bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 36: The association between intracranial atherosclerotic disease and cortical thinning is not modified by age-related neuropathologies in the National Alzheimer’s Coordinating Center
Authors: Soh Hyeon , Cherian Laurel , Arfanakis Konstantinos , Schneider Julie , Gutierrez Jose , Aggarwal Neelum , Yang Dixon
Published: January 2025

Background:
Intracranial atherosclerotic disease (ICAD), a common cause of stroke, is associated with cerebral atrophy and cognitive impairment, but the underlying pathophysiology remains unknown. We sought to determine if common age-related neuropathologies modified the association between ICAD and cerebral atrophy.

Methods:
This cross-sectional analysis included deceased participants from the National Alzheimer’s Coordinating Center database who had MRI morphometry and autopsy assessments for vascular pathologies and Alzheimer’s disease (AD). We represented ICAD, arteriolosclerosis, and AD dichotomously based on autopsy-determined Circle of Willis atherosclerosis (none-mild vs moderate-severe), arteriolosclerosis (none-mild vs moderate-severe), and National Institute of Aging-Alzheimer’s Association ABC score (none-low vs intermediate-high likelihood of AD), respectively. Our primary outcome of interest was total cortical thickness (mm) on MRI. We conducted adjusted linear regression to determine the association between ICAD and cortical thickness, then tested for multiplicative interaction between arteriolosclerosis and AD substrata.

Results:
Among 449 included participants (age at enrollment 77 years [interquartile range 70-83], 45% female, 87% non-Hispanic white), 39% had ICAD, 56% had arteriolosclerosis, and 72% had AD. In fully adjusted models, we found ICAD and AD to be independently associated with cortical thinning (ICAD β-estimate [95% confidence interval, CI] = -2.89 [GJD1] [-5.65, -0.13]; AD β-estimate [95% confidence interval, CI] = -5.61 [-8.44, -2.78]). In interactions models, we found significant associations between ICAD and cortical thickness only in subgroups with coexistent arteriolosclerosis or AD pathology, [GJD2] but we did not detect a significant multiplicative interaction (arteriolosclerosis, p = 0.50, AD, p = 0.35).

Conclusion:
In this cross-sectional study, we found ICAD to be independently associated with cortical thinning. Coexistent arteriolosclerosis and AD pathologies did not seem to modify the effect of ICAD on cortical thickness, but we may have been limited by sample size.
Abstract 38: Evolocumab added to statin is superior to statin alone in reversing symptomatic intracranial atherosclerotic stenosis
Authors: Liu Yiyang , Hu Xinzhi , Yuan Weizhuang , Li Shun , Zhang Yuelun , Li Mingli , Xu Yan , Xu Wei-hai
Published: January 2025

Background and Purpose:
We aimed to investigate the effects of evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor for intensive lipid-lowering, on intracranial atherosclerotic stenosis (ICAS).

Methods:
From a prospectively established high-resolution magnetic resonance imaging (HR-MRI) database, consecutive ICAS (>50%) patients with two detections of HR-MRI over six months were included in this study. The patients were divided into two groups: those with (evolucomab+) or without (evolocumab-) evolocumab add-on therapy. The primary outcomes were the percentage change in plaque burden and plaque response (plaque regression >5%) rate. The second outcome was the percentage change in stenosis degree. Cox regression analysis was used to estimate the association between evolocumab add-on therapy and the above outcomes in both general and subgroup (intensive statin vs. non-intensive statin) analysis.

Results:
The data of 179 patients receiving statins and/or ezetimibe, 50 of which with evolucumab and 129 without, were analyzed. Evolocumab add-on therapy over six months showed a significant reduction in the percentage change of plaque burden (evolocumab+, median [IQR]: 0.08 [0.02-0.11] vs. evolocumab-: 0.02 [0.04-0.07]), increase in plague response rate (evolocumab+: 68.0% vs. evolocumab-: 34.1%), and reduction in the percentage change of stenosis degree (evolocumab+: 0.15 [0.01-0.34] vs. evolucumab-: 0.05 [-0.12-0.26]). After adjusting for potential confounders, evolocumab was significantly associated with the percentage reduction in plaque burden (estimate [95% CI], 0.074 [0.029-0.119]), the increase in plague response rate (6.70 [2.81-16.99]), and the percentage reduction in stenosis degree (0.198 [0.074-0.321]). In both intensive and non-intensive statin groups, evolocumab add-on therapy was still significantly associated with better outcomes in the percentage reduction in plague burden (intensive: 0.063 [0.004-0.121], P < 0.05; non-intensive: 0.126 [0.045-0.208], P < 0.01), the increase in plaque response rate (intensive: 3.75 [1.09-14.10], P < 0.05; non-intensive: 11.60 [2.55 – 52.82], P < 0.01), and the percentage reduction in stenosis degree (intensive: 0.148 [-0.015-0.312], P = 0.075; non-intensive: 0.331 [0.118-0.544], P < 0.01).

Conclusions:
Evolocumab add-on therapy over six months is superior to statin alone in reversing symptomatic ICAS.
Abstract 40: GENETIC INSIGHTS INTO NOAC THERAPY FAILURE: IMPLICATIONS FOR PRECISION ANTICOAGULATION
Authors: V Ashique , Vinod Gopika , Sunil Gopika , K ANAGHA , Ratan Chameli , PT Karthika , P Narmadha , Ahamed Hisham , Biswas Lalitha , Vali Jaffar , NAMBIAR VIVEK
Published: January 2025

Introduction:
Atrial fibrillation (AF) significantly elevates the risk of ischemic stroke and systemic embolism. Novel Oral Anticoagulants (NOACs) have improved stroke prevention in AF, offering superior efficacy and safety compared to warfarin. However, NOAC therapy can fail due to genetic variations, inappropriate dosing, non-adherence, renal dysfunction, hepatic impairment, and drug-drug interactions.This study investigates the potential determinants of NOAC failure, which refers to patients who experienced recurrent thromboembolic events despite being on NOAC therapy.

Objectives:
To determine the genetic factors (CES1, ABCB1, and ABCG2 polymorphisms) and other contributing factors associated with NOAC therapy failure.

Methods:
This six-month prospective observational study included adult patients on NOACs for AF, stroke, pulmonary embolism, and other thrombotic events. Exclusions were malignancy and pregnancy/lactation. Data on demographics, medical history, concurrent medications, and clinical outcomes were collected. Genetic polymorphisms were assessed using High-Resolution Melting (HRM)-PCR. Medication adherence was evaluated via the Medication Adherence Rating Scale (MARS), and drug-drug interactions were analyzed using UpToDate software. Statistical analysis was performed using chi-square tests, with a p-value <0.05 considered significant.

Results:
The study included 62 patients (43.5% female, mean age 68 ± 8.9 years). Of these, 46 were on Apixaban, 12 on Dabigatran, and 5 on Rivaroxaban. Recurrent thromboembolic events occurred in 13 (21%) patients within 3.5 months of NOAC initiation. Renal and hepatic impairments had minimal association with NOAC failure; no significant drug-drug interactions were noted. Of the 46 Apixaban users, 17 (37%) carried SNP rs2231142, with 4 (24%) experiencing recurrent events (p=0.039), and 11 (24%) carried SNP rs4148738, with 3 (27%) having recurrent events (p=0.000). For Dabigatran, 4 (33%) carried SNP rs8192935, with 2 (50%) having recurrent events (p=0.083). No polymorphisms were found in Rivaroxaban users.

Conclusion:
SNPs rs2231142 and rs4148738 were significantly associated with recurrent thromboembolic events in Apixaban users, suggesting that genetic testing could enhance the prediction of NOAC failure. The findings support the potential role of genetic profiling in optimizing NOAC therapy, given the minimal impact of renal/hepatic impairments and drug-drug interactions.
Abstract 41: Territorial Stroke in SAMMPRIS: Critical Analyses of Stroke Prevention in Intracranial Atherosclerosis
Authors: Hegde Sheetal , Tariq Muhammad Bilal , Kaneko Naoki , Hinman Jason , Liebeskind David
Published: January 2025

Introduction:
Current guidelines do not support the use of stenting for severe symptomatic intracranial atherosclerotic disease (ICAD) over maximal medical therapy (MMT) as first line treatment. This is largely due to the Stenting and Aggressive Medical Management Therapy for Preventing Recurrent Stroke in Intracranial Arterial Stenosis (SAMMPRIS) trial results which featured a high periprocedural stroke rate. In this study, we examined the rates of ischemic stroke in the territory of the qualifying artery (SIT) periprocedurally as well as over time between MMT alone and stent+MMT.

Methods:
The primary outcome of interest was SIT. Periprocedural stroke was defined as <7d from stent placement. Log-rank analysis and Kaplan-Meier survival curves were performed to compare time to SIT between MMT and stent+MMT (with day of stent set as day 0 to account for periprocedural stroke and arterial changes post-stent).

Results:
Of 451 patients in SAMMPRIS, 435 were included (MMT: n=227; stent+MMT: n=208). The SIT event rate was 15.6% (68 total SIT events- MMT: n=31; stent+MMT: n=37). The median time from qualifying ischemic event (QIE) to stent+MMT in all patients with SIT was 8d (range: 1-34d) with median time of stent to SIT of 4d (IQR:1,215). Thirteen patients with SIT were stented early (<7d from QIE) with median time to stent+MMT of 4d (IQR:3,5) and median time of stent to SIT of 6d (IQR:0,233). Twenty four patients had SIT after delayed stent (>7d) with median time to stent+MMT of 10.5d (IQR:8.75,19) and median time of stent to SIT of 3d (IQR:1,161.75).

Twenty of the 37 stented patients had periprocedural SIT (7 early; 13 delayed). However, over the course of the entire follow up period (1626d), the difference in SIT between MMT and stent+MMT was not significant (p=0.2, Figure 1), with 31 strokes in MMT and 17 non-periprocedural strokes in stent+MMT.

Conclusions:
Contrary to guidelines, periprocedural SIT rates did not vary by time of stenting relative to QIE of the parent artery. The majority of SIT were isolated to the periprocedural period, and the difference over time was not significant between MMT and stent+MMT. The rate of SIT over the full study period was higher in MMT when excluding periprocedural strokes from stent+MMT, suggesting that MMT alone may not be the most effective treatment for ICAD. This also suggests that with improvements in safety of stenting in the periprocedural period, intracranial stenting may remain a viable treatment option for ICAD.
Abstract 43: Projecting United States Population Eligibility for Minimally Invasive Surgical Evacuation of Acute, Spontaneous Intracerebral Hemorrhage
Authors: Wechsler Paul , Sucharew Heidi , Robinson David , Flaherty Matthew , Stanton Robert , Horn Paul , Maloney Thomas , Williamson Brady , Wang Lily , Khandwala Vivek , Gangatirkar Shantala , gaskill-shipley mary , Haverbusch Mary , Tomsick Thomas , Wang David , Cornelius Rebecca , Woo Daniel , Kleindorfer Dawn , Kissela Brett , Vagal Achala , Khatri Pooja
Published: January 2025

Background:
The Early MiNimally-Invasive Removal of ICH (ENRICH) trial established minimally invasive surgical evacuation as an effective therapy for acute, spontaneous, lobar intracerebral hemorrhage (ICH). We aimed to estimate the annual number of US patients in 2020 eligible for minimally invasive hematoma evacuation by extrapolating Greater Cincinnati Northern Kentucky (GCNK) Stroke Study epidemiologic data to US census data.

Methods:
We ascertained all adults (
>
18 years) with acute (<24 hours from last known well), spontaneous ICH presenting to the ED in GCNK in 2015. Cases were identified by ICD codes, clinical data abstracted, and physician adjudicated. The location and volume of ICH was centrally adjudicated by neuroradiologists. We calculated conservative and liberal estimates of the number of GCNK patients with acute, spontaneous, lobar ICH that met ENRICH trial eligibility for minimally invasive surgical evacuation. Lobar ICH was analyzed separately given the benefit of surgical hematoma evacuation was attributable to intervention for lobar ICH in ENRICH. Conservative estimates considered all clinically relevant ENRICH trial eligibility criteria. Liberal estimates removed anticoagulant use as exclusion criterion because these patients were included in ENRICH if coagulopathy was rapidly reversed. The derived estimates of ENRICH eligible patients were then extrapolated to the 2020 US adult population using characteristics of ICH patients in GCNK and 2020 US census data.

Results:
Over the 2015 GCNK study period, 197 patients with acute, spontaneous ICH were identified (median age 74, 55% female, 28% Black). In conservative estimates applying all clinically relevant ENRICH criteria, 5.7% (n=6) of lobar ICH patients were eligible for minimally invasive surgical evacuation. Including those on anticoagulants resulted in 6.7% (n=7) of lobar ICH patients being eligible for minimally invasive surgical evacuation. After extrapolation to the 2020 US population, of an estimated 96,120 ICH cases in 2020, we calculated that 1,972 (conservative) to 2,318 (liberal) patients with acute lobar ICH would be eligible for minimally invasive surgical evacuation based on ENRICH eligibility criteria (Figure 1).

Conclusion:
It is estimated that 1,972-2,318 acute, spontaneous, lobar ICH patients in the US in 2020 met eligibility for minimally invasive surgical hematoma evacuation. US stroke systems of care should be designed to meet the demand for this new therapy.
Abstract 44: Minimally Invasive Surgery is Associated with Improved Outcomes Compared to Open Craniotomy with Clot Evacuation after Spontaneous Intracerebral Hemorrhage in the AHA Get With The Guidelines Registry
Authors: Murthy Santosh , Zhang Cenai , Garton Andew , Mac Grory Brian , Shah Shreyansh , Fonarow Gregg , Schwamm Lee , Bhatt Deepak , Smith Eric , Falcone Guido , Payabvash Sam , Ziai Wendy , Knopman Jared , Matouk Charles , Mocco J , Kamel Hooman , Sheth Kevin
Published: January 2025

Introduction:
Data are lacking on outcomes of minimally invasive surgery (MIS), an emerging surgical treatment for spontaneous intracerebral hemorrhage (ICH), compared to conventional open craniotomy with clot evacuation. We therefore sought to evaluate ICH outcomes after MIS vs conventional clot evacuation in a real-world, nationally representative US cohort.

Methods:
We performed a retrospective cohort study of patients with ICH from 2011-2021 in the Get With The Guidelines-Stroke registry. The exposure was the type of surgery, classified as open craniotomy with clot evacuation versus MIS (either endoscopic surgical evacuation or stereotactic evacuation with fibrinolytic therapy). The primary outcome was in-hospital mortality, and secondary outcomes included discharge disposition, ambulatory status at discharge, and modified Rankin score at discharge. Using overlap propensity matching, we matched patients with MIS versus open craniotomy on age, sex, race, NIH Stroke Scale, prior antithrombotic therapy, external ventricular drain use, and withdrawal of care. The overlap weighting creates exact balance on the mean of every measured covariate when the propensity score is estimated by logistic regression, and therefore, mimics the attributes of a clinical trial. Each MIS patient was matched with multiple patients who received open craniotomy, based on the propensity score. Logistic regression was used to study the relationship of the type of surgery with outcomes. Pre-specified subgroup analyses were stratified by age, sex, race, NIHSS, EVD use, and annual ICH volume.

Results:
Among 555,964 patients with ICH, MIS was performed in 703 patients (330 had stereotactic surgery and 373 had endoscopic surgery) and open craniotomy was performed in 7067 patients. In the matched cohort, in-hospital deaths occurred in 60/446 (13.5%) with MIS and 648/3675 (17.6%) with open craniotomy. In regression analyses, MIS was associated with lower odds of in-hospital mortality (aOR, 0.7; CI, 0.5-0.9), unfavorable discharge (aOR, 0.7; CI, 0.6-0.9), and higher odds of discharge to rehabilitation (aOR, 1.3; CI, 1.1-1.5), but not with functional outcomes (Table). In pre-specified subgroup analyses, lower mortality was noted with MIS in older patients and men (Figure).

Conclusions:
In a large, diverse US cohort of ICH patients, MIS was associated with lower odds of in-hospital mortality and better discharge disposition compared to open craniotomy with clot evacuation.
Abstract 59: Results of a Pilot Multimodal Quality Improvement Intervention to Accelerate Blood Pressure Reduction and Anticoagulant Reversal for Acute Spontaneous Intracerebral Hemorrhage
Authors: Do Rachel , Sharma Latisha , Liebeskind David , Chatfield Fiona , Alfonso Rodel , Vespa Paul , Buitrago Manuel , Colby Geoffrey , Choe Judy , McCullough Lynne , Nour May , Chaudhari Amit , Saver Jeffrey
Published: January 2025

Background:
Rapid blood pressure reduction and anticoagulant reversal have been associated with lower mortality and improved outcomes in patients with acute spontaneous ICH, prompting the establishment of time-based quality measures for acute ICH care, similar to those for acute ischemic stroke. Multimodal systems of care interventions need to be developed and validated that drive organizational change to achieve these quality targets.

Methods:
We developed a multimodal systems of care intervention to enhance attainment of 3 acute ICH care process outcomes: 1) door-to-treatment (DTT) time for initiation of an antihypertensive agent with initial SBP ≥160 mmHg, including targets of ≤60m, ≤45m, and ≤30m; 2) door-to-blood pressure control (DTC) time with goal SBP <160, including targets of ≤120m, ≤90m, and ≤60m; and 3) DTT for initiation of an anticoagulant reversal agent, including targets of ≤90m, ≤60m, and ≤45m. Quality improvement interventions included use of a specialized emergency hemostatic order set for ICH management, a post-case feedback form to all providers (Image 1), and serial care process analysis and refinement. Here we analyze results during the intervention development and pilot period at a single comprehensive stroke center between July 2022 and June 2024.

Results:
During the study period, 77 adult, acute, non-transfer, ED-arriving ICH patients presented, including 42 (54.5%) with initial SBP ≥160 and 10 (13.0%) on anticoagulation. Outcomes for care process time metrics are shown in Images 2 and 3. Among the patients with initial SBP ≥160, median DTT time for initiation of an antihypertensive agent was 42 minutes (IQR 27-74), including 66.7% within 60m, 54.8% within 45m, and 28.6% within 30m. Median DTC time for first achievement of blood pressure control was 86 minutes (IQR 55-121), including 73.8% within 120m, 57.1% within 90m, and 31.0% within 60m. Among the patients with anticoagulation-associated ICH, median DTT time for initiation of an anticoagulant reversal agent was 76 minutes (IQR 64-113), including 60.0% of patients within 90m, 20.0% within 60m, and 20.0% within 45m. Patients with faster DTT times had higher NIHSS and ICH scores on presentation.

Conclusions:
Development and pilot period implementation of a multimodal systems of care intervention resulted in achievement of ICH quality measures in a majority of patients. These findings support the establishment of national Target: Stroke initiatives to improve emergency ICH care.
Abstract 6: HRS8179 in Patients with Cerebral Edema after Large Hemispheric Infarction: A Multicenter, Randomized, Double-blinded, Placebo-controlled, Phase 2 Study
Authors: Wang Ziran , Du Huishan , Zhang Xiaojie , Hou Deren , Dai Hongguo , Zhong Di , Zhang Zhuobo , Li Runxiong , Hao Junfang , Yang Yi , Wu Chenglong , Gao Yu , Wang Xinning , Liu Liping
Published: January 2025

Background:
Large hemispheric infarction (LHI) shows a high risk of cerebral edema and neurological deterioration, even leading to death, but it still has limited treatment options. HRS8179 is a selective sulfonylurea receptor 1 inhibitor, which can block the up-regulated sodium channel after ischemic stroke and reduce cerebral edema. This study assessed HRS8179 in patients with cerebral edema after large hemispheric infarction.

Methods:
In this multicenter, randomized, double-blinded, placebo-controlled, phase 2 clinical trial (NCT05690711), patients who had a clinical diagnosis of LHI for <10 hours (confirmed by diffusion-weighted image or computed tomography perfusion lesion volume of 80-300 cm
3
) and National Institutes of Health Stroke Scale (NIHSS) ≥10 were randomized (1:1) to receive HRS8179 or placebo administered as a 0.15 mg intravenous injection followed by a 0.1 mg/h continuous intravenous infusion for 72 hours. The primary endpoint was the change in midline shift from the baseline after 72 hours of treatment.

Findings:
A total of 40 patients were randomized (20 in the HRS8179 group, 20 in the placebo group). Baseline characteristics were similar between groups (Table). HRS8179-treated patients had a LS mean change in midline shift relative to baseline at 72 hours of 7.92 mm, compared with 9.17 mm in placebo-treated patients (difference, -1.25 mm [95% CI, -5.50 to 3.00]). The 90-day mortality rate in the HRS8179 group and the placebo group were 30.0% (95% CI, 11.9% to 54.3%) and 50.0% (95% CI, 27.2% to 72.8%), respectively. Distribution of modified Rankin Scale scores at 90 days for both groups is shown (Figure). The increase in NIHSS ≥4 points at 72 hours occurred in 5 patients (26.3%) in the HRS8179 group and 7 patients (41.2%) in the placebo group. At 2 weeks of symptom onset, 6 patients (30.0%) in the HRS8179 group and 13 patients (65.0%) in the placebo group experienced brain herniation or death. The most common treatment-related adverse events (TRAEs) in the HRS8179 group were hypoglycemia (7 [35.0%]). The incidence of hypoglycemia with blood glucose levels <3.9 mmol/L was 30.0% and levels <3.0 mmol/L was 15.0%, which were rapidly resolved by intravenous glucose supplementation. No TRAEs led to death.

Interpretation:
HRS8179 showed potential efficacy in reducing the severity of cerebral edema in patients with LHI, particularly in lowering the 90-day mortality rate, even in patients without reperfusion, with an acceptable safety profile.
Abstract 73: The importance of goals: Does achieving door to device time of 90 minutes or less result in improved patient outcomes?
Authors: Rosales Meg , Stuchiner Tamela , Szweda Kamila , Kisiler Jennifer , Marginean Horia , Fitzgerald Darcie , Tarpley Jason
Published: January 2025

Introduction:
The American Stroke Association goals for Target: Stroke – Phase III include achieving a door to device (DTD) of 90 minutes or less for direct arriving patients in at least 50% of patients who undergo endovascular thrombectomy (EVT) or acute ischemic stroke patients with large vessel occlusion (LVO). While it is generally held that faster reperfusion is associated with better patient outcomes, the magnitude of benefit in achieving the goal of DTD </= 90 has not been systematically studied.

Methods:
This is a retrospective analysis of acute ischemic stroke (AIS) patients from a multi-state stroke registry between January 2016 through March 2024. Mixed effects logistic regression models were fit to obtain an odds ratio of favorable mRS (</=2) and an odds ratio for discharge to home for DTD <= 90 vs. DTD > 90 groups, adjusting for age, race, sex, last known well to arrival time, hypertension, chronic renal insufficiency, diabetes, dementia, and initial NIHSS score in the final model, and clustering by hospital site. The final models included 1,317 patients with available MRS data and 1,789 patients with available discharge disposition data respectively. We used a mixed effects linear regression model to examine the relationship between DTD group and length of stay, controlling for age, race, sex, last known well to arrival time, initial NIHSS, atrial fibrillation, and alcohol/drug abuse and clustering by hospital site. The final model included 1,790 patients with complete data.

Results:
Overall the predicted probability of 90 day MRS </= 2 was 43% in patients with DTD</=90 compared with only 32% of patients with DTD>90. Compared to the DTD > 90 group, the DTD <= 90 group had significantly higher odds of a favorable 90-day MRS with an adjusted OR of 1.57 (p = 0.002, 95% CI = [1.17, 2.09]). No significant difference was found across DTD groups in the odds of discharge to home (adjusted OR = 1.10 , p = 0.40, 95% CI = [0.87, 1.38]) or on length of stay (beta = 0.0, p = 0.90, 95% CI = [-0.9, 0.9]).

Conclusions:
Direct arriving AIS patients who receive EVT with a DTD </= to 90 minutes are 1.57 times more likely to have a favorable outcome than those who do not achieve this goal. There was no affect of DTD</=90 on length of stay or discharge to home.
Abstract 8: Modified Rankin Score at 90 Days vs. NIH Stroke Scale at 24 Hours as Primary Outcome in Acute Stroke Trials
Authors: Ospel Johanna , Brown Scott , Bosshardt Salome , Stebner Alexander , Uchida Kazutaka , Demchuk Andrew , Saver Jeffrey , White Phil , Muir Keith , Dippel Diederik , Majoie Charles , Jovin Tudor , Campbell Bruce , Mitchell Peter , Bracard Serge , guillemin francis , Hill Michael , Goyal Mayank
Published: January 2025

Background:
We investigate whether the NIHSS at 24 hours could serve as an alternative primary outcome measure in acute ischemic stroke trials, and whether combining 90-day modified Rankin Score (mRS) and 24-hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using EVT as an exemplary study intervention.

Methods:
Post-hoc analysis from the HERMES collaboration that pooled data from 7 randomized controlled EVT trials. Validity of 24-hour NIHSS as a surrogate outcome for 90-day mRS was assessed in a causal mediation model (Figure 1). A 7-point ordinal NIHSS score was generated by grouping 24-hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24-hour NIHSS, ordinal 24-hour NIHSS, 90-day mRS, and hierarchical outcome (win-ratio) that combines 90-day mRS and 24-hour NIHSS. Subgroup analyses were performed in patients with baseline NIHSS<10 and ≥25.

Results:
A total of 1720 patients were included. Median 90-day mRS in the EVT/control arms was 3.0(IQR:1.0-4.0)/4.0(IQR:2.0-5.0) and median 24-hour NIHSS was 9.0(IQR:3.0-17.0)/14.0(IQR:7.5-19.0), see Figure 2. 24-hour NIHSS mediated the association between EVT and 90-day mRS and met the criteria for a surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90-day mRS(240) and ordinal 24-hour NIHSS(242), see Table 1. In subgroup analyses of patients with baseline NIHSS<10 and≥25, ordinal 24-hour NIHSS resulted in the highest effect size/ smallest sample size.

Conclusion:
24-hour NIHSS may be a valid surrogate outcome for 90-day mRS in acute ischemic stroke patients undergoing EVT, with a similar EVT effect size compared to 90-day mRS. It could potentially enhance detection of EVT benefit in patient subgroups with very low or very high baseline NIHSS. Combining 90-day mRS and 24-hour NIHSS in an ordered hierarchical could improve detection of EVT treatment effect compared to 90-day mRS.
Abstract 85: The Association Between Hourly Systolic Blood Pressure Fluctuations and Outcomes in Patients with Intracerebral Hemorrhage is Time Dependent: Post Hoc Analysis of ATACH-2 Trial.
Authors: Qureshi Adnan , Baskett William , Lakhani Pashmeen , Rabinstein Alejandro , Rose David , Suarez Jose , Steiner Thorsten , Shyu Chiren
Published: January 2025

Background:
Systolic blood pressure (SBP) fluctuation is linked to increased death or disability in intracerebral hemorrhage (ICH) patients. We analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 trial to explore whether the association between SBP fluctuation and 90-day outcomes varies with time from randomization.

Methods:
We calculated hourly SBP fluctuation based on the difference between maximum and minimum SBP during the first 24 hours post-randomization. Logistic regression models assessed the impact of SBP fluctuation on: 1) death or disability (modified Rankin scale [mRS] 4-6 at 90 days); 2) hematoma expansion (>33% increase in volume on 24-hour CT scan); 3) neurological deterioration within 24 hours (defined as ≥2-point decrease on Glasgow Coma Scale or ≥4-point increase on NIH Stroke Scale); and 4) acute kidney injury (AKI) within 72 hours. Adjustments were made for baseline Glasgow Coma Scale score, intraventricular hemorrhage, hematoma volume, and maximum SBP.

Results:
The hourly SBP fluctuations according to 90-day outcomes (dichotomized into good outcome, mRS 0-3, and poor outcome, mRS 4-6) in 961 patients with ICH are presented in Figure. The SBP fluctuation at 5 hours (p=0.014) and 6 hours (p=0.014) post randomization were significantly associated with death or disability at 90 days, with positive, but not statistically significant associations observed at all other points up to 13 hours after randomization. Risk of neurological deterioration within 24 hours was highly associated with SBP fluctuation, with the largest association observed between 1 (p<0.001) and 5 (p<0.001) hours following randomization, with significant associations observed up to 22 hours following randomization. Risk of hematoma expansion was associated with SBP fluctuation between 3 (p=0.015) and 8 (p=0.002) hours post randomization. Statistically significant associations between SPB fluctuations and risk of AKI were not observed.

Conclusions:
The first 8 hours following randomization are critical for reducing SBP fluctuations, as this period most strongly influences both short- and long-term outcomes in ICH patients. These findings suggest this time window is crucial for future interventions aimed at controlling SBP in ICH patients.
Abstract 87: Eligibility for Minimally Invasive Surgical Evacuation of Acute, Spontaneous Intracerebral Hemorrhage: A Population-Based Study
Authors: Wechsler Paul , Sucharew Heidi , Flaherty Matthew , Robinson David , Stanton Robert , Horn Paul , Maloney Thomas , Williamson Brady , Wang Lily , Khandwala Vivek , Gangatirkar Shantala , gaskill-shipley mary , Haverbusch Mary , Tomsick Thomas , Wang David , Cornelius Rebecca , Woo Daniel , Kleindorfer Dawn , Kissela Brett , Vagal Achala , Khatri Pooja
Published: January 2025

Background:
Minimally invasive surgical evacuation improved outcomes for patients with acute, spontaneous intracerebral hemorrhage (ICH) in the Early MiNimally-Invasive Removal of ICH (ENRICH) trial. Eligibility for this therapy amongst ICH patients encountered in routine clinical practice is unknown. Using a population-based study, we aimed to determine the percentage of patients with acute ICH eligible for minimally invasive surgical evacuation based on the ENRICH trial inclusion and exclusion (I/E) criteria.

Methods:
We ascertained all adults (
>
18 years) with acute (<24 hours from LKW), spontaneous ICH presenting to the ED in Greater Cincinnati/Northern Kentucky in 2015. Cases were identified by ICD codes, clinical data abstracted, and physician adjudicated. Location and volume of ICH was centrally adjudicated by neuroradiologists. We sequentially applied clinically relevant ENRICH I/E criteria to calculate the percentage of patients excluded from minimally invasive surgical evacuation based on each criterion. We calculated conservative and liberal estimates of the percentage of patients with 1) any ICH, 2) lobar ICH, and 3) basal ganglia (BG) ICH eligible for minimally invasive surgical evacuation after application of ENRICH I/E criteria. Although lobar and BG ICH were both included in ENRICH, lobar and BG ICH were analyzed separately given the benefit of surgical hematoma evacuation was attributable to intervention for lobar ICH.

Results:
Over the 2015 study period, we identified 197 patients presenting to the ED with acute, spontaneous ICH and no missing I/E criteria values. Median age was 74, 55% were female, 53% had lobar ICH, and 42% had deep cerebral ICH (12% BG ICH) (Table 1). The number of patients excluded after sequential application of each criterion is shown in Table 2. After application of all ENRICH I/E criteria, 3.0% (n= 6) of all acute ICH patients (5.7%, n=6 of lobar ICH and 0%, n=0 of BG ICH) were eligible for minimally invasive surgical evacuation. In a liberal estimate removing anticoagulant use, INR >1.4, mechanical valve, and ESRD as exclusion criteria, 3.6% (n= 7) of all acute ICH patients (6.7%, n =7 of lobar ICH and 0%, n=0 of BG ICH) were eligible for hematoma evacuation.

Conclusion:
In a population-based study, only 3.0% of all acute ICH patients and 5.7% of lobar ICH patients were eligible for minimally invasive surgical evacuation. Further research is needed to establish effective therapies for more patients with acute ICH.
Abstract 90: Astrocytic Cluster of Differentiation 38 Contributes to Hippocampal Synaptic Plasticity Deficits following Focal Cerebral Ischemia
Authors: Jackson Charles , Waits Paxton , Browning Sydney , Orfila James , Herson Paco
Published: January 2025

Introduction:
Post-Stroke Cognitive Impairment (PSCI) is increasingly recognized as a major factor in long-term disability. Therefore, new therapies that enhance post-stroke brain function (plasticity) are appealing in translational research. Activation of the cation channel TRPM2 after middle cerebral artery occlusion (MCAO) induces PSCI-like symptoms, such as memory impairment and deficits in Long-Term Potentiation (LTP). Determining the mediator of chronic TRPM2 channel activation may implicate a novel contributor to LTP deficit. The enzyme CD38 may be this mediator, as it produces the TRPM2 activator ADPr. Here, we investigate astrocytic CD38’s role in MCAO and TRPM2-induced deficits.

Methods:
LTP was assessed through Extracellular Field Recordings from CA3-CA1 synapses of Acute Hippocampal Slices. Immunofluorescence stained for GFAP and CD38 in hippocampal sections. Wt or CD38
-/-
mice were subjected to 60-minute MCAO, or Sham, and assessed for LTP 7 days later. Wt or TRPM2
-/-
mice received Intracranial Administration (200nL, 10
12
gc/mL) of AAV-CD38-eGFP (astrocyte CD38 overexpression) or AAV-eGFP (control) to the right ventral CA1 and assessed for LTP after 21 days. All mice were 8-12-week-old males. Differences between groups were determined with either Welch’s T-Test or One-Way ANOVA followed by post-hoc test.

Results:
We observed increased expression of CD38, colocalized with GFAP (astrocyte marker), in the hippocampus 7 days post-MCAO. Sham Wt mice exhibited robust LTP, not observed in Wt MCAO (Wt-Sham: 176% +/- 33.9 vs Wt-MCAO: 135% +/- 23, p < 0.05). Conversely, CD38
-/-
mice displayed robust LTP after either Sham or MCAO, depicting protection of synaptic plasticity (CD38
-/-
-Sham: 175.2% +/- 24.1, CD38
-/-
-MCAO: 184.8% +/- 27.3). AAV-CD38-eGFP astrocytic overexpression vector produced impairment in LTP in the Wt mice compared to the empty vector control (Wt-eGFP: 195.6% +/- 46 vs Wt-CD38:141.5% +/- 38.7, p < 0.05). No differences were observed in TRPM2
-/-
mice injected with either virus. (TRPM2
-/-
-eGFP: 180.3% +/- 39.4, TRPM2
-/-
-CD38 174% +/- 54.1)

Conclusions:
Our study implicates astrocytic CD38 as a novel inducer of hippocampal synaptic plasticity impairment. CD38 is increased following injury and required for MCAO-induced LTP deficit. Additionally, overexpression is sufficient to impair LTP in uninjured mice, in a TRPM2-dependent manner. Astrocytic CD38 is a novel target for PSCI and the likely upstream mediator of chronic TRPM2 activation.
Abstract 94: MRI Outcomes in the Multicenter Stroke Preclinical Assessment Network (SPAN) Trial
Authors: Morais Andreia , Lynch Kirsten , Imai Takahiko , JIN XUYAN , Aykan Sanem A , Lamb Jessica , Nagarkatti Karisma , Lyden Patrick , Ayata Cenk
Published: January 2025

Introduction:
Ischemic stroke is a leading cause of death and disability worldwide, but there has been limited success in translating putative treatments from preclinical trials to patients. The Stroke Preclinical Assessment Network (SPAN) is a large-scale multicenter trial (six sites plus a coordinating center).

Methods:
SPAN implemented a multiparametric MRI protocol with minimal human input to assess tissue outcomes after mouse endovascular middle cerebral artery occlusion (MCAO). Imaging from 1766 mice was used in this study. The sample size includes three comorbidity models (Young mice, Aging mice, and diet-induced hyperglycemia/ obesity mice.

Results:
Infarct volumes were variable across the network but right-skewed at all sites. Striatal and cortical infarcts were more common than thalamic and hippocampal infarcts (present in 75%, 65%, 20%, and 22% of mice, respectively). Total lesion was more associated with striatal and cortical infarct volumes (R=0.94 and 0.97). Infarct volumes were strongly associated with midline shift on days 2 (R=0.74) and 30 (R=-0.80), reflecting ischemic swelling and encephalomalacia, respectively. Factor analysis identified the underpinnings of the covariance among MRI variables (Figure 1). We found 13 MRI readouts linked to the injury severity after MCAO. These included the total, striatal, and cortical infarct volumes, indices of ischemic edema on day 2, and indices of tissue loss on day 30. Five variables were linked to infarction involving the posterior cerebral artery. Another set of five variables was linked to ventricular volume, suggesting an independent contributing factor, such as age. Average R2
rate
in the contralateral tissue was lower in diet-induced obesity and aged mice compared with normal young mice, suggesting higher brain water content. Within the infarct, the R2
rate
was significantly lower only in diet-induced obese mice versus the other groups.

Conclusion:
Our data revealed critical insight into the stroke model regarding lesion distribution, swelling, and atrophy. Our findings also shed light on previously underappreciated biological associations among these variables.
Abstract 97: Association of Post-Stroke Cognitive Impairment with Impaired Glymphatic Function and Neurotoxin Waste Removal in Patients with Intracerebral Hemorrhage
Authors: Nariman Nina , Boren Seth , Hasan Khader , Suchting Robert , de Dios Constanza , sitton clark , Aronowski Jaroslaw , Savitz Sean , Haque Muhammad
Published: January 2025

Objective:
To evaluate a potential relationship between post-stroke cognitive impairment (PSCI) and a radiographic measure of glymphatic function after intracerebral hemorrhage (ICH).

Introduction:
PSCI has been less studied in patients with ICH. Here we aim to evaluate the role of glymphatic function after ICH and its association with PSCI. Glymphatic cleanup occurs in the perivascular space (PVS) formed by astroglial end-feet loosely surrounding small arteries and veins. Here we applied non-invasive diffusion tensor imaging (DTI) to measure changes in brain diffusion due to dynamics changes of interstitial fluid (ISF) and CSF along the PVS. The application of DTI-along the perivascular space index (DTI-ALPSI) has been validated to evaluate glymphatic function. It computes the diffusivity ratio between projection and association fibers oriented orthogonally with the medullary veins at the level of the lateral ventricle body (Fig-1A).

Methods:
We serially imaged 18 patients with deep ICH at 9.3±9.1 (V1) and 109±28 (V2) days of onset on a 3T MRI system. Cognitive assessment was obtained via MoCA scores. Fractional anisotropy (FA) and mean diffusivity (MD) maps were registered to the T1W and SWI images. Three regions of interest (ROI), remote from a lesion, in the association and projection fibers, orthogonal to the medullary veins at PVS were used to compute diffusivity (Fig-1C). Using the equation shown, the DTI-ALPSI was calculated. DTI-ALPSI = Mean (Dx proj, Dx assoc) / Mean (Dy proj, Dz assoc)

Using 3D-Flair images, hematoma (HV) and edema (EV) volumes were segmented. The ipsilesional DTI-ALPSI was correlated with MoCA, HV, and NIHSS. Contralesional DTI-ALPSI was used as a control. A non-linear regression model was used for statistical analysis.

Results:
We enrolled 12M/6F with an average age of 49.3±13.3y. Compared to the control, the ipsilesional DTI-ALPSI was significantly decreased (p=0.036) at V2. Temporally the MoCA scores were significantly increased (19±8.5 to 23±6.0, p<0.001) whereas the NIHSS (8±6 to 3±3), HV (9.3±8.6 to 2.6±2.7 cm
3
), and EV (26.9±23.2 to 3.1±4.0 cm
3
) were significantly decreased (p<0.001). Ipsilesional DTI-ALPSI was positively associated with MoCA (r=0.59, p=0.02) (Fig-1D) and negatively associated with NIHSS (r=-0.58, p=0.02) (Fig-1E) and HV (r=-0.53, p=0.04) at V2.

Conclusion:
Our data showed that DTI-ALPSI can be applied to evaluate the role of glymphatic dysfunction and its association with post-ICH cognitive impairment.
Abstract DP2: Effect of Tirofiban on 90-day Functional Outcomes in Patients with Presumed Non-Embolic Stroke
Authors: Olive-Gadea Marta , Bajrami Arsida , PAMIDIMUKKALA VIJAYA , Flores Alan , Rubiera Marta , AKSOY SENA , YELAMANCHI Rama Chandra , Estrada Edgardo , POLAVARAPU NAREN , Behra Usha kiran , geyik serdar , Rizzo Federica , Rodrigo-Gisbert Marc , Garcia-Tornel Garcia-Camba Alvaro , Muchada Marian , Simonetti Renato , Ribo Marc
Published: January 2025

Introduction:
Tirofiban has shown a potential effect in reducing early neurological deterioration and improving clinical outcomes in selected patients with non-embolic stroke. We aim to analyze the effect of tirofiban versus standard acute therapy on 90-day outcomes in patients with presumed non-embolic stroke.

Methods:
Multicentric retrospective cohort study including consecutive AIS patients presenting within 24h from symptom onset, baseline mRS 0-1, absence of cortical symptoms, identifiable vessel occlusion or other imaging features suggestive of embolic stroke; anticoagulated patients were excluded from the analysis. Patients received either tirofiban (±ASA) or standard acute therapy (IVT or oral antiplatelets). Primary outcome was functional independence at 90 days (mRS 0-2); secondary efficacy and safety outcomes included: excellent outcome (mRS 0-1); sICH, systemic bleeding and neurological deterioration (4 point increase in NIHSS). Exploratory subgroup analysis was performed for severity (NIHSS ≥5 vs <5) and standard therapy (IVT vs oral APT) groups.

Results:
Of 290 patients included, 138 (48%) received tirofiban; 60(21%) IVT and 92(31%) oral antiplatelets. Median age was 63 (54-72) years, 65% were male, NIHSS at presentation was 5 (3-7). Baseline characteristics for each treatment group are summarized in the table. After adjusting by age, baseline mRS, NIHSS and time since onset, tirofiban was associated with higher odds of mRS 0-2 (93% vs 77%; aOR 3.7 [1.4-9.4]) and mRS 0-1(79% vs 59%; aOR 3.5 [1.7-6.9]). No sICH or severe systemic bleedings occurred in either group, minor bleedings included GI (T:1% vs ST:1%), hematuria (T:4% vs ST:0, p<0.01). Rate of neurological deterioration was T:0 vs ST:1%.

Tirofiban was associated with better outcomes irrespective of baseline NIHSS and control arm group (figure). Safety outcomes were not analyzed in subgroups due to low incidence of events.

Conclusion:
Tirofiban is safe and may improve 90-day functional outcome in presumed non-embolic, non-LVO stroke, warranting further prospective randomized trials
Abstract DP27: Reversibility of White Matter Damage, Neuroinflammation, and Oxidative Stress from Diesel Exhaust
Authors: Tang-Tan Angela , Shkirkova Kristina , Demetriou Alexandra , Chen Selena , Daggupati Sindhu , Bent Christine , Zhao Lifu , Thorwald Max , Godoy-Lugo Jose , Sauri Ariel , Sioutas Constantinos , Pike Christian , Finch Caleb , Mack William
Published: January 2025

Introduction:
Air pollution derived from diesel exhaust has been linked with cognitive decline and cerebrovascular diseases. In previous studies, subacute diesel exhaust exposure has been shown to increase neurotoxicity and white matter damage; however, few studies have modeled the effects of air quality improvement. Our previous data from the same cohort showed persistent microglial activation (Iba-1) after an 8-week recovery period. The objective of this study was to further investigate the extent of recovery after neurotoxic diesel exhaust particulate (DEP) exposure.

Methods:
Female and male 8-week-old C57BL/6 mice were exposed to inhaled Filtered Air (FA) and DEP (NIST SRM 2975) at concentration of 100μg/m3. There were three arms in this study: 1) 8 weeks of FA or DEP exposure (n=16/group); 2) 8 weeks of FA or DEP exposure followed by 8 weeks of recovery (n=16/group); and 3) 16 weeks of FA or DEP exposure (n=16/group). Mice were humanely euthanized and brain hemispheres sectioned at 5 µm. Corpus callosum levels of C5 complement protein, C5a anaphylatoxin, 4-hydroxynonenal (4-HNE), 8-Oxo-2'-deoxyguanosine (8-OHDG), and degraded myelin basic protein (dMBP) were assayed via immunofluorescence.

Results:
The 8-week DEP group demonstrated increases in C5 (+39%), C5a (+45%), 4-HNE (+107%), 8-OHDG (+26%), and dMBP (+118%) in comparison to the 8-week FA group. The 8-week DEP recovery group demonstrated no significant elevation in C5, C5a, 4-HNE, and 8-OHDG in comparison to the 8-week FA recovery group. However, dMBP remained elevated (+87%) after in the 8-week DEP recovery group compared to the 8-week FA recovery group. The 16-week DEP group demonstrated increases in C5 (+44%), C5a (+58%), 4-HNE (+106%), 8-OHDG (+57%), and dMBP (+94%) in comparison to the 16-week FA group (p-values in Figure 1).

Conclusions:
DEP exposure results in increased oxidative stress, neuroinflammation, and myelin breakdown at 8 weeks and 16 weeks. Unlike neuroinflammation and oxidative stress that recovered, white matter damage showed a persistent effect after an 8-week washout period. Combined with our previous data on persistent microglia activation, this suggests that prolonged neuroimmune response may contribute to the white matter injury that persists several months after DEP exposure termination.