bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5: “Early Mobilization Protocol” Can Be Initiated In The Intensive Care Unit In Acute Ischemic Stroke Patients After Receiving Intravenous Alteplase
Authors: Bhagavan Sachin , ISHFAQ Muhammad F , Pullimamidi Shruthi , Sweeney Megan , Yelam Anudeep , Beladakere Ramaswamy Swathi , Katyal Nakul , bhatia kunal , Lybeck-Brown Eric T , Huang Wei , Jaura Attiya , French Brandi R , Gomez Camilo R , Siddiq Farhan , Qureshi Adnan I
Published: February 2022

Context:
Current guidelines recommend bed rest for 24 hours after receiving intravenous alteplase which may not be necessary and delay rehabilitation in a large proportion of acute ischemic stroke patients.

Objective:
To determine the feasibility of “early mobilization protocol” within the intensive care unit (ICU) in patients with acute ischemic stroke who received intravenous alteplase.

Methods:
All consecutive patients were admitted to the ICU with an acute ischemic stroke who received intravenous alteplase from October 2019-June 2021 were considered for “early mobilization protocol”. Patients≥18 years of age with minor, moderate or severe ischemic stroke (NIHSS score ≤22) were eligible and mobilization was initiated within 13-24 hours after intravenous alteplase administration. Exclusion criteria included hemodynamic instability, on mechanical ventilation, unstable neurological examination or progressive symptoms, or presence of external ventricular drain for hemorrhagic transformation within 24 hours of intravenous alteplase.

Results:
A total of 137 patients (56.8%) patients were eligible among 241 patients who were admitted to our institution with acute ischemic stroke after receiving intravenous alteplase. Mean age (±SD) was 63.4±16.6 and 66.2±17.0 years for the patients included and excluded in the early mobilization protocol, respectively. The mean NIHSS score (±SD) at baseline was 5.3±4.4 and 9.9±7.3 for the patients included and excluded in the early mobilization protocol, respectively. Early mobilization protocol was initiated at 18.3±3.6 hours in eligible patients compared with routine mobilization initiated at 41.6±19.8 hours in excluded patients (p<0.001). The mean NIHSS score (±SD) at discharge (1.0±2.2 versus 4.2±7.0, p<0.001) was significantly lower and rate of modified Rankin scale 0-1 at discharge (86.9% versus 67.3%, p=0.0003) was significantly higher in patients in the early mobilization protocol compared with those who were excluded.

Conclusion:
Early mobilization protocol in patients post intravenous alteplase treatment can be initiated in the ICU in appropriately selected patients without any adverse effects on neurological and functional outcomes.
Abstract 50: Testing Procedures Influence Allocentric And Egocentric Neglect Associations
Authors: Durfee Alexandra Z , Joseph Briana , Hillis Argye E
Published: February 2022

Testing Procedures Influence Allocentric and Egocentric Neglect Associations

Hemispatial visual neglect is common after right hemisphere (RH) stroke and can impact attention to the left side of view (egocentric) or the left side of objects irrespective of location (allocentric). Allocentric and egocentric neglect correlations have been reported as high as 0.80; however, others report low correlations and dissociations between them using the same task but with different administration procedures.
To determine if divergent results are due to distinct procedures, we compared allocentric and egocentric neglect presence and severity between the two.

Thirty-eight adults (21 female, age 65±15 years, 14±2 years education, 21 black/16 white) completed neglect testing within 10 days of RH stroke. Neglect testing comprised circling 10 complete circles (egocentric task) and crossing out 20 circles with gaps (10 left gaps, 10 right gaps; allocentric task). All participants completed testing once with allocentric and egocentric tasks on separate pages and once with both tasks on the same page. We used paired
t
-tests, Pearson correlations, and Fisher’s Exact test for analyses.

Neglect severity did not differ across single- and separate-page conditions (
allocentric
:
t
(32)=0.68,
p
=0.50;
egocentric
:
t
(36)=-1.27,
p
=0.21). Single- and separate-page severity scores were strongly associated (
allocentric
:
r
=0.65,
p
<0.001;
egocentric
:
r
=0.52,
p
=0.004). Allocentric and egocentric neglect severity were moderately associated for single-page (
r
=0.45,
p
=0.008) but not separate-page (
r
=0.10,
p
=0.60) conditions. Diagnosis of allocentric (
single-page
: 6%,
separate-page
: 3%), egocentric (
single-page
: 12%,
separate-page
: 9%), or allocentric and egocentric (
single-page
: 27%,
separate-page
: 39%) neglect was not dependent on page condition (
p
=0.75).

To conclude, assessment procedures influenced association of allocentric and egocentric neglect severity but not categorical diagnosis, and presence of both appeared more common than either alone. Studies that reported high correlations between the allocentric and egocentric neglect on the same task may have included participants with lesions causing both types of neglect due to their size and/or location.
Abstract 55: Improved Efficiency, Analysis And Reporting Of Stroke Data By Automating Manual Data Extraction With Stroke Specific Data Fields Built In The Electronic Health Record
Authors: Laclair Karissa , Carter Amber , Stowe Debra , Broomer Olivia , Bell Hannah , Hunnicutt Sharley , Harris Dana , Cates Angie , Schull Elizabeth
Published: February 2022

Data collection and analysis is essential for stroke center certification, registries and as a public responsibility. When large amounts of data need to be extracted, manual data collection is extremely time consuming. The existing challenge for stroke centers is leveraging technology for efficient data collection and analysis. The purpose of this project was to improve efficiency, analysis and reporting of stroke data by automating manual data extraction with stroke specific data fields built in the electronic health record. The data collected would create individual patient summaries, data reports and a stroke dashboard. The method chosen to accomplish this was by using data moved through an EPIC Clarity Database, our Enterprise Data Warehouse Suite of products, Subject Area Mart (SAM) and Instant Data Entry Application (IDEA app) and 5 SSRS Reports. Use of the innovative IDEA app allows for updating data behind the scenes. This 8-month collaborative project included IT support from a project manager, quality analyst, Power BI developer and SAM/data layer developer. This project resulted in over 250 discrete data points and 25 separate dashboard tabs, including volume, demographics, stroke metrics and outcomes. System-wide stroke data over a 10-month period included an overall volume of 2,814 patients, with 280 receiving tPA or thrombectomy. The option to run individual patient summaries and 5 different auditing reports was included. Estimated staff time savings is over 50 hours per month. In conclusion we have demonstrated it is possible to pull discrete data points from the electronic health record to be used in a dashboard, patient summaries and stroke data reports. The biggest challenge was dividing the large scope of work into manageable stages. A next step is to pull in EMS data through health data exchange. Streamlining data collection and analysis efficiency is essential for the future of a stroke center of excellence.
Abstract 56: Predictors Of Post Stroke Discharge Follows-ups In The Stroke Clinic And Role Of A Stroke Navigator To Improve Follow-ups
Authors: Pope Leslie , dellostretto nicole , Hackett Chris , Heintz Rebekah , Noah Patty , Cerejo Russell , Tayal Ashis H
Published: February 2022

Objective:
We aimed to evaluate which factors contributed to acute ischemic stroke (AIS) following up in stroke clinic post hospitalization.

Methods:
Single center retrospective analysis of AIS patients from January 2016 to April 2021. Patients were excluded if: died during index hospitalization, discharged to hospice or had incomplete data. We evaluated our primary outcome: factors contributing to patients attending post-discharge appointments and secondary outcome: factors contributing to patients scheduling post-discharge appointments utilizing binomial stepwise logistic regression models. Subgroup analysis compared latency to be seen in follow-up clinic between patients who had an appointment scheduled at discharge compared to those who did not using a Mann-Whitney test.

Results:
Out of 7960 AIS patients, 2734 were included in this study, 2130 (77.9%) of those patients scheduled an appointment post-discharge, whereas 1649 (60.3%) attended an appointment post-discharge. Patients were more likely to attend a follow-up appointment if scheduled while hospitalized, OR=3.48 [95%CI, 2.94-4.14], p<0.001 and less likely if: older OR=0.98 [95%CI 0.97-0.98], p<0.001; admitted for a longer duration, OR=0.98 [95%CI, 0.96-1.00], p=0.05; lived farther away OR=0.99 [95%CI, 0.96-0.99], p<0.001 or had higher modified Rankin Scale (mRS) at discharge OR=0.73 [95%CI, 0.69-0.79], p<0.001. Patients were more likely to schedule a follow-up appointment after initiation of the AIS navigator program, OR=8.52 [95%CI, 6.59-10.57], p<0.001.Patients with follow-up appointments scheduled during their initial hospitalization were seen in clinic sooner; 27 days (IQR 19-36) versus 37 days (IQR 22-61), p<0.001.

Conclusion:
Patients with AIS were more likely to schedule an appointment after initiation of a nurse navigator program. Patients were also more likely to attend post-discharge stroke clinics if their appointments were scheduled during index hospitalization.
Abstract 57: Seeking Support For Symptoms Of Stroke Delays Emergency Medical Service Activation For Thai Women And Men
Authors: Potisopha Wiphawadee , Vuckovic Karen M , Devon Holli A , Park Chang , Phutthikhamin Nichapatr , Hershberger Patricia
Published: February 2022

Background:
National stroke campaigns have been implemented to improve stroke knowledge and awareness for the Thai public. Despite these efforts, only a minority of people recognize stroke symptoms and seek treatments within 4.5 hours after symptom onset. Studies reveal sex differences in stroke knowledge, which contributes to delayed treatment-seeking actions.

Purpose:
This study aimed to examine sex differences in stroke knowledge, symptoms, stroke recognition, and initial action between men and women after experiencing acute strokes.

Methods:
A cross-sectional study was conducted at three hospitals in Thailand between September and November 2020. Medical record reviews and patient interviews were completed within seven days of admission. Standardized questionnaires for prior stroke knowledge (stroke warning signs & proper actions), clinical manifestation, stroke recognition, first action, and the activation of the emergency medical service (EMS) were used.

Results:
A total of 170 patients (54% men) with a median age of 63 years were included. Mean scores for prior stroke knowledge were higher in men compared to women (2.97 vs. 2.23, p = .02). Men were more likely than women to identify sudden numbness or weakness and sudden trouble walking or dizziness as stroke warning signs (62% vs. 42%, p = .01; 57% vs. 40%, p = .03, respectively). Women more frequently experienced severe headache (37% vs. 18%, p < .01). No significant differences between men and women were found in stroke recognition (20% vs. 26%) and activation of the EMS system (22% vs. 19%). Seeking support from someone nearby or on the phone was the most frequent first action in men (47%) and women (55%), which often delayed EMS activation.

Conclusion:
Even though men scored higher in stroke knowledge than women, challenges to activating the EMS were found in both sexes, highlighting the need to explore targeted educational material and knowledge translation among high-risk stroke patients and their relatives, regardless of sex.
Abstract 59: Prevalence And Predictors Of Food Insecurity Among Stroke Survivors In The United States
Authors: Kim-tenser May A , Ovbiagele Bruce , Markovic Daniela , Towfighi Amytis
Published: February 2022

Introduction:
Social determinants of health have a substantial impact on stroke. Food insecurity (FI) - lack of consistent access to food due to poor financial resources – is a barrier to a healthy diet, a cornerstone for stroke prevention. The prevalence and predictors of FI among stroke survivors are unknown.

Methods:
Using NHANES data from 1999-2015, we assessed prevalence, predictors, and temporal trends in FI in adults >=20 years with and without prior stroke. FI was based on response to the Food Security Survey Module. Full/marginal food security were considered food secure, while low/very low food security were considered food insecure. Stroke history was self-reported. Prevalence of FI among persons with/without stroke across time was adjusted for age. Factors associated with FI among persons with stroke were determined using multivariable logistic models, adjusting for year and sociodemographic factors.

Results:
Among 48,242 participants, 1,877 reported history of stroke. FI was more prevalent among persons with prior stroke (17%) vs. those without prior stroke (12%), p<0.001. Prevalence of FI increased over time from 6.3% in 1999 to 29.9% in 2015 among stroke survivors and from 8% to 17% among individuals without prior stroke (p<0.001). The age standardized prevalence of FI over the entire time was 23.8% among stroke survivors vs 10.9% among individuals without prior stroke (p < 0.001). Factors associated with FI among stroke survivors included non-White race, younger age, lower education, non-married status, poverty income ratio (PIR) < 130%, comorbid MI or diabetes, current smoking, and obesity. In the adjusted model, FI was associated with younger age (aOR 0.96, 95% CI 0.95-0.97, p<0.01), Hispanic ethnicity (aOR 2.12,1.36-3.31, p<0.01), lower education (aOR 1.67, 1.17-2.38, p<0.01), non-married status (aOR 1.49, 1.01-2.19, p=0.04), and PIR< 130% (aOR 3.78, 2.55-5.59, p<0.01).

Conclusions:
One in three stroke survivors have FI, nearly double the prevalence in those without stroke. Addressing the fundamental drivers of FI (e.g. socioeconomic status) and targeting vulnerable demographic groups may have a profound influence on stroke prevalence. To our knowledge, this is the first study of FI among stroke survivors in the U.S.
Abstract 61: Population Incidence Of Cerebral Venous Thrombosis (CVT) From A Large Canadian Cohort 2001-2017
Authors: Zhou Lily , Ngo Long H , Field Thalia S
Published: February 2022

Background:
Previous estimates of CVT incidence vary widely (3-20 per million per year), with more recent studies reporting a higher incidence. Here we present CVT incidence obtained from a large inclusive cohort from the province of British Columbia (BC), Canada (population 5 million) identified through linkage of provincial administrative data.

Methods:
A retrospective population-based cohort of CVT patients was constructed using ICD 9/10 codes to capture CVT hospitalizations from 2001-2017 in the BC subset of the Canadian Institute for Health Information’s Discharge Abstract Database. The first instance of CVT was extracted and a one-year look-back period was used to exclude prevalent cases. Linkages were made to outpatient prescription data, cancer and prenatal registries to determine patient risk factors.

Results:
Five hundred and fifty-four unique CVT cases were identified (mean age 50.9, SD 19.4; 55.4% female) (Table 1). Males were more likely to have cases associated with head trauma (12% male vs 7% female,
p
=0.03) and head and neck infections (13% vs 6%,
p
=0.009). Cases were diagnosed in the peripartum setting (within 3 months of delivery) for 11% of females. Overall annual incidence was 8.7 (95% CI 8.0-9.4) per 1 000 000 inhabitants. Annual CVT incidence increased over the study period for both men and women (Figure 1).

Conclusions:
Annual incidence of CVT diagnosis increased from 2001-2017 in BC Canada, similar to trends reported within the United States. This may be due in part to improved ascertainment with increased use of routine vascular neuroimaging over time. Nearly half of cases were male but were more likely to have CVT in the context of trauma or infection.
Abstract 67: Observed And Genomic Life’S Simple 7 Influence Brain Health-related Neuroimaging Traits In Persons Without Stroke Or Dementia
Authors: Acosta Julian , Both Cameron , Rivier Cyprien , Leasure Audrey C , Gill Thomas M , Payabvash Sam , Sheth Kevin N , Falcone Guido J
Published: February 2022

Background:
The AHA Life’s Simple 7 (LS7) promote cardiovascular health. We hypothesized that a better LS7 profile translates into significant brain health benefits in persons without stroke or dementia. We also evaluated whether genomic information can effectively recapitulate the observed LS7.

Methods:
We conducted a nested study within the UK Biobank, restricting analysis to stroke- and dementia-free participants with brain MRI and genomic data. We ascertained the LS7 (blood pressure, LDL cholesterol, HbA1c, smoking, exercise, diet and BMI) clinically and genomically. For the latter, we used genetic variants known to influence each trait. The total LS7 score ranges from 0 (poor) to 14 (optimal), and was categorized as poor (≤4), average (49). We tested for association between observed/genomic LS7 and two neuroimaging markers of brain health: white matter hyperintensities (WMH) volume and brain volume.

Results:
We analyzed 35,914 participants. For WMH, compared to persons with poor observed LS7, those with average and optimal had 18% (beta -0.17; se=0.02; p<0.001) and 43% (beta -0.37; se=0.02; p<0.001) lower volumes. Similar results were obtained when using the genomic LS7 (all p<0.001). For brain volume, those with average and optimal LS7 had 0.86% (beta 0.12; se=0.02; p<0.001) and 2.4% (beta 0.18; se=0.02; p<0.001) higher volumes. The genomic LS7 were not associated with brain volume (all p>0.05). Blood pressure and HbA1c were the most powerful contributors to WMH and brain volume, respectively (Figure).

Conclusions:
Better LS7 profiles are associated with better profiles of 2 brain health-related neuroimaging markers in persons without stroke/dementia. Genomic information appropriately recapitulated one of these associations. These results emphasize the beneficial role of cardiovascular health optimization in persons without stroke/dementia and point to genomic data as potentially useful to identify high risk individuals.
Abstract 68: Acute Myocardial Infarction Is Associated With Acute And Progressive Decline In Global Cognition: A Pooled Cohort Analysis Of The Aric, Mesa, Cardia, Chs, Fos And Nomas Studies
Authors: Johansen Michelle C , Gross Alden , Gottesman Rebecca F , Han Dehua , Tilton Nicholas , Whitney Rachael , Briceno Emily M , Giordani Bruno , Shore Supriya , Elkind Mitchell S , Manly Jennifer , Sacco Ralph L , Griswold Michael , Psaty Bruce , Sidney Stephen , Sussman Jeremy B , Yaffe Kristine , Moran Andrew E , Heckbert Susan R , Hughes Timothy M , Galecki Andrzej , Levine Deborah A
Published: February 2022

Introduction:
Apart from stroke, cognitive change after incident myocardial infarction (MI) is unclear. We aim to determine associations between incident MI and acute and long-term changes in cognitive function, controlling for risk factors and pre-MI cognitive trajectories, censoring for stroke.

Methods:
We performed a pooled analysis of 31,377 participants, ≥18 years, free of MI and dementia, from 6 longitudinal cohort studies (1971-2017): Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Outcomes were changes in global cognition (primary), memory, and executive function. Linear mixed-effects models were used to estimate the association between incident MI and acute cognitive decline at the time of MI (Model A), and decline in cognition over the years after MI (Model B).

Results:
Median study follow up was 6.4 years (IQR 4.9-19.7 years) and 1,047 participants had incident MI. Incident MI was associated with significant acute decline in global cognition and executive function, but not memory, after the MI event (Models A, Table 1). After including change in cognitive function (slope) after incident MI in the model, the effect estimates indicating acute declines in global cognition and executive function were not significant (Models B, Table 1). However, participants with incident MI demonstrated significantly faster declines in global cognition (-0.15 points/year faster [95% CI, -0.21 to -0.10]), memory (-0.13 points/year faster [95% CI, -0.23 to -0.04]), and executive function (-0.14 points/year faster [95% CI, -0.20 to -0.08]) compared to those without MI (Models B, Table 1).

Conclusions:
Incident MI is associated with faster declines in global cognition, memory, and executive function over years following the MI event.
Abstract 72: Risk Of Dementia Following First-ever Hemorrhagic Or Ischemic Stroke In The General Population
Authors: Waziry Reem , Dufouil Carole , Hofman Albert , Ikram Kamran , Debette Stephanie , Wolters Frank J , Fani Lana , Romero Rafael J , Aparicio Hugo J , Lioutas Vasileios , Viswanathan Anand , Sullivan Kevin , Goudsmit Jaap , Seshardi Sudha , Ikram Mohammad A
Published: February 2022

Objective:
To assess risk of dementia after first-ever hemorrhagic or ischemic strokes in three prospective cohort studies (Three City, Framingham Heart Study and Rotterdam Study).

Methods:
Prospective data on incident hemorrhagic or ischemic strokes and matched stroke free comparison was used for each stroke subtype. 5-year risk of dementia after hemorrhagic or ischemic stroke was assessed using a matched case-cohort design. A random effects meta-analysis was used to combine hazard ratios for each study and variations in risk stratified by
APOE
ε4 allele were assessed. A direct comparison of risk of dementia after hemorrhagic compared with ischemic strokes was evaluated. In a sensitivity analysis Fine & Gray models were conducted after adjusting for competing deaths and subdistribution hazard ratios were computed. Pre-event and post-event cumulative incidence of dementia at 3, 6, 12, 24, 36 and 60 months were assessed.

Results:
A total of 4,922 persons, including 247 incident hemorrhagic strokes and 1,427 ischemic strokes were included. The combined hazard ratios of dementia were 2.78 (95% CI 1.28, 6.03) after hemorrhagic and 3.35 (1.51, 7.43) after ischemic stroke compared to stroke free individuals. The combined risk of dementia was 0.71 (0.14, 3.68) after hemorrhagic compared with ischemic stroke. Among individuals with
APOE
ε4 allele, the risk of dementia was 3.88 (1.16, 12.98) after hemorrhagic stroke and 2.10 (1.28, 3.42) after ischemic stroke compared to stroke-free individuals. The cumulative incidence post-event for hemorrhagic strokes flattened between 6 and 24 months with slight increase thereafter, in-contrast to a steady increase in dementia risk over time after ischemic strokes.

Conclusions:
No difference was observed in overall 5-year risk of dementia after hemorrhagic or ischemic stroke, while the risk was about 3 times higher compared to stroke-free individuals of similar risk profiles.
APOE
ε4 allele doubles the risk of dementia among hemorrhagic stroke survivors. Risk of dementia after ischemic stroke follows a stepwise pattern overtime, in contrast, dementia risk after hemorrhagic stroke is highest in the early phase.
Abstract 87: Chronic Kidney Disease Induces Cerebral Microhemorrhages In Aged Mice
Authors: Fang Chuo , Lau Wei Ling , Sun Jessica , Vallejo Adrian , Liu Jihua , Liu Han , Paganini-Hill Annlia , Sumbria Rachita K , Cribbs David H , Fisher Mark
Published: February 2022

Introduction:
Chronic kidney disease (CKD) is increasingly recognized as a risk factor of cerebral microvascular disease, but its association with common neuropathologic changes is not well understood. We investigated the relationship between CKD and development of cerebral microhemorrhages (CMH) in a mouse model of aging. We also examined the effect of CKD on endothelial cell function in an
in vitro
blood-brain barrier (BBB) model.

Methods:
CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We performed standard histology using Prussian blue staining to examine CMH formation. Correlations between CMH burden and serum creatinine levels were assessed. In cell culture studies, human brain microvascular endothelial cells (ihBMECs) derived from induced pluripotent stem cell line IMR90-4 were treated with serum from healthy or CKD patient donors for up to 3 days. Transendothelial electrical resistance (TEER) and tracer (sodium fluorescein) permeability across the ihBMEC monolayer were measured to assess the integrity of the
in vitro
BBB.

Results:
CKD induction in aged C57BL/6J mice caused a significant increase in both serum creatinine level (0.09±0.01 mg/dL to 0.43±0.03 mg/dL, p<0.001) and CMH number (p<0.05), without alteration of systolic or diastolic blood pressure. Number of CMH was positively correlated with serum creatinine level (r=0.41, p<0.001). Incubation of CKD serum with ihBMECs significantly reduced TEER by 26% (p<0.05) and increased sodium fluorescein permeability by 100% (p<0.01) across the ihBMEC monolayer.

Conclusions:
Adenine-induced CKD promotes the development of CMH in aged C57BL/6J mice independent of blood pressure, and extent of CMH development is directly proportional to degree of renal insufficiency. Moreover, serum-derived factors in CKD disrupt BBB integrity
in vitro.
These findings suggest CKD provokes microvascular injury at the capillary level, leading to CMH formation in this model.
Abstract 90: Meta-analysis Of Early Treatment Of Hypertension In Acute Ischemic Stroke And Functional Outcome
Authors: Gordon Weston , Ilorah Chike
Published: February 2022

Introduction:
Elevation in blood pressure (BP) in the early period following acute ischemic stroke (AIS) is frequent and likely due to a physiologic response to neurologic insult, damage to specific structures, and failure of cerebral autoregulation. It remains unclear whether early treatment of elevated BP after AIS influences clinical outcome in these patients. This meta-analysis aimed to investigate if treatment of sustained elevations in BP in the early period following AIS leads to a reduced risk of poor functional outcome.

Method:
Systematic review identifying randomized-controlled, double-blinded trials of AIS patients between 1994-2020 comparing those who receive anti-hypertensive medications within 72 hours of symptom-onset to those who do not receive medication. The primary outcome was poor functional outcome (defined by mRS > 2 at 90 days). Results were pooled using inverse variance random effects meta-analyses. Conclusions accounted for the magnitude of effect, precision, and risk of bias in the studies using the modified GRADE process of the American Academy of Neurology (AAN).

Results:
Ten randomized-controlled double-blinded studies totaling 15762 AIS patients met inclusion criteria. Baseline patient characteristics were without significant confounders. Mean symptom-onset to treatment time was 3-72 hours. The duration of treatment ranged from 3-90 days. Antihypertensive medications used included calcium-channel blockers, angiotensin receptor blockers, ACE-inhibitors, nitrates, and diuretics. Overall, poor functional outcome occurred in 32.4% of patients. There was no statistical difference in poor functional outcome in patients treated with antihypertensive medications within 72 hours of symptom-onset vs no treatment (OR=1.05, CI 95% 0.93-1.18).

Conclusion:
For the early period following AIS, treatment of sustained elevations in BP does not reduce the risk of mRS > 2 at 90 days. Confidence in the evidence is strong, anchored by selection of large randomized-controlled, double-blinded trials. Limitations include variable BP medications, initial stroke severities, and AIS mechanisms.
Abstract 94: Prospective Clinical Evaluation Of The Modified CDC Criteria For Diagnosis And Management Of Stroke Associated Pneumonia
Authors: Bustamante Alejandro , Faura Julia , Olive-gadea Marta , Ezcurra Garbiñe , VIDAL DIANA , DomínguezMayoral Ana , Avellaneda-Gomez Carla , Mari Mar Freijo , Zapata-Arriaza Elena , Serrano Gemma , Fernandez-Perez Isabel , Rubiera Marta , Dorado Laura , Montaner Joan R
Published: February 2022

Objective:
Stroke-associated infections (SAI) and specially pneumonia (SAP) frequently complicate stroke, leading to poor outcome. The modified Center of Disease Control and Prevention (mCDC) diagnostic criteria for SAP have been proposed, but not yet validated. We aimed to analyze the fulfillment of these criteria for SAP diagnosis and antibiotic guidance, as well as compare clinical outcomes between mCDC-defined SAP and physician’s diagnosed pneumonia.

Methods:
The PROTEUS study was a prospective, multicenter, observational study including ischemic stroke patients with baseline stroke severity (National Institutes of Health Stroke Scale) NIHSS≥4. Patients with concurrent infection or antibiotic use were excluded. During the first week after stroke, the mCDC criteria for SAP were daily assessed by the study investigators. Clinical diagnosis of pneumonia and other infections, and antibiotic use were recorded by treating physicians. Clinical outcome was assessed with the modified Rankin scale (mRS) at three months, and categorized into poor (mRS>2) and favorable (mRS≤2) outcome. The effect of criteria-defined SAP and physician-diagnosed SAP on clinical outcome was evaluated by logistic regression analysis.

Results:
From July-2018 to May-2021, 340 patients were included in 9 stroke units from Spain. Of them, any SAI was diagnosed in 75 patients (22.1%), being 41 (12.1%) diagnosed as pneumonia by physicians. SAP according to mCDC criteria was diagnosed in 26 cases (7.6% of the cohort, 63.4% of physician’s diagnoses). Antibiotics were used in 88.5% of criteria-defined SAP and 73.3% in physician-diagnosed pneumonia (50% in patients with pneumonia not fulfilling mCDC criteria). In logistic regression analysis, criteria-defined SAP was an independent predictor of 3-month poor outcome (OR=7.13 (1.58-32.12)). However, physician-diagnosed pneumonia not fulfilling mCDC criteria was not an independent predictor of poor clinical outcome (OR=1.40 (0.38-5.08)).

Conclusions:
Despite being associated with clinical outcome, mCDC criteria are not used in clinical practice, neither for SAP diagnosis nor to guide antibiotic therapy. Adherence to these criteria might reduce variability in clinical diagnosis and antibiotic overuse in stroke units.
Abstract TMP1: Multi-omic Biomarker Development In A Mendelian Neurovascular Disease, Cavernous Angioma
Authors: Srinath Abhinav , Romanos Sharbel , Li Ying , Xie Bingqing , Chen Chang , Moore Thomas , Lightle Rhonda , DeBiasse Dorothy , Sone Je Yeong Y , Shen Le , McCurdy Sara G , Lai Catherine , Stadnik Agnieszka , Piedad Kristina , Dorrestein Pieter , Weldon Kelly , Snellings Daniel , Shenkar Robert , Gilbert Jack , D'Souza Mark , Sulakhe Dinanath , Ji Yuan , Lopez-ramirez Miguel A , Kahn Mark L , Marchuk Douglas A , Ginsberg Mark H , Girard Romuald , Awad Issam A
Published: February 2022

Introduction:
Cavernous Angioma (CA) is a hemorrhagic neurovascular disease characterized by either a familial form with autosomal dominant germline mutations in one of three CCM genes or a sporadic form with somatic mutations of the same genes. Circulating proteins have been previously investigated as possible diagnostic and prognostic biomarkers of disease activity, with up to 86% and 88% sensitivity and specificity, respectively. We hypothesize that differentially expressed (DE) plasma microRNAs and metabolites in CA patients can be integrated with plasma proteins to increase the sensitivity and specificity of circulating CA biomarkers.

Methods:
Mechanistically relevant homologous DE miRNAs were identified between familial CA patients and preclinical murine models and validated in an independent cohort of patients using real time qPCR. In conjunction, DE metabolites were determined in CA patients using liquid-chromatography mass spectrometry. The interactions of these metabolites with the previously established CA transcriptome, proteome, and microbiome were queried to assess for mechanistic relevance. Optimal diagnostic models of proteins, DE miRNAs, and DE metabolites alone were next established. Plasma metabolites and miRNAs were then separately integrated with protein, using a machine learning-implemented, Bayesian approach to develop diagnostic CA biomarkers.

Results:
The optimal diagnostic biomarker model with only DE miRNAs performed at up to 68%, while proteins and metabolites achieved up to 68%, and 82% accuracy respectively. The optimal combination for proteins with miRNAs improved the diagnostic association of familial-CA disease to up to 94.7% sensitivity and 100% specificity. Integrating metabolites and proteins improved the diagnosis of CA disease and its clinical manifestations to 100% sensitivity and 100% specificity.

Conclusion:
Combining plasma proteins with miRNAs or metabolites can improve diagnostic accuracy of CA disease and its disease characteristics above any single molecular modality alone. Future studies should incorporate proteins, miRNAs, and metabolites to further increase diagnostic accuracy, and validate these in a larger cohort with control for demographic and disease features.
Abstract TMP105: Time Varying Depression And Incident Stroke In Geographic And Racial Diverse Population
Authors: Andrabi Mudasir S
Published: February 2022

Introduction:
Depression is a risk factor for stroke; however, the impact of changes in the level of depressive symptoms on the risk of incident stroke is less well described.

Methods:
The study included participants from REGARDS, a national longitudinal cohort study of 30,239 Black and White adults aged ≥ 45 years at baseline 2003-2007. Depressive symptoms were assessed longitudinally using the 4-item Center for Epidemiologic Studies Depression Scales (CES-D-4), and scores of 4+ were categorized as “high.” Over up to 18 years of follow-up, for each participant with each serial assessment, we categorized the transition in depression as moving from low to low (LL), low to high (LH), high to low (HL), and high to high (HH), and used Cox regression to assess stroke risk subsequent to the transition, with incremental adjustment for risk factors.

Results:
Among 20,691 participants, we observed over 80,447 transitions in depressive symptom level and 832 incident strokes. Participants in the HH group had a higher risk for stroke compared to the LL group in both unadjusted {[HR] = 1.46, 95% confidence interval (CI) = 1.08–1.97}, and adjusted models, regardless of adjustment for demographics [HR] = 1.63, (CI = 1.21–2.20), plus SES [HR] = 1.50, (CI = 1.11–2.03), and stroke risk factors [HR] = 1.38, (CI = 1.01–1.90). However, full adjustment attenuated the effect. In both unadjusted and adjusted models, participants in the LH group were at marginally higher risk than LL and those in the HL group had a low risk like that of the LL group (see Table).

Conclusion:
Transition in levels of depression symptoms directly impacts the risk for stroke. Screening and intervention delivery for depressive symptoms may consider the level of symptoms as a dynamic process.
Abstract TMP107: Association Between Apixaban Concentration And Clinical Outcomes In Asians With Atrial Fibrillation
Authors: Lin Shin Yi , Kuo Ching-Hua , Ho Li-Ting , Liu Yen-Bin , Huang Chih-Fen , Tang Sung-Chun , Jeng Jiann-Shing
Published: February 2022

Background and Purpose:
Real-world data regarding apixaban concentrations are sparse. This prospective study aimed to investigate the association between apixaban concentration and thromboembolic or major bleeding events among Asians with atrial fibrillation.

Methods:
Atrial fibrillation patients older than 20 years, administered apixaban, and had a CHA2DS2-VASc score ≥2 points were enrolled. Peak and trough blood samples were collected to measure apixaban concentrations using ultra-high-performance liquid chromatography with tandem mass spectrometry. A Cox proportional hazard model was used to investigate the factors associated with thromboembolic or major bleeding events. Univariate followed by multivariate logistic regression analyses were performed to determine the factors associated with high or low apixaban concentrations.

Results:
From November 01, 2016 to February 28, 2021, 279 participants (56.3% male) were enrolled. Compared to clinical trials, 22 (7.9%) patients had trough concentration lower than the expected range, and 76 (27.2%) patients had peak concentration higher than the expected range. The average follow-up duration was 1.52±1.20 years. Low trough concentration was associated with thromboembolic events (hazard ratio [HR] and 95% confidence interval [CI], 6.75 [1.10 to 41.21]; p=0.04). Conversely, high creatinine clearance was inversely associated with thromboembolism (HR and 95% CI, 0.94 [0.90 to 1.00]; p=0.04). Off-label underdose regimen and suboptimal adherence were identified as significant factors (odds ratio and 95% CI, 4.12 [1.49 to 11.42], and 3.50 [1.11 to 11.03], respectively) for predicting lower-than-expected trough concentration.

Conclusions:
Thromboembolic events in apixaban therapy were associated with low trough concentrations. Further, unnecessary reduction in apixaban dose and impaired apixaban adherence predicted low trough concentrations. Measurement of apixaban concentrations may be required in certain populations.
Abstract TMP109: Isosorbide Mononitrate And Cilostazol Treatment Prevents Temporal Changes In The Brain Microstructure Of Diabetic Rats Following Microemboli Injection: Relevance To Vascular Cognitive Impairment And Dementia (VCID)
Authors: Chandran Raghavendar , Li Weiguo , Nie Xingju , Voltin Joshua , He Lianying , Jamil Sarah , Falangola Maria Fatima , Ergul Adviye
Published: February 2022

Diabetes doubles the risk of VCID, but underlying reasons for this are not understood and preventive therapeutic strategies are lacking. We showed that diabetic but not control rats develop progressive cognitive decline in a microemboli (ME) model of VCID. Given that cerebrovascular dysfunction is a common pathology between diabetes and VCID, we hypothesized that improvement of endothelial function in diabetes prevents ME-mediated white matter injury. Our treatment paradigm was based on the ongoing LACI-2 trial which assesses the efficacy of isosorbide mononitrate (ISMN) and cilostazol (CZL) in the prevention of small vessel disease (SVD) progression. Seven-eight weeks after diabetes onset, control and diabetic rats were treated with ISMN/CZL for 4 weeks, then injected with cholesterol ME and monitored longitudinally using three different MRI parameters - diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI) and cerebral blood flow (CBF). We previously reported decreased fractional anisotropy and increased diffusivity at 12 weeks after ME injection in diabetic rats, indicating possible loss of tissue integrity in the cortex and hippocampus. In the current study, we detected a time effect in both groups for DTI and DKI metrics (measured in cortex and corpus callosum as shown in the table as well as in hippocampus, internal and external capsule) but in most of them there was no disease/group-effect. Also, CBF was higher in diabetic rats at all time points. This suggests that drug treatment with ISMN/CZL before ME injection prevented the possible deleterious effects of the latter in the diabetic rats by improving the endothelial integrity and it is a viable preventive and possibly therapeutic strategy for VCID.
Abstract TMP111: The Detrimental Effects Of Post-stroke Social Isolation On Microglial Activation Is Mediated By MicroRNAs
Authors: Banerjee Anik , Lee Juneyoung , Venna Venugopal R , McCullough Louise
Published: February 2022

Introduction:
Social Isolation (SI) is a risk factor for a wide array of psychological disorders. SI significantly enhances the incidence of developing neurological diseases, including stroke within the elderly population. Recent studies have shown microRNA (miRNA) signatures in the brain and the circulation are altered in social defeat models and under stressful environmental conditions. Although SI has shown to influence post-stroke recovery, potential targetable interventions to mitigate these inflammatory events are limited.

Hypothesis:
Post-stroke SI influences temporally distinct miRNA networks in the brain that regulate acute microglial activation and contribute to chronic depressive phenotypes.

Methods:
Aged (18-20 month) C57BL/6 male mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) followed by reperfusion. Mice were randomly assigned to either continued pair housing (PH), or SI three days after a 60-minute MCAO. Mice were euthanized at post-stroke SI Day 1, 4, and 27 and ipsilateral hemispheres were collected for miRNA sequencing and downstream analysis. Behavioral tests and brain cell analysis using flow cytometry were performed using independent experimental cohorts.

Results:
The top 10 differentially expressed miRNAs were identified in SI vs. PH mice across three time points (FC ≥ 1.5, FDR adjusted
P
<0.05, n=4/group). Interactional network analysis revealed miR-466i-3p, miR-10a-5p, and miR-10b-5p as pivotal nodes that regulated the expression of the largest subset of genes involved in microglial-specific immune activation and chronic depression after stroke at SI D4 and D27, respectively. Flow cytometry analysis showed that microglia are significantly activated at post-stroke SI Day 4, as assessed by the downregulation of microglia-specific homeostatic protein purinergic receptor P2RY12 (
P
<0.05, n=7-8/group) and interestingly, chronic SI induced depressive-like behaviors in aged stroke mice; consistent with our miRNA-based pathway analysis.

Conclusion:
This is the first comprehensive miRNA expression profiling study using NGS technique in aging, stroke, and SI. Our data revealed that SI-specific miRNAs are involved in microglial activation and chronic depression in aged mice.
Abstract TMP115: Increased Expression Of Cd38 In Activated Astrocytes Contributes To Impaired Synaptic Plasticity Following Middle Cerebral Artery Occlusion
Authors: Burch Amelia , Mitchell Danae , Orfila James E , Quillinan Nidia , Herson Paco S
Published: February 2022

Introduction:
Emerging evidence has implicated post-stroke cognitive impairment (PSCI) as a major contributor to long-term disability following acute ischemic stroke. While the hippocampus is shown to contribute to PSCI, the exact mechanisms underlying PSCI have yet to be elucidated. Interestingly, a preclinical model of large artery stroke (middle cerebral artery occlusion; MCAO) causes hippocampal dysfunction, despite direct ischemic insult to brain regions distant from the hippocampus, suggesting the injury causes perturbations in neural circuits. Thus, we utilize electrophysiological recordings of hippocampal LTP as an indicator of network health following ischemia. We hypothesize activated astrocytes in the hippocampus following MCAO increase expression of the ectoenzyme, CD38, which signals to neurons to impair plasticity.

Methods:
Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared 30 days after recovery from MCAO in adult (8-12 week) mice. Immunohistochemistry was performed to assess hippocampal CD38 expression and astrogliosis. Acute slices were treated with CD38 inhibitors (78c & apigenin) to assess plasticity.

Results:
Recordings obtained in brain slices 30 days after MCAO exhibited a significant reduction in LTP; 161±9%, n=6 in sham compared to 115±4%, n=7 30 days after MCAO, in both ipsilateral and contralateral hippocampi. Immunohistochemical (IHC) staining indicates CD38 levels are increased and colocalize with activated astrocyte marker, GFAP, 30 days following MCAO. Bath application of CD38 inhibitors, 78c (vehicle n=6, 4.0±8.5% vs. 100nM 78c n=6, 78.3±15.8%; p<0.05) and apigenin (vehicle n=7, 23.9±7% vs. 10μM apigenin n=7, 65.5±2.5%; p<0.05), restored LTP in MCAO brain slices 30 days following injury.

Conclusion:
These data indicate that MCAO provides a reproducible model of post-stroke memory dysfunction (PSCI) and that remote astrogliosis in the uninjured hippocampus may contribute to altered neuronal function (plasticity). Our data implicates increased levels of CD38 impair plasticity following stroke. Therefore, reducing CD38 activity at chronic timepoints following ischemia may represent a novel strategy to treat the symptoms of PSCI.
Abstract TMP117: Optogenetic Stimulation Effects On Cortico-thalamic Circuit Plasticity After Stroke
Authors: Chiang Terrance , Vahdat Shahabeddin , Pendharkar Arjun , Harvey Sean , Uchino Haruto , Cao Zhijuan , Kim Anika , Choy Mankin , Chen Hansen , Lee Hyun Joo , Cheng Michelle Y , LEE JIN HYUNG , Steinberg Gary
Published: February 2022

Introduction:
Post-stroke optogenetic stimulation in the ipsilesional primary motor cortex (iM1) can promote functional recovery. Recent brain imaging data indicate that iM1-stimulated stroke mice restore activation of the ipsilesional cortico-thalamic tract. To determine whether iM1 stimulation enhanced post-stroke plasticity in the cortico-thalamic tract, we investigate the expression of plasticity markers in the ipsilesional thalamus (iTH). We selectively stimulate the cortico-thalamic circuit to investigate its influences on plasticity changes and functional outcome.

Methods:
C57BL6 male mice (6-7 weeks old) were injected and implanted in iM1 with AAV1-CaMKIIa-hChR2 virus and optical fiber for iM1 stimulation. Another set of mice were injected with AAV1-CaMKIIa-hChR2 virus in iM1 with an optical fiber implanted in ipsilesional thalamus (iTH) to selectively stimulate the cortico-thalamic circuit. Six weeks after virus injection, mice underwent transient middle cerebral artery occlusion (tMCAo, 30min), followed by optogenetic stimulations from PD5-14. Functional recovery was evaluated by rotating beam tests at pre-stroke and post-stroke days (PD) 4, 7 and 14. Brain sections were immunostained with plasticity marker synaptophysin and imaged for co-localization with ChR2. Thalamic tissues were processed with western blot for plasticity markers.

Results:
iM1-stimulated mice (Stim group) exhibited significant functional recovery at post-stroke day14 on the rotating beam test, when compared to non-stimulated mice (NoStim group) (p<0.05). GAP43, an axonal growth marker, was significantly higher in iTH of iM1-stimulated mice (p<0.05). Moreover, we detected higher co-localization of ChR2
+
/Synaptophysin
+
terminals in iTH of iM1-stimulated mice (p<0.05). Robust ChR2 is detected in the iM1-iTH motor cortico-thalamic circuit and selective stimulation of this cortico-thalamic circuit is sufficient to improve recovery (p<0.05).

Conclusion:
Our results show that cortico-thalamic circuit plays a key role in functional recovery after stroke. Ongoing studies investigates the transcriptome and plasticity changes in the cortico-thalamic circuit circuit.