bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 129: Optogenetic Inhibition of Striatal Neurons Improves the Survival of Implanted Neural Stem Cell and Neurological Outcomes After Ischemic Stroke
Authors: Lu Yifan , Jiang Lu , He Xiaosong , Yang Guo-Yuan , Wang Yongting
Published: March 2022

Background:
Administration of neural stem cell (NSC) into peri-infarct region is a promising treatment to improve the outcome after brain ischemia. However, whether the survival of implanted NSC is influenced by endogenous neuronal activity remains unclear. Using optogenetic technique, we regulated the activity of striatal neuron and investigated whether the excitation or the inhibition of striatal neuronal activity could improve NSC survival and overall neurological outcome.

Methods:
Adeno-assosiated virus carrying ChR2 or ArchT gene under the control of promoter CaMKII was injected into mice striatum two weeks before the surgery of 60 minutes transient middle cerebral artery occlusion (tMCAO). NSCs cultured from transgenic mice expressing fluorescent protein or isometric phosphate buffer saline was transplanted into peri-infarct region at striatum at 4 days after tMCAO. The striatal neurons were stimulated 15 minutes daily by 473nm pulse or 530nm constant laser via implanted optical fiber from 7 to 13 days after tMCAO. Neurological severity score (NSS) was assessed at 3 and 14 days. After sacrificing the animals at 14 days after tMCAO, brain infarct volume was measured with cresyl violet staining. The fluorescence intensity and the diffuse area of implanted NSC were calculated to evaluate the survival of NSC.

Results:
Mice received NSC transplantation and optogenetic inhibition showed smaller infarct volume compared to that only received NSC transplantation or PBS (p<0.05). The fluorescence diffuse area of transplanted NSC was larger in mice with optogenetic inhibition than that without optogenetic inhibition (p<0.05). Mice received NSC transplantation and optogenetic excitation had larger infarct volume and higher NSS than mice only received NSC transplantation (p<0.05), but showed no differences compared to mice received PBS (p>0.05). The fluorescence diffuse area and the mean optical density of transplanted NSC was smaller in mice with optogenetic excitation than that without optogenetic excitation (p<0.05).

Conclusion:
Inhibition of striatal neuronal activity at sub-acute phase after ischemia can improve the treatment of implanted NSC. To the opposite, excitation of striatal neuronal activity can reduce the NSC treatment.
Abstract 130: Induced Neural Stem Cell Treated Stroke Pigs Show Improved White Matter Integrity and Brain Metabolism Post-ischemic Stroke
Authors: West Franklin D , Platt Simon R , Holmes Shannon P , Wang Liya , Lau Vivian W , Baker Emily W , Grace Harrison E , Howerth Elizabeth W , Duberstein Kylee J , Stice Steven L , Hess David C , Mao Hui
Published: March 2022

Recent studies in rodent stroke models have shown that induced pluripotent stem cell derived neural stem cells (iNSCs) can lead to a significant decrease in lesion size, immune response and improvement in functional deficits. These improvements are linked to the iNSC potential dual mode of action as they can perform as a cell replacement therapy and produce neuroprotective and regenerative signaling. These results are promising yet the vast majority of therapies developed in rodent stroke models have failed to translate in clinical trials; suggesting that iNSC therapy should be tested in a more human like model such as the pig. We hypothesize that iNSC treatment will lead to improved white matter integrity, brain metabolism and cerebral blood flow (CBF) as determined by magnetic resonance imaging and spectroscopy (MRI and MRS) in stroked pigs. Eight male landrace pigs underwent middle cerebral artery occlusion stroke surgery. After 5 days, 4 pigs received iNSCs intraparenchymal injections and 4 pigs received vehicle only injections. Pigs underwent MRI and MRS assessment at 24 hrs post-injury and 1, 4 and 12 wks post-injection. MRI results at 24 hrs showed that all pigs had an ischemic stroke. At 1 wk post-injection, fractional anisotropy measurements of white matter integrity showed the affected side of the brain was 71% and 52% of normal, non-treated and treated respectively. At 12 wks, iNSC treated pigs showed a significant improvement in FA at 93% of normal, while non-treated pigs showed no improvement. MRS results demonstrated a significant decrease in NAA, Cr and Cho at 1 wk post-injection in treated and non-treated pigs. However, treated pigs showed a significant improvement in NAA, Cr and Cho at 12 wks post-injection, while non-treated pigs showed no improvement. At 12 wks, ischemic tissue in iNSC treated pigs had trending increases in CBF, while non-treated pigs showed no improvement. These results demonstrated that iNSC treated stroke pigs show improved white matter integrity, brain metabolism and CBF post-ischemic stroke and that iNSCs may one day be a viable clinical option for human stroke patients.
Abstract 131: Effect of Fetal Alcohol Exposure on Stroke Severity and Blood Flow in Adult Mice
Authors: Bake Shameena , Miranda Rajesh , Sohrabji Farida
Published: March 2022

Background and Purpose:
Metabolic and cardiovascular disease in later life may have developmental origins. The present study specifically tested the hypothesis that fetal alcohol exposure (FAE) will persistently influence blood flow in adulthood and result in greater impairment following ischemic stroke.

Methods:
Timed-pregnant C57Bl/6 female mice (GD12) were intragastrically gavaged with ethanol (3g/kg/bwt) or water twice per day from GD12 through 15. At 3 months of age, FAE and control males and females were subject to high-resolution ultrasound pulsed-wave Doppler imaging to record blood flow in carotid, abdominal, renal and femoral arteries. Blood flow was quantified. Thereafter, mice were subjected to middle cerebral artery occlusion (MCAo) using an intraluminal filament and sacrificed at 24 h post-stroke. Stroke induced brain damage was assessed by behavioral assays (adhesive tape test), neurological score and infarct volume.

Results:
Blood flow measurements indicated that fetal alcohol exposure increased acceleration in renal lobar arteries of ethanol exposed females (P<0.003), indicating that alcohol exposure may lead to impairment vascular tone and early signs of hypertension in end organs like kidney. In animals subject to MCAo, FAE adults exhibited greater neurological deficits at 24h post-stroke, as determined by their higher scores on a combination of different parameters of motor impairment and behavioral measures (neurologic score) compared to controls (P<0.0004). Sensorimotor deficits assessed by sticky tape test also showed that fetal alcohol exposed animals were severely affected (p<0.05) indicating that developmental alcohol exposure can impair adaptation in adult brain to an acute neural damage. There is also a significant correlation between the neurological scores and infarct volume in FAE females (p<0.05) but not FAE males, suggesting sex differences in response to FAE modify the relationship between stroke and outcomes.

Conclusions:
Our findings support a hypothesis that fetal alcohol exposure has long lasting and sexually dimorphic effects on adult health, resulting in impaired renal blood flow and poor stroke outcomes.
Abstract 137: Gastrointestinal Bleeding in Acute Ischemic Stroke: A Nationwide Inpatient Sample Study
Authors: Rumalla Kavelin , Reddy Adithi Y , Berger Paul A , Mittal Manoj K
Published: March 2022

Introduction:
Gastrointestinal bleeding (GIB) has been reported as a complication in acute cerebrovascular ailments. Here, we examined the incidence, risk factors, and outcomes of GIB in acute ischemic stroke (AIS) using the largest all-payer inpatient database in the U.S.

Methods:
The Nationwide Inpatient Sample (2002-2011) was queried to identify all adult patients with a primary diagnosis of AIS both with and without a secondary diagnosis of GIB. We utilized multivariate analyses, adjusting for patient and hospital factors, to identify risk factors for GIB in AIS patients and to determine the effect of GIB on in-hospital complications and outcomes.

Results:
Of 3,988,667 patients admitted with AIS, there were 49,348 cases of GIB (1,237 per 100,000 patients) with 25.7% receiving blood transfusions. Multivariate analysis revealed several independent predictors of GIB in AIS: age 55-64 (OR: 1.39, 95% CI: 1.33-1.45), age 65-74 (OR: 1.52, 95% CI: 1.44-1.59), age 75+ (OR: 1.79, 95% CI: 1.71-1.88), alcohol use (OR: 1.23, 95% CI: 1.17-1.30), coagulopathy (OR: 1.69, 95% CI: 1.62-1.77), cancer (OR: 1.70, 95% CI: 1.60-1.80), fluid/electrolyte disturbance (OR: 1.91, 95% CI: 1.87-1.96), liver disease (OR: 2.44, 95% CI: 2.29-2.60), and history of peptic ulcer disease (OR: 2.47, 95% CI: 2.13-2.86) (all p<0.0001). Administration of thrombolytic therapy decreased the likelihood of GIB by 10% (p<0.0001). In further multivariate models, GIB was determined to be an independent predictor of septicemia (OR: 1.47, 95% CI: 1.39-1.55), gastrostomy (OR: 1.75, 95% CI: 1.70-1.81), pulmonary embolism (OR: 1.75, 95% CI: 1.55-2.00), intubation (OR: 2.04, 95% CI: 1.95-2.13), and blood transfusion (OR: 11.31, 95% CI: 11.00-11.63; all p<0.0001). The occurrence of GIB increased hospital length of stay by an average of 5.8 days and total costs by $14,120 per patient (all p<0.0001). GIB was independently associated with a 46% increased likelihood of severe disability and 82% increased likelihood of in-hospital death (all p<0.0001).

Conclusion:
Age and several preexisting comorbidities are strong risk factors for GIB in AIS. GIB occurrence precipitates further in-hospital complications and adverse clinical outcomes in AIS, significantly increasing disability and mortality.
Abstract 140: Incidence of Stroke in and Around Pregnancy: A UK Population-based Cohort Study
Authors: Ban Lu , Sprigg Nikola , Abdul Sultan Alyshah , Nelson-Piercy Catherine , Bath Philip M , Tata Laila J
Published: March 2022

Introduction:
There are very few population-based studies on the incidence of stroke in women of childbearing age, stratifying by stroke types and pregnancy-related periods.

Methods:
We used an open cohort study design including all women aged 15-49 years from UK linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records in 1997-2014. The exposure of our study was pregnancy resulting in a live or a stillbirth and associated antenatal and postpartum periods. The outcome of the study was the first ever stroke diagnosis, defined using ICD-10 codes (I60-I64, O22.5 and O87.3) or relevant Read codes, and classified as having ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) or unspecified. We calculated the absolute rates of stroke per 100,000 person-years and 95% confidence intervals (95%CI) for different exposure periods. We stratified the analysis by maternal age and types of stroke.

Results:
Of 2,047,858 women, we identified 336,957 women with 453,776 deliveries. There were totally 2,526 women with a first incidence of stroke: IS 1,140 (45.1%), SAH 684 (27.1%), ICH 368 (14.6%) and unspecified 334 (13.2%). The overall incidence rate of stroke was 24.9 (95%CI 23.6-26.2) per 100,000 person-years in the non-pregnant period (IS 11.2 [10.4-12.1], ICH 3.6 [3.2-4.2], SAH 6.8 [6.2-7.5] and unspecified 3.3 [2.9-3.8]). The incidence was however higher around delivery (281.9 [141.6-561.2]) and in the first six weeks postpartum (43.8 [25.3-75.9]) and the rate ratios compared to the non-pregnant period after adjusting for age were 19.2 (9.6-38.3) and 3.0 (1.7-5.2) respectively.

Conclusions:
Although the incidence of stroke for young women was relatively low, the incidence around delivery or in the early postpartum was significantly higher compared to other periods, regardless of maternal age.
Abstract 145: MiR-15a/16-1 Mediates Blood-Brain Barrier Dysfunction in Ischemic Stroke
Authors: Zhu Tianqing , Song Jun , Hamblin Milton H , Chen Y E , Yin Ke-Jie
Published: March 2022

The blood-brain barrier (BBB) maintains a stable brain microenvironment, and is a primary target of ischemic stroke. Breakdown of BBB integrity has been shown to initiate a devastating cascade of events and eventual neuronal loss in cerebral ischemia. Thus, it is important to identify mechanisms by which BBB integrity can be maintained or loss of BBB integrity can be reduced under ischemic stroke conditions. MicroRNAs (miRs) function as a novel class of small noncoding RNAs that negatively modulate protein expression. We and others have recently shown the involvement of miRs in the pathogenesis of ischemic brain injury. However, the functional significance and molecular mechanisms of miRs in regulating cerebrovascular pathology are poorly understood in ischemic stroke. In this study, we investigate the essential role of the miR-15a/16-1 cluster in the regulation of post-ischemic BBB dysfunction. We demonstrated that expression of the miR-15a/16-1 cluster is significantly increased in the cerebral vasculature and cultured BMECs after
in vivo
and
in vitro
ischemic stimuli. EC-selective miR-15a/16-1 genetic deficiency leads to reduced BBB leakage and smaller brain infarct in mice after middle cerebral artery occlusion (MCAO). In contrast, EC-selective miR-15a/16-1 transgenic overexpression aggravates BBB damage and brain infarct. Mechanistically, we found that the miR-15a/16-1 cluster can bind to the 3’-UTRs of major BBB tight junctions, Claudins, and inhibit their translation. Genetic manipulation of miR-15a/16-1 level by lentivirus significantly alters the expression of Claudin 2, 5 and 12 in BMECs under the Oxygen Glucose Deprivation (OGD) conditions. Accordingly, EC-selective miR-15a/16-1 transgenic overexpression remarkably inhibits cerebral expression of Claudins in mice following MCAO. These findings suggest that the miR-15a/16-1 cluster functions as a novel master regulator in BBB pathologies and increases brain injury after ischemic stroke. Elucidating the molecular mechanisms of miR-15a/16-1-mediated BBB dysfunction may lead us to discover novel pharmaceutical targets for the development of effective therapies against ischemic stroke.
Abstract 157: Hyperintense Acute Reperfusion Marker is an Important Risk Factor of Stroke Recurrence in Patients With Transient Ischemic Attack
Authors: Yum Kyu Sun , Chang Jun Young , Chung Jin-Heon , Yeo Min-Ju , Hong Jeong-Ho , Shin Dong-Ick , Han Moon-Ku
Published: March 2022

Objectives:
Diffusion weighted MRI image (DWI) improves the prediction of the early risk of stroke after transient ischemic attack (TIA). Hyperintense acute reperfusion marker (HARM) is occasionally observed in patients with TIA. The predictive value of HARM in TIA is not well known.

Methods:
This is a retrospective study of patients who were diagnosed as TIA. From June 2008 to June 2014, 759 consecutive patients with TIA underwent DWI and axial postcontrast fluid attenuated inversion recovery images (FLAIR) within 24 hours after onset of symptoms. Presence of positive DWI findings, HARM on postcontrast FLAIR image, atrial fibrillation (AF), other risk factor of cardioembolic stroke, and recurrence of stroke were assessed.

Results:
DWI and HARM was positive in 276 (36.4%) and 28 (3.7%) patients. 45 (5.9%) patients had AF and 123 (16.2%) patients were diagnosed cardioembolic TIA. Recurrence of stroke was higher in patients with HARM (25.0%) than patients with DWI (6.5%) and lesion negative TIA (5.1%). Cardioembolic TIA (26.1% vs 10.3%) and AF (11.6% vs 2.6%) were common in patients with DWI than lesion negative TIA significantly. There were no statistically significant difference of cardioembolic TIA (14.3% vs 26.1%) and AF (3.6% vs 11.6%) between HARM and DWI group.

Conclusion:
TIA with HARM is associated with the high risk of stroke recurrence. Taking postcontrast FLAIR image improves the prediction of the risk of stroke after TIA.
Abstract 162: Sustained Improvement of Door-to-Needle Times Using Toyota's LEAN Manufacturing Principles: The Washington University Experience 2003-15
Authors: Panagos Peter , Williams Jennifer , Sampson Tomoko , Khoury Naim , McCammon Craig , Heitsch Laura , Lee Jin-Moo , Ford Andria
Published: March 2022

Background and Purpose:
Earlier tissue-type plasminogen activator (tPA) treatment for acute ischemic stroke (AIS), demonstrated by fast door-to-needle times (DNTs), leads to improved patient outcomes. Discrete interventions can improve DNTs, but often this improvement is not sustained over the long term.

Hypothesis:
LEAN quality improvement methodology can sustain and improve DNTs over a course of decade.

Methods:
Since 2003, a multidisciplinary quality improvement team has been continually monitoring and modifying the tPA protocol to eliminate inefficiencies using LEAN tools such as value stream analysis or rapid improvement events. We report our quality metrics (DNT, onset-to-treatment time (ONT), NIHSS, symptomatic intracranial hemorrhage (sICH) and favorable discharge clinical outcomes) as they relate to specific LEAN events.

Results:
Over a 10-year period, process improvement events have dramatically accelerated DTN times for AIS patients in a single hospital ED. The first event in 2004 (resident-based protocol) led to 25% improved DNT (81 vs. 60, P<0.001). In 2011, a new protocol (routing patients directly to CT, using parallel process workflow, and point-of-care labs) improved DNTs 35% (60 vs. 39 minutes, P<0.0001). Finally, in 2014 a treat-in-CT protocol was adopted and lowered DNTs 24% (38 vs. 29 min, P=0.002), for overall 58% improvement in DTN since 2004 (P<0.0001). To ensure efficiency gained was not at the expense of patient safety, sICH, favorable discharge location and percentage of stroke mimics (available only since 2011) were compared and did not differ over time.

Conclusions:
Application of LEAN and ongoing process improvement measures led to sustained improvement in DNTs for over a decade without compromising safety.
Abstract 174: Development of a Novel Anti-inflammatory and Anti-osteoplastic Peptide Based on De-loop and Ef-loop in Rankl for Treatment of Ischemic Stroke
Authors: Kurinami Hitomi , Shimamura Munehisa , Nakagami Hironori , Shimizu Hideo , Koriyama Hiroshi , Kawano Tomohiro , Mochizuki Hideki , Morishita Ryuichi
Published: March 2022

Background & Purpose:
We previously showed that stimulation of RANKL (receptor activator of nuclear factor-B ligand)/ RANK (receptor for RANKL) signal with recombinant RANKL worked as protective in ischemic brain through inhibiting TLR signaling pathways. However, augmentation of RANK signaling is also causative for increasing osteoclast differentiation and osteoporosis. To overcome the problem, we developed a novel RANKL-based peptide, which is anti-inflammatory and anti-osteoclastic.

Methods:
We made four peptides: MHP1 with complete DE loop and 66.7% of EF loop including complete βE and 72.3% of βD; MHP2 with complete DE loop, 22.2% of EF loop, and 10% of CD loop including complete βE and βD; MHP3 including complete CD loop and DE loop including complete βD; MHP4 including complete DE loop and βD. The action of the peptides were evaluated in MG6 cells, RAW 264.7 cells, primary osteoclast precursor cells, and 40 min-transient cerebral artery occlusion (tMCAo) model in C57BL6/J mice.

Results:
In LPS-stimulated MG6 and/or RAW 264.7 cells, MHP1 and MHP2 inhibited expression of IL-6 and TNFα, whereas MHP3 and 4 showed no effects. Knocking down of RANK revealed that the effects of MHP1 was dependent on RANK signaling, indicating that some components of DE loop, EF loop, βD, and βE in RANKL were required to show the anti-inflammatory effects in TLR4-induced inflammation. The anti-inflammatory effect was also effective in TLR2/6-induced inflammation but not RAGE-dependent inflammation, suggesting that effects of MHP1 might be specific TLRs signaling. In primary osteoclast precursor cells, MHP1 did not stimulate osteoclast differentiation and also inhibited RANKL-induced osteoclast differentiation. In the ischemic mice, the i.c.v. injection of MHP1 at 4 hrs after the ischemia showed less infarct volume and less activated microglia/macrophages in ischemic brain at 72 hrs after ischemia.

Conclusions:
Thus, MHP1 has a unique property, such as stimulation of RANK related anti-inflammatory signaling with inhibitory effects for RANK-induced osteoclast differentiation. This indicated that MHP1 could be one of novel candidates for preventing inflammation and osteoporosis in ischemic stroke.
Abstract 176: Clinical and Imaging Characteristics Associated With Poor Outcomes in Patients Not Thrombolysed Due to Mild or Rapidly Improving Symptoms
Authors: Ali Syed F , Siddiqui Khawja , Shinohara Yuki , Ay Hakan , Singhal Aneesh , Viswanathan Anand , Silverman Scott , Rost Natalia , Lev Michael , Schwamm Lee
Published: March 2022

Introduction:
Several studies have reported poor outcomes in patients “too good to treat” with tPA (TGTT) due to mild or rapidly improving symptoms. We sought to evaluate clinical and imaging factors associated with poor outcomes in these patients

Methods:
Using our institutional GWTG stroke registry, we analyzed 4,745 consecutive stroke admissions (2009-2015). Univariate and multivariable analysis determined factors associated with poor outcome (i.e., not being discharged home).

Results:
Of the total 4,745 patients, there were 380 TGTT patients’ symptoms. Of these, 67.8% were discharged home, 25.1% to inpatient rehabilitation, 4.2% to a skilled nursing facility and 2.9% expired/hospice. Patients with poor outcome were older, more often Hispanic had more vascular risk factors and higher median NIHSS. Imaging characteristics associated with poor outcomes included large, multifocal or insular infarcts and proximal occlusion or poor collaterals. In multivariable analysis, age, Hispanic ethnicity, diabetes, NIHSS, and infarct distribution (posterior/anterior+posterior) remained significant.

Conclusion:
A substantial percentage of patients deemed “too good” for IV tPA were unable to be discharged home. Factors such as advanced age, stroke risk factors, higher NIHSS and infarct location independently predicted poor outcome in patients who are considered TGTT and could be considered in tPA decision-making to optimize outcomes.
Abstract 182: The CLEAR Trials: A Pooled Analysis of rt-PA plus Eptifibatide for Treatment of Acute Ischemic Stroke
Authors: Cornwall Danielle , Khoury Jane , Pancioli Arthur , Schmit Pamela , Sucharew Heidi , Broderick Joseph , Adeoye Opeolu
Published: March 2022

Background:
The Combined approach to Lysis utilizing Eptifibatide And Rt-PA in Acute Ischemic Stroke (CLEAR), CLEAR-Enhanced Regimen (CLEAR-ER) and CLEAR-Full Dose Regimen (CLEAR-FDR) trials were phase 2 trials that examined escalating doses of recombinant tissue-type plasminogen activator (rt-PA) combined with eptifibatide in acute ischemic stroke (AIS). We pooled data from these trials and compared outcomes of the escalating doses of rt-PA plus eptifibatide to rt-PA alone.

Methods:
The combination arms of the CLEAR trial were: tier 1 - 0.3mg/kg of rt-PA and tier 2 - 0.45mg/kg both combined with eptifibatide 75mcg/kg bolus and 0.75mcg/kg/min for 2 hours. CLEAR-ER combined 0.6mg/kg of rt-PA and 135mcg/kg bolus of eptifibatide and 0.75mcg/kg/min for 2 hours. CLEAR-FDR combined full dose rt-PA (0.9mg/kg) and 135mcg/kg bolus of eptifibatide and 0.75mcg/kg/min for 2 hours. The control groups for both CLEAR and CLEAR-ER received full dose rt-PA only. The primary outcome was 90-day modified Rankin score (mRS) of 0-1 or return to baseline. Logistic regression was used for the analysis.

Results:
A total of 247 subjects were available for analysis; 69 from the combination arm of CLEAR (29 in tier 1 and 40 in tier 2), 101 from the combination arm of CLEAR-ER, and 27 from CLEAR-FDR. Fifty rt-PA only subjects (25 from CLEAR and 25 from CLEAR-ER) served as controls. Characteristics and outcomes adjusted for age, sex, race, NIHSS and time to IV rt-PA are shown in the Table.

Conclusion:
In the CLEAR trials, eptifibatide added to rt-PA showed a progressive increase in odds of a favorable outcome, without safety concerns. A phase 3 trial of full dose rt-PA plus the eptifibatide dose used in CLEAR-ER and CLEAR-FDR is warranted to establish the efficacy of the combination for improving AIS outcome.
Abstract 186: PROs in Clinical Practice: SIS-16 Better at Detecting Change in Functional Status Than the Modified Rankin
Authors: Katzan Irene L , Thompson Nicolas , Uchino Ken
Published: March 2022

Background:
To evaluate the benefits of collecting patient-reported outcome measures (PROMs) in clinical practice, we assessed the ability of the SIS-16 to detect changes over time compared to the provider-reported modified Rankin scale.

Methods:
Observational cohort study of 3,308 ischemic stroke patients seen in a cerebrovascular clinic 9/14/12 - 6/16/15 who completed the routinely collected PROMs: Stroke Impact Scale 16 (SIS-16), EQ-5D, PHQ-9, PROMIS Physical Function (PF), and PROMIS Fatigue. Providers completed the NIHSS and modified Rankin (mRankin). We calculated spearman correlations for all outcome measures. For the 1,455 patients with ≥ 2 visits, we calculated the proportion with meaningful change (SIS-16 ≥8, PROMIS PF and Fatigue ≥ 5, NIHSS ≥2, mRankin ≥1, PHQ-9 ≥ 5, EQ-5D ≥ 0.11). To provide insight on whether changes seen in the SIS-16 and mRankin represented true change in patient status, we calculated the proportion of change in other measures among subgroups with change in SIS-16 and no change in mRankin and for those with a change in mRankin and no change in SIS-16.

Results:
Median SIS16 was 85.9, median mRankin was2. Correlations between mRankin and PROMs was highest for SIS-16 (r= -0.64). Of patients with worsening or improvement in SIS-16 and no change in mRankin, significantly more patients had worsening or improvement in other measures, respectively, compared to those with stable SIS-16 and mRankin. In contrast, in those with worsening or improvement in mRankin but no change in SIS-16, there was no corresponding increase in % with change in other measures compared to those with stable SIS-16 and mRankin. (Figure)

Conclusion:
PROMs provide additional information compared to the mRankin alone. Changes in the SIS-16 corresponded to changes in other outcome measures, while changes in mRankin did not. This may be due to better ability of SIS-16 to identify change in functional status.
Abstract 189: Mail Order Pharmacy Use is Associated with Greater Adherence to Secondary Preventive Drugs Among Stroke Patients
Authors: Neil William , Chew Chrislynn , Stapleton David B , Ovbiagele Bruce
Published: March 2022

Background:
Mail order pharmacies are increasingly being used to deliver medications for chronic disease management. Their use is linked to similar or even greater medication adherence than local pharmacy use. Medication adherence is associated with improved outcomes, including reduced cardiovascular events, health care costs, and mortality. We are unaware of any studies that have evaluated the association of mail order pharmacy use with drug adherence among stroke patients.

Objective:
To investigate whether stroke patients who use mail-order pharmacies were more likely to have good medication adherence than those who used local pharmacies.

Methods:
We conducted cross-sectional analyses of patients discharged with ischemic stroke from 24 hospitals who received a new anticoagulant and/or lipid-lowering medication between 31/DEC/2006 and 26/JUN/2015. We defined good adherence as medication availability at least 80% of the time (i.e, a continuous measure of medication gaps value of less than or = 20%) and compared adherence between mail-order users (at least 66% of refills by mail) and local pharmacy users (all refills in person). Adherence was calculated from the initial dispensing based on the average percentage adherence and days between fills.

Results:
A total of 48,746 eligible patients refilled an index medication. There were 205,085 prescriptions for statins (136,722 by pharmacy and 68,363 by mail), and 50,483 prescriptions for anticoagulants (34,682 by pharmacy and 15,801 by mail). Overall, patients were adherent 46.48% of the time if they picked up their prescriptions from the pharmacy versus 73.87% of the time if they had their prescriptions mailed to them (p <.0001). Compared with those who only used local pharmacies, patients who received medications by mail were more likely to have good adherence to lipid modifiers (87.61% vs. 56.4%, OR 5.43, 95% CI = 5.3 - 5.57, p < .0001) and anticoagulants (44.88% vs. 56.16%, OR 1.57 95% CI 1.52 - 1.63, p < .0001).

Conclusions:
Stroke patients who obtain medication by mail are more likely to have good medication adherence than those who obtain them from local pharmacies. Future studies should examine the impact of mail-order pharmacy use on vascular risk marker control and events after stroke.
Abstract 191: Development and Validation of a Novel Risk Score for Assessing Risk of In-hospital Seizure Following Aneurysmal Subarachnoid Hemorrhage
Authors: Jaja Blessing N , Schweizer Tom A , Macdonald R. L ,   SAHIT Collaborators
Published: March 2022

Introduction:
A simple tool that could support individualized approach to anticonvulsant prophylaxis during hospital admission in patients with subarachnoid hemorrhage (SAH) would have clinical utility. This study was aimed at developing such a tool.

Methods:
We developed a risk score in 1500 patients from the SAH outcomes project of Columbia University, and validated it in 825 patients derived from the Washington University Database of SAH including patients from the CONSCIOUS 1 trial. Candidate predictors were identified by systematic review of literature and included in a backward stepwise logistic regression model with in-hospital seizure as dependent variable. The performance of the risk score was assessed using the area under the receiver operator characteristics curve (AUC) and calibration plots.

Results:
The SAFARI score (Seizure AFter aneurysmal subarachnoid hemorrhage RIsk score) based on four items including age > 60 years, seizure occurrence prior to hospitalization, aneurysm location and hydrocephalus had AUC = 0.77 (95% Confidence Intervals [CI]: 0.73 – 0.82) in the development cohort. In the validation cohort, the AUC was 0.65 (95% CI: 0.56 – 0.73). Calibration plots demonstrated excellent agreement between observed and predicted risk of in-hospital seizure.

Conclusions:
We have developed a simple tool for predicting the likelihood of seizure during hospitalization for SAH. The SAFARI score could be helpful to guide treatment choices regarding the use of anticonvulsants during admission, and to optimize patient enrolment for clinical trials evaluating seizure management after SAH, among other benefits.
Abstract 200: Collaterals in SWIFT PRIME: Imaging Correlates and Ultimate Impact
Authors: Liebeskind David S , Raychev Radoslav , Nogueira Raul G , Sanossian Nerses , Goyal Mayank , Mattle Heinrich P , Siddiqui Adnan H , Levy Elad I , Saver Jeffrey L , Albers Greg W , Jahan Reza ,   for the SWIFT PRIME Investigators
Published: March 2022

Background:
The overwhelming benefit of endovascular stroke therapy established in recent trials fueled by rapid workflow, modern devices and favorable noninvasive imaging profiles newly question the impact of collateral grade. We analyzed the SWIFT PRIME trial to evaluate the role of collaterals with respect to advanced imaging selection, the pace of infarct growth and ultimate clinical outcomes.

Methods:
Conventional angiography of the endovascular arm in SWIFT PRIME (n=98) was reviewed by 3 independent readers that scored ASITN/SIR collateral flow grade, followed by consensus adjudications. Angiographic collaterals were scored only when available, prior to use of the Solitaire stent retriever. Statistical analyses investigated the relationship of collateral grade with clinical and imaging variables in the main trial dataset.

Results:
70 endovascular arm subjects (mean age 65.2±12.1 years, 35 (50%) women) had angiographic collaterals scored by 3 independent readers (
W
=0.93). Pretreatment CT or MR perfusion imaging was obtained in 92% of cases, associated with a relatively wide range of angiographic collateral grades (1, n=6 (9%); 2, n=25 (36%); 3, n=37 (53%); 4, n=2 (3%)) with a preponderance (79%) of M1 occlusions. Worse collaterals were associated with prior myocardial infarction (33% (grade 1), 8% (grade 2), 3% (grades 3, 4); p=0.03) but unrelated to age, sex, or other co-morbidities or time from stroke onset. Baseline ASPECTS (median 9, r=0.20) trended higher (p=0.09) in those with more robust collaterals. Collaterals were unrelated to degree of TICI reperfusion, yet the presence of distal emboli at procedure end was linked with worse collaterals (p=0.008). More robust collaterals exhibited a potent and graded link with better day 90 mRS (r=- 0.3, p=0.03) and lower mean NIHSS at 27 hours (r=-0.3, p=0.03), whereas infarct growth at 27 hours was unrelated (r=-0.07, p=0.60).

Conclusions:
Use of advanced noninvasive perfusion imaging enrolls patients with more robust collateral grades, yet a diverse range of collaterals may be seen. Even with rapid workflow, mismatch based selection and successful reperfusion, the degree of angiographic collaterals continues to be strongly associated with clinical outcomes at all timepoints.
Abstract 206: High False Positive Rates of Atrial Fibrillation Detection Among Stroke Patients who Receive Medtronic Implantable Loop Recorders
Authors: Maddox Spencer , Hoskins Michael , Lloyd Michael , Mengistu Andenet , Rangaraju Srikant , Henriquez Laura , Davis Brittaine , Nahab Fadi
Published: March 2022

Introduction:
Atrial fibrillation is a known risk factor for the development of stroke. Implantable loop recorders (ILRs) have specific algorithms to detect occult atrial fibrillation and can be used in patients with cryptogenic stroke. There is limited data on the frequency of false positive atrial fibrillation detected by the Medtronic ILR.

Hypothesis:
Medtronic ILRs have a high rate of false positives but despite this are still effective at detecting atrial fibrillation in patients with cryptogenic stroke.

Methods:
All stroke patients who underwent ILR placement from Jan 1, 2013 to June 30, 2015 were prospectively collected through an administrative database. Baseline and clinical characteristics were retrospectively obtained. A random sampling of ILR tracings identified as atrial fibrillation by the Medtronic algorithm was adjudicated by a board certified electrophysiologist for accuracy.

Results:
Among 52 patients with a history of ischemic stroke or TIA (mean age 68±14 years, 58% male, 83% white), there were 166 rhythm strips identified as atrial fibrillation by the Medtronic algorithm which were adjudicated. Of the 166 strips reviewed, 140 (84%) were incorrectly identified as atrial fibrillation; of those false positives, adjudication identified 57% as premature atrial complexes(PACs), 22% as T wave over-sensing, 10% due to noise, 5.0% due to premature ventricular complexes (PVCs), 2.9% due to under-sensing, and 2.9% due to sinus arrhythmia. Of the 38 (73%) patients who had ILR implantation for cryptogenic stroke, 4 (11%) were identified as having true atrial fibrillation by ILR after adjudication over 413 patient-months of monitoring; mean time to atrial fibrillation detection was 93 days after implantation.

Conclusions:
Stroke patients who undergo Medtronic ILR placement have high false positive rates of atrial fibrillation detected with the Medtronic algorithm. When adequately reviewed by a trained cardiologist for accuracy, the Medtronic ILRs remain effective at detecting atrial fibrillation in cryptogenic stroke patients.
Abstract 209: High Yield of Long-Term Implantable Cardiac Monitoring Following Cryptogenic Ischemic Stroke
Authors: Schneider Jordana S , Burshtein Reuben D , Golyan Daniel , Kahen Michael , Arora Rohan , Salamon Elliott , Wright Paul , Libman Richard B , Katz Jeffrey M
Published: March 2022

Introduction:
Long-term post-hospitalization cardiac monitoring has detected occult paroxysmal atrial fibrillation and atrial flutter (PAF) in a substantial minority of cryptogenic ischemic stroke (CIS) patients. Herein, we aim to better define the frequency and clinical significance of PAF detection using the Reveal LINQ insertable cardiac monitor in a population of CIS patients treated at a comprehensive stroke center.

Methods:
A retrospective consecutive series of CIS patients (n=95; mean age 65.9 years; 56.8% female) with no prior history of PAF had a LINQ placed during the index hospitalization, or soon thereafter, following a negative stroke evaluation. The study cardiac electrophysiologist confirmed the presence of PAF, and other potentially relevant cardiac arrhythmias, and the characteristics of the episodes and any changes in management were recorded.

Results:
PAF was detected in 22/95 patients (23.2%; atrial fibrillation (AF) 13; atrial flutter (A-flutter) 6; both 3). Median time to first episode was 26 days (range less than 1 day to 398 days). Median longest episode duration for AF was 2.4 hours (range 6 minutes to greater than 99 hours) and for A-flutter was 49 seconds (range 5 to 174 seconds). Antiplatelet therapy was switched to anticoagulation in 20/21 (95.2%) patients with known follow-up, including all newly diagnosed AF patients. Additional potentially relevant arrhythmias included sinus bradycardia (5/95; 5.3%), sinus pauses (5/95; 5.3%) and bigeminy (7/95; 7.4%).

Conclusions:
LINQ insertion during, or soon after, in-hospital stroke evaluation detected PAF in a substantial proportion of CIS patients with a higher frequency and earlier detection than previous studies. Most episodes were deemed clinically relevant, resulting in anticoagulation initiation in almost all patients. Long-term invasive cardiac monitoring following CIS may have important implications in terms of secondary stroke prevention and the detection of other potentially relevant arrhythmias.
Abstract 216: Incidence and Severity of Catheter Tract Hemorrhage and EVD Placement Accuracy in the CLEAR-III Trial
Authors: Mould W. Andrew , Müller Achim , Ziai Wendy , McBee Nichol , Lane Karen , Awad Issam , Hanley Daniel
Published: March 2022

Introduction:
CLEAR III trial is a multicenter, double-blind, randomized trial comparing external ventricular drainage (EVD) plus intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD plus placebo for treatment of IVH in patients with obstructive IVH and intracerebral hemorrhage (ICH) volume <30cc. New hemorrhage along the catheter tract (CTH) associated with EVD placement is known to occur but magnitude and significance of CTH is not well understood. We investigated incidence and severity risk factors for CTH in the CLEAR-III trial.

Methods:
Retrospective analysis of 4698 CT scans from EVD placement through EVD removal in all 500 patients enrolled in CLEAR III. CTH was characterized using an ordinal severity scale and quantified using both manual and threshold based segmentation to calculate a volume. EVD location was graded using a modification of the Kakarla scale for each CT scan. Demographic and clinical data were assessed for pre-specified associations.

Results:
Incidence of CTH was 44.8% (224/500) which included 318 CTHs (single:160 patients; two:51; three:8; four:8). CTH occurred within first 24 hours of placement in 102 (32%), after 24 hours in 132 (41%), after EVD repositioning/manipulation in 19 (6%), after EVD replacement in 15 (5%), and after EVD removal in 50 (16%). The mean CTH volume was 2.01 ml with a range of 0.1 ml - 57.95 ml. CTH volume was not associated with EVD accuracy, nor number of doses given but increased significantly with the number of catheters placed per patient (p<0.001). Furthermore, Grade 2 or 3 CTH (larger than trace, with or without edema) occurred in 31.8% and were significantly associated with lower platelet count (p=0.047) while grade 2/3 CTH on initial placement were significantly associated with pre-admission antiplatelet agent use (p=0.02).

Conclusion:
Our data suggest that EVD tract hemorrhages can occur at any point within the acute treatment period with varying severity. Hematologic factors, especially history of antiplatelet agent use may increase risk of larger potentially symptomatic CTH.
Abstract 218: Omega-3 Fatty Acid Supplement Prevents Progression of Intracranial Atherosclerosis
Authors: Stevenson James , Shen Jiamei , Geng Xiaokun , Li Fengwu , Wang Sainan , Narayanan Sandra , Ding Yuchuan
Published: March 2022

Introduction:
Intracranial atherosclerotic stenosis (ICAS) is a disease state that has been implicated as a leading cause of recurrent ischemic stroke. While popular media has promoted the use of omega-3 fatty acid (OFA) supplementation for its purported health benefits, few studies have looked at the molecular mechanisms at play within the cerebral vasculature. We adapted a rat model for atherosclerosis and applied it to the brain, for the first time to our knowledge, to study intracranial atherosclerosis (ICA). In this study we investigated the hypothesis that dietary supplementation of OFA attenuated the progression of ICA.

Methods:
Twelve week old male Sprague-Dawly rats were placed on a 1% cholesterol diet. During the first two weeks, NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL) was added to their drinking water to induce intimal changes making the rats susceptible to atherosclerosis. One group of rats had their diet supplemented with OFA (5mg/kg/day). Animals were sacrificed at three, six of supplementation. Histological sections of the brains were made to study middle cerebral artery (MCA) morphometry and intimal thickening was quantified by measuring lumen and vessel wall areas. Additionally at each time point blood lipids and glucose were measured before animal sacrifice.

Results:
The rats subjected to the high cholesterol diet and L-NAME administration displayed blood markers of atherosclerosis which became more severe in time. The levels of LDL, glucose, cholesterol, and triglycerides were significantly elevated compared to control. In the OFA treatment group, these biomarkers were dramatically attenuated. Furthermore, while the atherogenic treatment led to stenosis of the lumen and intimal thickening in the MCA, dietary OFA prevented these characteristic morphological changes, in which the infiltration of the vessel walls by macrophages was observed, supporting the antiatherogenic nature of this treatment.

Conclusions:
Long term dietary supplementation with OFA thwarts the development of ICA. It prevents the infiltration of the vessel walls by macrophages thus reducing inflammation and intimal thickening. Omega-3 fatty acids are an inexpensive and widely available dietary supplement which shows promise in preventing ICAS.
Abstract 24: Using a Tele-Presence Platform as a Neuro-ICU Nursing Education Tool: a Collaboration Between Two Comprehensive Stroke Centers
Authors: LaBella Giuliana , Pavlish Nikki , Hollup Nicole , Houser Jessica , Lockhart Dana , Randazzo Salvadore , Vibbert Matthew , Urtecho Jacqueline , Caliguri Dennis , DePrince Maureen
Published: March 2022

Background and Purpose:
Many authors have reported the effectiveness of telemedicine in healthcare and medical education. There has been limited research addressing its use with nursing education. We sought to examine the impact and effectiveness of education in the Neuro-ICUs of two Comprehensive Stroke Centers.

Methods:
Guided by a knowledge needs assessment completed by critical care nurses at an academic medical facility in Louisiana, a topic of Intracranial Pressure Crisis in Hemorrhagic Stroke was chosen for an educational course conducted via telepresence. The Neuro-ICU nurses from an academic medical facility in Pennsylvania developed the course content. The course consisted of a 10 questions pre-test, a 30 minute didactic session, an interactive case scenario, and a 10 question post-test. The didactic session reviewed basic neuro pathophysiology and interventions to treat increased intracranial pressure. The interactive case scenario used 3G simulation to allow real time implementation of interventions to treat increased intracranial pressure in the setting of hemorrhagic stroke. The session concluded with a debriefing and post- test. The entire session was completed using telepresence. 15 ICU nurses participated in the course. Participants subsequently completed an anonymous survey. Results of the pre- and post-test were compared via a paired-samples t-test.

Results:
The mean pre-test score was 7.5/10 (sd 2.378). The mean post-test score was 9.57/10 (sd 1.089). This represents a significant improvement (t=3.64, p= 0.003). All course participants completed the anonymous survey. 89% of participants felt that tele-education was a valuable learning tool. 100% agree that they will change their current bedside practice based on the information provided during the tele-education session.

Conclusion:
These results demonstrate improved knowledge in the management of elevated intracranial pressure. A tele-presence platform may be an effective means of delivering of educational content to neuro ICU nurses separated by geographic barriers.
Abstract 39: Systematic Review of Radiographic and Symptomatic Brain Infarcts in Carotid Artery Interventions
Authors: Cho Sung-Min , Deshpande Abhishek , Hernandez Adrian , Uchino Ken
Published: March 2022

Introduction:
Reports vary in incidence of silent brain infarcts after cardiovascular and cerebrovascular procedures. In a systematic review we compared rates of radiographic brain infarcts (RBI) and clinical strokes among different carotid artery procedures: carotid endarterectomy (CEA), and carotid stenting (CAS) with or without protection devices.

Methods:
We searched MEDLINE and 4 other databases for subject headings and text related to brain infarcts in carotid artery interventions from inception through February 2015. We included articles with carotid interventions if brain MRI was performed systematically, RBI and stroke incidence were reported, and compared infarct rates between different devices in CAS.

Results:
Of 6332 articles retrieved, 65 studies (5982 patients) met the inclusion criteria. There were 26 cohorts in CEA, 39 in CAS with distal protection, 8 in CAS with proximal protection with or without flow reversal, 10 in CAS with unspecified devices and 10 in CAS without protection. MRI diffusion-weighted imaging scan was performed pre-procedure in 64 studies and post-procedure in all 65 studies. Overall, 1761 subjects (29.4%) had infarcts on MRI, whereas only 191 (3.2%) manifested as clinical strokes. Only 11% of subjects with infarcts were found to have clinical strokes and the rate did not differ between 36 studies that determined strokes systematically and the remainder without systematic examination. CEA had lower incidence of RBI compared to CAS (15.9% (239/1524) vs 34.0% (1522/4482), p<0.001) but not of strokes (2.5% (37/1500) vs 3.4% (154/4482), p=0.07). RBI incidences differed among embolism protection methods in CAS: 24.3% (70/288) in proximal protection, 35.7% (740/2075) in distal protection, 32.6% (489/1502) in unspecified devices, and 36.1% (223/617) without protection; incidence of stroke were not significantly different among the procedures with 2.4% (7/288), 3.3% (69/2075), 3.1% (46/1502), and 5.2% (32/617), respectively.

Conclusion:
Only 1 of 9 periprocedural radiographic infarcts during carotid endarterectomy or stent result in clinical strokes. CEA has a lower incidence of RBI compared to CAS.