bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 155: Proving CT Angiography of Collaterals Prior to Endovascular Therapy: TREVO & TREVO 2
Authors: Liebeskind David S , Sanossian Nerses , Scalzo Fabien , Xiang Bin , Gupta Rishi , Jovin Tudor G , Albers Gregory W , Lutsep Helmi L , Smith Wade S , Killer-Oberpfalzer Monika , Macho Juan M , Jansen Olav , Wahlgren Nils , Nogueira Raul G ,   for the TREVO and TREVO2 Investigators
Published: March 2022

Background:
CT angiography (CTA) has become the predominant mode of imaging selection prior to endovascular stroke therapy. The added value of CTA collaterals beyond ASPECTS and validation with digital subtraction angiography (DSA) remain unaddressed. We determined the impact and validity of CTA collateral grade with DSA in the multicenter TREVO and TREVO 2 trials.

Methods:
Pooled analyses of the TREVO and TREVO 2 CTA dataset prior to endovascular therapy were conducted. CTA collaterals were scored (0-20) with the regional leptomeningeal collateral score (rLMC) and directly compared with the ASITN/SIR (0-4) collateral grade. Statistical analyses included descriptive statistics and Spearman correlation analysis among CTA, DSA collaterals and ASPECTS. Logistic regression analysis was used to model 90-day good outcome and revascularization success.

Results:
CTA and DSA collaterals were compared in 116 subjects with anterior circulation occlusions. ASPECTS was median 8 (range 3-10; 49% 0-7 versus 51% 8-10), with CTA collaterals on rLMC score of median 16 (range 4-20) and DSA collaterals median 2 (range 1-4; 13% grade 1, 50% grade 2, 26% grade 3 and 11% grade 4). ASPECTS exhibited only moderate correlation with collaterals at CTA (ρ=0.35, p<0.001) and DSA (ρ=0.41, p<0.001). Similarly, only moderate correlation was noted between CTA collaterals and DSA (ρ=0.43, p<0.001). Baseline ASPECTS better predicted (OR 1.50 95%CI [1.08-2.09], p=0.017) good clinical outcome (90-day mRS 0-2) compared to CTA collaterals (OR 1.10 95%CI [1.00-1.22], p=0.058), whereas DSA collaterals were most predictive (OR 1.99 95%CI [1.20-3.29], p=0.008). Multivariate logistic regression revealed DSA collateral grade 3 or greater as paramount for achieving good outcomes (OR 3.00 95%CI [1.31-6.89], p=0.01).

Conclusions:
Single-phase CTA collateral scoring prior to endovascular therapy provides marginal value beyond ASPECTS and limited correlation with the extent of collaterals on DSA. CTA of collaterals may perform differently at very high ASPECTS or with further development of imaging acquisition or post-processing techniques.
Abstract 158: The Malignant CTP Imaging Profile Predicts Worse Functional Outcomes
Authors: Mlynash Michael , Christensen Soren , Kemp Stephanie M , Mishra Nishant , Federau Christian , Tsai Jenny P , Kim Sun , Frankel Michael , Dehkharghani Seena , Devlin Thomas G , Yavagal Dileep R , Akhtar Naveed , Jovin Tudor , Nogueira Raul , Bammer Roland , Straka Matus , Zaharchuk Greg , Albers Greg W , Marks Michael P , Lansberg Maarten G ,   CRISP Investigators
Published: March 2022

Introduction:
The Malignant MRI profile, defined as a large lesion on DWI or PWI (Tmax>10s), has been proposed as a marker of poor outcome despite reperfusion. It is not known if a corresponding malignant CT perfusion (CTP) profile can be used to identify stroke patients with a poor prognosis despite timely reperfusion.

Hypothesis:
The Malignant CTP profile identifies stroke patients with poor clinical outcomes despite endovascular reperfusion.

Methods:
The NIH-funded CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) prospectively enrolled acute ischemic stroke patients undergoing intra-arterial thrombectomy. CTP was obtained prior to the procedure and followed by a post-procedural MRI within 36 hours. The CTP Malignant profile was pre-specified as an infarct core (rCBF <30%) ≥70mL or a lesion with severe hypoperfusion (Tmax>10s) ≥100mL. Poor functional outcome was defined as a mRS 5-6 at 90 days. We evaluated performance of the pre-specified Malignant CTP profile for predicting poor functional outcome. We then performed an ROC analysis to optimize the ischemic core and Tmax>10s volumes for predicting poor outcome with high specificity (≥90%).

Results:
Among 190 patients who underwent endovascular therapy, and had technically adequate CTP and 90-day outcome data, 51 (27%) had the Malignant CTP profile (45 on Tmax10 criteria alone, 6 on both infarct core and Tmax10 criteria). The Malignant CTP profile was associated with an increased rate of poor outcome (26% vs 14%; OR = 2.2; 95% CI 0.98-4.8; p=0.08). In patients with reperfusion (n=170), the percent of poor outcomes was significantly higher among patients with the Malignant CTP profile (27% vs 12%, p=0.02; OR = 3.1; 95% CI 1.3-7.4, adjusted for age). Based on ROC analysis, a CTP infarct core >50 mL or a Tmax>10s lesion >150 mL predicted poor outcome with high specificity (90%), but corresponding sensitivity was low (28%) and PPV was modest (36%, or 9/25).

Conclusion:
Although presence of the Malignant CTP profile doubled the likelihood of poor outcome, only 1 out of 3 patients with this profile who had endovascular reperfusion experienced a poor outcome. This suggests that a subset of patients with the Malignant CTP profile may benefit from endovascular therapy.
Abstract 167: Intracerebral Hemorrhage After Emergency Department Visits for Hypertension
Authors: Navi Babak B , Parikh Neal S , Lerario Michael P , Merkler Alexander E , Lappin Richard I , Fahimi Jahan , Iadecola Costantino , Kamel Hooman
Published: March 2022

Introduction:
Although common, severe hypertension in the emergency department (ED) has not been well studied. Current guidelines recommend against aggressive treatment of acutely hypertensive ED patients without end-organ failure and instead recommend initiation of oral antihypertensive agents and outpatient follow-up. However, recent data suggests that intracerebral hemorrhage (ICH) often occurs shortly after an acute rise in blood pressure.

Hypothesis:
We hypothesized that patients discharged from the ED with hypertension face an increased risk of ICH in subsequent weeks.

Methods:
Using administrative claims data from CA, NY, and FL, we identified all patients discharged from the ED from 2005 through 2011 with a primary diagnosis of hypertension (ICD-9-CM codes 401-405). Patients were excluded if they were hospitalized from the ED or had prior histories of cerebrovascular disease at the index visit with hypertension. Using the Mantel-Haenszel estimator for matched data, we compared each patient’s odds of ICH during days 8-38 after ED discharge to the same patient’s odds during days 373-403 after discharge. This cohort-crossover design with a one-week washout period enabled individual patients to serve as their own controls, thereby minimizing confounding bias.

Results:
Among 552,569 patients discharged from the ED with a primary diagnosis of hypertension, 93 (0.017%) were diagnosed with ICH during days 8-38 after discharge compared to 70 (0.013%) during days 373-403 (OR 1.33, 95% CI 0.96-1.84). The odds of ICH were increased in certain subgroups of patients (≥60 years of age and those with secondary discharge diagnoses besides hypertension), but absolute risks were low in all subgroups.

Conclusions:
Contrary to our hypothesis, patients with ED visits for hypertension did not face an increased short-term risk of ICH after discharge. These findings support current guidelines for the ED management of patients with acute hypertension.
Abstract 187: Are Limitations in Activities of Daily Living the Best Predictor of Well-Being After Stroke?
Authors: Zahuranec Darin B , Skolarus Lesli E , Feng Chunyang , Freedman Vicki A , Burke James F
Published: March 2022

Objective:
Limitations in activities of daily living are major components of most stroke outcome scales. We examined whether activity limitations or other factors predicted self-reported well-being among stroke survivors in a large nationally representative survey.

Methods:
Individuals with a self-reported history of stroke were identified from the National Health and Aging Tends Study (NHATS wave 1, year 2011). Self-reported well-being (primary outcome) was defined based on a previously validated 7-item measure (higher=greater well-being) assessing emotions (feeling cheerful, bored, full of life, or upset) and self-realization (purpose in life, self-acceptance, and environmental mastery). Activity limitations were defined by the need for assistance in any of 11 activities of daily living/instrumental activities of daily living (ADLS/IADLS). Multivariable linear regression was used to identify factors associated with well-being.

Results:
738 stroke survivors 65 or older were included (57% female, 9% African American, 6% Hispanic). The final multivariable model (see Table) only modestly explained the total variability in well-being (R-squared=0.28). Number of ADL/IADL limitations was not associated with well being. Notable predictors of lower well being included depressive symptoms, chewing problems, pain that limited activity, and restricted ability to participate in valued life activities. Income was modestly associated with improved well-being, while social network support and access to communication technology were not associated.

Conclusions:
Limitations in ADLs/IADLs were not predictive of well-being in this population of stroke survivors, which raises the question of whether existing outcome scales adequately measure the most important patient-centered outcomes. Much of what determines well-being among stroke survivors remains unexplained.
Abstract 220: Neurovascular Uncoupling in Acute Ischemic Stroke Correlates Well With Clinical Fluctuations in Acute Ischemic Stroke
Authors: Kulkarni Amit , Rathakrishnan Rahul , Seow Philip A , Paliwal Prakash R , Ting Eric Y , Yeo Leonard L , Wong Lily Y , Teoh Hock-Luen , Chan Bernard P , Sharma Vijay K
Published: March 2022

Background and aims:
Fluctuations in neurological status are frequently seen during first few days in thrombolysed acute ischemic stroke (AIS) patients. Underlying mechanisms for these fluctuations often remain unclear. Cerebral homeostatic balance is regulated by autoregulation and neurovascular coupling (NVC). We hypothesized that neurovascular uncoupling in AIS contributes to the fluctuations in neurological status.

Methods:
In this ongoing prospective study, consecutive and thrombolyzed AIS patients were recruited within 12 hours of symptom-onset. Serial CT perfusion (CTP) imaging (within 12 hours, at 24 and 72 hours after symptom-onset) were performed. Serial Quantitative EEG (QEEG) were performed, close to CTP imaging. Power within the alpha band (8-15Hz) was determined in each channel using epochs of 10-seconds % calculated for each hemisphere. Continuous transcranial Doppler (TCD) recording were obtained from both middle cerebral arteries, simultaneously with EEG. Neurological status was monitored with serial NIH stroke scale (NIHSS) scores. Neurovascular uncoupling was defined as a mismatch among CTP, QEEG and clinical findings. QEEG, CTP and TCD data were analysed independently by investigators blinded to the clinical findings.

Results:
A total of 32 patients (19 male, median age 68 years (range 56-86) were included. Median NIHSS score at recruitment was 8 points (range 1-24). NIHSS fluctuations by 4 or more points (deterioration followed by improvement or deterioration following improvement in absence of re-occlusion) were noted in 13 (40%) cases. Increasing cerebral edema (2 cases) and regional hyperperfusion (4 cases) were seen on serial CTP. Remaining 7 cases showed serial improvement in CTP. QEEG showed significantly increased inter-hemispheric alpha band power ratio (unaffected hemisphere/affected hemisphere ratio more than 1.5), irrespective of the CTP and TCD results, suggestive of neurovascular uncoupling as the underlying mechanism for early neurological fluctuations.

Conclusion:
Neurovascular uncoupling is a relatively frequent phenomenon during first few days of acute ischemic stroke. Multi-modal monitoring is useful in identifying these patients for appropriate therapeutic decision making.
Abstract 223: Leptomeningeal Arteriole Vasoconstriction during Hypertension: Targeting Pial Collaterals in Stroke Treatment
Authors: Chan Siu-Lung , Sweet Julie , Cipolla Marilyn
Published: March 2022

Introduction:
Collateral perfusion via leptomeningeal arterioles (LMAs) between middle and anterior cerebral artery (MCA/ACA) territories sustains the penumbra during MCA occlusion (MCAO) and is a key variable in stroke outcome. Hypertension is associated with poor stroke outcome, little penumbral tissue and larger infarctions. Here, we investigated the vasoactive properties of isolated and pressurized LMAs from normotensive and hypertensive animals as a contributor to poor collateral flow.

Hypothesis:
Compared to normotensive animals, LMAs from hypertensive animals are vasoconstricted that limits collateral perfusion and penumbral tissue.

Methods:
LMAs between MCA and ACA distal branches were dissected from 18 wk old male normotensive Wistar Kyoto (WKY, n=14) and spontaneously hypertensive rats (SHR; n=16), mounted on glass cannulas and studied pressurized.

Results:
LMAs from WKY had little basal tone and responded passively to increased pressure from 5 to 80 mmHg. In contrast, LMAs from SHR had considerable tone and responded to pressure with vasoconstriction (Figure 1). Dilatory responses were also diminished in LMAs from SHR vs. WKY, including to the voltage operated calcium channel inhibitor diltiazem (63±6% vs. 88±2% at 10
-5
M; p<0.01), the NO donor sodium nitroprusside (23±6% vs. 74±6% at 10
-5
M; p<0.01), and to 15mM KCl that activates inward rectifier K
+
channels (-5±45% vs. 78±10%; p<0.01). Structurally, passive diameters of LMAs from SHR were smaller but not significantly different from WKY, suggesting therapeutic opening of collaterals may be possible.

Conclusions:
The relatively passive nature of LMAs from WKY would be conducive to retrograde flow during MCAO whereas the vasoconstrictive response of LMAs from SHR could limit collateral perfusion. Therapies that alleviate LMA vasoconstriction may help sustain penumbral flow and extend the time for treatment in those patients that have poor collaterals.
Abstract 25: Evidence Based Aspiration Risk Tool: Improving Stroke Care
Authors: Berger Lynn D , Olson-Mack Lindsay , Johnson Melissa , Aguilar-Tabora Giselle , Merrill Persaud Julie , White Ann Marie
Published: March 2022

Introduction:
According to the American Heart Association, approximately 65 percent of stroke patients will have swallowing impairment that needs evaluation prior to oral intake or medications. Per the Joint Commission Guidelines, all stroke patients must be screened for aspiration risk using an evidence-based tool prior oral intake.

Hypothesis:
We hypothesized that combining the MetroHealth dysphagia screen and 3 oz. water test as a 2-tiered evidence-based screening tool will properly identify stroke patients at risk for aspiration pneumonia.

Method:
A retrospective cohort analysis of 266 patients was conducted of transient ischemic attack, ischemic, and hemorrhagic stroke patients admitted to a small community hospital from July 2014-June 2015. The hospital implemented a 2-tiered aspiration risk screen (ARS), in addition to standard ARS. Inclusion criteria: stroke patients discharged with additional diagnosis of pneumonitis due to inhalation of food or vomitus (ICD9 507.0). Exclusion criteria: all stroke patients that were discharged without discharge diagnosis of ICD9 507.0.

Results:
Of the 266 patients, 11 (4.1%) were diagnosed with pneumonitis. Eight patients (72%) were screened for aspiration utilizing both screens. Three of the 8 patients (37.5%) passed the hospital’s standard ARS tool, but were identified to have aspiration risk utilizing the 2-tiered screen. Three of the 11 patients (27%) were identified at risk for aspiration utilizing the 2-tiered ARS only. Two patients were found to have questionable infiltrates on admission. The other patient passed the ARS on admission, and later failed upon rescreen for change in mental status. All patients were evaluated by speech prior to oral intake.

Conclusion:
This study reveals that the 2-tiered ARS can be utilized to identify stroke patients at risk for aspiration. Despite proper recognition of aspiration risk upon admission, a small number of patients, 4% in our study, will go on to aspirate. An opportunity exists for closer collaboration between nursing, speech language pathology, and medical staff to streamline processes to encourage screening of all patients admitted for stroke in an effort to reduce occurrence of pneumonitis for high risk stroke patients.
Abstract 49: Cerebral Microbleeds are Associated With Incident Dementia: The Framingham Heart Study
Authors: Romero Jose R , Beiser Alexa S , Himali Jayandra J , Shoamanesh Ashkan , DeCarli Charles , Wolf Philip A , Seshadri Sudha
Published: March 2022

Background:
CMB represent hemorrhage-prone small vessel disease (SVD), attributed to hypertensive vasculopathy or cerebral amyloid angiopathy (CAA). CMB are associated with adverse outcomes including prevalent stroke and dementia, but the relation with incident dementia in the community has not been studied.

Objective:
To study the association of cerebral microbleeds (CMB) on MRI and incidence of dementia in a community based cohort.

Methods:
We evaluated 1296 dementia-free Framingham Original and Offspring Cohort participants (mean age 72years; 54% women) with available brain MRI and incident dementia data (mean follow-up 6.7 years). Using Cox-proportional hazards models we related all CMB and CMB stratified by brain location to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic SVD.

Results:
CMB were observed in 10.8% of subjects (64% lobar, 36% deep and mixed). Incident dementia was observed in 85 participants (6.6% over study period). We observed a 1.74 times higher risk of dementia in participants with any CMB (HR 1.74, 95% CI 1.00-3.01), and three fold higher risk in those with deep and/or mixed CMB (HR 2.99, 95% CI 1.52-5.90). The associations remained significant after adjusting for vascular risk factors. Although they were attenuated after adjustment for MRI markers of ischemic SVD, they remained significant for participants with deep and/or mixed CMB (HR 2.44, 95% CI 1.22-4.88). Purely lobar CMB were not associated with incident dementia.

Conclusions:
CMB were associated with increased risk of incident dementia, and for non-lobar CMB, the associations were independent of vascular risk factors and ischemic markers of small vessel disease. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and cerebral amyloid angiopathy in risk of dementia, and highlight the role of CMB as markers of adverse neurological outcomes.
Abstract 62: Extending the Time for Thombolysis in Emergency Neurological Deficits (EXTEND) - Penumbral Patterns Among Patients 4.5-9 Hrs and Wake - Up Stroke
Authors: Ma Henry , Campbell Bruce C , Parsons Mark W , Levi Christopher , Meretoja Atte , Churilov Leonid , Howells David , Carey Leeane , Sharma Gagan , Christenen Soren , Yan Bernard , Michell Peter , Yassi Nawaf , Connelly Alan , Chung Hsu Y , Davis Stephen M , Donnan Geoffrey A ,   EXTEND Investigators
Published: March 2022

Background:
EXTEND is a randomised, double-blind, placebo-controlled Phase III trial of intravenous alteplase vs. placebo among patients with ischemic stroke 4.5-9 hours from stroke onset or wake-up-stroke (WUS). There is uncertainty about the extent of salvageable tissue in this crucial time window for exploring therapeutic options. Whether WUS represents a plausible patient group for therapy is worthy exploring

Objective:
To determine the penumbral mismatch and ischaemic core volumes in the EXTEND cohort and compare these characteristics between WUS and non-WUS subsets.

Methods:
Patients with ischemic stroke within 4.5-9 hours from stroke onset and WUS patients (time of WUS onset defined as the midpoint between time to sleep and awakening with the stroke symptoms) are eligible for enrollment. Criteria for trial entry include perfusion-diffusion mismatch using a perfusion threshold of Tmax>6sec and a perfusion:diffusion lesion volume ratio of >1.2. Ischemic core must be <70mL based on assessment by automated RAPID software on MR or CT platforms (Stanford).

Results:
105 patients have been randomised to date with median age of 78.0 (IQR 66.5, 82 yrs), median admission NIHSS of 14.0 (8.0, 18.0) and half being female. WUS patients (n=69, 66%) compared to non-WUS patients, WUS patients had comparable median NIHSS of 14 (8, 18) vs 14.5 (8.0, 14.3 p =0.5), larger ischemic core volume of 15.5 ml (7.0, 33ml) vs 4.0 ml (0, 24.0ml p =0.005), perfusion deficit volume of 86.0 ml (58.5, 121.8ml) vs 73.0 ml (48.0, 124.0 ml p=0.6), mismatch ratio of 4.4 ml (2.6, 8.6 ml) vs 5.9 ml (2.7, 24.4 p=0.8) and mismatch volume of 64.0 ml (38.5, 91.8ml) vs 62.0 ml (42.5ml, 103.5ml p=0.5).

Conclusion:
Within the EXTEND cohort, there is a clinically significant amount of salvageable penumbral tissue within the 4.5-9 hr time window. Patients with WUS have larger ischemic core compared to those in the non-WUS group. However, comparable salvageable mismatch volumes and baseline NIHSS are noted between groups. Tissue salvage has the potential to lead to clinical improvement in both groups.
Abstract 67: Novel and Safe Oxygen Carrier Prevents Brain Damage After Focal Ischemia and Improves Functional Outcomes
Authors: Leung Philberta , Bedard Catherine , Davis Tina , Ng Sarah , Liang Carol , Lamb Jessica , Boitano Paul D , Lapchak Paul A , Winger Jonathan A , Krtolica Ana , Albers Gregory W , Cary Stephen P , Le Moan Natacha
Published: March 2022

Introduction:
After vascular occlusion, there are two major zones of injury: the infarct core that rapidly dies, and the surrounding penumbra, which is hypoxic and at risk for infarction. Restoring blood flow by vascular recanalization (ie. endovascular +/- IV tPA) to prevent the penumbra from infarcting has become the new standard of care for acute ischemic stroke patients presenting with salvageable tissue. However, not all patients benefit from recanalization. Regardless of successful or partial reperfusion, secondary hypoxic events within the rescued penumbra can cause selective neuronal loss (SNL) that may account for suboptimal clinical recovery. OMX is a breakthrough oxygen delivery protein tuned to release oxygen specifically in hypoxic tissue and reduce hypoxia to prevent SNL within the reperfused penumbra.

Methods:
To mimic the clinical situation whereby occlusion is followed by gradual reperfusion after spontaneous or therapeutic thrombolysis, we used the endothelin-1 induced middle cerebral artery occlusion (MCAO) model. OMX was administered intravenously up to 2h post-MCAO. Short and long-term histological and behavioral outcomes were used to assess hypoxia, apoptosis, gliosis, SNL, infarct volume and sensorimotor functions.

Results:
Despite reperfusion, hypoxic tissue persists and progressively infarcts in vehicle-treated rats. However, OMX-treated rats showed no infarct expansion over 7d, indicating that OMX prevents infarction of the majority of hypoxic tissue. OMX reduces hypoxia and caspase 3/9 activity in a dose-dependent manner and significantly prevents SNL and gliosis. When administered post-MCAO, OMX significantly improves both sensory and motor functions (∼30-80% improvement, *
p
<0.05) in aged rats up to 28d post-MCAO. Moreover, extensive toxicology studies demonstrate that OMX is well tolerated in multiple species and can be used safely in combination with tPA.

Conclusions:
OMX is a promising therapeutic candidate that can be administered in combination with reperfusion therapies to stabilize the at-risk hypoxic tissue and ameliorate long-term clinical outcomes in stroke patients.
Abstract 7: Thrace Study: Final Results
Authors: Bracard Serge , Guillemin Francis , Ducrocq Xavier ,   THRACE Investigators
Published: March 2022

Thrace is a French randomized, multicenter, controlled trial on mechanical thrombectomy for large cerebral arteries acute occlusions.

Primary objective was to determine whether a combined IVT/IAMT is superior to standard IV rTpa alone when initiated within 4h of acute ischemic stroke onset in adult patients with moderate-to-severe strokes (NIHSS>10) due to large artery occlusion. The primary outcome measure was the good clinical outcome (mRs 0-2) at 3 months.

Complete data were analyzed for the 2
nd
intermediate analysis using O’Brien and Fleming stopping rules.

Results:
412 patients were included. For the second intermediate analysis, 395 patients were considered. Data were complete and monitored for 385 patients (195 IV/ 190 IV+IAMT).

The mean age of our population was 62.5 years and the median NIHSS= 18. Occlusions were located on C1 in 57 (14,8%) and M1 in 326 cases (84,6%) At 3 months, the difference of good outcome between the two arms was significant according to the O’Brien-Fleming boundaries.

Conclusion:
After this intermediate analysis, THRACE was considered as positive and the Scientific Committee, following the DSMB advice, decided to stop the study. The final results will be presented.
Abstract 86: Hemorrhagic Complications Associated With New Oral Anticoagulant Use for Stroke Prevention in Atrial Fibrillation Patients: The Impact of Combination Treatment With Clopidogrel
Authors: Bekelis Kimon , Smith Jeremy , Skinner Jonathan , Morden Nancy
Published: March 2022

Background:
The safety of combination treatment with new oral anticoagulants (NOACs) and clopidogrel remains an issue of debate. We investigated the association of such combination therapy with major hemorrhagic complications in a real-world cohort of elderly atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) with stenting.

Methods:
We used a 40% random sample Medicare denominator file and corresponding inpatient, outpatient (2003-2013) and prescription (2006-2013) claims to conduct a cohort study of AF patients receiving cardiac stents, between 2006 and 2013. Cox models were employed to investigate the association of combination therapy (oral anticoagulant and an antiplatelet medication) with major hemorrhagic complications.

Results:
We identified 182,242 AF patients undergoing stenting (average age 73.8 years, 51.3% female). Mean follow up was 36.8 months. Current combination therapy including a NOAC was associated with an increased risk of intracranial hemorrhage (ICH) (HR 3.21; 95% CI 1.59-6.47), upper gastrointestinal hemorrhage (HR 2.77; 95% CI 2.21-3.49), other significant hemorrhage (HR 2.87; 95% CI 2.27-3.62), or any hemorrhage (HR 2.73; 95% CI 2.31-3.21) in comparison to clopidogrel alone. The corresponding effect for combination treatment with warfarin was smaller (HR 2.05; 95% CI 1.97-2.13 for all hemorrhages).

Conclusions:
In a cohort of elderly AF patients undergoing PCI and stenting we identified an association of combination treatment with NOACs and antiplatelets with an increased risk of major hemorrhagic complications, in comparison to antiplatelets alone. This effect was larger than the corresponding risk associated with combination treatment including warfarin.
Abstract 89: Trends in Long-term Case-mortality After Stroke From the International Stroke Outcomes Study (INSTRUCT): An Individual Participant Data Meta-analysis of Incident Strokes
Authors: Gall Seana , Phan Hoang T , Blizzard Leigh , Thrift Amanda , Cadilhac Dominique , Heeley Emma , Sturm Jonathan , Reeves Mathew ,   INSTRUCT Study Investigators
Published: March 2022

Introduction:
Reductions in early case-mortality after stroke have occurred over the past few decades, but whether this has translated into increases in longer term survival is unknown.

Hypothesis:
Case-mortality at 1 and 5 years after stroke will have decreased over time.

Methods:
Individual participant data on sociodemographics, pre-stroke dependency, stroke type and severity (e.g. NIH Stroke Scale, Glasgow Coma Scale) and vital status (including date of death) were obtained from study investigators from 12 high-quality population-based stroke incidence studies undertaken in Australasia, Europe, South America and the Caribbean between 1987 and 2012. We used random effects Poisson regression to model changes in case-mortality at 1 and 5 years after stroke between 1987 and 2013, adjusted for age, sex and stroke severity.

Results:
There were 16,557 participants with 1 year follow-up (mean [SD] age 73.6 [14] years; 53% female, 79% ischaemic stroke, 21% intracerebral hemorrhage) and 12,839 with 5 year follow-up. In 1987, case-mortality was 42.9% at 1 year and 61.5% at 5-years. By the end of the study period, 1-year case-mortality was 31.3% and 5-year case-mortality was 49.6%. During the period 1987 to 2013 adjusted 1-year case-mortality following stroke decreased by 0.56% (95% CI 0.55, to 0.57) per year independent of age, sex and stroke severity (Figure, black line). Similarly, the adjusted 5-year case-mortality decreased by 1.19% (95% CI 1.17 to 1.20) per year (Figure, blue line).

Conclusion:
Long term survival after stroke has improved since 1987. Further work is required to determine the relative role of changes in natural history, secondary prevention and clinical care on these findings.

Figure.
Reduction in 1 year (12 studies during 1987-2013, n=16,557) and 5 year (7 studies during 1987-2008, n=12,839) case-mortality according to year of stroke estimated with random effects Poisson regression.
Abstract 92: Cerebral Microbleeds in Transient Ischemic Attack and Minor Cerebrovascular Events
Authors: Zerna Charlotte , Modi Jayesh , Bilston Lisa , Shoamanesh Ashkan , Coutts Shelagh , Smith Eric
Published: March 2022

Background:
Transient focal neurological episodes (TFNE) can occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA).

Hypothesis:
Risk factors and outcomes of patients with minor stroke or TIA would differ in patients with and without cerebral microbleeds (CMB), including in patients with lobar microbleeds potentially consistent with CAA.

Methods:
431 of 510 patients with high-risk TIA (motor or speech deficits > 5 minutes) or minor stroke in the previously reported CATCH (CT and MRI in the triage of TIA and minor cerebrovascular events to identify high risk patients) study underwent baseline MRI. 416 scans with sufficient quality were analyzed for presence and location of CMB and cortical superficial siderosis. Clinical symptoms, baseline characteristics, recurrent TIA or stroke and 90 day modified Rankin scale (mRs) were prospectively collected.

Results:
CMB were detected in 65/416 (15.6 %), with a predominantly lobar pattern (75.4 %), and superficial siderosis in 11/416 (2.6 %). In a multivariable logistic regression model adjusted for number of risk factors age was associated with presence of CMB (odds ratio (OR) 1.04; 95 % confidence interval (CI) 1.02 - 1.06, P = 0.001). Presence of CMB was not associated with recurrent stroke or TIA (9.2 % vs. 11.1 %, P=0.65) or unfavorable mRS (> 1) at 90 days (20 % vs. 16 %, P =0.42). Superficial siderosis was present in 11/416 (2.6%). 42 patients (10.1 %) fulfilled modified Boston criteria for possible or probable CAA. Presenting symptoms were not different between patients with vs. without possible/probable CAA, when considering either all patients or just those with TIA. Possible/probable CAA was not associated with recurrent stroke or TIA (7.1 % vs. 11.2 %, P = 0.42) or unfavorable mRs (> 1) at 90 days (23.8 % vs. 15.8 %, P = 0.18).

Conclusions:
CMB in TIA and minor stroke patients are moderately common but do not strongly predict clinical recurrence and or 90-day functional outcome. Clinical presentations for CAA-related TFNE and TIA might be overlapping, suggesting that MRI may be needed to differentiate them.
Abstract 93: MR Black-Blood Thrombus Imaging (BTI) for the Early Detection and Quantification of Cerebral Venous Thrombosis
Authors: Yang Qi , Fan Zhaoyang , Duan Jiangang , Ji Xunming , Li Kuncheng , Li Debiao
Published: March 2022

Introduction:
Cerebral venous thrombosis (CVT) is an unusual but important cause of stroke mainly affecting young individuals. Accurate diagnostic assessment of potential CVT is a major clinical challenge because the positive findings of intraluminal thrombus are not always evident. The purpose of this study was to prospectively evaluate the diagnostic performance of a novel MR black-blood thrombus imaging(BTI)technique in patients with suspected CVT.

Methods:
A total of 58 consecutive patients who were suspected of CVT were prospectively enrolled for the BTI study. The clinical diagnosis based on conventional imaging techniques was used as the reference standard. Diagnostic performance of BTI on both per-segment and per-patient basis were analyzed. Informed consent was obtained from all participants, and all protocols were approved by the Institutional Review Board.

Results:
BTI was successfully performed in all 58 patients without complications. BTI correctly identified CVT in 36 patients and correctly ruled out CVT in 20 patients. The sensitivity and specificity of BTI for detecting CVT were 95.6% (152 of 159), 98.0% (653 of 640), and 84.1% (657 of 781), respectively, on a per-segment basis. These values were 97.3% (36 of 37) and 95.2% (20 of 21), respectively, on a per-patient basis. Figure 1 demonstrates detection and volume quantification of thrombus in the superior sagittal sinus, the right transverse and sigmoid sinuses, and the cortical veins.

Conclusion:
BTI allows for selective visualization of thrombus with high sensitivity and high specificity. The current findings support that BTI can be used as a promising first line diagnostic imaging tool.
Abstract NS9: ARN Professional Rehabilitation Nurse Competency Model: Application to Stroke Care
Authors: Vaughn Stephanie
Published: March 2022

As the nursing profession continues to become more specialized, there have been more models developed to define specific practice areas. Rehabilitation nursing is practiced in diverse settings along the healthcare continuum with clients who have experienced a disability/chronic illness, such as stroke. No framework was noted in the literature that defined the necessary competencies of the rehabilitation nurse

Purpose:
To develop a Competency Model for Professional Rehabilitation Nursing and its application to clinical practice.

Method:
An Association of Rehabilitation Nurses’ (ARN) task force was convened, conducted a literature review and participated in “brainstorming” that yielded four domains of professional practice: nurse-led evidence-based interventions; promotion of health and successful living, leadership, and interprofessional practice; and essential role competencies. The competencies were further defined into three levels of proficiency: beginner, intermediate, and advanced (ARN, 2014).

Results:
Model is a circle with professional rehabilitation nurse at the center surrounded by four domains and the role competencies, separated by broken lines illustrating the crossover of knowledge and skills represented in each domain. This practice Model can be used to inform stroke care in various settings across the healthcare continuum; and competencies such as facilitating safe and effective care transitions can be used in plan for the stroke survivor and caregiver. Facilitating the stroke survivor’s transition to the right level of care is an essential rehabilitation nurse competency and promotes better outcomes (Camicia et al., 2014). Using competencies, such as interventions based on best evidence, are essential in managing stroke sequela: neurogenic bladder, dysphagia, hemiplegia, etc. The Model can also be used to address the caregiver role and frame the assessment to determine education, community resource, and support needs.

Conclusion:
ARN Rehabilitation Professional Nurse Competency Model reflects diversity of rehabilitation nursing in the current healthcare arena; and is an efficacious tool which can assist rehabilitation nurses at various levels to provide optimum stroke care and contribute to best practice.
Abstract TMP20: Effect of Carotid Artery Revascularization for Ocular Circulation and Chronic Ocular Ischemic in Carotid Artery Stenosis
Authors: Kawaguchi Shoichiro , Fujimoto Takatoshi , Nakano Ryo
Published: March 2022

Background:
We evaluated the effect of carotid revascularization surgery for ocular circulation and chronic ocular ischemic syndrome (OIS).

Methods:
We examined ninety-nine patients with carotid artery stenosis (more than 50% stenosis) at its origin treated by carotid endarterectomy (N=65) or carotid artery stenting (N=34). Twenty-six patients (26%) complained of chronic OIS. Ocular circulation was examined before and after revascularization surgery using ophthalmic artery (OphAr) and central retinal artery (CRA) color Doppler flow imaging.

Results:
1) Ocular circulation: Preoperatively, the average OphAr peak systolic flow velocity (Vs) was 0.05 m/sec, and the average CRA Vs was 0.07 m/sec. At 1 week after surgery, the average OphAr Vs significantly increased to 0.32 (p < 0.05), and the average CRA Vs significantly increased to 0.11 m/sec (p < 0.05). These significant improvements were sustained throughout the three months of the follow up.2) OIS: During the follow-up period (mean: 3.6 years), 16 patients (62%) showed visual acuity improvement, and no patients complained of amaurosis fugax or worsening of the chronic OIS.

Conclusion:
Carotid revascularization surgery was effective in improving the ocular circulation, and it was also useful for the chronic OIS due to the carotid artery stenosis.
Abstract TMP33: ATTEND (Family Led Rehabilitation After Stroke in India) Trial: Potential for Health System Change in India
Authors: Lindley Richard I , Felix Cynthia , Pandian Jeyaraj D , Anderson Craig S , Mohammed Alim , Gandhi Dorcas B , Verma Shweta J ,   ATTEND Collaborative Group
Published: March 2022

Introduction:
For India, with a population of over 1.2 billion, there is less than one neurologist per million population and only one physiotherapist per 24,000. In rural areas, these figures are much worse.

Hypothesis:
The ATTEND trial is testing the hypothesis that family-led rehabilitation can improve outcome after stroke.

Methods:
The ATTEND Trial is a prospective randomised outcome blinded (PROBE design) multicentre study in India with a sample size of 1,200. Patients allocated the intervention received evidence-based rehabilitation techniques taught to a nominated family member, supported by a stroke coordinator. Patients allocated control received usual care. The primary outcome is functional independence measured by the modified Rankin Score at six months. Funding is from the Australian National Health and Medical Research Council.

Results:
By August 2015, 870 patients had been randomised from 14 sites across India. For data received (n=788 baseline data, n= 345 for 6 month follow-up), the average age was 57.9 years SD 13.5 (median 59), 66% male and 91% were married. Hypertension (76%), diabetes (43%) and smoking (24%) were common risk factors. The nominated caregiver was the spouse in 44%, son/son-in-law 26%, daughter/daughter-in-law 24%. The mean NIHSS was 10, 23% of strokes were due to haemorrhage. At six months 42% were dead or dependent. Loss to follow-up is currently <1%.

Conclusions:
These data illustrate the devastating effects of stroke in India with a higher proportion of haemorrhagic stroke and much younger age than typical of Western acute trial populations. The potential public health impact of a positive trial (results expected late 2016) in India is large.
Abstract TMP55: TGF-β1 Induces Microglial BDNF Production and Improves Functional Outcome After Intracerebral Hemorrhage
Authors: Taylor Roslyn A , Ai Youxi , Sansing Lauren H
Published: March 2022

Introduction:
Intracerebral hemorrhage (ICH) results in the activation of microglia. Microglia can become classically activated, promoting neurotoxicity or alternatively activated, promoting tissue repair. Our lab has previously shown that microglia become alternatively activated between 3 and 14 days after ICH. This transition is critical to recovery, yet the mechanism is unknown. The anti-inflammatory cytokine TGF-β1 has a critical role in microglial development and homeostasis. We hypothesize that TGF-β1 is the mediator of microglia alternative activation after ICH and that TGF-β1 promotes microglial secretion of BDNF to promote tissue repair.

Methods:
Primary microglial cultures from C57BL/6 (WT) P0-P2 pups were used to study the mechanism of alternative activation. Microglia were activated with thrombin with or without TGF-β1 for 8 and 24 hours. BDNF was measured by intracellular cytokine staining (ICS) (flow cytometry) and ELISA from cell supernatants. ICH was induced by injecting 25ul of whole blood into the right striatum of male WT mice. Mice were treated with either 10ng TGF-β1 or PBS intracerebrally immediately prior to blood injection to target microglia. Behavioral outcomes were measured by cylinder test and beam walking. Brains were harvested at 7 days for immunohistochemistry (IHC).

Results:
Primary microglia that were activated with thrombin and TGF-β1 had more BDNF+ cells by ICS at 8 hours and secreted more BDNF by ELISA at 24 hours compared to thrombin alone
in vitro
(fig 1). Mice treated with TGF-β1 had better functional outcomes by cylinder test and beam walking than PBS treated mice 24 hours after ICH. TGF-β1 treated mice had significantly more BDNF+ CD11b+ cells (microglia/macrophages) than PBS treated 7 days after ICH by IHC.

Conclusions:
TGF-β1 treatment induces microglial BDNF production and improves functional outcomes 24 hours after ICH. Ongoing work will determine whether microglial BDNF production is the link to improved outcomes.
Abstract TMP64: Patients With Mild Cognitive Impairment Less Likely to Receive t-PA for Stroke
Authors: Levine Deborah A , Morgenstern Lewis B , Zahuranec Darin Z , Langa Kenneth M , Baek Jonggyu , Sanchez Brisa N , Lisabeth Lynda D
Published: March 2022

Background and Objectives:
Many adults with mild cognitive impairment (MCI) live years with good quality of life and do not progress to dementia. It is unclear whether patients with pre-existing MCI (without dementia) are less likely to receive effective treatments for acute ischemic stroke than patients without MCI. We measured differences in intravenous (IV) tissue plasminogen activator (t-PA) treatment for ischemic stroke between MCI patients and cognitively normal patients in a population-based stroke surveillance project.

Methods:
Cross-sectional analysis of prospectively obtained data of 626 first-ever ischemic stroke subjects 45 years or older without dementia in the Brain Attack Surveillance in Corpus Christi (BASIC) project from 2008 to 2012. We compared receipt of IV t-PA from chart abstraction between subjects with prestroke MCI (Informant Questionnaire on Cognitive Decline in the Elderly [IQCODE] score >3 and <3.44, a valid measure of prestroke MCI) and those with normal cognition (IQCODE score ≤3). We examined associations between receipt of t-PA and cognitive status using logistic regression and adjusting for age and sex as well as variables that were significantly associated with both MCI and receipt of t-PA.

Results:
Stroke patients with MCI (median age, 70 years; interquartile range (IQR), 60-79 years; n=233) were more likely than cognitively normal patients (median age, 63 years; IQR, 55-73 years; n=393) to be older and women (both P<0.01), and to have a do-not-resuscitate (DNR) order (P=0.01). Patients with MCI were less likely to receive IV t-PA for acute ischemic stroke compared with cognitively normal patients (6% vs. 10.7%; unadjusted odds ratio (OR), 0.53; 95% CI, 0.29-1.00; P=0.05). MCI patients remained significantly less likely to receive t-PA compared with cognitively normal patients after adjusting for age, sex, DNR status, and stroke severity (adjusted OR, 0.48; 95% CI, 0.23-0.97; P=0.04).

Conclusion:
Patients with MCI are less likely to receive t-PA for acute ischemic stroke compared with cognitively normal patients. Research is needed to determine whether these treatment differences are the result of differences in treatment eligibility, patient/ family preferences, or a less aggressive approach to MCI patients.
Abstract TMP7: The Effect of Admission Systolic Blood Pressure on Mortality in Patients With Acute Ischemic Stroke
Authors: Khawaja Ayaz M , Boehme Amelia K , Shiue Harn , Sisson April , Arora Kanika , Lyerly Michael , Kaur Manmeet , Gropen Toby
Published: March 2022

Background:
It is unknown what significance different initial Systolic Blood Pressure (SBP) values have for patients presenting with acute ischemic stroke (AIS). We investigated factors associated with admission SBP, including hemorrhagic transformation (HT) and discharge outcome.

Methods:
This is a retrospective study of consecutive AIS patients presenting from April 2014 to March 2015. Demographic and clinical data were collected, including admission SBP divided into three tiers: <140, 140-165 and >165. Primary measure of outcome was in-hospital mortality.

Results:
A total of 776 patients were included with mean age 64, 49.2% females and 36.5% Black Race. Most patients with Black Race, hypertension (HTN) and hyperlipidemia (HLD) had SBP between 140-165 and >165, whereas most patients with heart failure had lower SBP (<140) (Table 1). The median SPB was 123 (113-133) in the <140 group, 152 (146-158) in the 140-165 group, and 188 (177-201) in the >165 group. A similar number of patients amongst the three groups were on BP medications (63.5% vs. 69.3% vs. 64.1%), and there were no differences in proportion of HT (15.7% vs. 18.7% vs.12.6%). Although the proportion of patients treated with IV TPA were evenly distributed among tiers (14.4% vs. 13.6% vs. 15.7%), more patients with blood pressure <166 were treated with endovascular therapy (7.8% vs. 8.9% vs. 3.7%; p=0.0321). In comparison to SBP<140, SBP>165 was associated with lower odds of in-hospital mortality (OR 0.536, 95%CI 0.295-0.975, p=0.041). This was significant after adjusting for age and NIHSS (OR 0.431, 95%CI 0.193-0.962, p=0.0399).

Conclusions:
Normal presenting SBP in patients with AIS was associated with in-hospital mortality. This may be related to heart failure. Further research is needed to define the ideal range to maintain SBP after AIS.