bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP574: Persistent Glial Activation in the Forceps Minor of Corpus Callosum is Associated With Impairment in Paired-Associate Learning
Authors: Chow Wei Zhen , Walker Frederick Rohan , Ong Lin Kooi , Nilsson Michael
Published: January 2019

Two-thirds of stroke survivors experience cognitive impairment which reduces the quality of life by affecting the ability to return to work and social participation. Our understanding of the neuropathology of cognitive impairment post-stroke is limited, hence requires clarification in order to design interventions to improve cognitive function after stroke. We hypothesize that inflammation in one or more brain regions regulating paired-associate learning (PAL) contributes to visuospatial impairment after stroke. Focal ischemia was induced in the prefrontal cortex at the somatosensory and motor cortex using photothrombosis in eight weeks old C57BL/6 male mice. We assessed visuospatial function daily at 22 weeks post-stroke using PAL task performed on the mouse touchscreen platform (Campden Instruments Ltd, UK). Tissue loss in the medial prefrontal cortex, corpus callosum and hippocampus was calculated using Nissl-stained brain sections. Changes in neuronal, astrocyte and microglia markers were measured in the peri-infarct and associated brain regions using western blot. At 27 weeks post-stroke, stroke mice had significantly lower mean correct rate in PAL compared to sham (57.1% vs 69.1%, p=.032). Significant tissue loss was identified in the ipsilesional hemisphere and corpus callosum in stroke compared to sham. At the peri-infarct, sustained astrogliosis and neuronal loss was marked by increased expression of glial fibrillary acidic protein, and decreased mature neurons and postsynaptic density protein 95. Examination of other brain regions revealed a significant increase in the expression of CD68 and Iba1 in the forceps minor after stroke, indicating microglial activation. No changes were observed in brain regions remote to the infarct. In conclusion, we show that persistent glial activation in the peri-infarct and forceps minor of corpus callosum may be associated with visuospatial impairment following stroke.
Abstract TP584: Higher Prevalence of Congestive Heart Failure (CHF) in Hereditary Hemorrhagic Telangiectasia (HHT) Secondary to Anemia and Artero-venous Malformations (AVMs)
Authors: Vigil Catherine , Qeadan Fares , Farooqui Mudassir , Quadri Syed A , Ikram Asad , Suriya Sajid , Ortega-Gutiérrez Santiago , Zafar Atif
Published: January 2019

Introduction:
Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder with vascular anomalies of various organ systems including the skin, brain, heart, lungs, and liver. While the most commonly recognized disease burden of HHT are epistaxis and mucocutaneous telangiectasia, the development of vascular malformations can result in more severe symptoms such as cerebral hemorrhage, liver cirrhosis, and stroke. Various case reports/series have reported high output cardiac failure, secondary to presence of a single large AVM or multi organ AVMs, as a major cause of morbidity and mortality in HHT population. To the best of our knowledge, this is the first study analyzing the cardiovascular disease burden in HHT patients from a large national database.

Methodology:
All HHT patients were identified using ICD-9 code 448.0 using the 2014 National Inpatient Sample (NIS) database. Comorbidities - intracerebral hemorrhage (431), cerebrovascular anomaly (747.81), congestive heart failure (428.0), anemia (285.9) were also identified using the ICD-9 coding system. Descriptive and inferential statistical analysis were performed using SAS 2015.

Results:
A total of 842 HHT patients were identified with relatively older patients having increased prevalence of anemia (29% vs 15%), congestive heart failure (16% vs 8%), intra-cerebral hemorrhage (0.5% vs 0.3%), hypertension (47% vs 42%) compared to general population, respectively. We report HHT to be linked with having higher odds (p < 0.05) of congestive heart failure (1.6 times), chronic pulmonary lung disease (1.7 times), liver disease (3 times), anemia (1.6 times), cerebrovascular anomaly including cerebral AVMs (26 times), and other neurological disorders than patients without HHT, after adjusting for confounders.

Conclusion:
This is the first database study confirming higher prevalence of CHF in HHT. We infer that chronic anemia and AVM/AVF can cumulatively cause high output congestive heart failure causing increased morbidity and mortality in HHT population especially in advanced ages.
Abstract TP6: Periprocedural Intravenous Heparin During Endovascular Treatment for Acute Ischemic Stroke: Results From the MR CLEAN Registry
Authors: van de Graaf Rob A , Chalos Vicky , van Es Adriaan C , Emmer Bart J , Lycklama à Nijeholt Geert J , Schonewille Wouter J , van der Lugt Aad , Dippel Diederik W , Roozenbeek Bob ,   on behalf of the MR CLEAN Registry
Published: January 2019

Background:
Intravenous (IV) administration of heparin during endovascular treatment (EVT) for ischemic stroke may improve functional outcome. However, the risks and benefits of this adjunctive therapy remain uncertain. We aimed to evaluate the use of periprocedural IV heparin in Dutch stroke intervention centers, and to assess its efficacy and safety.

Methods:
Patients registered between March 2014 and June 2016 in the MR CLEAN Registry, including all patients treated with EVT in the Netherlands, were analyzed. We quantified between-center variation and used multilevel logistic and ordinal regression analysis to compare patients treated with and without periprocedural IV heparin, adjusted for center-effects, prognostic factors and time. The primary outcome was functional outcome (modified Rankin Scale) at 90-days. Secondary outcomes were successful recanalization (extended thrombolysis in cerebral infarction ≥ 2B), symptomatic intracerebral hemorrhage (sICH) and mortality at 90-days. To account for possible unobserved confounding by indication we also analyzed the effect of center-preference to administer heparin, defined as percentage of patients treated with heparin in a center, on outcome.

Results:
A total of 1488 patients from 16 centers were analyzed, of which 398 (27%) patients received IV heparin (median dose 5000 IU). There was substantial between-center variability in heparin use (range: 0%-94%). Analysis at center-level showed that functional outcomes were better in centers with higher percentages of heparin administration (acOR 1.07 per 10% more heparin, 95% CI 1.01-1.13). However, there was no significant difference in functional outcome between patients actually treated with and without IV heparin (adjusted common odds ratio (acOR) 1.17, 95% confidence interval (CI) 0.88-1.56), successful recanalization (aOR 1.21, 95% CI 0.87-1.68), sICH (6% vs. 6%; aOR 1.10, 95% CI 0.63-1.94) and mortality (aOR 0.94, 95% CI 0.65-1.35).

Conclusion:
Among patients treated with EVT, substantial between-center variability exists in periprocedural IV heparin use. Periprocedural IV heparin use seems a safe adjunctive therapy to EVT. A randomized trial is needed to to assess the effects of periprocedural IV heparin .
Abstract TP64: IV tPA Treatment of Minor Stroke Using MRI Targets Rather Than Clinical Severity
Authors: Hsia Amie W , Luby Marie , Benson Richard T , Kalaria Chandni , Lynch John K , Nadareishvili Zurab , Burton Shannon , Leigh Richard , Latour Lawrence L
Published: January 2019

Background:
It is unknown whether patients with non-disabling minor acute ischemic stroke (mAIS) at presentation benefit from IV tPA. The CT-based PRISMS trial suggested no benefit, but was inconclusive due to early termination for low enrollment. Conversely, we have observed an increasing trend in IV tPA treatment of mAIS patients screened with MRI. In this study, we sought to determine our IV tPA treatment rate of patients with mAIS and describe the frequency of MRI targets of acute ischemic stroke (AIS) for these patients stratified by clinical severity.

Methods:
Patients were included in this study if: 1) treated with IV tPA for AIS from 2015-2017, 2) baseline MRI, and 3) NIHSS<6. Baseline MRI was evaluated (2-rater with 3rd tie breaker) for AIS targets on DWI, PWI, GRE, FLAIR, and MRA. Patients were retrospectively categorized as “disabling” vs. “non-disabling” based on NIHSS (“non-disabling” defined as maximum 1 point each for visual fields, facial palsy, sensation, and dysarthria only). Frequency of AIS targets on MRI were compared between the two groups.

Results:
Of 305 patients treated with IV tPA, 140 (46%) had mAIS (NIHSS<6), 119 of 140 (85%) had baseline MRI, 53 of 119 (45%) were “non-disabling.” There was no difference in presence of these imaging targets between “disabling” vs. “non-disabling” mAIS patients: DWI lesion, 86.4% vs. 88.7%, p=0.705; PWI lesion, 80.3% vs. 79.2%, p=0.685; PWI/DWI mismatch, 62.1% vs. 50.9%, p=0.337; FLAIR HVS, 48.5% vs. 43.4%, p=0.775; MRA LVO, 24.2% vs. 26.4%, p=0.829, MRA LVO location, p=0.91. There was a trend toward greater visualization of GRE thrombus in the “disabling” group: 40.9% vs. 24.5%, p=0.060. “Non-disabling” mAIS patients treated based on MRI target accounted for 17% of all IV tPA-treated patients.

Conclusions:
In MRI-screened patients with mAIS, there is no difference in frequency of AIS imaging targets in those with “disabling” vs. “non-disabling” deficit. These findings suggest that these MRI targets rather than clinical severity could be used to drive the decision to treat mAIS patients with IV tPA and greatly expand the pool of patients for thrombolytic therapy. The similarities of these imaging targets in mAIS patients with and without disabling deficit can be used to justify an MRI-based treatment trial.
Abstract TP76: Combined MRI and Next Generation Sequencing of mRNA in Acute Ischemic Stroke Patients Reveal a Correlation Between Early Changes in Infarct and Angiogenesis
Authors: Simpkins Alexis N , Johnson Kory , Nadareishvili Zurab Nadareishvili , Kelley Devon , Leigh Richard , Luby Marie , Benson Richard , Hsia Amie , Lynch John K K , Hallenbeck John , Latour Lawrence
Published: January 2019

We previously showed that early changes in infarct volume (ECS) perform better as a predictor of early neurologic outcome in acute ischemic stroke (AIS) patients receiving thrombolysis when compared to percent recanalization (PER) and infarct volume at 24 hours (InVol), but the biologic explanation is unclear. We combined MRI and RNA Seq to compare the biologic associations.

Methods:
Pretreatment, 2-, and 24-hours post-thrombolysis MRIs were analyzed in 15 enrolled AIS patients treated with thrombolysis. ECS on the apparent diffusion coefficient sequence and PER on the perfusion scan were measured by comparing the pretreatment and 2-hour post thrombolysis MRI using automated co-registered MRI sequences within a region of interest defined by a > 4 second delay in time-to-peak on perfusion imaging using Matlab. InVol was measured on diffusion weighted images by a blinded reviewer. Blood samples were collected 2-hours and 24-hours post thrombolysis. RNA Seq was performed with HiSeq 25000 Illumina platform. After correcting for age, gender, and race, “leave one out testing” was used to select mRNA that correlated with the imaging variables (FDR corrected P-value < 0.05).

Results:
PER only correlated with 2 mRNA from 2-hour blood. InVol was associated with 20 mRNA from 24-hour blood. Both lacked significant disease and function associations. ECS correlated with 24 mRNA from 2-hour blood, with significant association with a decrease in IPA Ingenuity disease and functions annotations for both development of vasculature (P=0.005, Z-score -2.2) and angiogenesis (P=0.02, Z-score -2.2). Interestingly, IPA annotations for vascular development and angiogenesis include epoxyeicosatrienoic acid, a mediator of neurovascular coupling induced by cerebral ischemia, and degraded by soluble epoxide hydrolase enzyme (SEH). SEH inhibitor 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) was a potential upstream regulator (P=5.03E-04), and AUDA has previously been shown to reduce infarct size in an animal model of ischemic stroke. Here we demonstrate the benefit of the combined MRI/blood biomarkers approach for elucidating biologic responses in AIS in identifying potential novel new therapeutics in humans, such as the epoxyeicosatrienoic pathway.
Abstract TP84: Agreement Between Alberta Stroke Program Early Computed Tomography Score and Computed Tomography Perfusion in Patient Selection for Mechanical Thrombectomy After Large Vessel Occlusion Acute Ischemic Stroke
Authors: Karamchandani Rahul R , Rhoten Jeremy B , Strong Edwin , Singh Sam J , Raheem Enayet , Clemente Jonathan D , Asimos Andrew W
Published: January 2019

Introduction:
CT ASPECTS and CT Perfusion (CTP) are used to select patients for mechanical thrombectomy, an evidence-based treatment for Large Vessel Occlusion (LVO) Acute Ischemic Stroke (AIS). However, discordant results between the two imaging modalities creates uncertainty with respect to the volume of ischemic and infarcted brain tissue, and thus whether to offer revascularization. We sought to investigate the agreement between CT ASPECTS and CTP in selecting patients for mechanical thrombectomy.

Hypothesis:
CT ASPECTS determined by a neuro-radiologist demonstrates moderate agreement with CTP in selecting patients with anterior circulation, LVO AIS for mechanical thrombectomy.

Methods:
Over a 7-month period beginning in January 2018, we conducted a retrospective analysis from a large healthcare system’s stroke network database comparing the agreement between favorable CT ASPECTS (defined as score ≥ 6) and favorable CTP. Favorable CTP was defined according to the inclusion criteria from EXTEND-IA, DEFUSE 3, and DAWN, in the 0-6 hour, 6-16 hour, and 6-24 hour time windows, respectively, for patients with ICA or proximal MCA occlusions.

Results:
Cases were identified in the 0-24 hour window with an ICA or M1 occlusion, baseline CT ASPECTS calculated by a neuro-radiologist, and CTP. The overall raw agreement between CT ASPECTS and CTP for the 145 cases in the 0-6 hour window was 81%, and Cohen’s kappa (κ) was 0.17 (no agreement). In the 6-16 hour window, the overall raw agreement for 46 cases was 78% (κ = 0.38, minimal agreement). In the 6-24 hour window, the overall raw agreement for 58 cases was 53% (κ = 0.14, no agreement).

Conclusions:
In both early and extended time windows, CT ASPECTS and CTP demonstrate minimal to no agreement beyond chance in patient selection for mechanical thrombectomy. Additional studies are required to determine the most appropriate imaging selection criteria to guide treatment decisions in patients with anterior circulation, LVO AIS.
Abstract TP88: Optimal Detection of Plaque Hemorrhage in Acute Ischemic Stroke With Mild to Moderate Carotid Stenosis: Does Time-of-Flight Magnetic Resonance Angiography Represent Intraplaque Hemorrhage?
Authors: Gwak Dong-Seok , Kim Jun Yup , Lee Keon-Joo , Chung Inyoung , Han Moon-Ku
Published: January 2019

Background:
Carotid intraplaque hemorrhage (IPH) is well known for a risk indicator for thromboembolism, but not easy to detect it rapidly in acute symptomatic carotid disease. The aim of this study was to assess usefulness of time-of-flight (TOF) MRA for the detection of IPH in patients with acute symptomatic carotid diseases.

Methods:
We retrospectively identified consecutive patients with acute symptomatic carotid disease who were admitted within 12 hours after stroke onset. Fifty-nine patients underwent TOF MRA at admission and were divided according to the presence of intraplaque high signal intensity (HSI). The severity of carotid stenosis and diffusion weighted imaging (DWI) MRI lesion patterns were evaluated.

Results:
Intraplaque HSI was detected in 28.8% of total enrolled patients (17/59). Mild to moderate symptomatic carotid stenosis was more in the intraplaque HSI positive group (70.6%) than the intraplaque HSI negative group (42.8%) (p=0.025). The patients with intraplaque HSI more frequently demonstrated disseminated small infarction pattern (76.5% in the intraplaque HSI positive, 47.6% in the negative group), and did not show border-zone infarction pattern (0% in the positive, 16.7% in the negative group).

Conclusion:
TOF MRA in acute symptomatic carotid disease may be noninvasive and rapid tool to detect the IPH. The IPH was common in smaller degree of carotid stenosis and demonstrated disseminated small infarction pattern. Intraplaque HSI on TOF MRA in acute symptomatic carotid disease may help determine the mechanism of stroke and establish treatment plan early.
Abstract TP9: Variability in Endovascular Thrombectomy Treatment in San Diego County
Authors: Kenner Brininger Amelia , Olson-Mack Lindsay , Koenig Kristi L , Hemmen Thomas
Published: January 2019

Background:
Endovascular thrombectomy (EVT) after Acute Ischemic Stroke (AIS) has shown to improve outcomes in multiple large clinical trials. Most participating centers, however, were large academic hospitals. We studied EVT use in a community setting covering a population of 3.2 million that includes 16 teaching and non-teaching facilities of variable sizes across San Diego County. This provides one of the first comprehensive community-based analyses on early adoption of EVT.

Methods:
We included all AIS cases treated at an EVT-capable stroke receiving center from the San Diego County EMS Stroke Registry from July 2016 through June 2017. Documented groin puncture date and time indicated EVT treatment. We analyzed the frequency of EVT by center, baseline demographics, admission source, treatment times, use of tPA and discharge disposition.

Results:
In total, 3,033 AIS patients were treated from July 2016 through June 2017; 266 (8.8%) underwent EVT. The rate per center varied from 1.7 to 17.5%. The mean (±SD) initial NIHSS was 18.0 (±8.4); mean age 74.4(±14.2) years; 48.9% women, 64.7% arrived by EMS, 29.0% by interfacility transfer, 55.3% received tPA, in-hospital mortality was 15.0%, discharge to home 20.7%, to nursing facility 24.4%. Last known well (LKW) was documented in 249 cases (93.6%) of which 201 (80.7%) received EVT within 6 hours of LKW. Mean (±SD) LKW to EVT time for EMS cases was 4.9(±5.9) hours versus 5.8(±6.4) hours for interfacility transfers. The range of mean LKW to EVT was 0.7 hours to 71.4 hours (IQR=2.7-5.3 hours). Arrival to EVT time was documented in 253 cases (95.1%), of which 40.3% received EVT within 90 minutes of arrival at the treating center. The frequency of treatment within 90 minutes from arrival varied between centers from 0.0% to 63.0%. The mean (±SD) time from arrival to EVT was 2.5(±3.9) hours, ranging from 1.6 hours to 11.5 hours between centers (IQR=1.2-2.5 hours).

Conclusion:
Endovascular thrombectomy treatment rates vary across centers within San Diego County. The overall treatment rate is 8.8%. Nearly three in ten patients arrived to an embolectomy capable center via interfacility transfer, with slightly longer last known well to treatment times. Continued analysis will provide data to support future policy and protocol changes.
Abstract TP98: Diabetes Mellitus Predicts Symptomatic Intracerebral Hemorrhage Following Thrombectomy in Acute Ischemic Stroke
Authors: Montalvo Mayra , Yakhind Alexandra , Jayaraman Mahesh , McTaggart Ryan , Chang Andrew , Akiki Ronald , Mac Grory Brian , Cutting Shawna , Burton Tina , Reznik Michael , Thompson Bradford , Wendell Linda , Rao Shyam , Potter Stevenson , Sheth Kevin N , Willey Joshua Z , Furie Karen , Khatri Pooja , Yaghi Shadi
Published: January 2019

Introduction:
Diabetes mellitus has deleterious effects on blood vessel integrity via several mechanisms including blood brain barrier injury, excitatory chemokines, acidosis, and edema. It has been associated with symptomatic intracerebral hemorrhage (sICH) after alteplase administration for ischemic stroke. We aim to determine the association between diabetes and sICH in patients undergoing thrombectomy.

Methods:
Data was abstracted from the Rhode Island Hospital prospective stroke registry and included consecutive patients who were selected for thrombectomy at our institution over a period of 24 months with the goal of identifying risk factors for sICH. The primary predictor was history of diabetes and the primary outcome was sICH defined based on the modified SITS-MOST criteria (parenchymal hematoma along with increase in NIHSS by 4 points or more). We compared baseline characteristics between patients with and without sICH using univariate and multivariable analyses. Statistical analysis was performed using SPSS version 20.0 and a p value of <0.05 was statistically significant.

Results:
Out of 307 patients, 12 (3.9%) experienced sICH. The mean age was 73 years; 49.2% were men. On univariate analyses, diabetes mellitus was associated with sICH (50.0% vs. 17.3%, p= 0.012). This association persisted on multivariable models adjusting for age, NIHSS score, ASPECTS score, time to reperfusion, and TICI score (Odds Ratio 6.0, 95% CI 1.5-23.3, p=0.011). We performed sensitivity analyses excluding patients who received intravenous tPA (n = 189) and the results remained unchanged (OR 8.5, 95% CI 0.84-83.3, p = 0.071).

Conclusion:
Diabetes mellitus is an independent predictors of sICH in patients with acute ischemic stroke undergoing mechanical thrombectomy, with or without IV tPA. More studies are needed to confirm our findings and to determine blood sugar control in the post-thrombectomy reduces this risk.
Abstract WMP1: Mechanical Thrombectomy Alone vs Combined Mechanical Thrombectomy With Intravascular Thrombolysis in Patients With Acute Ischemic Stroke-Analysis on Propensity Matched National Cohort
Authors: Kumar Varun , Savani Chirag , Singh Tejinder , yi Xiyan , Motwani Reena , Pathak Ambarish , Chib Anjula
Published: January 2019

Background:
Comparative analysis between Mechanical thrombectomy (MT) alone vs Combined mechanical thrombectomy with intravascular thrombolysis (IVT) in patients with Acute ischemic stroke (AIS) has never been studied on nationwide patient population.

Method:
Nationwide Readmissions Database (NRD) from 2010-14 was utilized to identify AIS using appropriate ICD-9CM codes in primary diagnosis fields. MT was identified by ICD9 procedure code 39.74 and IVT by 99.10 in any procedural field. We used Greedy’s algorithm for propensity score match (1:1) to adjust for clinically important confounders and simple logistic regression to generate odds ratio.

Results:
We identified 10,344 patients who underwent combined MT and IVT therapy (Mean age 67.9 years, female 49.9%) and 10,428 who underwent MT alone (Mean age 67.7 years, female 50.8%). In hospital mortality among combined group was 19.7% vs 17.7% in MT alone (p value=<.001), 30-day readmission 10.8% vs 10.7% (p value=0.843) and Mean Length of stay (LOS) 13 days vs 13 days (p value=0.366). After propensity match (1:1) we identified 3,844 matched pairs without any statistically significant difference in baseline characteristics. Among combined group vs MT alone group, cardiac complication was (4.2% vs 3.9%, P value=0.524), Major Bleeding (24.4% vs 24.4%, P value=0.958), Sepsis (4.9% vs 4.2%, P value=0.154), AKI requiring dialysis (0.2% vs 0.2%, P value=0.438), in hospital mortality (19.3% vs 17.6%, P value=0.064),30-day readmission (11.1% vs 11.4%, P value=0.613), Mean LOS (13.5 days vs 12.9 days, P value=0.298), Mean Cost of hospitalization $(48,950 vs 52,270 P value=<.0001).

Conclusion:
Our study represents that treatment of AIS patients with combined MT and IVT therapy does not appear to provide clinical and statistical advantage over MT alone as suggested by previous studies. Further research exploring impact of these therapy on outcomes including mortality benefit and complication rates in AIS is warranted.
Abstract WMP10: A Closer Look at Late Window Thrombectomy Selection
Authors: Leslie-Mazwi Thabele M , Hamilton Scott , Mlynash Michael , Patel Aman B , Schwamm Lee H , Lansberg Maarten G , Marks Michael P , Hirsch Joshua A , Albers Gregory W
Published: January 2019

Introduction:
The DAWN and DEFUSE 3 studies established thrombectomy as standard care for patients with emergent large vessel occlusions (ELVO) presenting 6-24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3 we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN.

Methods:
Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 Non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large (CTL), NIHSS 6-9 and mRS 2. Subgroups were compared to the DEFUSE 3 Non-Dawn and entire DEFUSE 3 cohorts.

Results:
There were 71 DEFUSE 3 Non-DAWN patients; 31 patients with NIHSS 6-9, 33 with CTL, and 13 with pre-morbid mRS 2 (some patients met multiple criteria). For CTL patients, median 24-hour infarct volume was 119ml (IQR 74.6-180) versus 31.5ml (IQR 17.6-64.3) for Core Not Too Large (CNTL) patients, p= <0.001. Complications and functional outcomes were similar between the groups. Thrombectomy in CTL patients compared to the remaining DEFUSE 3 Non-Dawn patients conveyed benefit for functional outcome (OR 20.9, CI 1.3-337.8). Comparing the NIHSS 6-9 group with the NIHSS ≥10 patients, mRS 0-2 outcomes were achieved in 74% versus 22% (p=<0.001), with mortality in 6% versus 23% (p=0.024) respectively. For patients with NIHSS 6-9 compared to the remaining DEFUSE 3 Non-Dawn patients thrombectomy conveyed a better chance of functional outcome (OR 1.86, CI 0.36-9.529); results lacked statistical significant in this small subgroup.

Conclusions:
Patients with pretreatment core infarct volumes <70ml but too large for inclusion by DAWN criteria demonstrate robust benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. Despite a trend towards benefit of thrombectomy in patients with NIHSS 6-9 additional data regarding late window thrombectomy for these patients is needed.
Abstract WMP106: Haptoglobin is Present as Zonulin in the Brain and Overexpression Improves Intracerebral Hemorrhage Outcomes
Authors: Leclerc Jenna , Lampert Andrew S , Phillips Harrison , Esfandiary Tina , Dang Alex , Santiago-Moreno Juan , Dore Sylvain
Published: January 2019

Intracerebral hemorrhage (ICH) most commonly results from a hypertensive spontaneous bleed into the brain parenchyma and is a devastating stroke subtype. Hemolysis ensues and large quantities of hemoglobin (Hb) are released that initiate a toxic oxidative and neuroinflammatory cascade. Hp is an abundant plasma glycoprotein that binds and detoxifies extracorpuscular Hb with strong affinity, although very little Hp is made endogenously within the brain. Of note, Hp undergoes a complex biosynthesis into a single polypeptide prohaptoglobin that is co-translationally processed in the endoplasmic reticulum to form the α- and β-subunits, which subsequently dimerize. We hypothesized that overexpressing Hp locally in the brain would lead to improved outcomes following ICH. Overexpression was achieved using adeno-associated viral vectors and ICH was induced using the intrastriatal autologous whole blood injection model. Functional outcomes were assessed by a 24-point neurological deficit score. Western blotting under reducing and non-reducing conditions and mass spectrometry were utilized to confirm the identity of the overexpression product, which surprisingly was prohaptoglobin, also known as zonulin. At 72h post-ICH, zonulin-overexpressing mice have smaller lesion volumes with less blood accumulation and better neurologic function (p<0.05) when compared to controls (n=11-13/group). Zonulin-overexpressing mice also demonstrate less heme oxygenase-1 expression, lipid peroxidation, and peripheral neutrophil infiltration, and significantly increased microgliosis and astrogliosis. No differences in iron content were seen. Importantly, these results provide evidence that Hp in its fully processed form is not made endogenously within the brain, but instead transcription from this gene results in the formation of zonulin, which has very distinctly different functions. Notably, zonulin does not bind Hb or provide redox protection, but is a strong regulator of intercellular tight junctions, which has important implications for intracranial bleeding. Interestingly, we show that zonulin-overexpression improves ICH outcomes and thus this pathway represents a new potentially targetable avenue for the treatment of ICH.
Abstract WMP109: Transitional Care Matrix to Improve the Coordination of Stroke Care Between Inpatient and Outpatient Care Settings
Authors: Skeels Katelyn , Leung Lester Y
Published: January 2019

Background and Purpose:
Transitions of care, specifically between inpatient and outpatient care settings can be a point of vulnerability in the care of stroke patients. As patients transfer from inpatient care facilities to outpatient clinics, information can become lost resulting in delays in care, a slower recovery, and patient and family frustration. The purpose of this program is to provide a link between the inpatient and outpatient care settings and improve the coordination of care along the continuum by communicating to the outpatient providers essential information about the stroke patients they will be seeing for follow up.

Methods:
In order to improve the transition of care between care settings, a two-part program was used. First, the Stroke Advanced Practice Nurse along with the inpatient Neurology team completes a discharge timeout to collect and verify essential information, such as the final diagnosis, suspected stroke etiology, discharge medications, follow up appointments, and transitional care issues such as pending studies. This information is then compiled into a transitional care matrix, which is shared on a weekly basis with the outpatient clinicians who will be seeing the patients that week, allowing them to anticipate and prepare for the follow ups and the patients’ needs. Since initiation in April 2018, 95 stroke patients’ plans of care have been reviewed using the above process.

Results:
Use of the discharge timeout and transitional care matrix has resulted in improved transitions of care. The process has resulted in more consistent and prompter scheduling of follow up appointments in the outpatient stroke clinic. Furthermore, the transitional care matrix that is shared with outpatient clinicians has helped them to be more prepared for appointments and has created an atmosphere of collaboration between different stroke providers.

Conclusions:
In conclusion, the discharge timeout and transitional care matrix process has shown to be a valuable tool in the transition of care for stroke patients between the inpatient and outpatient settings, resulting in fewer delays in care and improved anticipation of care needs.
Abstract WMP111: Family Perceptions of Quality of End-of-Life Care in Stroke: The OASIS Study
Authors: Zahuranec Darin B , Shafie-Khorassani Fatema , Cornett Bridget A , Kim Sehee , Ortiz Carmen , Lank Rebecca J , Case Erin , Morgenstern Lewis
Published: January 2019

Introduction:
Stroke remains the fifth leading cause of death in the US, yet there has been little effort to formally assess the quality of end-of-life stroke care. We explored family surrogate decision maker perceptions of the quality of end-of-life care in stroke and predictors of higher or lower quality.

Methods:
Surrogate decision makers for stroke patients in the Brain Attack Surveillance in Corpus Christi (BASIC) study were invited to participate in the Outcomes Among Surrogate decision makers In Stroke (OASIS) study. We report findings from the validated Quality of End-of-Life Care (QEOLC) questionnaire, which assesses 10 elements of end-of-life care on a 0-10 scale. Responses to individual QELOC items were dichotomized into low (0-7) or high (8-10) scores. The univariate association between pre-specified patient and surrogate factors and overall QELOC score were explored with generalized estimating equations.

Results:
71 surrogates for 59 deceased stroke cases were enrolled. Characteristics were patient mean age 77, ischemic stroke (73%), patient female (56%), Mexican American (58%), surrogate mean age 58, surrogate female (70%), relationship (spouse 21%; child 68%; other 11%), and mean time from stroke to death 9.5 days. QELOC responses are summarized in the table. None of the hypothesized factors were associated with overall QEOLC score, including patient or surrogate demographics, stroke type, location of death, time to death, presence of advance directives, or surrogate self-reported confidence or understanding of patient wishes.

Conclusions:
Although we did not identify patient or surrogate predictors of overall quality of end-of-life care, the relatively lower ratings on consistency of information and treating the whole person may represent opportunities for improvement. Further study in larger samples is warranted, though modifications to the QELOC may be needed in stroke due to a high proportion of non-response to several items.
Abstract WMP116: Acute Infarct Volume in Childhood Stroke Can Be Accurately Estimated by Modelling Contraction of Chronic Infarction
Authors: Reddy Kartik , Mirsky David , Kenny Amanda , Thornhill Dianne , Bernard Timothy , Stence Nicholas
Published: January 2019

Introduction:
Arterial ischemic stroke (AIS) occurs in 1-2 children/100,000/year. Most children have neurologic deficits post-AIS, but the influence of infarct volume on neurologic outcome is understudied. While acute infarct volume {best measured as a percentage of total brain volume infarcted (%aTBVi) in the growing brain} likely predicts outcome, acute scans are not always available in children. Chronic infarct volumes are underestimated by direct measurement due to contraction. A method for estimating acute infarct volumes from chronic scans is needed. We developed and compared the reliability of three methods for estimating the %aTBVi from values measured on chronic images.

Methods:
A retrospective IRB-approved study studying children (age 1 month-17 years) with AIS enrolled 158 patients. Those with acute (<3 days) and chronic (>90 days) MRIs were manually segmented by a pediatric neuroradiologist. Method 1 (direct method, used as control) estimated %aTBVi by measuring chronic infarct volume (cVI) and dividing by total brain volume. Method 2 (OFC method) estimated %aTBVi by subtracting the total non-infarcted brain volume from an extrapolated total brain volume based on orbitofrontal circumference (OFC). Method 3 (contraction method, Figure 1) used a regression model to apply a correction factor to the direct measurement of cVI that was then divided by total brain volume to estimate %aTBVi. Intraclass correlation compared estimated %aTBVi of the three methods to the gold standard %aTBVi calculated from manual segmentation of acute scans.

Results:
Inclusion criteria were met by 86 patients. The control direct method had excellent reliability (ICC 0.79), although it was exceeded by the contraction method (Figure 1, ICC=0.86), while the OFC method reliability was poor (ICC=0.42).

Conclusion:
%aTBVi is reliably estimated in children with AIS with only chronic imaging via the contraction method.
Abstract WMP118: The Association Between Sleep Related Breathing Disorders and Neuropsychological Function in Pediatric Stroke
Authors: Slim Mahmoud , Westmacott Robyn , Grbac Elena , Toutounji Sandra , Narang Indra , Weiss Shelly , Pontigon Ann-Marie , Singh Jaspal , Andres Kathleen , MacGregor Daune , deVeber Gabrielle , Moharir Mahendranath , Dlamini Nomazulu
Published: January 2019

Introduction:
Sleep-related breathing disorders (SRBDs) in childhood are associated with adverse outcomes including developmental and behavioral disorders. The association of SRBDs with pediatric stroke is poorly understood. We aimed to assess the risk of SRBDs in children with stroke or non-stroke high risk arteriopathies (NSA) and to evaluate their association with cognitive and behavioral function.

Hypothesis:
Children with stroke or NSA have a higher rate of SRBD and associated poor cognitive and behavioral function.

Methods:
We conducted a cross-sectional study of children with arterial ischemic stroke (AIS), cerebral sinovenous thrombosis (CSVT) and NSA such as moyamoya. All children completed the Pediatric Sleep Questionnaire (PSQ). High risk for SRBDs was defined as a PSQ score ≥0.33. Children completed the Adaptive Behavior Assessment System (ABAS-2) parent and teacher forms and/or The Wechsler Intelligence Scale for Children (WISC-V) within 1 year of completing the PSQ.

Results:
Overall, 213 were included (54% males, median age: 9 years [IQR 5-14]). Forty-nine children (23%) were at high risk of SRBDs. The risk of SRBDs did not vary with age, gender or stroke subtype: AIS (25%), CSVT (20%), other stroke subtypes (20%) and NSA (24%) (p= 0.8). Children with SRBD had higher mean BMI z-scores (0.9±1.5 vs 0.4±1.3, p=0.06). Twenty-four and 15 children underwent ABAS-2 parent and teacher assessment, respectively. The global adaptive composite scores of both forms significantly correlated with the total PSQ scores (r
s
=-0.6, p<0.01 for the parent form and r
s
=-0.63, p=0.01 for the teacher form). Correlation coefficients remained statistically significant upon controlling for BMI. In 19 children who completed the WISC-V, those at risk of SRBDs (n=7) had significantly lower Full Scale IQ (70±24.7 vs 91±17, p=0.03), processing speed (55±44 vs 96±19, p=0.02) and working memory (77±23 vs 98±15, p=0.02) compared to children at no risk. Cognitive and behavioral function did not differ across stroke subtypes.

Conclusions:
Pediatric stroke or NSA is commonly associated with SRBDs which in turn is linked to significant decline in cognitive and behavioral function. Further studies are required to understand the underlying pathological mechanisms.
Abstract WMP13: 3D Convolutional Neural Network Segmentation of Intracerebral Hemorrhage on CT
Authors: Sharrock Matthew F , Muschelli John , Ali Hasan , Mould W Andrew , Hanley Dan F
Published: January 2019

Introduction:
Intracerebral Hemorrhage (ICH) accounts for 15% of strokes with a disproportionate impact on functional outcome and economic burden. In clinical trails, ICH volume on computed tomography (CT) is treated as both a criterion for inclusion and a radiographic outcome measure. Accurate assessment of ICH volume by manual segmentation is time consuming and clinical trials often use simple linear metrics such as ABC/2 despite their difficulty with large, irregular or lobar hematomas. Convolutional Neural Networks (CNNs) have shown to be adept at handling complex neuroimaging segmentation problems and have yet to be applied to an ICH clinical trial dataset.

Methods:
Initial pre-randomization CT scans from 112 patients with primary intracerebral hemorrhage from the MISTIE II trial dataset were manually segmented by two expert raters in OsiriX MD (Pixmeo) and divided into a training set (n = 72) and validation set (n = 40). The intracranial volume was extracted and data augmentation was applied to the training set using random axial rotation and elastic deformation. Each scan was then fed en bloc into a customized 3D CNN written in Tensorflow (Google) and trained over 50 data epochs in 24 hours. After standardized preprocessing, the validation dataset was fed into the network sequentially.

Results:
Individual segmentation predictions were generated in less than one second. Preliminary results, reported in median and interquartile range, include a Dice score of 0.90 (0.88 - 0.92). For ICH < 30cc (n = 15), 30 - 60cc (n = 19) and >60cc (n = 6), the Dice scores were 0.91 (0.87 - 0.93), 0.91 (0.87 - 0.92) and 0.89 (0.89 - 0.90) respectively. The median difference between predicted and actual volumes was 2.4cc (1.4 - 5.0cc) and the correlation between volumes was 0.97.

Conclusion:
Our results indicate that 3D CNNs can perform fast, accurate segmentation of ICH, including large hematomas. This model constitutes a potential tool for investigators requiring rapid analysis or working on large datasets.
Abstract WMP18: Regional Comparison of Functional Connectivity Between “Salvaged” Peri-Infarct and Infarcted Tissue
Authors: Ng Felix C , Venkatraman Vijay , Yassi Nawaf , Parsons Mark , Bivard Andrew , Sharma Gagan , Desmond Patricia , Davis Stephen , Campbell Bruce C
Published: January 2019

Introduction:
Even when accounting for lesion topography, radiological Final Infarct Volume (FIV) after acute ischemic stroke (AIS) correlates only moderately with clinical outcome. Pathology in normal-appearing “salvaged” peri-infarct tissue and partial preservation within radiologically infarcted tissue may contribute to the variance between FIV and clinical outcome. We sought to evaluate the degree of neuronal dysfunction within infarcted, peri-infarct and remote regions on follow-up MRI after AIS.

Methods:
In a single-centre prospective study, twenty AIS patients underwent resting state functional MRI at 1 month. Asymmetry compared to the contralateral hemisphere in connectivity values (CV) was compared between 4 Regions of Interest (ROIs) defined on admission CT perfusion and 1-month MRI: (1) Early Ischemic Core with severe oligemia at presentation (>10s Tmax on admission CTP and FLAIR positivity); (2) Evolved Infarct with mild-moderate oligemia at presentation (4-8s Tmax on CTP and FLAIR positivity); (3) Peri-infarct “salvaged penumbral” tissue (>6s Tmax on CTP and FLAIR negativity); (4) remote non-ischemic tissue (normal CTP and FLAIR).

Results:
Asymmetry in CV were significantly different between all ROIs (p=0.018) in a preliminary analysis (n=9). Early Infarct and Evolved Infarct both showed dysfunction when compared to the contralateral hemisphere (CV = 0.384 & 0.247 respectively, p=0.717). Peri-Infarct Tissue had more dysfunction than remote tissue (CV = 0.427 vs 0.838, p=0.03) despite both being normally-appearing. Overall, Asymmetry in CV was greatest in Infarcted tissue followed by Peri-infarct Tissue and Remote Tissue.

Conclusion:
Peri-infarct tissue demonstrates dysfunction despite being radiologically normal. Our data suggest a gradient of neuronal injury extending beyond conventionally-delineated infarct boundaries is present in the chronic post-stroke phase.
Abstract WMP31: Plasma Soluble Human Elastin Fragments as an Intra-Aneurysmal Localized Biomarker for Ruptured Intracranial Aneurysms
Authors: Nakagawa Daichi , Zanaty Mario , Hudson Joseph , Teferi Nahom , Ishii Daizo , Allan Lauren , Jabbour Pascal , Ortega-Gutierrez Santiago , Samaniego Edgar A , Hasan David M
Published: January 2019

Background:
Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms.

Methods:
One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent-assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a micro-catheter. The tip of the microcatheter was placed inside the aneurysm’s sac in close proximity to the inner wall of the dome. Plasma levels of elastin fragments were measured using an ELISA-based method.

Results:
The mean plasma level of soluble human elastin fragments was significantly greater in ruptured aneurysms when compared to non-ruptured aneurysms (102.0 ± 15.5 vs. 39.3 ± 9.6 ng/ml, P<0.001). The mean plasma level of soluble human elastin fragments did not have significant correlation with age, gender, size, or aneurysm location.

Conclusions:
The present study revealed that a significantly higher concentration of soluble human elastin fragments in the lumen of ruptured intracranial aneurysms when compared to non-ruptured ones.
Abstract WMP34: One Year Follow-Up on the Utility of the Penumbra SMART COIL System for Treatment of Intracranial Aneurysms and Malformations in 500 Patients
Authors: Spiotta Alejandro , Liu Kenneth , Schirmer Clemens , Bohnstedt Bradley , Bellon Richard , DeLeacy Reade , Fiorella David
Published: January 2019

Introduction:
The Penumbra SMART COIL System includes a novel generation of embolic coils comprised of complex and WAVE shape properties with varying levels of softness to promote dense packing and durable long-term occlusion. We report an interim analysis of the first 500 patients enrolled in the SMART registry to assess the utility of the SMART COIL System in the treatment of intracranial aneurysms and other malformations.

Methods:
The SMART registry is a prospective, multi-center registry study. Procedures must employ ≥75% of the Smart, PC400, or POD coils to meet the registry criteria. SMART registry endpoints include retreatment rates through one year follow-up, procedural device-related serious adverse events (SAE), the ability to achieve adequate occlusion at immediate post-procedure, and the number of times re-access with guidewire was required due to catheter kickout.

Results:
The interim analysis of the first 500 patients enrolled (70.6% female; mean age 60.0±13.2 years) includes cerebral aneurysms (91.0%, 454/499), of which 30.4% were ruptured; arteriovenous malformations (1.4%); fistulae (4.4%); and other lesions (3.2%). Aneurysms were small (87.9%), large (11.9%), and giant (0.2%); 64.3% (275/428) were wide-neck. Stent-assisted coiling was performed in 30.2% of patients and balloon-assisted coiling in 20.2% of patients. Median packing density for all aneurysms was 29.3% (IQR 21.3-38.4). In aneurysm patients, Raymond Class I and II was observed in 79.5% (357/449) at immediate post-procedure, and 88.8% (229/258) at one year follow-up. In all patients, the retreatment rate through one year follow-up was 6.7% (19/282). Procedural device-related SAE were observed in 3.2% subjects (16/500). One year follow-up data collection is ongoing.

Conclusion:
Interim Results suggest that the SMART COIL System achieves adequate embolization in a variety of neurovascular lesions with low retreatment rates over one year.