bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P66: White Matter Hyperintensity Volume Predicts Long-Term Full Recovery in Patients with Mild Acute Ischemic Stroke
Authors: Cougo-Pinto Pedro T , Cloonan Lisa K , Kanakis Allison , Fitzpatrick Kaitlin , Furie Karen , Rosand Jonathan , Rost Natalia
Published: March 2022

Background/Objective:
Severity of white matter (WM) disease has been implicated in cerebral tissue and clinical outcomes of patients with acute ischemic stroke (AIS). We sought to assess whether WM disease burden is an independent predictor of outcome in patients with mild AIS and its effect on intravenous tissue plasminogen activator (IV TPA) treatment in this population.

Methods:
Patients with a National Instituted of Health Stroke Scale (NIHSS) score <8 (“mild AIS”) and acute brain ischemia on diffusion-weighted MRI were selected from the hospital-based, prospective AIS cohort. Normalized White Matter Hyperintensity Volumes (nWMHV) were obtained using a validated, semi-automated volumetric measurement tool. Bivariate and multivariate regression analyses were performed to identify independent predictors of full recovery on follow-up modified Rankin Scale (mRS) at 90 days. Interaction between nWMHV and IV TPA was tested in multivariate regression analysis.

Results:
Of 465 patients with mild AIS, 29 (6%) received IV TPA and 128 (33%) achieved full recovery (mRS 0) outcome. On bivariate analysis, greater nWMHV and admission NIHSS, as well as presence of hypertension, diabetes mellitus (DM), hyperlipidemia and prior stroke were associated with long-term persistence of symptoms (p<0.05). In multivariable analysis, higher admission NIHSS (OR 0.83, 95% CI 0.74-0.93), history of DM (OR 0.46, 95% CI 0.24-0.84) and prior stroke (OR 0.30, 95% CI 0.13-0.64), as well as increasing quartiles of nWMHV (OR 0.48, 95% CI 0.25-0.92) independently decreased the odds of favorable outcome. There was no interaction between nWMHV and IV TPA treatment (p=0.96).

Conclusion:
Patients with mild AIS often have worse functional outcomes than expected. Our data indicate that severe WM disease is an independent predictor of long-term full recovery in mild AIS, and nWMHV might be a useful tool to use for prognostic stratification and to gauge therapeutic intervention in this challenging population. IV TPA should not be precluded in mild AIS patients based on WM disease burden.
Abstract W P67: Defining A Therapeutic Window For Successful Intravenous Fibrinolytic Therapy In Central Retinal Artery Occlusion: A Subject Level Meta-analysis
Authors: Schrag Matthew , Youn Teddy , Schindler Joseph , Kirshner Howard , Greer David M
Published: March 2022

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency which results in blindness in a high percentage of affected patients. A wide variety of treatment methods have been proposed to manage the resulting retinal ischemia; however, all but fibrinolysis have proven unsuccessful and fibrinolytic therapy, while promising, remains of unproven and controversial benefit. The purpose of the current analysis is to assemble the published literature on systemic fibrinolysis in CRAO at the subject level and compare the results against the natural history of this illness to determine a time-window of clinical effectiveness of fibrinolytic interventions for use in future clinical trials. Subject level data was obtained for 157 cases. We conclude that systemic fibrinolysis is likely to be beneficial in the first 4.5 hours after symptom onset (odds ratio 3.5 [95% confidence interval 1.8 to 6.9, p<0.001], 31.4% relative risk reduction with a number need to treat of 3.9 [95% confidence interval 2.4 to 10.7). We argue that a clinical trial of fibrinolytic therapy for CRAO in this time window is likely to be successful. Interestingly, we also found that the conventional treatment with ocular massage, hemodilution and/or anterior chamber paracentesis significantly worsen visual acuity outcomes after central retinal artery occlusion.
Abstract W P7: Intra-Arterial Therapy is Safe and Effective in Patients Aged ≥80
Authors: Frei Donald , Salottolo Kristin , Njau Grace , Fanale Christopher V , Wagner Jeffrey C , Whaley Michelle , McCarthy Kathryn , Loy David , Bar-Or David
Published: March 2022

Introduction:
Acute ischemic stroke (AIS) occurs most frequently in old age. Currently, conflicting evidence exists on the safety and efficacy of intra-arterial treatment (IAT) in the management of AIS in the elderly. We purported to compare the outcomes of patients ≥80 years receiving IAT after AIS to those of patients 55-79 years old. Methods: Data were retrospectively abstracted for consecutive AIS patients ≥55 years treated with IAT at an urban comprehensive stroke center between 2010 and 2013. The following outcomes were compared between patients 55-79 vs. ≥80 years following IAT: safety was assessed by incidence of sICH and in-hospital mortality; efficacy was examined using discharge mRS (favorable, ≤2) and improvement in NIHSS (decreased score at discharge). All analyses were performed with Pearson or Fisher’s exact chi-square tests. The subset of patients receiving IAT only was also examined. Results: IAT was performed in 300 patients, of which 241 were aged ≥55 and comprise our study cohort; of the 241, 104 received IAT only. There were no significant differences between the two age groups receiving IAT in race, presence of comorbidities and time to IAT while significant differences were observed for gender and NIHSS, with the ≥80 population presenting with lower mean stroke severity and more females (p <0.05 for both comparisons). Mortality and sICH rates were not significantly different following IAT between age groups, both in the overall cohort as well as the subset that received IAT only (table). Efficacy was similar between age groups in the overall cohort (table); in the subset that received IAT only, there was a trend towards a higher proportion of patients 55-79 years with improved NIHSS following treatment compared to those ≥80 years (p=0.07). Conclusion: These findings suggest that IAT is safe and effective in patients ≥80 years and age should not be used as a contraindication to IAT.
Abstract W P77: Ruptured Aneurysms Tend To Have Prominent Blood Flow Changes At Aneurysm Neck
Authors: Lau Vicki , Sayre James , Qi Tiewei , Chien Aichi
Published: March 2022

Introduction:
Hemodynamics is thought to play an important role in the pathogenesis, progression, and rupture of aneurysms. Reports have suggested that aneurysm rupture, regardless of aneurysm size, may be due to the collision of incoming flow forming a prominent jet stream directed towards the aneurysm head. The objective of this study was to gain insight into the effect of aneurysm neck, body, and dome cross section geometries on local flow rates.

Hypothesis:
Aneurysm neck, body, and dome cross section geometries affect local flow rates within the aneurysm head.

Methods:
Blood flow through the aneurysm neck, body, and dome were evaluated with respect to the cross section size of each region in 33 cases of ruptured posterior communicating artery aneurysms. Computational fluid dynamic analysis was performed and quantitative hemodynamic variables were extracted from the simulation results.

Results:
All aneurysms generally experienced similar incoming systole volumetric flow rates regardless of the inlet cross-section geometry. Aneurysms with smaller necks experienced greater and more uniform flow reductions than medium or large sized necks. The overall reductions of flow volume through the neck for small, medium, and large necks were 97.8 ±1.4%, 90.0 ±2.7%, and 41.1±22.4%, respectively. Blood flow through the aneurysm body was not affected by body size in small and medium cross sections but still appeared to have some dependence on the aneurysm neck size. Aneurysms with large body geometries, however, further experienced flow reductions of 99.1 ±0.43%. Aneurysm dome cross section size was not found to have a significant effect on volumetric flow rate.

Conclusion:
Regardless of shape, we found that certain aneurysm neck, body, and dome cross section sizes may have a large influence on flow reduction and energy transmission to the aneurysm apex. By analyzing a group of ruptured aneurysm cases, we found small aneurysms necks have the most drastic flow changes, indicating that aneurysm neck shape may be important for clinical assessment of rupture risk.
Abstract W P9: Recanalization in Wake-up Strokes
Authors: Huang Josephine F , Liebeskind David S , Saver Jeffrey
Published: March 2022

INTRODUCTION:
Current treatments for acute ischemic stroke are approved based on time of onset, providing a dilemma for stroke patients with unknown onset time. About 25% of patients present as wake-up strokes (WUS). Our aim was to identify characteristics associated with the clinical outcomes of WUS patients receiving acute revascularization therapies.

METHODS:
We retrospectively reviewed medical records of consecutive patients with ischemic stroke who received treatment at a large academic medical center from 1994-2014. We identified patients with symptoms upon awakening and those with indefinite time of onset presenting within 24 hours of last known normal time. Demographics, NIHSS, diffusion-weighted imaging-based Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS), treatment, and modified Rankin Scale (mRS) at 90-day follow-up were obtained. A good outcome was defined as 90-day mRS 0-2.

RESULTS:
Patients with unknown stroke onset time comprised 25.6% (90/351) of acute strokes treated in our series. Seventy-two were WUS, and 18 were indefinite time of onset not upon awakening. Median age was 70.5 (range 2-92), median NIHSS 13 (range 2-27), and median DWI-ASPECTS 8 (range 1-10). Large vessel occlusions were as follows: 39 M1 middle cerebral artery (MCA), 16 M2 MCA, 9 intracranial internal carotid artery (ICA), 8 basilar artery, 6 extracranial ICA, 2 M3 MCA, 2 distal MCA, 1 A2 anterior cerebral artery, 1 posterior cerebral artery, and 1 vertebral artery. Five cases did not have an occlusion. Forty-six were treated with thrombectomy, 11 with IV thrombolysis, 14 IA thrombolysis, 10 IA thrombolysis + thrombectomy, 3 IV + IA thrombolysis, 5 IV thrombolysis + thrombectomy, and 1 IV + IA thrombolysis + thrombectomy. Sixty-one patients had MRI on initial evaluation, and 51 (77%) had DWI-ASPECTS≥7. Of those, 16 (31.4%) had a good outcome at follow-up. Only 1 patient with DWI-ASPECTS<7 had good outcome, and 14/33 patients with DWI-ASPECTS≥7 had good outcome (p=0.04). Lower age (65 vs 74, p=0.03) was a predictor of good outcome at follow-up.

CONCLUSIONS:
Patients with anterior circulation strokes with unknown onset time and DWI-ASPECTS≥7 have potential for good outcome with acute treatment.
Abstract W P92: Attenuated GFAP/Vimentin Retards Motor Behavioral Recovery and Axonal Remodeling and Up-regulates Axonal Growth-Inhibiting Molecules in Mice After Stroke
Authors: Qian Jian Y , Chopp Michael , Li Yi , Cui Yisheng , Roberts Cynthia , Liu Zhongwu
Published: March 2022

To investigate whether reactive astrocytes contribute to neurological recovery, we compared behavioral outcome, axonal remodeling of the corticospinal tract (CST) and the levels of axonal growth-inhibiting/promoting molecules in the central nervous systems (CNS) between wild-type (WT) and glial fibrillary acidic protein/vimentin double knockout (GFAP-/-Vim-/-) mice subjected to Rose Bengal induced cerebral cortical photothrombotic stroke in the right forelimb motor area. Both foot-fault test and single pellet reaching test were performed prior to stroke and at 3 days after stroke and weekly thereafter, to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to label the CST axons anterogradely. Compared with WT mice, the motor functional recovery and BDA-positive CST axonal length in the denervated side of the cervical gray matter were significantly reduced in GFAP-/-Vim-/-mice (n=10/group, P<0.01). Western blot data (prior to and on 3, 7 or 14 days after stroke, n=6/group) showed that in GFAP-/-Vim-/- mice, axonal growth-inhibiting molecules, Nogo R and neurocan, were up-regulated time-dependently in the CNS compared with WT mice (P<0.01). However, no increase was detected in the expressions of Nogo A and Oligodendrocyte myelin glycoprotein (P>0.05). There was no difference in the levels of axonal growth-promoting molecules (Myelin-Associated Glycoprotein and phosphor-ERK) between GFAP-/-Vim-/-mice and WT littermates (p>0.05). Our results suggest that attenuated astrocytic reactivity impairs or delays neurological recovery by reducing CST axonal remodeling in the denervated spinal cord and increasing some axonal growth-inhibiting molecules in CNS. Manipulation of astrocytic reactivity post stroke may represent a therapeutic target for neurorestorative strategies.
Abstract W P95: Disordered Breathing in a Mouse Model of Ischemic Stoke
Authors: Patrizz Anthony , Kolb Adam , Mulkey Daniel , McCullough Lousie
Published: March 2022

Background:
Stroke induced respiratory dysfunction is a common complication after stroke prolonging recovery and increasing mortality. Animal models are lacking. Central chemoreceptors play a vital role in regulating breathing patterns in response to changes in CO2/H+. The retrotrapezoid nucleus (RTN) in the caudal brainstem contains a population of chemoreceptors that regulate frequency and tidal volume. Activity of these neurons may be regulated by KCNQ channels. We hypothesize that targeting KCNQ channels is a viable option for the treatment of stroke induced breathing disorders.

Methods:
Whole body plethysmography was performed on WT C57/B6 male mice to establish baseline frequency (BPM), tidal volume (TV), minute volume (MV), periods/durations of apnea and approximate entropy of the system (ApEn). Mice were then subjected to 90 minute MCAO or sham surgery. 72 hours after surgery whole body plethysmography was performed again to identify the stroke disordered breathing phenotype. Mice were randomly assigned to one of two treatment groups: Retigabine (a KCNQ channel activator) or saline at a dose of 50ul/10g SQ, respiratory activity was monitored during a 5 day drug treatment regime.

Results:
All MCAO-treated mice exhibited disordered breathing characterized by pronounced decrease in respiratory frequency (254.3 ± 15.8 vs.478.2 ± 24.5 BPM) and MCAO-treated mice showed lower ApEn values compared to Sham (0.64 ± .04 vs. 1.02 ± 0.09). There was also a trend for increased number of apneic events in post-stroke animals. No significant differences were observed in TV, suggesting the respiratory phenotype observed in MCAO mice is not due to phenomena. Systemic injection of retigabine suppressed basal respiratory activity of Sham and MCAO-treated animals.

Conclusions:
Our results suggest that ischemic stroke results in hypoventilation and decreased respiratory stability as evidenced by a decrease in ApEn. Further, considering that retigabine worsened stroke-disordered breathing also suggests that stroke-induced respiratory problems do not result from over activation of the chemoreflex as previously proposed.
Abstract W P96: Evidence of In Vivo Ischemic LTP Caused by Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Orfila James E , Deng Guiying , Herson Paco S , Quillinan Nidia
Published: March 2022

Objective:
Experience-dependent memory acquisition, in vitro tetanic stimulation and simulated ischemia results in long-term potentiation (LTP) of hippocampal CA1 synapses. The goal of this study was to determine whether in vivo cerebral ischemia results in iLTP of CA1 synapses. We hypothesized that iLTP resulting from CA/CPR prevents physiological LTP.

Methods:
Cardiac arrest (8 minutes) followed by cardiopulmonary resuscitation (CA/CPR) or sham surgery was performed on adult (8-12 week) male mice. Electrophysiology was performed in hippocampal slices from sham and 7 and 30 days after CA/CPR. Field excitatory postsynaptic potentials (fEPSP) resulting from Schaffer collateral stimulation were recorded and rising slope was analyzed. Theta burst stimulation (TBS) was used for LTP induction and low frequency stimulation for reversal of LTP (depotentiation). Western blot analysis of synaptic isolations were performed from hippocampi collected from shams and 7 and 30 days after CA/CPR.

Results:
TBS resulted in an increased fEPSP to 164±9.8% (n=7, P<0.05) of baseline in sham controls, however no increase was observed at 7 (106±15.9% n=4) and 30 days (109±13.9% n=7) after CA/CPR. A depotentiation stimulus had no effect in sham controls, but caused a reduction in fEPSP in control slices that received LTP induction and slices from CA/CPR mice. Importantly, LTP induction protocol applied subsequent to depotentiation stimulus resulted in physiological LTP to 126.9±11.8% (n=3) of the original baseline, an effective increase of approximately 40%. Glutamate receptor subunit GluR1 phosphorylation and expression in synaptic fractions were increased at 7 and 30 days after CA/CPR.

Conclusions:
Depotentiation in slices from CA/CPR mice suggests CA1 synapses are in a chronically potentiated state. Increased GluR1 phosphorylation and expression after CA/CPR also suggest in vivo ischemia causes iLTP. Our ability to induce physiological LTP after depotentiation in slices from CA/CPR suggests that reversing iLTP allows for normal synaptic plasticity. The results of this study are significant as they demonstrate in vivo iLTP and suggest a physiological stimulus has the potential to reverse synaptic impairments in the chronic phase after cerebral ischemia.
Abstract 104: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED): a Simple and Accurate Pre-hospital Scale to Detect Large Vessel Occlusion Strokes
Authors: Lima Fabricio O , Furie Karen L , Frankel Michael H , Silva Gisele S , Lev Michael H , Faye Érica C , Haussen Diogo , Singhal Aneesh B , Koroshetz Walter J , Smith Wade S , Nogueira Raul G
Published: March 2022

Background:
Intravenous tPA has a limited efficacy in large vessel occlusion strokes (LVOS). Thus LVOS patients may be better served by direct transfer to endovascular capable centers. We aimed to develop a field scale to identify LVOS.

Methods:
The FAST-ED scale was designed based on items of the NIHSS with higher predictive value for LVOS: Facial Palsy (scored 0-1), Arm Weakness (0-2), Speech Changes (0-2), Eye Deviation (0-2), and Denial/Neglect (0-2). The scale was tested in the STOPStroke cohort, a prospective study of patients who underwent CT angiography (CTA) within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the ICA-T, MCA-M1, MCA-2, or basilar arteries. Patients with partial, bi-hemispheric, and/or anterior + posterior circulation occlusions were excluded. Receiver operating characteristic (ROC) curve, sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of FAST-ED were compared with the Rapid Arterial oCclusion Evaluation (RACE) scale and Cincinnati Prehospital Stroke Severity Scale (CPSSS).

Results:
LVO was detected in 240 out of the 727 qualifying patients (33%). FAST-ED had a strong correlation with NIHSS (r=0.92; P<0.001). FAST-ED had comparable accuracy to predict LVO to the more complex NIHSS and higher accuracy than RACE and CPSS (area under the ROC curve: 0.81, 0.80, 0.77 and 0.75 respectively). Better performance of FAST-ED could be shown at two distinct thresholds depending on the desired sensitivity/specificity trade-offs with scores ≥3 and ≥4 having sensitivity for LVO of 0.71 and 0.60, specificity 0.78 and 0.89, PPV 0.62 and 0.72, and NPV 0.84 and 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, 0.79 and CPSS ≥2 of 0.56, 0.85, 0.65, 0.78, respectively.

Conclusions:
FAST-ED is a simpler field scale that can be used by medical emergency professionals to accurately identify LVOS in the pre-hospital setting enabling rapid triage of patients to primary vs. endovascular capable stroke centers.
Abstract 109: The Long-Term Risk of Seizures After Stroke
Authors: Merkler Alexander E , Dunn Lauren E , Lerario Michael P , Morris Nicholas A , Gialdini Gino , Kummer Benjamin R , Lahiri Shouri , Navi Babak B , Kamel Hooman
Published: March 2022

Introduction:
Few data exist on the long-term risk of seizures after stroke.

Hypothesis:
Stroke is associated with a similar long-term risk of seizures as compared with traumatic brain injury (TBI), a well-established long-term seizure risk factor.

Methods:
Using administrative claims data on all acute care hospitalizations and emergency department (ED) visits at nonfederal facilities in California, Florida, and New York from 2005-2012, we identified patients at the time of a first documented stroke. Stroke was comprised of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), as defined by previously validated ICD-9-CM codes. As a control group, we identified patients at the time of a first documented TBI. The primary outcome was an ED visit or hospitalization with a discharge diagnosis of seizure. In sensitivity analyses, we limited the outcome to primary discharge diagnoses of seizure or diagnoses of status epilepticus. Survival statistics and Cox proportional hazards analysis was used to compare the rates and hazard of seizures between groups while adjusting for demographic characteristics and Elixhauser comorbidities.

Results:
We identified 568,659 patients with stroke and 270,796 patients with TBI. During 2.5 (±2.1) years of follow-up, the cumulative risk of a seizure was 37.6% (95% confidence interval [CI], 37.3-37.8%) in patients with stroke and 29.9% (95% CI, 29.5-30.0%) in patients with TBI. After adjustment for demographic characteristics and comorbidities, stroke remained associated with a slightly higher hazard of seizures when compared with the risk after TBI (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13). This finding was unchanged in sensitivity analyses of only primary discharge diagnoses of seizure or only status epilepticus cases. In subgroup analyses, the cumulative rate of any seizure was 26.2% (95% CI, 25.6-26.9%) after SAH, 33.6% (95% CI, 33.4-33.7%) after ischemic stroke, and 35.0% (95% CI, 34.5-35.4%) after ICH.

Conclusions:
We found that a substantial proportion of patients with stroke develop a seizure. The long-term risk of seizure after stroke appears similar to that after TBI, which is widely recognized as a strong long-term seizure risk factor.
Abstract 11: Intra-arterial Infusion of Allogeneic Mesenchymal Stem/Stromal Cells is Safe and Enhances Histological Healing in Rabbit Elastase Aneurysms
Authors: Adibi Amin , Eesa Muneer , Sen Arindom , Mitha Alim P
Published: March 2022

Introduction:
Poor healing of coiled intracranial aneurysms results in recanalization and recurrence of the aneurysm in one in five patients. One recent study has shown that intra-arterial infusion of Mesenchymal Stem/Stromal Cells (MSCs) can stop dilation of experimental aneurysms in rabbits. Another study in a mouse model suggests that intravenous delivery of MSCs reduces the risk of aneurysm rupture. MSCs are known for their ability to establish a regenerative microenvironment by inhibiting inflammation, producing trophic factors, and recruiting local progenitors to replace lost cells. In this study, we have conducted a randomized preclinical trial to assess the potential of MSC therapy in improving the healing of coiled aneurysms.

Hypothesis:
Combined coiling and intra-arterial injection of 5 million allogeneic MSCs will be safe, and will result in superior histological healing of experimental elastase-induced aneurysms in rabbits at 4 weeks post-treatment.

Methods:
Bone marrow-derived MSCs were isolated from three rabbit donors in a serum-free fashion and were characterized individually. Elastase-induced carotid aneurysms were created in 9 New Zealand White Rabbits. Each subject was randomized to receive one of the following treatments: 1) coiling (treatment group), 2) coiling with an intra-arterial injection of saline solution (vehicle group) and coiling with an intra-arterial injection of 5 million allogeneic MSCs (treatment group). The animals were followed up for 4 weeks, at the end of which a final angiogram and histological analysis was performed.

Results:
Intra-arterial cell therapy with 5 million allogeneic MSCs did not result in any major adverse events. Histological results showed consistent superior healing in cell therapy group compared with vehicle and control groups. Angiographic results were not significantly different among different study arms.

Conclusions:
Intra-arterial MSC therapy for intracranial aneurysms is feasible, safe and effective at a proof-of-concept level.
Abstract 110: A Multicenter, Double Blind Trial to Evaluate the Efficacy of Escitalopram for the Prevention of Poststroke Emotional Disturbances, and for Improvement of Neurologic, Cognitive Function and Quality of Life (emotion)
Authors: Kim Jong S , Lee Eun-Jae , Chang Dae-Il , Park Jong Ho , An Seong-Hwan , Cha Jae Kwan , Heo Ji Hoe , Sohn Sung Il , Lee Byung-Chul , Kim Dong-Eog , Kim Hahn Young , Kim Seongheon , Kwon Do-Young , Kim Jei , Seo Woo-Keun , Lee Jun , Park Sang-Won , Koh Seong-Ho , Kim Jin Young , Choi-Kwon Smi
Published: March 2022

Background and hypothesis:
Post-stroke emotional symptoms are common and adversely influence the patients’ outcome. We aim to evaluate the efficacy of escitalopram in patients with acute stroke for the prevention of various emotional disorders, and for improvement of neurologic, cognitive function and patient quality of life.

Method:
In this multicenter, placebo-controlled, double-blind trial, 405 stroke patients (within 21 days after onset) were randomized either to the escitalopram (n = 217) (5 mg -10mg) or placebo (n = 188) for 3 months. Depressive symptoms (Montgomery-Asberg Depression Rating Scale [MADRS] and mini-international neuropsychiatric interview [MINI]), emotional incontinence (Kim’s criteria), anger proneness (Modified Spielberger trait), cognition (MOCA test), Modified Rankin scale (MRS), and quality of life (Stroke Specific QOL) were assessed initially, and at 3 and 6-months.

Results:
Baseline characteristics were similar between the groups. Proportions of patients with MADRS≥16, the primary outcome, were not different at 3-month (placebo vs. escitalopram group, 13.8% vs. 12.0%, p=0.579). However, new development of depression determined by MINI was lower in the escitalopram group (0 vs. 4 patients, P = 0.046). For the secondary outcomes, anger proneness score was lower in the escitalopram group (21.5 vs 20.1 at 3-month, P = 0.011). There were no significant differences in other items at 3-months: emotional incontinence (% of patients, 8.5% vs. 10.2%, p=0.565), MOCA score (21.1±6.8 vs. 20.9±7.2, p=0.704), MRS (3.1±1.2 vs. 3.0±1.3, p=0.822), and patient quality of life (165.0±38.8 vs. 166.7±39.1, p=0.667). When chronological changes of MADRS were analyzed after categorizing patients into normal (0-6), mild (7-15), and moderate/severe (≥16) depression groups, escitalopram significantly improved MADRS of patients with mild depression (10.30 to 7.23 vs. 10.91 to 5.06, p = 0.036).

Conclusion:
Escitalopram was not effective in the prevention of post-stroke depressive symptoms, and did not improve cognitive function, neurologic severity, and patient quality of life. However, it prevented development of depression defined by MINI, anger-proneness and seems to improve depressive symptoms in patients with mild depression.
Abstract 111: Factors Associated With New-onset Depression Following Ischemic Stroke: Results From the Women’s Health Initiative
Authors: Salinas Joel , Ray Roberta M , Nassir Rami , Lakshminarayan Kamakshi , Dording Christina , Smoller Jordan , Wassertheil-Smoller Sylvia , Rosand Jonathan , Dunn Erin C
Published: March 2022

Background:
Although poststroke depression is a common and devastating consequence of stroke, few studies have examined the occurrence and correlates of developing depression among stroke survivors without a history of depression before the stroke.

Hypothesis:
Using data on post-menopausal women from the Women’s Health Initiative (WHI), we estimated the odds of new-onset depression poststroke (NDPS) and assessed the associations of psychosocial and other factors with NDPS.

Methods:
We analyzed data from 1433 respondents who were stroke-free at enrollment and had no self-reported history of depression prior to their non-fatal ischemic stroke, and had information regarding stroke severity. NDPS was assessed in the five-year period after stroke using the Center for Epidemiologic Studies Depression Scale or new antidepressant medication use. Unadjusted 5-year depression rates are presented by demographic, comorbid, and psychosocial factors measured pre-stroke. Vascular territory of stroke is given by the Oxfordshire classification. Logistic regression provided odds ratios of NDPS controlling for multiple covariates.

Results:
New-onset depression post ischemic stroke occurred in 21.4% (306/1433) of the analytic cohort and varied by stroke outcome as measured by the Glasgow scale ranging from 16.7% of those with good recovery to 31.5% of those severely disabled. Women with total anterior circulation infarction had the highest level (45.8%) of NDPS while those with lacunar infarction had the lowest (19.1%). Among those with ischemic stroke and good recovery (n=754), moderate level of optimism was associated with a reduced odds of NDPS (compared to low optimism, OR, 0.29; 95%CI, 0.14-0.63) adjusting for demographics, behavioral factors, and comorbidities. Cynical hostility, social support, and traumatic life events were unassociated with NDPS.

Conclusions:
New-onset depression is common after ischemic stroke among post-menopausal women. Though rarely studied in poststroke depression, psychosocial factors (specifically optimism) may play a role in reducing risk for new-onset depression after stroke.
Abstract 113: Kentucky SEQIP Statewide Collaboration Improves TPA Administration Rates and Decreases Door to Needle Times
Authors: Moore Kari D , Bobo Bonita , Bellamy Lisa , Hollander Cathy , Hundley Lynn , Rock Peter , Block Starr
Published: March 2022

Background and Issues:
Despite consistent evidence that functional outcome and quality of life are improved with early administration of IV rt-PA, Kentucky continued to struggle with achieving door-to-needle (D2N) times within 60 minutes of hospital arrival. The Kentucky Stroke Encounter Quality Improvement Project (SEQIP) hospital group voluntarily collaborated to increase treatment rates for rt-PA and decrease D2N times through sharing of data, best practice and adoption of the Target: Stroke 10 Key Best Practice Strategies.

Purpose:
The aim of this project was to utilize and share evidence based practice models among certified stroke centers and those pursuing certification in Kentucky to improve rt-PA utilization and D2N times throughout the Commonwealth.

Methods:
A statewide quality improvement plan (QI) was developed and targeted toward improvement of stroke patient care with regard to rt-PA administration. Each facility committed to examine data and recruit teams to identify barriers and implement best practice strategies within the confines of available resources. Accountability was achieved with expected sharing of barrier solutions, best practices and ongoing Get With The Guidelines data tracking at face to face meetings.

Results:
SEQIP’s participating hospitals achieved improvement compared to 2009 baseline data. Between 2009 and 2014, SEQIP achieved a 25.2% increase in proportion of patients eligible to receive rt-PA (Arrive by 2, Treat by 3 Hours) (n=1387) from 60.4% to 85.7%. Additionally, SEQIP hospitals increased the proportion of eligible patients receiving rt-PA (D2N <60 minutes) from 22.3% to 75.5%, an increase of 53.2%. This resulted in a decrease in median door to needle time of 24 minutes (from 75 to 51 minutes). Statistically significant (p<0.001) improvements occurred in years 2012-2014 compared to baseline in both rt-PA administration and D2N.

Conclusions:
With deployment of a strategically targeted action plan and expected accountability, competing hospitals can collaborate on a statewide level. Sharing of best practice across organizations can empower stroke teams to implement the strategies that can be effective within the confines of their resources to achieve their goals.
Abstract 119: Can CREST Procedural Results be Reproduced in General Practice in Post CREST Era?: Analysis of National Surgical Quality Improvement Program (NSQIP) Registry
Authors: Jani Vishal B , Zafar Aiman , Afzal Mohammad R , Yousaf Muhammad H , Patel Achint , Qureshi Adnan I
Published: March 2022

Background:
The Carotid revascularization for primary prevention of stroke assessed in CREST trial (year 2010) revealed risk of the composite outcome of stroke, myocardial infarction, or death were almost similar in carotid artery stenting (CAS) and carotid artery endarterectomy (CEA) group. This study analyzed such current clinical practice and outcome (year 2011 to 2013) from multicenter national registry described below.

Methods:
Cohort of non-high risk patients who underwent targeted CAS or CEA were collected from American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Registry in post CREST era. This registry prospectively collects around more than 300 variables across the nation pertaining to patient characteristics, co-morbid conditions, operative details, and 30-day postoperative outcomes. Frequency analysis of such outcome was performed to assess the re-validation of CREST trial in current clinical practice.

Results:
In Post CREST NSQIP Registry we identified 142 (CAS) and 7834 (CEA) patients. In Post CREST era (current clinical practice) the rates of any stroke among CEA patients (1.9%, 95% CI 1.57-2.17, CREST Ref 2.3%) (p=0.25) and CAS patients (2.1%, 95% CI 0.54-5.75, CREST Ref 4.1%) (p=0.25) observed in clinical practice were comparable to those observed in CREST trial. The rates of MI/arrhythmia among CEA patients (1.7%, 95% CI 1.47-2.06, CREST Ref 2.3%) (p=0.22) and CAS patients (2.8%, 95% CI 0.89-6.79, CREST Ref 1.1%) (p=0.13) are comparable from CREST trial. The rates of 1 month mortality among CEA patients (0.6%, 95% CI 0.42-0.76, CREST Ref 0.3%) (p=0.27) and CAS patients (0.7%, 95% CI 0.04-3.47, CREST Ref 0.7%) (p=0.92) were also similar. The rate of cranial nerve injury in CEA patients has declined (2.1%, CI 1.83-2.47, CREST Ref 4.7 %) (p<0.0001).The combined primary endpoint for CEA patients (3.7%, 95% CI 3.32-4.17, CREST Ref 4.5%) (p=0.19) and CAS patients (5.6%, 95% CI 2.62-10.7, CREST Ref 5.2%) (p=0.81) was similar to CREST trial.

Conclusions:
Our results support reproducibility of CREST procedural outcomes for both CEA and CAS in general practice in post-trial period.
Abstract 125: Subacute Decline in Serum Cholesterol Precedes the Occurrence of Primary Intracerebral Hemorrhage: Results From a Longitudinal Study
Authors: Phuah Chia-Ling , Raffeld Miriam R , Ayres Alison M , Biffi Alessandro , Gurol M. Edip , Viswanathan Anand , Greenberg Steven M , Rosand Jonathan , Anderson Christopher D
Published: March 2022

Introduction:
Dyslipidemia plays a paradoxical role in some forms of cerebrovascular disease. Unlike its relationship with ischemic stroke, hypercholesterolemia has been associated with reduced risk of intracerebral hemorrhage (ICH). However, serum lipid levels have wide variation coefficients, and point estimates are likely not representative of long-term exposures. Understanding the temporal trends in serum lipid levels and their association with ICH may improve understanding of the biology of dyslipidemia in ICH. We sought to determine the course of temporal variations in total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG) and high-density lipoprotein (HDL) over 48 months before and after primary ICH.

Methods:
We performed a single-center retrospective longitudinal case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a clinical data registry of patients hospitalized for acute non-cerebral events. Piecewise linear mixed-effects models were used to compare the impact of ICH or hospitalization on lipid trends.

Results:
212 ICH cases and 301 control subjects were analyzed. Overall trends in serum TC and LDL levels differed between ICH subjects and non-ICH controls (p<0.0001). ICH subjects experienced significant decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 to 24 months pre-ICH (TC: -29.25mg/dL, p=0.001; LDL: -21.48mg/dL, p=0.0038), which were not observed in non-ICH controls (TC: -4.32mg/dL, p=0.41; LDL: -1.56mg/dL, p=0.85). Subgroup analysis confirmed that this phenomenon could not be attributed to statin or alcohol exposure. Trends for serum TG and HDL did not differ between groups.

Conclusions:
Longitudinal serum TC and LDL levels demonstrate decline within 6 months preceding primary ICH, independent of statin or alcohol use. Subjects hospitalized for non-cerebral events did not exhibit this phenomenon. These temporal trends suggest changes in serum TC and LDL levels herald a generalized process that may precipitate ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury.
Abstract 128: Human Tau Protects Ischemic Brain Injury
Authors: Ren Xuefang , Hu Heng , Lewis Sara E , Hunsberger Holly , Reed Miranda , Simpkins James W
Published: March 2022

Stroke is a complex vascular and neurological syndrome that can lead to death and disability. The primary stroke injury is induced by the occlusion of directly supplied artery, and the secondary brain damage could be affected by the synaptic connections with the primary ischemic lesion. Tau protein is a microtubule associated cytoskeletal protein, expressed predominantly in neurons of the central nervous system. Tau protein plays a role in maintaining synaptic neuronal integrity and axonal transport, including promoting microtubule assembly and modulating stability of microtubules, which are regulated by tau phosphorylation state. Phosphorylated tau protein is induced by stroke. To investigate the role of human Tau protein in stroke, we employed female mice overexpressing normal human Tau (rTg(Tau)21221), female mice overexpressing P301L mutant human tau (rTg(TauP301L)4510, and age-matched female littermate wild type (WT) controls at 12 months old. Transient middle cerebral artery occlusion (tMCAO) was performed on diestrus as identified by virginal smears microscopically. Following a mild stroke injury of 30 min tMCAO, overexpression of normal human Tau significantly reduced infarction at 48 hours of reperfusion (P = 0.0157); following a moderate stroke injury of 60 min tMCAO, overexpression of normal human Tau also resulted in significantly reduced infarction compared to WT controls and mice expressing human tau with the P301L mutation (P = 0.0142). These novel data suggest that normal human Tau plays a protective role in acute stroke and support the view of targeting human tau as a new treatment for acute stroke.
Abstract 136: Stroke Incidence in the Greater Cincinnati/ Northern Kentucky Stroke Study is Decreasing Significantly in Men but Not Women
Authors: Madsen Tracy E , Khoury Jane C , Alwell Kathleen A , Moomaw Charles J , Flaherty Matthew L , Woo Daniel , Mackey Jason , Martini Sharyl , Ferioli Simona , Adeoye Opeolu , Kissela Brett M , Kleindorfer Dawn
Published: March 2022

Introduction:
It is widely accepted that stroke incidence is higher in men than women. Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent.

Methods:
Within our population of 1.3 million, all strokes among area residents (≥20 years old) were ascertained at all local hospitals during 7/93-6/94 and calendar years 1999, 2005 and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Only first-ever strokes were included in this analysis. Sex-specific incidence rates were adjusted for age and race, standardized to the 2000 U.S. Census population, and reported per 100,000. Trends over time by sex were compared between first and last study periods; a Bonferroni correction was applied for multiple comparisons.

Results:
Across all study periods, there were 7710 incident strokes (ischemic, ICH, and SAH); 57.2% (n=4412) were women, and 19.2% (n=1482) were black. Mean age for women was 71.6 (SD 15.1) vs. 67.3 (SD 14.1) for men (p<0.001). Incidence of all strokes and of ischemic strokes decreased over time in men (p<0.001, p<0.01) but not significantly in women (p=0.15, p=0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010 (p=0.50, p=0.31) (Table)). ICH and SAH incidence did not decrease significantly over time in women (p=0.99, p=0.70) or men (p=0.46, 0.16).

Conclusions:
The decrease in stroke incidence over time appears to be driven by a decrease in incidence of ischemic stroke in men. Contrary to previous data, stroke incidence rates were similar in men and women at the end of our study period. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men than in women and whether the current trend for men will be reflected in women after 2010.
Abstract 138: Dolichoectasia of the Basilar Artery is Associated With Cerebral Small Vessel Disease and Microbleeds in Young TIA and Ischemic Stroke Patients
Authors: Thijs Vincent , Grittner Ulrike , Fazekas Franz , McCabe Dominick , Giese Anne-Katrin , Kessler Christoph , Martus Peter , Norrving Bo , Tanislav Christian , Ringelstein Bernd , Tatlisumak Turgut , Rolfs Arndt , Enzinger Christian ,   SIFAP1 Investigators
Published: March 2022

Background and purpose:
Intracranial dolichoectasia is associated with markers of cerebral small vessel disease in older stroke patients. We evaluated whether this holds true for dolichoectasia of the basilar artery in younger stroke patients.

Methods:
We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young (<55 years) TIA/stroke patients in whom detailed clinical data and brain MRI were obtained and stroke subtyping with the TOAST classification was performed. MRI analysis was performed by three experienced readers blinded to clinical and demographic data. The tortuosity of the basilar artery (BA) was rated as none, mild (some tortuosity of BA with a deviation from the midline of > 5 mm to ≤ 10mm), moderate (deviation of BA from midline by > 10 mm and / or diameter > 5mm); or severe (tortuosity with impression of brainstem and /or diameter > 10 mm). The maximum BA artery diameter was also directly measured at its maximum on axial MRI scans. Dolichoectasia was defined in this study as a moderate to severe tortuosity of the BA.

Results:
Dolichoectasia was found in 508 of 3850 (13.2%) of patients. Dolichoectasia was associated with increasing age (odds ratio per decade, 1.26, 95% confidence interval 1.09-1.44), male sex (1.96 [1.59-2.42] and hypertension (1.39, [1.13-1.70]). Dolichoectasia was more common in patients with small infarctions (33.9% vs. 29.8% for acute lesions, p=0.065; 29.1% vs. 16.5% for old lesions, p<0.001), infarct location in the brainstem (12.4% vs. 6.9%, p<0.001), and in white matter (27.8% vs. 21.1%, p=0.001). Microbleeds (16.3% vs. 4.7%, p=0.001), higher grades of white matter hyperintensities (p<0.001) and small vessel disease subtype (18.1% vs. 12.4%, overall p for differences in TOAST: p=0.018) were more often present in patients with dolichoectasia.

Conclusion:
Dolichoectasia is common and is associated with imaging markers of small vessel disease, as well as brainstem localization of acute and old infarcts in younger patients with TIA and ischemic stroke.
Abstract 139: Relative Improvements in Country-level Measures of Stroke Mortality, Incidence, and Disability From 1990 to 2010 are Associated With Higher Baseline Gross National Income Per Capita
Authors: Kim Anthony S
Published: March 2022

Background:
Age-standardized mortality and disability burden from stroke has been improving on a global level, but these improvements have been uneven across nations.

Hypothesis:
Higher gross national income per capita is strongly associated with relative improvements in stroke indicators on a national level.

Methods:
We conducted an ecological analysis using estimates of age-standardized stroke indicators (Global Burden of Disease Study 1990 and 2010), non-communicable disease risk factor data (WHO Global Health Observatory), and gross national income per capita estimates (World Bank). We generated choropleth maps to highlight outliers with changes that differed from global trends. We evaluated the association between gross national income per capita and changes in risk factors burden and age-standardized mortality, incidence, mortality incidence ratio, and DALY losses from stroke over 20 years.

Results:
Of the 186 countries with available data, most experienced a decrease in age-standardized stroke mortality (164; 88%; mean decrease 23%), mortality incidence ratio (175; 94%; mean decrease 25%), and stroke DALY losses (168; 90%; mean decrease 27%) but not stroke incidence (76; 40%; mean increase 10%) over 20 years (Figure). Relative improvements in mean systolic blood pressure (p<0.0001), mean serum cholesterol (p<0.0001) and smoking prevalence (p=0.006) were associated with higher gross national income, but not mean fasting serum glucose (p=0.43). Relative improvements in age-standardized mortality, incidence, mortality incidence ratio, and DALY losses for stroke tracked with higher income per capita (Cuzick’s test of trend, p<0.001 for each indicator).

Conclusion:
Incidence, mortality, and DALY burdens from stroke are higher in low-income countries, but the greatest relative improvements in these indicators over the past 20 years have been in high-income countries.
Abstract 142: Extended Therapeutic Window of a Novel Peptide Inhibitor of TRPM2 Channels Following Focal Cerebral Ischemia
Authors: Cruz-Torres Ivelisse , Strnad Frank A , Shimizu Takeru , Traystman Richard J , Quillinan Nidia , Herson Paco S
Published: March 2022

Introduction:
Recent data demonstrates that inhibition of TRPM2 channels protect the brain against ischemia, specifically in males. A major hindrance to our research has been the lack of specific TRPM2 inhibitors. The current study characterized the specificity and neuroprotective efficacy of a novel TRPM2 inhibitor developed in our laboratory.

Methods:
Fluorescent calcium imaging was used to determine inhibitor efficacy of the TRPM2 peptide inhibitor (tat-M2NX) in HEK293 cells stably expressing hTRPM2. tat-peptides were detected by immunohistochemistry using an anti-tat antibody. Adult (2-3 mo) and aged (18-20 mo) were subjected to 60 min middle cerebral artery occlusion (MCAo) and injected iv with tat-M2NX (20 mg/kg), control tat-SCR (20 mg/kg) or clotrimazole (CTZ) (30 mg/kg) either 20min prior or 3hr after reperfusion. Infarct size was assessed using TTC staining.

Results:
Successful TRPM2 inhibition in HEK293 cells was observed by decreased Ca2+ influx following H2O2 exposure. Male mice pre-treated with tat-M2NX had smaller infarct volume compared to tat-SCR; 29.2±4.6% (n=8) vs. 43.4±3.2% (n=8; p<0.01), respectively. No effect of tat-M2NX was observed in female mice. Immunostaining demonstrates tat-M2NX accumulation in striatal and cortical neurons 4-6 hours of IV injection. Importantly, male TRPM2-/- mice were not further protected by tat-M2NX, demonstrating selectivity of our new inhibitor. Administration of tat-M2NX at a delayed time point (3hr) provided significant protection to males when analyzed at 24 hr (28.33 ± 5.1% (n=7) vs. 46.45 ± 3.0% (n=6; p<0.01) or 4 days after MCAo (23.84 ± 4.416, (n=8) vs. 41.41 ± 2.831; (n=8; p<0.01). In contrast, delayed administration of CTZ failed to reduce infarct volume. Finally, we observed that tat-M2NX reduced ischemic injury in aged male mice.

Conclusions:
These data demonstrate the development of a new peptide inhibitor of TRPM2 channels that provides protection from ischemic stroke in young adult and aged male animals with a relatively wide therapeutic window. Furthermore, we took advantage of TRPM2-/- mice to confirm specificity of tat-M2NX protection.