bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 109: Trevo 2000: Results of the Largest Real-World Registry for Stent Retriever for Acute Ischemic Stroke
Authors: Binning Mandy J , Veznedaroglu Erol , Budzik Ronald , English Joey , Baxter Blaise , Bartolini Bruno , Liebeskind David , Krajina Antonin , Gupta Rishi , Nogueria Raul
Published: October 2018

Objective:
The Trevo Registry was designed to assess real world outcomes of the Trevo Retriever in patients experiencing ischemic stroke. It is the largest prospective study for acute stroke intervention, with 2010 patients enrolled and 90 day outcomes in 1873 patients. The primary endpoint is revascularization status based on post-procedure TICI score and secondary endpoints include 90-day mRS, 90-day mortality, neurological deterioration at 24 hours and device/procedure related adverse events.

Methods:
The study was a prospective, open-label, consecutive enrollment, multi-center, international registry of patients who underwent mechanical thrombectomy for acute stroke using the Trevo stent retriever as the initial device.

Results:
The median NIHSS at admission was 16 (IQR 11-20). Most patients (70.8%) were treated at <= 6 hours from last known normal with a median procedure time of 50 minutes (32-77). The occlusion site was M1 or M2 in 73.9%. General anesthesia was employed in 43.5% of procedures. TICI 2b or 3 revascularization was 92.8% with an average of 1.7 passes with the device. Median NIHSS at 24 hours and discharge was 6 and 4 respectively. Fifty-five percent (55.2%) of patients had mRS ≤2 at 3 months and the overall mortality rate was 13.8%. Patients treated after 8 hours of symptom onset had a 95% revascularization rate and 51.2% mRS ≤2 at 3 months. The symptomatic ICH rate was 1.6%. Patients who met the revised AHA criteria for thrombectomy were found to have 59.5% mRS 0-2 at 90 days.

Conclusions:
The Trevo Retriever Registry represents the first real world data with stent retriever use in the era of clinical trials showing the overwhelming benefit of stent retrievers to treat acute ischemic stroke. Due to the fact that this data represents real world use of the Trevo Retriever, (e.g. subjects pre-stroke mRS >1 (29%) and those treated 6-24 hours after stroke symptoms (29%), this data cannot be compared to the results from recent trials with restricted eligibility criteria. Future subgroup analysis of this large cohort will help to identify areas of future research to enhance outcomes further with this treatment modality.
Abstract 111: Endovascular Therapy for Mild Strokes: How Low Should We Go?
Authors: Sarraj Amrou , Hassan Ameer , Grotta James C , Farrell Christine M , Goyal Nitin , Elijovich Lucas , Reishus Katelin , Krishnan Rashi , Sangha Navdeep , Wu Abel , Costa Renata , Malik Ruqayyah , Cai Chunyan , Parsha Kaushik N , Mir Osman , Hasan Rashedul , Snodgrass Lindsay M , Requena Manuel , Graybeal Dion , Abraham Michael , Chen Michael , McCullough Louise , Savitz Sean I , Ribo Marc
Published: October 2018

Background:
Endovascular therapy (EVT) is the standard of care for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) with NIHSS ≥ 6. LVO patients may present with mild (NIHSS <6) but disabling deficits and were not well represented in RCTs resulting in a NIHSS cutoff of ≥ 6 on AHA guidelines. Milder deficits may not justify EVT risk-benefit ratio. To generate practice level data, we evaluated EVT treatment effect in mild stroke.

Methods:
A retrospective cohort from 8 USA and Spain centers of AIS with LVO in the anterior circulation with NIHSS ≤ 6 presenting within 24 hrs (1/12 to 3/17) was pooled. EVT patients were compared with those only treated with medical management (MM). 90 day mRS (0-1 excellent) was chosen as the primary outcome as an appropriate goal for mild stroke. Multivariable analyses compared the treatment effects and their interactions with NIHSS, both as an ordinal and dichotomized (0-3 vs 4-5) variable. Adjustment was made for age, time LSN to EVT center arrival, IV-tPA, occlusion site and ASPECTS. Within center correlation was accounted for.

Results:
223 patients were included (EVT 105, MM 118). The two groups had similar baseline age (65.7 and 66.3 yrs, p=0.73), ASPECTS (9.4 and 9.3 p=0.53), %IV t-PA (39% and 36% p=0.65) and median (IQR) time mins to EVT center 156(66.5-301) and 212(90-387) p=0.09, EVT and MM respectively. There was no difference in outcomes (54.6% EVT vs 53.4% MM) when all patients (NIHSS 0-6) were assessed (aOR 0.94, 95% CI 0.62-1.40, p=0.94); same for NIHSS 0-5 (55.1% EVT vs 55.6% MM), (aOR 0.95, 95% CI 0.71-1.26, p=0.95). For NIHSS 0-3, MM had better outcomes (51.9% EVT vs 74.6% MM), (aOR 0.39, 95% CI 0.25-0.61, p<0.01). For NIHSS 4-5, results favored EVT (57.1% EVT vs 22.2% MM), (aOR 4.04, 95% CI 2.56-6.38, p<0.01). Fig 1, 2 show CIs of EVT and MM as related to NIHSS.

Conclusion:
Though limited by a non-randomized comparison, the data suggest a possible benefit for EVT in mild strokes with NIHSS 4-5. In NIHSS ≤3, the intervention had no additive benefit.
Abstract 118: Quantitative Cerebral Blood Flow Measured With Arterial Spin Labeling MRI in the Unaffected Hemisphere Predicts Outcome in Acute Ischemic Stroke
Authors: Thamm Thoralf , Guo Jia , Rosenberg Jarrett , Liang Tie , Christensen Soren , Marks Michael P , Do Huy M , Kemp Stephanie M , Eyngorn Irina , Ryan Emma A , Lansberg Maarten G , Albers Greg W , Zaharchuk Greg ,   iCAS Study Investigators
Published: October 2018

Introduction:
Arterial spin labeling (ASL) MRI can non-invasively measure quantitative CBF. Evaluation of hemodynamics in the ipsilateral hemisphere is a common practice for selecting patients for therapy. In this study, we hypothesized that the contralateral CBF (cCBF) may identify patients with high collateral capacity and better outcome.

Hypothesis:
In acute stroke, higher CBF in the unaffected hemisphere is associated with better neurological outcome.

Methods:
Patients were part of the prospective ‘iCAS’ (imaging the Collaterals in Acute Stroke) study. Inclusion criteria were: ischemic hemispheric stroke (< 16 hrs onset to imaging time [OIT]), age>=18, informed consent, and technically adequate imaging including GRE, DWI, and 3D pseudocontinuous ASL. Outcomes were assessed by NIHSS at baseline, day 1, and day 5; and mRS at day 30 and day 90. After image registration to an MNI template, mean cCBF was calculated at standard ASPECTS levels in the contralateral hemisphere. Patients were dichotomized by median cCBF into low and high cCBF groups. Results are reported as medians with interquartile ranges [IQR]. Outcome differences were assessed with Wilcoxon (NIHSS) and Fisher’s exact test (mRS).

Results:
61 patients met inclusion criteria: 32 F, age 66 yrs [54-77], OIT 4.8 hrs [3.4-7.2], baseline NIHSS 13 [8-19], 36 underwent thrombectomy [28 with final TICI >= 2b], cCBF 38.8 [31-46] ml/100 g/min. There was no difference between groups in age, gender, OIT, or reperfusion. Median NIHSS at baseline/day1/day5 for low and high cCBF groups was 13/14/11 and 12/6/4, respectively, which was significantly different on day 1 (p=.009) and day 5 (p=.031). Patients with higher cCBF had lower contralateral arterial transit time (p=.029) and better day 90 mRS (p=.029).

Conclusion:
Higher ASL cCBF predicts better outcome in acute stroke independent of baseline NIHSS and reperfusion status. This may reflect a better underlying capacity for collateral flow to the ischemic hemisphere.
Abstract 119: Predicting a Target Diffusion-Perfusion Mismatch at Extended Time Windows: Findings From the Lesion Evolution in Stroke and Ischemia on Neuroimaging (LESION) Study
Authors: Warach Steven , King Ben , Dula Adrienne N , Luby Marie , Latour Lawrence
Published: October 2018

Introduction:
The decrease in efficacy of reperfusion/recanalization interventions over time may be due in part to decreases in the presence a salvageable ischemic penumbra, which can be imaged as the perfusion-diffusion mismatch on MRI. Recent clinical trial evidence supporting the efficacy of endovascular interventions at later time windows suggest that a small core with a high NIHSS may also serve as a marker of the ischemic penumbra. We investigated the relationship of time, the site of arterial occlusion and NIHSS to the probability of a diffusion-perfusion mismatch.

Method:
The LESION study was a prospectively collected cohort of 1,092 consecutive subjects, NIHSS>3, scanned within 24 hours of symptom onset of time last known well. Target diffusion-perfusion mismatch was qualitatively assessed by a method previously demonstrated as equivalent to volumetric methods or clinical-diffusion core mismatch. Endovascular target (EVT) was defined as an arterial occlusion of intracranial ICA or MCA-M1.

Results:
Within the first 6 hrs, 26.8% (174 of 475 patients) had an EVT occlusion compared to 19.4% (62 of 258) between 6-24 hrs. Of all EVT occlusions, 26.3% occurred later than 6 hrs. Images with an EVT occlusion had a target mismatch 77.1% of the time, compared to 39.5% for occlusions in other arterial branches (p < 0.001). While mismatch was present more often between 0-6 hrs compared to 6-24 hrs (OR = 1.706; p < 0.001), mismatch was still present in 40.1% of images collected after 6 hrs (vs 53.3% 0-6 hrs). Overall, the presence of mismatch declined over time (OR = 0.934; p<0.001). Multivariate modeling of target mismatch was best fit by including: time (OR= 0.943; p< 0.001), NIHSS (OR= 1.037; p< 0.005), EVT occlusion (OR= 9.450; p< 0.001), and an interaction between NIHSS and endovascular target (OR= 0.950; p=0.026).

Discussion:
Overall, within the first 24 hrs three quarters of patients with EVT occlusions have target diffusion-perfusion mismatch. Approximately one quarter of all EVT occlusions occur between 6-24 hrs. Multivariate models including time from last known well, NIHSS on presentation, and the presence of EVT occlusion best predicted the presence of a target diffusion-perfusion mismatch.
Abstract 125: Validation of a Clinical Risk Score for Predicting Atrial Fibrillation in Cryptogenic Stroke Patients With Insertable Cardiac Monitors: Insights From the CRYSTAL AF Study
Authors: Passman Rod S , Ziegler Paul D , Kwong Calvin , Crawford Michael H , Koehler Jodi L , Zhao Susan X
Published: October 2018

Introduction:
Insertable cardiac monitors (ICMs) have been shown to be superior to standard monitoring for the detection of underlying atrial fibrillation (AF) in patients (pts) with cryptogenic stroke (CS). However, identifying a subset of CS pts who would benefit most from ICMs is desirable. We evaluated whether a recently developed risk score for the prediction of clinically-detected AF in CS pts (the HAVOC score) also predicted the presence of subclinical AF as detected by ICMs.

Methods:
Pts who received an ICM in the CRYSTAL AF study were included. HAVOC scores were retrospectively calculated by assigning points based on the presence of hypertension (2), age ≥75 (2), valvular disease (2), vascular disease (1), obesity (1), congestive heart failure (4), and coronary artery disease (2), resulting in scores from 0-14 with pts assigned to Group A (0-1), B (2-3), or C (≥4) based on their score. The ICM monitored cardiac rhythm continuously for up to 3 years to identify the presence of AF. AF detected by the ICM (≥2 minutes) was correlated with HAVOC score groupings via the chi-square test.

Results:
A total of 214 ICM pts (mean age 61±11 years, 66% male) were followed for 1.8±0.7 years. Mean and median HAVOC scores were 2.4±2.6 and 2 [1-3], respectively, with 89% having scores ≤4. The AF detection rate at 3 years was 27%. Mean HAVOC scores tended to be higher among pts with vs. without AF detected (2.9±1.8 vs. 2.3±2.1, p=0.07). The proportion of patients with AF increased significantly from 11% to 18% to 32% as HAVOC scores progressed from Groups A to B to C, respectively (p=0.02).

Conclusions:
In a cohort of CS pts with ICMs, the prevalence of AF increased significantly with increasing HAVOC score groups. This parameter should be considered when comparing AF detection rates between different studies, as the vast majority of CRYSTAL AF pts had very low HAVOC scores. Further validation of this risk score in CS pts with ICMs is warranted across a broader spectrum of risk measured by this novel score.
Abstract 127: Untreated Hypertension After Intracerebral Hemorrhage
Authors: Van Sanford Carson , Walsh Kyle B , Sekar Padmini , Moomaw Charles J , Woo Daniel
Published: October 2018

Objective:
We previously reported that 46.9% of acute intracerebral hemorrhage (ICH) patients had untreated hypertension (HTN) on admission. We sought to investigate the prevalence of untreated HTN among patients at follow-up after ICH.

Methods:
ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) is a prospective multi-center study of ICH among whites, blacks, and Hispanics. Cases were enrolled at 42 recruitment sites. Subjects’ ethnicity, history of HTN, type of insurance, HTN medications, and level of education were collected. Patients were considered to have HTN if they received this diagnosis prior to or during initial ICH admission. Stroke events at follow-up included ischemic stroke, transient ischemic attack, subarachnoid hemorrhage, and recurrent ICH. Medication use was also recorded at follow-up.

Results:
Of 3,000 cases of ICH, there were 1,822 with HTN who had at least one follow-up, of which 9.4% had untreated HTN. Compared with treated patients at 3 months, those untreated at 3 months more frequently were white or Hispanic (p=0.0064), female (p=0.0236), over 65 years old (p<0.0001), or on Medicare (p<0.0001). Among those treated at 3 months, 60.5% were prescribed beta blockers, 54.9% calcium channel blockers, 52.9% ACE inhibitors, 31.5% diuretics, 16.6% vasodilators, 12.6% angiotensin receptor blockers, 10.3% alpha agonists, 2.8% nitrates, 2.5% alpha blockers, and 3.7% others. Stroke events occurred by 12 months in 5.5% of treated compared with 5.6% of untreated patients.

Conclusions:
Despite a high rate of untreated HTN at admission, the rate at follow-up was substantially lower. Overall, Hispanics were more likely and blacks less likely to be untreated than whites. Despite the lack of difference in stroke events identified among treated versus untreated patients, there was limited power to identify differences in a short-term follow-up due to a low rate of stroke recurrence and a low proportion of untreated HTN.
Abstract 130: Intracerebral Hemorrhage and Subsequent Risk of Arterial Thromboembolism
Authors: Murthy Santosh B , Diaz Ivan , Merkler Alexander , Iadecola Costantino , Navi Babak , Sheth Kevin , Kamel Hooman
Published: October 2018

Introduction:
Ischemic stroke and acute myocardial infarction (MI) have been reported as complications after intracerebral hemorrhage (ICH), but it is unclear if ICH is an independent risk factor for ischemic stroke and acute MI.

Hypothesis:
ICH is independently associated with a short-term heightened risk of ischemic stroke and acute MI.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. The exposure of interest was hospitalization with ICH. Our primary outcome was a composite of ischemic stroke and acute MI. We used validated
ICD-9-CM
diagnosis codes to identify our predictor and outcomes. To avoid inclusion of patients with ICH as a complication of stroke or MI, we did not count an event as ICH, if it occurred before or during a hospitalization for ischemic stroke or acute MI. Using Cox Regression, we calculated the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge. Confidence intervals (CI) were computed using the nonparametric bootstrap method.

Results:
Among 1,760,439 Medicare beneficiaries, the 5,924 who experienced an ICH were older (79.4 vs. 73.4 years) and had a higher prevalence of hypertension, coronary heart disease, and atrial fibrillation. Compared to patients without ICH, the risk of an arterial thromboembolic event was markedly higher in the first month after ICH (hazard ratio [HR], 6.7; 95% CI, 5.0-8.6), was substantially higher in the second month (HR, 4.6; 95% CI, 3.0-6.2), and remained significantly higher through the first 6 months (Figure).

Conclusions:
We found a strong association between ICH and subsequent arterial thromboembolic events such as ischemic stroke and acute MI. The risk was highest in the first 2 months after ICH and remained significantly elevated for approximately half a year.
Abstract 133: Cerebellar Hematoma Location: Implications for the Underlying Microangiopathy
Authors: Pasi Marco , Marini Sandro , Morotti Andrea , Boulouis Gregoire , Xiong Li , Charidimou Andreas , Ayres Alison , Lee Myung Joo , Biffi Alessandro , Goldstein Joshua N. , Rosand Jonathan , Gurol M. Edip , Greenberg Steven M. , Viswanathan Anand
Published: October 2018

Background:
Previous pathologic reports have suggested that the underlying vasculopathy in cerebellar intracerebral hemorrhage (ICH) patients may be related to the location of the bleed whithin the cerebellum. We sought to determine whether the location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small vessel disease pathology (hypertensive vasculopathy or cerebral amyloid angiopathy, CAA).

Methods:
Consecutive cerebellar-ICH patients were recruited from January 1998 to January 2016. Based on data from pathologic reports, patients were divided according to the location of the primary cerebellar hematoma (superficial,
Figure, panel A-B, blu circles in panel E
vs deep,
Figure, panel C-D, orange circles in panel E
). Location of cerebral microbleeds (CMB; strictly-lobar, strictly-deep and mixed-CMB) was evaluated on MRI.

Results:
One-hundred and eight patients (84%) had a deep cerebellar hematoma and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in superficial cerebellar-ICH patients (89% vs 65%, respectively; p<0.05). Among the 80 patients who underwent MRI, those with superficial cerebellar-ICH had higher prevalence of strictly lobar-CMB (46%) and lower prevalence of strictly deep or mixed-CMB (0%) compared to those with deep superficial cerebellar-ICH (6% and 54%, respectively). Presence of lacunes was significantly higher in deep cerebellar-ICH than superficial cerebellar-ICH (53 vs 21%, respectively; p<0.05). In a multivariable model, presence of strictly lobar-CMB was associated with superficial cerebellar-ICH (OR: 3.8; 95% confidence interval: 1.5-8.5; p=0.004).

Conclusions:
Our study showed that superficial cerebellar-ICH is related to the presence of strictly lobar-CMB, a pathologically proven marker of CAA. Cerebellar hematoma location may thus help to identify those patients likely to have CAA pathology.
Abstract 135: Door in Door Out Time at Primary Stroke Centers Predicts Outcome for Patients With Large Vessel Occlusion Stroke
Authors: McTaggart Ryan A , Moldovan Krisztina , Oliver Lori A , Hemendinger Morgan L , Yaghi Shadi , Baird Grayson , Haas Richard A , Jayaraman Mahesh V
Published: October 2018

Introduction:
We have previously shown that a transfer protocol for patients with suspected large vessel occlusion (LVO) stroke which includes early vessel imaging at the Primary Stroke Center (PSC) is associated with decreased onset to recanalization times driven entirely by improved initial hospital processes at the PSC and reflected in the PSC Door-in Door-out (DIDO) time. In this study, we examined the association between DIDO and outcomes.

Methods:
We collected prospective data on 195 patients transferred to our Comprehensive Stroke Center (CSC) with PSC-confirmed LVO between July 1, 2015 and June 30, 2017. The patients were accepted from 2 states and 16 different PSCs (only 2 of which were part of our hospital system) and the furthest PSC being 56 miles away. We included all patients with LVO stroke (ICA, M1, Basilar) with an NIHSS of 6 or higher. We examined PSC workflow factors associated with shorter DIDO times. Outcomes were examined by DIDO using generalized mix modeling assuming a binomial distribution with SAS 9.4.

Results:
The median [IQR] age and NIHSS of the 195 ELVO transfers was 75 [62-84] and 17 [12-22]. IV tpA was administered to 64% of patients. Regarding specific workflow metrics, Median [IQR] times (in minutes) for PSC door to CT was 12 [9-20], PSC door to CTA 26 [19-50], PSC door to tPA 58 [46-78], DIDO 87 [68-113], PSC door to CSC groin puncture 140 [115-179], and PSC door to CSC recanalization of 169 [136-216]. As can be seen in the Figure, longer DIDO were associated with more deleterious scores on discharge NIHSS (p=0.04), discharge mRS (p=0.009) and 90d mRS (p=0.002). Full execution of the PSC LVO protocol and “hold, drip and go” strategy for EMS transport were associated with shorter DIDO times.

Conclusion:
For patients diagnosed with LVO at a PSC, longer DIDO time appears to have a deleterious effect on outcome at discharge from the CSC and at 90 days. All PSCs should take measures to decrease DIDO and use it as a quality metric.
Abstract 149: CD36 in Perivascular Macrophages Contributes to Neurovascular and Cognitive Dysfunction and Amyloid Angiopathy in Mice Overexpressing the Alzheimer Aβ Peptide
Authors: Uekawa Ken , Park Laibaik , Hattori Yorito , Zhou Ping , Murphy Michelle , Anrather Josef , Iadecola Costantino
Published: October 2018

Amyloid-β (Aβ) exerts deleterious effects on the cerebral microcirculation, which may play a role in Alzheimer’s disease and mixed dementias. In mouse models of amyloid precursor protein (APP) overexpression, the vascular effects of Aβ require the innate immunity receptor CD36 in perivascular macrophages (PVM), immune cells located in the Virchow-Robin space surrounding penetrating cerebral vessels. PVM, in turn, induce vascular oxidative stress and dysfunction via NADPH oxidase (Park et al., Circ Res 2017). However, whether CD36 in PVM is involved in the cognitive impairment induced by Aβ remains unknown. We transplanted CD36
-/-
bone marrow (BM) into irradiated male APP-overexpressing mice (Tg2576) (age 12 months) to repopulate their perivascular space with CD36
-/-
PVM. Three months later, cerebral blood flow (CBF) was measured by laser-Doppler flowmetry in the somatosensory cortex of anesthetized mice with a cranial window (n=5/group). Cognition was also tested (n=10/group). In Tg2576 mice transplanted with WT BM (Wt→Tg), CBF responses induced by whisker stimulation (WS) or neocortical superfusion of the endothelium-dependent vasodilator acetylcholine (ACh) were attenuated compared to WT mice receiving WT BM (Wt→Wt) (WS, -35%; ACh, -36%; p<0.05). CD36
-/-
BM transplantation in Tg2576 mice (CD36
-/-
→Tg) prevented the cerebrovascular dysfunction (CBF increases: WS: Wt→Tg, 9±1% vs. CD36
-/-
→Tg, 21±2%; ACh: Wt→Tg, 9±1% vs CD36
-/-
→Tg, 17±2%; p<0.05), and reduced cerebrovascular amyloid deposition (thioflavin-S-based vascular amyloid load: -58%; p<0.05 from Wt→Tg). Wt→Tg mice spent more time finding the escape hole at the Barnes maze test, indicating impairment in spatial memory (Wt→Wt, 965±166 sec; Wt→Tg, 1807±166 sec; p<0.05), and showed impaired nest building ability (nesting score: Wt→Wt, 4.6±0.2; Wt→Tg, 1.8±0.2; p<0.05). These cognitive deficits were ameliorated in CD36
-/-
→Tg mice (Barnes maze: 1217±136 sec; nesting score: 2.7±0.3; p<0.05 from Wt→Tg). We conclude that CD36 in PVM is critically involved in the cerebrovascular and cognitive dysfunctions induced by Aβ, and in cerebral amyloid angiopathy. CD36 in PVM may be a new therapeutic target to counteract the detrimental neurovascular and cognitive effects of amyloid pathology.
Abstract 163: Natural History of Infectious Intracranial Aneurysms Undergoing Antibiotic Treatment
Authors: Rice Cory J , Cho Sung-Min , Zhang Lucy , Khoury Jean , Thatikunta Prateek , Wisco Dolora , Hussain M. Shazam , Uchino Ken
Published: October 2018

Introduction:
Infectious intracranial aneurysm (IIA, or mycotic aneurysm) is a cerebrovascular complication of infective endocarditis. We aimed to describe the clinical course of IIAs during antibiotic treatment.

Methods:
We reviewed medical records of persons with infective endocarditis who underwent cerebral angiography at a single tertiary referral center from 2011-2016. Aneurysms were followed with subsequent angiography for bad outcome (growth, rupture or new IIA formation) or good outcome (regression or resolution) until endovascular therapy, aneurysm resolution, or end of observation.

Results:
Of 618 patients included, 40 (6.5%) had 43 IIAs. Eighteen (42%) aneurysms underwent initial endovascular treatment. Twenty-five unruptured aneurysms were treated with antibiotics alone for a median 36 days (interquartile range (IQR) 9-57). Nine (36%) aneurysms had bad outcome (2 new IIA formation, 7 enlargement) at median 8 days, IQR 1-25. Angiography revealed good outcome in 7 (28%) patients (6 resolution, 1 regression) at median 36 days, IQR 16-49. Two patients had no IIA change after median 27 days, and both underwent endovascular treatment. Seven aneurysms had no angiographic reevaluations but no rupture during clinical follow-up for median 4 days, IQR 3-12. There were no aneurysmal ruptures during observation.

Conclusion:
IIAs represent a dynamic disease. Only a quarter of IIAs resolve with antibiotics alone.
Abstract 164: Changes in Retreatment Rates of Cerebral Aneurysms Over a 10-Year Period in a Population-Level Cohort
Authors: Daileda Taylor , Vahidy Farhaan S , Chen Peng Roc , Kamel Hooman , Liang Conrad , Sheth Sunil A
Published: October 2018

Introduction:
Prior studies have reported higher retreatment rates (RR) for cerebral aneurysms (CAs) after endovascular coiling (EC) compared to surgical clipping (SC). However, RRs have largely been derived from studies in the early 2000s and may not represent current practice.

Methods:
Using administrative data on all discharges from acute care hospitals in California (2005-2011) and Florida (2005-2014), we identified patients with ruptured and unruptured CAs who were treated with EC or SC. Retreatments within 3 months were excluded, to minimize the inclusion of planned retreatments. Logistic regression was used to assess factors associated with retreatment, and results are presented as OR [95% CI].

Results:
Among 19,650 patients with CAs, 12,441 (63.3%) were treated with EC and 7,209 (36.7%) with SC. Mean age was 57 ± 13, 72% were female and 12% were black. Between 2005 and 2014, the use of EC increased relative to SC (50% vs. 81%, p<0.0001). Retreatment occurred in 1488 (7.6%) patients (10.1% vs. 3.2%, EC vs. SC), with 89% of retreatments within 2 years of index treatment. Retreatment was associated with age > 80 (OR 0.3 [0.2-0.5]), female sex (OR 1.6 [1.4-1.9]), black vs. white race (OR 0.8 [0.7-0.9]) and EC vs. SC (OR 3.5 [3.1-4.1]). Adjusted two-year RR decreased from 2005 to 2011 for patients with unruptured CAs treated with EC (8.7% vs. 6.8%, OR 0.95 [0.90-1.00] and Figure). Adjusted RR was unchanged for SC (mean RR 3.6% and 2.7%, unruptured and ruptured) and ruptured CAs treated with EC (mean RR 9.9%).

Conclusions:
Analysis of two-year RR of CAs in a large real-world cohort demonstrates a continuous reduction in RR for unruptured CAs treated with EC in the last decade. These findings may reflect improving obliteration rates of EC for unruptured CAs.
Abstract 165: Accuracy of Detecting Enlargement of Aneurysms Using Different MRI Imaging Modalities and Measurement Protocols
Authors: Nakagawa Daichi , Nagahama Yasunori , Policeni Bruno , Madhavan Raghavan , Schumacher Anna , Sarathy Srivats , Huston John , Cloft Harry , Wintermark Max , Torner James , Brown Robert , Hasan David
Published: October 2018

Objective:
Aneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, it is still unknown how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical magnetic resonance imaging (MRI) imaging. The purpose of this study is to assess the agreement rate of detecting aneurysm enlargement using generally used MRI imaging modalities.

Methods:
Three silicone flow phantom models each with eight aneurysms of various sizes in different sites were used in this study. The aneurysm models were identical except for an incremental increase in size of the 8 aneurysms ranging from 0.4mm to 2mm. The phantoms were imaged on 1.5 tesla (T) and 3T MRI units with both time-of-flight (TOF) and contrast enhanced magnetic resonance angiography (MRA). Three independent expert neuroradiologists measured the aneurysms in a blinded fashion utilizing different measurement approaches. The individual and agreement rate among the three experts in detecting aneurysm enlargement were calculated.

Results:
The average detection rate of any increase in any aneurysmal dimensions was 95.7%. The detection rate for the three readers (A, B and C) was 98.0%, 96.6% and 92.7%, respectively (
P
=0.22). The detection rate in each MRI modality was 91.3% using 1.5 T TOF, 97.2% using 1.5T gadolinium (Gad), 95.8% using 3.0T TOF and 97.2% using 3.0T Gad (
P
=0.31). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. Use of Gad in 1.5T improved the detection rate in small incremental enlargement (e.g. 0.4 - 1mm) of the aneurysm (
P
=0.04). The locations of the aneurysms also affected detection rate for aneurysm enlargement (
P
<0.0001).

Conclusions:
The detection rate and interobserver agreement was very high for aneurysm enlargement of 0.4mm to 2 mm. Detection rate of any increase in any aneurysmal dimensions did not depend on the choice of MRI imaging modalities and measurement protocols.
Abstract 169: Neurovascular Disease is the Second Leading Cause of Death in the United States (US): A Modern Disease Burden Analysis
Authors: Fan Frances , Saver Jeffrey L
Published: October 2018

Introduction:
The World Health Organization (WHO) in 2017 voted to return cerebrovascular disease from Circulatory Disorders to its historic home in Neurologic Disorders (forthcoming ICD-11), due to advances in cerebrovascular disease therapy and increased recognition of neurovascular contributions to dementia.

Methods:
Analyzing the WHO Global Burden of Disease Project 2015 data, we calculated the impact on attributable deaths and attributable disability (disability-adjusted life years lost - DALYs) of: 1) return of cerebrovascular diseases to the Neurologic Disorders category, and 2) use “neurovascular disease” state to include both “cerebrovascular diseases” and proportion of dementia due to neurovascular insults.

Results:
Reclassification of cerebrovascular disease as a Neurologic Disorder, in the US, increased the number of deaths attributable to Neurologic Disorders by 50.5%, from 326,000 to 490,000 per year, and increased DALYs lost by 37.3% (6.0 to 8.3 million). Worldwide, this reclassification increased the number of deaths attributable to Neurologic Disorders by 280% (2.3 to 8.6 million), and increased DALYs lost by 136%, (87.1 to 205.7 million). Systematic literature review shows vascular brain lesions contribute to 51% of clinically diagnosed Alzheimer disease and 65% of clinically diagnosed vascular dementia. Adding these cases to focal strokes, in the US, the number of deaths attributable to neurovascular disease increased by 90% (164,000 to 313,000), and DALYs lost increased by 37.3%, (2.3 to 3.7 million). Worldwide, the number of deaths attributable to neurovascular increased by 18% (6.3 to 7.5 million), and DALYs lost increased by 10.4% (119 to 131 million).

Conclusions:
When correctly classified according to modern pathophysiology, neurovascular disease moves from the 5
th
to the 2
nd
leading cause of death in the US; Neurologic Disorders moves from the 12
th
to the 4
th
leading cause of disability worldwide. This more accurate delineation of the national and global burden of neurovascular disease, should guide more informed allocation of resources for neurovascular research and clinical care.
Abstract 176: Enhancing the Efficacy of Current Management of Ischemic Stroke Using Injury-Site Targeted Complement Inhibition - A Preclinical Study
Authors: Langley Farris , Alawieh Ali , Tomlinson Stephen
Published: October 2018

Ischemia leads to the cellular expression of damage-associated molecular patterns (DAMPs), recognition of which by natural IgM antibodies (NIgM) results in activation of the complement system and the propagation of inflammation. We identified an IgM mAb, termed B4IgM, that recognizes a DAMP (annexin IV) and that reconstitutes cerebral ischemia reperfusion injury in otherwise protected antibody-deficient Rag1-/- mice. We took advantage of this injury recognition system by linking a complement inhibitor (Crry) to a B4IgM-derived single chain antibody (scFv) for site-targeted delivery of a therapeutic after stroke. Using a murine model of transient middle cerebral artery occlusion (MCAO), we show that a single dose of B4Crry administered IV up to 24 h after MCAO inhibited IgM and complement deposition in the ischemic brain and provided sustained neuroprotection up to 30 days. B4Crry treatment resulted in a significant reduction in cell death and tissue scarring (70% reduction, p<0.01), and significant improvements in neurological deficit scores (p<0.05), forelimb asymmetry (corner test, <0.05), and spatial learning (Barnes maze, p<0.05). We further investigated B4Crry treatment in the context of tissue-plasminogen activator (tPA) therapy using a microembolic model of ischemic stroke. A single dose of B4Crry administered at 2h, 4h, or 6h after ischemia demonstrated significant improvements in motor and cognitive recovery compared to vehicle with a comparable outcome to 2h t-PA therapy. However, administration of tPA at 4h or 6h was associated with increased risk of mortality and hemorrhage. Combination of B4Crry and tPA expanded the therapeutic window of tPA (more than 6 h) and reduced the incidence of post-stroke mortality and tPA-induced intracerebral hemorrhage. Combination therapy also showed an additive effect on motor and cognitive recovery measures over 30 days. Finally, we demonstrated that B4Crry does not increase the risk of post-stroke pneumonia in a mouse model, and demonstrate that B4Crry specifically targets the ischemic stroke hemisphere in both murine and human brains. These data indicate that B4Crry is a promising translational stroke therapeutic that can also augment the efficacy and safety profile of tPA therapy.
Abstract 177: Exosomal Micrornas From Ischemic Cerebral Endothelial Cells and Neural Stem Cells Regulate Coupling of Neurogenesis and Angiogenesis
Authors: Liu Xianshuang , Pan Wanlong , Li Chao , Zhang Ruilan , Fan Baoyan , Wang Xinli , Zhang Xiaoming , Hu Jia Ni , Chopp Michael , Zhang Zheng Gang
Published: October 2018

Introduction:
Molecular mechanisms underlying coupling of angiogenesis and neurogenesis remain unknown. We tested the hypothesis that exosomes mediate coupling of stroke-induced angiogenesis and neurogenesis by transferring exosomal cargo miRNAs between ischemic cerebral endothelial cells (CECs) and neural stem cells (NSCs).

Methods and Results:
Cell-type specific
e
xosomes were purified from conditional media of cultured CECs and NSCs harvested from non-ischemic and ischemic rats, respectively. Exosome markers and size distribution were verified with Western blot and transmission electron microscopy, respectively. Using an advanced Cre-Loxp system, we found CEC-exosomes carrying Cre recombinase were taken up by recipient NSCs to induce genome recombination. We then tested if exosomal miRNAs mediated cell-to-cell interplay. First, using miRNA array, we identified that miR-146a and miR-125a were the most upregulated miRNAs in ischemic CECs-exosomes. Incubation of non-ischemic NSCs with ischemic CECs-exosomes substantially increased these two miRNA levels in recipient NSCs, which led to downregulation of their target genes, IRAK1, TRAF6 as well as BAK1 and KLF13, consequently leading to an increase in Tuj1
+
and NG2
+
cells (p<0.05). These data suggest that CEC-exosomes transfer miRNAs to NSCs and thereby promote neuronal differentiation. Moreover, stroke increased miR-106b and miR-125b in NSCs-exosomes. Incubation of non-ischemic CECs with ischemic NSC-exosomes elevated both miRNAs in CECs, which resulted in a significant increase in capillary tube formation, suggesting that ischemic NSC-exosomes promote angiogenesis. The effect of ischemic CEC-exosomes and ischemic NSC-exosomes on differentiation of NCSs and CECs, respectively, is specific, because ischemic CEC- and NSC-exosomes derived from cells with knockdown of Rab27, a protein that regulates miRNA sorting into exosomes, completely abolished elevation of listed miRNAs in recipient cells.

Conclusion:
Our data demonstrate that exosomes derived from ischemic CECs and NSCs mediate NSC and CEC function, respectively, by transferring their cargo miRNAs, suggesting that these exosomes can be used as a therapy for amplifying angiogenesis and neurogenesis in ischemic brain.
Abstract 178: Adipose Derived Mesenchymal Stromal Cell Sheet Transplantation Induces Functional Angiogenesis and Enhances Endogenous Neurogenesis in a Rat Stroke Model
Authors: Ryu Bikei , Sekine Hidekazu , Honma Jun , Kobayashi Tomonori , Kobayashi Eiji , Kawamata Takakazu , Shimizu Tatsuya
Published: October 2018

Introduction:
Adipose-derived mesenchymal stromal cell (ASC) injection reportedly improves neuronal function in animal stroke models. However, the difficulties in transplanting many cells to the affected area and ensuring that the grafted cells remain in their position continue to be problems. We devised a scaffold-free, cell sheet-based regenerative method. We evaluated the effectiveness of allogeneic ASC cell sheet transplantation in a stroke model.

Methods:
Intraluminal middle cerebral artery occlusion model was made. Cultured rat ASC cell sheets were harvested from temperature-responsive culture dishes. Layered cell sheet was transplanted onto infarcted rat brain surfaces. Cell sheet survival was compared with single cell injection by bioluminescence imaging (n=5 each). Histology was evaluated and functional analyses were performed 14 days after transplantation. (CS: cell sheet, VE: vehicle, n=10 each).

Results:
Cell sheets showed greater cell survival than single cell injections in allografts (Fig A). ASC cell sheets induced functional angiogenesis in affected hemispheres. Newly formed vessels were anastomosed with host ischemic intracerebral vessels. At 7 days, GFP-expressing ASCs migrated along vessels into host ischemic brain and engrafted as vessel wall cells like pericytes (Fig B, C, D). At 14 days, significant angiogenesis and increased doublecortin (DCX)-positive cells were noted at the subgranular zone with significant functional improvement in CS (CS vs. VE: vessel length 21,130±1,823 μm vs. 14,795±2,976 μm, DCX-positive cells 40±7 vs. 17±8, rotarod 108±90% vs. 41±21%).

Conclusion:
Allogeneic ASC cell sheets with high cell survival induced functional angiogenesis and endogenous neurogenesis in a rat stroke model.
Abstract 19: Clinical and Neuroimaging Profile of Children With Arterial Ischemic Stroke Due to Cerebral Arteriopathy - Results From the International Pediatric Stroke Study (IPSS)
Authors: Rafay Mubeen F , Shapiro Kevin , Kirton Adam , deVeber Gabrielle , Fullerton Heather , Dowling Michael , Dlamini Nomazulu , Amlie-Lefond Catherine , Carpenter Jessica L , Weschke Bernhard , Rivkin Michael , Mackay Mark , Bernard Timothy
Published: October 2018

Introduction:
Cerebral arteriopathies are frequently identified in children with arterial ischemic stroke (AIS), and are distinguished by high stroke recurrence. However, the clinical and neuroimaging profiles of AIS due to cerebral arteriopathy versus non- arteriopathy have not been compared.

Hypothesis:
We hypothesized that children with AIS due to arteriopathy would differ in their demographic, clinical, and radiographic presentation from those without arteriopathy.

Methods:
We report a large, prospective, multicentre cohort of children, 1 month - 17 years, with AIS, enrolled in the International Pediatric Stroke Study, 2003-2014. Those with arteriopathy including focal cerebral arteriopathy, dissection, moyamoya, vasculitis and non-specific arteriopathies, were compared to those with non-arteriopathic stroke etiologies.

Results:
Of 2127 children with AIS, 725(34%) had arteriopathy (58% male, mean age 8.1years). The remaining 1402(66%) had non-arteriopathic AIS. Arteriopathy was associated with older age, but not a specific gender or ethnicity. Geographic differences were observed. Children with arteriopathy were likely to present with hemiparesis, dysarthria, ataxia, headache, preceding/concurrent thromboembolic events and without seizures. Risk factors associated with arteriopathy included sickle anemia, head/neck trauma and lack of acute systemic disease. Radiological associations with arteriopathy included right sided unilateral or bilateral stroke, multiple infarcts and relative reduction in occurrence of intracranial hemorrhage. On multivariate analysis, headache (p=0.006), additional thromboembolic events (p=0.007), multiple infarcts (p=0.002) and lack of seizures (p=0.001) were independently associated with arteriopathy.

Conclusions:
Specific clinical profiles are associated with arteriopathy in children with AIS and may guide the clinician in early diagnostic evaluations and management.
Abstract 192: Anticoagulation Decision-Making in ICH Patients With Atrial Fibrillation: Quality-Adjusted Decision Model Outcomes
Authors: Kleindorfer Dawn O , Mark Eckman , Moomaw Charles J , Stanton Robert , Haverbusch Mary , Flaherty Matthew L , Woo Daniel
Published: October 2018

Background:
While patients (pts) with atrial fibrillation (AF) face a risk of ischemic events, AF pts with intracerebral hemorrhage (ICH) are at increased risk of bleeding with anticoagulation (AC). Optimal decision-making must weigh the tradeoffs between these competing risks. Our goal was to analyze the impact of AC decisions on projected quality-adjusted life years (QALYs) pts with both ICH and AF within a population.

Methods:
The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study is a population-based evaluation of spontaneous ICH among residents of the five-county Greater Cincinnati/Northern Kentucky study region. The study period was 7/08-12/12. Pts with ICH and AF surviving the hospital stay were included. Medical history and demographics were entered into the Atrial Fibrillation Decision Support Tool, which is a 29-state Markov decision analytic model that projects patient-level QALYs for 7 thromboprophylaxis treatment strategies, using published event rates from CHADSVASC, HAS-B(L)ED, the Friberg ICH prediction model and clinical trials of anticoagulants (including warfarin and direct anticoagulants, DOACs), as well as published rates of outcomes for each possible event.

Results:
In the study period, there were 1186 cases of spontaneous ICH, 232 with a-fib, of which 123 were excluded because of inpatient death/discharge to hospice. Among the 109 cases, the aggregate net loss for AC was 16.9 QALYs; however there were 10 cases (9%) that gained > 0.1 QALYs with AC. The table displays a heat map showing aggregate gain/loss of QALYs with AC (compared with no treatment) for the cohort, displayed by their CHADSVASC and HASBED scores.

Conclusion:
We found that 91% of our ICH pts with AF would have either no change or a loss of QALYs with AC. However, given lower bleeding rates with DOACs, anticoagulation may be beneficial in a very select subset of AF pts with ICH. Thresholds for AC treatment should be considered carefully in this population.
Abstract 193: The 2CAN Score: A Novel Inpatient Stroke Recognition Instrument
Authors: Chang Philip , Ruff Ilana , Bergman Deborah , Mendelson Scott , Prabhakaran Shyam
Published: October 2018

Introduction:
A quarter of strokes occur in patients hospitalized for another reason. Inpatient stroke alerts are challenging due to complex medical situations. A stroke recognition instrument may be useful for general practitioners to discern neurologic deficits due to hemorrhagic or ischemic stroke from mimics such as seizures, delirium, and hypoglycemia.

Hypothesis:
Clinical factors present at the initial evaluation of suspected inpatient stroke patients will distinguish strokes from mimics.

Methods:
This was a retrospective review of inpatient stroke alerts from 9/1/2014 to 7/31/2016. Final diagnosis of stroke was based on stroke attending documentation and imaging confirmation if available. We evaluated predictors of stroke diagnosis including demographics, stroke risk factors, stroke alert reason, post-operative status and time from admission, NIHSS and CPSS scores abstracted from notes, vital signs, and laboratory values. Using the first 165 patients for derivation and the second 165 for validation, we used univariate and multivariate logistic regression and c-statistics to derive and validate a scoring system to predict stroke diagnosis.

Results:
Among 394 alerts, 64 were excluded due to incomplete documentation. Of 330 remaining patients, 116 (35.2%) were diagnosed with stroke, 43 (13.0%) had a neurological mimic (e.g., seizure), and 171 (51.8%) had a non-neurologic mimic (e.g., sepsis, drug effect, or delirium). In multivariate analysis in the derivation cohort, we identified 4 independent predictors of inpatient stroke: abnormal CPSS, post-
C
ardiac procedure, history of
A
trial fibrillation, and being a
N
ew (admitted within 24 hours) patient. The 2CAN score gives one point for each positive variable above, with additional 2 points for a CPSS ≥2 for a total score range from 0 to 6. The 2CAN score had c-statistic 0.93 (95% CI 0.88-0.97) in the derivation and 0.88 (95% CI 0.82-0.94) in the validation cohorts, respectively. A 2CAN score ≥2 had 92.2% sensitivity, 69.6% specificity, 62.2% positive predictive value, and 94.3% negative predictive value for identifying stroke.

Conclusion:
The 2CAN score is a sensitive screening tool for identifying inpatient stroke. Further external and prospective validation of this score is warranted.