bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 126: Phenotypic Features of Murine Models of Cerebral Cavernous Malformations
Authors: Zeineddine Hussein , Girard Romuald , Moore Thomas , Lightle Rhonda , Cao Ying , Hobson Nicholas , Shenkar Robert , Shen Le , Fam Maged , Tan Huan , Polster Sean , Lopez-Ramirez Miguel , Tang Alan , Gallione Carol , Kahn Mark , Ginsberg Mark , Marchuk Douglas , Awad Issam
Published: June 2021

Introduction:
Cerebral cavernous malformations (CCM) are hemorrhagic lesions causing stroke and epilepsy. They develop with loss of function of three known genes in endothelial cells (ECs). Mice heterozygous for
Ccm 1, 2
or
3
genes develop CCMs stochastically during life (“chronic models”), especially when bred in a background predisposing to somatic mutations (
p53
or
Msh2
loss)
.
CCM lesions can also be generated in the developing hindbrain and retinas by Cre-recombinase induced homozygous loss of
Ccm 1, 2,
or 3 genes in the immediate postnatal period (“acute models”). We hypothesized that the CCM lesions which develop in the various models reflect different phenotypic features of the human disease.

Methods:
Eight murine models of CCM were used in this study and defined as being chronic (
Ccm1
+/-
Msh2
-/-
,
Ccm3
+/-
and
Ccm3
+/-
Trp53
-/-
) or acute (

Pdgfb
iCreERT2
Ccm1
fl/fl
, Pdgfb
iCreERT2
Ccm3
fl/fl
and Cdh5
CreERT2
Ccm1
fl/fl

). Volumetric lesion burden was assessed using micro-CT after adjusting for total brain volume. Other phenotypic markers were assessed including the prevalence of ECs with Rho-associated protein kinase (ROCK) activity, and quantitation of B and T cells infiltration and non-heme iron deposition in the CCM lesions.

Results:
The acute neonatal models showed higher adjusted volume lesion burden than the paired chronic model (p=0.013). CCM EC ROCK activity was similar in the acute and chronic models. Background brain EC ROCK activity in chronic models was higher than that in acute model (p=0.012). CCM lesions in chronic models (16 lesions/13 mice) had higher integrated iron intensity per lesion area compared to the acute lesions (12 lesions/9 mice) (p=0.03). Chronic lesions had a higher number of B cells (p=0.005), more T cells (p=0.04) per lesion area, and more combined lymphocytes (p=0.002) per lesion area compared to the acute model.

Conclusion:
The acute model harbored a significantly higher lesion burden making them suitable for studying lesion genesis mechanisms. The chronic model however is more suited to study the role of inflammation and iron deposition in CCM, hallmark features of clinically relevant CCM lesions in man.
Abstract 129: Clinical-imaging Mismatch versus Perfusion Imaging Mismatch Selection for Stroke Patients Undergoing Mechanical Thrombectomy
Authors: Bouslama Mehdi , Bowen Meredith , Haussen Diogo C , Dehkharghani Seena , Grossberg Jonathan A , Rebello Leticia C , Rangaraju Srikant , Schindler Kiva , Frankel Michael , Nogueira Raul G
Published: June 2021

Background and Purpose:
The best approach to select patients for reperfusion therapy in acute ischemic stroke remains to be established. Different methodologies have been proposed using different clinical, vascular, and parenchymal imaging parameters. Our aim is to compare Perfusion-imaging Mismatch (PIM) and Clinical-Core Mismatch (CCM) patient selection and assess their ability to predict outcomes.

Methods:
We reviewed our prospectively collected endovascular database at a tertiary care academic institution for patients with acute anterior circulation strokes, adequate CT perfusion imaging maps and a National Institute of health Stroke Scale (NIHSS) ≥10 from September 2010 to March 2015. Patients were categorized according to the PIM and CCM definitions. PIM was defined as follows: Core Lesion ≤50cc; Tmax >10sec <100cc; Mismatch (Tmax> 6s lesion - core lesion) ≥15cc and ratio >1.8. CCM was defined as: NIHSS ≥ 10 and core infarct <31 cc (and age < 80) or NIHSS ≥ 20 and core infarct <51 cc (and age < 80) or NIHSS ≥ 10 and core infarct <21 cc (and age ≥ 80). The ability of PIM and CCM to predict good outcomes (modified Rankin scale 0-2) was evaluated using the area under the receiver operating characteristic curves (AUC), Akaike information criterion (AIC) and Bayesian information criterion (BIC).

Results:
A total of 368 patients qualified for the study. PIM had a lower number of qualifying patients compared to CCM (n=231, 62.8% vs n=303, 82.3%). The two groups were statistically different (p<0.001) with the following disagreement: 12 PIM+/CCM- and 84 PIM-/CCM+. There were no differences in good outcomes between PIM+ and PIM- patients (52% vs 48%, p=0.5). CCM+ patients had higher rates of good outcomes than CCM- (53% vs. 35%, p=0.015). There were no differences between PIM and CCM in predicting good outcomes as assessed by the AUC, AIC and BIC (0.82, 323.64 and 330.61 vs 0.82, 323.56 and 330.53 respectively)

Conclusion:
We were unable to demonstrate a difference between the PIM and CCM in predicting clinical outcomes. However, PIM seems to unjustifiably disqualify a significant proportion of patients that still benefit from reperfusion. In contrast with CCM, PIM does not seem to be a good discriminator of good outcomes. Future prospective studies are warranted.
Abstract 13: The Effect of Circadian Light on Depressive Mood in Post Stroke Patient During Admission for Rehabilitation
Authors: West Anders , Simonsen Sofie , Zielinsky Alexander , Cyril Niklas , Schønsted Marie , Sander Birgit , Jennum Poul , Iversen Helle
Published: June 2021

Introduction:
Stroke is a major cause of acquired cerebral disability among adults, frequently accompanied by depression. New ways of intervention to prevent post stroke depression is therefore needed. The blue light spectrum is the strongest zeitgeber (time-giver) and is known to stabilize the circadian rhythm. Patients admitted for rehabilitation are often lacking the blue light in daytime due to the long indoor admission; furthermore, they are often exposed to blue light in the evenings, as blue light is contained in standard lightning.

Hypothesis:
Circadian light will reduce depressive mood in stroke patients admitted for rehabilitation.

Methods:
The study is a prospective parallel longitudinal randomized controlled study (quasi randomization). Stroke patients in need of rehabilitation were included at the acute stroke unit and randomized to either the intervention unit (IU)(circadian lighting) or the control unit (CU)(standard lighting). The circadian light was installed in the entire IU (Cromaviso, Denmark). Examination was done in the acute unit and at discharge after at least 2 weeks in the IU/CU. Change in depressive mood was measured by the Hamilton Rating Scale for Depression (HAM-D
6
) and The Major Depression Inventory scale (MDI).

Results:
Patients were included over a year (N=90), 6 did not reach randomization, 45 were randomized to the IU, and 39 to the CU. A sample of 59 and 62 patients were able to answer the HAM-D
6

(N=30IU;N=29CU) and MDI (N=30IU;N=29CU) score, respectively. Both scores were significantly lower in the intervention group at discharged compared with the control group (ANCOVA, antidepressants medicine was included as a confounder, HAM-D
6
,
P=0.018,
Estimate=-2.25;SEM=0.92, MDI,
P=0.009,
Estimate=-4.72;SEM=1.74).

Conclusion:
Our findings show for the first time circadian light as a beneficial intervention on depressive mood on long-term hospitalized patients in a real hospital setting. The circadian lightning should be considered as an integrated segment in the environment of rehabilitation units.
Abstract 139: Trends in Ischemic Stroke Subtype Over a 17-Year Period
Authors: Demel Stacie L , Khoury Jane C , Moomaw Charles J , Alwell Kathleen , Kissela Brett M , Khatri Pooja , Woo Daniel , Flaherty Matthew , Ferioli Simona , Mackey Jason , De Los Rios la Rosa Felipe , Maritini Sharyl , Adeoye Opeolu , Broderick Joseph P , Kleindorfer Dawn O
Published: June 2021

Introduction:
Overall US stroke incidence rates have declined. Prior analysis of the Cincinnati region has demonstrated more thorough diagnostic workups coinciding with decreased proportion of cryptogenic and increased proportion of cardioembolic strokes over time in those patients presenting to the ED. We now examine trends in population-based incidence rates of stroke subtypes.

Methods:
Within the Greater Cincinnati/Northern Kentucky catchment area of 1.3 million, all strokes were ascertained between July 1993 and June 1994 and in 1999, 2005 and 2010. Incidence rates per 100,000, age-, race- and sex-adjusted to the 2000 US population, and associated 95% confidence intervals were calculated. Changes in stroke-subtype proportions over time were examined using a general linear model.

Results:
There were a total of 6859 incident ischemic strokes (1709 in 1993/94, 1778 in 1999, 1681 in 2005, and 1691 in 2010; age ≥20 years), of which 1290 (18.8%) were black and 3846 (56.1%) female. The Table shows subtype-adjusted incident rates by study period. Incidence rates of both small- and large-vessel etiology showed no significant change over time. Incidence rates of both cardioembolic and other known etiology increased significantly over time, whereas incidence rates of unknown subtype decreased significantly.

Conclusions:
In our large, biracial population-based cohort, while overall stroke incidence rates have been stable or declining over the last 17 years, trends for individual stroke subtypes have varied. Consistent with our prior analyses, more strokes have been attributed to cardioembolic etiology, whereas strokes attributable to small-vessel and large-vessel etiology have remained stable. The increase in cardioembolic strokes may be due to age and/or prolonged cardiac monitoring. Future analysis of age-adjusted rates for atrial fibrillation over time is warranted.
Abstract 140: Association Between Epilepsy and the Risk of Ischemic Stroke or Myocardial Infarction
Authors: Mercuri Matthew A , Merkler Alexander E , Parikh Neal S , Reznik Michael E , Kamel Hooman
Published: June 2021

Background:
Vascular brain injury can result in epilepsy. It is posited that seizures in elderly patients might reflect subclinical vascular disease and thus herald future clinical vascular events.

Hypothesis:
Seizures in elderly patients are associated with an increased risk of ischemic stroke or myocardial infarction (MI).

Methods:
We obtained inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries ≥66 years of age. The predictor variable was epilepsy, defined as two or more inpatient or outpatient claims with a diagnosis of seizure. The primary outcome was a composite of ischemic stroke or acute MI. The predictors and outcomes were all ascertained with previously validated
ICD-9-CM
code algorithms. Survival statistics and Cox proportional hazards models were used to assess the relationship between epilepsy and incident ischemic stroke or MI while adjusting for demographic characteristics and vascular risk factors. Patients were censored at the first occurrence of a stroke or MI, at the time of death, or on December 31, 2014.

Results:
Among 1,548,556 beneficiaries with a mean follow-up of 4.4 (±1.8) years, 15,055 (1.0%) developed epilepsy and 121,866 (7.9%) experienced an ischemic stroke or acute MI. Patients with seizures were older (76.1 versus 73.7 years) and had a significantly higher burden of vascular comorbidities than the remainder of the cohort. The annual incidence of stroke or acute MI was 3.28% (95% confidence interval [CI], 3.10-3.47%) in those with seizures versus 1.79% (95% CI, 1.78-1.80%) in those without (unadjusted hazard ratio [HR], 1.89; 95% CI, 1.78-2.00). After adjustment for demographics and risk factors, epilepsy had a weak association with the composite outcome (adjusted HR, 1.36; 95% CI, 1.29-1.44), a stronger association with ischemic stroke (adjusted HR, 1.77; 95% CI, 1.65-1.90), and no association with acute MI (adjusted HR, 0.95; 95% CI, 0.86-1.04).

Conclusions:
We found an association between epilepsy in elderly patients and future ischemic stroke but not acute MI. Therefore, seizures might signify occult cerebrovascular disease but not necessarily occult disease in other vascular beds.
Abstract 143: Long Non-coding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke
Authors: Zhang Xuejing , Tang Xuelian , Yin Ke-Jie
Published: June 2021

Accumulative studies have demonstrated the important regulatory roles of microRNAs in vascular and neural damage after ischemic stroke. However, the functional significance and mechanisms of other classes of non-coding RNAs in cerebrovascular pathophysiology after stroke are less studied. Using RNA-sequencing technology, we previously profiled long non-coding RNAs (lncRNAs) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), and identified that metastasis associated lung adenocarcinoma transcript 1 (Malat1) is one of the most highly upregulated OGD-responsive endothelial lncRNAs. Here, we sought to determine the role of Malat1 in cerebrovascular pathogenesis of ischemic stroke. Increased Malat1 levels were found in cultured mouse BMECs after OGD as well as in isolated cerebral microvessels in mice after transient middle cerebral artery occlusion (tMCAO) and 24h reperfusion by quantitative PCR. Loss-of-Malat1 function by LNA-GapmeRs significantly increased OGD-induced cell death and Caspase 3 activity in BMECs. It appears that Malat1 plays anti-apoptotic and anti-inflammatory roles in cerebral endothelium, showing that loss-of-Malat1 function significantly aggravated OGD-induced expression of pre-apoptotic factor Bim, pro-inflammatory cytokines MCP-1, IL-6 and E-selectin at both mRNA and protein levels. Moreover, Malat1 KO mice presented larger brain infarct size and worse neurological score after tMCAO compared to WT controls. A battery of behavioral tests, including adhesive tape removal, foot fault, cylinder were performed to assess sensorimotor functions after ischemic stroke. Malat1 KO mice exhibited reduced ability to perform all the above tests. Consistent with
in vitro
findings, significantly increased expression of Bim, MCP-1, IL-6 and E-selectin at mRNA and protein levels were also found in Malat1 KO mouse cortex after ischemic stroke in comparison with WT controls. Taken together, these findings suggest that Malat1 plays critical vascular and neuroprotective roles in ischemic stroke.
Abstract 149: Patterns, Determinants and Outcomes of Ultra-early Neurological Deterioration (U-END) in Intracranial Hemorrhage
Authors: Shkirkova Kristina , Wong Gregory , Weng Julius , Saver Jeffrey L , Starkman Sidney , Hamilton Scott , Liebeskind David S , Eckstein Mark , Stratton Samuel , Pratt Frank , Conwit Robin , Sanossain Nerses
Published: June 2021

Background:
The patterns and outcomes of deterioration during prehospital transport and the first phase of ED care are important for planning for design of prehospital intracranial hemorrhage (ICH) treatment trials.

Methods:
Patients were enrolled in the NIH Phase 3 Field Administration of Stroke Therapy - Magnesium (FAST-MAG) prehospital trial within 2h of last known well (LKW). Deterioration was defined as worsening by ≥2 on the Glasgow Coma Scale (GCS), performed serially by paramedics in the field, upon ED arrival, and after the early ED course

Results:
Among 213 patients with ICH, age was 65.4 (±13.4), 33.3% female. Times from LKW to GCS assessments were: paramedic, 23 mins (IQR 14-39); ED arrival, 57 mins (IQR 45-75); and after early ED course, 89 mins (IQR 65-107). Overall, 38.5% experienced neurological deterioration, including 12.7% in prehospital phase only, 12.2% in early ED phase only, and 10.3% in both. Granular patterns of deficit progression were: Prehospital Sustained - prehospital deterioration, then stable early ED phase, 6.1% (13); Dippers - prehospital deterioration, then early ED improvement, 6.6% (14); Delayed - stable prehospital, then ED deterioration, 12.2% (26); and Continuous - prehospital deterioration, then further deterioration in ED, 10.3% (22) (Figure). ICH patients who experienced any U-END had lower prehospital GCS scores, 15 (IQR 12-15) vs 15 (IQR 15-15), p<0.001, greater prehospital focal weakness, LAMS 4.4 vs 3.9, p<0.001, history of hypertension, 87.4% vs 74.9%, p<0.001, higher ED SBP, 186 vs 174, p<0.001, and larger ICH volume, 45.8 vs 21.8 cm
3
, p<0.001. U-END was associated with higher dependence or death (mRS 3-6) at 90d, 90.1% vs 61.6%, p<0.001.

Conclusions:
Ultra-early neurological deterioration occurs in more than one-third of EMS-transported ICH patients, is associated with elevated BP, and leads to unfavorable outcome. Clinical trials testing prehospital initiation of BP-lowering therapy for ICH are desirable.
Abstract 151: CD163 Has Distinct Temporal Influences on Intracerebral Hemorrhage Outcomes
Authors: Leclerc Jenna L , Lampert Andrew S , Loyola Amador Claudia , Schlackman Brandon , Vasilopolous Terrie , Svendsen Pia , Moestrup Søren K , Doré Sylvain
Published: June 2021

Extracorpuscular hemoglobin (Hb)-induced toxicity following intracerebral hemorrhage (ICH) precipitates secondary brain damage and poor outcomes. CD163 is the Hb scavenger receptor with potent anti-inflammatory effects and CD163-positive macrophages/microglia accumulate in the brain with time post-ICH, yet no studies have investigated the role of CD163 after ICH. ICH was induced in wildtype and CD163
-/-
mice and various anatomical and functional outcomes were temporally assessed by histology and neurobehavioral testing. Acutely, CD163
-/-
mice have 33.2±4.5% (p<0.0001), 43.4±5.0% (p=0.0002), and 34.8±3.4% (p=0.0003) less lesion volume, hematoma volume, and tissue injury, respectively. Whereas, at 10d, CD163
-/-
mice have 49.2±15.0% larger lesion volumes (p=0.0385). Temporal data inspection revealed an inflection point at 4d, where CD163
-/-
mice perform significantly better on neurobehavioral testing and have less mortality before 4d, but increased mortality and worse function after 4d (p<0.05). Histology at 72h shows that CD163
-/-
mice have significantly less Hb, iron, and blood-brain barrier dysfunction, increased astrogliosis and cortical neovascularization, and no change in HO1 expression. At 10d, CD163
-/-
mice have increased iron and hematomal VEGF immunoreactivity, no change in HO1 expression, and decreased astrogliosis. These novel findings reveal that CD163 deficiency has distinct temporal influences on ICH outcomes, with early beneficial properties but delayed injurious effects. While it is unclear why CD163 deficiency is initially beneficial, the late injurious effects of absent CD163 are consistent with the key anti-inflammatory role of the receptor in the recovery phase of tissue damage. CD163 may represent a key targetable immunomodulatory receptor after ICH.

Funding: This work was supported by NIH grants F31NS086441 (JLL) and R01NS046400 (SD).
Abstract 156: Tailored Multipotent Mesenchymal Stromal Cell Harvested Exosomes Carrying Elevated miR-17-92 Cluster Enhance Neurovascular Remodeling & Improve Functional Recovery After Stroke in Rats
Authors: Xin Hongqi , Katakowski Mark , Wang Fengjie , Qian Jianyong , Santra Manoranjan , Liu Xian S , Ali Meser M , Buller Ben , Zhang Zheng G , Chopp Michael
Published: June 2021

Introduction:
MSC generated exosomes mediate therapeutic benefits of MSCs for stroke, which are at least in-part attributed to their miRNA contents. In vitro, the miR-17-92 cluster promotes oligodendrogenesis, neurogenesis and axonal outgrowth, and tailored MSC exosomes enriched with the miR-17-92 cluster promote axonal outgrowth of primary cortical neurons. We therefore investigated whether the miR-17-92 cluster enriched exosomes (Exo-miR-17-92
+
) harvested from MSCs enhance neurological recovery compared to control MSC derived exosomes (Exo-Con).

Methods:
Rats (n=8/group) subjected to 2 hours of transient MCAO were intravenously administered Exo-miR-17-92
+
, Exo-Con, or liposomes, and were sacrificed 28 days post MCAO. Foot-fault test, and a modified neurologic severity score (mNSS) were carried out at 1, 3, 7, 14, 21 and 28 days after MCAO by an investigator blinded to the treatments. Histochemistry, immunohistochemistry and Golgi-Cox staining were used to assess dendritic, axonal, synaptic and myelin remodeling. Expression of PTEN and activation of its downstream proteins, Akt, mTOR and GSK-3β in the peri-infarct region were measured by means of Western blots.

Results:
Compared with the liposome treatment, both exosome treatment groups exhibited significant improvement of functional recovery (P<0.05, respectively), but Ex-miR-17-92
+
treatment had more robust effects on improvement of neurological function (P<0.05), and enhancements of oligodendrogenesis, neurogenesis and neurite remodeling/neuronal dendrite plasticity in the ischemic boundary zone (IBZ) than the Ex-Con treatment (P<0.05, respectively). Moreover, Ex-miR-17-92
+
treatment substantially inhibited PTEN, a validated miR-17-92 cluster target gene, and subsequently increased the phosphorylation of PTEN downstream proteins, Akt, mTOR, and decreased the activity of GSK-3β by phosphorylating GSK-3β in neurons compared to Ex-Con treatment (P<0.05, respectively).

Conclusions:
Our data suggest that treatment of stroke with tailored exosomes enriched with the miR-17-92 cluster increases neural plasticity and functional recovery after stroke, possibly via targeting PTEN to activate the PI3K/Akt/mTOR/GSK-3β signaling pathway.
Abstract 16: A Discrete Event Simulation to Assess the Impact of EMS Routing Algorithms on the Number Needed to Route and Transport Time
Authors: Bogle Brittany M , Asimos Andrew W , Rosamond Wayne D
Published: June 2021

Introduction:
Proposed EMS routing algorithms permit additional transport time to an endovascular center (EC) beyond the closest non-EC for patients with suspected large vessel occlusion acute ischemic stroke (LVO). The effectiveness of these algorithms depends on screening tools and patient location relative to EC and non-ECs. We implemented routing algorithms in a discrete event simulation to examine their impact on one region.

Methods:
We simulated stroke and stroke mimic patients screened by EMS over a year using hospital locations and demographics of Mecklenburg County, NC. We used an 8% LVO prevalence among those screened and geographically distributed patients using published stroke incidence rates and census tract population estimates, stratified by age, sex, and race. We estimated distance from census tract centroids to the nearest EC and non-EC using real road travel times. Last known well (LKW) was probabilistically assigned using county data. A patient was EC-routed if they screened positive, had LKW ≤6 hours and were within an allowable additional transport time. We simulated policies that varied by stroke severity screen (LAMS
≥
4, RACE
≥
5, C-STAT
≥
2) and allowable additional transport time (10, 20, and 30 minutes). We define Number Needed to Route (NNR) as the number of patients enduring additional transport time to route one LVO patient to an EC.

Results:
Over 100 replications, EMS screened an average of 3102 patients annually; 249 were LVOs. NNRs were 2.6 (LAMS
≥
4), 5.3 (RACE
≥
5), and 9.3 (C-STAT
≥
2). The number of EC-routed non-LVOs ranged from 87 (LAMS
≥
4, 10 minutes) to 859 (C-STAT
≥
2, 30 minutes). The proportion of LVOs within 10 and 20 minutes of added transport time to an EC was 67% and 99.6% respectively. EC-routing added a mean of 5.5 and 9.5 minutes to transport time for 10 and 20 minute policies respectively. A 20 minute policy EC-routed 1.8 times more patients than a 10 minute policy (e.g. C-STAT: 957 vs. 535). Increasing from a 20 to 30 minute policy routed only 4 more patients, thus these policies had similar results.

Conclusions:
We designed and tested a simulation tool to evaluate LVO routing policies. It is easily modifiable to aid in tailoring routing policies to a specific region. We propose using NNR as an intuitive metric of non-LVO overtriage.
Abstract 161: Age and Sex Influence the Neutrophil Response to Ischemic Stroke in Mice and Humans
Authors: Roy-O’Reilly Meaghan , Bravo-Alegria Javiera , Ahnstedt Hilda , Spychala Monica , McCullough Louise
Published: June 2021

Background and Purpose:
Age and sex have important effects on stroke-induced inflammation. We conducted CBC analysis and RNA-sequencing of ischemic stroke patient blood, with follow-up studies in an experimental mouse model, to test the hypothesis that there are sex differences in neutrophil function and neutrophil-mediated damage after ischemic stroke.

Methods:
Blood from male and female stroke patients was collected 24 hours after stroke, with transient ischemic attack patients serving as controls. Absolute neutrophil count was quantified and RNA-sequencing was performed on an age and severity matched subset of patients. Results were analyzed by multivariate regression and differential expression analysis, respectively. For animal experiments, aged (18-20 month) and young (8-10 week) male and female mice were subjected to 60 minute middle cerebral artery occlusion and sacrificed at 24 hours. Neutrophils from blood, bone marrow, lung, brain and spleen were quantified and phenotyped by flow cytometry. Results were analyzed by student T-test and two way ANOVA.

Results:
Absolute neutrophil counts increased significantly after stroke in both sexes (p=.01). Interestingly, females had more differentially expressed genes after stroke than males, including matrix metalloproteinase 9 and TNFa. In animal experiments, aged animals were found to have higher percentages of neutrophils in the blood, spleen, lungs and bone marrow than young animals. In addition, aged female animals were found to have more activated neutrophils 24 hours after stroke than aged males (p=<.05).

Conclusion:
These results suggest that the immune response to ischemic stroke differs in aged males and females. Female neutrophils appear to exhibit enhanced activation, which may contribute to the poorer stroke outcomes seen in aged female patients. Understanding sex and age differences in the acute immune response is crucial to developing future immunomodulatory drugs for the safe and effective treatment of ischemic stroke in both sexes.
Abstract 162: Processes of Care that are Associated With Reduced Risk of Recurrent Vascular Events Among Patients With a Transient Ischemic Attack and Minor Stroke
Authors: Bravata Dawn , Myers Laura , Reeves Mat , Cheng Eric , Baye Fitsum , Ofner Susan , Miech Edward , Damush Teresa , Sico Jason , Zillich Alan , Phipps Michael , Williams Linda , Chaturvedi Seemant , Johanning Jason , Ferguson Jared , Yu Zhangsheng , Arling Greg
Published: June 2021

Background:
Interventions that emphasize early evaluation and management of patients with TIA and minor stroke have demonstrated reductions in recurrent vascular events.

Objective:
To identify processes of care that were associated with reduced risk of recurrent vascular events after TIA or minor stroke.

Methods:
We identified patients with a TIA or minor stroke cared for in a Department of Veterans Affairs (VA) Emergency Department or inpatient ward (fiscal year 2011). Recurrent vascular events included ischemic stroke, myocardial infarction, heart failure, arrhythmia or death within 90-days and 1-year of discharge. 32 processes of care were examined. Defect-free care was assessed for a set of 6 processes (brain imaging, carotid artery imaging, hypertension management, high or moderate potency statin, antithrombotics, and anticoagulation for atrial fibrillation); patients who received all processes for which they were eligible passed the defect-free measure. Multivariable logistic regression with a random facility effect was used to model recurrent events. Clinically important potential confounders were forced into all models; other significant covariates were identified by backward selection.

Results:
Among 8107 patients, 14.0% had a recurrent vascular event within 90-days; 26.5% within 1-year. Three processes were associated with lower 90-day events after adjustment for 24 covariates: carotid artery imaging (adjusted OR, 0.74 [95%CI, 0.65-0.85], lipid measurement (0.80 [0.68-0.94]), and anticoagulation quality for atrial fibrillation (0.56 [0.35-0.88]). Three processes were associated with reduced 1-year events: carotid artery imaging (0.80 [0.71-0.89]), lipid measurement (0.85 [0.75-0.97]), and timely carotid stenosis intervention (0.49 [0.26-0.94]). The defect-free care rate, observed in 17.4%, was also associated with a reduction in recurrent vascular event risk both within 90-days (0.78 [0.65-0.93]) and 1-year (0.82 [0.71-0.94]).

Conclusions:
The delivery of a comprehensive set of clinical processes was associated with clinically meaningful reductions in short and longer-term risk of recurrent vascular events. Widespread implementation of these processes should be strongly considered.
Abstract 163: Early Outpatient Followup Associated With Lower Readmission Among Medicare Patients With Ischemic Stroke
Authors: Terman Samuel W , Burke James F , Skolarus Lesli E
Published: June 2021

Introduction:
Reducing hospital readmission is an important target for reducing morbidity and cost in acute ischemic stroke. However, strategies to reduce readmissions are lacking. We examined the association between time to first outpatient contact and readmission to inform interventions to optimize the inpatient-outpatient transition.

Methods:
We performed a retrospective cohort study of all Medicare fee-for-service patients discharged home after an acute ischemic stroke in 2012. Stroke hospitalizations were identified with ICD-9-CM codes 433.x1, 434.x1 and 436. Our primary explanatory variable was whether patients had a primary care or neurology visit within 30 days of discharge. Our primary outcome variable was all-cause 30-day hospital readmission. This relationship was evaluated using mixed-effects logistic regressions adjusted for patient demographics and comorbidities, hospital quality of care (using Hospital Compare data), stroke volume, regional socioeconomic (SES) variables and a random hospital-level intercept. Secondary analyses explored timing of follow-up, provider continuity, combined provider effects, follow-up-SES interactions and time-to-event analyses.

Results:
The cohort included 69,981 Medicare beneficiaries with acute ischemic stroke. A primary care physician (OR 0.82, 95% CI 0.77-0.86) or neurologist (OR 0.84, 95% CI 0.78-0.91) visit within 30 days of discharge were associated with decreased odds of readmission. On secondary analyses, return visits within 15 days were associated with further reductions in the odds of readmission for primary care (OR 0.79, 95% 0.75-0.84), but not for neurology follow-up (OR 0.94, 95% 0.85-1.05). The primary findings differed minimally when adjusting for provider effects simultaneously, accounting for provider-SES interactions or in time-to-event analyses.

Conclusion:
Early outpatient follow-up was associated with a lower odds of hospital readmission among elderly stroke patients who are discharged from the hospital to home. Our data suggest that outpatient care may be crucial in reducing preventable hospital readmissions and identifies a potentially important target for future interventions aimed at reducing the cost and burden of stroke.
Abstract 164: The Michigan Stroke Transitions Trial: Assessment of Unmet Needs and Case Management Activities from an In-home Patient-Centered Social Work Case Management Program
Authors: Fritz Michele , Hughes Anne , Woodward Amanda , Freddolino Paul , Reeves Mathew J
Published: June 2021

Background:
Inadequate stroke transitions adversely affect survivors, caregivers and families, contributing to hospital readmissions, recurrent stroke, and poor quality of life. Unfortunately few evidence-based transitional care programs exist for stroke. We report preliminary experience with a patient-centered Social Work Case Management (SWCM) program, including frequency and type of unmet patient needs and duration of case management services.

Methods:
The Michigan Stroke Transitions Trial (MISTT) is a pragmatic randomized trial testing the efficacy of an in-home SWCM program against Usual Care for improving stroke survivor and caregiver recovery experiences. The 60 day intervention offers patient-centered case management services addressing psychosocial and medical needs to improve quality of life and increase patient activation and self-management. The SWCM program is designed to address patient identified unmet needs and includes providing support, improving preparedness, and managing stroke prevention.

Results:
During the first 6 months, 46 patients were randomized to the SWCM intervention group. Initial assessments were initiated a median of 5 days after returning home. Twenty-five patients (56%) identified at least one unmet need during the initial assessment. The mean number of unmet needs was 1.7 (range 0-10) and covered a wide range of psychosocial (n=9) and medical (n=5) domains. Mental health (22%), symptoms requiring assistance (20%), and monthly expenses (20%) were the most common unmet needs. Among cases who completed the intervention (n=35), the intervention duration ranged from 18-118 days (mean= 69). For 8 of these cases (22%) case management exceeded 60 days. Total case interaction time averaged 5.5 hours (0.5 to 21 hours) and communication occurred across diverse individuals and organizations.

Conclusion:
Psychosocial unmet needs are prevalent among stroke survivors during the first 60 days of in-home recovery. These needs require considerable time to manage and involve communication across multiple service organizations. Given the complexity of in-home stroke transitions, stroke survivors can benefit from short-term case management, with some cases requiring longer term management.
Abstract 172: Medical and Demographic Predictors of Long-term Cognitive Outcomes of Pediatric Stroke
Authors: Holland Alice A , Goodspeed Kimberly D , Plumb Patricia , Stavinoha Peter L , Dowling Michael
Published: June 2021

Introduction:
Studies examining cognitive outcomes for pediatric stroke are sparse, and few account for stroke severity. The Pediatric Stroke Outcome Measure (PSOM) provides an objective, comprehensive rating of neurological impairment. This study investigated the relationship between initial PSOM score and long-term cognitive outcomes. It was hypothesized that greater severity of stroke (worse initial PSOM score) would predict lower IQ at long-term follow-up. Other factors considered were age at stroke and months post stroke. Age-related studies in broad cognitive outcomes for pediatric stroke are sparse and somewhat inconsistent in findings. It was hypothesized that severity of stroke would be more relevant than age of stroke for long-term cognitive outcomes.

Methods:
PSOM scores at initial visit and IQ scores at long-term follow-up (M=3.77 years) were obtained for 84 survivors of pediatric stroke ages 4:0-25:6 (M=11:5 years; 37 females). A one-sample t-test was conducted to compare mean IQ to the normative sample. To examine the hypotheses, all variables of interest (PSOM, age at stroke, and months s/p) were entered into a stepwise regression equation.

Results:
Mean IQ for the sample was 84.77 (SD=17.26), significantly below average relative to healthy norms (
t
=-8.088,
p
=.000). PSOM scores ranged 0-5.5 (median/mode=1.0). The regression was significant (
F
=8.798;
p
=.000), with both PSOM score (
b
=-.350;
t
[80]=-3.483;
p
=.001) and months post stroke (
b
=-.355;
t
[80]=-3.005;
p
=.004) significantly contributing to the model, but not age at stroke.

Conclusions:
PSOM was more relevant than age at stroke in predicting long-term cognitive outcomes, and greater stroke severity was associated with lower IQ at follow-up. Finding suggest that initial PSOM score and greater time since stroke may be more relevant to long-term cognitive outcomes than age at stroke. The present study lends validity to using the PSOM both as a marker of functional severity of stroke and a potential indicator of relative risk for poorer long-term cognitive outcomes. Better predictors of cognitive outcomes for pediatric stroke are greatly needed in order to facilitate earlier intervention/rehabilitation and improve the efficacy of such efforts.
Abstract 173: Accuracy and Reliability of Brain Attack Diagnoses Including Stroke in the Pediatric Emergency Department
Authors: MacKay Mark T , Yock-Corrales Adriana , Churilov Leonid , Monagle Paul , Donnan Geoffrey A , Babl Franz E
Published: June 2021

Objectives:
Access to acute stroke interventions in the emergency department (ED) relies on correct clinical diagnosis. Our aims were to determine the accuracy and reliability of pediatric ED physician diagnosis of childhood stroke and other conditions presenting with brain attack symptoms.

Methods:
Prospective study of consecutive children aged one month-18 years presenting to the ED from June 2009-December 2010 with focal neurological deficits. Accuracy (sensitivity, specificity, receiver operator characteristic curves (ROCs)), and inter-rater agreement (kappa (κ )) were determined, between ED physician diagnoses, as recorded in the electronic hospital administrative software system, and final neurological diagnosis, following completion of diagnostic work-up.

Results:
Two-hundred-eighty seven children with 301 consecutive presentations were recruited. The most common final brain attack diagnoses included migraine in 84 children, first seizure in 48, Bell’s palsy in 29, stroke in 21, and conversion disorders in 18 children. Sensitivity of ED physician stroke diagnosis was 62% and specificity was 98% (ROC 0.8). Inter-rater agreement for ED physician and final stroke diagnosis was substantial (κ 0.61). ED physician diagnostic accuracy and reliability was highest for Bell’s palsy (ROC 0.98, κ 0.96), and lowest for CNS demyelination (ROC 0.5, κ -0.01) and cerebellitis (ROC 0.50, κ 0.50).

Conclusions:
ED physician diagnostic accuracy and reliability varies considerably across disorders presenting with brain attack symptoms. Clinical recognition tools are required to assist pediatric ED physicians with diagnosis of stroke and other serious neurological disorders.
Abstract 175: Cerebral Vasoreactivity is Impaired in Children with Sickle Cell Disease
Authors: Macedo Rejane , Pellegrini Braga Josefina , Figueiredo Maria Stella , Silva Gisele S
Published: June 2021

Background:
Sickle cell disease (SCD) is the most common cause of stroke in children. Impairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with SCD and might play a role in the pathophysiology of stroke in such patients. We assessed the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared to healthy age-matched subjects.

Patients and Methods:
Patients were selected from the pediatric outpatient clinic of the Department of Hematology at our University Hospital. All those patients with SCD disease (diagnosis confirmed by hemoglobin electrophoresis on cellulose acetate) without a history of symptomatic stroke aged 10 to 18 years old were evaluated. Healthy children of similar age and gender were also studied. Transcranial Doppler (TCD) was performed in all patients and controls subjects, with breath-holding maneuver and calculation of the breath-holding index (BHI) to assess cerebral vasoreactivity. The BHI was obtained by dividing the percentage increase in mean flow velocity occurring during breath holding by the length of time (seconds) subjects hold their breath after a normal inspiration. BHI was considered abnormal if < 0.69.

Results:
TCD was performed in 42 patients (mean age 12.7 +/-2.2 years) and 20 controls (mean age 13.90 +/-3.04 years). Blood flow velocities were higher in patients with SCD than in healthy volunteers in all arteries evaluated (p<0.01). Cerebral blood flow velocities were negatively correlated with hemoglobin levels (p<0.05). BHI values in patients with SCD were significantly lower than in control subjects (1.27 +/-0.65 versus 1.74 +/- 0.15, p=0.01 at left and 1.16 +/- 0.45 versus 1.61 +/- 0.11, p<0.01 at right). BHI was abnormal in 19% of the patients and none of the healthy controls (p=0.04).

Conclusions:
In conclusion, children with SCD may have impaired cerebral vasoreactivity, with low BHI values suggesting a reduced autoregulation capacity in these patients.
Abstract 180: Cerebral Microbleeds Are Associated with Higher Mortality Among Stroke Patients
Authors: Zand Ramin , Tsivgoulis Georgios , Singh Mantinderpreet , McCormack Michael , Noorbakhsh-Sabet Nariman , Shahripour Reza B , Goyal Nitin , Alexandrov Andrei V
Published: June 2021

Introduction:
There is limited data on the clinical significance of cerebral microbleeds (CMB) among patients with cerebral ischemia. The purpose of this study is to determine the prevalence of CMB in this population and assess the risk of in-hospital death.

Methods:
We analyzed consecutive stroke patients at two tertiary stroke centers in a two-year period. Patients without magnetic resonance imaging (MRI) or imaging confirmation of an ischemic stroke were excluded from this study. T2*-weighted MRIs were assessed for the number, location, and topography of CMBs as well as other acute and chronic cerebrovascular diseases. We compared the baseline characteristics and clinical information between patients with and without CMBs.

Results:
Out of 793 stroke patients evaluated in this study (mean age 62±14 years, 52% men, 60% African American, median admission NIHSS: 7), 127 patients (16%) had CMB on their brain imaging. Microbleeds were more prevalent among stroke patients with hypertension (OR: 2.3, 95% CI: 1.3-4.1), moderate-severe leukoaraiosis (OR 3.8, 95% CI: 1.6-6.2), and recurrent stroke (OR 1.7, 95% CI: 1.1-2.6). There was no significant difference between patients with and without CMBs in terms of sex, race, NIHSS, and discharge mRS. There was a trend toward higher risk of in-hospital mortality among patients with CMB and patients who had CMB in deep brain structures but neither reached a significant difference. However, the risk of in-hospital mortality was higher among patients with multiple (≥5) CMBs. After adjusting for potential confounders, the presence of ≥5 CMBs on T2*-MRI was independently (p<0.001) associated with a higher likelihood of in-hospital death (OR: 9.3, 95% CI: 3.0-29.2) in multivariable logistic regression analyses.

Conclusion:
Our results indicate that multiple CMBs are associated with higher mortality among stroke patients.
Abstract 182: Thermal Imaging as a Diagnostic Biomarker in Acute Ischemic Stroke
Authors: Aulmann Linda F , Busch Kira , Zegelin Andrea , Eckey Thomas , Neumann Alexander , Boppel Tobias , Brehmer Moritz , Moritz Christian , Schlüter Anneke , Royl Georg , Schramm Peter , Kemmling André
Published: June 2021

Purpose:
With highly portable mobile infrared cameras thermal imaging during acute stroke triage has become possible. The purpose of this pilot study was to evaluate the pattern of superficial facial skin temperature in patients with acute proximal arterial occlusion of the anterior circulation compared to non-ischemic controls. We hypothesize, that temperature dysregulation in stroke with associated thermal pattern may be used to predict presence of proximal vessel occlusion.

Methods:
In 46 patients suffering from acute occlusion in the anterior circulation (ICA: 17, M1-MCA: 13, M2-MCA: 16) infrared thermal imaging of the face was performed before endovascular treatment. Asymmetric temperature patterns were evaluated visually. Quantitative temperature values were obtained from regions of interest (ROIs) placed symmetrically on the left and right half of on the facial thermal image. Presence and side of vessel occlusion was correlated with temperature measurements.

Results:
Regional facial asymmetric temperature was readily visible at 0.5°C. Temperature differences ranged from 0.5 to 1.5° C in stroke patients, and <0.5°C in controls. In 16 of 17 patients with ICA occlusion, facial asymmetric temperature was detected (in 13 lower temperatures on ipsilateral side, in 3 on the contralateral side). In 11 of 13 patients with M1-MCA occlusion, facial asymmetric temperature was detected (in 8 lower temperatures on the contralateral side, 3 on the ipsilateral side). In 15 of 16 patients with an occlusion of M2-segment, asymmetric temperature pattern was apparent, however no clear trend with regard. In 16 of 20 controls, no asymmetric temperature pattern >0.5°C was observed.

Conclusion:
Thermal imaging could serve as a fast point-of-care test to detect asymmetrical pattern in facial temperature as a predictor of proximal vessel occlusion in stroke. However, the current method is prone to imaging artifacts and reliability of detected asymmetry is moderate.
Abstract 185: Association of Antiplatelet Pretreatment With Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis: A Systematic Review and Meta-analysis of Randomized Clinical Trials
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Zand Ramin , Sharma Vijay K , Köhrmann Martin , Giannopoulos Sotirios , Dardiotis Efthymios , Alexandrov Anne W , Schellinger Peter D , Alexandrov Andrei V
Published: June 2021

Background & Purpose:
In a recent randomized controlled trial (RCT) of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) antiplatelet pre-treatment (APP) was associated with adverse outcomes. We conducted a systematic review and meta-analysis of available RCTs to investigate the association of APP with outcomes of AIS patients treated with IVT.

Methods:
The outcome events of interest included symptomatic intracranial hemorrhage (sICH), complete recanalization (CR), 3-month favorable functional outcome (FFO, mRS-score: 0-1), functional independence (FI, mRS-score: 0-2), and mortality. Both unadjusted and adjusted (for baseline stroke severity and age) analyses were performed using random effects methodology.

Results:
We included 8 RCTs (5,332 total patients, 34% with APP). In unadjusted analyses (Figure 1), APP was associated with higher likelihood of sICH (OR=2.01, 95%CI: 1.53-2.63) and death (OR=1.59, 95%CI: 1.24-2.03; 1C) and lower likelihood of 3-month FI (OR=0.69, 0.56-0.85). No association was detected between APP and 3-month FFO (OR=0.79, 95%CI: 0.58-1.07) and CR (OR=0.64, 95%CI: 0.04-11.66). In adjusted analyses (Figure 2), APP was related to higher odds of sICH (OR=1.89, 95%CI: 1.14-3.12). There was no association between APP and 3-month FI (OR=0.94, 95%CI: 0.70-1.26) or death (OR=1.01, 95%CI: 0.55-1.86). In all analyses no evidence of heterogeneity was detected.

Conclusion:
Despite APP association with a higher risk of sICH after thrombolysis, three-month functional outcomes appear un-affected by APP. APP before IVT should not be used as an excuse to withhold or to lower the dose of IVT.