bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 91: Physicians’ Attitudes Toward Elevated Blood Pressure and Recurrent Events After Acute Ischemic Stroke
Authors: Kim Beom Joon , Cho Yong-jin , Hong Keun-sik , Lee Jun , Kim Joon-tae , Choi Kang Ho , Park Tai Hwan , Park Sang-soon , Park Jong-moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae-kwan , Kim Dae-hyun , Nah Hyun-wook , Lee Byung-chul , Yu Kyung-ho , Oh Mi-sun , Kim Dong-eog , Ryu Wi-sun , Choi Jay Chol , Kim Wook-joo , Shin Dong-ick , Yeo Min-ju , Sohn Sung Il , Hong Jeong-ho , Lee Ji Sung , Lee Juneyoung , Han Moon-ku , Bae Hee-joon
Published: January 2019

Background:
Strict blood pressure (BP) control among acute ischemic stroke (AIS) survivors would improve prognosis and decrease recurrent vascular events, which, however, has not been investigated in detail.

Methods:
AIS survivors at discharge who was admitted between 2010 and 2011 were included in the analysis dataset. Baseline characteristics were gathered through a multicenter prospective stroke registry (CRCS-K). BP measurements, clinic visit and prescription of BP-lowering medications after discharge were collected through medical records until 1 year (± 2 months of grace period). Recurrent vascular events until 1 year after stroke including stroke, myocardial infarction and death were gathered through a structured telephone interview by trained research registrars or medical records review. Individual treatment intensification (TI) scores were calculated by the following equation; (observed medication change - predicted medication change by a standard guideline) / number of clinic visit. TI scores were categorized into quintile groups and their associations with recurrent events were assessed by Cox proportional hazard models.

Results:
Of the 3482 AIS survivors, 2675 (77%) were diagnosed of hypertension and 1977 (57%) had BP-lowering medication prescription at discharge. Median NIHSS score at admission was 3 [1 - 6] points and 1573 (45.3%) had mRS score 0f 0 - 1 at discharge. TI score over 1-year after discharge was mean - 0.24 ± 0.30 and median - 0.15 [- 0.42, 0]. Compared to Q3 (third quintile; group TI score, - 0.15 ± 0.05), Q5 (group TI score, 0.04 ± 0.08) had higher proportion of cardioembolic stroke (32% vs 20%) and higher median NIHSS score (4 vs 3). Extreme groups of TI scores, Q1 or Q5, showed increased hazard for having mortality or composite events (see Table).

Conclusions:
Physicians’ attitudes toward elevated BP, represented by the TI score, was significantly associated with long-term vascular outcomes.
Abstract 94: Blood Pressure After Endovascular Stroke Therapy (BEST): Final Results of a Prospective Multicenter Cohort Validation Study
Authors: Mistry Eva A , Sucharew Heidi , Mistry Akshitkumar M , Mehta Tapan , Arora Niraj , De Los Rios La Rosa Felipe , Starosciak Amy K , Siegler James E , Barnhill Natasha R , Patel Kishan , Assad Salman , Tarboosh Amjad T , Dakay Katarina , Cruz Aurora , Wagner Jeff , Fortuny Enzo , Bennett Alicia , James Robert , Jagadeesan Bharathi , Streib Christopher , O'Phelan Kristine , Kasner Scott E , Weber Stewart A , Chitale Rohan , Volpi John J , Mayer Stephan , Yaghi Shadi , Jayaraman Mahesh , Khatri Pooja
Published: January 2019

Background:
Limited data currently inform optimal post-endovascular therapy (EVT) blood pressure management. Systolic BP (SBP) >160 mmHg during the 24-hrs post-EVT correlated with worse outcomes in our retrospective multicenter study. To prospectively determine and potentially validate the specific post-EVT SBP threshold that discriminates functional outcomes, we designed a multicenter, prospective cohort study - “Blood Pressure after Endovascular Stroke Therapy (BEST)” - with a prespecified analysis plan.

Methods:
Consecutive EVT-treated adult patients with ICA, M1, or M2 occlusions were enrolled at 12 comprehensive stroke centers, excluding those with disability, terminal diagnoses, LVAD, and in-hospital stroke. Baseline, treatment characteristics, and all SBP values during the 24 hrs post-EVT were captured. The primary outcome was 90d mRS (0-2 vs 3-6) adjusted for age, baseline NIHSS, glucose, ASPECTS, time to reperfusion, and history of hypertension. Secondary outcomes were intracerebral hemorrhage (ICH), symptomatic ICH, mRS distribution, and early neurologic recovery (ENR). A sample size of 340 was calculated to provide 80% power to detect a 1.36 odds ratio (i.e., 8% difference in mRS 3-6 rate) at α=0.05; inflated to 450 patients for up to 25% loss to follow up. The threshold of peak SBP that best discriminates mRS 0-2 vs. 3-6 will be identified with Youden’s index, and its association with outcomes will be quantified using logistic regression. Subgroup analysis by mTICI score and associations of other BP parameters with outcomes will be explored. Missing 90d outcomes will be imputed.

Results:
We enrolled 457 patients from 11/2017 to 7/2018 with mean age 68y (±15), 52% females, median NIHSS 16 (IQR 11,20), and ASPECTS 8 (IQR 7,10). 221 (48%) patients received alteplase and 402 (88%) achieved mTICI 2b-3. Mean peak SBP was 165±24 mmHg in mTICI2b-3 group and 171±22 in mTICI 0-2a group, and 352 (77%) received an IV antihypertensive. 331 (73%) patients have outcomes available at 90d; rest are expected by 10/2018. Final results will be presented at ISC.

Conclusion:
Expected results from BEST will inform clinical care and guide a developing randomized trial of targeted antihypertensive treatment in EVT-treated stroke patients.
Abstract 95: Exceeding Personalized Blood Pressure Targets After Endovascular Stroke Therapy is Associated With Hemorrhagic Transformation and Worse Functional Outcome
Authors: Petersen Nils H , Wang Anson , Strander Sumita , Kodali Sreeja , Silverman Andrew , Gilmore Emily J , Sansing Lauren H , Schindler Joseph L , Hebert Ryan M , Cord Brandon , Matouk Charles , Sheth Kevin N
Published: January 2019

Background:
Effective blood pressure (BP) management after endovascular stroke therapy (EVT) is critical for maintaining optimal cerebral perfusion and to protect the brain from hyperperfusion. A single, universal BP target below 180/105 mmHg is likely inadequate in this highly heterogeneous patient population. We calculated individualized BP thresholds at which cerebral autoregulation was best preserved and analyzed how exceeding these limits correlates with hemorrhagic transformation (HT) and functional outcome.

Methods:
51 patients with large-vessel occlusion (LVO) stroke who underwent EVT were prospectively enrolled. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy and mean arterial pressure (MAP). The resulting autoregulatory index was used to identify and trend the BP range at which autoregulation was most preserved (Figure 1A). The percent time that MAP exceeded the upper limit of autoregulation (ULA) was calculated for each patient. HT was identified on CT imaging at 24 hours. Functional outcome was assessed using the modified Rankin Scale (mRS). Associations among percent time above ULA, HT and mRS were analyzed using ordinal or logistic regression, adjusting for age, TICI score and baseline NIHSS.

Results:
Personalized limits of autoregulation could be computed in 36 patients (mean age 71±15, 12 F, mean admission NIHSS 15±6, average monitoring time 26±19 hours, HT=17). Optimal BP and limits of autoregulation were calculated for 83±11% of the total monitoring period. Percentage of time with MAP above ULA was associated with HT (p=0.016, OR 1.15, 95% CI 1.02-1.29) and worse functional outcome at discharge (p<0.004, OR 1.13, 95% CI 1.04-1.22) and 90 days (p=0.003, OR 1.22, 95% CI 1.06-1.38) (Figure 1B - D).

Conclusions:
Non-invasive determination of personalized BP thresholds for LVO stroke patients is feasible; exceeding these limits may increase the risk of HT and worse clinical outcomes.
Abstract 96: Efficacy and Safety of Oral Anticoagulants in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis
Authors: Malhotra Konark , Ishfaq Muhammad F , Goyal Nitin , Parissis John , Alexandrov Anne , Alexandrov Andrei , Tsivgoulis Georgios
Published: January 2019

Introduction:
Data regarding the efficacy and safety of oral anticoagulants [vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC)] among patients with chronic kidney disease (CKD) remain scarce.

Methods:
We conducted a systematic review and meta-analysis of studies involving CKD patients treated on OACs. The following outcomes were evaluated: ischemic stroke (IS), intracerebral hemorrhage (ICH), combined ischemic and hemorrhagic stroke (stroke
combined
), stroke or systemic embolism (S/SE), mortality, and major bleeding events. CKD was defined based on creatinine clearance (CrCl) as determined by Cockgroft-Gault formula, ranging from mild (CrCl: 60-89 ml/min), moderate (CrCl: 30-59 ml/min) and severe (CrCl: 15-29 ml/min). Patients with CrCl<15ml/min on hemodialysis or underwent transplantation were excluded.

Results:
We identified 16 studies (7 comparing DOAC vs. VKA & 9 comparing VKA vs. no VKA) comprising 88,610 patients. VKA use (vs. no VKA) was associated with reduced risk of IS [RR=0.71 (95%CI: 0.58-0.88), I
2
=55%] and mortality [RR=0.70 (95%CI: 0.62-0.78), I
2
=66%], but increased the risk of ICH [RR=1.57 (95%CI: 1.22-2.02), I
2
=0%]. In comparison to VKA, DOAC use demonstrated lower risk of ICH [RR=0.43 (95%CI: 0.33-0.56), I
2
=13%], stroke
combined
[RR=0.83 (95%CI: 0.72-0.96), I
2
=0%], S/SE [RR=0.73 (95%CI: 0.62-0.85), I
2
=45%] and major bleeding [RR=0.77 (95%CI: 0.66-0.90), I
2
=72%]. In adjusted analyses, VKA use (vs. no VKA) was associated with reduced mortality [HR
adj
=0.68 (95%CI: 0.61-0.76), I
2
=49%], whereas DOAC (vs. VKA) use reduced the risk of ICH [HR
adj
=0.39 (95%CI: 0.30-0.50), I
2
=0%] and S/SE [HR
adj
=0.75 (95%CI: 0.65-0.88), I
2
=14%]. Our sensitivity analyses comparing different DOACs showed that factor Xa inhibitors consistently reduced stroke
combined
[RR=0.84 (95%CI: 0.73-0.96), I
2
=0%], mortality [RR=0.84 (95%CI: 0.70-1.00), I
2
=0%], ICH [RR=0.45 (95%CI: 0.24-0.85), I
2
=42%] and major bleeding [RR=0.76 (95%CI: 0.64-0.91), I
2
=48%].

Conclusions:
Amongst CKD patients treated with OAC, DOACs present with a better safety and efficacy profile in various cardiovascular outcomes.
Abstract 98: Neurofilament Light Chains Predict Outcome After Ischemic Stroke
Authors: Uphaus Timo , Gröschel Sonja , Kuhle Jens , Weber-Krüger Mark , Wachter Rolf , Gröschel Klaus
Published: January 2019

Introduction:
Serum neurofilament light chains (sNFL) are a marker of axonal injury in various neurologic diseases. We aimed to address their diagnostic and prognostic value in patients following acute ischemic stroke.

Methods:
We selected patients from the Find-AF trial (ISRCTN 46104198) with available serum samples 24 h after hospital admission and further brain imaging (MRI or CT-Scans with minimum 3 days after symptom onset). sNFL levels were measured using the SIMOA technique. Infarct size on brain imaging was classified as lacunar (< 10 cm
3
) or non-lacunar (>10 cm
3
). We assessed whether sNFL was associated with: (I) clinical severity on admission (II) lesion volume in brain imaging and (III) functional outcome after 3 and 12 months.

Results:
58 patients fulfilled the inclusion criteria with a median age of 73 years (IQR 61-79), median NIHSS at baseline of 4 (IQR 2-8) and median modified Rankin Scale (mRS) at baseline of 3 (IQR 2-4). Among patients with acute ischemic stroke, sNFL levels were not associated with clinical severity (measured by NIHSS and mRS; p = 0.83 and p = 0.43, respectively) or lesion size in brain imaging at baseline (lacunar 80.3 pg/ml, non-lacunar 122.9 pg/ml, p = 0.16). Nevertheless, baseline sNFL levels correlated with functional outcome as measured by mRS after 90 days: mRS ≤ 2, 75.9 pg/ml; mRS > 2, 110.8 pg/ml; p = 0.018. This prognostic ability of sNFL was preserved for functional outcome measurements after 12 month: mRS ≤ 1, 71.3 pg/ml; mRS > 1, 99.7 pg/ml; p = 0.044. The prognostic accuracy for prediction of stroke outcome is reflected by an AUC of 0.71 for the 3-month outcome and an AUC of 0.69 for the 12-month outcome (see Figure 1).

Conclusion:
sNFL levels after ischemic stroke predict clinical outcome after 3 and 12 months.
Abstract NS2: Electronic Stroke Outcome Reporting to Enhance Practice Improvement and Education Among Emergency Nurses, A Pilot Study
Authors: Espaillat Kiersten , Closser James B , Froehler Michael T , Ebersole Joseph , Scheving William L , Ward Michael J
Published: January 2019

Background:
Feedback is an effective mechanism to change provider behavior. However, emergency department (ED) nurses who transfer acute stroke patients, rarely receive patient outcomes. Interviews with ED nurses found that knowledge of outcomes was a source of job satisfaction, education, and potential process improvement.

Purpose:
The purpose of this program was to develop an electronic tool to report acute stroke patient outcomes to ED nurses. We sought to evaluate the feasibility and usability of this tool.

Methods:
We piloted this project in May 2018 in Nashville, TN at three EDs. Staff were identified through leadership using emails and fliers and they could specify their communication preference (email or text). Clinical presentation, operational metrics (e.g., ED arrival-to- CT), 72 hour clinical status, and interesting images (e.g., CT scan) for patients with a stroke alert were reported in a de-identified manner (
Figure
). We assessed usefulness and likelihood to change, and were able to claim continuing education credit. Simple descriptive statistics were calculated.

Results:
We enrolled 107 nurses and identified 56 stroke outcomes, 55 of which had at least one nurse registered. Nurses preferred email updates (79.4%) over text and viewed outcomes 41 out of 113 opportunities (36.2%). Nurses reported (N=17) a mean usefulness score (out of 100) of 81.9 (SD 15.3) and a likelihood to change (N=14) of 38.4 (SD 28.9). Four nurses either initiated or completed the continuing education activity.

Conclusions:
Electronic stroke outcome reporting is feasible and useful to ED nurses. Continuing education may not influence patient follow-up. The time required to summarize and create the update limits scalability but may be addressed through automatic electronic data pulls. In conclusion, an electronic tool may be an effective mechanism to communicate inter-organizational patient outcomes and may be a source of education of best practices in acute stroke care.
Abstract NS3: Engaging Nursing Students in Stroke Research & Practice
Authors: Girouard Shirley , Carr Suzanne
Published: January 2019

Problem & Background:
Residents of an urban, ethnically & racial diverse & resource-limited community where the college of nursing is located are at high risk for stroke. Recognizing this as a major population health issue for our community & nursing’s essential role improving health outcomes, faculty engaged with stroke center leadership to determine concerns. In addition, a curricular audit revealed stroke care competencies (knowledge, skills & attitudes-KSAs) were not well reflected in the curriculum & thus, the need for enriched graduate and undergraduate stroke curriculum. Also, we needed to build our research & EBP capacity with relevant & meaningful activities.

Purpose:
To increase student KSA’s in stroke care & stroke related nursing research/EBP.

Methods:
Faculty leading the stroke initiative worked with the stroke center nursing & physician leaders to identify teaching content & clinical practice opportunities for undergraduate & graduate students to integrate into existing courses. Stroke was an exemplar for population health teaching & learning in several courses. Faculty also identified stroke related research & EBP topics for students in a graduate research course.

Results:
Faculty & students are involved in several inter-professional projects & are applying for grants to support their work. Other learning opportunities include: stroke nursing unit as a designated education unit; student-led stroke support groups; & reducing missed appointments & readmissions. Community health course undergrads are conducting a study to describe the organization & delivery of community stroke services. Graduate students developed 4 stroke EBP project proposals presented at graduate & nursing research days on campus. Faculty & students presented their research & EBP proposals at outside conferences & have been recognized as STTI Rising Stars.

Conclusions:
All involved have expressed excitement & satisfaction with the stroke initiative. Students have demonstrated significant learning about stroke, their role in care across the continuum & stroke related research & EBP. Thus, this effort contributes to nursing engagement in stroke research & practice that promises to improve stroke related outcomes in our at risk community.
Abstract NS5: Is the Extended Time Window Approach Safe in Pediatric AIS? Lessons Learned From 3 Cases
Authors: Kousa Yussef , McCullough Michael , Khademian Zarir , Carpenter Jeffrey , Rai Ansaar , Mayson Douglas , Stemer Andrew , Denny M. Carte , Chalifoux Ashley , Berkowitz Frank , Pergami Paola
Published: January 2019

Background:
Pediatric stroke is a rare but important cause of mortality and morbidity in this population. Endovascular therapy up to 24 hours after symptoms onset is beneficial in adults LVO acute ischemic stroke (AIS), but no safety or efficacy data of this approach is available for patients <18.

Methods and Results:
We present three pediatric AIS cases (age 15-17) treated at GUH and WVU with endovascular techniques using extended time-window with selection based on perfusion criteria.
Case 1
: 17 year old patient with history of Ebstein’s anomaly presented the day after a cardiac catheterization procedure with right hemiparesis and aphasia (NIHSS = 22). CTP identified left proximal ICA occlusion (ASPECTS score 7). Using the Penumbra device successful clot retrieval was achieved at 9:19 hours from onset. She was found to have a venous clot and right-to-left shunt from an atrial septal defect. 3 months mRS was 1.
Case 2
: 17 y.o. female with 2 weeks history of intermittent right arm numbness presented with left hemiparesis and hemi-sensory loss (NIHSS 12). ER arrival time was 18:43 hours from the onset of sensory symptoms. CTP demonstrated complete right M1 occlusion secondary to right sub-clavian thrombus (ASPECTS score 8). Using the Solitaire stent retriever, recanalization was obtained at 20:05 hours after clinical onset. 3 months mRS was 1.
Case 3
: 15 y.o female with Down syndrome, recently started on BCP woke up with right hemiparesis and aphasia (NIHSS = 22). MR perfusion demonstrated a distal M1/M2 clot with a large mismatch in the left MCA territory. Using a stent retriever device complete recanalization was obtained at 14:46 hours from the last time she was well. On the day of discharge her NIHSS was 7. Complete recanalization (TICI 3) was obtained in all three patients. No complications were observed during or following the procedure. NIHSS before and after the procedure improved by 11-to-17 points.

Conclusions:
A controlled study regarding endovascular approach in pediatric stroke is unlikely to occur. Therefore, case series must be reported in order to understand the safety of this approach. Strict patient selection and a team approach involving multiple pediatric and adult expertise are needed for a pediatric AIS response that includes endovascular intervention.
Abstract NS9: Nurse Advocacy in the Development of Outpatient Stroke Clinics: Led and Managed by Nurses
Authors: James Amanda , Debenham Ellen , Hegedus Mary , Davis Sherry , Turner Nancy , Holmstedt Christine
Published: January 2019

Background:
Telestroke has significantly improved acute stroke care in intensive care and inpatient settings, but post discharge care has been lacking and fragmented resulting in poor secondary stroke prevention, post-stroke complications, and inadequate patient education. Immediate need for stroke follow up ignited the development of telemedicine outpatient stroke clinics led and managed by nurses and nurse practitioners. Nurses identified these gaps and advocated for telestroke clinics in rural areas.

Purpose:
The purpose of this program was to develop a nurse led telemedicine outpatient stroke clinic and improve access to expert neuro consults.

Methods:
Through affiliate relations with healthcare facilities and nurse advocacy, the continuity of stroke care in local communities was expanded to 2 telemedicine outpatient clinics. A specialized nurse practitioner was credentialed, privileged, and trained to conduct telemedicine appointments. Telehealth nurse coordinators trained clinics on the neurological assessment and telepresenter role. Data was analyzed assessing appointment compliance rates, miles saved, and cost of travel.

Results:
Between October 2017 and August 2018, 48 patients were seen at nursing led telestroke outpatient clinics. Data showed a decrease in no show appointments from fiscal year 2016 (16.29%) to 2018 (15.3%). On average, patients saved 5896 miles round trip (122.8 miles per patient) and saw a cost savings of $655.11 in gas (at $2.50/gallon). Community facilities received downstream revenue from ancillary studies; however, coordinating pre appointment scans initially exhibited interruptions in patient care. Further challenges included training clinicians on technology platforms, while simultaneously assisting remote neuro specialists with hands on patient assessments.

Conclusion:
Nursing advocacy for the development of telestroke outpatient clinics has shown promising improvements in no show appointment rates, increased access to specialty care, and reduction in travel burdens. Further growth and expansion of telemedicine outpatient clinics by nurses is essential in providing a holistic approach for specialized patient care and empowering nurses to be an advocate in the continuum of stroke care.
Abstract TMP1: Time From Image Acquisition to Interventional Team Notification: A New Target for Enhancing Acute Stroke Workflow
Authors: Yaeger Kurt , Shoirah Hazem , Pai Akila , Mocco J , Fifi Johanna T
Published: January 2019

Background:
Reducing time to reperfusion for emergent large vessel occlusion (ELVO) has consistently shown to correlate with favorable outcome after ischemic stroke. However, there are many barriers to the efficient delivery of care. We hypothesize that the time from radiological image acquisition to interventional neuroradiology (INR) team activation makes up a significant, yet modifiable period of time within the acute stroke workflow.

Methods:
An institutional, prospectively-maintained registry was queried for patients who underwent endovascular thrombectomy (EVT) for ELVO during the one-year period between August 1, 2017 and July 31, 2018. Patients were excluded if imaging was obtained after activation of the INR team, or if times were not recorded. We calculated the time from image acquisition, defined as time of first CT imaging, to INR notification.

Results:
The time from initial CT acquisition to INR activation was available in 151 out of 183 patients (83%) who underwent thrombectomy during this one-year period. The team was notified after imaging in 62 patients (34%). The remainder either underwent imaging after INR notification (49%) or times were not recorded (17%). On average, this time was calculated to be 50.8 minutes (range 1-310 mins, SD 63 mins), and made up on average 11% of the total time from presentation to final reperfusion (range 0.4-55%, SD 7.0%). When broken down between stroke codes with rapid (≤30 min) and delayed (>30 mins) notification times, the overall time to reperfusion increased from 168 minutes to 307 minutes (p<0.001). The proportional time delay as caused by lagging imaging notification increased from an average of 9% to 26% of the total time delay until reperfusion, in rapid and delayed cases respectively (p<0.001).

Discussion:
We have identified delays in the time between initial CT imaging acquisition to notification of the INR team, and further observe that delays in this time period lead to proportionally greater delays in overall time to reperfusion. Imposing a more efficient communication process to reduce this time would decrease overall time to reperfusion, including automating neuroradiological interpretations, enhancing stroke team mass notification, and streamlining the chain of communications.
Abstract TMP103: Relationship Between Parent Brain Large Arteries and Their Penetrating Arterial Offspring
Authors: Gutierrez Jose , Morgello Susan , Dwork Andrew , Brickman Adam , Mohr Jay P , Elkind Mitchell S , Marshall Randolph
Published: January 2019

Introduction:
Brain arteries, large and small, are exposed to aging and acquired risk factors simultaneously. Therefore, we hypothesize that pathological changes noted with brain large artery aging, such as intima thickening, luminal dilatation and/or atherosclerosis, will be observed in their penetrating arterial branches.

Methods:
We extracted 1,695 brain large arteries and 1,233 corresponding penetrating arteries from 211 autopsied brains (mean age 67 ± 18 years, 60% men, 73% non-Hispanic white, 17% with brain infarcts). From each arterial segment we obtained measures of lumen, wall, intima and interadventitial diameters, and percentage stenosis using a semi-automated method based on color-thresholding. We visually rated the presence of concentric intima thickening and/or atheromas. We used hierarchical models to relate large artery characteristics to their penetrating arteries.

Results:
Of the 1695 large arteries, 182 (11%) were sectioned in continuity with the ostia of penetrating arteries and 1,233 (42%) exhibited cross-sections of their penetrating arteries at their peripheries (Figure 1). Of the 182 penetrating artery ostia, 123 (67%) exhibited intima thickening and in 46 (37%), the ostia was the only location in the cross-section of the large artery that had intima thickening. The mean luminal diameter of penetrating branches was 280 ± 231 μ and 19% had intima thickening (Figure 1). Large artery characteristics were associated with measures of penetrating artery disease (table 1).

Conclusion:
We found evidence that pathological changes in brain large arteries are observed in their penetrating arterial branches, supporting the notion that brain arterial aging occurs as a continuum. The unique geometric configuration of the penetrating artery ostia may predispose them to intimal thickening early on. Segregating brain arterial disease into small or large artery underestimates the extent of cerebrovascular disease attributed to each category.
Abstract TMP104: Upregulation of Tissue-Nonspecific Alkaline Phosphatase in Endothelial Cells Leads to Intracranial Vascular Calcification: A Useful Model of Primary Familial Brain Calcification
Authors: Uts Alla , Mayr Yevgeniy , Singla Pranav , Khan Mohammad , Kampton Elias , Millán José Luis , Savinova Olga V , Ramos Raddy L
Published: January 2019

Introduction:
Vascular calcification is an important pathophysiological factor contributing to neurodegenerative diseases such as primary familial brain calcification (PFBC) and is a potential therapeutic target.

Hypothesis:
Given the essential role of tissue-nonspecific alkaline phosphatase (TNAP) in biomineralization, we tested the hypothesis that upregulation of TNAP activity can lead to intracranial calcification.

Methods:
We previously reported that overexpression of TNAP in endothelial cells (eTNAP) leads to arterial calcification. Here we analyzed intracranial calcification in eTNAP on the original B6;129 and on the C57BL/6 (B6) genetic backgrounds. Histology was performed on formalin-fixed cryo-preserved tissues. Locomotion testing was performed at 23 weeks and analyzed in Matlab. Gene expression was analyzed by qPCR.

Results:
On the B6;129 background, eTNAP mice developed progressive intracranial calcification (0% were affected at 8 weeks, 71% at 13 weeks, and 100% at 23 weeks, n=7 per group). At 23 weeks, calcification was undetectable in the middle cerebral arteries but was associated with microvasculature in the basal ganglia, thalamus, hindbrain, and cerebellum. Calcified lesions were accompanied by astro- and micro-gliosis. Extravasation of IgG into the brain parenchyma was evident in eTNAP; blood-brain barrier was intact in controls (n=3 per group; 23 weeks). There were no significant differences in the locomotion or behavior (open field exploration) between the eTNAP and controls on the B6;129 background (n=6 per group). On B6 background, eTNAP mice displayed significant motor deficits - reduced ambulation (p<0.01), rearing (p< 0.01), speed (p<0.05), and acceleration (p<0.05; n=7-9 per group). There were no changes in osteogenic gene expression or phosphate transporters in eTNAP brains compared with controls. However, we detected significant regional differences between the thalamus and cortex in the levels of
RumX2
,
Spp1
,
SLC17a7
,
SLC17a6
of both control and eTNAP mice.

Conclusions:
Upregulation of TNAP activity can lead to intracranial vascular calcification. Given the similarities in presentation between eTNAP mice and PFBC patients, this model can advance the understanding of PFBC disease progression.
Abstract TMP108: Evaluation of Cerebral Arteriovenous Malformations using Flow Distribution Network Graphs and Dual-VENC 4D Flow MRI
Authors: Aristova Maria , Vali Alireza , Ansari Sameer , Shaibani Ali , Jahromi Babak , Potts Matthew , Hurley Michael , Alden Tord , Markl Michael , Schnell Susanne
Published: January 2019

Introduction:
Cerebral arteriovenous malformation (AVM) is the most common cause of hemorrhagic stroke in young adults. AVM affects the total blood flow to the brain as well as the extranidal flow distribution, yet quantitative data relating AVM hemodynamic parameters to hemorrhage risk are lacking. 4D Flow MRI provides time-resolved 3D blood flow velocity with full volumetric coverage of principal arteries and veins. This study aims to investigate the impact of anatomical differences in vessel connectivity on blood flow, and to identify potential quantitative biomarkers for AVM stroke risk stratification.

Methods:
4D flow MRI was obtained for healthy controls (n = 26) and patients with unruptured AVM (n = 5, Fig. 1A). A semiautomated in-house tool was used to compute blood flow and peak velocity at multiple points per vessel from 4D flow data (Fig. 1B). Results and vessel connectivity are schematically summarized as a Flow Distribution Network Graph (FDNG) for group comparison and secondary metrics.

Results:
In the healthy cohort, we identified 3 main COW variants: A (complete COW, n = 13), B (no RPCOM, n = 5) and C (both PCOMs missing, n = 4). Group comparison FDNGs (Fig. 1C) show significant differences between groups A and B in RICA flow (p = 0.026) and right A/P flow ratio (p = 0.036). AVMs were characterized by total cerebral blood flow and flow diversion to the nidus. AVM draining veins had significantly higher peak velocity (p = 0.032) relative to feeding arteries than non-draining veins relative to non-feeding arteries and control venous/arterial ratios (p = 0.002, Fig. 1D).

Conclusions:
Network analysis of 4D flow MRI data can identify significant differences in flow distribution between normal variant groups and provide standardized metrics of AVM hemodynamics, including peak velocity, which specifically distinguishes AVM nidal flow. These metrics account for individual vascular network variation and may provide a path forward for risk stratification.
Abstract TMP109: Loss of Gray-White Contrast in Cerebral Amyloid Angiopathy: An in-vivo and Ex-Vivo Exploratory Approach
Authors: Fotiadis Panagiotis , van Veluw Susanne , Salat David , Warren Andrew , Grill Sarah , Schwab Kristin , Zollei Lilla , Viswanathan Anand , Gurol M. Edip , Greenberg Steven M
Published: January 2019

Background/Purpose:
Cerebral Amyloid Angiopathy (CAA) is associated with cortical and white matter atrophy. We hypothesized that changes in neural tissue signal properties could reflect microstructural alterations in diffusion, and hence demyelination.

Methods:
Two cohorts of non-demented CAA patients were examined (3T: 45 CAA patients vs 16 age-matched Healthy Controls [HC]; 1.5T: 66 CAA patients vs 18 matched HC), and dichotomized into moderate (3T: n=19; 1.5T: n=24) and severe CAA.
FreeSurfer
was employed to calculate gray and white (GW) matter signal intensities from a T1-weighted sequence, and their ratio was used to assess GW contrast. Two diffusion markers (fractional anisotropy [FA]; apparent diffusion coefficient [ADC]) were measured via Diffusion Weighted Imaging. In addition, brains of 13 deceased patients with CAA were scanned ex-vivo, sectioned, and stained using Luxol Fast Blue, to assess myelin content. GW ratio was calculated the same way as in the in-vivo cohorts.

Results:
CAA patients displayed loss of GW contrast, expressed by increased GW intensity ratio (3T: 0.802±0.01; 1.5T: 0.757±0.02), when compared to HC (3T: 0.789±0.01,p=0.003; 1.5T: 0.738±0.01,p<0.0001). Patients with severe CAA showcased even lower GW contrast (3T: 0.806±0.01; 1.5T: 0.763±0.02) than patients with moderate CAA (3T: 0.797±0.01,p<0.05; 1.5T: 0.745±0.02,p<0.05) [
Fig
]. Moreover, loss of GW contrast within CAA correlated with lower FA (r=-0.30,p=0.049) and increased ADC (r=0.52,p<0.0001). Within the ex-vivo CAA cohort, loss of GW contrast was highly linked to a decrease in underlying myelin concentration (p=0.0025).

Conclusions:
CAA patients consistently displayed lower GW contrast compared to HC. This loss of contrast became more pronounced with increased disease severity, and correlated with lower anisotropy and increased water diffusivity. Indeed, an ex-vivo CAA cohort revealed that loss of GW contrast corresponded to a decrease in myelin concentration.
Abstract TMP111: Prediction of Cognitive Impairment after Intracerebral Hemorrhage using MRI Small Vessel Disease Score
Authors: Pasi Marco , Sugita Lansing , Xiong Li , Charidimou Andreas , Boulouis Gregoire , Pongpitakmetha Thanakit , Singh Sanjula , Kourkoulis Christina , Schwab Kristin , Greenberg Steven M , Anderson Christopher , Gurol M. E , Rosand Jonathan , Viswanathan Anand , Biffi Alessandro
Published: January 2019

Introduction:
Survivors of Intracerebral Hemorrhage (ICH) are at high risk for cognitive impairment. Previous studies clarified that Cerebral Small Vessel Disease (CSVD) is a primary contributor to post-ICH dementia, but these observations have failed to transform clinical or research practice standards to date. We sought to determine whether a validated MRI CSVD scoring system could readily predict cognitive impairment after ICH.

Methods:
We analyzed data from ICH survivors with no history of prior cognitive impairment, enrolled in a single-center prospective study. We reviewed MRI scans to compute: 1) a validated 6-point score for CSVD burden based on presence of microbleeds, white matter hyperintensities, lacunes and >20 basal ganglia enlarged perivascular spaces; 2) cortical atrophy. We quantified cognitive performance by: 1) administering the Telephone Interview for Cognitive Status (TICS) test; 2) identifying diagnosis of dementia based on medical records. We utilized linear mixed model analyses to identify predictors of changes in TICS score, and Cox regression to identify predictors of new-onset dementia. We calculated CSVD score cut-offs to maximize sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosis of dementia.

Results:
We enrolled 612 primary ICH survivors, and followed them for a median of 46.3 months (Inter-Quartile Range: 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Increasing CSVD scores were associated with faster cognitive decline (Coeff -0.25, Standard Error 0.02) and dementia diagnosis (Hazard Ratio 1.33, 95% CI 1.08-1.64). Age, increasing atrophy scale score, lower TICS score at baseline and systolic blood pressure were also independently associated with faster cognitive decline and new-onset dementia (all p<0.001). A CSVD score cut-off of ≥ 2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis, with PPV of 84% and NPV of 91% respectively.

Conclusion:
This validated CSVD score is strongly associated with cognitive performance after ICH, with excellent predictive performance for future diagnosis of dementia. Our results support its implementation in clinical care and in future studies of post-ICH dementia.
Abstract TMP115: Carotid Atherosclerosis Progression and Hippocampal Volume
Authors: Romero Jose R , Demissie Serkalem , Beiser Alexa , DeCarli Charles , Baradaran Hediyeh , Polak Joseph F , Ramachandran Vasan , Seshadri Sudha
Published: January 2019

Background:
Carotid atherosclerosis is a known risk factor for stroke and dementia. Carotid atherosclerosis may play a role in neurodegeneration and be a potential target for treatment and preventive efforts for stroke and dementia in asymptomatic individuals. We studied the association of carotid intima media thickness (CIMT) with hippocampal volume (HV) in community-dwelling individuals, and hypothesize that persons with carotid atherosclerosis progression would have a lower HV.

Methods:
We studied 1,376 Framingham Offspring participants (age 67±8.7 years; 53% women) with two carotid ultrasound measurements (1995-1998 and 2005-2008) and brain MRI scans at or near the second ultrasound, who were stroke, dementia, or other neurological illnesses-free at MRI. We used multivariable linear regression analyses to relate annualized carotid IMT change at internal [ICA] and common carotid [CCA] to HV volume (as a percentage of total cranial volume). Models were adjusted for age, sex, time interval between second carotid duplex and MRI, systolic blood pressure, hypertension treatment (HRx), diabetes, total cholesterol level, smoking, cardiovascular disease and baseline CIMT. We additionally assessed effect modification by HRx and statin use.

Results:
Mean (±SD) carotid IMT change per year was 0.064±0.082mm in ICA and 0.008±0.008 mm in CCA. Participants with higher ICA IMT progression had significantly lower HV after adjustment for vascular risk factors and baseline IMT (β±SE [standardized beta±standard error]: -0.067±0.027, p= 0.01), but not CCA IMT progression (β±SE: 0.01± 0.0276 p= 0.72). In subgroup analyses, we observed weaker association between ICA IMT change and HV among subjects with HRx (β = -0.047, p=0.19 vs. β =-0.096, p=0.026 in untreated individuals), but HRx by IMT change interaction was not statistically significant (p-interaction=0.39). Effects were similar in statin subgroups and statistically non-significant for CCA IMT progression.

Conclusions:
Cumulative vascular risk factor exposure, as reflected by ICA IMT progression, are associated with neurodegeneration represented by lower hippocampal volumes. Such changes occur prior to onset of clinical dementia, suggesting that carotid IMT may be a target for preventive efforts.
Abstract TMP118: The Gut Microbiota Can Protect Against the Onset of Symptoms in an Animal Model of Cerebral Small Vessel Disease
Authors: Bryan Robert M , Nelson James W , Zhang Bojun , Durgan David J
Published: January 2019

It has become increasingly evident that disruption of the gut microbiota plays an important role in multiple host disease states. We hypothesize that maintaining a healthy gut microbiome protects against the development of cerebral small vessel disease (CSVD), an inflammatory disease accompanied by blood-brain barrier (BBB) breakdown and neuroinflammation. To test our hypothesis, we altered the gut microbiota of spontaneously hypertensive stroke-prone rats (SHRSPs), a model of CSVD associated with hypertension, to resemble that of healthy/asymptomatic WKY control rats. At birth SHRSP pups were removed from their birth moms and nursed by either WKY (SW rats) or SHRSP (SS) foster dams until 21 days of age. At 20 weeks, markers associated with neuroinflammation were significantly decreased in SW rats compared to SS rats (NF-κB1 by 68%, TLR-2 by 58%, and TLR-4 by 54%, P≤ 0.01, n=5-6/ group). When compared to SS rats, SW rats showed a 33% (P=0.045) decrease in IgG extravasation into brain indicating greater BBB integrity. Systolic blood pressure at 20 weeks in SW was 173±6 mm Hg compared to 201±6 mm Hg in SS rats (P=0.003) and these pressures remained stable for until at least 30 weeks. Analysis of microbiota in feces revealed that gut microbiota of SW rats were significantly different from SS rats (P<0.05, principal components analysis of weighted Unifrac distances, n=5-6), resembled the microbiome in WKY rats, and showed > 2-fold increase in the abundance of the genus, Akkermansia, in SW compared to SS rats (6.1% vs 3.0%, P=0.01). Akkermansia can enhance gut integrity by stimulating epithelial cell mucus production and enhancing tight junctions. We conclude that the gut microbiota can influence the onset of CSVD-like symptoms even in the genetic SHRSP model. Maintaining a microbiota similar to WKY control rats, which includes an increased abundance of Akkermansia, appears to protect against the onset of CSVD. Altering the gut microbiota in humans could be an effective prophylactic measure to protect against CSVD.
Abstract TMP12: Pre Procedure Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Does Not Reduce the Risk of Distal Embolization with Mechanical Thrombectomy in Acute Ischemic Stroke: A Diffusion Weighted Magnetic Resonance Imaging (MRI) Study
Authors: Aytac Emrah , Asif Ahmer , Gurkas Erdem , Ahsan Humera , Chandrasekaran Premkumar N , French Brandi R , Qureshi Adnan I
Published: January 2019

Background:
It has been hypothesized that intravenous recombinant tissue plasminogen activator (rt-PA) prior to mechanical thrombectomy reduces the risk of intraprocedural distal embolization in acute ischemic stroke patients.

Methods:
We analyzed the diffusion-weighted imaging (DWI) acquired with 1.5- or 3- Tesla magnetic resonance imaging (MRI) scans obtained within 24 hours of mechanical thrombectomy in consecutive acute ischemic stroke patients. DWI was performed with single-shot echo-planar technique at b values of 0-1000 s/mm
2
. An independent physician identified distal embolization related foci of restricted diffusion on ipsilateral and contralateral hemispheres. Distal embolization was defined as discrete foci of restricted diffusion independent of the primary area of infarction on MRI. Patients were stratified based on whether they had or did not receive intravenous rt-PA prior to thrombectomy.

Results:
Distal embolization was seen in 48 of 50 patients (mean age ± SD; 62.9 ± 15.5 years) who underwent mechanical thrombectomy (mean number 9.1; range 0-22). The mean number of distal embolization was not significantly different between patients who had and those who did not receive intravenous rt-PA prior to mechanical thrombectomy (9.5 ± 6.2 versus 8.7 ± 6.5; p=0.67 by ANOVA). There was no difference in mean number of ipsilateral hemispheric distal embolization between the two groups (8.5 ± 6.4 versus 7.6 ± 6.4, p=0.61 by ANOVA). There was no relationship between mean number of emboli and age of the patient (regression coefficient 0.004; p=0.94) or time interval between symptom onset and thrombectomy (regression coefficient -0.02; p=0.67) on linear regression analyses.

Conclusion:
Although distal embolization is very common after thrombectomy, we did not find any evidence that intravenous rt-PA prior to procedure reduces the risk of intraprocedural distal embolization.
Abstract TMP16: IV tPA Does Not Delay Endovascular Thrombectomy and is Associated With Improved Clinical Outcomes
Authors: Sarraj Amrou , Hassan Ameer , Albers Gregory , Sitton Clark , Chen Peng R , Cai Chunyan , Pujara Deep , Cutter Gary , Imam Bita , Reddy Sujan , Kamal Haris , Vora Nirav , Abraham Michael , McCullough Louise , Grotta James , Gupta Rishi , Savitz Sean
Published: January 2019

Background:
Whether bridging therapy with IV tPA delays endovascular thrombectomy (EVT) or alters clinical outcomes is unknown.

Methods:
In this prospective multicenter cohort study of imaging selection for EVT (SELECT), consecutive patients with anterior circulation (ICA, M1, M2) occlusions who presented within 24 hrs from last known well were enrolled at 9 centers. We stratified patients into those who received IV tPA prior to EVT vs those who did not.

Results:
Of 445 enrolled, 284 received EVT; 222 (78%) treated within 6 hrs and 62 (22%) >6-24 hrs. 65% received IV tPA. Baseline characteristics were similar between the tPA and no tPA groups. There were no workflow delays associated with IV tPA: arrival to groin puncture, median (IQR) 92 (64-117) min in the tPA group vs. 82 (64-113) no IV tPA, p=0.52. The rate of functional independence (90 day mRS 0-2) was 57% with IV tPA vs. 47% without, aOR 1.7 (95% CI 0.95-3.05), p=0.07. The ordinal analysis showed a significant shift towards better 90 day mRS scores in the tPA group, aOR 1.9, 95% CI: 1.19-3.00, p=0.007. Mortality was 11% (tPA) vs 18% (no tPA), p=0.07 and sICH rates were 7% (tPA) vs. 5% (no tPA), p=0.5. Restricting the analyses to patients presenting directly to EVT centers within 4.5 hours (N=115), no significant delays were evident; arrival to puncture with tPA 95 (76-121) min vs 86 (68-114) without tPA, p=0.4. Functional independence was 62% with tPA vs 51% without, aOR 1.73 (95% CI 0.78-3.83, p=0.18) with a statistically significant shift in favor of tPA on the ordinal analysis, aOR 1.8, 95% CI: 1.08-3.45, p=0.038. Patients with M2 occlusions, smaller baseline infarct core volume, earlier treatment, and milder strokes were most likely to have better outcomes with tPA vs no tPA (Fig 1).

Conclusion:
IV tPA administration did not result in delays to EVT and was associated with higher rates of good outcome. Randomized trials are required to more definitively establish the efficacy of bridging therapy with tPA prior to EVT.
Abstract TMP17: Dodecafluropentane Emulsion in Acute Ischemic Stroke, a Phase One Randomized and Controlled Trial
Authors: Culp William C , Onteddu Sanjeeva , Brown Aliza , Nalleballe Krishna , Sharma Rohan , Skinner Robert , Witt Taylor , Marsh James
Published: January 2019

Introduction:
In Acute Ischemic Stroke (AIS) the effective therapeutic window remains very short for the vast majority of patients and severely limits those who qualify for acute therapy. The oxygen transporting nanodroplet Dodecafluoropentane emulsion (DDFPe) (NuvOx Pharma, Tucson, AZ) given IV within 3h of onset can reduce AIS symptoms and stroke volumes markedly in animal studies and may widen the window significantly for therapy. We conducted a randomized, placebo-controlled, double blinded, dose escalation AIS trial to demonstrate the Maximum Tolerated Dose, characterize adverse events and explore impacts on acute NIHSS values and long-term outcomes.

Methods:
AIS patients with NIHSS of 2-20 were randomized to either 3 doses of IV DDFPe or placebo, one every 90 minutes, starting within 12 hours of symptom onset. Doses were given as soon as possible between unmodified standard stroke care elements. Each dose cohort included 8 patients, with 2 receiving placebo and 6 DDFPe. Primary outcomes were SAEs, AEs, NIHSS values, and mRS.

Results:
No Dose Limiting Toxicities were encountered and no maximum dose defined. One unrelated delayed death occurred in the DDFPe group and one in the placebo group while SAEs and AEs were similar. Early DDFPe treatment of any dose had better NIHSS values at 4.5h than late doses, p=0.03. In high dose DDFPe mRS outcomes suggested improvement, p=0.01 at 30 days and p=0.03 at 90 days.

Conclusions:
IV DDFPe appeared safe at all doses. Early DDFPe treatment showed NIHSS improvements and high dose DDFPe patients suggested improved outcomes. Larger trials are warranted.