteplase (TNK) is a first-line treatment for acute ischemic stroke. The most serious risk associated with IV thrombolytics is symptomatic intracranial hemorrhage (sICH). Patients are usually monitored in intensive care units for neurologic decline signaling sICH for 24 hours, after which follow up neuroimaging is performed and antithrombotic secondary prevention may be initiated. However, the evidence surrounding the onset of neurologic decline in post-thrombolytic sICH is limited. The current study seeks to provide data regarding onset of clinical worsening in post-thrombolytic sICH, and to identify a subset of patient characteristics for a future clinical trial to test whether earlier imaging, transfer from ICU, and initiation of secondary prevention is feasible and safe.Methods:The current study is a multi-center collaboration between University of Texas – Dell Medical Center, Ascension Seton, and Ascension Saint Thomas. We reviewed stroke databases from 2017 to 2024 for patients who received IV thrombolysis with either tPA or TNK and developed sICH within 36 hours of treatment. sICH was defined as a hemorrhage that caused an increase in NIHSS by 4 or more points. Patient charts were reviewed to determine if a decline in neurologic exam prompted neuroimaging that discovered sICH, and for documentation of the timing of clinical worsening that prompted neuroimaging.Results:40 patients were identified during the study period to have sICH. Of those, 25 patients were discovered to have sICH after a decline in neurologic exam. 7 patients received tPA and 18 patients received TNK. The median time to documented neurologic decline in all patients was 251 mins (range: 7 mins to 1185 mins). For patients with pretreatment NIHSS < 10, the median time to documented neurologic decline was 134 mins (range: 57 to 259 mins).Discussion:All patients with neurologic decline resulting in neuroimaging and discovery of sICH had this decline documented within 20 hours. Among patients with NIHSS < 10, all patients had this decline within 5 hours. Our preliminary data suggests that there may be patients who receive IV thrombolysis who may be candidates for expedited neuroimaging or transition to step-down units and secondary preventive measures. Candidates would likely require stable neurologic exams that could be tracked over time. Further investigation to confirm these results on a larger sample is planned.

Stroke, Volume 56, Issue Suppl_1, Page A22-A22, February 1, 2025. Introduction:Though clinical practice guidelines support high repetitions of walking after stroke, practice is slow to change with low levels of walking activity in stroke rehabilitation units. We undertook an implementation trial to change practice; we enabled entire stroke units to use the Walk ‘n Watch protocol and determined the effect of implementation on the 6 Minute Walk Test (6MWT) at hospital discharge.Methods:This 12-site clinical trial across 7 Canadian provinces used a stepped-wedge cluster design to randomize when each site switched from Usual Care to the Walk ‘n Watch protocol. At the start of the Walk ‘n Watch phase, we trained all front-line physical therapists on the unit with training workshops, manuals, hands-on practice, and videos. Each site was provided onboarding materials to address staff changes so therapists who did not attend the initial training could adopt the protocol. Each site also identified a ‘protocol champion’ to facilitate initial weekly huddles with therapists to discuss barriers to implementation. Therapists were trained to complete safety screening and to determine eligibility. The Walk ‘n Watch protocol focused on completing a minimum of 30-minutes of daily weight-bearing, walking-related activities that progressively increased in intensity informed by activity trackers measuring heart rate and step number. Blinded assessors completed the outcomes at baseline and 4-weeks later (near discharge). Primary analysis used a linear mixed-effects model adjusted for stratum, date of enrollment, age, sex and baseline 6MWT.Results:The total number of participants was 306 (162 Usual Care, 144 Walk ‘n Watch, 188 males/118 females) with a mean(SD) age of 68(13), 29(17) days since stroke, and a baseline 6MWT of 152(106) m. The improvement on the 6MWT was 43.6m (95%CI 12.7, 76.1) greater in the Walk ‘n Watch group compared to the Usual Care group. Further, the Walk ‘n Watch group improved quality of life (EQ5D), balance and mobility (Short Physical Performance Battery) and gait speed.Conclusions:The implementation trial design enabled the protocol to be tested under real-world conditions, involving all therapists on each unit to deliver the protocol. The trial had a deliberate aim to facilitate changes in practice that resulted in clinically meaningful improvements in walking and quality of life.

Stroke, Volume 56, Issue Suppl_1, Page ATMP115-ATMP115, February 1, 2025. Background/Aims:The Stroke Preclinical Assessment Network (SPAN) is a randomized, placebo-controlled, blinded, multi-laboratory preclinical study using a Multi-Arm Multi-Stage statistical design to select one or more putative stroke treatments with an implied high likelihood of success in future human clinical stroke trials.Methods:Through a rigorous NIH-managed peer review process, six independent research laboratories were selected for testing five promising cerebrovascular interventions. A Coordinating Center at the University of Southern California leads the trial. The Interventions, also selected through an NIH peer review process, included NanO2 (NuvOx) an oxygen delivery emulsion, tatCN19o (Neurexis) a CaM-kinase II inhibitor, GSK2256098 (GlaxoSmithKline/ETSU) a focal adhesion kinase inhibitor, GSK2256294 (GlaxoSmithKline/OHSU) a soluble epoxide hydrolase inhibitor, and BPN-27332 (Loxagen/MGH) a lipoxygenase inhibitor. After a pilot trial to evaluate several behavioral measures, we designated the primary endpoint for SPAN 2 to be a multi-item functional test battery, the Simplified SPAN Score. All other procedures, including behavior tests and magnetic resonance imaging were performed as they were in SPAN 1. Per the SPAN 2 pre-specified protocol, an interim analysis was performed after Stage 1, aka, SPAN 2.1.Results:SPAN 2.1 enrolled 774 subjects, divided among 4 animal co-morbid models in whom a transient filament MCAo was performed: young healthy mice (n=193), diet-induced obese mice (n=197), aged mice (n=192), and spontaneously hypertensive rats (192). Nine subjects were found ineligible, leaving an ITT population of 765, of whom 13 were dropped during the stroke procedure—the primary analysis population (mITT) included 751 subjects. Protocol compliance was evaluated: over 99% of subjects received the correct assigned intervention, but dose timing was protocol adherent in only 61%. Animals who did not receive all assigned doses (n=100) were excluded, leaving a Full Treatment population of 651. Mortality after treatment included 158 subjects, 21% of the mITT group. Among the animal comorbid models, mortality was greatest (40%) in aged mice.Conclusions:The feasibility and protocol compliance seen in SPAN 1 have been replicated in stage 1 of the second trial, SPAN 2.1. Mortality resembles previous experience, with an improved survival in aged mice. SPAN 2 has advanced to Stage 2 where improved dose timing is implemented.

Stroke, Volume 56, Issue Suppl_1, Page ATP169-ATP169, February 1, 2025. Introduction:The prevalence of Mismatch (MM) profiles on admission perfusion imaging in large core ischemic strokes, stratified by time since last known normal (LKN) and MM profile definition, is not well described.Methods:We used a retrospective multicenter study of patients with anterior circulation large vessel occlusion, baseline MR or CT perfusion (MRP, CTP), and definitive LKN within 24 hours. We studied four MM profile definitions: 1) Mismatch ratio (MR)≥1.2, penumbral volume (Pen)≥10ml, and (if CTP) core volume defined by CBF

Stroke, Volume 56, Issue Suppl_1, Page A33-A33, February 1, 2025. Introduction:Net water uptake (NWU) is a novel biomarker which measures edema and tissue injury from the degree of hypoattenuation on non-contrast CT and may serve as a precision tool for predicting outcomes after acute ischemic stroke (AIS). Using our recently developed algorithm, this study aimed to evaluate the relationship between NWU and post-stroke neurologic outcomes, including language impairment and motor weakness.Methods:Consecutive patients treated for AIS at certified stroke centers in Houston, TX were included. Patients’ precise functional outcomes at hospital discharge were recorded including decreased level of consciousness, presence of language impairment, visual deficit, arm and leg weakness, need for walking assistance, and gastrostomy placement. The primary outcome for this study was the performance of calculated NWU and clinical variables to predict language impairment at discharge. Baseline characteristics were compared, and then univariate and multivariate logistic regression were used to evaluate the association between clinical variables, imaging data, and the precise neurological outcomes.Results:Among 776 patients with AIS, average age was 67.0 +/- 14.8, 47.8% were female, median NIHSS was 10 [5,18], median ASPECTS was 9 [7,10], 42.6% received tPA, and 67.1% had a large vessel occlusion (see Table 1). In univariate logistic regression, higher NWU (OR 1.45, CI 1.30-1.63) and lower ASPECTS (OR 0.68, CI 0.63-0.74) were both significantly associated with higher likelihood of language impairment and other deficits at discharge (see Table 2). Additionally, higher NWU in all ten regions was significantly associated with deficit at discharge. In multivariate logistic regression, certain clinical and imaging variables remained significantly associated as described in Table 3. The ASPECTS and NWU-based regression models were directly compared when predicting language impairment using ROC curve analysis, and areas under the curve were 0.838 vs. 0.851 respectively (p = 0.152 with Delong test, see Figure 1).Conclusion:The novel NWU biomarker was significantly associated with precise post-AIS outcomes at discharge. When controlling for confounders, NWU was non-inferior to ASPECTS. Moving forward, region-based and overall NWU will need to be studied with long-term patient outcomes. Ultimately, this novel and open-access imaging biomarker could be used in the emergency setting to guide treatment decision-making and patient counseling.

Stroke, Volume 56, Issue Suppl_1, Page ATP395-ATP395, February 1, 2025. Introduction:Ischemic stroke is one of the leading causes of death in the United States and is a known risk factor for Alzheimer’s Disease (AD) development. One of the characterizations of AD is the accumulation of β-amyloid peptide due to the proteolysis of Amyloid Precursor Protein (APP) by the protein Presenilin 1 (PS1) among others. In APP/PS1 mice, which contain an additional human copy of APP and PS1, a 15-minute Middle Cerebral Artery Occlusion (MCAO) model was developed. Here we investigate the effects of increased β-amyloid peptide on motor coordination when subjected to local ischemia.Methods:APP/PS1or Wt male mice are initially subjected to either a 15-minute MCAO or Sham surgery. Injury volume using MRI is assessed at 3-days using T2 imaging. To test motor coordination the mice went through a tapered beam analysis at the 7-day time point. Following the tapered beam test, Cresyl Violet was used to stain brain slices. All mice were 8-12 weeks old at the time of surgery. Differences between groups were determined by Welch’s T-Test. Significance was determined as p < 0.05.Results:No significant difference in infarct volume was observed between the APP/PS1-MCAO and Wt-MCAO groups. In the hind legs, it was observed that there is a significant difference in the number of slips off the tapered beam in the APP/PS1-MCAO group when compared to the Wt-MCAO group (9.4 ± 3.356, n=7, p < 0.05 and 2.5 ± 0.289, n=4, p < 0.05 respectively). No significant difference was found in the Cresyl Violet staining.Conclusions:Our study shows motor deficit in the APP/PS1-MCAO experimental group when compared to the Wt-MCAO group as measured on hind-limb coordination. Therefore, further studies are warranted to assess the interaction between ischemia and β-amyloid peptide on histological injury and functional recovery.

Stroke, Volume 56, Issue Suppl_1, Page ATP391-ATP391, February 1, 2025. Background:Calcitonin gene-related peptide (CGRP) is a potent vasodilator that plays a role in migraine. Monoclonal antibodies targeting CGRP, such as fremanezumab, is now widely used for migraine prevention. However, inhibition of CGRP system may also lead to vasoconstriction, raising concerns about whether the long-term treatment with these antibodies in migraine patients might increase the risk of stroke or worsen outcomes if a stroke occurs while taking these medications. Here, we aimed to investigate whether fremanezumab exacerbates stroke outcomes in a mouse model of ischemic stroke.Methods:Two middle cerebral artery occlusion (MCAO) models were used: a 12-minute occlusion simulating a transient ischemic attack (TIA) and a 60-minute occlusion representing a conventional stroke model. Fremanezumab was administered intraperitoneally at either 2 days or 7 days before MCAO induction in both models; one cohort received treatment 28 and 7 days before MCAO. On day 2 after reperfusion, brain tissues were harvested for TTC staining to evaluate infarct volume. Neurological function was assessed using a neuro score and corner test. Additionally, an angiogram using black ink was performed to visualize cerebral vasculature, and vessel diameters were measured to determine the impact of fremanezumab on vascular dimensions.Results:Angiographic arterial diameters in the fremanezumab arm did not differ from the saline arm, suggesting that fremanezumab does not cause vasoconstriction. In the TIA model, the fremanezumab group exhibited a trend towards increased infarct incidence and volume and hemorrhagic transformation, although these did not reach statistical significance. Additionally, there were no substantial changes in neurological scores and the corner test. In the 60-minute MCAO model, no significant changes or trends were observed in infarct volume or other outcomes between the two treatment arms. Outcomes were similar when fremanezumab was administered 2 or 7 days before MCAO.Conclusion:Despite previous concerns that long-term use of fremanezumab might exacerbate stroke risk by promoting vasoconstriction, our findings do not support this hypothesis and suggest that fremanezumab does not worsen stroke outcomes in these models. These findings have important implications for the management of stroke risk in patients using fremanezumab for migraine prevention, suggesting that it may be used with confidence regarding its impact on stroke risk.

Stroke, Volume 56, Issue Suppl_1, Page A23-A23, February 1, 2025. Background:Functional impairments following stroke remain a significant therapeutic challenge. Vivistim, FDA-approved since 2021, has shown consistent results, providing 2-3 more improvement in arm and hand function compared to intensive rehabilitation alone. At Atlantic Health System, 25 patients underwent Vivistim implantation and received Paired VNS rehabilitation.Methods:A multidisciplinary team at AHS identified, educated, and implanted Vivistim in 25 post-acute stroke patients with moderate-to-severe motor impairments in the arm and hand. Post-implantation, patients were referred to one of 11 sites. Regular follow-ups were conducted by the implanting team to monitor side effects, safety and efficacy of this novel intervention.Results:All 25 patients successfully underwent outpatient implantation, with no reported infections at the implant sites. One patient developed a hematoma that resolved without intervention. Another required device explantation approximately 410 days post-therapy due to tingling sensations near the implant site likely unrelated to the device. This patient maintained a 25-point improvement on the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) despite explantation, indicating sustained benefits. Of the 25, 22 completed the therapy protocol. The remaining three discontinued therapy due to unrelated complications: one experienced two grand mal seizures linked to changes in seizure medication, another sustained an arm injury from a fall, and the third developed double vision, impairing her ability to drive. Patient ages ranged from 40 to 80 years (mean 62.6), with time to implantation post-stroke ranging from 1 to 11 years (mean 3.6). The interval from implantation to therapy initiation varied from 8 to 32 days (mean 15.3). The baseline FMA-UE score averaged 33 (range 19-56), with an average post-therapy score of 43 (range 24-63), for a mean improvement of 9.53 points. Notably, the patient with the longest follow-up (22 months) showed continued progress, reducing her 9-Hole Peg Test time by 61.42 seconds over her assessment 6 months prior.Conclusion:This case series represents the largest cohort reported to date from a single implanting site in a real-world setting. Vivistim was implanted safely, with no infections or surgical complications. Patients showed positive responses to Paired VNS despite an average of 3.6 years post-stroke, supporting the efficacy of this innovative treatment in the chronic stroke population.

Stroke, Volume 56, Issue Suppl_1, Page ATMP109-ATMP109, February 1, 2025. Background:The Stroke Preclinical Assessment Network (SPAN), a multi-center network consisting of a coordinating center and testing laboratories, was created to enhance the rigor of preclinical research, including testing of potential therapies in animals of different species, sex, age, and co-morbidities, with blinding and randomization. SPAN evaluated six potential therapies with the goal of identifying one or more efficacious agents to advance toward a clinical trial. Remote ischemic post-conditioning (RIC) was selected as a candidate therapy for testing.Methods:In Stage I, young, healthy mixed-sex mice were randomized into treatment groups by the coordinating center. In Stage II, aged mice, mice with high-fat diet-induced obesity, and spontaneously hypertensive rats were utilized. Each stage included 25% of the study population and efficacy/futility was determined after each stage. RIC was bilaterally administered as the first session occurred immediately after reperfusion, and the second session occurred as close as possible to 12 ± 2 hours at post-MCAo, using an automated blood pressure cuff that delivered 200-mmHg to the hindlimbs for 4 cycles x 5 minutes/cycle and then once per day x 5 days under anesthesia. Sham-conditioned animals were treated with a cuff that did not inflate. The primary outcome measure was a modified corner test on days 7 and 30 post-stroke. MRI was performed at 48 hours and 30 days. Probabilistic index models, which adjusted for covariates of interest, were fit to estimate the probability of a lower corner test index (better outcome) between sham and RIC.Results:A total of 266 mice (132 sham, 134 RIC) were enrolled in the study, with 50 sham and 51 RIC-treated mice dying within 5 days of stroke. Analysis of all data revealed no significant differences in day 30 alternative corner test index between sham and RIC-treated mice after stroke in young, healthy mice (p=0.449), aged mice (p=0.079), mice with diet-induced obesity (p=0.135), or in spontaneously hypertensive rats (p=0.807). The secondary analysis found that RIC improved day 30 tissue infarction volume by MRI in young, healthy mice (p=0.024 vs. sham) but not in other co-morbid conditions.Conclusions:After advancing through Stages I and II, RIC was deemed futile at the end of Stage II, as determined by the modified corner test on day 30. The requirement for repeated daily general anesthesia during RIC administration may have been a complicated factor.

Stroke, Volume 56, Issue Suppl_1, Page ATMP111-ATMP111, February 1, 2025. Introduction:VWF is an endothelial protein with known roles in hemostasis and thrombosis. We previously demonstrated abnormal deposition of VWF in themurallayer of leptomeningeal collateral arterioles (LMCs) during flow-induced outward remodeling. Additionally, LMC remodeling was attenuated in VWF KO mice, suggesting a modulating role for VWF. We now test the hypothesis that intramural VWF potentiates LMC remodeling in response to sustained increased luminal flow.Methods:VWF protein was infused into the cisterna magna (CM) of WT and VWF KO C57BL/6 mice (3-7 mos females) to deliver VWF to the perivascular space around the leptomeningeal arteries (2.5 mg/ml at 1 ul/min; 5-7ul total). To confirm successful delivery of VWF to the wall of the leptomeningeal vessels, brain surface preparations containing the cortical leptomeningeal vessels were “planed off” and evaluated for VWF and smooth muscle actin (SMA) immunofluorescence at one hour after VWF infusion (cohort 1). In a subsequent experiment, right common carotid artery ligation (rCCAL) was performed on VWF KO and WT mice to induce increased flow in collateral vessels supplying the right MCA territory (cohort 2). VWF or vehicle was injected via CM at 16 hours after the rCCAL. At 3 days post-rCCAL, the intact leptomeningeal vessel preparations were evaluated by immunofluorescence (Ki67&SMA) and morphometric analyses.Results:[Cohort 1] WT and VWF KO mice demonstrated exogenous VWF protein surrounding the leptomeningeal vessels and within the mural layer. VWF KO mice were used to distinguish between endogenous and exogenous VWF. [Cohort 2] At 3 days, rCCAL induced endothelial cell proliferation (Ki67+) and outward vascular remodeling of collateral vessels supplying rescue flow following carotid ligation. In the VWF infusion group, there was a significant increase in Ki67+ ECs, 14.1 ± 3.1 vs. 5.4 ± 1.2 per mm of vessel of the control group (p= 0.042). In VWF KO mice, VWF infusion also increased the number of Ki67+ ECs, showing 18.3 ± 3.2 vs. 6.1 ± 2.8 per mm of vessel in the control group (p< 0.0001). In both WT and VWF KO mice, VWF infusion promoted non-uniform LMC remodeling.Conclusions:Our study demonstrates that VWF in the vascular wall of LMCs potentiates the adaptive response to increased luminal flow, albeit with irregular resulting vascular morphology. These finding suggest that the presence of intramural VWF may contribute to abnormal vascular remodeling in the brain.

Stroke, Volume 56, Issue Suppl_1, Page ATP162-ATP162, February 1, 2025. Background:Detection of intracranial aneurysms (IAs) is a time consuming and error prone process. Therefore, solutions that can localize IAs with a high sensitivity are required. Several artificial intelligence (AI)-based automated diagnoses on medical images have recently been reported. We aimed to develop an automated diagnosis system for the location and maximum diameter of IAs on MRI images in the present study.Methods:In 1310 patients with or without IAs, 937 MRIs were used for training data and 373 cases for test data. The definition of the correct diagnosis of the location was that the center of the aneurysm diagnosed by the AI system is within the area of the IA of ground truth. The nnU-Net was used for the deep learning. Developed AI system was verified with 5-fold cross validation with test data. The maximum diameter was automatically calculated from extracted domes of IAs.Results:Of the 937 patients used for the model development, 778 (83%) had IAs including 146 patients (19%) with multiple aneurysms and 159 (17%) had no IA. In total 1213 IAs, 78% were small aneurysms of 2 to 5 mm. Of the 373 cases for the validation, 17 (4.5%) had IAs, which is close to the real-world setting. Internal validation of the developed diagnosis model for IA locations showed high efficiency of AUC = 0.92, sensitivity = 15/17 (88%), and false negative rate = 0.44 aneurysms/person. The diameter diagnosis model for the maximum diameter also achieved high accuracy within 1.2 mm of mean absolute error.Conclusion:We successfully developed a powerful diagnosis model for IAs with AI technique. The present model potentially reduces human effort required for the IA diagnosis.

Stroke, Volume 56, Issue Suppl_1, Page ATP167-ATP167, February 1, 2025. Purpose:White matter hyperintensities (WMH), also known as leukoaraiosis (LA), are common brain abnormalities in elderly individuals. Evaluating LA on CT is challenging due to the less distinguishable hypoattenuation against white matter. We aimed to develop and validate a segmenting algorithm of LA using CT-MRI paired data.Methods:We included 744 CT-MRI paired dataset of patients with ischemic stroke from 4 stroke centers. An external test set comprised 411 patients from non-overlapping hospitals. WMH on MRI was segmented using validated software and the segmentation mask was registered onto NCCT space. We compared predicted LA versus ground-truth registered LA and WMH on MRI using Dice similarity coefficient (DSC) and concordance correlation coefficient (ρ).Results:Mean age (SD) for training and external test datasets were 68.1 (SD 12.7) and 69.2 (SD 13.5) years and 33.2% and 47.9% were female, respectively. In the internal validation dataset, the algorithm achieved a DSC of 0.53, with a volumetric correlation (ρ) of 0.848 with registered LA volume on CT. External validation showed a DSC of 0.527, with ρ values of 0.919 and 0.760 for predicted LA volumes compared to registered LA and WMH volumes on MRI, respectively. Subgroup analysis demonstrated consistent performance across different CT vendors and infarct volumes.Conclusion:Our deep learning algorithm offers a significant advancement in LA segmentation on CT, bridging the gap between CT and MRI assessments. It improves patient care by providing a consistent, accessible, and accurate method for evaluating LA, supporting both clinical practice and large-scale research.

Stroke, Volume 56, Issue Suppl_1, Page A28-A28, February 1, 2025. Introduction:Chronic gait deficits after stroke are prevalent. Current therapy fails to restore normal gait for many stroke survivors. Transcranial Direct Current Stimulation (tDCS), a form of non-invasive brain stimulation, is a promising adjunct intervention that may enhance motor-learning induced neuroplasticity. tDCS is readily deployable into the clinic owing to its safety, ease of set-up, and feasibility to be paired with gait therapies. Our objective was to test whether bihemispheric tDCS would improve response to stance-phase focused gait therapy in a double-blind randomized control trial.Methods:44 subjects (65.2±9.8 y/o; 27.3% female; 4.5±4.2 years post-stroke) were randomized to active or sham tDCS+gait training. Ten treatment sessions consisted of 30 min of virtual-reality obstacle clearance training on a treadmill followed by 30 min of overground stance phase training. 2mA tDCS with anode over ipsilesional primary motor cortex (M1) and cathode over contralesional M1 was applied during the first 15 min of training. Individuals were assigned custom home exercises. Primary outcome was fastest gait speed with 10-meter walk test(10MWT) and secondary outcomes were preferred gait speed during 2-min walk test(2MWT), Fugl-Meyer(FM), Timed Up and Go(TUG), Functional Gait Assessment (FGA), and Gait Assessment and Intervention Tool(GAIT). Outcomes were collected at baseline, mid-treatment, post-treatment, and 6-week follow up. Statistical analyses included longitudinal linear mixed-effects models and analysis of treatment group by time interaction effects.Results:At baseline(mean(SD)): 10MWT=0.71(0.40) m/s, 2MWT=0.55(0.28) m/s, FM=25.0(3.7), TUG =33.2(30.6) s; FGA=12.7(4.1) points, GAIT=16.9(7.3) points. None of the longitudinal linear mixed-effects models detected a significant group by time interaction. However, there were significant improvements from baseline for all measures as follows (median(95%CI)): 10MWT(m/s) of 0.12(0.08, 0.16) post-treatment, and 0.11(0.07, 0.16) at follow-up; 2MWT(m/s) of 0.05(0.03, 0.07) and 0.05(0.02, 0.09); FM (points) of 2.5(2, 3) and 3(2.5,3.5); TUG(s) of 3.9(2.5, 5.6) and 3.3(2, 5.2); FGA(points) 3(2.5,3.5) and 3(2,3.5); GAIT(points) of 2.5(2, 3.5) and 3(2,4).Conclusions:Bihemispheric tDCS did not enhance improvements that were achieved by a 10-session gait training intervention targeting stance phase.

Stroke, Volume 56, Issue Suppl_1, Page ATP102-ATP102, February 1, 2025. The recovery process for stroke patients requires ongoing reinforcement of critical health information. Traditional education methods of written handouts often fail to adequately meet patient needs, particularly for those with limited literacy, or busy lifestyles. Podcasts are emerging as a powerful tool in patient education, offering a flexible, accessible, and engaging format that can be accessed anytime, anywhere.The hypothesis was that by prescribing podcasts, we could ensure patients have continuous access to vital information, allowing for repeated exposure and improved retention of key concepts. Studies have shown that podcasts can significantly enhance knowledge retention and listener engagement, even when listeners are engaged in other activities, as verified by EEG. This makes podcasts a practical solution for reinforcing key health messages and catering to diverse learning preferences, offering an alternative for patients who may struggle with written materials. Since neurological patients struggle to retain complex medical information provided during brief consultations, this can lead to gaps in understanding, and consequently suboptimal outcomes.Putting this hypothesis to the test, our method was to create a podcast with episode topics selected by a multidisciplinary stroke team, focusing on the frequently asked questions posed by stroke survivors and caregivers. Each podcast episode features interviews with expert guests or stroke survivors who discuss strategies and resources relevant to the topic. To enhance accessibility, links to printable information and specialist directories are provided in the show notes of each episode.The results demonstrate global demand for access to such specialized information, with regular listeners in 56 countries, all 50 of the United States and over 1600 downloads in outlying US territories. Each new episode consistently averages 300 audio downloads or video views in the first week they are released.In conclusion, neurology providers are encouraged to incorporate podcasts as a standard component of their stroke patient education strategy. Also, future research should focus on developing specialized neurological podcasts tailored to community needs, providing insight into how to aid them to better understand and manage their conditions, ultimately contributing to improved adherence to treatment plans and better quality of life.

Stroke, Volume 56, Issue Suppl_1, Page ATP394-ATP394, February 1, 2025. Introduction:Electrical stimulation has proven itself to be a powerful and novel tool in stroke recovery. However, it is unknown why this therapy significantly improves behavioral outcomes in rodent models of stroke. In a hypoxic environment, neural cells lack the proper glucose and oxygen to survive leading to many cell death pathways like Ca2+toxicity. Healthy neural cells can uptake excess intracellular Ca2+through the mitochondria as mitochondrial membrane potential increases. Neural cells under hypoxic conditions, however, are unable to uptake as much calcium due to mitochondrial dysfunction. We hypothesize that electrical stimulation therapy increases mitochondrial membrane potential in neural cells under hypoxia leading to increased Ca2+uptake and less Ca2+toxicity in the cell.Methods:To test our hypothesis, we used two innovative methodologies: (1) neuron conversion from induced pluripotent stem cells (iPSCs) with neurogenin-2 (Ngn2) overexpressed for a period of 28 days developed in the Wernig Lab, and (2) a customin vitrostimulation setup consisted of a gold layer sputtered onto cell culture inserts and a copper sheet placed below the 24-well plate creating an electric field across the iN cells (Figure 1). Induced neurons (iN) underwent oxygen glucose deprivation (5% CO2,10% H2, and 85% N2) for a period of four hours in glucose deprived media. One hour after exposure, iN cells were electrically stimulated at 50mV, 100Hz, and a 20% duty cycle for 20 minutes at 37°C. One day after stimulation, iN cells were stained with Rhod-2, a labeled calcium indicator that increases in fluorescence as a function of mitochondrial Ca2+, and DAPI to confirm cell presence.Results and Conclusions:Stimulation significantly increased mitochondrial Ca2+concentration in healthy iN cells seen in Figure 2 (N = 5, p = 0.014). In Figure 3, stimulation also significantly increased mitochondrial Ca2+in hypoxic cells (N = 5, p = 0.0024). Increased mitochondrial Ca2+in both cases indicates that mitochondrial calcium uptake appears to be improving. Electrical stimulation increasing mitochondrial membrane potential and improving calcium uptake could be a mechanism by which electrical stimulation facilitates stroke recovery. Future work will include additional staining for cytosolic calcium concentration (Calcium Green) and mitochondrial membrane potential (TMRM) to better track the relationship between the two.