bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W MP5: Successful Revascularization in Octogenarians with Acute Ischemic Stroke Predicts Good 90-day Outcomes
Authors: Moftakhar Parham , Bakhtmand Armita , Tolley Ursula , Sachdev Harmeet , Guisado Raul , Padidar Arash , Malek Reza
Published: March 2022

Background:
Octogenarians represent one of the fastest growing populations in the US. Yet, limited data exists about endovascular therapy in this population because of the tendency not to treat this population too aggressively. We present the largest single group experience of multimodal endovascular treatment of ischemic stroke in patients ≥80 years.

Methods:
Retrospective review of our neurointerventional database was conducted to include patients age ≥80 years treated with endovascular therapy from 2008 to 2014. Seventy patients were identified (42 females, average age 84 years, range 80-93). Recanalization was assessed by the TICI grade (0-3). Outcomes were assessed by the 90-day mRS.

Results:
Fifteen (21%) patients received IA TPA±IV TPA. Thirty-one(44%) received IA TPA/older thrombectomy devices(Merci or Penumbra)±IV TPA. Twenty-four were treated with stent retrievers±IV/IA TPA. Prior to introduction of stent retrievers, 29/46(63%) achieved successful revascularization (TICI 2b or 3) versus 22/24(92%) after introduction of stent retrievers (p=.01). An improvement in the NIHSS was seen in 46% of patients at discharge prior to stent retrievers and 67% with stent retrievers(p=0.07). Before stent retrievers 25% had good outcomes (mRS≤2) and 38% had good outcomes with stent retrievers (p=0.2). All patients with good outcomes were successfully recanalized with TICI score of 2B/3. If we could not recanalize patients, none of the patients had good outcomes (patients TICI 0-2A all had poor outcomes or died). Twenty-three (33%) patients died. However, if the patient lived, 27 (61%) patients were independent or needed only minimal assistance (mRS≤3). There were 6 hemorrhagic complications.

Conclusion:
Multimodal endovascular therapy in the treatment of acute ischemic stroke is relatively effective and safe in the elderly, especially with the advent of stent retrievers. If the occluded vessel can be successfully recanalized and the patient survives, they can continue with a good quality of life. Unsuccessful revascularization leads to poor outcomes. This study and other future prospective studies are essential in helping guide families in making difficult treatment decisions about elderly family members.
Abstract W MP51: Insulin-like Growth Factor (igf-1) Enhances The Angiogenic Response Of Aging Endothelial Cells
Authors: Bake Shameena , Dave Jui , Bayless Kayla , Sohrabji Farida
Published: March 2022

Background and Purpose:
IGF-1 is recognized as a neuroprotective agent in ischemic stroke models. Our microRNA profiling and KEGG analysis studies identified brain endothelial cells as principal target of IGF-1 action in post-stroke middle-aged females (Bake et al., PLOS One, 2014). Although IGF-1 is known to promote cell survival, the mode of action on injured brain endothelial survival is poorly understood. The present study specifically tested the hypothesis that IGF-1 prevents cell death and enhances angiogenic response of endothelial cells ex vivo. Additionally, since clinical evidence show that older women are at increased risk for stroke occurrence and greater severity, the present study used middle-aged female rats.

Methods:
Brain microvascular endothelial cells were harvested from acyclic Sprague-Dawley female rats (9-10 mo old). Confluent cultures grown on 24 well plates were exposed to hypoxia (1%O2) in glucose free media for 6h with and without IGF-1 (10ng/ml), followed by re-oxygenation in growth media. Cell death was analyzed by LDH assay in media. For invasion analysis, cells were suspended in media supplemented with VEGF, FGF and reduced serum and were plated onto 96 well plates containing collagen matrix with 1um sphingosine-1-phosphate. Cells were treated as before for hypoxia/aglycemia with and without IGF-1. Gels were fixed (3% glutaraldehyde), stained (toluidine blue in 30% methanol) and sectioned (1mm slices). Invasion density was quantified using Olympus CK2 inverted microscope.

Results:
Hypoxia resulted in 2-fold increase in media LDH, however, IGF-1 did not alter LDH levels after hypoxia or hypoxia/re-oxygenation, indicating that the peptide does not regulate ischemic cell death in the short-term. However, IGF-1 treatment resulted in a 50% increase in the number of sprouting endothelial cells after hypoxia/re-oxygenation (p<0.05), as compared to the vehicle treated group.

Conclusions:
These findings support the hypothesis that endothelial cells are target for IGF-1-induced stroke neuroprotection and that IGF-1 promotes angiogenic capacity in aging endothelial cells.
Abstract W MP54: Increased Collisions and Errors at Intersections During Simulated Driving in Patients after Aneurysmal Subarachnoid Hemorrhage
Authors: Vesely Kristin A , Hird Megan A , Manoel Airton Leonardo de Oliveira , Macdonald R. Loch , Schweizer Tom A
Published: March 2022

Introduction:
It is well established that cognitive and functional impairments persist despite good clinical outcomes in patients who suffer aneurysmal subarachnoid hemorrhage (aSAH). The impact of these impairments on real-world tasks such as driving a motor vehicle is currently unclear. This study aimed to investigate driving ability of aSAH patients using a driving simulator. We hypothesized that patients would exhibit more driving errors during the most cognitively demanding aspects, particularly while executing left turns at busy intersections, where the driver must quickly integrate many complex and dynamic visual stimuli to make a rapid decision and turn safely.

Methods:
Nine functionally independent aSAH patients (>3 months post-ictus) and nine healthy control participants matched for age (patients: 58±13; controls: 59±14, p > 0.05) completed two driving scenarios (STISIM). The total number of errors committed and errors associated with intersections were compared between groups. Errors included collisions, speeding, centerline crossings, road edge excursions, stop signs missed and traffic light tickets.

Results:
The mean number of total errors did not differ between the patient and control groups (28 versus 22, p > 0.05); however, patients committed a greater number of hazardous errors, including collisions (2.4 versus 0.1, p < 0.05) and road edge excursions (3.7 versus 0.3, p < 0.01), than controls. Total errors at intersection turns were greater for patients (7.7 versus 3.2, p < 0.05). When stratified by type of turn, patients experienced more errors than controls during left turns (1.6 versus 0.2, p < 0.01) and left turns with oncoming traffic (2.3 versus 0.8, p < 0.05) but not during right turns (3.8 versus 2.2, p > 0.05).

Conclusion:
Our results suggest probable driving impairment in some aSAH patients during more difficult aspects of driving, such as making left turns at a busy intersection, which is where most real-world accidents occur. This analysis was limited by a small sample, and further research should explore the clinical and cognitive correlates of driving ability in a large sample of aSAH patients.
Abstract W MP56: Corticospinal Tract Injury And Motor Impairment After Stroke
Authors: Tran George , Quinlan Erin B , Cramer Steven C
Published: March 2022

INTRODUCTION:
Restorative therapies improve outcomes by promoting plasticity in specific neural systems. Imaging biomarkers may provide a useful measure of injury to these systems and so might help determine if a patient has sufficient substrate remaining to derive therapeutic benefit. The pyramidal system is affected in most patients with stroke and has features useful for biomarker testing, especially the anatomy of the corticospinal tract (CST) in the cerebral peduncle (CP). The current study compared clinical performance of 3 published metrics of CST injury.

METHODS:
Patients with stable motor deficits 3-24 months after stroke were enrolled in 1 of 2 trials that provided 3-4 weeks of arm motor therapy. From baseline MRI, ipsilesional CST [1] white matter integrity (DTI FA in CP), [2] atrophy (CP area), and [3] extent of injury (% lesion overlap with stroke) were measured and compared to Fugl-Meyer (FM) score at baseline, as well as change in FM score across treatment.

RESULTS:
The 47 patients had substantial baseline motor deficits (FM= 36±14), medium-sized infarcts (30±45cc), and were 5±2.5 mo post-stroke. Baseline motor deficits were related to CST white matter integrity (r=0.49, p=0.0005) more than to % CST injured (r=-0.40, p=0.006). On the other hand, treatment-related motor gains were related only to % CST injured (r=-0.45, p=0.002). A global injury measure (total infarct volume) was weaker than CST injury in correlating with FM scores. None of the 3 CST injury measures were correlated.

CONCLUSIONS:
The CST injury characteristics related to motor outcome are different from the CST injury characteristics that predict capacity for improvement with therapy. In both cases, these measures did not explain the majority of variance in motor status/improvement, emphasizing that many factors in addition to CST injury are important to motor outcome after stroke. The finding that motor gains are related to % CST injured but not CST integrity provides insights into the neurobiology of brain repair in humans.
Abstract W MP58: High Intensity Interval Training May Be Superior to Moderate Intensity Continuous Exercise in Chronic Stroke
Authors: Boyne Pierce , Dunning Kari , Carl Daniel , Khoury Jane C , Gerson Myron , Rockwell Bradley , Buhr Sarah , Keaton Gabriella , Westover Jennifer , Barney Brian , Wilkerson John , Kissela Brett
Published: March 2022

Introduction:
Aerobic deconditioning is a major barrier to stroke recovery. Post stroke guidelines recommend moderate intensity continuous exercise (MICE) to improve aerobic fitness and mobility. High-intensity interval training (HIT) has been shown to be more effective than MICE for improving aerobic fitness among healthy adults and persons with heart disease. However, no previous study has compared HIT and MICE among persons with stroke. We hypothesized that HIT would elicit significantly greater improvement in both aerobic fitness and gait function relative to MICE in this population.

Methods:
Fourteen subjects (mean ± SD age, 58 ± 10 years; years post stroke, 4.3 ± 2.9) were randomized to HIT (n=11) or MICE (n=5); each 25 min, 3x/week for 4 weeks. HIT involved repeated 30 sec bursts of treadmill (TM) gait at maximum tolerated speed (based on gait stability), alternated with 30-60 sec rest periods. MICE involved continuous TM gait at 45-50% heart rate reserve. Outcomes were measured by a blinded rater before and after intervention, including peak oxygen uptake and ventilatory threshold during graded exercise testing, energy cost of gait, 10m walk test (comfortable and fastest speeds) and TM speed (comfortable and fastest). Mixed effects models tested for significant (p<0.05) differences over time within groups and between the groups. Standardized effect sizes were also calculated.

Results:
In the HIT group, significant improvement was found for all outcomes save peak oxygen uptake. No significant differences were found in the MICE group. Ventilatory threshold and fastest TM speed improved significantly more in HIT compared to MICE and moderate to large effect sizes were found for all outcomes.

Conclusion:
HIT is a potent intervention for improving aerobic fitness and gait function in chronic stroke that appears to be more effective than MICE. Further study with a larger sample is warranted.
Abstract W MP59: Thyroid Hormones And Functional Outcomes After Ischemic Stroke
Authors: O'Keefe Lena M , Doran Sarah J , Czap Alexandra , Benashski Sharon , Staff Ilene , McCullough Louise D
Published: March 2022

Background:
Hypothyroidism can lead to hypertension, hypercholesterolemia, and cardiac dysfunction, which are risk factors for stroke. Activity of the hypothalamic-pituitary-thyroid axis may contribute to functional stroke outcomes. Low levels of thyroid stimulating hormone (TSH) correlate with an increased risk of ischemic stroke. However, once a stroke occurs, hypothyroidism is associated with more favorable outcomes. It is well known that thyroid hormone levels drop rapidly in critically ill patients (“sick-euthryoid” syndrome), which may be prevented by the exogenous thyroid replacement provided to hypothyroid patients. We directly assessed thyroid function with measurements of TSH, free T3 (fT3) and free T4 (fT4) in patients with ischemic stroke and evaluated acute and long-term outcomes.

Methods:
Blood was collected prospectively from patients with radiologically confirmed ischemic stroke (AIS) (n=136) 24 hours after symptom onset. Serum levels of TSH, fT4, and fT3 were quantified by ELISA. Primary outcomes were in-hospital mortality and admission NIH Stroke Scale (NIHSS). Secondary outcomes were admission to discharge change in NIHSS, modified Barthel Index (mBI) and modified Rankin score (mRs) at 3 and 12 months (mo), and mortality at 3 and 12 mo.

Results:
AIS patients show a negative correlation in fT3 with age (r=-.332,
p<0.01
). AIS patients with a higher pre-stroke mRS had higher levels of fT3, and fT4 ,
p=0.01, p=0.03
). Patients that died or went to hospice had significantly lower levels of fT3 and TSH (1.99pg/ml (1.75-2.48), 0.52 pg/ml (0.30-0.76)).TSH levels were lower in AIS patients with worsened NIHSS (0.72 pg/ml (0.36-1.12)). Higher fT3 levels were significantly associated with better mRS and mBI at 3 and 12 mo (
p=0.01, p=0.01, p=0.03, p=0.02
), whereas lower levels of TSH were significant for worse mRS at 3mo (0.87pg/ml (0.59-1.48)).

Conclusion:
While higher levels of fT3 correlate with stroke risk factors, high fT3 is seen in patients with better functional outcome at 3 and 12mo post-stroke. Ischemic stroke patients with low TSH levels at 24 hrs have higher mortality. Thus, monitoring the hypothalamus-pituitary-thyroid axis during acute stroke may improve long-term stroke outcomes.
Abstract W MP68: Brain Arterial Diameters and Risk of Vascular Events
Authors: Gutierrez Jose , Cheung Ken , Bagci Ahmet , Cespedes Sandino , DeRosa Janet , Rundek Tatjana , Alperin Noam , Sacco Ralph , Wright Clinton , Elkind Mitchell
Published: March 2022

Objective:
Inward and outward remodeling of cerebral vessels may represent alternate pathological vascular phenotypes. Our aim was to test whether extremes of brain arterial diameters increase risk of death and vascular events.

Methods:
Cerebral large artery diameters were measured in 1,034 stroke-free participants from Northern Manhattan. Arteries from the Circle of Willis (8) and posterior circulation (5) were measured in regions free of stenosis, adjusted for head size, standardized, and added to create a global measure of diameters in each person. Participants were categorized into the top 5% of the diameter distribution (“outward remodelers”) and bottom 5% (“inward remodelers”), as well as an intermediate referent category (90% of population). We used logistic regression to calculate associations with risk factors and Cox models to calculate risks of outcomes after adjusting for demographic and vascular risk factors.

Results:
Mean follow-up was 5 ± 2 years. Inward remodelers were more likely to be men (OR 3.3, 95%CI 1.8-6.1) and less likely to be hypertensive (OR 0.5, 95%CI 0.3-0.9) or Hispanic (OR 0.3, 95%CI 0.2-0.6), while outward remodelers were more likely to be women (OR 14.6, 95%CI 3.5-60.5) and Hispanic (OR 8.7, 95%CI 1.2-65.0) compared to participants with less extreme diameters. Inward remodelers had a higher risk of death (HR 1.8, 95%CI 1.1-3.0), vascular death (HR 2.8, 95%CI 1.4-5.7), myocardial infarction (HR 2.5, 95%CI 1.0-6.4) and ischemic stroke (HR 3.4, 95%CI 1.0-10.2). Outward remodelers were not at increased risk of death or vascular events. Compared to those with less extreme diameters, risk of cardioembolic stroke was higher among inward remodelers (11.3 vs. 1.4%, HR 13.9, 95%CI 4.4-44.0) while strokes due to large or small artery disease were more frequent in outward remodelers (3.8 vs 1.8 %, HR 3.4, 95%CI 0.7-16.3).

Conclusions:
Individuals with the smallest brain arterial diameters are at greater risk of death, myocardial infarction, and ischemic stroke, while those with the largest brain arterial diameters were not. Cerebral arterial phenotypes might identify people at greater risk of cardiac disease and stroke, and direct targeting of primary preventive measures at likely stroke subtypes.
Abstract W MP7: Good Outcomes After Endovascular Therapy For Ischemic Stroke In Octogenarians Are Consistently Present If Final Infarct Volume Is Less Than 20 Cubic Centimeters
Authors: Giurgiutiu Dan-Victor , Jadhav Ashutosh P , Aghaebrahim Amin , Jankowitz Brian T , Ducruet Andrew F , Jovin Tudor G
Published: March 2022

Background and Purpose:
Octogenarians are thought to have uniformly poor outcomes following endovascular therapy for stroke. We sought to verify whether this contention hold true when low final infarct volumes (FIV) are achieved following endovascular reperfusion.

Methods:
Retrospective analysis of an acute stroke endovascular database. Inclusion criteria: age ≥ 80, anterior circulation large vessel occlusion stroke, available outcomes and post procedural MRI allowing for FIV analysis.

Results:
A total of 1298 patients were identified of which 192 (15%) were octogenarians. Of those 95 with available brain MRI and follow up data were included. Baseline: Median age: 83, female: 67%, median admission NIHSS: 16.4, and median time to treatment: 4.7 hours. Occlusion location: M1 in 71 (73%), M2 in 7 (7%), ICA terminus in 17 (17%), and tandem occlusions in 9 (8.8%) of cases. Atrial fibrillation was found in 57% of cases. Median ASPECTS: 9.

Successful recanalization rate (TICI 2b, 3) was achieved in 74%, with a favorable outcome (mRS 0-2) in 23 patients (24%). Median FIV was 38.4 cc (mean 72.2 cc). In patients with favorable outcome, median FIV was 15 cc (interquartile range- IQR 2.4 to 24.5 cc), versus 55.8 cc (IQR 21.1 to 120.5 cc), p=0.0007 in patients with poor outcomes. In 31 patients (32.5%), the FIV was < 20 cc, and of those patients 14 (45%) had a favorable outcome, while only 9 (14%) of patients with FIV > 20 cc achieved favorable outcome, p=0.001. Mean ASPECTS in patients with FIV of < 20 cc was 9.23, versus 8.38 with FIV > 20 cc, p=0.0013.

In multivariate analysis, predictors of good outcome included FIV of < 20 cc (odds ratio (OR) 6.6, 95% CI 1.4-27.1), successful recanalization (OR 15.9, 95% CI 1.4 to 1.9), but not age, admission NIHSS, time to treatment or occlusion location.

Conclusions:
Final infarct volumes of < 20 cc after endovascular acute stroke intervention in octogenarians are associated nearly half of the times with good outcomes while larger final infarcts rarely result in good outcomes. Different baseline infarct thresholds may be necessary when selecting octogenarians vs younger stroke patients for endovascular therapy.
Abstract W MP70: Short and Long-term Risk of Stroke After a Transient Neurological Attack (TNA) versus TIA: Population-based Study
Authors: Gaziano Liam C , Tuna Maria , Li Linxin , Mehta Ziyah , Rothwell Peter M
Published: March 2022

BACKGROUND:
The distinction between a TIA and a transient neurological attack (TNA i.e. a TIA-like event not satisfying the NINDS Criteria for a clinically definite TIA) has important implications for clinical practice. Patients with TIA require intensive long-term secondary prevention of stroke, but there are conflicting estimates of the risk of stroke after TNA.

METHODS:
In a United Kingdom population-based study (Oxford Vascular Study) of all incident and recurrent TNAs and TIAs from 2002-2012, we prospectively classified all first events in the study period as TIAs (based on NINDs criteria) versus TNAs (including isolated transient neurological symptoms not satisfying the NINDS criteria) versus other conditions (migraine aura, epilepsy, etc). Kaplan-Meyer (KM) risk of stroke was determined at 10-years by long term regular face-to-face follow up.

RESULTS:
Among 1648 first events, 594 were NINDS-defined TIAs (mean/SD age= 73.5/13.1 years), 658 were TNAs (67.1/15.5) and 396 were other diagnosis (62.8/18.2). During 8328 person/years of follow-up there were 195 recurrent strokes: 106 in patients with a first TIA, 83 after a TNA and 6 in patients with another diagnosis. The actuarial risk of stroke at 10 years was higher after a TIA than after a TNA (22.9% vs 17.6%, adjusted HR= 1.46, 1.09-1.95, p=0.01), but the risk after a TNA was considerably higher than in patients with other diagnoses (17.6% vs 3.0%, p<0.0001). Rates of use of preventive medication at one-month follow-up in patients with TIA versus TNA were 97.1% vs 75.4% for antithrombotics, 71.4% vs 53.3% for statins, and 72.9% vs 64.1% for antihypertensives. However, medication rates declined more rapidly on longer-term follow-up in patients with TNA versus TIA.

CONCLUSION:
The long-term risk of stroke after a TNA was almost as high as after a strictly-defined TIA, although use of preventive medication was more intensive after TIA. The relatively high risk of stroke in patients with TNA appears to justify detailed investigation and similar levels of intensity of secondary prevention to patients with TIA.
Abstract W MP74: Development And Validation Of A Modified Stroke Thrombolytic Predictive Instrument To Improve Implementation And Ease Of Use
Authors: Kent David M , Ruthazer Robin , Decker Carole , Jones Philip G , Saver Jeffery L , Bluhmki Erich , Spertus John A
Published: March 2022

Introduction:
The Stroke Thombolytic Predictive Instrument (Stroke TPI), derived on data from the first 5 randomized clinical trials of standard dose rtPA, predicts the probability of good and bad outcomes with and without rtPA. We sought to rebuild and externally validate a simpler Stroke TPI to support implementation in routine clinical care.
Methods:
Using a derivation cohort of 1,983 patients from a combined database of randomized clinical trials (NINDS 1 and 2; ATLANTIS A and B; ECASS 2), we simplified the Stroke TPI by: 1) removing lower credibility interaction terms; and 2) exploring reduced stroke severity scores, including previously developed 8-item and 3-item measures. Additionally, we included alternative thresholds of a good 90-day functional outcome (i.e. prediction of both modified Rankin Score [mRS] ≤ 1 and mRS ≤ 2). Bootstrapping methods were used for internal validation. External validation was performed on the ECASS 3 trial (n=821).
Results:
The following 6 variables were included to predict good outcomes: age, systolic blood pressure (SBP), diabetes, stroke severity, symptom onset to treatment time (OTT) and rtPA therapy. Treatment effect modifiers (interaction terms) included OTT and SBP. For the models predicting a bad outcome (mRS ≥ 5), significant variables included: age, stroke severity, and serum glucose. rtPA therapy did not change the risk of a poor outcome. As compared to models using the full NIHSS, models employing the 3-item severity score showed similar discrimination, with c-statistics on bootstrap (internal) validation of: 0.76 (mRS ≤ 1); 0.78 (mRS ≤ 2); and 0.76 (mRS ≥ 5), and with excellent calibration. External validation on ECASS 3 showed similar performance (c-statistics 0.75 [mRS ≤ 1] and 0.80 [mRS ≤ 2]), with good calibration.
Conclusion:
A simpler prediction model using a 3-item, instead of the 15-item NIHSS stroke severity score, has similar prognostic value and may be easier to use in routine care. Future studies are needed to test whether the reduced model can improve treatment rates, time to treatment, and outcomes.
Abstract W MP77: Effects of Emergency Medical Services Stroke Center Routing on Sites of Care and Enrollment in a Prehospital Research Study: The FAST-MAG Experience
Authors: Sanossian Nerses , Liebeskind David S , Starkman Sidney , Eckstein Marc , Stratton Samuel , Pratt Franklin D , Koenig William , Hamilton Scott , Conwit Robin , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: March 2022

Background:
Emergency Medical Services (EMS) routing of acute stroke patients to designated stroke centers has the potential to increase the proportion of patients receiving care at facilities meeting national standards and to augment recruitment rates for prehospital stroke research.

Methods:
We analyzed a prehospital stroke treatment trial dataset to determine the number of patients cared for at certified primary stroke centers (PSC), prehospital care time intervals, and trial enrollment rates prior to and following implementation of a Los Angeles County-wide regional acute stroke care system in November 2009, with preferential routing of likely acute stroke patients, within 2 hours of symptom onset, to designated centers PSC certification. Analyses were performed in the overall study (1/2005 to 12/2012) as well as the period encompassing the year before and after implementation.

Results:
There were 863 subjects enrolled in LA County before and 764 after EMS routing and proportion transported to PSC increased substantially, from 10% prior to 91% following implementation (P<0.001). Routing was associated with a slight decrease in total time from paramedic on-scene to ED arrival, 34.5 minutes (SD 9.1) vs. 33.5 (SD 10.3), p=0.045. When comparing the year before to the year after implementation, enrollment increased by 18.6%, (215 at 44 hospitals vs. 255 at 27 hospitals), and proportion transported to PSC increased from 17% to 88%. During the study, the number of PSCs increased from 1 in 2005 to 28 in 2012, including from 7 to 17 in the year before to the year after EMS routing policy adoption.

Conclusions:
The establishment of a regionalized EMS system of acute stroke care dramatically increased the proportion of acute stroke patients cared for at Primary Stroke Centers, from 1 in 10 to more than 9 in 10, with no increase in prehospital care times, and enhanced recruitment of patients into an ongoing prehospital stroke trial.
Abstract W MP80: Effects of Comprehensive Stroke Care Capabilities on In-hospital Mortality of Patients With Ischemic and Hemorrhagic Stroke: J-ASPECT Study 2010-2013
Authors: Iihara Koji , Nishimura Kunihiro , Kada Akiko , Kamitani Satoru , Nishimura Ataru , Kurogi Ryota , Sayama Tetsuro ,   J-ASPECT Investigators
Published: March 2022

Background:
The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke.

Methods and Results:
Of the 1,369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Among the institutions that responded, data on patients hospitalized for stroke between April 1, 2010 and March 31, 2013 were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality was analyzed using logistic regression analysis adjusted for age, sex, level of consciousness on admission, comorbidities, and the number of fulfilled CSC items (total CSC score). Data from 417 institutions and 21,8579 emergency-hospitalized patients were analyzed. CSC capabilities of the participating hospitals were classified into quintiles (Q1: 2-13, Q2: 14-16, Q3: 17-18, Q4: 19-20, Q5: 21-24). Mortality rates were 4.9% for patients with ischemic stroke, 15% for patients with intracerebral hemorrhage (ICH), and 27% for patients with subarachnoid hemorrhage (SAH). Mortality adjusted for age, sex, hypertension, diabetes mellitus, hyperlipidemia, and level of consciousness was significantly correlated with total CSC scores in patients with ischemic stroke (adjusted OR of Q2-5 compared with that of Q1 as control: 1.06, 0.97, 0.97, 0.88*, respectively, * P<0.01), ICH (adjusted OR of Q2-5 compared with that of Q1 as control: 0.89*, 0.85#, 0.81#, 0.80#, respectively, * P<0.01, #P<0.001) and SAH (adjusted OR of Q2-5 compared with that of Q1 as control: 0.94, 0.96, 0.82*, 0.75#, respectively, * P<0.01,#P<0.001).

Conclusions:
CSC capabilities were associated with reduced in-hospital mortality rates in all types of stroke.
Abstract W MP82: False Negative Results on Acute Stroke Recognition Tool Has No Impact on Stroke Prognosis
Authors: Silva Gisele S , Miranda Renata C , Massaud Rodrigo M , Vacari Andreia M , Cendoroglo Neto Miguel
Published: March 2022

Introduction:
Stroke recognition tools can be useful in expediting stroke care in the acute phase. The Los Angeles Prehospital Stroke Screen (LAPSS) is one such tool, an instrument designed to allow acute stroke identification with high sensitivity and specificity. Conversely, the impact of a negative result can potentially delay stroke recognition and treatment with unknown prognostic consequences. Hypothesis We assessed whether LAPSS status affect acute stroke care and prognosis.

Methods:
We evaluated consecutive patients admitted to a tertiary hospital with acute ischemic stroke from February 2009 to March 2014. All triage nurses from the emergency department were trained in the application of LAPSS, which they documented at hospital arrival on all suspected stroke patients. When LAPSS criteria for stroke were met (LAPSS positive), the stroke code was activated. We used logistic regression analysis to investigate the influence of LAPSS results upon clinical outcome (modified Rankin Scale (mRs) < 3) at discharge.

Results:
We evaluated 415 patients, 82 of whom (19%) had a negative LAPSS. Patients with positive and negative LAPSS had similar time from symptoms onset to hospital arrival. Patients with a negative LAPSS had lower National Institutes of Health Stroke Scale (NIHSS) at admission (7 [3,15] versus 0 [0,0], p<0.01), higher door to neuroimaging (42 [28,51] versus 27 [19, 44] minutes, p=0.02) and door to radiologic report times (54 [36,84] versus 37 [26, 55] minutes, p<0.01), as well as a lower length of stay (5 [2,5] versus 8 [5, 17] days, p<0.01). Only patients with a positive LAPPS (26.9%) received recanalization therapies, either intravenous thrombolysis or endovascular procedures. Age 0.98 [0.96-0.99] p=0.02, NIHSS at admission 0.78[0.73-0.82] p<0.01 and treatment with thrombolysis 2.07 [1.02-2.44] p=0.04 were independent predictors of good clinical outcome (mRS< 3) at discharge, but not LAPSS status.

Conclusion:
In conclusion, patients with negative LAPPS had less severe strokes as compared to those with positive screen. Although time to neuroimaging was longer in patients with negative LAPSS, short term outcome did not seem to be affected by LAPSS status.
Abstract W MP83: Use of Optic Nerve Sheath Diameter in Emergency Department to Predict Stroke Outcome
Authors: Shushrutha Hedna Vishnumurthy , Rastogi Vaibhav , Weeks Emily , Patel Rohit P
Published: March 2022

Introduction:
Elevated intracranial pressure (ICP) reflects long-term neurologic deficit and death in patients with stroke. Deterioration in neurologic exam is an early indicator of increasing ICP, however has limitations enabling accurate detection of elevated ICP due to confounding factors including fluctuations in mental status and sedation/ paralysis as part of the acute management. Optic ultrasound (OUS) represents a non-invasive technique that can be used to measure the optic nerve sheath dimension providing valuable ICP monitoring data.

Hypothesis:
Optic ultrasound (OUS) can measure optic nerve sheath size and may be used as a screening tool to identify patients at risk of mortality from increased ICP.

Methods:
In a prospective convenience sample study, 86 stroke patients were studied at a tertiary care center. On the day of admission and following day, bedside OUS was performed to measure Optic nerve sheath diameter (ONSD). A longitudinal and transverse measurement were taken on both eyes of each patient. Data analysis includes paired t- tests and Chi-Square to compare means and proportions as appropriate. Regression analysis assessed ONSD and patient outcome relationships.

Results:
There was a significant difference in mean ONSD between patients who died in comparison with those who survived in both ischemic stroke category (0.582 vs 0.533; p=0.0092), and intracerebral hemorrhage category (0.623 vs 0.572; p=0.0187) respectively. Overall, for every 0.1 cm increase in ONSD, the mortality odds were 4.239 times the odds of no death among ischemic stroke patients (95% CI 1.317, 13.642 p=0.0155), and 6.222 times the odds of no death among intracerebral hemorrhage patients (95% CI 1.160, 33.382 p=0.0329). Increased ONSD measurements show a moderately strong correlation (r=0.44 p<0.0001) with poorer Modified Rankin Scale scores at 6 months.

Conclusions:
Increased ONSD measurements correlated with poor short term (in-hospital) and long term (6 months) mortality. OUS may be used as a screening tool to identify patients at risk of poor outcome from increased ICP. OUS in the future may enable the treating physician to utilize this reliable non-invasive monitoring technique to predict elevated ICP and initiate early therapeutics to improve patient care.
Abstract W MP9: Preliminary Results from the Survival and Outcome After Stroke (SOS) Trial: Natural History of Acute Ischemic Stroke from Large Vessel Occlusion
Authors: Grunwald Iris Q , Sneade Mary , Clarke Alison , Yarnold Julia , Warburton Elizabeth , Nagel Simon , Guyler Paul , Fassbender Klaus , Roffe Christine , Chapot René , Briley Dennis , Dixit Anand , Harrington Frances , Perry Richard , Bath Philip , Douglass Christopher , Mangion David , Manawadu Dula , Monyham Barry , Bock Birgit , Ammar Lynne , Buell Hope , Boose Arani , Sit Siu Po ,   on behalf of the SOS-Penumbra Trial Investigators
Published: March 2022

Purpose:
Limited literature is available on the natural history of the stroke cohort eligible for mechanical thrombectomy. Reported herein are data in a stroke cohort eligible for but untreated by mechanical thrombectomy and ineligible or refractory to IV rtPA. The goal of this study (SOS) is to obtain the natural demographics and functional outcome of patients with acute ischemic stroke from large vessel thromboembolism.

Methods:
The SOS Trial is a prospective, single-arm, multicenter study based in the United Kingdom and Germany. Patients can be enrolled presenting with symptoms of acute ischemic stroke within 8 hours from symptom onset from a large vessel occlusion and a NIHSS of at least 10. The primary endpoint is functional outcome at 90 days as defined by mRS of 0-2. Interim data was collected and analyzed. The secondary endpoints include good neurological outcome as defined by an NIHSS score of 0-1 or a 10 points or more improvement in this scale at discharge, all cause mortality, and the incidence of hemorrhage.

Results:
To date, 137 patients were enrolled at 16 centers. Data was available for 42/137 (30.7%) patients. The mean age was 62.4+21.2; median admission NIHSS was 18 (10-31). Occlusions were in the MCA (71.4%), ICA (21.4%), ACA (4.8%), and other (2.4%). Good 90-day outcome was achieved in 13.9% (5/36); 15.0% (6/40) died. The serious adverse event rate was 24.4 (32/131). A total of 7 (17.1%) patients suffered intracerebral hemorrhage. Good neurological outcome rate was 14.7% (5/34).

Conclusion:
Preliminary data showed that large vessel acute ischemic stroke leads to poor patient outcomes if untreated. With further data collected from the remaining patients enrolled, this can help advance our knowledge of the natural course of stroke and serve as a benchmark for future endovascular trials.
Abstract W MP95: Deletion of the Hemopexin or Heme Oxygenase-2 Gene Aggravates Brain Injury Following Stroma-free-hemoglobin Induced Intracerebral Hemorrhage
Authors: Ma Bo , Day Jason , Tolosano Emanuela , Doré Sylvain
Published: March 2022

Introduction:
The breakdown of heme-hemoglobin released after intracerebral hemorrhage (ICH) contributes to brain injury. Hemopexin (HPX) has highest binding affinity to heme as its transporter and heme oxygenase 2 (HO2) is heme rate-limiting enzyme for its degradation. However, the significance and role of HPX and HO2 on hemoglobin clearance in brain remains understudied.

Methods:
Intracerebral injection of stroma-free hemoglobin (SFHb) was used in our study to induced ICH. The HPX or HO2 knockout (KO) mice were injected with 10μL SFHb into the striatum. Behavioral/functional tests were performed along with anatomical changes. Iron deposition and neuronal degeneration was shown by Perl’s or Fluoro Jade B staining, respectively. Immunohistochemistry with anti-Iba1 was used to detect microglial activation around the injured site.

Result:
This study reveals that microglia contribute to hemoglobin clearance after SFHb injection. Deletion of HPX or HO2 aggravated the SFHb-induced brain injury. Both of HPX or HO2 KO mice showed larger lesion volume (P<0.05) and more degenerating neurons (P<0.01) compared with the littermate controls in peri-lesion area at 24h post-injection. However, their activated microglial cells in peri-lesion area were significantly decreased (P<0.05), accompanied with markedly increased iron positive glial cells (both P<0.001), which are confirmed to be microglial cells by double-staining. The data suggested that activated microglia engulfed the injected SFHb and conferred protective effects after ICH. To further address this point, primary microglial cells were treated with SFHb and the results showed that microglial cells take up extracellular SFHb and that SFHb can activate microglial cells. In addition, our in vivo work revealed that activated microglial cells were increased from 24h to 72h after injection in both HPX KO and HO2 KO mice (P<0.05). Also, notable improvements on neurological deficits scoring and locomotor activities indicated that the brain damages in mice were recovering from 24h to 72h post-injection, supporting activated microglia exerted beneficial effects after ICH.

Conclusions:
This study suggests that HPX and HO2 contribute to hemoglobin clearance after ICH and microglia play the crucial role.
Abstract W P102: Predominant Activation of M2 Macrophages by Group-specific Component Protein-derived Macrophage Activating Factor in the Late Phase of Cerebral Ischemia may Contribute to Neurogenesis
Authors: Kurashiki Yoshitaka , Kitazato Keiko T , Shimada Kenji , Yagi Kenji , Tada Yoshiteru , Kinouchi Tomoya , Sumiyoshi Manabu , Miyamoto Takeshi , Satomi Junichiro , Kageji Teruyoshi , Uto Yoshihiro , Nagahiro Shinji
Published: March 2022

Background and Purpose:
Peripheral macrophages include M1- and M2 macrophages; they produce pro-inflammatory and anti-inflammatory cytokines, respectively. Inflammation produces group-specific component protein-derived macrophage activating factor (GcMAF). The role of M1- and M2 macrophages activated by GcMAF in the post-ischemic brain remains unclear. We hypothesized that the role of GcMAF after ischemia is time-dependently different and that the dominant activation of M2 macrophages facilitates brain repair.

Methods:
After subjecting 7-week-old male Wistar rats to 2-hr middle cerebral artery occlusion they were divided into a group injected for 7 days with GcMAF and a group serving as the vehicle control in the early- and late phase after ischemia induction.

Results:
Within 3 days of post-ischemia, the predominant increase in M1 macrophages was associated with expanded ischemic brain damage that was exacerbated by GcMAF. At the 7th post-ischemic day the infarct size was stabilized and M1 macrophages were decreased, although the higher expression in M1- than M2 macrophages persisted. Interestingly, GcMAF treatment from this point cleaned the infarct area, which was associated with phagocytosis via a predominant increase in microglia and M2 macrophages. The effect of GcMAF was abrogated by macrophage-depleting clodronate liposomes. Furthermore, the increase in M2 macrophages was associated with increased BrdU incorporation and the appearance of survival-related molecules and neurovascular unit, suggesting the promotion of neurogenesis.

Conclusion:
The activation of M2 macrophages by GcMAF in the late phase of cerebral ischemia may be associated with brain repair.
Abstract W P103: Modulation of Motor Network Activities by Dual-mode Non-invasive Brain Stimulation in Stroke Patients
Authors: Kim Yun-Hee , Lee Minji , Lee Ahee , Cho Jae Yong , Chang Won Hyuk
Published: March 2022

Objective:
Combination of two non-invasive brain stimulation (NBS) modes, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have been tried to enhance motor function in stroke patients. We aimed to investigate the changes of motor network after dual-mode NBS using Electroencephalogram (EEG).

Methods:
Seven subacute ischemic stroke patients (mean age of 60.6 years; 4 males) and 8 healthy controls (mean age of 29.3 years; 4 males) participated. Participants received simultaneous application of 2mA cathodal tDCS over contralesional M1 and 10 Hz rTMS over the ipsilesional M1. Motor function was assessed before and after stimulation by serial reaction time task (SPTT). Eyes-closed resting state EEG was measured for 5 mins using the Neuroprax® EEG system (NeuroConn GmbH, Germany) before and after stimulation, respectively. The EEG signals were preprocessed using the SPM12b (http://www.fil.ion.ucl.ac.uk/spm/). In stroke patients, we flipped EEG signals from affected hemisphere to the left side. We confirmed event-related dynamics of brain oscillations through topography, and connectivity between ipsilesional M1 and contralesional M1 in mu band (8-12Hz) showing resting-state motor neurons over the bilateral M1s.

Results:
Pre-simulation Event-related desynchronization (ERD) topographic map showed balancing between both hemispheres in heathy controls, however in stroke patients, ipsilesional M1 appeared more ERD, with unbalancing between both hemispheres. After dual-mode NBS, ERD topographic map showed balanced ERD between bilateral hemispheres in both healthy and stroke groups. In other words, stroke patients showed more ERS over the ipsilesional M1 after NBS. Furthermore, in stroke patients, connectivity between ipsilesional M1 (C3) and contralesional M1 (C4) increased after NBS, whereas connectivity between C3 and C4 decreased in healthy controls.

Conclusions:
These results revealed that there were a balanced ERD and increase of connectivity between bilateral hemispheres after dual-mode NBS in stroke patients. The dual-mode NBS may modulate the pre-existing inter-hemispheric imbalance of both hemispheres in stroke patients.
Abstract W P105: Lipopolysaccharide Exacerbates Stroke Severity and Compromises Mitochondrial Function in Cerebral Endothelium
Authors: Ren Xuefang , Doll Danielle N , Hu Heng , Sun Jiahong , Lewis Sara E , Rellick Stephanie L , Simpkins James W
Published: March 2022

Stroke is the fourth leading cause of death in the U.S, with many cases leading to severe disabilities. Statistics reports present that more than 40% of ischemic stroke patients have recent prior infections. Acute infections initiate rapid inflammation and can be a trigger for acute ischemic stroke in people. Ischemia-reperfusion injury following ischemic stroke induces blood-brain barrier (BBB) breakdown, hyperpermeability and brain edema. Cerebral vascular endothelial cells (CVEC) lining the BBB play a key role in fluid leakage into the brain tissue. The expression of toll-like receptor 4 (TLR4, specific for bacteria-sourced lipopolysaccharide, LPS) on CVEC implicates that acute bacterial infections may directly target CVEC and regulate BBB permeability and integrity. High mitochondrial contents in BBB capillaries suggest mitochondrial mechanisms are important to maintain BBB integrity.

In order to test the hypothesis that bacterial infections regulate BBB permeability via mitochondrial mechanisms in stroke, we designed a series of studies both in vivo and in vitro. First, we used LPS challenged mice, then evaluated stroke outcomes including: infarct size, neurological deficits, BBB permeability and infiltration of neutrophils in the brain after transient middle cerebral artery occlusion (tMCAO). Second, we treated cultured CVEC with various concentrations of LPS and evaluated their mitochondrial function. Third, we impaired mitochondrial function in CVEC and investigated the BBB permeability in vitro.

Our results demonstrated that LPS (100ug/kg) prior to tMCAO administration significantly exacerbates stroke infarct volume, BBB permeability and neutrophil infiltration in the brain, and worsens neurological deficits in murine experimental stroke in vivo. In vitro, LPS significantly impaired mitochondrial oxidative phosphorylation and decreased maximal respiration and spare capacity in CVEC. Finally, pharmacological inhibition of mitochondria respiration disrupted tight junctions in CVEC monolayers and increased CVEC monolayer permeability in vitro.

These data are particularly important because they suggest a novel mitochondrial mechanism of the interactions between stroke and infections on BBB integrity.
Abstract W P108: Pharmacological Evaluation of a BDNF Nano-Particle Formulation after Experimental Stroke
Authors: Verma Rajkumar , Mancini Nickolas , Legore Shani , Harris Nia , Venna Venugopal , Manickam Devika S , Kabanov Alexander V , McCullough Louise
Published: March 2022

Backgrounds:
Brain Derived Neurotrophic factor (BDNF) is a well-recognized neuro-protective and neuro-restorative protein of the neurotrophin family. Unfortunately, systemically administered native BDNF has minimal therapeutic effects due to poor blood brain barrier permeability and short half-life. Therefore, the aim of this study was to utilize a novel nano-particle formulation of BDNF for enhanced delivery to the brain in mice after middle cerebral artery occlusion (MCAO).

Methods:
Male C57BL/6J (8-10 weeks) mice were randomly assigned to saline or BDNF nano (Exp group 1, n=6/group) or saline vs. BDNF native vs. BDNF nano (Exp group 2, n=8/group) and subjected to 60min of MCAO. The mice in Exp. group 1 were treated twice with either saline or BDNF Nanoparticles (250μg/kg i.v) 3 and 24 hrs after the onset of MCAO. Exp group2 was also treated twice with saline vs. BDNF native vs. BDNF nano (250μg/kg i.v) but treatment was delayed until 12 hrs after MCAO with a second dose at 24 hrs. Mice were tested weekly on several behavioral tests and were sacrificed on day 15 and brains used for histological analysis.

Results:
Treatment with BDNF nanoparticles 3 hours after MCAo (Exp group 1) led to a significant (p<0.0062) reduction in tissue loss (42.33±2.24 vs 31.02± 4.02) and earlier behavioral recovery. When we delayed treatment to 12 hrs after MCAO, neither native nor BDNF nanoparticles reduced tissue loss compared to saline. Neurological deficit scores were similar between groups. However, treatment with BDNF nanoparticles led to early improvements in memory/cognitive performance (Day 7) in the Novel Object Recognition Test (NORT) and reduced immobility (p< 0.05, 155.2± 18.56 Saline vs 162.8± 15.55 BDNF native vs.117.0±25.44 in BDNF nano) in the tail suspension test suggestive of a reduced depressive phenotype in BDNF nano treated mice.

Conclusions:
This study reveals that BDNF nanoparticle formulation is neuroprotective when given within three hours of stroke, and enhances neuronal repair and behavioral recovery beyond that seen with native BDNF even in the absence of decreased infarct size when treatment is delayed.