bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP79: Significant Correlations between Risk Factors for Rupture of Cerebral Aneurysms and Hemodynamic Factors by Using Computational Flow Dynamic (CFD) Analysis and Multivariate Analysis
Authors: Shimogonya Yuji , Fukuda Shunichi ,   the CFD ABO Study Group
Published: October 2018

Background and purpose:
Although it is thought that hemodynamic factors are involved in cerebral aneurysm rupture, details are unknown. Using multivariate analysis and computational flow dynamic (CFD) analysis, we investigated here correlations between well-known aneurysm rupture risk factors and hemodynamic factors.

Methods:
Patient-specific inflow velocities and arterial geometries of 86 cerebral aneurysms (43 Anterior Communicating artery and 43 MCA aneurysms) were acquired from patients who consented to participate in the multi-institutional prospective clinical study, CFD ABO Study. Pulsatile blood flow was simulated using ANSYS-CFX, based on the Navier-Stokes equations for incompressible fluid. Multivariate regression analysis was performed to find independent predictors for wall shear stress (WSS) magnitude-based metrics (WSS, NWSS) and WSS disturbance-based metrics (OSI, NtransWSS) on the CFD modelling to predict potential factors, including maximum diameter, site, sex, age, history of hypertension and smoking.

Results:
The associations between maximum diameter and hemodynamic metrics were all significant [WSS: regression coefficient (RC), -0.65, 95%CI, -1.1 to -0.18; NWSS: RC, -0.96, 95%CI, -1.6 to -0.36; OSI: RC, 0.0032, 95%CI, 0.0018 to 0.0046; NtransWSS: RC, 0.013, 95%CI, 0.0075 to 0.018], while relations between site and WSS, NWSS, and NtransWSS, but not OSI, were significant (WSS: RC, -2.1, 95%CI, -3.1 to -0.10; NWSS: RC, -2.9, 95%CI, -4.1 to -1.6; NtransWSS: RC, 0.013, 95%CI, 0.0015 to 0.024). Among aneurysm maximum diameter, surface area, volume, and diameter-ratio between parent artery and aneurysm, diameter-ratio was the strongest correlation with all hemodynamic metrics (WSS: RC, -1.2, 95%CI, -2.2 to -0.23; NWSS: RC, -1.9, 95%CI, -3.1 to -0.64; OSI: RC, 0.0052, 95%CI, 0.0022 to 0.0082; NtransWSS: RC, 0.022, 95%CI, 0.011 to 0.034).

Conclusions:
The data suggest that a difference in rupture rate according to aneurysm site and size are hemodynamically dependent; lower WSS and increased disturbed flow may be associated with aneurysm rupture. Since diameter-ratio is most correlated with these hemodynamic factors, this index may be a good indicator for hemodynamic factors.
Abstract TP80: Improving Perioperative Stroke Detection During Intracranial Aneurysm Surgery Using Somatosensory Evoked Potential Waveform Analysis
Authors: Saca Eyad E , Kashkoush Ahmed I , Crammond Donald J , Balzer Jeffrey R , Thirumala Parthasarathy D
Published: October 2018

Background:
Current alarm criteria for evaluating impending perioperative stroke using somatosensory evoked potential (SSEP) intraoperative monitoring is a 50% reduction in amplitude or a 10% increase in latency. In this study, we aim to evaluate the diagnostic accuracy of SSEP changes for predicting perioperative stroke during intracranial aneurysm surgery.

Methods:
We retrospectively reviewed the intraoperative neurophysiological records of 100 patients who underwent intracranial aneurysm clipping at our institution between 2009-2013. Of those 100 patients, 25 patients incurred a new onset perioperative stroke and 75 age- and sex-matched controls did not. Quantitative analysis was done to evaluate SSEP amplitude and latency changes during various surgical events including pre-incision, incision, dural opening, before clipping (both temporary and permanent), after clipping, and during dural closure. Diagnostic accuracy was calculated as the area under the receiver operating characteristic curve (AUC) for maximum SSEP amplitude and latency changes from a baseline set at incision. Statistical analysis was performed using R Statistical Software v3.4.1.

Results:
The mean age (with standard deviation) of our cohort was 55.3 ± 11.2 yrs (24 male, 76 female). Preoperative rupture rate was similar in patients with perioperative stroke (36%) and controls (25%) (p=0.440). SSEP amplitude reduction was significantly greater in patients with perioperative stroke relative to controls after temporary clipping (54.6% vs. 24.3%, p<0.001). AUC for maximum amplitude reduction was calculated to be 0.80 (95% CI, 0.70-.0.90). Notably, latency prolongation was found to be a non-significant discriminator of stroke, with an AUC of 0.60 (95% CI, 0.47-0.73). AUC for 50% SSEP amplitude reduction was calculated to be 0.73 (95% CI, 0.63-0.84) and the AUC for 10% latency prolongation was found to be 0.54 (95% CI, 0.44-0.64).

Conclusion:
SSEP amplitude changes, but not latency changes, are strongly predictive of stroke during intracranial aneurysm surgery. However, the current alarm criteria of 50% reduction in amplitude have limited value in informing the surgeon of impending perioperative stroke due to their predictive nature.
Abstract TP83: Age-Related Intra-Pipeline Stenosis: Complication or Benign Endothelial Healing
Authors: Atallah Elias , Bekelis Kimon , Rosenwasser Robert H , Jabour Pascal , Tjoumakaris Stavropoula , Chalouhi Nohra
Published: October 2018

Background:
The use of flow diverters has stretched to address several sets of aneurysms such as giant, small blister, fusiform, distal IAs of the anterior and posterior circulation. Only very few studies considered addressing the rate and the characteristics of intra-pipeline stenosis(IPS).

Objective:
we aimed to appraise the prevalence, the predictors and outcomes of IPS and the consequent clinical implications.

Method:
We reviewed the charts of 537patients treated with pipeline for their IAs between 2011 and 2017. We consecutively gathered clinical and angiographic data related to IPS. Stenosis was interpreted by the operating neurointerventionist: mild<50%, moderate50-75% and severe>75%. To control confounding, we used multivariable logistic regression and propensity score conditioning.

Results:
Of 537patients, 31(15.6% were females) had an angiography perceived IPS. 8(25.8%) of our patients were >65yo. 23(74%) patients had their IPS detected at 6moths follow-up. The mean follow-up time to detect IPS was 7.2months(SD=6.33). 23(74.2%) and 8(25.8%) patients had their aneurysms located in the anterior & posterior circulation respectively. The average pipeline size was 3.8x19.4mm. Six patients had an IPS located, at the proximal (n=3) and distal end (n=3) of the pipeline, 25 patients had IPS somewhere along the body of the pipeline. 20/31 patients had mild IPS, 5/31 had moderate IPS and 6/31 had severe IPS. Regression of IPS was perceived in 9/31 patient. IPS progression was noted in one patient from 70% to 90%. 4(12%) patients had >90% IPS, all were symptomatic: 3 had a right hemispheric stroke and 1 patient precipitated an intra-cerebral hemorrhage. In multivariable analysis, patients of older age (>65yo) were less likely to develop IPS (OR0.96;CI95%,0.9-1;p=0.03). Those with a history of hypertension were more prone to develop IPS (OR3.3;CI95%,1.1-9.8;p=0.03). Per-procedural use of balloon angioplasty, aneurysm size and ruptured aneurysm were not independent predictors of IPS.

Conclusion:
Young patients <65yo and patients with hypertension are more prone to develop IPS. Balloon angioplasty does not predict IPS. IPS remains a benign development, most likely to regress than to progress into a clinically manifest stenosis.
Abstract TP84: Safety and Effectiveness of Ticagrelor in Patients With Clopidogrel Resistance Undergoing Angioplasty, Stent or Flow Diverter Placement
Authors: Hassan Ameer E , Shariff Umar , Qureshi Adnan
Published: October 2018

Background and Purpose:
Nearly 30% of the patients have clopidogrel resistance and are at high risk for in-stent thrombosis and adverse ischemic events. Ticagrelor is an allosteric platelet antagonist that reversibly inhibits the P2Y12 platelet receptor more potently than clopidogrel. We report upon the safety and effectiveness of ticagrelor in patients with cerebrovascular diseases and clopidogrel resistance undergoing angioplasty and/or stent or flow diverter placement.

Methods:
We analyzed data from our prospectively maintained endovascular database and identified patients treated with ticagrelor and underwent treatment with a stent or flow diverter. The patients were divided into an acutely loaded dose group and those converted from clopidogrel due to clopidogrel resistance, defined by platelet aggregation value of 200 PRU VerifyNow P2Y12 test. Patients received standard dual antiplatelet therapy, however, despite repeat clopidogrel loading doses, were found to be clopidogrel non-responders and were then administered ticagrelor 180mg loading dose and maintained on 90mg BID dosing. We ascertained occurrence of any bleeding complications, classified as major (hgb decrease >5 g/dl), minor (hgb decrease 3-5 g/dl), or insignificant.

Results:
A total of 36 (13.8%) patients (mean age 64.7±13.8 years; 58.3% females) had clopidogrel resistance out of 260 patients screened. Of those, 29 patients were switched from clopidogrel to ticagrelor due to an elevated PRU (avg 294.76±41.32 PRU) and 7 patients without previous antiplatelet use received a bolus and maintenance dose. Only one patient experienced a transient ischemic event within 24 hours after starting ticagrelor. Patients who were acutely loaded did not experience any ischemic events. No patient experienced symptomatic or asymptomatic hemorrhage on ticagrelor in the post-op period. A total of 43 procedures were performed in 36 patients with clopidogrel resistance: 26 pipeline placements, 8 wingspan stent placements, 2 LVIS stents, 1 neuroform stent with pipeline, and 7 angioplasties.

Conclusions:
Our study demonstrates the safety and effectiveness of loading or switching patients to ticagrelor with cerebrovascular diseases undergoing angioplasty, stent or flow diverter placement.
Abstract TP85: Reversible Brain Swelling After Flow Diverter Stents Placed From Middle Cerebral Artery to Internal Carotid Artery
Authors: Narata Ana Paula , Cottier Jean-Philippe , Bibi Richard , Herbreteau Denis , Janot Kevin
Published: October 2018

Introduction:
Flow diverter stent (FDS) positioning for internal carotid artery (ICA) requires sometimes a placement of the distal part of the stent in the middle cerebral artery (MCA) and the proximal part in the ICA (MCA-ICA) to insure complete neck coverage and, occasionally, we observed that patients could develop transient neurologic deficits by brain swelling. We hypothesized that this positioning can increase flow disruption at the MCA and can be associated to temporary neurological impairment.

Methods:
151 patients with ICA aneurysms were treated with flow diverter stents from January 2013 to December 2016. We considered only patients with FDS placed from MCA-ICA and at least 3 months of follow-up.

Patients’:
clinical and radiological records were assessed during hospitalization and follow-up. Ischemic lesions and intracranial hemorrhage after procedure were differentiate from generalized brain swelling by MRI using diffusion-weighted imaging, fluid-attenuated inversion recovery (FLAIR) and high-resolution 3D T1-weighted imaging with contrast injection.

Results:
FDS were placed from MCA-ICA in 7 patients and 5 of them presented temporary neurological impairment and brain swelling. 1 patient presented reversible localized contrast enhanced lesions considered nickel allergy or foreign body reaction, and another patient did not develop any symptom. All 5 patients improved during hospitalization (48-96 hours after symptoms onset). MRI at 3 months did not show any permanent lesion.

Conclusions:
In our experience, most of the patients with FDS placed from MCA-ICA developed transient deficit with brain swelling. Even being a transitory event, further investigation is necessary to understand flow changes into the vessels where FDS are placed.
Abstract TP87: Hemodynamic Differences Observed between Growing and Stable Symmetric MCA Bifurcation Aneurysms
Authors: Chang Dennis , Lau Vicki , Hildebrandt Michelle , Duckwiler Gary , Vinuela Fernando , Chien Aichi
Published: October 2018

Introduction:
The analysis of symmetric aneurysms can control for genetic differences in studies of aneurysm growth. This study aims to evaluate the differences in hemodynamic flow between growing and stable aneurysms symmetrically located at the middle cerebral artery (MCA) bifurcation.

Hypothesis:
Differences in the hemodynamic flow exist between growing and stable symmetric aneurysms at the MCA bifurcation.

Methods:
6 patients with symmetric pairs of MCA bifurcation aneurysms were followed with CTA imaging for a mean of 19.82 ± 7.68 months, across 2.67 ± 0.52 imaging scans. In three patients both aneurysms were stable, while in three others one of the aneurysms exhibited growth. 16 computational flow simulations of the complete Circle of Willis, each including a pair of symmetric aneurysms, were run based on the CTA imaging studies. Blood flow at the neck, body, and dome of each aneurysm was analyzed. Welch’s t-test was used to compare growing and stable groups.

Results:
The mean diameters were 4.46±2.29 mm for the growing aneurysms and 4.24±1.99 mm for the stable aneurysms (p=0.8). No significant difference in wall shear stress (WSS) was found between growing and stable aneurysms (p=0.14). However, the growing aneurysms exhibited a significantly higher neck pulsatility index (PI) (1.33±0.27 vs 1.02±0.52, p=0.05) and a lower body PI (1.04±0.41 vs 1.69±0.76, p<0.01). Stable aneurysms in patients with a growing symmetric aneurysm had significantly lower dome PI (1.61±0.32 vs. 2.56±1.26, p=0.01) and overall higher WSS (p=0.02) (5.49±4.42 vs. 3.16±3.54) than bilaterally stable aneurysms.

Conclusion:
Stable aneurysms with symmetric growing aneurysms share similar hemodynamic characteristics and may be at risk for future growth. In general, interpatient aneurysm hemodynamic differences were more significant than intrapatient differences. Such patient-specific differences may arise from the tortuosity of the cerebral vascular tree.
Abstract TP9: Complete Recovery After Endovascular Treatment. a Predictable Outcome
Authors: Cardona Pedro , Quesada Helena , Lara Blanca , Barranco Roger , Luttich Alex , Aixut Sonia , Paipa Andres , De Miquel Ma , Escrig Ana , Mora Paloma
Published: October 2018

Background:
Multiple randomized trials have demonstrated that endovascular treatment(EVT) in selected stroke patients is associated with good clinical outcome (90 days mRankin 0-2: 33-60%). The percentage of complete functional recovery (mRankin Score: 0) is the most optimist and desirable result after endovascular treatment and their predictor factors are unknown.

Methods:
Consecutive patients with ischemic stroke who received endovascular reperfusion treatment were retrospectively analyzed between August 2010 and May 2017. We review the percentage of recanalization (TICI 2b-3), good outcome in 90days follow-up(mRS0-2) and complete recovery(mRS 0) after EVT. We evaluate which variables are associated to complete recovery and excellent outcome.

Results:
We reviewed 802 endovascular treatments. Ninety-five percent of occlusions were located in middle cerebral artery or terminal internal carotid, (45% women, mean age 67+/-13 years; NIHSS at admission 17. Successful recanalization (TICI 2b-3) was achieved in 82%. At 90 days good functional outcome (mRS 0-2) was seen in 51% . A complete functional recovery was achieved in 19% of EVT. We compare patients who achieve 90d mRS:0 vs 90d mR:1-2; in this analysis baseline NIH (14 vs 17) and OSTP (Onset Stroke Time to Puncture: 256 vs 281 min) were predictor variables significantly associated to complete functional recovery after adjustment (p:0.001). Radiologic variables: baseline ASPECTS>9, M1-M2 occlusion, a single pass of stent-retriever and absence of hemorrhagic transformation in 24hCT are related in multivariate analysis to 90d mRS 0. Nine percent of patients showed abscence of infarct in DWI sequence of MRI performed in acute phase of stroke.

Conclusions:
Excellent functional outcome after thrombectomy could be achieved in highly percentage of patients with short OSTP. Good radiological findings warrant excellent results.
Abstract TP90: Disruption of Connexin30/32 Contributes to Impaired oligodendrogenesis in Ischemic White Matter Injury
Authors: Han Lijuan , He Dongsheng , Zhang Xi , Xu Yun
Published: October 2018

Hypothesis:
Astrocytes expressing connexin (Cx) 30 forms gap junctions with oligodendrocytes expressing Cx32. Gap junctions are the molecular basis for the panglial syncytium and are vital for oligodendrocyte survival as well as white matter integrity. Disruption of astrocyte-oligodendrocyte (A/O) gap junctions has been shown in several demyelinating central nervous system disorders. However, their involvement in cerebral ischemia remains largely unknown.

Methods:
Ischemic white matter injury in mice was induced by long-term bilateral carotid artery sclerosis (BCAS). White matter injury was examined by MBP staining and 7T-MRI. Cognitive impairment of BCAS mice was assessed by Novel object recognition and Morris water maze test. Expression of connexin30 and connexin32 in astrocytes and oligodendrocytes, respectively, was measured by real-time PCR and immunofluorescence. Brdu was used to label pre-oligodendrocytes and newly generated oligodenrocytes. Oligodendrogenesis was calculated by the ratio of newly generated oligodendrocytes among total oligodendrocytes.

Results:
White matter injury was induced in BCAS mice at 30 days post ischemic injury. BCAS mice show reduced novel object recognition ability. Compared to the control group, the learning and memory ability was impaired in BCAS mice. Both the expression of Cx30 and Cx32 in astrocytes and oligodendrocytes was decreased in BCAS. Moreover, co-localization of Cx30 and CX32 was damaged in BCAS mice, indicating that A/O gap junction was damaged in ischemic white matter injury. In addition, oligodendrogenesis was inhibited in BCAS mice as demonstrated by decreased Brdu-labeled newly generated oligodendrocytes.

Conclusions:
Disrupted A/O gap junction contributes to the impaired oligodendrogenesis in ischemic white matter injury, and eventually lead to cognitive impairment.
Abstract TP91: Multiple Intra-arterial Dosing of the Mesenchymal Stem Cells Reduces Ischemic Brain Injury in a Rat Stroke Model
Authors: Watanabe Mitsuyoshi , Bhattacharya Pallab , Khan Aisha , Hare Joshua M , Perez-Pinzon Miguel , Raval Ami P , Yavagal Dileep R
Published: October 2018

Background:
Cell therapy is emerging as a promising novel treatment for ischemic stroke. Intra-arterial (IA) mesenchymal stem cells (MSCs) delivery in ischemic stroke has a high potential for clinical translation. Recently, we demonstrated the safety and efficacy of IA delivery of MSCs at 24h in a reversible middle cerebral artery occlusion (rMCAo) rodent model. Given the trophic mechanism of action of cell therapy in stroke, a second dose of cells may be beneficial. However, it is unclear if a second IA-MSCs administration is safe and efficacious. Therefore, we aimed to evaluate administration of two doses of IA-MSCs in the rodent stroke model.

Methods:
Female ovariectomized Sprague–Dawley rats were exposed to MCAo for 90 min. Rats were treated with IA-MSCs (1x10
5
cells) or phosphate-buffered saline (PBS) at 1 and 6 days (1D-6D) after MCAo. To test neurological and motor function, the standardized neurobehavioral test battery and the rotarod test were performed. The mean duration (in seconds) on the device was recorded from 3 rotarod measurements. The rats were tested at 7, 15 and 30 days after MCAo. Rats were sacrificed at 30 days for infarct volume measurement using histology.

Results:
There were no neurological worsening or mortality seen in either treatment group. We observed significant reduction in infarct volume in 1D-6D MSCs group (21 ± 15mm
3
; n=5) compared to the PBS-treated group (86 ± 19 mm
3
; n=8, p<0.05). The 1D-6D MSCs group also showed improvement in rotarod test results (16.8 ± 5.8% vs 7.9 ± 3.4%, p=0.075) at 30 days and neurological scores (5.6 ± 1.2 vs 7.75 ± 0.6, p=0.15) at 15 days.

Conclusions:
Double dose IA-MSCs at 1D-6D post rMCAo is safe and reduces ischemic brain injury in female rats, with a trend towards functional improvement.
Abstract TP92: Microglial Kv1.3 Channels Are Rapidly Downregulated Following Transient Ischemic Stroke in Mice
Authors: Raza Syed Ali , Cheng Lihong , Xiao Hailian , Yepes Manuel , Rangaraju Srikant
Published: October 2018

Background:
Microglia and CNS-infiltrating macrophages (CNS MPs) perform opposing deleterious pro-inflammatory and protective functions in ischemic stroke. Kv1.3 channels regulate pro-inflammatory microglial functions and are promising therapeutic targets to curb neuroinflammation. Since Kv1.3 channel expression in CNS MPs following ischemic stroke is unknown, we characterized Kv1.3 expression in CNS MPs at different times following ischemic stroke.

Methods:
In the 30-min transient middle cerebral artery occlusion (MCAO) mouse model, we performed flow cytometric assays of cell surface Kv1.3 expression (fluorescent labeled Kv1.3 blocking peptide ShK-F6CA) and phycoerythrin-microsphere phagocytosis on acutely isolated CNS MPs from ipsi- and contralateral hemispheres (including sham surgery controls) at 30 min, 24h, 48h, 72h and 7d time points. Among CD11b
+
CNS MPs, resting microglia (CD45
low
Ly6c
low
), activated microglia (C45
high
Ly6c
low
) and infiltrating macrophages (CD45
high
Ly6c
high
) were monitored. By quantitative PCR, we measured Kv1.3, Kir2.1 potassium channel and COX2 gene expression in CD11b
+
CNS MPs.

Results:
After 48h following MCAO, proportions of activated microglia and infiltrating macrophages were increased ipsilaterally. Kv1.3 channels were highly expressed in CD45
high
Ly6c
low
activated microglia at baseline but significantly declined after 48 hours ipsilaterally with same trend contralaterally. Kv1.3 mRNA in CNS MPs also showed an overall decreasing trend ipsilateral to MCAO. No changes in phagocytic properties were observed following MCAO.

Conclusions:
Despite increased proportions of activated microglia and infiltrating macrophages, a precipitous downregulation of Kv1.3 channel expression occurs in CD45
high
activated microglia after 48 hours following transient cerebral ischemia in mice. Early microglial Kv1.3 channel blockade effects on neuroinflammation following ischemic stroke need to be determined.
Abstract TP94: Combined Chlorpromazine and Promethazine Induce Neuroprotective Hibernation Without Hypothermia in Experimental Stroke
Authors: Geng Xiaokun , Stone Christopher R , DeGracia Donald , Ding Yuchuan
Published: October 2018

Introduction:
Hibernation, in which the lowering of metabolism and body temperature reduces the energetic needs of brain cells, has emerged as a frontier in the search for neuroprotective agents against ischemia. In fact, it has been partially achieved clinically with therapeutic hypothermia. Metabolically slowed, hibernation-like states lead to a decrease in ischemic damage and improved neurologic outcomes. However, decreasing body temperature can cause serious systemic complications. Thus, finding ways to induce a hibernation-like drop in metabolism without also inducing hypothermia is clinically important. It was shown that pharmacological hibernation with Chlorpromazine and Promethazine (C+P) resulted in decreased brain activity and decreased body temperature. Here, by isolating these two effects, and by investigating effects on NADPH oxidase (NOX), the key component in the pathway most central to oxidative injury during ischemia, we sought to determine whether the neuroprotective effect of C+P is dependent or independent from its effect on body temperature.

Methods:
Sprague-Dawley rats were subjected to 2h MCAO, and 6 or 24 h reperfusion, upon which rats received an IP injection of saline or C+P (8 mg/kg). Temperature was maintained at 37°C, or allowed to spontaneously change. Infarct volumes and neurological deficits were examined. Oxidative stress was determined by levels of ATP, lactate, NADH and reactive oxygen species (ROS). NOX activity and expression of NOX subunits (p47
phox
, gp91
phox
, p22
phox
and p67
phox
) were measured at 6 and 24 h reperfusion.

Results:
In 2 h MCAO rats, body temperatures were significantly reduced by 1
0
C after C+P within 5 min. At 2 h, body temperatures reached 34
0
C and remained significantly low for up to 6 h. Following 6 and 24 h of reperfusion, C+P decreased infarct volume, neurological deficit, lactate and ROS levels, but increased ATP and NADH. NOX activity and subunit expressions were down-regulated. C+P-induced neuroprotection was not affected by maintaining temperature at 37
0
C.

Conclusion:
C+P administration provided neuroprotection in ischemic stroke independently of reductions in body temperature. Our results suggest temperature reduction may be a result of metabolic depression, rather than a cause.
Abstract TP95: Intra-arterial Interleukin-1 alpha is Well Tolerated and Neuroprotective After Experimental Ischemic Stroke
Authors: Salmeron Kathleen E , Maniskas Michael E , Wong Raymond , Trout Amanda L , Edwards Danielle N , Pinteaux Emmanuel , Fraser Justin F , Bix Gregory J
Published: October 2018

Endovascular thrombectomy combined with t-PA is the current standard of care for emergent large vessel occlusion (ELVO) stroke. Unfortunately, despite rising recanalization rates, stroke remains the leading cause of long-term disability worldwide suggesting that additional therapies are needed. Severe stroke morbidity may be due, partially, to the acute and sustained inflammatory stroke response. Preclinical research has shown some promise with anti-inflammatory agents in limiting brain injury and improving functional outcome; however, the post-stroke inflammatory cascade appears to have both beneficial and deleterious effects making the translation of such anti-inflammatory approaches perilous. We aim to show that the inflammatory cytokine interleukin-1alpha (IL-1α) is well-tolerated, neuroprotective, and conveys functional benefit after ischemic stroke. 3-month-old C57/BL6 mice were subjected to MCAo and given IL-1α via IV injection or IA infusion upon recanalization. Mice were allowed to recover for 7 days before sacrifice. Brains were flash frozen for IHC and serum for high sensitivity ELISA. We noted that IV IL-1α (1 ng) is neuroprotective (as measured by cresyl violet stained infarct volumes) and significantly improved functional recovery in open field behavioral tests. When given IV, IL-1α showed transient hemodynamic side effects that are typical of IL-1α’s known physiologic functions (fever, sterile inflammation, etc.) These effects are short lived with systemic (IV) administration and IA IL-1α (0.1 ng) administration showed neuroprotection without the side effects seen with IV treatment. Additionally, we noted that IL-1α is directly neuroprotective of primary mouse cortical neurons exposed to oxygen and glucose deprivation conditions
in vitro
. IL-1α’s profound, direct neuroprotective effects and its functional benefit, make IL-1α an attractive target for future study in ischemic stroke.
Abstract TP97: Physiological Plasma Concentrations of Atorvastatin and Simvastatin Enhance the Immunomodulatory Effects of Mesenchymal Stromal Cells on Stroke Derived Monocytes
Authors: Satani Nikunj , Giridhar Kaavya , Xi Xiaopei , McRuffin Courtney , Yang Bing , Olson Scott D , Aronowski Jaroslaw , Savitz Sean I
Published: October 2018

Background:
Mesenchymal stromal cells (MSCs) are being investigated as a stroke therapy both in preclinical and clinical trials. MSCs may promote recovery through secretome release and immunomodulation. Approximately one-third of stroke patients are on statins. With cell therapy gaining momentum, we explored the effect of two statins on MSCs.

Methods:
Clinical grade bone marrow MSCs from 3 healthy donors at passage 2 were thawed and re-suspended in serum free media. Monocytes (Mo) were isolated from peripheral blood of healthy humans and stroke patients. MSCs and Mo were cultured alone as well as in co-culture and exposed to different doses of atorvastatin and simvastatin. At 24 and 48 hours of incubation, viability of MSCs was measured using ATP assay. 5-bromo-2’-deoxyuridine (BrdU) assay was used to measure proliferation. Media from treated MSCs was analyzed for secretomes and treated cells were analyzed for gene expression changes. Data were averaged for 3 donors.

Results:
Both atorvastatin and simvastatin decreased the viability and proliferation of MSCs (Fig. 1A-B), but at physiologically relevant doses both were maintained above 90%. Clinically relevant doses of both drugs decreased the secretion of TNF-α and IL-6 from MSCs upto two fold (Fig. 1C-D). IL-6 expression decreased and IL-10 expression increased dose-dependently in MSCs (data not shown). When co-cultured with Mo from control vs stroke patients, both statins at physiologically relevant doses increased VEGF release and decreased the secretion of IL-6, IL-8 and MCP-1 (Fig. 1E-H).

Conclusion:
Exposure of MSCs to statins can alter their immunomodulatory function. Furthermore, these effects are consistent across two commonly prescribed drugs. Our results suggest that stroke trials involving use of intravenous MSCs should consider the impact of statins on MSC function.
Abstract TP98: A Therapeutic Time Window & Dosage of Early Exercise for Rats With Cerebral Ischemia
Authors: Zheng Haiqing , Zhang Liying , Yang Huaichun , Parashos Alexandra , Zhang Qingjie , Hu Xiquan
Published: October 2018

Background:
Although evidence from prior animal and clinical studies indicated exercise is a safe, cost-effective post-stroke rehabilitative intervention, the proper combination of time-window and dosage of exercise for maximal functional recovery, and its underlying mechanisms, are still unknown.

Purpose:
We aimed to determine the optimal combination of exercise time-window and intensity by assessing mortality, neurological recovery, and underlying neurochemical mechanisms in MCAO rats.

Methods:
The study contained two parts: the time-window and the dosage experiments. In the time-window experiment, 8 different groups (exercise initiated 24hr, 48hr, 72hr, 96hr and its corresponding control), along with moderate intensity exercise, were assessed. In the dosage experiment, 3 different intensity exercise groups (Low, Moderate, High) were assessed. Mortality (only for the time-window experiment), infarct volume and neurological function (measured by modified Neurological Severity Score at 14 days) were the main outcomes measures.

Results:
In the time-window experiment, the mortality was the highest in the EXCISE 24h group (40%) than any of other three group (
p=
0.030,
p=
0.030,
p=
0.045 respectively). Additionally, infarct volumes were high and neurological function was poor. In the dosage experiment, the relative infarct volume of the Moderate (0.190±0.026,
p
< 0.01) was significantly smaller than the CON (0.318±0.035) and High (0.294±0.037) group, but no different than the Low group (0.188±0.012). Similarly, neurological function at 14 days was not different between Moderate and Low group although they both better than High and CON group. Moderate group was the most effective in reducing inflammation by decreasing IL-1β and TNF-α(
p<
0.05,
p<
0.05, respectively).

Conclusions:
Exercise initiated within 24 hours was neither safe or effective. Moderate intensity exercise initiated within 48 hours post-stroke apears to be an optimal combination for maximal post-stroke functional recovery.
Abstract WMP101: Soluble St2 Predicts Functional Outcome After Spontaneous Intraparenchymal Hemorrhage
Authors: Bevers Matthew B , Wolcott Zoe , Leasure Audrey C , Falcone Guido J , Sansing Lauren H , Sheth Kevin N , Kimberly W. T
Published: October 2018

Introduction:
Soluble ST2 (sST2) is a member of the interleukin-1 receptor family known to predict outcome and mortality in cardiovascular disease and ischemic stroke. We sought to determine whether plasma sST2 concentration is associated with functional outcome after intraparenchymal hemorrhage.

Methods:
Concentration of sST2 was measured on plasma samples from a prospectively collected cohort of 75 patients who presented with spontaneous intraparenchymal hemorrhage. Blood samples were drawn between 24 and 72 hours after symptom onset. Soluble ST2 was measured using a commercially-available ELISA (Critical Diagnostics, San Diego, CA). Injury severity was determined using the admission Glasgow Coma Scale (GCS), with GCS ≤ 8 defined as severe injury. Outcome was assessed by modified Rankin Scale (mRS) at 90 days, with poor outcome defined as mRS 4-6. The association between sST2 and outcome, adjusted for clinical variables, was determined using ordinal logistic regression and receiver operating curve (ROC) analysis.

Results:
Median sST2 concentration was 54.6ng/mL [IQR 25.7-156.5] in the entire cohort. Patients with a more severe presentation (GCS ≤ 8) had a higher sST2 concentration (165.1ng/ml [IQR 91.2-238.3] vs. 36.8ng/ml [IQR 23.0-62.6], p<0.0001). ROC analysis demonstrated that sST2 concentration >114.0ng/mL predicted poor outcome with a sensitivity of 63.3%, specificity of 82.2%, and an area under the curve of 0.766. Plasma sST2 concentration was also associated with ordinal mRS at 90 days (OR 2.99, 95% CI 1.84-4.88, p < 0.0001). Other univariate predictors of ordinal mRS included admission GCS, admission NIHSS, hematoma volume, and ICH score. Plasma sST2 remained an independent predictor of mRS after adjustment for ICH score (adjusted OR 1.97, 95% CI 1.09-3.53, p = 0.024). Similarly, adjustment for admission NIHSS, admission GCS or hematoma volume demonstrated that sST2 remained an independent predictor of outcome.

Conclusion:
Plasma sST2 is independently associated with functional outcome after intraparenchymal hemorrhage. These results support the role of sST2 as a candidate biomarker for both ischemic and hemorrhagic stroke, and argue for further investigation of the ST2 pathway in the pathogenesis of neurologic injury.
Abstract WMP104: Sub-Acute Diffusion-Weighted MRI Lesions in Acute Intracerebral Hemorrhage Patients are Unrelated to Blood Pressure
Authors: Klahr Ana C , Dowlatshahi Dariush , Buck Brian , Gioia Laura , Kalashyan Hayrapet , Wilman Alan , Jeerakathil Thomas , Emery Derek , Butcher Kenneth
Published: October 2018

Introduction:
Diffusion-Weighted magnetic resonance imaging (DWI) studies have demonstrated sub-acute ischemic lesions in up to 41% of patients with intracerebral hemorrhage (ICH). Retrospective studies indicated an association with acute blood pressure (BP) reduction. We conducted a prospective study of DWI lesion incidence in ICH patients.

Methods:
Patients with computed tomography (CT) scan confirmed ICH were prospectively recruited within 6 hours of symptom onset. Acute systolic BP (SBP) targets were randomly assigned as part of an ongoing trial. The SBP target remained blinded for this analysis. Patients were assessed with serial DWI at 48 hours.

Results:
Eighty-three patients (48.2% male, mean±SD age 71.9±13.4) were enrolled. MRI was obtained in 42 patients. (11 patients were medically unstable, 11 refused consent, 19 died or were treated palliatively prior to the first MRI). Median (IQR) acute hematoma volume of the patients undergoing magnetic resonance imaging was 14.11 (4.40, 38.06) ml. Median baseline NIHSS score was 12.50 (9, 20). Median (IQR) 48 hour hematoma volume was 23.30 (9.10, 65.30) ml. DWI lesions were present in 13 (31%) of patients at 48 hours (median time to scan 54.22 (39.83, 65.5) hours). Mean SBP at 48 hours in patients with lesions (154.55±27.02 mmHg) was similar to those without (149.04±27.02;
p
= 0.514). Systolic BP at the time of the MRI was not a predictor of ischemic lesion development at 48 hours (OR=1.015, [0.972, 1.059],
p
=0.507), nor was the change in BP between baseline and the scan (OR=0.994, [0.962, 1.027],
p
=0.716). The only predictor of 48 hour DWI incidence was hematoma volume at 48 hours (OR= 1.025, 95% CI [1.001, 1.050],
p
=0.044).

Discussion:
When enrolled prospectively within 6 hours of onset, DWI was obtained in approximately half of all ICH patients. This selection bias may be relevant to the results of both retrospective and prospective DWI studies. This study demonstrated no evidence of a relationship between actual BP achieved and DWI incidence after ICH.
Abstract WMP105: A Meta-Analysis and Systematic Review of Antiepileptic Drugs for Seizure Prophylaxis on Long-Term Functional Outcomes in Patients With Acute Intracerebral Hemorrhage
Authors: Spoelhof Brian , Sanchez-Bautista Julian , Zorrilla-Vaca Andres , Kaplan Peter W , Farrokh Salia , Mirski Marek , Freund Brin , Rivera-Lara Lucia
Published: October 2018

Introduction:
Intracranial hemorrhage (ICH) is a devastating form of stroke that leads to development of seizures in up to 2%-40% of patients. Seizure prophylaxis in ICH remains controversial and it is unclear if the benefits of antiepileptic drugs (AEDs) outweigh the risk of potential adverse drug effects. The objective of this analysis is to assess the effect of AED on seizure prevention and long term functional outcomes in patients with acute ICH.

Methods:
Our group conducted a meta-analysis using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochran Library, and EMBASE databases using the keywords “Anticonvulsants”, “Intracerebral Hemorrhage”, and related subject headings. Articles were screened and included if they assessed the impact of AEDs on long-term functional outcomes in ICH population using multivariate logistic regression analysis. Overall effect sizes were evaluated with forest plots and publication bias was assessed with the Begg’s and Egger’s tests. Long term functional outcomes were assessed at ≥ 3 months post-ICH with either the National Institute of Health Stroke Scale (NIHSS) or the modified Rankin Score (mRS).

Results:
A total of 3,912 articles were identified during the intimal review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. The quality assessment criteria ranged from moderate to high for evidence synthesis. A total of 3,193 patients were included in the analysis. There were no significant association between the use of AEDs after ICH and poor outcome defined as mRS ≥3 or NIHSS ≥15 (OR 1.53 [95% CI: 0.81-2.88] p=0.18, I
2
=81.7%). Only one trial evaluated the effect AEDs had in prevent post-ICH seizures. Publication bias was not observed in the analysis (Egger’s bias=2.23, P=0.23).

Conclusion:
In conclusion, the use of prophylactic AEDs was not associated with improved or worse functional outcomes after acute ICH.
Abstract WMP108: Defining Optimal Thresholds for Achieving Clinical Benefit in Spontaneous Intraventricular Hemorrhage
Authors: Murthy Santosh B , Dlugash Rachel , McBee Nichol , Awad Isaam , Hanley Daniel F , Ziai Wendy C
Published: October 2018

Introduction:
Fibrinolytic therapy for spontaneous intraventricular hemorrhage (IVH) appears to reduce mortality with uncertain benefit on long-term functional outcomes. Threshold for volume of IVH which responds to intraventricular fibrinolytic therapy with therapeutic benefit has not been determined.

Methods:
CLEAR III, a randomized, multi-center, double-blinded, placebo-controlled trial was conducted to determine if pragmatically employed external ventricular drainage (EVD) plus intraventricular Alteplase improved outcome, in comparison to EVD plus saline. We analyzed of IVH volume strata from study randomization: Large IVH: volume ≥50 mL; small IVH: volume<20 mL. We assessed clinical variables and outcomes by IVH volume group. Outcome measures were blinded assessment of modified Rankin score (mRS) at 30, 180 and 365 days, (with mRS>3 signifying poor outcome). We performed logistic regression to evaluate outcomes by IVH volume group.

Results:
Among the 500 patients enrolled, 55 (11%) had IVH volumes >50 mL and 222 (44.4%) had IVH volume <20mL. Subjects with large volume IVH were older (mean, 62.3 vs. 58.1 years; p=0.01), had smaller ICH volume (6.1 vs. 9.9 mL; p<0.001), less thalamic ICH (16.4% vs. 63.6%; p<0.001), more pre-admission use of anticoagulants and antiplatelet agents and greater proportion of high intracranial pressure readings during monitoring at all thresholds (>20, 30, 40 mmHg), compared to those with IVH volume <50mL. Day 180 mortality and poor mRS were 49.1% and 81.8% in large volume IVH compared to 13.1% and 43.3% in small volume IVH. In logistic regression models adjusted for confounders, drainage of >85% IVH volume was significantly associated with higher odds of good outcome (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3) and lower odds of mortality (OR, 0.3; 95% CI, 0.1-0.8) compared to <85% drainage, in patients with baseline volumes <50mL. Removal of >85% IVH volume (n=3/55) was not associated with improved outcomes in patients with large IVH.

Conclusions:
IVH volume >50mL may represent a cohort without identified benefit from fibrinolytic treatment. Defining an upper limit for IVH volume would benefit from a larger sample and other methods of achieving IVH reduction.
Abstract WMP109: Poststroke Fatigue as an Indicator of Cellular Energy Crisis
Authors: Klinedinst N Jennifer , Fiskum Gary , Schuh Rosemary , Kittner Steven J , Regenold William , Puche Adam , Hoch Christine , Hackney Alicia
Published: October 2018

Purpose:
Post-stroke fatigue contributes to poor function, low quality of life and mortality. The etiology of post-stroke fatigue is unclear. We hypothesized that systemic inflammation impairs mitochondrial energy production, as reflected by decreased platelet respiration. The purpose of this study is to examine the association of systemic inflammation, platelet oxygen consumption rates (OCR) and fatigue in chronic ischemic stroke survivors.

Methods:
Data on fatigue (Fatigue Assessment Scale), depression (PHQ-9), pain (1-10 rating), sleep (Pittsburgh Sleep Quality Index), physical function (SIS 3.0), and whole blood were collected from 20 chronic ischemic stroke survivors. Cytokines were measured from plasma. Platelet OCR were measured using the Seahorse Extracellular Flux Analyzer.

Results:
Fatigue was negatively associated with C-reactive protein (CRP), but not IL-1β, TNF-α, IL-6. IL-9 or IL-1ra. Platelet OCR showed a U-shaped biphasic response with fatigue, initially decreasing then increasing as fatigue levels became more severe. Independent t-tests comparing data from extreme ends of the curve show that stroke survivors with high fatigue/high platelet OCR (right side of U; n=5) also have higher depression (p=0.03), poorer physical function (p=0.02) and higher pain levels (p=0.03) as compared to those with low fatigue/ high platelet OCR (left side of U; n=4) who have low depression, high physical function, and low pain. There were no differences in sleep quality or cytokines.

Conclusions:
These data suggest as platelets’ ability to make cellular energy becomes impaired, fatigue levels increase until a compensatory mechanism is initiated, which increases platelet cellular oxygen consumption, but does not resolve associated fatigue. Fatigue, depression, pain, poorer physical function and high OCR may indicate a systemic energy crisis in stroke survivors.
Abstract WMP11: Blood Biomarkers to Predict Futile Recanalization After Mechanical Thrombectomy
Authors: Bustamante Alejandro , Penalba Anna , Ventura Oriol , Rubiera Marta , García-Berrocoso Teresa , Ribø Marc , Montaner Joan
Published: October 2018

Introduction:
Despite the usefulness of mechanical thrombectomy (MT), around 50% of the patients had poor outcome after achievement of complete recanalization. We aimed to test blood biomarkers to predict futile recanalization (FR) in patients treated with MT.

Methods:
Consecutive stroke patients were enrolled from August-2012 to August-2014. Blood samples were collected at admission. Biomarkers were selected among pathophysiological pathways related to FR: inflammation (VCAM-1), thrombosis (ADAMTS13), lipid metabolism (ApoC-III). FR was defined as complete recanalization after endovascular procedure (TICI 2b-3) and poor functional outcome (mRS>2) at three months. Comparisons were performed between patients with futile and successful recanalization. Independent predictors of FR were determined by logistic regression. The additional predictive value of blood biomarkers was evaluated by integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes, considering thresholds of 25-75% risk categories for the later.

Results:
From 87 patients treated with MT, 73 were included. Complete recanalization was achieved in 58 patients, being futile in 33 patients (57%). Patients with FR had a trend towards lower levels of both ADAMTS13 and ApoC-III. The rate of FR when both biomarkers were under the 1
st
quartile was 100%. Both biomarkers were independent predictors of FR in logistic regression analysis [ADAMTS13; OR=8.01 (1.20-53.5), p=0.032. ApoC-III; OR=6.94 (1.32-36.62), p=0.022], together with previous mRS [OR=5.75 (1.73-19.05), p=0.004] and diabetes [OR=7.6 (1.26-45.1), p=0.032]. The addition of both biomarkers improved discrimination [IDI=13.8% (4.7-22.9), p=0.003], and reclassification [60.2% (31.4-89.1), p<0.0001]).

Conclusions:
Pre-treatment levels of ADAMTS13 and ApoC-III are predictors of FR. These blood markers might be used to guide reperfusion therapies.
Abstract WMP112: A 3-s=step Process Improves the Performance of Dysphagia Screens and Reduces Aspiration Pneumonia Rates Among Stroke Inpatients
Authors: Durm Laura Beth , Bonner Julie , Meyer Ellen , Brasher Cyndy , Schleuse Stuart , Stewart Ellen , Sinsley Debbie , Humphrey Jan , Reif Lisa , Omess Sarah , Baumgartner Celcilia , Danaie Elham , Kumarasamy Mathu , Nahab Fadi
Published: October 2018

Background:
Dysphagia occurs in up to 78% of stroke patients and is associated with poor patient outcomes. We have previously reported low concordance rates between dysphagia screens performed by neuroscience bedside nurses compared with Speech Language Pathologists (SLPs) using the 3oz water test.

Hypothesis:
A multidisciplinary intervention can improve concordance rates of dysphagia screening between bedside nurses and SLPs and reduce aspiration pneumonia rates among stroke patients.

Methods:
An interdisciplinary team including stroke quality nurses, clinical nurse specialists, SLPs, and nursing informatics developed a 3-step intervention including 1) modifications of the electronic dysphagia screen forms to simplify documentation and provide step-by-step instructions for nursing staff, 2) hospital-wide re-education to nurses on performing dysphagia screens and 3) adjustment of all stroke ordersets to include prechecked NPO orders to prevent diet orders prior to a dysphagia screen. Interventions were completed by August 31, 2016. All stroke patients admitted to a Comprehensive Stroke Center from March 1, 2016 to May 31, 2017 were included in this analysis to determine aspiration pneumonia rates pre- and post-intervention (N=988). To determine concordance rates in dysphagia screening, neuroscience nurses and SLPs performed the same screen on consecutive stroke patients within <24 hours of each other; concordance rates were compared before and after study intervention.

Results:
Overall aspiration pneumonia rates significantly declined after the intervention from 11.8% to 7.3% (p=0.03). Significant declines in aspiration pneumonia rates after intervention were seen in ischemic stroke (10.4% vs 4.3%, p=0.02) patients but not seen in intracranial hemorrhage (14.8% vs 10.1%, p=0.41) or subarachnoid hemorrhage patients (11.5% vs 10.1%, p=0.85). Concordance rates between nurses and SLPs significantly increased from 52% pre-intervention up to 73% post-intervention (p=0.04).

Conclusion:
Our 3-step multidisciplinary dysphagia screening intervention significantly reduced aspiration pneumonia rates among ischemic stroke patients and improved concordance rates in screening results among neuroscience nurses and SLPs.