bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21: Motor Tract Impairment is an Independent Predictor of Lower Limb Motor Recovery
Authors: Munsch Fanny , Sibon Igor , Dousset Vincent , Tourdias Thomas , Schlaug Gottfried
Published: October 2018

Introduction:
Initial motor impairment assessed in the acute stroke phase (as measured by the Fugl-Meyer (FM) Assessment) is a strong predictor of lower extremity (LE) motor impairment at 3 months (Smith et al., 2017). The predictive value of measures of motor tract integrity, lesion size and location is not known. For our analysis we combined two motor tracts that might be particularly important in the control of proximal leg muscles to create a canonical tract of the corticospinal tract proper (CST) and the corticorubrospinal tract (CRST)(Lindenberg et al., 2010; Rueber et al., 2012). In previous work (Feng et al., 2015) we have shown that weighted CST-Lesion Load (a combined variable of lesion size and location) is a significant predictor of 3 months outcome for the UE.

Hypothesis:
Weighted CST-CRST Lesion-Load (wCST/CRST-LL) can improve the FM-based predictions of lower limb motor recovery.

Methods:
Ischemic stroke patients with a upper limb paresis (UE-FM<66) and lower limb paresis (LE-FM<34) were assessed between 48-72h and 3 months poststroke with the FM scale. Lesion maps drawn on diffusion-weighted images were used to calculate lesion loads of a combined CST-CRST probabilistic tract derived from matched elderly healthy control subjects. Then, several variables that have been shown to predict outcome (e.g., FM, lesion load, age, hemisphere) were subjected to individual regression analyses. Significant variables (at p<0.05) were entered into a multiple regression model to assess predictors of lower limb motor recovery (i.e., actual difference in LE-FM between 3 months and initial stroke phase assessment).

Results:
Both baseline and 3-months follow-up were available for 134 patients. Initial motor impairment (FM-LE) and wCST/CRST-LL were independent strong predictors of lower limb motor recovery (respectively p<0.0001 and p=0.0005). Combining initial motor impairment and wCST/CRST lesion load was a much better model than FM-LE by itself (respectively R2=0.43 and R2=0.46, p=0.003) which was confirmed by the Akaike Information Criterion (AIC).

Conclusion:
wCST/CRST-LL, a combined measure of lesion size/location, adds significant power to a combined model with FM, but is also a strong predictor of lower limb motor recovery by itself.
Abstract 24: Nationwide Trends and Disparities in Utilization of Inpatient Rehabilitation for Stroke Patients
Authors: Vahidy Farhaan S , Ifejika Nneka L , Savitz Sean I
Published: October 2018

Introduction:
Transfer to an inpatient rehabilitation (IR) facility (IRF) provides multiple benefits to stroke patients including improvements in functional independence measures, neurological impairments, stroke-related medical complications, and reduction in readmissions. We report nationwide trends and disparities in post-stroke IR utilization.

Methods:
We analyzed the National Inpatient Sample for years 2006 - 2011 and used ICD-9 codes to identify adult patients with ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. Institutionalized care (IC) included transfer to skilled nursing and long term care facilities. We fit survey design multivariable logistic regression models to determine nationally representative trends in IR utilization and report crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for factors associated with IR utilization, including level of care (LOC) as defined by teaching status of the hospital.

Results:
Based on our criteria 3,112,120 patients were included in analyses, of whom 16.2% utilized IRF. There was a significantly increasing trend in post-stroke IR utilization over the period of investigation (OR 1.06, 95%CI 1.04-1.09), with 19.5% patients discharged to IRF in 2011 (Figure 1). Older age and female gender were independently associated with decreased IR utilization (Table 1). Patients utilizing IR had significantly greater odds of being discharged from a teaching hospital after controlling for demographic, clinical, comorbidity, and resource utilization factors (OR 1.40, 95% CI 1.23 - 1.47).

Conclusion:
Our analysis indicates overall low nationwide IR utilization. However, there is an increasing trend in utilization of IR, albeit with age, gender, and LOC disparities. After adjustments, patients discharged from non-teaching hospitals are 29% less likely to receive IR. Further studies should focus on barriers to utilizing post-stroke IR, including socioeconomic status.
Abstract 27: Risk Factors Associated With Post-Stroke Readmissions for Depression and Suicide Attempt in a Nationally Representative Dataset
Authors: Stein Laura K , Yevudza Wisdom , Kaur Gurmeen , Rossi Kyle , Tuhrim Stanley , Dhamoon Mandip S
Published: October 2018

Introduction:
Post-stroke depression (PSD) occurs in approximately one third of stroke patients. Existing literature has elucidated pathophysiology, risk factors, impact, and treatment for PSD. However, there is a lack of nationally representative data assessing patient characteristics and demographics associated with the most severe PSD, manifested by hospitalization for suicide attempt (SA) or depression.

Methods:
The 2013 Nationwide Readmissions Database contains >14 million U.S. readmissions for all payers and the uninsured. We used validated International Classification of Disease, Ninth Revision, Clinical Modification codes to identify index admission with stroke (n = 215, 802) and readmission with depression (n = 361) and SA (n = 108). We used Cox regression to calculate hazard ratios (HR) of hospital readmissions up to 1 year post-stroke for depression and SA, adjusting for patient and demographic characteristics.

Results:
Readmission rates with depression were 28 per 100,000, 59 per 100,000 and 82 per 100,000 at 30, 60, and 90 days respectively. Readmission rates with SA were 29 per 100,000, 38 per 100,000, and 43 per 100,000 at 30, 60, and 90 days respectively. For depression readmissions, psychiatric history had the greatest HR of 3.25 (95% CI 2.63-4.01, p <2x10
-16
), followed closely by alcoholism (HR of 2.36, 95% CI 1.60-3.50, p = 1.82 x10
-5
). For SA readmissions, alcoholism had the greatest HR of 3.96 (95% CI 2.22-7.05, p = 2.98 x10
-6
), followed by psychiatric history (HR 2.87, 95% CI 1.93-4.25, p = 1.52x10
-7
). Age >70 was protective against readmission with depression and SA, with a HR of 0.45 (95% CI 0.36-0.57, p = 1.86 x10
-11
) and 0.28 (95% CI 0.18-0.45, p = 1.47 x10
-7
) respectively. Discharge home was protective against readmissions due to depression only, with a HR 0.71 (95% CI 0.57-0.89, p = 3.1 x10
-3
).

Conclusion:
Stroke patients with a history of alcoholism or psychiatric illness are more likely to be admitted with depression or SA in the first year. Age >70 is protective against such readmissions, and discharge home is protective against depression readmissions but failed to reach statistical significance for SA readmission. These factors may be used to screen and identify stroke patients at risk of severe PSD requiring hospitalization.
Abstract 28: Inhibition of Interleukin-6 Signaling With Tocilizumab Ameliorates Ischemic Stroke Damage in Aged Male and Female Mice
Authors: Hudobenko Jacob , Chauhan Anjali , McCullough Louise
Published: October 2018

Introduction:
In stroke patients higher plasma IL-6 levels are correlated with increased stroke severity and poor long-term prognosis. Preliminary work in our lab has shown that tocilizumab, an FDA approved drug that blocks IL-6 receptors inhibiting the effects of IL-6, reduced infarct size and behavior deficits in young male mice following MCAO. Due to this promising preliminary data we hypothesized that tocilizumab will ameliorate injury in aged male and female mice. Testing both sexes and aged mice is important because the majority of stroke occurs in patients over 65 in both sexes.

Methods:
Aged (18-20month) C57BL/6J male (n=42) and female mice (n=45) were used to examine neuroprotection and behavioral deficits with treatment. Mice were randomly separated into 4 groups, stroke or sham then subdivided into drug or control treatment. Stroke was induced by 1 hour of transient MCAO followed by reperfusion for either 3 or 35 days. Four hours after the onset of ischemia mice were intraperitoneally injected with tocilizumab (20mg/1kg) or an IgG control. Behavior tests evaluated motor/sensory deficits, anxiety and locomotor activity. Depression and memory formation was also tested in the 35 day cohort.

Results:
Tocilizumab reduced mortality in aged male mice and significantly reduced anxiety levels in aged female mice 20 days after stroke (p=0.04). Treatment also led to a significant reduction (p=0.04) in infarct size 3 days post-ischemia. The corner test showed improved sensorimotor function in males on all testing days 3, 7 and 14 after stroke but was only significant for females on post stroke day 3 (p<0.05). Direct revisit error on the Y-maze was significantly reduced in tocilizumab treated aged male mice on day 7 after stroke (p=0.04) and aged female mice on day 3 after stroke (p=0.032) showing an improved spatial learning. Time to discover the escape hole in the Barnes maze 31 days post stroke was improved in aged male mice (p=0.05) conveying benefit to new memory formation post stroke by tocilizumab.

Conclusion:
This study showed that tocilizumab treatment reduced stroke damage and decreased behavioral deficits in both sexes. Therefore, this study concludes that inhibition of the IL-6 receptor may be a potential therapeutic approach for stroke treatment.
Abstract 3: Increasing Use of Intravenous Thrombolytic Therapy was Associated With Decline in Ischemic Stroke Mortality in Medicare Beneficiaries
Authors: Man Shumei , Schold Jesse D , Uchino Ken
Published: October 2018

Background:
Mortality due to stroke has declined over the past 2 decades. Intravenous thrombolytic therapy improves the functional outcome, but its contribution in reducing stroke mortality is not clear. We aim to examine the trend of ischemic stroke case fatality in recent years in relation to the utilization of thrombolytic therapy.

Methods:
We examined the trend of risk-adjusted one-year mortality and intravenous thrombolytic therapy in Medicare beneficiaries aged ≥65 years who were hospitalized between January 1, 2009 and December 31, 2013 with a primary discharge diagnosis of acute ischemic stroke. The data of the patient information were obtained from the Medicare Provider Analysis and Review file. Cox proportional hazards models were generated to adjust for patient demographics and comorbidities. All statistical analyses were performed using SAS Version 9.4 software.

Results:
This study included 1,165,960 Medicare Beneficiaries. The one-year risk-adjusted mortality showed a steady declined from 29.7% in 2009 to 24.4% in 2013, 17.8% decline over the five year period. This was parallel to the 59.7% increase of intravenous thrombolytic therapy utilization, from 5.21% in 2009 to 8.32% in 2013. The mortality decline was only observed in patients who received intravenous thrombolytic therapy (HR 0.86; 95% CI 0.82-0.91), but not in those who did not receive thrombolytic therapy (HR 0.99; 95% CI 0.97-1.01) (Table).

Conclusion:
The increasing use of intravenous thrombolytic therapy was associated with decline in risk-adjusted one-year mortality after ischemic stroke. The reasons for the mortality decline among those who received thrombolytic therapy needs further explanation.
Abstract 31: CaMKII-alpha Ubiquitination Induced by Cerebral Ischemia-Reperfusion Injury Reversibly Inhibits Post-Ischemic CaMKII Activity at the Post-Synaptic Density
Authors: Kahl Anja , Poon Carrie , Rodney-Sandy Reunet , Blanco Ismary , Iadecola Costantino , Hochrainer Karin
Published: October 2018

Background:
Brain calcium-calmodulin-dependent protein kinase II (CaMKII) is exclusively expressed in neurons, where it localizes to the post-synaptic density (PSD) to link calcium signals to changes in synaptic activity. Independent studies suggest that deregulation of CaMKII contributes to neuronal death associated with cerebral ischemia and could be a target for stroke therapy. However, the molecular events underlying CaMKII activity modification after ischemia are not understood. Cerebral ischemia induces ubiquitination of PSD proteins, raising the possibility that post-ischemic CaMKII function is modulated by ubiquitination. Here we investigate a novel link between CaMKIIα subunit ubiquitination and post-ischemic CaMKII regulation.

Methods:
Cerebral ischemia was induced in male C57BL6 mice by middle cerebral artery occlusion (MCAO) for 35 min. Whole tissue extracts as well as cytosolic, membrane and PSD fractions were prepared at different times after ischemia to assess CaMKIIα ubiquitination, protein levels and activity. Ubiquitination was reverted with recombinant USP2cc de-ubiquitinase.

Results:
MCAO induces CaMKIIα ubiquitination specifically in the neocortical PSD fraction peaking at 1-hour reperfusion. The ubiquitination is accompanied by translocation of CaMKIIα from cytosol/membrane to PSD (cytosol/membrane: 61±4%; PSD: 190±6% of sham, P<0.001, n=9/group), while total CaMKIIα protein levels are not affected (98±1% of sham, P=0.767, n=3/group). In the cytosol CaMKII activity normalized to protein content is not changed post-stroke (91±19% of sham; P<0.001, n=9/group), however at the PSD it is severely suppressed (31±6% of sham, P<0.001, n=9/group). De-ubiquitination leads to restoration of PSD-associated CaMKII activity (347±59% of untreated, P<0.001, n=6/group), identifying ubiquitination as reversible repressor of CaMKII activity at the PSD.

Conclusions:
CaMKIIα ubiquitination induced by cerebral ischemia-reperfusion constitutes a previously unappreciated mechanism of post-ischemic CaMKII regulation that may be important for modulating the ischemic outcome. Better understanding of how post-ischemic CaMKIIα ubiquitination is controlled may help to identify a new therapeutic stroke target.
Abstract 42: Validation of an Ordinal, 6-Item Functional Outcome Scale for Speech and Language Disability in Stroke: The Austin Speech Labs Communication Disability Scale
Authors: Warach Steven , King Ben , Shamapant Shilpa
Published: October 2018

Introduction:
Assessment of stroke outcomes specific to speech and language typically depends on lengthy batteries yielding a derived score that has little functional meaning to patients. Our aim was to develop a simple, highly reliable, ordinal outcome scale specific to language and communication disability.

Methods:
Modeled after the Rankin Scale, the Communication Disability Scale is a 6-item ordinal scale to assess degree of disability specifically related to communication deficits. Inter-rater reliability and criterion validity were tested on a cohort of 79 stroke patients with communication /speech deficits in an outpatient intensive speech therapy setting. Speech therapists independently assessed the patients.

0

- No speech or language deficits.

1

- Minor language deficits, without communication limitations.

2

- Language deficits causing limitations on communication, but not on ADLs.

3

- Limitations in ADLs caused or exacerbated by communication deficits*.

4

- Requires listener assistance and inference for most communications of basic needs*.

5

- No effective communication*.

*Needs caregiver assistance

Results:
Inter-rater reliability of the Communication Disability Scale scores (CDS) for all subjects (n=79) yielded an intra-class correlation of 0.823. The kappa statistic for agreement was 0.792. Comparison to a standardized language assessment, the Western Aphasia Battery Aphasia Quotient (WAB-AQ) (n=71) showed a strong correlation on Spearman rank rho = -0.815. When CDS and WAB-AQ were dichotomized as good (0-2, does not require caregiver assistance for communication needs) v bad, kappa was 0.6223 (p < 0.001).

Conclusion:
The Austin Speech Labs Communication Disability Scale has high inter-rater reliability and is highly correlated with a standard Aphasia Battery. The items link language deficits to limitations in activities of daily living (ADLs) attributable to communication deficits. This new scale may be valuable in assessing the effects of speech therapies in clinical trials and the need for caregiver assistance in practice.
Abstract 44: Plasma MicroRNA Markers of Upper Limb Recovery Following Human Stroke Associated With Neural Repair Mechanisms
Authors: Edwardson Matthew A , Zhong Xiaogang , Cheema Amrita , Dromerick Alexander
Published: October 2018

Introduction:
MicroRNAs are small, non-coding RNAs that control gene expression by inhibiting protein translation. Preclinical studies in rodent stroke models suggest that changes in microRNA expression contribute to neural repair mechanisms. To our knowledge, no one has previously assessed microRNA changes during the recovery phase of human stroke.

Hypothesis:
Patients with significant upper limb recovery following stroke will have alteration of neural repair-related microRNA expression when compared to those with poor recovery.

Methods:
Plasma was collected at 19 days post-stroke from 27 participants with mild-moderate upper extremity impairment enrolled in the Critical Periods After Stroke Study (CPASS). MicroRNA expression was assessed using TaqMan microRNA assays (Thermo Fisher Scientific). Good recovery was defined as ≥ 6 point change in the Action Research Arm Test (ARAT) score from baseline to 6 months. Bioinformatics analysis compared the plasma microRNA expression profiles of participants with good vs. poor recovery. Candidate biomarkers were identified after correcting for multiple comparisons using a false discovery rate < 0.05.

Results:
Eleven microRNAs had significantly altered expression in the good (n=22) vs. poor (n=5) recovery groups, with two showing increased expression - miR-371-3p and miR-520g, and nine showing decreased expression - miR-449b, miR-519b, miR-581, miR-616, miR-892b, miR-941, miR-1179, miR-1292 and miR1296. Three of these could be implicated in neural repair mechanisms. Elevated miR-371-3p levels increase the likelihood that pluripotent stem cells will differentiate into neural progenitors. MiR-892b decreases levels of amyloid precursor protein, which has been implicated as a regulator of synapse formation. Finally miR-941, the only known human-specific microRNA, downregulates the CSPα protein which is involved in neurotransmitter release.

Conclusions:
This preliminary study suggests that circulating microRNAs in the plasma may help serve as biomarkers of neural repair and aid in understanding human neural repair mechanisms. If validated in larger studies with appropriate controls, these markers could aid in timing rehabilitation therapy or designing recovery-based therapeutics.
Abstract 46: Six of One, Half a Dozen of the Other: Single-Center Retrospective Comparison of Prehospital Large Vessel Occlusion Tools
Authors: Ermak David , Richardson Alicia , Hogan Chelsea , Brinkley Amy , Niazi Muhammad , Cockroft Kevin
Published: October 2018

Introduction:
Large Vessel Occlusion (LVO) makes up about 30% of acute strokes. There are several published tools designed for detection of LVO for use in the prehospital setting. The ideal prehospital LVO tool should be simple and easy for prehospital staff to use and result in few LVO patients being missed as well as prevent over-testing and unnecessary transferring of patients without an LVO.

Methods:
From January 2015 to December 2016 1,108 acute ischemic stroke cases were identified; cases which did not present in the acute (<24hrs from onset) period and cases which did not have angiography (CTA, MRA, or catheter angiogram) performed were excluded, leaving 973 cases for analysis. The components of the initial NIHSS evaluation was utilized to calculate various prehospital LVO scales (PASS, VAN, RACE, FAST-ED, and CPSSS). Each chart was reviewed for the presence or absence of LVO defined as M1, M2, ICA or basilar occlusion. The relative performance of each of the prehospital LVO scales were compared using 2x2 analysis.

Results:
In the study population, 30% were LVO positive, 24% received IV tPA, and 9% received endovascular thrombectomy. Comparison of tools using previously defined cutoff points yielded the sensitivity and specificity characteristics depicted in table 1 which are compared to the NIH Stroke Scale cutoff point of 6 which has been previously defined as optimal for LVO detection.

Conclusion:
In this analysis, it is evident that there are distinct trade-offs, with no tool being superior when it comes to having both optimal sensitivity and specificity. Although the NIHSS is the most sensitive tool, use of this scale is not practical in the prehospital setting. Therefore, we support the use of simple tools such as PASS and VAN given the relative ease with which these tools can be learned and applied by EMS.
Abstract 47: Impact of EMS Field-telestroke With Hand-held Ipads on IV-tpa Therapy for Stroke
Authors: Andrefsky John , Rose Sheldon , Chase Noreen , Ellenberger Daniel , Fussner Julie M , Sila Cathy
Published: October 2018

Introduction:
Reducing the Door-to-Needle (D2N) time to IV-tPA has been shown to improve outcomes after acute ischemic stroke. Pre-hospital Telestroke using Mobile Stroke Units has been shown to reduce D2N times but the number of patients treated are underpowered to show improvement in stroke outcome. With deployment in urban areas near multiple comprehensive stroke centers and costs averaging $1M to purchase and $1M to operate annually, it is unlikely that Mobile Stroke Units will exert a major impact on the broader population of stroke victims.

Hypothesis:
Bringing Telestroke expertise to the patient by utilizing Advance Stroke Life Support (ASLS)- trained EMS crews equipped with hand-held iPADS for videoconferencing in the field with their Medical Control could enhance patient assessment and reduce D2N times for IV-tPA in acute stroke.

Methods:
Field-Telestroke training of 243 EMS personnel from 6 community squads associated with a 332-bed acute care Primary Stroke Center was conducted in 2q 2016 and included ASLS Certification, education on Stroke Protocols and videoconferencing in the field with the hospital’s Medical Control, and the use of HIPPA-compliant hand-held iPADs. A retrospective analysis of transports from July 2014- July 2016 pre-implementation and July 2016-June 2017 post-implementation included Stroke Alert process times of Door-to-CT completion (DCT) and D2N.

Results:
Pre-hospital use of Field-Telestroke from July 2016-June 2017 was associated with a shorter average DCT of 10.7 vs 34.5 minutes and shorter D2N time for IV-tPA therapy of 41 minutes vs 50 minutes with standard pre-hospital notification. Overall IV-tPA utilization from July 2016-June 2017 (12.7%, 26/204) was non-significantly increased from baseline July 2014- June 2016 (10.6%, 50/473, p=0.43).

Conclusions:
The use of Field- Telestroke was associated with faster DCT and D2N times for IV-tPA therapy. Field-Telestroke by ASLS-trained EMS squads is a promising low-cost approach to deliver high quality pre-hospital stroke care to communities.
Abstract 51: Organ- and Cell-Specific Immune Responses Are Associated With the Outcomes of Intracerebral Hemorrhage
Authors: Shi Kaibin , Zhang Jing , Li Zhiguo , li Minshu , Han Yujuan , Wang Lei , Zhang Zhecheng , Yu Changlu , Zhang Fang , Song Lijuan , Dong Jing-Fei , Liu Qiang , La Cava Antonio , Sheth Kevin N , Shi Fu-Dong
Published: October 2018

Background:
Severe brain injury significantly influences immune responses. However, the levels at which such influence occur and the involvement of neurogenic pathways are not well defined.

Methods:
39 eligible patients with supratentorial ICH within 24 hours of onset and 20 matched healthy controls were enrolled. Hematoma sizes at admission were calculated via computed tomography (CT). Perihematomal edema (PHE) and spleen volume at day 3 and 14 were measured via T2-weighted magnetic resonance imaging (MRI), respectively. Tissue diffusion and capillary perfusion of spleen were quantified by Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) with 9 b values. Peripheral lymphocyte subsets were quantified by flow cytometry. Neurotransmitters and stress hormone were detected by enzyme-linked immunosorbent assay (ELISA). Association of splenic and cellular alterations with progression of PHE and the outcomes of ICH patients were analyzed. Mechanisms governing the spleen and lymphocyte alterations after ICH were investigated in mouse models of ICH.

Results:
Average spleen shrinkage of 37ml accompanied by splenic capillary perfusion increase occurred in ICH patients at day 3 after disease onset. The magnitude of spleen shrinkage was associated with hematoma size upon admission. Concurrently, patients with severe spleen shrinkage (> 37ml) had less progression of PHE. Lymphopenia was observed in ICH patients after ictus and persisted up to 14 day, which was not parallel with spleen alteration. Patients with infections exhibited poorer functional outcome and significant T and NK cell deficiency. In ICH models, signals derived from adrenergic and hypothalamus-pituitary-adrenal (HPA) axis activation contributed to loss of white blood cells in the white pulp.

Conclusions:
Spleen shrinkage and lymphopenia reflect the impact of ICH on the immune system at the organ and cellular levels, such impacts are derived from coordinated action of sympathetic innervation and HPA axis. The magnitude of spleen shrinkage might be associative with the progression of PHE and clinical outcome of ICH patients. Additionally specific cellular immunity deficiency was associated with increased infection risk in patients.
Abstract 57: Arterial Dissection as a Cause of Intracranial Stenosis in East Asians: A High-resolution Magnetic Resonance Imaging Study of 558 Patients
Authors: Park Moo-seok , Cha Jihoon , Chung Jong-Won , Seo Woo-Keun , Kim Gyeong-Moon , Bang Oh Young
Published: October 2018

Background:
Intracranial occlusive disease is a common cause of stroke worldwide, and is more prevalent in Asians. We hypothesized that non-traumatic intracranial artery dissection (ICAD) may be a common hidden cause of large intracranial occlusive disease in Asian patients with ischemic stroke, and that many patients with ICAD may be misclassified as having intracranial atherosclerotic stenosis (ICAS).

Methods:
We prospectively recruited patients with acute symptomatic infarcts due to intracranial occlusive disease between January 2011 and October 2016. High-resolution magnetic resonance imaging (HR-MRI) was performed when vascular studies yielded ambiguous results for the diagnosis of ICAS, ICAD, or other causes. Clinical, laboratory, and HR-MRI findings were compared between the ICAS and ICAD groups.

Results:
Among 937 patients who showed intracranial stenosis on time-of-flight magnetic resonance angiography, HR-MRI was performed in 558. According to HR-MRI features, 123 were classified as ICAD and 252 as ICAS. Male sex, older age, hypertension, and diabetes were more frequent in the HR-confirmed ICAS group. Anterior circulation location, and the presence of vascular calcification and tandem stenosis were also more common in the ICAS group. However, clinical and radiological characteristics did not differ between patients with typical luminal changes of ICAD (n=69) and those with ICAD documented by HR-MRI but no typical luminal changes (n=123).

Conclusion:
Almost two thirds of ICAD patients in an Asian population were misclassified as having ICAS by standard luminal imaging techniques. Considering the different therapeutic and prognostic approaches in ICAD and ICAS, HR-MRI may be a useful diagnostic tool in this population.
Abstract 6: Frequency, Risk Factors, Causes, and Outcomes of Early Neurological Deterioration in Hyperacute Cerebral Ischemia
Authors: Brown Christa D , Avila-Rinek Gilda , Sanossian Nerses , Starkman Sidney , Hamilton Scott , Liebeskind David S , Young-Saver Dashiell F , Eckstein Marc , Stratton Samuel , Pratt Frank , Conwit Robin , Saver Jeffrey L ,   on behalf of the FAST-MAG Trial Coordinators and Investigators
Published: October 2018

Background:
Early neurological deterioration (END) is a feared complication of acute cerebral ischemia, but studies have provided widely varying estimates of END frequency, have often not systematically investigated END mechanism, and have not characterized END frequency among hyperacute patients presenting within the first 2h of onset, during the period of greatest neurologic deficit lability.

Methods:
We analyzed subjects with a final diagnosis of acute cerebral ischemia in the NIH Field Administration of Stroke Therapy-Magnesium Phase 3 multicenter clinical trial. END was defined as worsening by ≥ 4 NIHSS points up to Day 4. Causes of worsening were adjudicated by a central expert panel reviewing detailed medical records and imaging studies.

Results:
Among 1245 acute cerebral ischemia patients transported by EMS to 55 receiving stroke centers, time from last known well to ED arrival was median 59 mins (IQR 80-46). Overall, 211 (16.9%) experienced END by Day 4, including 17.4% within the first 6 hours of ED arrival, 32.2% between 6-24h, and 50.3% between 24h-Day 4. Patient features associated with END included older age (73.1 vs 70.5, p=0.01), worse initial deficits (NIHSS 13.1 vs 8.4, p<0.0001), history of hypertension, diabetes, higher serum glucose, BUN, and creatinine. Arrival imaging findings associated with END included more advanced acute ischemic change (ASPECTS 7.8 vs 8.8, p<0.0001) and presence of prior infarction. Leading causes of END were: extension of initial cerebral infarct (contributing in 50.6% of END patients), cerebral edema (25.3%), hemorrhagic transformation (23.0%), and infection (8.4%). END was associated with substantially reduced functional independence (mRS 0-2) at 90 days, 9.1% vs 67.9%, p<0.0001, and increased 90-day mortality, 42.1% vs 6.5%, p<0.0001).

Conclusions:
END occurs in 1 in 6 hyperacute cerebral ischemia patients, and is associated with dramatic reductions in functional independence and increases in mortality by 3 months. The leading causes of END are ischemia progression, cerebral edema, and hemorrhagic transformation, which collectively contribute to 4 in 5 of all END events, and are important treatment targets to improve ischemic stroke outcome.
Abstract 64: China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A Prospective, Multicenter, Randomized Controlled Trial After SAMMPRIS
Authors: Gao Peng , Jiao Liqun , Ma Yan , Wang Yabing , Chen Yanfei , Zhao Zhenwei , Wang Daming , Cai Yiling , Wu Wei , Li Tianxiao , Shi Huaizhang , He Weiwen
Published: October 2018

Background:
Patients with symptomatic stenosis of intracranial arteries are at high risk for future stroke. Since the SAMMPRIS trial, stenting is not recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we propose a refined prospective, randomised, multicenter study in a Chinese population with strictly defined patient and participating center inclusion criteria.

Methods:
The CASSISS trial is an ongoing, government-funded, prospective, multicenter trial (NCT01763320). It recruits patients with recent TIA or stroke caused by 70-99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients. For practice, CASSISS has been divided into 2 stages: lead-in and randomised phase. The lead-in trial recruited 100 consecutive patients for Wingpsan stent placement from July 2013 to February 2014 among 13 sites in China. The overall 1-month stroke and/or death rate was 2%, which demonstrated modifications in patient selection and procedural aspects can substantially reduce peri-procedural rate. The randomised phase started on Mar 2014, a total of 380 patients was randomised (1:1) to best medical therapy alone or medical therapy plus stenting among 8 sites in China. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. Recruitment has been finished on November 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019.

Conclusion:
The prospective multicenter single-arm trial has demonstrated acceptable results. The 1-year follow-up of the 380 patients will be finished in November 2017. We expect that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high-volume centers.
Abstract 7: Outcome Prediction in Acute Stroke Patients by Continuous Glucose Monitoring: COntinuous glucose Monitoring for acute stroke Patients receiving Latest treatment (COMPLEAT) Study
Authors: Wada Shinichi , Yoshimura Sohei , Inoue Manabu , Matsuki Takayuki , Arihiro Shjoji , Koga Masatoshi , Makino Hisashi , Hosoda Kiminori , Ihara Masafumi , Toyoda Kazunori
Published: October 2018

Background and purpose:
Association of dynamic variation of blood glucose during initial days after stroke onset with stroke outcomes has not been yet clarified. The purpose of this study was to examine the relationship between glucose barometers obtained by continuous glucose monitoring (CGM) and clinical outcomes in acute stroke patients.

Methods:
Continuous patients with acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH) within 24 hours after onset were included. CGM device (iPro2) was attached for the initial 72 hours after emergent admission. Seven glucose barometers were obtained from CGM: maximum, minimum, mean, and standard deviation of blood glucose levels, as well as area under the curve more than 8 mmol/L blood glucose (8AUC), distribution time more than 8 mmol/L blood glucose (8time-ratio), and presence of time less than 3.9 mmol/L during 72 hours. Primary outcome measure was unfavorable clinical outcome at 3 months (mRS ≥3). Secondary outcome measure was early neurological deterioration after stroke (an increase of ≥4 NIHSS scores from the baseline or death) within 7 days.

Results:
One hundred patients with AIS (n=58) or ICH (n=42) were included. Blood glucose level varied between 5.2±1.4 mmol/L and 11.4±3.3 mmol/L during 72 hours with 8AUC of 0.7±1.4 minхmmol/L, 8time-ratio of 31.7±32.7%, and presence of hypoglycemia in 15% of the overall patients. Mean glucose level (adjusted OR 1.59, 95% CI 1.13-2.25 /1 mmol/L), 8AUC (2.06, 1.14-3.72 /1 minхmmol/L) and 8time-ratio (1.25, 1.05-1.49 /10%)were related to unfavorable outcome for overall patients, as well as for AIS patients (2.11, 1.26-3.53; 2.43, 1.24-4.78; 1.72, 1.23-2.39, respectively). Only 8time-ratio was related to neurological deterioration for overall patients (adjusted OR 1.49, 95% CI 1.08-2.05 /10%).

Conclusion:
High mean glucose levels, 8time-ratio and 8 AUC levels were associated with unfavorable outcome at 3 months. High 8time-ratio levels were related to early neurological deterioration within 7 days.
Abstract 70: Targeting Myeloid Specific Neutrophil Integrin α9β1 Improves Stroke Outcome Following Transient Cerebral Ischemia in Comorbid Condition of Hyperlipidemia
Authors: Dhanesha Nirav , Nayak Manasa , Bathla Girish , Thedens Daniel , Jain Manish , Doddapattar Prakash , Chauhan Anil K
Published: October 2018

Background and Hypothesis:
Neutrophils infiltration following reperfusion is the hallmark of ischemic stroke. Integrin α9β1 is highly expressed on neutrophils, upregulated upon activation, stabilizes adhesion to activated endothelium in synergy with β2 integrin, and plays a role in transmigration. Fibronectin containing alternatively spliced extra domain A (Fn-EDA) is a ligand for integrin α9β1, and is known to be pro-thrombotic and pro-inflammatory. The role of α9β1 in ischemic stroke is not elucidated yet. Following STAIR guidelines, we tested the hypothesis that integrin α9β1/Fn-EDA axis contributes to the pathophysiology of ischemic stroke in comorbid condition of hyperlipidemia.

Methods:
Susceptibility to brain ischemia/reperfusion injury was evaluated in male and female mice (N=14-16) by transient occlusion of middle cerebral artery (1 hr) followed by 1, 3, and 7 days of reperfusion. Quantitative assessment of stroke outcome was evaluated by measuring infarct volume (MRI), neurological outcome (0-4), and post ischemic thrombo-inflammation (fibrin, neutrophil and inflammatory cytokines) within ischemic region (by Western and immunohistochemistry). Using intravital microscopy, susceptibility to arterial thrombosis was evaluated in FeCl
3
and laser injury-induced thrombosis models.

Results:
Irrespective of gender, myeloid specific
α
9
β

1
-/-

mice on wild-type and hyperlipidemic background
(
α

9
fl/fl
LysMCre

and
α

9
fl/fl
LysMCreApoe
-/-

) exhibited smaller infarcts and improved neurological outcomes at days 1, 3 and 7 concomitant with enhanced survival rate and decreased post ischemic thrombo-inflammation (P<0.05 vs.
α

9
fl/fl

or
α

9
fl/fl
Apoe
-/-

mice littermates). Intravital microscopy showed that myeloid specific
α
9
β

1
-/-

mice were less susceptible to arterial thrombosis compared to controls (P<0.05). Bone marrow transplantation experiments revealed that Fn-EDA contributes to α9β1 mediated stroke exacerbation. Infusion of a specific inhibitor of α9β1 into

Apoe
-/-

mouse 15 minutes after reperfusion significantly improved stroke outcome.

Conclusions:
Following STAIR guidelines, we provide genetic and pharmacologic evidence that targeting myeloid specific integrin α9β1 in hyperlipidemic mice improves stroke outcome.
Abstract 77: Circulating miRNome in Moyamoya Discordant MZ Twins - Implications for Endothelial Biofunctions
Authors: Uchino Haruto , Ito Masaki , Kazumata Ken , Hama Yuka , Hamauchi Shuji , Sasaki Hidenao , Kuroda Satoshi , Houkin Kiyohiro
Published: October 2018

Objective:
We aim to investigate circulating genome-wide microRNA (miRNome) profiles in Moyamoya disease-discordant monozygotic (MZ) twins with the RNF213 founder mutation (rs112735431), since the etiology remains unclear even after the identification of RNF213.

Methods:
Circulating miRNome was screened in a pair of Moyamoya-discordant MZ twins and a validation cohort (unrelated 9 cases and 8 normal controls) using microarray and validated by quantitative real-time PCR. Differential plasma microRNAs were quantified in endothelial cells differentiated from iPS cell line (iPSECs) derived from unrelated 3 cases and 3 controls. Gene expressions targeted by the significant microRNAs in iPSECs was studied using published iPSEC-transcriptome and bioinformatics tool.

Results:
A total of 537 circulating microRNAs were detected in the Moyamoya-discordant MZ twins and the validation cohort. Unsupervised cluster analysis demonstrated 2 discrete miRNome, predominantly by disease, but the MZ twins showed similar miRNome profiles, regardless of phenotypic discordance (Fig. 1A). Across the 143 and 98 differential microRNAs in the MZ twins and validation cohort, 23 microRNAs were overlapped (Fig. 1B). A cluster of plasma hsa-miR-6722-3p/-328-3p/150-5p was significantly up-regulated in patients in the validation cohort (p < 0.05) (Fig. 1C). In iPSECs, hsa-miR-6722-3p/-328-3p cluster was up-regulated with a greater than 3.0-fold change in patients. Bioinformatics analysis revealed that 94 target genes involving organismal injuries and cell survival/maintenance were significantly down-regulated in Moyamoya-iPSECs (p < 0.05, q < 0.1), suggesting the regulatory role of the miR-6722/-328 cluster in endothelial gene expression (Fig. 1D).

Conclusions:
Differential plasma-miRNAs in Moyamoya-discordant MZ twins may potentially serve as a diagnostic biomarker in Moyamoya disease and regulate endothelial gene expression.
Abstract 85: Is Progressively Worsening Severity of Internal Carotid Artery Stenosis by Carotid Doppler Ultrasound in Asymptomatic Patients a Risk Factor for Ischemic Stroke?
Authors: Qureshi Adnan I , Saeed Omar , Malik Ahmed A
Published: October 2018

Background:
Progressively worsening severity of ICA stenosis has been used as an indication for carotid revascularization in asymptomatic patients. However, limited data exists whether progression in severity is actually associated with ipsilateral cerebral ischemic symptoms.

Methods:
We analyzed data from the Cardiovascular Health Study participants aged ≥65 years who underwent serial carotid Doppler ultrasound (at baseline and 5 year follow up). The severity was classified into four grades by a central reader: 0-24%, 25-49%, 50-69%, 70-99%, and complete occlusion. We selected patients who were asymptomatic at baseline and not undergone carotid endertectomy. Progressively worsening severity of internal carotid artery stenosis was defined if the severity of ICA with highest velocity at baseline evaluation had increased by one grade or greater at 5 year follow up. Incident cardiovascular events were identified during annual follow-up examinations and at 6-month telephone contact and adjudicated by a central committee. Hazards ratio for cardiovascular events during follow up were estimated using Cox proportional Hazards analysis.

Results:
Progressively worsening severity of internal carotid artery stenosis was observed in 1551 (26.3%) of 5,888 study participants (57.2% women; mean baseline age, 72.7 ± 5.1 years). The rate of ipsilateral ischemic stroke was similar among patients with and without progressively worsening severity of internal carotid artery stenosis over a mean follow up period (mean ±SD) of 7.3 ± 1 years. The risk of any ischemic stroke was (HR 1.3, 95% confidence interval [CI] 1.0-1.6) but not ipsilateral ischemic stroke (HR 1.4, 95% CI 0.6 - 3.1) was statistically higher among patients with progressively worsening severity of internal carotid artery stenosis after adjusting for age, race, serum cholesterol, diabetes mellitus, blood pressure and cigarette smoking. The risk of MI (HR 1.3, 95% CI 1.1-1.7) was significantly higher among patients with progressively worsening severity of internal carotid artery stenosis.

Conclusions:
Patients with progressively worsening severity of internal carotid artery stenosis appear to be at higher risk of cardiovascular events but not ipsilateral cerebral ischemic symptoms.
Abstract 9: Compliance of a New Standard in Stroke Neuro Checks in a Comprehensive Stroke Center Compared to Primary Stroke Centers for IV Alteplase and Thrombectomy Patients
Authors: Swearingen Natalie , Cox Kailey , Lesko Alexandra , Lucas Lindsay , Clark Diane
Published: October 2018

Background:
Frequent neurological monitoring is required for patients who receive IV alteplase and/or thrombectomy. A new stroke neuro check called SNAP (Stroke Neuro Assessment by Providence) was introduced to this regional program. SNAP is defined by four components: (1) level of consciousness (LOC), 1a, 1b, 1c on NIH stroke scale (NIHSS) or GCS, (2) pupil reactivity, (3) movement of all extremities NIHSS 5a, 5b, 6a, 6b, and (4) trending originating symptoms of first NIHSS.

Purpose:
Examine SNAP check and provider follow-up compliance at a certified Comprehensive Stroke Center (CSC) with a neurocritical care unit and three certified Primary Stroke Centers (PSC) for all IV alteplase and/or thrombectomy.

Methods:
Data between January 2017 and March 2017 from four certified stroke centers were included. One low volume PSC, and patients treated by non-regular nursing staff were excluded from the analysis. SNAP check compliance was calculated as the number of documented SNAP checks divided by eligible opportunities and follow-up compliance as the number of contacted providers divided by all SNAP changes with an associated NIHSS change of 4 or more. Binomial regressions were used to test compliance for conducting SNAP by stroke certification type and components of SNAP.

Results:
Of 37 patients included, 59% were female, mean age was 72 (±15) years, and the median ED NIHSS was 9.0 [Interquartile range: 2.0, 17.5]. Provider follow-up compliance was 75% (6/8) and SNAP check compliance was 68% (3,131 completed/4,601 opportunities for 37 patients). There were significant differences in SNAP check compliance by assessment type with highest in LOC and lowest in trending originating symptoms (90% vs. 45%, p<.001). The CSC hospital had a statistically significant higher SNAP check compliance of 82% compared to PSCs which had a combined compliance of 62% (p=0.003).

Conclusions:
The CSC had significantly higher overall compliance than the PSCs. However, there is a need for increased compliance with trending originating symptoms at all three hospitals. Our analysis suggest that a neurocritical care unit impacts compliance with a standard stroke neuro check at a Joint Commission certified CSC.
Abstract 90: Geometric Characteristics of Middle Cerebral Artery Atherosclerosis and Clinical Stroke
Authors: Yu Yannan , Li Mingli , Xu Yuyuan , Gao Shan , Feng Feng , Trieu Harry , Liebeskind David S , Xu Weihai
Published: October 2018

Objectives:
We aimed to investigate the geometric characteristics of middle cerebral artery (MCA) atherosclerosis and their clinical relevance.

Methods:
Vessel wall magnetic resonance imaging was obtained in patients with recent stroke in MCA territory or suspected asymptomatic MCA atherosclerosis without cardioembolism or carotid artery stenosis. MCAs were classified as atherosclerotic or plaque-free based on whether plaque was present. Atherosclerotic MCAs were divided into MCAs with or without stroke. Geometric characteristics including M1 segment shape (Fig.1), plaque location, plaque length, plaque thickness, stenosis degree, and remodeling ratio were assessed. These geometric characteristics were compared between the groups.

Results:
A total of 1006 MCAs were analyzed, including 577 atherosclerotic MCAs (124 MCAs with stroke and 457 MCAs without stroke) and 429 plaque-free MCAs. Curvy MCAs were more prevalent than straight MCAs (79.2% vs 20.2%). The inferior-oriented M1 curve was the most prevalent (61.5%). In 90.4% of curvy atherosclerotic MCAs, the inner side of the M1 curve was involved by plaque. Only 9.6% of curvy atherosclerotic MCAs had no plaque involving the inner sides. Inferior and anterior plaque were found in 67.3% of atherosclerotic MCAs while superior and posterior plaque were found in 32.7%. The absence of an inferior-oriented M1 curve (OR 0.54, 95%CI 0.35-0.83), presence of superior plaque (OR 2.42, 95%CI 1.52-3.86), greater plaque length (OR 1.14, 95%CI 1.07-1.22), greater plaque thickness (OR 2.55, 95%CI 1.49-4.36), higher remodeling ratio (OR 1.15, 95%CI 1.04-1.27), and fewer quadrants involved by plaque (OR 0.68, 95%CI 0.51-0.91) were independently associated with MCAs with clinical stroke.

Conclusions:
MCA plaque tended to develop in the same orientation as the M1 inner curve. In addition, the inferior-oriented M1 curve was associated with MCAs without stroke, while superior plaque was associated with MCAs with stroke.