bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 53: Variation in DNA Mismatch Repair Genes Nominally Associated With Severity of Cerebral Cavernous Malformation Type 1
Authors: Choquet Hélène , Pawlikowska Ludmila , Nelson Jeffrey , McCulloch Charles E. , Akers Amy , Khan Yasir , Hart Blaine , Morrison Leslie , Kim Helen ,   for the Brain Vascular Malformation Consortium (BVMC) Study
Published: March 2022

Introduction:
Familial cerebral cavernous malformation type 1 (CCM1) is an autosomal dominant disease caused by
CCM1
mutations, and characterized by multiple brain lesions that can lead to intracerebral hemorrhage (ICH). In humans, CCM lesion genesis follows a two-hit mutation mechanism, where both germline and somatic mutations occur to inactivate the CCM1 protein. In mouse models,
Ccm1
+/-
mice need to be crossed into a mismatch repair-deficient
Msh2
-/-
or
Trp53
-/-
background, which increases the overall rate of somatic mutations, to exhibit CCM lesions. We hypothesized that common variants in
MSH2
and
TP53
may modify CCM1 disease severity, as manifested by ICH and greater total or large lesion counts.

Methods:
We analyzed 188 CCM1 patients all harboring the common Hispanic mutation (CHM, Q455X). ICH and lesion counts at enrollment were obtained by clinical assessment and MRI. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. After excluding variants with missing call rate >2%, minor allele frequency <1%, deviation from Hardy-Weinberg equilibrium (P<0.001), or in high linkage disequilibrium (
r
2
≥0.8), 16 and 11 variants within +/- 5kb of
MSH2
and
TP53
, respectively, were analyzed for association with ICH, total lesion count, and large lesion (≥5 mm) count using multivariable regression.

Results:
No variant was associated with ICH or total lesion count. Two
MSH2
variants (rs62139708 and rs17224794) were nominally associated with an increase in large lesion count independent of age and gender. Subjects carrying the minor allele at rs62139708 and at rs17224794 had 34% (
P
=0.024) and 63% more large lesions (
P
=0.039), respectively, compared to non-carriers. In contrast, subjects carrying the minor allele at
TP53
rs8073498 had 19% fewer large lesions (
P
=0.046) than non-carriers at baseline.

Conclusions:
Variants in
MSH2
and
TP53
contribute modestly to variability in large lesion count in CCM1 disease. As suggested by CCM1 mouse models, DNA mismatch repair genes may influence CCM lesion multiplicity and progression in the human disease.
Abstract 58: Ultra early CT-Perfusion May Overestimate Initial Infarct Core. The Ghost Infarct Core Concept
Authors: Boned Sandra , Tomasello Alejandro , Padroni Marina , Coscojuela Pilar , Cabero Jordi , Rodriguez-Luna David , Pagola Jorge , Muchada Marian , Rubiera Marta , Sanjuan Estela , Juega Jesus M. , Molina Carlos , Ribó Marc
Published: March 2022

Identifying infarct core or irreversible infarct on admission is essential in order to establish the amount of salvageable tissue and indicate reperfusion therapies. CT perfusion (CTP) has been reported to be useful differentiating the penumbra as the mismatch between infarct core and hypoperfused brain. Infarct core is established on CTP as the severely hypoperfused areas, however the correlation between hypoperfusion and infarct core may be time dependent and not always true as it is not a direct tissue damage indicator.

We aim to characterize those cases in which admission core lesion on CTP does not reflect an infarct on follow-up imaging.

Methods:
We studied patients with ICA/MCA occlusion who underwent CTP on admission but received endovascular thrombectomy based on initial non-contrast CT ASPECTS≥7. Admission infarct core was measured on initial CBV-CTP and final infarct on follow-up imaging. We defined ghost infarct core (GIC) as: initial core - final infarct>10cc. Time from symptom onset to CTP was recorded. Recanalization (TICI2b3) was assessed after thrombectomy.

Results:
79 patients were studied: ICA/MCA occlusion 21/58, median NIHSS 17(11-20), mean time from symptoms to CTP: 218±143minutes. Recanalization rate was: 77% Mean CBV infarct core was 44±59cc, and mean final infarct volume was 38±70cc. 30 patients (38%) presented a GIC>10cc and 22(29%) a GIC>20cc. GIC>10cc was associated with recanalization (TICI2b3:44 Vs 17%; p=0.034), admission glicemia (<185mg/dl:42% Vs 0%; p=0.028) and time to CTP (185:26%; p=0.033). An adjusted logistic regression model showed time from symptom to CTP imaging 10cc (OR: 2.89, 95%CI: 1.04-8.09). Similar results were observed if infarct core was defined with CBF maps.

Conclusion:
CT perfusion may overestimate final infarct core especially in the early window from symptom onset. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who may still benefit from reperfusion.
Abstract 69: Cerebellar Dentate Nucleus is an Effective Brain Stimulation Target for Post-stroke Recovery
Authors: Ishizaka Shunsuke , Cheng Michelle , Shah Aatman , Wang Eric , Bautista Alex , Sun Guohua , Steinberg Gary K
Published: March 2022

Objective:
Functional recovery after stroke has been observed in both human and animal studies. Post-stroke brain stimulations are promising neurorestorative techniques as they allow direct manipulation of the target area’s excitability. Previously we have demonstrated that optogenetic neuronal stimulation of the ipsilesional primary motor cortex (iM1) promotes functional recovery. To determine an optimal brain stimulation target, we test whether optogenetic neuronal stimulation of the contralesional cerebellar dentate nucleus (cLCN) can promote recovery. We hypothesize that stimulation of cLCN may be more effective, as it sends excitatory outputs to multiple motor and premotor areas.

Methods:
Thy-1-ChR2-YFP line-18 transgenic male mice were used. Mice underwent stereotaxic surgery to implant an optical fiber in cLCN or iM1, followed by an intraluminal middle cerebral artery suture occlusion. Three groups of mice were used: control non-stimulated stroke mice, short stimulated stroke mice (short-stim, day5-14 post-stroke) and long stimulated stroke mice (long-stim, day5-28 post-stroke). Sensorimotor behavior tests were used to assess their recovery.

Results:
Our data showed that cLCN-stimulated stroke mice recovered quickly, with significant improvement in distance traveled as early as day7 (p<0.05), and faster rotating beam spole speed at day14 post-stroke (p<0.001). The effect of cLCN stimulation was persistent, as the short stim group continued to recover after day14 without further stimulations. The long stim group did not further enhance recovery. Interestingly, cLCN-stimulated mice performed significantly faster than iM1-stimulated mice. Analysis of pCREB activation showed that cLCN stimulation activates the dentatothalamocortical pathway.

Conclusion:
Our data suggest that cLCN stimulations post-stroke can promote persistent functional recovery. Furthermore, cLCN-stimulated mice recovered faster than iM1-stimulated mice, indicate that cLCN may be a more effective brain stimulation target. Current studies examine the brain activation patterns of cLCN-stimulated mice, as well as the mechanisms of cLCN-induced recovery.
Abstract 76: Exploring Efficacy and Safety of Very Early Mobilization Within 24 Hours of Stroke Onset Versus Usual Stroke Unit Care (A Very Early Rehabilitation Trial, AVERT): Pre-specified Subgroup Analysis
Authors: Bernhardt Julie , Langhorne Peter , Lindley Richard I , Thrift Amanda G , Ellery Fiona , Collier Janice , Churilov Leonid , Moodie Marjory , Dewey Helen , Donnan Geoffrey A ,   on behalf of the AVERT Trialists' Collaboration
Published: March 2022

Introduction:
Potential benefits of starting out of bed activity early after stroke are tempered with concerns of harm. In this pre-specified subgroup analysis, we examine the potential influence of patient and process factors on outcome at 3 months.

Methods:
This parallel group, single blind, randomized controlled trial was conducted in 56 acute stroke units, in five countries. Eligible participants were admitted within 24 hours of stroke onset, (ischemic or hemorrhagic) meeting physiological safety criteria. Patients were randomized to very early mobilization (VEM), delivered by physiotherapists and nurses, commenced < 24 hours or to usual care (UC). Modified Rankin Scale (mRS) at 3 months was the primary outcome. Efficacy and safety analyses (serious adverse events [SAEs], deaths) and additional exploratory analysis of age, stroke severity, stroke type, treatment with rtPA, time to first mobilization and geographical region (AUS/NZ
vs
Asia
vs
UK), followed a pre-published statistical analysis plan.

Results:
2104 patients were enrolled; 1054 randomized to VEM and 1050 to UC and 2083 (99.0%) were followed to 3 months. 525 (50.2%) patients in UC versus 479 (46.2%) in VEM had a good outcome (mRS 0-2; adjusted odds ratio [OR] 0.73, 95%CI 0.59-0.9, p=0.003). 72 patients in UC died (6.9%) versus 88 in VEM (8.4%) (OR 1.34, 95%CI 0.93-1.93. p=0.194). There was no difference in the proportion of patients (UC 209[19.9%] versus VEM 201[19.1%]) experiencing a SAE (IRR 0.88, 95%CI 0.72-1.07). Over the course of the trial, UC shifted to begin a median of 28 minutes earlier each year (95%CI 11.3, 44.6, p<0.001). The efficacy subgroup analysis showed no significant treatment-by-strata interactions, but a more favorable outcome for the UC intervention in patients with intra-cerebral hemorrhage. Death subgroup analysis also favored UC intervention, with no significant treatment-by-strata interactions. Subgroup analysis of SAEs revealed a single significant age-by-treatment interaction (p=0.031), and more favorable outcomes for the VEM in those aged 65-80 years and treated in AUS/NZ.

Conclusion:
These findings will change the practice of very early stroke rehabilitation.
Abstract 9: A Novel Large Cerebral Aneurysm Model in Rats with Intraperitoneal Administration of Beta-AminoPropioNitril-Fumarate
Authors: Shimoda Yusuke , Moriwaki Takuya , Nakayama Naoki , Abumiya Takeo , Kazumata Ken , Shichinohe Hideo , Houkin Kiyohiro
Published: March 2022

Introduction:
Mechanisms of formation, enlargement, and rupture of cerebral aneurysm (CA) are not fully understood. Unveiling the mechanisms lead to the prevention of a life-threatening subarachnoid hemorrhage. Although several CA models in rats have been reported, most of CAs in the models are immature and insufficient for the close investigation into the mechanisms of enlargement and rupture. The establishment of a large CA model is required for full disclosure of the mechanisms.

Methods:
A new CA model in rats was designed by modifying the Hashimoto model in that high-dose β-aminopropionitril fumarate (BAPN-F) was administrated intraperitoneally. Seven-week-old male Sprague-Dawley rats were deeply anesthetized, the left common carotid artery was dissected and the bilateral posterior branches of the renal artery were ligated. After the operation, rats were fed food with 8% sodium chloride and divided into 4 groups according to the weekly dose amount of BAPN-F as well as the breeding periods (group 1: n=31, 400mg/kg for 4weeks, group 2: n=31, 400mg/kg for 8weeks, group 3: n=27, 2800mg/kg for 8weeks, group 4: n=13, 2800mg/kg for 12weeks). We then investigated aneurysmal development pathologically along with calculating CA induction rate and mortality rate in each group.

Results:
Continuous hypertension were induced in all groups. CA induction rate was 19.4%, 29%, 85.2%, and 84.6% while mortality was 12.9%, 16.1%, 7.4% and 30.1% in the group 1, 2, 3, and 4, respectively. Group 3 has statistically significant differences in both the induction rate (p=0.018) and mortality (p=0.027). Among 4 groups, CAs were located at anterior cerebral artery - ophthalmic artery bifurcation, anterior communicating artery (Acom A), and posterior communication artery (Pcom A). We defined the large CA as over one and a half times the size of its parent artery. Large CAs were predominantly detected at Acom A and Pcom A in the group 3 (22.2%) and 4 (23.1%). In addition, all large CAs were morphologically and histologically similar to that of human.

Conclusions:
Intraperitoneal administration of 2800mg/kg BAPN-F enabled us to induce large CAs with 20% induction rate and low mortality. A further investigation of this model should be promising for full disclosure of the CAs mechanisms.
Abstract NS1: Access and Use of Information Technologies Among Hypertensive Older Adults to Reduce Stroke Risk
Authors: Tailakh Ayman , Warren-Findlow Jan , Hook Jane , Vasquez Cinthya
Published: March 2022

Introduction:
Information technology could play a crucial role in enhancing hypertension self-care and reduction of stroke risk, but, little is known of the role and impact of access and use of information technology on blood pressure (BP) control in older adults.

Hypothesis:
Access and use of information technologies will be associated with increased adherence to self-care activities and BP control in hypertensive older adults?

Methods:
In this cross-sectional, descriptive study, a total of 151 participants completed a survey to assess hypertension self-care activities, technology utilization, and BP knowledge. Clinical measures were obtained by trained assistants (height, weight and BP). Three BP measurements were obtained at 60-second intervals after resting for 5 minutes. A Pearson product-moment correlation coefficient was used to assess the relationship between information technologies and self-care activities.

Results:
The mean age of participants was 75 years. Participants were predominantly women (61.7%), retired (78.1%), owned cellphones (76.5%), but most did not have internet access at home (59.7%). In bivariate analyses, having a cellphone was positively associated with Diastolic BP (DBP) (r = .20, p < .05), and a preference for receiving text or email reminders (r = .22, p < .05). Computer use was significantly associated with DBP (r = .17, p < .05), BP knowledge (r = .17, p < .05), seeking health information online (r =.49, p < .01), and belief that internet can be helpful to manage BP (r =.45, p < .01). Internet use was significantly associated with DBP (r = .17, p < .05) and BP knowledge (r = .16, p < .05).

Conclusion:
The use of electronic technology was significantly correlated with lower BP and better BP knowledge. Internet-based hypertension self-care interventions could promote patient involvement and patient centered-care leading to better adherence and BP control to reduce the risk for stroke. Electronic technologies may facilitate clinical data transmission and communication between patients and providers so providers can modify treatment regimens between visits. However, our results suggest that the lack of internet access could limit the feasibility of internet-based interventions to reduce blood pressure in this population.
Abstract NS4: Vigilant Nursing Glucose and Temperature Control for Stroke: Is There a Need in the United States?
Authors: Biby Sharon , Palazzo Paola , Doerr Abby , Lindstrom Anne , Dusenbury Wendy , Young Rhonda , Tsivgoulis Georgios , Alexandrov Andrei V , Neau Jean-Philippe , Middleton Sandy , Alexandrov Anne W
Published: March 2022

Background:
In the Australian QASC Trial (Lancet 2013), better glucose and fever control improved 90 day outcomes when nurses adhered to strict monitoring/treatment protocols. We examined variance from guideline specific care for glucose and fever in an American sample.

Methods:
An observational study was conducted to assess compliance with AHA/ASA stroke guidelines for glucose and fever control in consecutive acute stroke patients from 5 different U.S. Stroke Centers. The first 5-days of glucose/temperature data were analyzed along with demographics and outcome measures.

Results:
A total of 1669 consecutive glucose and 3782 consecutive temperature measurements were taken from a sample of 235 acute stroke patients; the sample was 87% ischemic and 13% ICH, with admission median NIHSS 4.0 (range 0-34) and ICH score median 1 (range 0-5). 26% of ischemic strokes received IVtPA and/or thrombectomy. HbA1c was 5.7
+
.65 (median range 4.8-11.2) in non-DM diagnosed patients vs. 8.3
+
2.3 (range 5.0-14.1; 95%CI=1.9-3.1; p<0.001) in DM patients. Glucose was >180 mg/dL for >4 hours in 33% during hospitalization (Table), and the most frequent method (35%) for glucose control was regular insulin sliding scale. Temperature was >37.5
o
(noncompliant with European/Australian [E/A] standards) for >4 hours in 27% of patients, and >38
o
(noncompliant with US standards) for >4 hours in 10% of patients; 8% were out-of-control >8 hours (range 9-96, median 16.5 hours out-of-control) and 39% did not have temperature measured in the ED. mRS and LOS were significantly worse if temperature exceeded the E/A and US standards (Table). Temperature control to <37.5
o
C was an independent predictor (p<0.001) of favorable (0-2) mRS at discharge.

Conclusions:
Our study underscores the need for more vigilant control of glucose and temperature by nurses at U.S. hospitals. Given the time-sensitive ability of brain to recover from ischemia, even short-term non-compliance may have detrimental effects.
Abstract TMP107: Intra-arterial Vasodilators Treat Vasospasm in Aneurysmal Subarachnoid Hemorrhage With Fair Angiographic & Neurological Response, but the Impact on Outcome is Unknown: a Meta-analysis of Observational Studies
Authors: Venkatraman Anand , Khawaja Ayaz , Deveikis John P , Harrigan Mark R , Kumar Gyanendra
Published: March 2022

Objective:
Previous meta-analyses have not reported pooled estimates of response to the treatment of vasospasm with intra-arterial vasodilators (IADs) in aneurysmal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to pool estimates of angiographic & clinical response, good outcome, & mortality rates following treatment of vasospasm with IADs.

Methods:
We searched PubMed using MeSH terms for “Subarachnoid Hemorrhage" AND ("Endovascular Procedures" OR "Infusions, Intra-Arterial") AND "Vasodilator Agents". Bibliographies of retrieved articles were also searched. Studies reporting clinical and angiographic response, mortality, and outcome, following IAD treatment of vasospasm in adult humans with aSAH were included. All IADs were allowed. Two authors independently selected studies & abstracted data. Mean weighted probabilities (MWP) were calculated using random effects model.

Results:
Inclusion criteria were met by 48 studies (n=1264). Heterogeneity was significant in all syntheses (I2 ≥50%; P< 0.5) and studies were of poor quality. Publication bias was significant for the synthesis of mortality. MWP for immediate angiographic response to IAD treatment was 90% (95% CI 84-95%), post-IAD neurological improvement 59% (95% CI 47-71%), good outcome 56% (95% CI 49-63%), and Mortality rate was 9% (95% CI 6-12%). Subgroup analysis is shown in the table.

Conclusion:
IAD treatment leads to a fair angiographic and neurologic response but the impact on outcome is unknown. Studies were of poor quality and bias was significant. Current evidence does not support the use of IADs for the treatment of cerebral vasospasm in aSAH. Randomized/pragmatic trials are needed to elucidate the role of IADs in vasospasm in aSAH.
Abstract TMP110: Minocycline Reduces Hypoxia-mediated BBB Disruption by Protecting TJP Degradation and Promoting Angiogenesis in SHR/SP With Chronic White-matter Injury
Authors: Yang Yi , Kimura-Ohba Shihoko , Thompson Jeffrey F , Salayandia Victor M , Cosse Millie , Raz Limor , Jalal Fakhreya Y , Rosenberg Gary A
Published: March 2022

Introduction:
Our previous study indicated that blood-brain barrier (BBB) disruption occurred secondary to hypoxia-induced and MMP-mediated neuroinflammatory white matter (WM) damage in spontaneously hypertensive/stroke prone rats (SHR/SP). Tight junction proteins (TJPs) maintain the normal BBB functions. Here, we investigated the effects of hypoxia on TJP degradation and hypoxia-induced angiogenesis, and tested the effect of long-term minocycline treatment on the BBB integrity and repair.

Methods:
Male SHR/SPs at 12W (weeks) old were subjected to unilateral carotid artery occlusion (UCAO) and fed a Japanese permissive diet (JPD) for 4W. For the treatment study, the SHR/SP/UCAO/JPD were given minocycline (50 mg/kg in DMSO, i.p.) and the vehicle rats received DMSO from 12W to 20W of life.

Results:
Sham-operated SHR/SP with normal chow had abnormal TJPs in blood vessels (BVs) at 16W compared to Wistar; they showed a slight increase of BBB permeability and NG2-positive microglia in WM. In the UCAO/JDP group, by 4W, multimodal MRI (T2, ADC, FA, and ASL) showed that WM damage of varying degree reflected the extent of injury corresponding to variable BBB leakage by dynamic contrast-enhanced MRI and IgG staining. TJP levels (claudin-5, occludin, and ZO-1) in WM were significantly decreased. Angiogenesis in WM was detected with increased expression of Ki67 and NG2 in vascular endothelial cells and/or pericytes. UCAO/JPD typically causes the death of SHR-SP/JPD/UCAO rats after 4W. However, minocycline treatment extended survival to 9W after UCAO/JPD and significantly reduced lesion size and vascular damage. TJPs, VEGF-A, and GST-π (mature oligodendrocytes) were increased by minocycline at 8W compared to sham and vehicle. Minocycline also increased the expression of factors involved in angiogenesis and WM repair (Ki67, NG2, MMP-2, MMP-3) in vascular endothelial cells, pericytes, astrocytes, and oligodendrocytes compared to controls.

Conclusions:
Our results support the hypothesis that damage to the BVs by chronic hypertension and UCAO/JPD produces TJP degradation and increases BBB permeability. Minocycline treatment significantly protects WM from damage by preventing BBB disruption and enhances TJP formation and angiogenesis.
Abstract TMP112: Procalcitonin and Mrproanp As Biomarkers of Subclinical Cerebrovascular Damage: The Northern Manhattan Study
Authors: Katan Mira , Moon Yeseon P , von Eckardsteind Arnold , Spanaus Katharina , DeRosa Janet T , Gutierrez Jose , DeCarli Charles , Wright Clinton B , Sacco Ralph L , Elkind Mitchell S
Published: March 2022

Background:
Chronic infections and hemodynamic dysfunction are risk factors for stroke. We hypothesized that blood biomarkers of infection (procalcitonin, or PCT) and hemodynamic stress (midregional pro-atrial natriuretic peptide, or MRproANP) would be associated with subclinical cerebrovascular damage (SCVD), including silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV).

Methods:
The Northern Manhattan Study was designed to assess risk factors for incident vascular disease in a multiethnic cohort. A subsample underwent brain MRI and had blood samples available for biomarker measurement (n=1178). We used logistic regression models to estimate the odds ratios and 95% confidence intervals (OR, 95%CI) for the association of these biomarkers with SBI, and linear regression for associations with logWMHV, after adjusting for demographic, behavioral, and medical risk factors.

Results:
Mean age was 70 ±9 years; 60% were women, 66% hispanic, 17% black, 15% white and 2% belonged to other ethnicities. After fully adjusting for risk factors, subjects with PCT or MRproANP in the top quartile, compared to the lowest quartile, were associated with greater odds of having SBI (adjusted OR for PCT 2.2, 95%CI 1.3-3.7; for MRproANP 3.3, 95%CI 1.7-6.3) and increased WMHV (adjusted mean change in logWMHV for PCT 0.29, 95%CI 0.13-0.44; for MRproANP 0.18,95%CI 0.003-0.36).

Conclusion:
Higher concentrations of PCT, a marker of infection, and MRproANP, a marker of hemodynamic stress, are independently associated with SCVD. Future biomarker- guided primary prevention studies may lead to new approaches to prevent cerebrovascular damage.
Abstract TMP117: Detecting Diseased Tissue in Normal Appearing White Matter of Transient Ischemic Attack and Minor Stroke Patients Using Texture Analysis
Authors: Mahajan Ajay , Campeau Stephen , Gupta Sah Rani , Carlson Helen L , Khan Saad , Tsang Adrian , Zhang Yunyan , Kirton Adam , Coutts Shelagh , Barber Phillip A
Published: March 2022

Introduction:
Patients with minor strokes and Transient Ischemic Attacks (TIAs) are at risk of recurrent strokes and cognitive decline. Stroke lesions appear as white matter hyperintensities on T2 MR images. We investigated microstructural changes in normal appearing white matter (NAWM) of patients with TIAs and minor stroke.

Hypothesis:
Longitudinal changes in texture analysis parameters (angular second moment [ASM] and entropy) of NAWM would correspond to a qualitative increase in diseased tissue.

Methods:
FLAIR MRI data was obtained within 24hrs of injury (baseline [n=86]), and at 3 follow-up times (90D, n=40; 18M, n=46; and 3Y, n=60). 14 regions of interest (ROIs) were manually placed bilaterally on the NAWM of the baseline FLAIR image in 2 locations in the medial temporal lobes (MDTL), genu, splenium, periventricular (PVT), frontal (FWM), parietal (PWM), and posterior cortex WM (COV). ASM and entropy were measured using the GLCM Texture Analysis tool in ImageJ. Friedman’s ANOVA addressed longitudinal changes.

Results:
Significant changes for 6 ROIs [MDTLR, Splenium, FWMR, PWMR, COVL, COVR (p<0.05)] were observed longitudinally. ASM decreases were seen at 90 days, with a return to baseline by 3 years (Fig1a). An increase in entropy was seen at 90 days; with no return to baseline for 5/6 ROIs (Fig1b).

Conclusion:
Texture analysis (ASM and entropy) may effectively quantify diseased tissue consistent with qualitative examination of NAWM in FLAIR sequences. Diseased tissue appears maximally present at 90 days with some return to baseline by 3 years.
Abstract TMP17: Statin Pretreatment is Associated With Better Early Outcomes in Acute Large-Artery Atherosclerotic Stroke
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Sharma Vijay K , Krogias Christos , Mikulik Robert , Vadikolias Konstantinos , Mijajlovic Milija , Safouris Apostolos , Zompola Christina , Faissner Simon , Weiss Viktor , Giannopoulos Sotirios , Vasdekis Spyros , Boviatsis Efstathios , Alexandrov Anne W , Voumvourakis Konstantinos , Alexandrov Andrei V
Published: March 2022

Background & Purpose:
Statin pretreatment is associated with better functional outcomes and lower risk of mortality in acute ischemic stroke (AIS). We hypothesized that this association may be accentuated in AIS due to large-artery atherosclerosis (LAA) that carries the highest risk of early stroke recurrence.

Methods:
Consecutive patients with acute LAA were prospectively evaluated from seven tertiary-care stroke centers during a three-year period. Statin pretreatment, demographics, vascular risk factors, admission and discharge NIHSS-scores were recorded. The outcome events of interest were neurological improvement during hospitalization (quantified as the relative decrease in NIHSS-score at discharge in comparison to hospital admission), favorable functional outcome (FFO, defined as mRS-score of 0-1), recurrent stroke and death at 1-month. Statistical analyses were performed using univariate and multivariate Cox regression models adjusting for potential confounders. All analyses were repeated following propensity score matching.

Results:
Statin pretreatment was documented in 192 (37.2%) out of 516 consecutive LAA patients (mean age: 65±13 years; 60.8% men; median NIHSS-score: 9 points, interquartile range: 5-18). Neurological improvement during hospitalization was greater in patients with than without statin pretreatment in unmatched and matched analyses (66.7% vs. 34.8%; p<0.001). Statin pretreatement was associated higher rates of 30-day FFO in unmatched and matched (OR for FFO: 0.48; 95%CI: 0.31-0.75) analyses. Statin pretreatment was related to lower risk of 1-month mortality and stroke recurrence in unmatched and matched analyses (HR for recurrent stroke: 0.11; 95%CI: 0.02-0.46, HR for death: 0.24, 95%CI: 0.08-0.75).

Conclusions:
Statin pretreatment in patients with acute LAA appears to be associated with better early outcomes in terms of neurological improvement, disability, survival and stroke recurrence.
Abstract TMP23: Increased VEGFA-165a/VEGFA-165b Ratio in Patients With Moyamoya Compared to Intracranial Atherosclerosis (ICAS) and Controls
Authors: Gonzalez Nestor R , Liou Raymond , Rao Neal , Ooi Yinn , Restrepo Lucas , Laiwalla Azim , Ali Latisha , Xing Hanning , Toscano Juan F , Martin Neil , Connolly Mark J , Saver Jeffrey
Published: March 2022

Introduction:
Recent work in cancer biology has identified splice variants of human VEGF-A that inhibit angiogenesis. These isoforms arise from differential splicing of exon 8: a proangiogenic VEGF-A165a and the antiangiogenic VEGF-A165b. The purpose of this study was to compare circulating VEGF-A165a / VEGF-A165b ratios in patients with ICAS to those of patients with moyamoya and controls with no vascular or tumoral disease. Identifying a potential target to facilitate the generation of spontaneous collaterals could open novel treatment avenues for ICAS patients.

Methods:
This is a prospective observational study of circulating VEGF-A165a and VEGF-A165b. Serum samples were collected at baseline, 1 week, 1 month, 3 months, and 6 months after enrollment. Levels of VEGFA-165a and VEGFA-165b were determined by a multiplex sandwich ELISA. All samples were run in duplicate with an acceptance threshold for intersample variability of less than 20%. A mixed model regression model was built to predict square root transformed VEGF-A165a / VEGF-A165b ratio using age and etiology as the predictor variables. A repeated autoregressive 1 structure was used to account for repeated measures and subject random effects were used to account for intersubject variability.

Results:
The study population consisted of 72 individuals with ICAS (age = 61.7±12.0), 8 with moyamoya (age = 42.7±12.6), and 7 controls (age = 44.3±13.9). A total of 230 samples were collected (ICAS: 188, moyamoya: 21, control: 21). One outlier was excluded due to an exorbitantly high VEGFA-165a concentration. VEGFA-165a/VEGFA-165b ratios were as follows for each etiology: ICAS (0.15±0.17), moyamoya (0.38±0.52), and control (0.10±0.12). Mixed model regression analysis found a significant independent positive association of moyamoya to elevated VEGF-A165a/ VEGF-A165b ratio (p=0.03).

Conclusion:
In this prospective analysis of VEGF-A165a/ VEGF-A165b ratio, moyamoya patients had elevated ratios compared to ICAS and controls. This finding supports the concept that VEGF-A165b could serve as a new pharmacological target to treat cerebral ischemia in patients with ICAS as its neutralization may augment the activities of proangiogenic growth factors in developing collaterals.
Abstract TMP25: Brain-computer Interface Therapy for Upper Extremity Stroke Rehabilitation Induces Corticospinal Tract Changes That Track With Individual Behavioral Gains
Authors: Young Brittany M , Stamm Julie M , Song Jie , Remsik Alexander , Nair Veena A , Tyler Mitchell E , Edwards Dorothy F , Caldera Kristin , Sattin Justin A , Williams Justin C , Prabhakaran Vivek
Published: March 2022

Introduction:
A better understanding of brain changes underlying functional gains with brain-computer interface (BCI) use in stroke rehabilitation is needed.

Hypothesis:
BCI therapy will produce observable neuroplastic changes, and behavioral gains will relate to changes in diffusion tensor imaging (DTI) metrics of the corticospinal tracts (CSTs).

Methods:
We obtained DTI and behavioral data from 16 stroke patients with upper extremity motor impairment before, during, and after BCI therapy. Additional DTI and behavior data were obtained from 9 control subjects at similar time intervals before receiving any BCI therapy. Behavioral measures included Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), 9-Hole Peg Test (9HPT), and grip strength. We performed deterministic tractography of the ipsilesional CST (iCST) and contralesional CST (cCST) and extracted DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, trace) from each. DTI and behavioral metrics were analyzed for changes from baseline between therapy and control groups. Individual changes in DTI metrics were analyzed for correlation with behavior changes during the therapy period.

Results:
Group by time interactions were identified in DTI metrics of the iCST, with multiple metrics increasing with therapy. Changes in individual SIS Activities of Daily Living and 9HPT scores correlated with individual changes in both the iCST and cCST. Similarly, changes in SIS Hand Function correlated with cCST changes, and changes in grip strength correlated with iCST changes. Correlations between changes in ARAT scores and cCST changes trended to significance. Correlations significant at p<= 0.05; trending at 0.05<p<0.1 after fdr correction.

Conclusions:
BCI therapy can induce structural neuroplastic changes during stroke recovery. These changes may be used to track both subjective and objective behavioral gains.
Abstract TMP29: Rehospitalizations Post-stroke: a 10 Year Follow-up
Authors: Rohweder Gitta , Salvesen Øyvind , Ellekjær Hanne , Indredavik Bent
Published: March 2022

Background and Purpose:
Rehospitalizations post-stroke can be considered to represent potential long-term complications of the incidental stroke and are most commonly caused by vascular events, infections, gastrointestinal and immobility related morbidity. The purpose of the study was to define the causes for rehospitalizations as well as their frequency, and to further explore the association between the incidental stroke, the burden of complications within 3 months, and rehospitalization for these long term complications.

Methods:
A cohort of 244 patients, acutely and consecutively admitted to our stroke unit in 2002/3 with information regarding medical complications over the first 3 months was evaluated in regards to hospitalizations during the ensuing 10 years. 1 patient was lost to follow-up. The hospital records were reviewed, the main admitting diagnosis was verified and assigned to one of 18 predefined categories of illness.

Results:
177 of the 243 patients had 1 or more acute hospital readmissions to a total of 831 rehospitalizations. The median number of rehospitalizations was 2 (range 0-24). Proportions (%): ischemic stroke 5.4, hemorrhagic stroke 1.1, cardiac events 10.5, peripheral vascular events 3.0, chest infection 9.0, serious infection 4.1, UTI 4.2, falls with fractures 6.1, falls without fractures 3.2, epileptic seizures 2.9, stroke sequelae 3.4, hemorrhagic events 5.7, thrombotic events 1.2, renal insufficiency 2.0, TIA 2.2, cardiac angina 2.8, cancer 8.5, other 24.7.

Rehospitalizations occurred in 73 % of stroke patients and were attributable to vascular causes in 20.0 %, to infections in 17.3 %, to falls with and without fractures in 9.3 % and to peripheral hemorrhagic events in 5.7 % of admissions.

Conclusion:
Rehospitalizations during 10 years following a stroke are common and have varying etiologies with vascular events and infections as the most frequent causes.
Abstract TMP32: Intra-arterial ALD401 Cell Therapy is Associated With Reduction in Stroke Volume at 90 Days in a Subset of the RECOVER-stroke Trial
Authors: Atchaneeyasakul Kunakorn , Dharmadhikari Sushrut , Sidani Charif , Ramdas Kevin , Guada Luis , Pafford Ryan , Huang David , Hinson Jim , Savitz Sean , Yavagal Dileep
Published: March 2022

Background:
Stroke is a leading cause of major long-term disability worldwide. Despite availability of IV tPA and mechanical thrombectomy, over half of treated patients have significant disability. Cell based therapy is a promising in pre-clinical studies in improving stroke recovery. Brain infarct volume is a major predictor of stroke outcome and may decrease with this treatment. We hypothesized that patients treated with intra-arterial stem cell therapy will have a significant reduction in stroke volume compared to non-treated patients.

Methods:
The RECOVER-Stroke trial is a randomized, sham-controlled study to determine the safety and efficacy of processed autologous bone marrow cells (ALD-401) injection via intracarotid infusion in ischemic stroke patients. Ischemic stroke patients were double-blind randomized into 2 groups, receiving ALD-401 injection or sham procedure between 9-19 days post anterior circulation ischemic stroke. All enrolled patients at 1 of 8 sites in the trial were included in this analysis. Two blinded physicians used OSIRIX software to analyze stroke volume on DWI/ 24h CT brain and MRI at 90, 180, 365 days post intervention. Volumes were compared between the 2 groups at these timepoints.

Results:
A total of 11 patients at our center (out of 48 multicenter patients) were included in this study, 6 patients receiving sham procedure and 5 patients receiving ALD-401. The two groups did not show any significant difference in their baseline variables including age, Mean baseline stroke volumes were not significantly different between ALD-401 (103.9±96.2ml) and sham groups (70.2±46ml), p=0.53. The stroke volume reduction in the ALD-401 was 22.9±15.5ml vs. 4.04±12.5ml in the sham group (p=0.046). On day 180 and 365, both groups did not show any further significant stroke volume reduction from day 90.

Conclusion:
In this exploratory analysis from one center in the multi-center RECOVER-Stroke trial, intra-arterial stem cell injection with ALD-401 was associated with significant reduction in stroke volume at 90 days post therapy compared to sham procedure in subacute ischemic stroke patients.
Abstract TMP36: Disability, Quality of Life and Institutionalization After Inpatient Rehabilitation and Skilled Nursing Facility Care for Ischemic Stroke Patients
Authors: Prvu Bettger Janet , Bushnell Cheryl D , Liang Li , Thomas Laine , Duncan Pamela W , Xian Ying , Fonarow Gregg C , Hoenig Helen , Lutz Barbara , Montalvo Cris , Stein Joel , Schwamm Lee , Peterson Eric D
Published: March 2022

Introduction:
Stroke patients are the second highest post-acute rehabilitation users but there are few comparisons of inpatient rehabilitation (IRF) and skilled nursing facility (SNF) care on patient-reported outcomes.

Methods:
We compared 3 and 12 month dependence (modified Rankin Scale score=3-6), quality of life (QOL) (Euro-qol-5D continuous variable max=1; death=0), and institutionalization (residence recorded as nursing home, hospice or dead) for acute ischemic stroke (AIS) patients in GWTG-Stroke and the AVAIL (Adherence eValuation After Ischemic Stroke Longitudinal) study living at home pre-stroke and discharged to an IRF or SNF immediately after hospital discharge. Binary and continuous outcomes were modeled by logistic and linear regression, respectively. Inverse propensity weighting (IPW) was used to adjust for measured differences in demographic, clinical and hospital characteristics.

Results:
Of 473 AIS patients, 72% were discharged to IRFs vs 27% to SNFs. IRF compared with SNF patients were 73 vs. 77 years, with 23% vs. 18% ambulating independently at hospital discharge. After IPW adjustment patients who received IRF care reported better QOL and were less likely to be institutionalized at 3- and 12-months than those who received SNF care but the difference in dependence was not statistically significant (Table). In sensitivity analyses among patients with a NIHSS score, QOL at 3-months was significantly better for IRF compared with SNF patients with no other differences between groups.

Conclusions:
AIS patients referred to IRFs had higher QOL at 3-months and lower odds of institutionalization at 3 and 12 months post stroke compared with patients referred to SNFs. Further research is needed to discern the mechanisms for potential differences in patient reported outcomes between settings.
Abstract TMP39: Brain FLAIR Ischemic Lesion Burden as a Biomarker of Intracranial Atherosclerosis in SAMMPRIS
Authors: Liebeskind David S , Woolf Graham W , Cotsonis George A , Scalzo Fabien , Prabhakaran Shyam , Romano Jose G , López-Cancio Elena , Lynn Michael J , Derdeyn Colin P , Fiorella David J , Turan Tanya N , Chimowitz Marc I , Feldmann Edward ,   for the SAMMPRIS Investigators
Published: March 2022

Background:
FLAIR lesion burden is an established biomarker in small vessel disease. To examine its role in intracranial atherosclerosis, we studied ischemic lesion burden throughout the brain at baseline or enrollment in the SAMMPRIS trial and also on serial MRIs in the medical arm, investigating its relationship with recurrent stroke.

Methods:
We performed blinded measurement of lesion burden on baseline and followup FLAIR and DWI images. Baseline FLAIR and DWI lesion volume and FLAIR vascular hyperintensities (FVH) were analyzed with respect to baseline variables including prior history, co-morbidities and angiographic measures and also correlated with subsequent ischemic stroke in the territory of the stenotic artery.

Results:
Of 451 SAMMPRIS subjects, baseline MRI included DWI in 309 (69%) with FLAIR in 293 (65%). Ischemic lesion burden on baseline FLAIR was median 2.7 cc (0-87.0) cc, with greater extent in those older than 60 years (p=0.03) and those on anti-thrombotics (p=0.01). Increased FLAIR lesion burden showed a trend towards worse collateral status by angiography (p=0.10). The presence of FVH in 72/194 (37%) anterior circulation stenoses reflected more robust collateral status (p=0.002). Corresponding baseline DWI lesion volume was median 5.16 cc (range 0-71.8). Baseline FLAIR lesion burden predicted subsequent stroke in the territory (HR 1.028 [95% CI 1.013-1.043], p=0.0002) in both medical and endovascular therapy arms, whereas baseline DWI size was not predictive of subsequent stroke in the territory. Serial FLAIR in the medical arm revealed interval burden growth in 31/47 (66%), whereas only 13/47 (28%) had clinical stroke outcomes.

Conclusions:
FLAIR MRI is a potent biomarker of ischemic lesion burden that reflects prior strokes and collateral status. Baseline FLAIR lesion burden throughout the brain may identify stroke risk in intracranial atherosclerosis. “Silent” ischemic lesion progression on serial MRI in this study may have clinical sequelae, such as cognitive impairment, and deserves greater scrutiny.
Abstract TMP4: Early Statin Intervention Can Reduce Progression in Acute Lacunar Stroke -An Analysis Using Propensity Score
Authors: Fukuma Kazuki , Yamagami Hiroshi , Toyoda Kazunori , Nagatsuka Kazuyuki
Published: March 2022

Background and Purpose:
Some patients with lacunar infarction show clinical neurological deterioration within few days after the onset. Otherwise, it is presumed that statins might prevent progression in acute lacunar stroke by its beneficial pleiotropic effects. We investigated whether early statin intervention (ESI) can reduce the early neurological deterioration and recurrence in acute lacunar stroke .

Methods:
We retrospectively studied 345 consecutive patients (217 men; mean age, 72 years) with a lacunar infarction admitted within 72 hours after the onset between Jan 2011 and Dec 2013 in our center. Of these, 151 patients (43.8 %) were treated with ESI (ESI group), defined as newly initiated statin (138 patients), dose-escalation of pre-treated statin (3 patients) or switching to strong statin (10 patients) within 72 hours after the onset. Progressive infarction (PI) was defined as an increase of ≥ 4 points in the NIHSS score or recurrence of symptomatic ischemic stroke within 30 days after the onset. Inverse probability of treatment weighting (IPTW) and propensity score-matching analysis were performed due to assess the association between ESI and PI.

Results:
Thirty-one patients (9.0%) had PI, 28 (8.1%) with neurological deterioration and 3 (1.0%) with symptomatic recurrence. PI of 10 patients (6.6 %) occurred in the ESI group and 21 patients (10.8%) in the non-ESI group (P = 0.18). Multivariable analysis showed that ESI was inversely related to PI (OR: 0.32; 95% CI: 0.12-0.81, P=0.02]. After adjustment with IPTW, PI was significantly less in the ESI group than non-ESI group [OR: 0.26; 95% CI: 0.10-0.68, P<0.01]. Propensity score matching yielded a well-balanced cohort of 182 patients (91 pairs with and without ESI). In this population, ESI was inversely associated with PI [OR: 0.36; 95% CI: 0.13-0.99, P=0.048]. Additionally, propensity score-matching analysis in the patient who had not received statin prior to admission (244 patients), newly initiated statin treatment was inversely related to PI [OR: 0.13; 95% CI: 0.02-1.00, P = 0.049].

Conclusion:
ESI was related to reduction in early neurological deterioration and recurrence in acute lacunar stroke.
Abstract TMP41: Assessment of Internal Carotid Artery Stenosis on CT-Angiography - Manual versus Semi-automated Vessel Analysis Software Measurements
Authors: Barlinn Kristian , Floegel Thomas , Kitzler Hagen H , Kepplinger Jessica , Siepmann Timo , Pallesen Lars-Peder , Bodechtel Ulf , Puetz Volker
Published: March 2022

Introduction:
To determine the diagnostic agreement between manual and semi-automated vessel analysis software measurements of extracranial internal carotid artery (ICA) steno-occlusive disease on CT-angiography (CTA).

Methods:
We studied consecutive patients with acute cerebral ischemia who were admitted (01/2012 to 12/2012) to our academic stroke center and underwent CTA for routine evaluation of stroke. NASCET-type percent stenosis was independently assessed on axial CTA source images by 1) manual caliper measurements and, 2) the semi-automated vessel analysis software syngo®.via (Siemens Healthcare, Germany) that provides area stenosis estimates. To correspond to clinically relevant NASCET strata, all stenosis measurements were stratified into ranges: normal, 1-49%, 50-69%, 70-99%, and occlusion.

Results:
A total of 330 patients (age 72±12yrs; 58% men; median NIHSS 4, interquartile range 8) provided 647 vessel pairs for comparative analysis. Manual caliper measurements revealed 50-69% stenosis in 29, 70-99% stenosis in 6 and occlusion in 34 internal carotid arteries, while semi-automated vessel analysis detected 50-69% stenosis in 27, 70-99% stenosis in 14 and occlusion in 34 internal carotid arteries (p=0.003). Bland-Altman analysis showed a mean difference of 1.55% in the degree of stenosis between both methods with lower and upper limits of agreement of -16.7 to 19.8%.

Conclusions:
Although we found an overall good agreement between both stenosis grading methods, the semi-automated vessel software analysis seems to overcall the stenosis in severe ranges when compared with manual caliper measurements.