bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP115: Acid-Sensing Ion Channels: Novel Mediator of Cerebrovascular Responses
Authors: Faraci Frank M , Taugher Rebecca , Fan Rong , Gupta Subhash , Wemmie John A
Published: October 2018

Carbon dioxide (CO
2
), via effects on extracellular pH, is one of the most potent regulators of cerebral blood flow. Clinically, CO
2
inhalation or acetazolamide treatment (to produce tissue acidosis) are used commonly to estimate vascular reserve, the degree of vascular stenosis, and the effectiveness of collateral vessels. Despite the physiological importance and the clinical use of CO
2
, mechanisms that mediated these responses are still not defined. A role for NO produced by neuronal NO synthase (nNOS) in intermediate signaling has been described, but the molecular sensor that initiates vascular responses to CO
2
and acidosis has not been identified. Acid-sensing ion channel-1A (ASIC1A) is a proton-gated cation channel that is activated by extracellular acidosis. Based on work which implicated ASIC1A in CO
2
-evoked and acid-evoked behaviors, we hypothesized that ASIC1A might also mediate microvascular responses to CO
2
. To test this hypothesis we genetically and pharmacologically manipulated ASIC1A and assessed effects on CO
2
-induced dilation of cerebral arterioles. Effects of inhalation of 5 or 10% CO
2
on arteriolar diameter in vivo was greatly attenuated in

Asic1a
-/-

mice or by local treatment with the ASIC inhibitor, psalmotoxin. Vasodilator effects of acetylcholine, which acts via endothelial NOS were unaffected, consistent with nNOS playing a key role for CO
2
responses. Using mice in which
Asic1a
was specifically disrupted in neurons, we found effects of CO
2
on arteriolar diameter were also attenuated. To further explore a role for ASIC1A in the regulation of NO production, we measured NO concentrations in whole brain lysates immediately after exposure to CO
2
. We found that inhalation of CO
2
induced NO production in wild-type mice, but not in mice lacking
Asic1a
globally or specifically in neurons. Together, these data are consistent with a model wherein activation of neuronal ASIC1A is critical for CO
2
-induced NO production and vasodilation. With these findings, ASIC1A emerges as major regulator of microvascular tone in brain.
Abstract WMP118: Neuroprotective Effects of IGF1 on Brain Microvascular Endothelial Cells Under Ischemic Conditions Can Be Replicated by Antagomirs to MicroRNA(Mir-92b) and Mir33a
Authors: Bake Shameena , Khosravianghadikolaei Homa , Sohrabji Farida
Published: October 2018

Background:
Insulin like growth factor (IGF1) treatment to middle aged female rats post stroke reduces infarct volume, and this is preceded by reduced permeability of the blood brain barrier (BBB) at 4h post stroke. Analysis of ischemic tissue at 4h showed that IGF1 treatment significantly reduced expression of 8 miRNA. To determine if these miRNA are mechanistically linked to barrier function, we tested the impact of these miRNA on barrier function using human brain microvascular endothelial cells (hBMECs) under ischemic conditions. Specifically, we mimicked the actions of IGF1 by using antagomirs to miR-29c, miR-33a and miR-92b.

Methods:
hBMECs were grown to confluence on collagen-coated dishes (5% CO2, 95% air) and exposed to acute oxygen-glucose deprivation (6h OGD, 1% O2 % and 5 % CO2) in the presence of IGF1 or vehicle. In addition, cultures were also treated with IGF1+JB-1 (IGFR antagonist), IGF1+ LY294002 (Akt inhibitor) and rapamycin (mTOR inhibitor), to establish IGF1 mediated pathways on barrier function. In parallel, cultures were exposed to antagomirs for mir29c, mir 33a and mir92b or scrambled oligo controls. Integrity of the cell monolayer was assessed by tomato-lectin staining and LDH assays for cell death. Lectin stained cell cultures (3 experimental replicates) were photographed, coded and analyzed for continuity of monolayer using a novel algorithm to determine intercellular ‘spaces’.

Results:
OGD caused significant retraction (11 fold increase, p<0.02) and discontinuous aggregates of cells, while IGF1 preserved the integrity of the endothelial monolayer and were no different from normoxic condition. JB-1 (13 fold increase,p<0.01) and Akt inhibitor (3.3 fold, p<0.02) abrogated the effects of IGF-1. Antagomirs to mir92b and mir33a also maintained cell integrity after OGD, (7 fold,p<0.03) while mir29c and scrambled oligos (10 fold damage, p<0.04) were ineffective. LDH assay was not significantly different in any of the treatment conditions, indicating that necrotic cell death was not altered.

Conclusions:
These findings provide direct evidence that IGF-1 actions at the endothelial barrier are replicated by specific miRNA and raise the possibility that IGF-1’s actions can be replicated by targeted suppression of miRNAs.
Abstract WMP119: Neurovascular Unit Protection Using Nitroxide Radicals-containing Nanoparticles (TEMPO-RNP) for Cerebral Ischemia-reperfusion Injury in Mice
Authors: Hosoo Hisayuki , Marushima Aiki , Nagasaki Yukio , Hirayama Aki , Ito Hiromu , Puentes Sandra , Mujagic Arnela , Tsurushima Hideo , Tsuruta Wataro , Suzuki Kensuke , Matsui Hirofumi , Matsumaru Yuji , Yamamoto Tetsuya , Matsumura Akira
Published: October 2018

Purpose:
Reperfusion injury after thrombolytic therapy or mechanical thrombectomy would adverse neurological outcome. Generation of reactive oxygen species (ROS) due to reperfusion is relevant for aggravation. The development of drug therapy for scavenging free radical is expected to lead to better neurological prognosis. We developed a new core-shell type nanoparticle, RNP (radical containing nanoparticle), which consists of micelle containing 4-amino-TEMPO. The purpose of this study is to evaluate an efficacy of intra-arterial injection of RNP after reperfusion using tMCAO mice model.

Methods:
C57BL/6J mice underwent tMCAO for 60 minutes and received RNP by intra-arterial injection from common carotid artery. We evaluated infarction size, neurological scale, and Evans blue extravasation at 24h after reperfusion. RNP distribution was detected by rhodamine labeling. We further examined immunofluorescense of CD31, Occludin, TUNEL, dihydroethydium, and 8-hydroxy-deoxyguanosine (8-OHdG). Multiple free radical scavenging capacity of ischemic hemisphere was analyzed by Electron Paramagnetic Resonance (EPR).

Results:
RNPs were detected in endothelial cells and around neuronal cells in the ischemic lesion. The infarction size, neurological scale, Evans blue extravasation of the mice treated by RNP were significantly lower than the mice treated by PBS , control group. Intra-arterial RNP treatment preserved endothelium and expression of occludin in the ischemic brain. Further, apoptosis of neuronal cells and production of superoxide anions and 8OHdG were suppressed. By using EPR, multiple ROS scavenging capacity (•OH, •ROO, •O
2
-
) of the ischemic brain treated by RNP were higher.

Conclusions:
These results suggest that intra-arterial injection of RNP have efficacy of neurovascular unit protection and reduce infarction volume by improving multiple ROS scavenging capacity.
Abstract WMP12: Feasibility of Permanent Stenting With Solitaire Fr as a Rescue Treatment for the Reperfusion of Acute Intracranial Artery Occlusion
Authors: Woo Ho Geol , Jung Cheolkyu , Kim Beom Joon , Han Moon-Ku , Bae Hee-Joon , Bae Yun Jung , Choi Byung Se , Kim Jae Hyoung , Sunwoo Leonard
Published: October 2018

Background and Purpose:
Solitaire FR can be used not only as a tool for mechanical thrombectomy but also as a detachable permanent stent. Our aim was to assess the feasibility and safety of permanent stenting with Solitaire FR (erv3, Irvine, CA, USA) compared with other self-expanding stents for intracranial artery recanalization for acute ischemic stroke.

Materials and Methods:
From January 2011 through January 2016, 2,979 patients with acute ischemic stroke were retrospectively selected. Among them, 27 patients who underwent permanent stenting (13 patients with Solitaire FR (Solitaire group) and 14 patients with other self-expanding stents (other stent group)) were enrolled. The post-procedural mTICI grade and angiographic and clinical outcomes at discharge and 3 months were assessed. The safety and efficacy of permanent stenting of Solitaire FR stent placement for acute large arterial occlusion were evaluated.

Results:
Stent placement was successful in all cases. mTICI 2b-3 reperfusion was noted in 84.6% of Solitaire group and in 78.6% of other stent group. Procedure time was significantly shorter in Solitaire group than other stent group (
P
= 0.022). No significant differences were found in mTICI grade, NIHSS score at discharge, mRS at 3 months, and rate of hemorrhagic transformation between the two groups. Acute in-stent thrombosis rate at discharge was significantly lower when glycoprotein IIb/IIIa inhibitor was injected during the procedure (
P
= 0.013).

Conclusions:
Permanent stenting of Solitaire FR compared with other self-expanding stents appears to be feasible and safe as a rescue tool for refractory intra-arterial therapy.
Abstract WMP14: Prognosis of Different Infarction Patterns in Single or Multiple Acute Infarction After Minor Stroke
Authors: Wang Yilong , Wang Guangyao , Jing Jing , Pan Yuesong , Zhao Xingquan , Liu Liping , Wang Yongjun
Published: October 2018

Objective:
To investigate whether different infarction patterns of single acute infarction (SAI) and multiple acute infarctions (MAIs) respectively have different risk of stroke recurrence after minor stroke.

Methods:
We derived data from the imaging subgroup of the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Minor stroke were categorized into SAI and MAIs according to infarction patterns in diffusion weighted imaging. SAI were classified as 1.Cortical lesion; 2.Subcortical lesion with diameter>15mm; 3.Subcortical lesion with diameter≤15mm; 4.Corticosubcortical lesion. MAIs were classified as 1.Unilateral anterior circulation; 2.Posterior circulation; 3.Multiple circulations; 4.Border-zone territories. The primary outcome was stroke recurrence at one-year follow-up.

Results:
A total of 834 patients with minor stroke from 45 of 114 participating centers of the trial undergoing baseline MRI were included in this imaging subgroup. SAI was observed in 553 and MAIs in 281, the risk of stroke recurrence was 9.9% and 15.3% in SAI and MAIs respectively. After adjustment for potential confounders, different infarction patterns in SAI (cortical lesion, subcortical lesion with diameter>15mm, subcortical lesion with diameter≤15mm, and corticosubcortical lesion) had different risk of stroke recurrence (5.0%, 16.3%, 7.6% and 20.0%, respectively) (p=0.018), however, different infarction patterns in MAIs (unilateral anterior circulation, posterior circulation, multiple circulations and border-zone territories) had no different risk of stroke recurrence (14.8%, 11.8%, 19.5% and 18.5%, respectively) (p>0.05).

Conclusions:
Patients with different infarction patterns had different risk of stroke recurrence in SAI but not in MAIs. Some specific infarction patterns of SAI had similar risk of stroke recurrence as MAIs.
Abstract WMP17: Time to Treatment, Collaterals and Recanalization in Basilar Artery Occlusion: Which Factors Determine Prognosis?
Authors: Alemseged Fana , Van der Hoeven Erik , Di GIuliano Francesca , Shah Darshan , Diomedi Marina , Kleinig Timothy , Yassi Nawaf , Dowling Richard J , Bush Steven , Yan Bernard , Davoli Alessandro , Sallustio Fabrizio , Marziali Simone , Gandini Roberto , Donnan Geoffrey A , Puetz Volker , Mitchell Peter J , Davis Stephen M , Schonewille Wouter J , Campbell Bruce C
Published: October 2018

Background:
Whether radiological factors influence the effect of time to recanalization on outcome in basilar artery occlusion (BAO) is uncertain. We evaluated the association between onset time to treatment (OTT), radiological prognostic factors (presence of collaterals and extent of the occlusion) and clinical outcome in endovascular BAO patients.

Methods:
Clinical and radiological data of consecutive endovascular-treated stroke patients with BAO diagnosed on CT angiography at Royal Melbourne Hospital (Australia), Royal Adelaide Hospital (Australia), University Hospital of Tor Vergata (Rome, Italy) and from the international BASICS registry were retrospectively analysed. The Basilar Artery on Computed Tomography Angiography (BATMAN) score and Posterior Circulation Collateral Score (PC-CS) were assessed by two investigators blinded to clinical outcome. Previously validated dichotomies for favorable BATMAN score (≥7) or PC-CS (≥6) were used. Good outcome was defined as modified Rankin Scale≤3 within 3 months; successful reperfusion as mTICI 2b-3 (or TIMI 2-3 in BASICS).

Results:
We included 155 BAO patients treated with intra-arterial urokinase and/or mechanical thrombectomy (86 with mechanical thrombectomy): mean(SD) age 65(14), median NIHSS 22 (IQR 12-30), median OTT 348.5 min [(IQR 246-480), 37% treated beyond 6hours]. In logistic regression adjusted for age and NIHSS, OTT>6h was associated with poor outcome (OR 3.0, 95%CI 1.4-6.6, p=0.006) but this association was only present in the subgroup with unfavourable BATMAN score (adjusted OR 4.6, 95%CI 1.7-12, p=0.002) or PC-CS (3.7, 95%CI 1.3-11, p=0.02) and not in those with favorable BATMAN score (adjusted OR 0.7, 95%CI 0.2-3.6, p=0.7) or PC-CS (2.7, 95%CI 0.6-12, p=0.2). When successful reperfusion was added to the model with age and NIHSS, OTT>6h remained significantly associated with poor outcome in patients with unfavorable BATMAN score (OR 5.0, 95%CI 1.8-14, p=0.002) or PC-CS (4.5, 95%CI 1.4-14, p=0.01), but not in patients with favorable BATMAN score (OR 1.6, 95%CI 0.2-13, p=0.6) or PC-CS (3.2, 95%CI 0.6-17, p=0.2).

Conclusions:
BAO patients with good collaterals and less extensive occlusion may have good outcome if recanalization is achieved even in a delayed time window.
Abstract WMP23: Automated ASPECTS Scoring of CT Scans for Acute Ischemic Stroke Patients Using Machine Learning
Authors: Kuang Hulin , Teleg Ericka , Najm Mohamed , Wilson Alexis T , Sohn Sung I , Goyal Mayank , Hill Michael D , Demchuk Andrew , Menon Bijoy K , Qiu Wu
Published: October 2018

Objective:
The Alberta Stroke Program Early CT Score (ASPECTS) method has been widely used to assess non-contrast CT scans from acute ischemic stroke (AIS) patients. Although the ASPECTS is a simple and systematic approach, ASPECTS scoring accuracy and reliability is still a challenge to clinicians, especially with limited experience. The objective of this study is to develop an automated ASPECTS scoring method, which could provide objective assessment and decision-making support.

Methods:
We collected 160 AIS patient NCCT images with thickness of 5mm (<8 hours from onset to scans) followed by DWI acquisition within 1 hour of NCCT. Expert ASPECTS readings on DWI with 20% thresholding (20% of a given ASPECTS region showed diffusion restriction to be scored as affected) were used as ground truth for evaluations. A NCCT template with ASPECTS regions manually contoured was non-linearly registered onto all NCCT images and ASPECTS regions were then automatically mapped onto subject NCCT images. Image features extracted from each ASPECTS region, such as regional intensity profile, neighbor context, and texture information, were used to train a random forest classifier to discriminate whether an ASPECTS region has ischemic changes. Leave-one-out validation was performed to evaluate the trained model against expert readings on DWI.

Results:
The proposed method generated an individual ASPECTS region level detection accuracy of 85.3% and only a 1-point discrepancy in total ASPECTS scores compared to expert reading on MRI. Bland-Altman plot of automated ASPECTS vs. expert MRI ASPECTS shows good agreement (Figure 1). The automated ASPECTS method has very high agreement (91.3%) and specificity (98.5%) when dichotomized (ASPECTS 0-4 vs. 5-10).

Conclusions:
The automated ASPECTS scoring approach is reliable and accurate and can potentially be used to make decisions in patients with acute ischemic stroke.
Abstract WMP24: Reperfusion Into Severely Damaged Brain Tissue is Associated With Impending Parenchymal Hemorrhage in Acute Ischemic Stroke Patients
Authors: Yu Songlin , Ma Samantha J , Liebeskind David S , Yan Lirong , Scalzo Fabien , Wang Danny J
Published: October 2018

Purpose:
Identifying acute ischemic stroke (AIS) patients with impending parenchymal hematoma (PH) after thrombolysis and/or endovascular treatments would be useful in guiding following treatment strategies.

Methods:
102 patients had MRI on Siemens 1.5 T Avanto or 3.0 T TIM Trio systems, using 12 channel head coils. A pseudo-continuous ASL pulse sequence with background suppressed 3D GRASE readout was applied along with other MR sequences within 24 hours after treatment with the following parameters: TR/TE/label time/post-labeling delay (PLD), 4000/22/1500/2000 ms; 30 pairs of label and control images with a scan time of 4min. Infarction core was acquired using ADC value < 550х10
–6
mm
2
/s. CBF within the infarction core and its contralateral counterpart was measured. CBF at the 25
th
, median and 75
th
percentiles in the contralateral part were used as thresholds to define reperfusion in the lesion. ASL reperfusion volume above the threshold was calculated and noted as vol-25, vol-50 and vol-75 respectively.

Results:
Both ADC threshold volume and ASL reperfusion volume at all three percentiles differed significantly between HT categories such as HT vs. no HT, HI vs. PH, PH vs. no PH and PH-2 vs. no PH-2. In the ROC analysis, ASL reperfusion vol-25 has the highest area under the curve (AUC) (Figure 1). ASL vol-25 had significantly higher AUC when compared with ADC threshold volume in prediction of PH (0.782 vs. 0.679, P=0.002) and in prediction of PH-2 (0.844 vs. 0.749, P=0.0027). In stepwise multivariate logistic regression analysis, only ASL reperfusion vol-25 emerged as an independent predictor of HT (OR=1.94, 95% CI 1.14-3.59, P=0.022). Similarly for the PH2 vs. no PH2 outcome, only ASL reperfusion vol-25 was an independent predictor (OR=2.34, 95% CI 1.22-5.28, P=0.02).

Conclusion:
Post treatment MRI-ASL can evaluate reperfusion status in AIS patients. Increasing volume of reperfusion within infarction core is highly associated with impending higher grade of HT.
Abstract WMP27: Current Generation Anticonvulsant Prophylaxis After Ischemic Stroke
Authors: Christie Carlton , Lehman Erik , Matthews Nicole , Cockroft Kevin
Published: October 2018

Introduction:
Ischemic strokes (IS) are the leading cause of seizure development in the elderly and recent reports associate post-IS seizures with increased morbidity and mortality. Yet, there is a scarcity of studies defining the role of anticonvulsant prophylaxis in the prevention of seizures after IS. As a result, AHA/ASA guidelines do not recommend the prophylactic administration of anticonvulsants in this setting. Here, the ability of newer generation anticonvulsants, mainly levetiracetam, to prevent post-IS seizures is analyzed.

Methods:
We performed a review of our clinical database from 2010-2015 including patients that suffered IS. Patient demographics, seizure incidence, and functional outcomes were collected. Patients that received prophylaxis and those who did not were divided. Logistic regression and quantile regression models assessed relationships between outcomes and risk factors, each analysis was corrected for age, gender, and initial NIH stroke scale (NIHSS) score.

Results:
From a total of 1771 patients included in this study, the mean age was 69 and 51.1% were male. Median initial NIHSS score was 6.0 (IQR, 2-14), with prophylaxis and 3.0 (1.0-7.0) without. Of the 534 patients that had prophylactic anticonvulsants, 352 (65.9%) first received levetiracetam and 127 (23.8%) received gabapentin. Those with prophylaxis had 36 (6.7%) seizures and without experienced 47 (3.6%). Despite correcting for the initial severity of stroke, prophylaxis independently and significantly increased the odds of a seizure (adjusted OR, 1.76; 95% CI, 1.09-2.87; p=0.02). Furthermore, prophylaxis was associated with an increased discharge NIHSS score (adjusted difference, 1.0; 95% CI, 1.0-1.0; p<0.001) but not an increase in mRS score at discharge. Patients with prophylaxis also had longer hospital stays (adjusted difference, 1.0 days; 95% CI, 0.7-1.3, p<0.001) and higher total hospital costs (adjusted difference, $9,103; 95% CI, 5,707-12,498; p<0.001).

Conclusions:
Post-IS anticonvulsant prophylaxis is not associated with improved outcomes or a reduced seizure incidence. Instead, prophylaxis here was associated with an increased odds of having a seizure after IS, a worse NIHSS score at discharge with longer hospital stays and higher costs.
Abstract WMP29: Hemorrhage Associated With Ventriculoperitoneal Shunt Placement in Aneurysmal Subarachnoid Hemorrhage Patients on Dual Antiplatelet Therapy: A Retrospective Analysis
Authors: Hudson Joseph S , Nagahama Yasunori , Nakagawa Daichi , Starke Robert M , Dlouhy Brian J , Torner James , Jabbour Pascal , Allan Lauren , Derdeyn Colin P , Greenlee Jeremy , Hasan David
Published: October 2018

Object:
Intracranial stenting and flow diversion requires the use of dual antiplatelet therapy (DAPT) to prevent in-stent thrombosis. DAPT may significantly increase the risk of hemorrhagic complications in patients who require subsequent surgical interventions. In this study, we sought to investigate whether DAPT is a risk factor for hemorrhagic complication associated with ventriculoperitoneal (VP) shunt placement in aneurysmal subarachnoid hemorrhage (aSAH) patients.

Methods:
Patients with aSAH who presented to our institution from July 2009 through November 2016 requiring VP shunt placement for persistent hydrocephalus were included. The rates of hemorrhagic complication associated with VP shunt placement were compared between patients who were on DAPT (Aspirin and Clopidogrel) for use of a stent or flow diverter, and patients who underwent microsurgical clipping or coiling only and were not on DAPT by way of a backward stepwise multivariate analysis.

Results:
443 patients were admitted for management of aSAH. Eighty of these patients eventually required VP shunt placement. 32 patients (40%) had been treated with stent-assisted coiling or flow diverters and required DAPT, whereas 48 patients (60%) had been treated with coiling without stents or surgical clipping and were not on DAPT at the time of VP shunt placement. A total of 8 cases (10%) of new hemorrhage along the intracranial proximal catheter of the VP shunt were observed. Seven of these hemorrhages were observed in patients on DAPT, while one occurred in a patient not on DAPT. After multivariate analysis, only DAPT was significantly associated with hemorrhage [OR: 31.23, 95% CI: 2.98-327.32, p=.0001]. One hemorrhage (1 of 32 [3%]) in a patient on DAPT required shunt revision for hemorrhage-associated proximal catheter blockage. The remaining seven hemorrhages were clinically insignificant.

Conclusions:
Our clinical series confirms that in patients with ruptured aneurysms that are candidates for stent assisted coiling or flow diversion, the risk of clinically significant VP shunt associated hemorrhage with DAPT is low. In an era of evolving endovascular therapeutics, stenting or flow diversion is a viable option in select aSAH patients.
Abstract WMP3: Unknown Onset Strokes With Anterior Circulation Occlusion Treated by Thrombectomy After DWI-FLAIR Mismatch Selection
Authors: Escalard Simon , Gory Benjamin , Kyheng Maéva , Desilles Jean-Philippe , Redjem Hocine , Ciccio Gabriele , Smajda Stanislas , Labreuche Julien , Mazighi Mikael , Piotin Michel , Blanc Raphaël , Lapergue Bertrand , Fahed Robert
Published: October 2018

Background and Purpose:
Unknown-onset strokes (UOS) have often been considered seperately from known-onset strokes (KOS), since emergency recanalization treatments are based on a time-window. Improvement in imaging-based selection and the advent of endovascular thrombectomy may lead us to reconsider this practice.

Methods:
We performed a retrospective, multicenter, cohort study of consecutive UOS treated by thrombectomy between December 2012 and December 2016. We compared UOS with proximal anterior circulation occlusion discovered beyond 6 hours from “last seen normal” with KOS for whom thrombectomy was started within 6 hours from onset. Time intervals from first found abnormal were recorded and compared with time intervals of KOS. Results were adjusted for age, initial National Institutes of Health Stroke Scale score, site of occlusion, diffusion weighted imaging Alberta Stroke Program Early CT Score, intravenous thrombolysis and use of general anesthesia.

Results:
Among 1246 strokes with anterior circulation occlusion treated by thrombectomy, 277 were UOS, with a “last time seen well” beyond 6 hours and DWI-FLAIR mismatch, and 865 were KOS who underwent groin puncture within 6 hours. Favorable outcome was achieved less often in UOS than KOS patients (45.2% vs. 53.9%, p=0.022). After pre-specified adjustment, this difference was not significant (adusted relative risk=0.91; 95%CI, 0.80 to 1.04; p=0.17). No differences in secondary outcomes were found except a marginal difference for excellent outcome (adjusted relative risk=0.83; 95%CI, 0.69 to 1.00; p=0.052), Time intervals from “first found abnormal” were significantly longer in UOS.

Conclusion:
Endovascular treatment of unknown-onset strokes with anterior circulation occlusion and DWI-FLAIR mismatch appears to be as safe and efficient as endovascular treatment of known-onset strokes within 6 hours from onset. This pattern of imaging could be used for patient selection when time of onset is unknown.
Abstract WMP32: Adaptive and Maladaptive Remodeling in Flow Loaded Rat Cerebral Arteries: Potential Significance to Pathogenesis of Cerebral Aneurysms
Authors: Abruzzo Todd , Pyne-Geithman Gail , Choutka Ondrej , Clark Joseph , Demel Stacie , Woo Daniel
Published: October 2018

Background and purpose:
In animal models, flow loading is a necessary and sufficient hemodynamic factor to express the cerebral aneurysm (CA) phenotype. Promotional biological factors may include variant forms of the adaptive response to flow loading. Using a rat model, this study characterizes molecular events that comprise cerebral arterial responses to flow loading and reveals their significance in relation to the CA phenotype.

Methods:
32 rats underwent bilateral common carotid artery ligation (BCL) (n=16) or sham surgery (SS)(n=16). Nineteen days later, vertebrobasilar arteries were harvested, histologically examined and analyzed for mRNA and protein expression. Flow (shear) induced changes in mRNA expression, protein expression and histology were determined by comparing BCL to SS rats. Differences between aneurysm-prone (Long Evans, LE) and resistant (Brown Norway, BN) strains were evaluated.

Results:
Basilar artery medial thickness/luminal diameter ratio was significantly reduced in BCL rats, without significant differences between LE (2.02 fold) and BN (1.94 fold) rats. BCL significantly altered basilar artery expression of mRNA and proteins that modulate wall structure and function but had no effect on blood pressure. Eight genes showed similarly large flow induced expression changes in LE and BN rats (TyrRS, Mfge8, Galnt13, GABRP, Pp1r1a, Dpt_predicted, Cd34_predicted, ApoE). Twenty six shear responsive genes showed significant differences in shear induced expression between LE and BN rats. The Cthrc1, Gsta3, Tgfb3, Ldha, Myo1d, Ermn, PTHrp, Rgs16 and TRCCP genes showed the strongest shear responsive expression, and the largest difference in shear responsive expression between LE and BN rats.

Conclusions:
Our study reveals specific molecular biological responses involved in flow induced expansive remodeling of cerebral arteries. A group of 9 strongly shear responsive genes showed major differences in flow induced expression between LE and BN rats and are implicated as having important roles in maladaptive remodeling associated with the CA phenotype.
Abstract WMP33: Real-World Clinical Outcomes of Ruptured Intracranial Arterial Aneurysm Treatment
Authors: Yuan Cindy , Karrison Theodore , Lee Seon-Kyu
Published: October 2018

Introduction:
Comparison of real world clinical outcomes between clipping and coiling for ruptured aneurysm is challenging, mainly due to confounding case severity and variation in physician expertise. We sought to compare outcomes and costs of coiling and clipping by utilizing a large national database.

Methods:
Ruptured intracranial aneurysm patients age 18 to 86 years were identified from the National Inpatient Sample (NIS) from 2007 to 2013. The clinical outcomes evaluated were in-hospital mortality, in-hospital stroke, discharge destination and other complications. Also, the total hospitalization cost was compared. Multivariate logistic regression and propensity-score matching were used. Confounding factors such as specific neurovascular comorbidities (e.g. hypertension, diabetes), Charleson comorbidity index (CCI), all patient refined diagnosis related group (APR-DRG) risk of mortality, APR-DRG severity index, and NIS-SAH severity score were also controlled for.

Results:
14379 patients with ruptured intracranial arterial aneurysms were identified (5966 clipping, 8413 coiling). Univariate analysis showed that coiling patients had higher preprocedural risks by CCI (p < 0.001) and APR-DRG mortality (p<0.001). Multivariate analysis showed no difference in in-house mortality (OR 0.96, p = 0.60), but coiling showed lower in-house strokes (OR 0.67, p < 0.001) and more discharge to a rehabilitation facility (OR 0.63, p<0.001). Coiling patients had higher odds of a hematoma (OR 1.44, p = 0.09) and hydrocephalus requiring treatment (OR 1.55, p<0.01), but lower odds of requiring a blood transfusion (OR 0.52, p<0.01). Analysis over time showed that in-house mortality has decreased over time (p=0.01) in coiling patients, but mortality after clipping has not changed. Coiling was slightly more expensive, but the difference was not significant ($2267, p=0.13).

Conclusions:
After adjusting for severity, there was no significant difference in mortality between coiling and clipping in ruptured aneurysm treatment. However, coiling patients had a lower chance of an in-hospital stroke and a higher chance of being discharged home. A limitation of the study is the possibility of unmeasured confounders.
Abstract WMP37: Temporal Changes in Carotid Endarterectomy (CEA) and Stenting (CAS) in Elderly Hospitalized With Symptomatic Carotid Stenosis in the United States, 2005 to 2014
Authors: Lin Michelle P , Markovic Daniela , Faigle Roland , Ovbiagele Bruce , Gottesman Rebecca
Published: October 2018

Introduction:
The CREST trial in 2010 showed higher complication rates with CAS than with CEA in elderly older than 70yo. Practice guidelines in 2011 have since recommended CEA for elderly patients if not contraindicated. However, the impact of CREST on contemporary trends of carotid revascularization in elderly is not well described.

Hypothesis:
We hypothesize a temporal increase of CEA and decrease in CAS in elderly (age>70yo) hospitalized for symptomatic carotid stenosis after the publication of CREST in 2010.

Methods:
Using data from the Nationwide Inpatient Sample, patients with symptomatic carotid stenosis admitted to hospitals from 2005 to 2014 with a discharge diagnosis of carotid artery stenosis with stroke or TIA were included. Primary analysis was the proportion of patients who received carotid revascularization (CEA or CAS) stratified by age (>70yo or ≤70yo) temporally. Survey
-
weighted logistic regression was used to estimate the rate for each year and compared across age.

Results:
Of 59,866 patients admitted for symptomatic carotid stenosis, 26.0% had CEA and 5.2% had CAS with mean age of 69.9±0.1. In the 5 years before CREST, the rate of CEA decreased from 29.9% to 22.8%, with a subsequent increase up to 25.7% in the 4 years after CREST. The rate of CAS, however, increased precipitously from 3.5% to 6.8% from 2005-2014. The magnitude of increase in CEA after CREST trended higher in elderly compared to younger group (absolute increase 4.1% vs 1.6%), whereas the magnitude of the increase in CAS trended lower in elderly compared to younger group (2.7% vs 3.9%). Elderly admitted to urban/teaching hospitals had greater odds of getting CAS (OR 6.4, 95% CI 4.1-10.0, p<0.001).

Conclusions:
The rate of CEA increased in elderly with symptomatic carotid stenosis in the United States since the publication of CREST in 2010. However, the hypothesized temporal decrease in CAS in elderly was not observed. Understanding more about decision making for CEA vs CAS in elderly is needed.
Abstract WMP4: Intravenous Thrombolysis Before Endovascular Treatment Leads to Higher Hospital Charges Without Improving Outcomes
Authors: Hassan Ameer E , Shariff Umar , Sanchez Christina , Malik Ahmed , Qureshi Adnan
Published: October 2018

Background and Purpose:
Large vessel occlusion strokes are less likely to respond to intravenous thrombolytics (IV TPA) with recent endovascular treatment (EVT) studies showing superiority of EVT vs IV TPA alone. Our study aims to compare outcomes and hospital charges for strokes treated with either EVT alone or with IV TPA+EVT.

Methods:
We utilized our prospectively maintained endovascular database and analyzed all the patients who underwent EVT, categorizing them into IV TPA+EVT and EVT alone, comparing total encounter charges at our hospital between the two groups. We collected baseline demographics, clinical characteristics, admission, 24-hour, discharge, and 3-months NIHSS, and modified Rankin Scale (mRS) at discharge and 90 days follow up. Hemorrhage rates were also recorded. Median NIHSS and mRS for the two groups were compared using the Mann-Whitney U test.

Results:
220 patients analyzed, 123 (55.9%) received EVT only and 97 (44.1%) received IV TPA+EVT. There was no statistical difference in baseline demographics, clinical characteristics, or NIHSS score on admission (Table 1). There was no difference in recanalization (p=.33) or favorable outcome (p=.997). There was a higher rate of intracranial hemorrhage in the IV TPA+EVT group vs EVT only group, 20 (20.6%) vs 10 (8.1%) respectively (p = .01). The mean [SD] total hospital encounter charges were $227,697.65 [±88,141.67] for EVT only group and $281,923.08 [±147,638.97] for IV TPA+EVT group (p=.001). Charges for IV TPA+EVT were $59,275.70 [95%CI (2636.13-115915.28)] higher than for EVT only group after adjusting for confounders (p=.04).

Conclusions:
The use of IV TPA did not improve functional outcomes for those patients undergoing combined endovascular therapy. Combined therapy was associated with significantly higher charges and increased hemorrhage rates than EVT alone. Prospective studies are warranted to study the cost/benefit ratio for IV TPA in combination with EVT.
Abstract WMP40: A Comparison of Three Different Endovascular Approaches for Extracranial Internal Carotid Artery Lesions in the Setting of Tandem Occlusions
Authors: Rodriguez-Villatoro Noelia , Rodriguez-Luna David , Ribø Marc , Muchada Marian , Requena Manuel , Pagola Jorge , Boned Sandra , Juega Jesús M. , Coscojuela Pilar , Vert Carla , Rubiera Marta , Molina Carlos , Tomasello Alejandro
Published: October 2018

Background:
Endovascular treatment (EVT) of extracranial internal carotid artery (ICA) lesions in the setting of tandem occlusions is a challenge, being angioplasty alone (AA) or angioplasty+stenting (AS) the two current approaches. Hemorrhagic transformation (HT) is a major problem when a conventional [self-expanding (SX)] stent is placed, regarding the need of early double antiplatelet therapy. Interestingly, balloon-expanding (BX) stents, due to their less thrombogenicity, may constitute an alternative, so they do not need early antiplatelets. We aimed to study differences in ICA restenosis, HT, clinical outcome and stroke recurrence between patients treated with AA or AS.

Methods:
Prospective study of consecutive patients with non-cardioembolic ischemic stroke and tandem occlusions, who underwent <6hours EVT from April 2013 to April 2017. We compared rate of ICA high-degree stenosis/occlusion at 24h, HT, clinical outcome (change in NIHSS at 24h and at discharge over NIHSS at admission, and mRS≥2 at 3 months) and stroke recurrence within 3 months between AA and AS (SX and BX stents) groups.

Results:
Ninety-two patients fulfilled inclusion criteria: mean age 64.6±12.6 years. Forty (43.5%) received AA and 52 (56.5%) AS (61.5% SX stents, 38.5% BX stents). Both groups were comparable in baseline characteristics. Fifty (54.3%) received IV rtPA. Patients who underwent AA presented ICA high-degree stenosis/occlusion at 24h more frequently than those who underwent AS (86.5% vs. 21.2%,
p
<0.001). No differences were found in HT, clinical outcome and stroke recurrence (
p
>0.05 for all comparisons). In the AS group, all SX stents received antiplatelets after EVT, whereas in 75% of cases in the BX group no antiplatelets were started within 24h. However, no differences were found in ICA high-degree stenosis /occlusion at 24h, clinical outcome and stroke recurrence (
p
>0.05). We neither found differences in HT. Nevertheless, all cases were asymptomatic in the BX stents group.

Conclusions:
Emergent ICA stenting seems to have a lower risk of restenosis compared to AA, without a significant increase of HT and stroke recurrence or a worse clinical outcome. BX stents, without early antiplatelet therapy, are a promising alternative to conventional carotid stents.
Abstract WMP43: Bright Signals of MCA Plaque on T2 Weighted Vessel Wall Imaging are Associated With Ischemic Stroke
Authors: Yu Yannan , Liu Mengwei , Li Mingli , Xu Yuyuan , Gao Shan , Feng Feng , Liebeskind David S , Scalzo Fabien , Xu Weihai
Published: October 2018

Objective:
Hyperintensity of intracranial atherosclerotic plaque on T2 weighted vessel wall imaging (VWI) may indicate certain components such as fibrous caps, juxtaluminal thrombus, or intraplaque hemorrhage. We aim to explore if the plaque signal of middle cerebral artery (MCA) stenosis on T2 weighted VWI is associated with ischemic stroke.

Methods:
Patients with recent stroke (<2 weeks) were reviewed in our institutional and prospectively-collected VWI database. Patients with cardioembolism, carotid artery stenosis, or non-atherosclerotic MCA stenosis were excluded. Culprit MCAs and contralateral asymptomatic MCAs that exceeded 50% stenosis were analyzed. Stenosis degree and remodeling ratio were measured on the maximal narrowing site. Plaque area was manually delineated on T2 weighted VWI. The plaque signal was normalized (divided by masseter or buccinator muscle signal, Fig1). The thresholds of normalized plaque signal (≥1.0 to 1.8 with an increment of 0.1) were tested. Logistic regression and Receiver operating characteristic (ROC) analysis were performed to determine the optimal signal threshold of predicting culprit MCA.

Results:
Eighty-two MCAs were analyzed (from 66 patients, 51 male, mean age 58±16 years, mean stenosis degree 68±14%, mean remodeling ratio 1.10±0.21), including 60 culprit MCAs and 22 contralateral asymptomatic MCAs. Logistic regression analysis indicated the model of pixel number with normalized plaque signal ≥1.4 (OR 1.08 per 1-pixel increase, 95% CI 1.01-1.15) and remodeling ratio (OR 1.90 per 0.1 increase, 95% CI 1.25-2.89) was of the highest diagnostic value (AUC 0.861, 95% CI 0.779-0.943). Stenosis degree was not independently associated with culprit MCA. Other tested thresholds from 1.0 to 1.8 also had good diagnostic value with AUC 0.814-0.858.

Conclusions:
The bright signals of MCA plaque on T2 weighted VWI are associated with ischemic stroke. Further study is required to clarify the underlying pathophysiology.
Abstract WMP45: Gene Expression Profile of Cervical Artery Dissection by Time of Event (CADEX Study)
Authors: Southerland Andrew M , McMurry Timothy L , Green Ilana E , Williams Stephen R , Keene Keith L , Owens Debra L , Odell Valerie A , Hsu Fang-Chi , Bekiranov Stefan , Sale Michele M , Worrall Bradford B
Published: October 2018

Introduction:
Cervical artery dissection (CeAD) of the carotid and vertebral arteries is a prevalent cause of stroke in young adults. While the pathogenesis of incident CeAD remains poorly understood, clinical and genetic associations suggest a systemic arteriopathy at time of event.

Hypothesis:
Individuals suffering CeAD express a distinct gene expression profile at time of event compared to (1) age and sex-matched controls and (2) convalescent profiles within the same individual at a later time point.

Methods:
We enrolled 37 consecutive patients with carotid or vertebral artery dissection (with and without ischemic stroke) from 2013-2016, excluding concurrence of major trauma. Cases were age and sex matched to non-CeAD ischemic stroke controls (n=16) and healthy controls (n=11). Whole blood samples were collected within four weeks from time of event, and again at 3 and 6-month follow-up. We used IlluminaHT-12 microarrays to assess differential gene expression at time of CeAD relative to controls, and relative to gene expression at >3 month follow-up within CeAD cases. Mixed effects regression models included relevant covariates of age, sex, race/ethnicity, time of enrollment, and occurrence of stroke. We used a False Discovery Rate (FDR) cutoff of 5% to account for multiple testing as well as a 1.5 fold change cutoff to identify robust, differential gene expression.

Results:
We identified 538 differentially expressed genes between CeAD patients and healthy controls with 30 of these genes reaching our predetermined 1.5x fold change limit. Within CeAD cases, 1,238 genes showed differential expression at a 5% FDR compared to time points at 3-6 month follow-up, with 31 genes showing at least a 1.5 fold change. Compared to controls and convalescent profiles, 12 genes were significant using the 5% FDR and 1.5 fold change cutoffs. Preliminary gene-ontology analysis indicate the largest differential expression for genes associated with oxygen and gas transport.

Conclusion:
In this consecutive cohort of individuals with CeAD, we identified a distinct gene expression profile associated with incident dissection. These data are limited by small sample size and results are hypothesis generating. Replication in larger, independent cohorts is warranted.
Abstract WMP46: Genetic Coding Variation in Young Stroke With Dolichoectasia
Authors: Thijs Vincent , Grittner Ulrike , Giese Anne-Katrin , Böttcher Tobias , Enzinger Christian , McCabe Dominick , Putaala Jukka , Martus Peter , Norrving Bo , Fazekas Franz , Tatlisumak Turgut , Rolfs Arndt
Published: October 2018

Objective:
To evaluate the role of coding variation in younger stroke patients with severe dolichoectasia of the basilar artery.

Methods:
We rated dolichoectasia in younger (<55 years) TIA/stroke patients from a large, multicenter, prospective, hospital-based cross-sectional study of stroke in young adults (Stroke in Fabry Patients 1, NCT004414583). Targeted sequencing was used to identify variants in 7 genes (PKD1, PKD2, COL4A1, COL4A2, GAA, MMP3, SCLA10) which were previously reported in patients with dolichoectasia. We assessed whether there was an increased burden of variants which were pathogenic, ‘likely pathogenic’ or variants of unknown significance (VUS) in these genes in patients with severe dolichoectasia compared with 929 controls.

Results:
Dolichoectasia was severe in 91 of 3850 patients (2.4%). Amongst the 85 tested Caucasian patients with severe dolichoectasia, 44 (52%) carried potentially pathogenic variants or VUS. The burden of variants was higher in cases than in 929 controls, with two or more variants simultaneously identified in 9/85 (11%) cases compared with 18/929 controls (2 %; p<0.001). The following variants were identified: PKD1/PK2 variants in 34 (40%) patients (2 pathogenic mutations; 32 with VUS); COL4A1/COL4A2 variants in 7 (8%) (all VUS with one homozygote); MMP3 variants in 2 (2%)(1 likely pathogenic, one VUS); GAA variants in 6 (7%), including 2 compound heterozygotes and one likely pathogenic variant in SCLA10. The frequency of variants was significantly higher in cases than controls for the PKD1 gene (44%
vs
. 3%, p<0.001), PKD2 (4.7%
vs
. 0.5%, p=0.004), MMP3 (2.4%
vs.
0%, p=0.007) and GAA genes (9%
vs.
1.2%, p=0.001).

Interpretation:
Severe dolichoectasia is associated with a high burden of coding variation in target genes.
Abstract WMP47: Cholesterol Crystals in Embolic Debris Correlate Postoperative Silent Cerebral Embolism in Carotid Artery Stenting
Authors: Maekawa Kota , Shibata Masunari , Nakajima Hidetaka , Kitano Yotaro , Seguchi Masaru , Kobayashi Kazuto , Sano Takanori , Yabana Tadashi , Naito Yutaka , Miya Fumitaka
Published: October 2018

Introduction:
Very few studies have investigated the relationship between the histopathology of the embolic debris in embolic protection devises and postoperative cerebral embolism in carotid artery stenting (CAS). The aim of this study was to evaluate embolic debris and its association with clinical, laboratory, and neurointerventional findings in patients treated by CAS due to internal carotid stenosis.

Hypothesis:
Cholesterol crystals in embolic debris are associated with postoperative cerebral embolism in CAS.

Methods:
All embolic debris was stained with hematoxylin-eosin. Embolic debris underwent quantitative analysis to quantify three main components: red blood cells, white blood cells and fibrin, by color based segmentation. Histopathological assessment included presence of calcifications, cholesterol crystals, foamy cells, and endothelial cells. Diffusion weighted image (DWI) was evaluated 1 to 3 days after CAS, and patients were classified by presence of new lesions on DWI after CAS. Exclusion criteria were emergency CAS for stroke in evolution or crescendo transient ischemic attack.

Results:
From November 2015 to April 2017, 40 patients were treated in our hospital by CAS due to internal carotid artery stenosis. Exclusion criteria were fulfilled in 5 patients. 24 patients had new lesions on DWI after CAS and 11 patients did not have those. Single patient had symptomatic cerebral embolism. Patients with new lesions on DWI after CAS had higher rate of cholesterol crystal in embolic debris (80% vs 18%, p<0.01) and higher rate of patients taking strong statin on admission (71% vs 18%, P=0.02) than those without new lesions on DWI after CAS. There is no significant difference with blood levels of LDL-cholesterol [111 mg/dl (79-197) vs 108 mg/dl (62-167); p=0.85]. Main components of embolic debris were not significantly different between two groups.

Conclusion:
Cholesterol crystals in embolic debris and treatment history of dyslipidemia were significantly associated with post-operative high intensity lesion on DWI in CAS.