bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP119: The Second Report of Japanese Sub-Analysis of TIAregistry.org
Authors: Uchiyama Shinichiro , Hoshino Takao , Sissani Leila , Linsay Monteiro T , Kamiyama Kenji , Nakase Taizen , Kitagawa Kazuo , Minematsu Kazuo , Todo Kenichi , Okada Yasushi , Nakagawara Jyoji , Nagata Ken , Yamagami Hiroshi , Yamaguchi Takenori , Amarenco Pierre
Published: October 2018

Background:
TIAregistry.org is an international, multicenter-cooperative, prospective registry in patients with TIA or minor stroke within 7 days after the onset. Main analyses of one-year follow-up data have been reported (N Engl J Med 2016;374:1533-42). This was the second report on Japanese sub-analysis of TIAregistry.org.

Methods:
The patients recruited in TIAregistry.org were classified into two groups (345 Japanese and 3,238 non-Japanese). We compared subtype of acute cerebrovascular syndrome (ACVS) at baseline and recurrent ischemic stroke subtype according to the TOAST classification during one-year follow-up period as well as short- to long- term risk of stroke between Japanese and non-Japanese patients. We also determined predictors of one-year stroke in Japanese patients.

Results:
There was significant difference between Japanese and non-Japanese in the baseline ACVS subtype (38.3% vs 22.9% in small vessel occlusion, and 13% vs 33.9% in undetermined cause, p <0.001) and recurrent stroke subtype (8.0% vs 17.4% in cardio-embolism, 24.0% vs 3.7% in other determined cause, and 4.0% vs 24.2% in undetermined cause, p< 0.001). The risk of stroke at 2-day was similar between Japanese and non-Japanese, while the risk at 7-, 30- and 90-day, and 12-month were higher in Japanese than in non-Japanese. The risks of recurrent stroke in Japanese were diabetes mellitus (HR 2.88, 95% CI 1.06-4.90, p = 0.03), regular alcohol consumption (HR 2.56, 95% CI 1.15-5.78, p = 0.02), and large artery atherosclerosis in TOAST classification (HR 8.35, 95% CI 1.16-63.43, p = 0.02). In multi-variate analysis, the significant predictors of one-year stroke risk were prior coronary artery disease (HR 6.08, 95% CI 1.28-28.81, p = 0.02) and regular alcohol consumption (HR 2.28, 95% CI 1.02-5.17, p = 0.04).

Conclusions:
There were differences in baseline TOAST classification and recurrent TOAST stroke subtype between Japanese and non-Japanese. The very short-term risk of stroke was similar between Japanese and non-Japanese, while the later-term risk was higher in Japanese than in non-Japanese. The independent predictors of one-year stroke were history of coronary artery disease and regular alcohol drinking in Japanese patients.
Abstract TMP13: Individual Patient Data Meta-analysis of Hypothermia for Acute Ischaemic Stroke
Authors: Flaherty Katie , De Georgia Michael A , Hemmen Thomas M , Kollmar Rainer , Krieger Derk W , Lyden Patrick , Petersson Jesper , Piironen Katja , Poli Sven , Van de Worp Bart , Bath Philip M
Published: October 2018

Background:
It remains unclear whether inducing hypothermia is safe and effective for improving outcome after hyperacute ischaemic stroke. An individual patient data meta-analysis of completed trials was performed.

Methods:
Following electronic searches for trials comparing hypothermia to control, Chief Investigators were approached to share individual patient data (IPD). Odds ratios (OR, 95% confidence intervals, 95% CI) were analysed with ordinal logistic regression and binary logistic regression with adjustment for trial, cooling method (endovascular, surface or unknown) and age.

Results:
Data were obtained for 10 trials (320 participants): COAST-I, COAST-II, COOL AID pilot, COOL AID, COOLIST, HAIS-SE, ICTuS-L, ICTuS-2, MASCOT and MHAIS; IPD were not available for two studies. Trial designs varied and most had a small sample size, mean (SD) age 66 (11.5) years, female 42%, NIHSS 13.4 (5.3), time to treatment 4.5 (1.2) hours, thrombolysis 53%. In patients whose temperature was recorded (n=74), the lowest achieved temperature was in the hypothermia arm: 34.3
o
C vs. 36.6
o
C (p<0.001). Functional outcome (modified Rankin Scale) at day 90 did not differ between cooling vs. no cooling: n=297 OR 0.93 (95% CI 0.63-1.39, p=0.74). Serious adverse events (n=287) were increased in the cooling arm: 81.5% vs. 65.5% (p<0.001); pneumonia: 30.2% vs. 10.9% (p<0.001) and aspiration: 13.3% vs. 3.5% (p=0.004). There was no difference in death: 17.2% vs. 13.6% (p=0.21).

Conclusion:
Hypothermia lowered temperature by 2.3 C, did not alter functional outcome or mortality, but was associated with more SAEs. Larger trials are needed to assess hypothermia in hyperacute stroke.
Abstract TMP16: Perspectives of Emergency Department Providers in a Telestroke Network
Authors: O’Donnell Steven M , Smith Jaleen , Ledyard Holly K , Majersik Jennifer J
Published: October 2018

Introduction:
The experience of Emergency Department (ED) providers’ using telestroke (TS) is not well studied. It has been suggested that TS could create learned helplessness or reduce local confidence in ED services. We aimed to understand if TS changes ED practice patterns and to measure ED provider confidence with stroke treatment within a TS network.

Methods:
We used prior published telemedicine assessment surveys to design a new survey tailored to ED provider TS users. Content included perceptions of value and counterfactuals. ED providers were eligible if we had contact information and they participated in a TS consult at 1 of 26 sites in a 6-state TS network between Jan-May 2017. After a TS consult, an e-mail with a survey link was sent to the ED provider. Only first-time surveys were included in this analysis.

Results:
We sent surveys to 64 ED providers with a response rate of 48% (31/64) (Table 1). The most common reason (71%) for using TS was for expert opinion on IV tPA eligibility. No ED providers felt their medical knowledge would be doubted by a patient or family member because of using TS. ED providers reported high confidence for diagnosing ischemic stroke (97%) and giving IV tPA (81%), but only 10% were confident determining eligibility for mechanical thrombectomy. Consults changed patient care by changing the diagnosis in 16% and enabling 2 additional patients (10% of those with ischemic stroke) to receive IV tPA and 6 (19%) additional patients to transfer (Table 2.)

Conclusions:
ED providers surveyed had high confidence in stroke care. Discomfort in determining eligibility for thrombectomy points to educational opportunities and need for new clinical care pathways.
Abstract TMP20: Small Vessel Occlusion is a High Risk Etiology of Early Recurrent Stroke After Transient Ischemic Attack
Authors: Ohara Tomoyuki , Uehara Toshiyuki , Suzuki Rieko , Sato Shoichiro , Hayakawa Mikito , Toyoda Kazunori , Minematsu Kazuo
Published: October 2018

Introduction:
Early stroke risk in patients with transient ischemic attack (TIA) due to small vessel occlusion (SVO) is underestimated. We assessed whether TIA patients due to SVO are at a higher early stroke risk, using the data of a prospective, multicenter, observational registration study in Japan (PROMISE-TIA registry).

Methods:
The study subjects were 1,320 TIA patients (470 women, 69±12 years, median ABCD2 score 5) within 7 days of onset. The primary outcome was recurrent stroke within 30 days after TIA. SVO-TIA was defined as having lacunar TIA syndrome without cardiac source of embolism or large artery stenosis, as the exact determination of TIA due to SVO is difficult. Lacunar TIA syndrome was defined as unilateral weakness or sensory disturbance of at least two of three body parts (face, arm, and leg) in the absence of cortical dysfunction. Predictors for 30-day recurrent stroke were estimated using a Cox proportional hazards model.

Results:
Recurrent stroke within 30 days after TIA was observed in 61 patients (4.6%). In multivariable analysis, SVO-TIA (hazard ratio, 1.87; 95%CI, 1.11-3.11), higher systolic blood pressure at presentation (hazard ratio, 1.18 (per 10mmHg increase); 95%CI, 1.08-1.28) and presentation within 3 hours after onset (hazard ratio, 2.25; 95%CI, 1.30-4.10) were independently associated with recurrent stroke. Furthermore, SVO-TIA with an evidence of subcortical or brainstem infarcts on diffusion weighted imaging (definite TIA due to SVO) was a stronger predictor for recurrent stroke (hazard ratio, 3.63; 95%CI, 1.59-7.23). The presence of cardiac source of embolism and symptomatic large artery steno-occlusion were not significant predictors.

Conclusions:
The data from a Japanese large TIA registry suggested that patients with TIA due to SVO were at a higher risk of early recurrent stroke.
Abstract TMP22: Safety of Pretreatment With Dual Antiplatelet Therapy in Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Goyal Nitin , Tsivgoulis Georgios , Kerro Ali , Katsanos Aristeidis H , Krishnan Rashi , Malhotra Konark , Pandhi Abhi , Duden Peter , Deep Aman , Shahripour Reza Bavarsad , Bryndziar Tomas , Nearing Katherine , Chulpayev Boris , Alexandrov Anne W , Alexandrov Andrei V
Published: October 2018

Introduction:
There are preliminary data indicating that pretreatment with dual antiplatelet therapy (DAPT) may increase the risk of symptomatic intracranial hemorrhage (sICH) following intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). We sought to identify the safety and efficacy of pretreatment with DAPT in IVT for AIS in a prospective, multi-center study.

Methods:
AIS patients treated with IVT during a five-year period in two tertiary care stroke centers were evaluated. Baseline stroke severity and early hypodensity on baseline CT were assessed by NIHSS-score and ASPECTS by certified physicians. Three-month functional status was assessed using modified Rankin Scale (mRS). We compared the following outcomes between DAPT (+) and DAPT (-) patients before and after propensity score matching (PSM): 1.sICH, 2. asymptomatic intracranial hemorrhage (aICH) 3. favourable functional outcome (FFO; mRS scores of 0-1), 4. 3-month mortality.

Results:
Out of total 790 IVT-treated AIS patients, we identified 58 (7%) pretreated with DAPT (mean age 68±13 years; 57% men; median NIHSS-score 8, IQR: 4-14). The two groups did not differ (p>0.05) in terms of sICH [DAPT(+): 3% vs. DAPT(-): 3%], FFO (64% vs. 50%) and 3-month mortality (9% vs. 9%) in unmatched analyses. DAPT pretreatment was associated with higher odds of aICH before (17% vs. 6%) and after adjustment (OR: 2.4; 95%CI: 1.1-5.5) for potential confounders. After PSM, patients with (n=41) and without (n=82) DAPT pretreatment did not differ in any of the baseline characteristics. The differences in rates of all outcome events were non-significant in the two groups including sICH (2% vs. 1%, p=0.63), aICH (17% vs. 7%, p=0.06) and 3-month mRS (p=0.60; Figure).

Conclusions:
Pretreatment with DAPT is not associated with higher rates of sICH or three-month mortality and does not reduce the odds of FFO following IVT for AIS. IVT should not be withheld in otherwise eligible candidates due to pretreatment with DAPT.
Abstract TMP24: Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)
Authors: Muir Keith , Murray Alicia , Wardlaw Joanna , Ford Ian , Ford Gary
Published: October 2018

Background:
IV thrombolysis with alteplase, the only medical treatment currently approved for acute ischaemic stroke, significantly increases the probability of excellent recovery. A recent trial has demonstrated that the modified tissue plasminogen activator tenecteplase at a dose of 0.4mg/kg is of similar safety and efficacy to alteplase in acute stroke. In addition to having simpler administration, tenecteplase 0.25mg/kg is also potentially superior to alteplase with respect to efficacy, based on meta-analysis of small trials. More data are required to establish the true risk-benefit profile compared with alteplase.

Objectives & Methods:
ATTEST-2 will establish whether tenecteplase is superior to alteplase by undertaking a prospective randomised open blinded end-point (PROBE) trial in patients eligible for IV thrombolysis based on non-contrast CT imaging. The study opened to recruitment in Dec 2016. 60 UK centres will recruit 1870 patients.

Outcome:
Primary outcome is the distribution of modified Rankin Scale (mRS) outcomes at day 90, determined by the Rankin Focused Assessment method, analysed by ordinal distribution ("shift") analysis of the of scores in intervention and control groups.

Conclusion:
An agent with superior risk:benefit ratio to alteplase would potentially extend thrombolytic treatment a greater proportion of patients than at present and reduce the need for mechanical thrombectomy. This trial will contribute to the optimisation of reperfusion strategies.
Abstract TMP27: Tgfalpha Protects Oligodendrocytes Against Ischemic Injury and Promotes White Matter Integrity After Stroke
Authors: Dai Xuejiao , Zhao Jingyan , Xu Fei , Cai Wei , Chen Jun , Hu Xiaoming
Published: October 2018

Introduction:
The loss of white matter integrity after ischemic stroke contributes to long-term sensorimotor and cognitive deficits. Elucidating the mechanisms for white matter protection or recovery is therefore important to improve stroke outcomes. This study investigates the function of TGFα, a member of the epidermal growth factor family, in white matter recovery after stroke and elucidate the mechanisms of action.

Methods:
Cerebral ischemia was induced by transient (60 min) middle cerebral artery occlusion (tMCAO) in wild type and TGFα knockout mice. The spatiotemporal pattern of TGFα expression was evaluated by immunofluorescent staining at 1, 3, 5, 14, 21 and 35 days after tMCAO. Sensorimotor (rota-rod test, adhesive-remove test and open field test) and cognitive (Morris water-maze test) functions were assessed up to 35 days after stroke. White matter injury was quantified by MBP (myelin basic protein) and SMI32 (recognizes damaged non-phosphorylated neurofilament proteins) staining. The direct effect of TGFα on oligodendrocytes were evaluated in vitro using primary cultures. Live/dead cell staining and LDH (lactate dehydrogenase) assay were used to assess oligodendrocytes death after 90 min oxygen and glucose deprivation (OGD).

Result:
Cerebral ischemic induced an abrupt and transient increase of TGFα in the brain. The expression of TGFα was mainly increased in microglia and neurons. TGFα deficiency resulted in exacerbation in sensorimotor and cognitive deficits up to 35 days after tMCAO. MAP2 (microtubule-associated protein 2) staining at 3 days and 35 days showed lager tissue loss in TGFα knockout mice as compared with wild type stroke mice. Importantly. TGFα knockout mice also exhibited impaired white matter integrity, as revealed by the loss of MBP staining and elevation in SMI32 staining, at 35 days after stroke. Correlation analysis demonstrated positive correlation between white matter integrity and functional outcomes after stroke in TGFα knockout mice and wild type mice. In vitro study confirmed that TGFα (5, 10 or 20 ng/ml) protected oligodendrocyte precursor cells and oligodendrocytes against OGD.

Conclusion:
TGFα is important for maintaining white matter integrity and improving neurological recovery after stroke.
Abstract TMP28: Inhibition of Integrin α
5
β
1
With the Small Peptide Atn-161 Reduces Infarct Volume and Improves Functional Recovery Through Reduction of Blood-brain Barrier Permeability
Authors: Edwards Danielle , Salmeron Kathleen , Fraser Justin F , Bix Gregory J
Published: October 2018

Reperfusion-induced injury after recanalization is exacerbated by blood-brain barrier (BBB) dysfunction after ischemic stroke. Endothelial cell integrin receptors, specifically the β
1
subtype, play a direct role in BBB dysfunction through regulation of barrier-forming tight junction (TJ) proteins. We hypothesize that inhibition of an endothelial specific β
1
integrin, α
5
β
1
, after oxygen-glucose deprivation (OGD)
in vitro
and also after experimental stroke
in vivo
will stabilize the BBB through the TJ claudin-5, reducing infarct volumes and improving functional recovery. First, stroke was simulated
in vitro
by OGD or TNF- α treatment of brain endothelial cell monolayers. Treatment with the small peptide α
5
β
1
inhibitor ATN-161 (10 μM) resulted in decreased barrier permeability as measured by trans-endothelial cell electrical resistance and FITC-dextran permeability. Immunocytochemistry showed extracellular localization and upregulation of claudin-5 with ATN-161 treatment. Next, transient tandem middle cerebral artery occlusion was performed on 12-week-old male mice for 1 hour. On confocal and SEM imaging, post-stroke α
5
β
1
expression was upregulated primarily in the

luminal vascular surface by post-stroke day (PSD) 2 rather than at the basement membrane (next to its extracellular matrix ligands). IP injection of ATN-161 (1 mg/kg) immediately after reperfusion and on PSD 1, and PSD2 caused a significant, but transient and acute (after the initial dose only) change in animal pulse distension, but no change in body temperature or heart rate. Infarct volumes, measured by TTC stain, were significantly reduced in ATN-161 treated animals. Furthermore, BBB integrity was improved by ATN-161 as determined by IgG staining and FITC-Dextran injection. Functional recovery, assessed by a 5-item Neuroscore, was also significantly improved. In conclusion, inhibition of α
5
β
1
by ATN-161 was well tolerated, reduced infarct volume, and improved behavioral recovery. Additional studies showed this result was likely due to reduced BBB permeability through the TJ claudin-5. Therefore, inhibition of α
5
β
1
with ATN-161 could represent a novel therapeutic approach for stroke worthy of further investigation.
Abstract TMP30: Activation of Neuronal NMDA Receptors After Ischemia as Signal to Trigger Neuronal Il-4 Production: Role in Microglia Polarization
Authors: Ting Shun-Ming , Zhao Xiurong , Sun Guanghua , Mobley Alexis S , Zheng Xueping , Aronowski Jaroslaw
Published: October 2018

After cerebral ischemia, the loss of blood supply triggers a series of pathological changes known as ischemic cascades. One of the key components of this cascade is excitotoxicity, triggered by the excessive extracellular glutamate level, overactivation of N-methyl-D-aspartate (NMDA)-glutamate subtype receptor, calcium overload and neuronal injury. Another component of this cascade is microglia (MΦ) over-activation with harmful pro-inflammatory responses. Recent studies from our group suggest that the viable neurons in the ischemic penumbra produce and release anti-inflammatory IL-4. This neuron-derived IL-4 could act as a signal to local MΦ to prevent their over-activation and to enhance their reparative phenotype. In this study, we investigated the mechanisms underlying IL-4 production and release by neurons under the sublethal ischemia and how this process may affect MΦ. By using an
in vitro
ischemic injury model (oxygen glucose deprivation, OGD) in rat primary cortical neurons, we showed that only a brief transient OGD that causes minimal injury (LDH release assay), rapidly induced neuronal IL-4 (mRNA and protein) production lasting for 6-24h after reperfusion. To elucidate what aspect of OGD triggers IL-4 production/release, we exposed neurons to different insults and found that 50μM glutamate (dose causing no to mild injury), via NMDA receptor (effect reversed by NMDA, but no Kainate or AMPA antagonists), is optimal for induction of IL-4 production and release. NMDA at a low 50μM dose reproduced this effect. D-serine, an agonist to the glycine binding site on the NMDA receptor, enhanced the IL-4 release, but not mRNA expression. A role of downstream calcineurin and NFAT in transcriptional regulation of IL-4 synthesis is investigated. Finally, conditioned media from OGD- or sublethal dose of NMDA-treated neurons was capable of polarizing MΦ toward an anti-inflammatory” and phagocytic phenotype, without inducing MΦ proliferation. For the first time, this study demonstrate that ischemia-induced excitatory transmission may have important task in regulating microglia phenotype through IL-4/IL-4R signaling. This cross-talk between neurons and microglia through IL-4 could be a potential therapeutic target for ischemic stroke.
Abstract TMP32: Ischemic Stroke Causes Vascular Regression in Type-II Diabetic Male Rats: Potential Role of Regulated Cell Death Mechanisms
Authors: Abdul Yasir , Li Weiguo , Ward Rebecca , Hafez Sherif , Abdelsaid Mohammed , Dong Guangkuo , Fagan Susan , Ergul Adviye
Published: October 2018

Diabetes not only increases the risk of stroke, it also worsens recovery after stroke. We previously showed that ischemic stroke causes cerebral vasoregression that is associated with poor outcomes in a lean model of diabetes. Current experiments were designed to 1) study the effect of ischemic stroke on cerebral vasculature in male and female rats using a diet-induced model of diabetes, and 2) identify mechanisms involved in vascular regression.

Methods:
Diabetes was induced in male and female Wistar rats using high fat diet and low dose of streptozotocin. After 8 weeks of diabetes animals were subjected to embolic stroke or sham surgeries. After 14 days of stroke, vascular indices (vascular volume, surface area and branch density) were measured in cortex and striatum of both hemispheres using confocal images of FITC filled brain sections. Regulated cell death markers (necroptosis and ferroptosis) were tested in brain sections by immunohistochemistry.

Results:
In male animals, diabetes alone promoted pathological vascularization. There was an interaction such that stroke increased vascular volume and branch density in control rats while decreasing it in diabetes in both ipsilateral and contralateral side. However, in females, diabetes did not impact vascularization with the exception that branch density was decreased in ipsilateral cortex. Cell death markers of necroptosis (TLR-4) and ferroptosis (IREB2, citrate synthase) were upregulated in male diabetic animals.

Conclusions:
Ischemic stroke impairs cerebral vasculature in diabetic male animals and it was associated with upregulation of newly described regulated cell death pathways.
Abstract TMP34: Effects of Exercise Training on Splenocytes and Recovery in a Stroke Model
Authors: Yang Bing , Nghiem Duyen M , xi Xiaopei , Aronowski Jaroslaw , Savitz Sean
Published: October 2018

Background:
Exercise training increases brain-derived neurotrophic factors associated with stroke recovery. However, exercise training, as a stressful stimulus, might lead to spleen contraction, and affect peripheral immune responses to impact stroke recovery.

Methods:
48 C57 male adult mice were subjected to middle cerebral artery occlusion (MCAo) for 60 mins. 3 days later, they were randomly divided into two groups: 1) placed on running wheel for 20 mins daily up to 2 weeks after MCAo (RW) 2) standard housing without running wheel (no-RW). At day 5 and 7 after MCAo, the spleen and the brain were harvested. Spleen mass, splenocytes and microglia were analyzed. In another experiment, circling and corner testing were performed as neuro-functional evaluations up to 3 weeks after MCAo.

Results:
At day 5, compared to no-RW group, RW mice have smaller ratio of spleen weight to body weight (2.0±0.4 vs.2.6±0.4, p=0.10) but higher CD3/CD8 T-cells (13.3%±2.3 vs. 8.3%±4.0, p=0.15), and significant higher neutrophils (CD11b
+
/Ly6C
low
/Ly6G
+
cells) (2.5%±0.2 vs.1.8%±0.2, p=0.02). In the brain, RW mice have higher CD11b
+
cells (26.3%±3.7% vs. 17.6%±5.0, p=0.07). At day 7, compared to no-RW group, RW did not change the spleen mass, CD3/CD8 T-cells and neutrophils, but decreased inflammatory monocytes (CD11b
+
/CD11c
-
/Ly6C
high
/Ly6G
-
) (0.13%±0.06 vs. 0.24%±0.04%, p=0.09) in the spleen. In the brain, although RW did not change the total CD11b
+
level, RW decreased the ratio of CD11b
+
/CD45
low
to CD11b
+
/CD45
high
cells compared to no-RW group (7.7±0.7 vs. 11±2.6, p=0.08). Furthermore, on the corner test, RW group delayed the spontaneous recovery compared to no-RW group.

Conclusion:
Exercise training in the early phase after stroke may affect the spleen, which may in turn to affect stroke recovery. The intensity and time window of exercise training after stroke needs to be further investigated from the perspective of exercise effects on the spleen and the peripheral immune responses.
Abstract TMP36: Sex Differences in Neutrophil-T Cell Immune Responses and Outcome After Ischemic Stroke in Aged Mice
Authors: Ahnstedt Hilda , Patrizz Anthony , Roy-O’Reilly Meaghan , Spychala Monica , Bravo Alegria Javiera , Chauhan Anjali , McCullough Louise D
Published: October 2018

Introduction:
Sex differences in ischemic stroke are seen in clinical and experimental studies. Men have a higher risk of stroke throughout most of the life-span. Women have greater stroke mortality than men, however a recent multi-continental meta-analysis showed lower mortality in women when adjusted for age, pre-morbid function, stroke severity and other confounding factors. In experimental models, middle-aged female mice have larger strokes, likely due to the loss of estrogen. Less is known about outcomes in very aged animals.

Hypothesis:
Inflammatory responses are key determinants of stroke outcome and there are important sex differences in the immune response in aged mice.

Methods:
Male and female C57BL/6 mice (21-22 months) were subjected to 60 min middle cerebral artery occlusion (n=28-32), or sham surgery (n=16). Neutrophils and T cells were quantified in brain and blood at 24 h and 15 days post-stroke by flow cytometry. Functional outcomes were assessed at day 3, 7 and 14.

Results:
Male mortality was significantly higher than in females (41% vs 16%, P<0.05). Hemorrhagic transformation was seen in 55% of the males that died (6/11) and in none of the females (0/4). Aged males had greater stroke-induced loss of body temperature, splenic contraction and gut permeability (FITC-dextran assay, n=6-7, P<0.05). Acutely after stroke (24 h), aged males had significantly higher brain infiltration of neutrophils and plasma levels of MCP-1 and G-CSF compared to females. Aged males had elevated levels of CD8
+
T cells in the blood compared to females at day 15 (73±5% of CD3
+
T cells vs 52±3%, P<0.001). Brain T regulatory cells were increased after stroke in males (P<0.01), but not in females. Open-field test showed decreased center visits after stroke at day 3, however males spent more time immobile (P<0.01), indicating decreased locomotor activity/anxiety. This difference equalized at 7 and 14 days post-stroke.

Conclusion:
Higher mortality and hemorrhagic transformation rates were seen in aged males compared to females after ischemic stroke. This was associated with higher levels of neutrophils/Tregs in the brain and CD8
+
T cells in the blood suggesting a greater stroke-induced immune response in aged males.
Abstract TMP38: Comorbidities Drive Chronic Post-Stroke Fatigue
Authors: Chen Karen , Marsh Elisabeth B
Published: October 2018

Introduction:
Post-stroke fatigue (PSF) is a debilitating part of stroke recovery with long-term effects. Risk factors contributing to PSF, whether they are modifiable, and if they change over time remain understudied. In this study, we determine factors associated with PSF and how they evolve from the subacute to chronic phase of recovery.

Methods:
A consecutive series of patients presenting to our urban tertiary referral comprehensive stroke center with acute ischemic stroke were seen in follow-up 2-3 months post-event and given the Functional Assessment of Chronic Illness (FACIT) to evaluate for PSF. It was re-administered via telephone 1-2 years post-infarct. Demographics, stroke characteristics (NIH Stroke Scale (NIHSS), size and location of infarct), medical comorbidities, and outcomes (modified Rankin scale (mRS)) were also evaluated. Regression analyses were used to determine factors associated with PSF at each time point.

Results:
108 patients were seen in follow-up a mean 2 months post-stroke, 59 of whom were reached by phone a mean 21 months post-event. The characteristics of those reached were similar to those not reached. Stroke attributes such as follow-up NIHSS (p=.035) and mRS (p<.001) were associated with lower FACIT scores in the subacute setting, while comorbid medical conditions including chronic obstructive pulmonary disease (COPD, p=.038) and body mass index (p=.020) were associated with chronic PSF. Anxiety was associated with PSF both subacutely (p<.001) and chronically (p=.002).

Conclusions:
PSF in the subacute period appears to be due to stroke characteristics (most notably stroke severity), while chronic fatigue occurs in the setting of other comorbid medical conditions such as obesity and COPD. This has significant clinical implications when considering both patients at risk for PSF and potential treatments, which appear to differ significantly between different recovery time points.
Abstract TMP4: Hemorrhage and Reocclusion Rates in Stroke Patients on Antiplatelets Treated With Mechanical Thrombectomy
Authors: Peabody Taylor K , Pride Glenn L , Froehler Michael T
Published: October 2018

Introduction:
The aim of this study was to characterize the impact of both pre-stroke antiplatelet therapy and post-procedure administration on patients who underwent mechanical thrombectomy alone or in combination with IV tissue plasminogen activator (tPA). We hypothesized that antiplatelets may reduce the reocclusion rate for patients treated with mechanical thrombectomy and confer less hemorrhagic risk when tPA is not used.

Methods:
We identified patients from two comprehensive stroke centers who (1) were diagnosed with acute ischemic stroke due to large vessel occlusion, (2) underwent mechanical thrombectomy, and (3) were at least 18 years old. Along with antiplatelet use, we recorded incidence of hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and reocclusion, using univariate analyses to determine predictors for each outcome. Additionally, we used logistic regression to compare the timing of post-stroke antiplatelet administration with HT and 90-day modified Rankin score (mRS).

Results:
A total of 216 patients met our criteria. There were 91 patients with HT, 18 with sICH, and 19 with reocclusion. We found an increased risk of sICH among patients on prior aspirin monotherapy (p=0.02; odds ratio 3.02, 95%CI 1.13-8.03) and those who received intra-arterial tPA (p=0.02; odds ratio 4.33, 95%CI 1.37-13.67). Intra-arterial tPA was also independently associated with an increased reocclusion rate (p=0.02; odds ratio 4.69, 95%CI 1.47-14.94). After stratification based on tPA and prior antiplatelet use, there were no significant differences in outcome between the tPA+AP+, tPA+AP-, tPA-AP+, and tPA-AP- groups. However, patients already taking antiplatelets who received tPA were more likely to experience sICH than patients on pre-stroke antiplatelets or tPA alone (21% vs. 6.5% and 6.7%, p=0.11).

Conclusions:
Acute stroke patients on antiplatelets who receive tPA prior to mechanical thrombectomy are at higher risk for sICH than patients who do not receive this combination. Further study is warranted to examine the risk of administering tPA to patients on antiplatelets prior to mechanical thrombectomy.
Abstract TMP44: Neurological Severity and Activities of Daily Life in Patients With Ischemic Stroke at Convalescent Rehabilitation
Authors: Senda Joe , Ito Keiichi , Kotake Tomomitsu , Kanamori Masahiko , Kishimoto Hideo , Katsuno Masahisa , Sobue Gen
Published: October 2018

Background and purpose:
There are discrepancies between neurological severity and activities of daily life (ADL) after stroke. We investigated associations between neurological severity and ADL in patients with ischemic stroke at the convalescent rehabilitation stage. We particularly focused on the condition of leukoaraiosis on magnetic resonance imaging (MRI) and various clinical factors.

Methods:
The participants included 723 patients with ischemic stroke (484 men and 239 women; mean age, 73.2 ± 8.5 years; subtypes, lacunar infarction [n = 54], atherothrombosis [n = 305], artery-to-artery embolism [n = 105], cardiogenic embolism [n = 129], undetermined embolism [n = 93], and uncategorized ischemic stroke [n = 37]) which were transferred from acute care hospitals for inpatient convalescent rehabilitation. Leukoaraiosis was graded according to periventricular hyperintensity (PVH) and deep white matter hyperintensity on MRI. The National Institutes of Health Stroke Scale (NIHSS) was used to measure neurological severity and the Functional Independence Measure (FIM) was used to assess ADL at admission and discharge.

Results:
Multiple regression analysis revealed that total FIM scores were significantly associated with leukoaraiosis as estimated by PVH grade (P = 0.001) and NIHSS score (P < 0.001) both at admission and discharge for all patients, in addition to clinical factors, such as age, history of heart disease, and bilateral infarction lesions. In contrast, multiple regression analysis of NIHSS scores revealed no association with PVH.

Conclusions:
Our study revealed that ADL were associated with the degree of leukoaraiosis as indicated by PVH at the convalescent rehabilitation stage in patients with ischemic stroke. However, neurological severity was not associated with leukoaraiosis, likely because the progression patterns and anatomic backgrounds of PVH affect ADL and rehabilitation outcomes in post ischemic stroke.
Abstract TMP53: Risk Profile of Stroke Among Young Africans: Evidence From the SIREN Study
Authors: Owolabi Mayowa O , Sarfo Fred , Ovbiagele Bruce , Gebregziabher Mulugeta , Akpa Onoja M , Wahab Kolawole
Published: October 2018

Background:
Compared with High-Income Countries, stroke in low and middle income countries affects a young and productive age group. Yet, data on risk factors and phenotypic characteristics of stroke in the young are sorely lacking from these regions severely challenging efforts at stroke prevention.

Objective:
To identify and quantify the unique traditional and emerging risk factors for stroke among young Africans defined as stroke occurring at age <50years old.

Methods:
Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Nigeria and Ghana. Cases included adults aged >18 years with CT/MRI confirmed stroke. Controls were age-and-gender matched stroke-free adults recruited from the communities in catchment areas of cases. Comprehensive data were collected using standard instruments. We used conditional logistic regression to estimate odds ratios (OR) and population attributable risks (PAR) with 95% CIs.

Results:
515 (24.3%) out of 2,118 cases enrolled were <50 years old. The mean ages of case-control pairs <50 years were 41.0±6.6 and 40.1 ± 6.5 years respectively. Hemorrhagic stroke constituted 52.5%. of the 8 topmost modifiable risk factors for stroke in descending order of PAR were higher educational attainment: (3.98, 1.09-14.46;) hypertension: (31.8, 11.3-88.98 ), dyslipidemia (2.76, 1.33-5.69; ), elevated waist-to-hip ratio:(2.16, 1.00-4.70), stress(2.39, 1.05-5.44), diabetes mellitus :(5.50, 1.93-15.48; 11.9%), cardiac disease(7.67, 1.75-33.60), while green leafy vegetable consumption:(0.32,0.14-0.73) was protective.

Interpretation:
Cardio-metabolic factors are the key determinants of stroke risk among young Africans. Hemorrhagic stroke frequency is particularly striking in this population. Evidence-based, culturally tailored, interventions targeting these factors are urgently required to curtail the rising burden of stroke among young Africans.

Funding:
U54-HG007479
Abstract TMP57: Left Atrial Dilatation: A Cohort Analysis With Strong Implications for Future Atrial Fibrillation and Stroke Monitoring
Authors: Affan Muhammad , Modi Sumul , Smoot Tom , Schultz Lonni , Mahajan Abhimanyu , Miller Daniel
Published: October 2018

Introduction:
Atrial fibrillation (AF) increases the risk of thromboembolism five-fold. Left atrial dilatation (LAD) is a known predictor of AF. It is necessary to better understand the association of LAD, AF and stroke to determine if screening with cardiac monitoring as a prevention measure for stroke is potentially warranted in patients with LAD and no history of cryptogenic stroke.

Aim:
To evaluate the high risk association of LAD on routine echocardiography with AF and stroke.

Methods:
A retrospective review of all patients with an echocardiogram performed within Henry Ford Health System from Mar 6th to Sept 6th 2016 was conducted. Patients were categorized based on the degree of LAD (mild, moderate and severe). Chi-squared tests and two-sample t-tests were used to compare characteristics and multivariate logistic regression analyses were done with AF and stroke as outcomes in two separate models adjusting for the exposure variables.

Results:
From a total of 8679 patients, 54% were female and 41% were African American. The mean age was 64.9 years (SD=16.9). Patients were divided into normal LA size (55%), mild LAD (15%), moderate LAD (12%) and severe LAD (18%). Patients with any LAD were older (70.7±15.0 vs 60.1±17.0 p<0.001), had higher prevalence of AF (36% vs 11% p<0.001), stroke (21% vs 16%, p<0.001) and CHADS2Vasc scores (2.9 ± 1.9 vs 4.0± 1.9 p<0.001). In multivariate analysis, AF was more common in any LAD compared to normal (OR 2.51 CI 2.15-2.93 p<0.001). The odds of AF increased significantly with LAD severity (Mild 1.8, Moderate 2.0 and Severe 3.7). There was no significant association between LAD and stroke in the multivariate analyses (OR 0.97 CI 0.85-1.11, p=0.69). Female gender (OR 0.60, p<0.001) and African American race (OR 0.54, p<0.001) were protective against AF, although not against stroke which was increased in African Americans (OR 1.42, p<0.001).

Conclusion:
Left atrial dilatation is commonly found on routine echocardiography and AF is established in only one-third of those patients. Structural LAD represents a significant marker for AF, although many patients with LAD are yet to be diagnosed with AF. Left atrial dilatation is an attractive high risk marker for occult AF that may warrant prolonged cardiac monitoring for primary identification of AF.
Abstract TMP58: Is Lactate Dehydrogenase Level a Biomarker of Ischemic Stroke in Ventricular Assist Device?
Authors: Hassett Catherine , Cho Sung-Min , Rice Cory , Starling Randall , Uchino Ken
Published: October 2018

Introduction:
Lactate dehydrogenase (LDH) is used as a biomarker of pump thrombosis in patients with left ventricular assist device (LVAD). The relationship of LDH level to ischemic stroke remains unclear. We aimed to explore the relationship of LDH as a marker for LVAD-associated ischemic stroke.

Methods:
We reviewed consecutive patients with ischemic stroke in a prospectively collected data of LVAD patients in a single, tertiary center from October 2004 to December 2016. LDH values from various time points were collected: at the time of stroke, and 1, 3, and 6-month (± 2 weeks) prior as controls. The clinical reference used for LDH’s normal range was 110 - 200 U/L. Pump thrombosis was diagnosed by isolated power elevations, LDH rise, evidence of hemolysis, and new heart failure symptoms as defined by the International Society for Heart and Lung Transplantation. The LDH levels were compared using Rank Sum test.

Results:
Of 477 persons with LVAD, 61 (12.7%) developed ischemic stroke within a median of 143.5 days (Interquartile range [IQR] 10.5 - 410.2) from implantation to stroke event. Nineteen of 61 patients were diagnosed with pump thrombosis at the time of ischemic stroke. The LDH was significantly higher at the time of ischemic stroke with a median level of 500 [IQR 279 - 958] than at 6 months prior to stroke (median 294 [IQR 247 - 380], p= 0.001) or at 3 months prior to stroke (median 316 [IQR 270 - 420], p = 0.01), but not compared to those at 1 month prior to stroke (406 [IQR 228 -749], p= 0.28) (Figure).

Conclusion:
Elevated LDH may not only be indicative of pump thrombosis but may start to rise before stroke occurrence and might serve as a risk marker for ischemic stroke.
Abstract TMP61: Acute Ischemic Stroke Emergency Department Arrival Times in the Extended Time Window Within a Population
Authors: Kleindorfer Dawn O , Moomaw Charles J , Alwell Kathleen , Khatri Pooja , Woo Daniel , Flaherty Matthew L , Adeoye Opeolu , Martini Sharyl , Mackey Jason , De Los Rios La Rosa Felipe , Ferioli Simona , Kissela Brett M
Published: October 2018

Introduction:
With the recent positive clinical trial extending the time window for endovascular therapy out to 24 hours, we sought to describe the arrival times of acute ischemic stroke patients within the 6-24 hour time frame within a large biracial population representative of the US in terms of % black, age, and socioeconomic indicators.

Methods:
We identified all ischemic stroke (IS) cases by screening all local hospital ICD-9 codes 430-436 among residents of the Greater Cincinnati/Northern Kentucky Stroke Study region, a biracial population of 1.3 million in 2010. Study nurses abstracted relevant information from the medical record, including symptom onset and ED arrival times, and all potential cases were physician reviewed. Arrival time was defined as the elapsed time between symptom onset time (either the witnessed onset time, or time last seen normal) and time of ED arrival. Only cases presenting to an ED were included in this analysis. Student’s t-test and Wilcoxon rank sum tests were used as appropriate.

Results:
In 2010, there were 1980 IS cases presenting to a local emergency department, who were 21.3% black, 55.1% female, with a median age of 69.4 (SD 14.9). See Figure for distribution of arrival times. Patients arriving > 6 hours were significantly younger (age 68.8 vs. 70.7, p=0.007), more frequently female (56.6% vs. 52.0%, p = 0.05) and had less severe infarcts (NIHSS median (IQR) was 3 (1-6) vs. 4 (1-11), p<0.0001), compared to those arriving </= 6 hrs. No significant differences by race or baseline disability were observed.

Discussion:
In our population, inclusion of 6-24hr ED arrival times allows 34% more of our ischemic stroke population to be arriving within a timeframe of possible intervention/reperfusion therapy. Further exploration of eligibility criteria, in addition to time, for extended time-window embolectomy within a population is needed to assist centers as they change their systems of care.
Abstract TMP62: Initial Neutrophil-Lymphocyte Ratio Predicts Ischemic Stroke Outcomes After Thrombolytic Therapy
Authors: Malhotra Konark , Sheth Sunil A , McFarland Miesca , Goyal Nitin , Broce Mike , Tsivgoulis Georgios
Published: October 2018

Introduction:
Peripheral leukocyte counts and neutrophil-lymphocyte ratio (NLR) are readily available biomarkers that predict infarct size and mortality in acute ischemic stroke (AIS). Prognostic value of NLR in AIS patients treated with intravenous thrombolysis (IVT) remains to be determined.

Methods:
Data on consecutive AIS patients who received intravenous thrombolysis (IVT) was prospectively evaluated during a five-year period. NLR was determined within 12-hours of admission. Receiver operating characteristic and area under curve (AUC) values were used to obtain optimal NLR cutpoints, and predict functional outcomes: discharge disposition, functional independence (FI) [mRS 0-2], functional dependence (mRS 3-5), and mortality at discharge and 3 months.

Results:
Among 144 consecutive IVT-treated AIS patients, mean age was 70±13, 50% were female and median NIHSS was 12 [IQR 9-18]. In univariate analysis, lower NLR suggested association with FI (3.11±2.56 vs. 4.29±3.64, p=0.07). Optimal NLR cutpoints for FI and mortality were 3.6 (C-statistic [AUC] 0.63; 95CI 0.52-0.73) and 6.5 (C-statistic [AUC] 0.63; 95CI 0.45-0.82) respectively (Figure). In multivariate analysis after adjusting for age and NIHSS, NLR≤3.6 was a strong predictor for FI at discharge (OR: 4.1; 95CI 1.49-11.27; p=0.006), while NLR≥6.5 was an excellent predictor for mortality (OR 10.06; 95CI 2.51-40.31; p=0.001). Half of the patients with NLR≤3.6 were discharged home, in contrast to half with NLR≥6.5 discharged to either hospice or died (p=0.04).

Conclusions:
Initial NLR is a relevant biomarker for risk stratification and prediction of functional outcomes in AIS patients while evaluating for thrombolytic therapy. Elevated NLR likely reflects immune dysregulation and portends poor post-stroke outcomes.
Abstract TMP64: Appropriateness of Hemorrhagic Stroke Destination Facilities in Severity-Based Triage Algorithms for Emergency Medical Services
Authors: Dozois Adeline , Hampton Lorrie , Kingston Carlene , Lambert Gwen , Porcelli Tom , Sorenson Denise , Templin Megan , Asimos Andrew W
Published: October 2018

Background:
Severity-based prehospital stroke triage protocols aim to identify patients with large vessel occlusion (LVO) acute ischemic strokes (AIS) who should be transported directly to comprehensive stroke centers (CSCs). Whether or not hemorrhagic stroke patients should be included in the stroke population targeted for direct routing to CSCs is unclear. We hypothesized that a majority of patients with hemorrhagic strokes who were initially transported to the ED of non-CSCs would be immediately transferred to CSCs for admission.

Methods:
We conducted a cross-sectional study of suspected stroke patients transported by our county’s EMS agency from December 2015 – October 2016. We categorized patient’s initial EMS destination facility as CSC or non-CSC, and determined if, after emergency department (ED) evaluation, patients were transferred to a CSC for admission. We determined acute stroke diagnoses from medical record review.

Results:
Among 2,402 EMS patients screened for stroke, 777 (32%) had a diagnosis consistent with acute stroke, of whom 10.9% (n=85) had an intracranial hemorrhage (ICH) and 2.1% (n=16) had a subarachnoid hemorrhage (SAH). Among all stroke patients, 51% (95% CI 48-55%) were initially transported to a non-CSC, including 42% (95% CI 32-54%) of all ICH and 38% (95% CI 15-65%) of all SAH patients. Among the ICH and SAH patients initially evaluated at a non-CSCs, 86% (95% CI 71-95%) were transferred to a CSC for admission. N
o
SAH or ICH patients initially transported to a CSC were transferred to another facility for admission.

Conclusions:
In our metropolitan region, most hemorrhagic stroke patients initially transported by EMS to non-CSCs are transferred to CSCs for admission after their ED evaluation. These data suggest that when determining acceptable rates of over- and under-triage in severity-based stroke triage algorithms for EMS, hemorrhagic stroke patients should be included, along with LVO AIS patients, in the population considered appropriate for initial transport to a CSC.