bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T MP76: Acute Kidney Injury in Acute Ischemic Strokes is Associated with Worse Outcomes
Authors: Khursheed Faraz , Adil Malik M , Saeed Fahad , Branch Lionel A , Vidal Gabriel A , Qureshi Adnan I
Published: March 2022

Background:
Acute Kidney Injury (AKI) in setting of acute ischemic stroke (AIS) is associated with worse outcome.

Objective:
To determine the effect of AKI on outcomes of AIS patients treated in a large national cohort. In a sub-analysis we looked at the outcomes of AKI in AIS patients treated with and without thrombolytic.

Methods:
Data from all patients admitted to US hospitals between 2002 and 2010 with a primary discharge diagnosis of ischemic stroke and secondary diagnosis of AKI treated with or without IV thrombolysis were included. The effect of AKI on rates of intracerebral hemorrhage (ICH) and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis.

Results:
Of 7,068,334 patients with AIS, 372,223 (5.3%) had AKI. AIS patients with AKI had higher rates of moderate to severe disability (41.3% versus 30% p=<0.0001), ICH (1.0% versus 0.5% p=<0.0001) and In-hospital mortality (8.4% versus 2.9% p=<0.0001) compared to those without AKI. After adjusting for potential confounders AIS patients with AKI had higher odds of moderate to severe disability [Odds ratio (OR) 1.4, 95% confidence interval (CI) (1.3-1.4, p=<0.0001)], ICH [(OR) 1.6, 95% (CI) (1.5-1.8, p=<0.0001)] and death [(OR) 2.6, 95% (CI) (2.5-2.8, p=<0.0001)]. In a sub-analysis, AIS patients with AKI who were treated with thrombolytic had higher rates of moderate to severe disability (54.5% versus 41.1% p=<0.0001), ICH (7.4% versus 0.8% p=<0.0001) and In-hospital mortality (21.4% versus 8.2% p=<0.0001) compared to those were not treated with thrombolytic. After adjusting for potential confounders AIS patients with AKI who were treated with thrombolytic had higher odds of moderate to severe disability [(OR) 1.7, 95% (CI) (1.5-2.0, p=<0.0001)], ICH [(OR) 8.0, 95% (CI) (6.1-10.2, p=<0.0001)] and death [(OR) 2.7, 95% (CI) (2.3-3.2, p=<0.0001)] compared to those were not treated with thrombolytic.

Conclusion:
AKI in patients with AIS is associated with significantly higher rates of disability at discharge, ICH and in-hospital mortality. In such patients, administration of thrombolytic treatment further worsens the outcome.
Abstract T MP78: Real Time Prediction of Early Neurologic Deterioration using A Blood Pressure Volatility Model in Acute Ischemic Stroke
Authors: Kang Jihoon , Noh Maeng Seok , Lee Youngjo , Jang Min Uk , Hong Jeong-Ho , Kim Beom Joon , Yeo Min Ju , Han Moon-Ku , Bae Hee-Joon
Published: March 2022

Objectives:
We aimed to develop a blood pressure (BP) embedded real time prediction model for early neurologic deterioration (END) in patients with acute ischemic stroke

Methods:
We identified consecutive ischemic stroke patients hospitalized within 48 hours of symptom onset from a prospective stroke registry database. BP data during hospitalization were obtained from the electric medical records. Probability of END at each time point of BP measurement was estimated using logistic model with covariates derived from two models for clinical information and BP parameters. A model for clinical information was fitted by using logistic model with patients’ clinical characteristics to predict END. A model for BP was fitted by random-effects models with temporal correlations at each time point of BP measurement with irregular intervals for mean as well as dispersion. Prediction performance was evaluated by calculating receiver operating characteristic (ROC) curve, and the cut-off value of high probability of END was determined at each time point. An alarm criterion for a proportion of high probability of END at each time point was defined as more than 50% of point probabilities being above the cut-off during the prior 24 hours. Predictive values of the prediction model were analyzed.

Result:
Of 1805 subjects, 18.3% experienced END. The predicted model for END within 24h hours from each time point of BP measurement was fitted by the model for clinical information of age, sex, history of stroke, time to arrival, baseline NIHSS score, diabetes mellitus, initial glucose level, atrial fibrillation, leukocyte count, stroke subtypes, recanalization therapy, and location of symptomatic vessel and by estimated mean of systolic BP and dispersion of diastolic BP from the temporal model for BP. Prediction performance was determined (Area Under Curve of ROC = 0.72) and the cut-off probability of END at each time point was set as > 0.01 (sensitivity = 50% and specificity = 81%). Using these criteria, about 70% of patients with END could be alarmed within 24 hours before the occurrence of END although 20% of those without END were falsely alarmed.

Conclusion:
This BP-embedded real time prediction model would helpful to predict and give a warning of the following END.
Abstract T MP83: Comparison of Pharmacologic versus Mechanical Venous Thromboemoblism Prophylaxis in Patients with Intracranial Hemorrhage
Authors: Frontera Jennifer A , Jovine Maximo , Hunter Samuel , Catalano Ashley , Gordon Errol
Published: March 2022

Introduction:
The use of pharmacologic venous thromboembolism (VTE) prophylaxis in patients with acute intracranial hemorrhage has been controversial due to concerns of hemorrhage expansion. We hypothesize that pharmacologic VTE prophylaxis is associated with better functional outcomes, without excess bleeding risk, compared to mechanical prophylaxis alone.

METHODS:
In a prospective study of intracranial hemorrhage patients (SAH N=116; intracerebral hemorrhage N=125 and subdural hemorrhage N=130) conducted between 7/2008-11/2011, we compared bleeding complications, VTE rates and 3-month functional outcomes between patients who received pharmacologic VTE prophylaxis (either heparin or enoxaparin) plus compression boots versus mechanical prophylaxis (compression boots) alone.

RESULTS:
Of 371 patients, 265 (70%) received pharmacologic prophylaxis in addition to compression boots, while 106 (29%) received compression boots alone. The median time to initiation of pharmacological prophylaxis was 4 days post hemorrhage onset and 2 days from surgical intervention, while mechanical prophylaxis was started at hospital admission. Compared to mechanical prophylaxis alone, those who received pharmacologic prophylaxis were younger (median age 60 versus 69, P=0.002), more likely to have a SAH (41% versus 8%, P<0.0001), less likely to have SDH (25% versus 60%, P<0.0001) and less likely to be DNR/comfort care (14% versus 27%, P<0.0001). Admission GCS and APACHE 2 scores did not vary between groups. ICH expansion was less common in those receiving pharmacologic prophylaxis (7% versus 2%; P=0.030) and there were no differences in other bleeding events (EVD associated hemorrhage, new ICH, new SDH, SDH reaccumulation, bleeding at the craniotomy site, GI bleeding or anemia requiring transfusion) or thombotic events (DVT or PE). Pharmacologic prophylaxis was significantly protective against death at 3 months after adjusting for age, admission GCS, bleed type, and DNR/comfort care status (aOR 0.2, 95% CI 0.1-0.5, P<0.0001).

CONCLUSIONS:
In intracranial hemorrhage patients, pharmacological VTE prophylaxis is not associated with higher bleeding risks and predicts improved 3-month mortality rates compared to mechanical VTE prophylaxis alone.
Abstract T MP92: Patient Valuation of Each Level of the Modified Rankin Global Disability Scale: Insights from the Stroke Impact Scale
Authors: Chaisinanunkul Napasri N , Starkman Sidney , Hamilton Scott A , Chatfield Fiona , Conwit Robin A , Saver Jeffrey L
Published: March 2022

Background:
The modified Rankin Scale (mRS) assessment of global disability is the most commonly used primary endpoint in acute stroke clinical trials and is endorsed for use by US and European drug/device regulatory authorities. However, the mRS is an ordinal scale with ranks an unknown distance apart, hampering identification of minimally clinically important differences in scale outcome distributions. The Stroke Therapy Academic Industry Roundtable and other authorities have called for studies to assign utility weights to each scale level, permitting construction of a “utility-weighted mRS”.

Methods:
Consecutive patients undergoing 3 month final outcome visits in the NIH FAST-MAG phase 3 trial were assessed with the mRS and the Stroke Impact Scale, a patient-reported, stroke specific quality of life instrument. The SIS has 8 subscales, assessing different outcome dimensions.

Results:
Among 44 alive patients, mean age was 71.9 (SD±13.9), 68% were male, and entry NIHSS was 9.3 (SD±8.6). At 90d, the median mRS was 1 (IQR 0 - 3, lower better). On the SIS patient global judgment of recovery, the 90d median value was 80 (IQR, 60-95, higher better). Score distributions of the 8 SIS functioning domains showed varied patterns across the 6 Rankin levels. At low mRS scores, SIS-QOL scores were modestly lowered in the domains of strength, emotion, activities of daily living, and social participation; lower SIS-QOL in the domains of memory and thinking, communication, and mobility only began to accrue at moderate to severe mRS scores. Utility weights for the mRS, derived from a cross-dimension average SIS score, were: mRS 0 - 0.95, mRS 1 - 0.90; mRS 2 - 0.74; mRS 3 - 0.67; mRS 4 - 0.44; mRS 5 - 0.36. The utility values were monotonic, with natural clusters at mRS 0-1, mRS 2-3, and mRS 4-5.

Conclusion:
Mild scores on the modified Rankin Scale are particularly associated with quality of life deficits in the domains of strength, emotion, activities of daily living, and social participation, while more severe mRS abnormalities compromise QOL across all domains of functioning. Utility values for the modified Rankin Scale derived from the Stroke Impact Scale show a decrement with each mRS level, with a natural tetrachotomization of the mRS at 0-1, 2-3, 4-5, and 6.
Abstract T MP98: Guideline-directed LDL Management Prior to Onset of Acute Ischemic Stroke in Patients with and Without Pre-existing Cardiovascular Disease: Findings from GWTG-stroke
Authors: Saposnik Gustavo , Fonarrow Gregg C , Pan Wenqin , Hernandez Adrian F , Schwamm Lee , Smith Eric E ,   on behalf of the AHA Get-With-The-Guidelines (GWTG)
Published: March 2022

Context:
Limited information is available whether high risk patients had achieved guideline-directed LDL goals prior to presenting with an acute ischemic stroke.

Objective:
To evaluate differences in the attainment of current LDL guidelines, based on admission LDL testing, in patients with acute ischemic stroke.

Methods:
Observational study, using data from the AHA-Get With The Guidelines Registry including 913,436 patients with an acute ischemic stroke or transient ischemic attack from April 2003 to September 2012. Participants were classified as high risk if they had prior history of TIA, stroke, and/or coronary artery disease (CAD). We used a previously created algorithm to determine the pre-stroke NCEP ATP-III goal.

Results:
Of the 913,436 patients admitted with an acute stroke or TIA, 283,162 (31.0%) had prior stroke/TIA, and 148,833 (16.3%) had prior CAD. Overall, only 68% of stroke patients were at their pre-admission NCEP III guideline-recommended LDL target on admission testing; 51.3% had LDL <100 mg/dL and only 19.8% had LDL100 mg/dL. Compared to patients with CAD, patients with prior TIA/Stroke were less likely to have LDL <100 mg/dL or <70 mg/dL (Table 1). In multivariable analysis, older age, male, white race, lack of major vascular risk factors, prior use of cholesterol-lowering therapy, and care provided in larger hospitals or West/Midwest hospitals were associated with meeting NCEP III LDL targets on admission testing.

Conclusion:
Current management of dyslipidemia in high risk patients with pre-existent CAD or stroke continues to be suboptimal. Only one in four patients with prior TIA/Stroke have LDL levels at the strict target <70 mg/dL.
Abstract T P1: Higher Recanalization Rate with Stentrievers, but Outcome Not Improved
Authors: Simonsen Claus Z , Sørensen Leif H , Karabegovic Sanja , Juul Niels , Andersen Grethe
Published: March 2022

Introduction:
Intraveneous (iv) recombinant tissue plasminogen activator (tPA) is the evidence based treatment in acute stroke. Intraarterial treatment with tPA and/or instrumentation of the vessel with the attempt to manipulate the clot and remove it (called Intra Arterial Therapy (IAT)) is emerging as a tool for treating patients with contraindications to iv tPA or for patients with large clot burden, where iv tPA is often unsuccessful. IAT has been shown to have better recanalization rates than iv tPA (1), but in a randomized trial, IAT did not prove itself better than traditional iv tPA (2). Stentrievers (ST) are a new form of removable stent and it has shown promise in improving recanalization and outcome in IAT (3).

Materials and methods:
At our institution, 237 patients underwent IAT from 2004-2012. STs were used as part of the recanalization procedure in 92 patients.

Results:
Recanalization (defined as TICI 2b or 3) was achieved among 76 of the 92 patients=83 % in the ST group and in 61/145=42 % of the patients in the non-ST group, giving an odds ratio (OR) for recanalization using ST on 6.54 (p<0.0001). Good outcome defined as a modified Rankin Score (mRS) of 0-2 90 days after the stroke was achieved among 44/92=48% in the ST group and among 63/145=43% in the non-ST group. There was no statistical difference between these rates.

Univariate analysis showed no differences in demographic data between ST and non-ST groups: Mean age 68 vs. 67 years (p=0.37), mean presenting NIHSS 17 vs. 16 (p=0.07) and time to groin puncture was 235 minutes in the ST group and 240 minutes in the non-ST group (p=0.17) (Mann-Whitney test).

Conclusion:
Recanalization is important for good outcome, but even though recanalization was achieved much more often in the ST group, this did not translate into better outcomes. Our findings are in line with the SWIFT study (3) where outcome defined as mRS 0-2 after 90 days were also not different between the ST group and the MERCI group. Manipulating the clot with the risk of distal embolization has been speculated to offset the benefit of recanalization (4).

References:
1) Stroke 2007;38:967-973

2) NEJM 2013;368:893-903

3) Lancet 2012;380:1241-1249

4) Stroke 2013;44:1761-1764
Abstract T P105: Cognitive Impairment is Common After Both Lacunar and Non-Lacunar Stroke and Persists at One Year
Authors: Makin Stephen , Dennis Martin S , Wardlaw Joanna M
Published: March 2022

Background:
Few data exist on long term cognitive outcome after lacunar stroke. We assessed cognition 1-6 weeks and 1 year after lacunar and mild cortical stroke, whilst correcting for age, SVD, depression and pre-morbid IQ.

Methods:
We recruited consecutive patients with lacunar and mild cortical stroke, diagnosed with DWI-MRI and careful clinical assessment. At 4-6 weeks and 1 year after index stroke we assessed white matter hyperintensities (WMH; Fazekas scale), cognition (Addenbrookes Cognitive Assessment, ACE-R), pre-morbid IQ (National Adult Reading Test, NART) and depression (Beck Depression Index, BDI). We defined 'dementia' as an ACE-R<88.

Results:
At 4-6 weeks post-stroke, 61/157 (38%) had dementia; at 1 year 56/151 (37%) had dementia; 136 were tested twice. Of the 45 who had dementia at first assessment & 9(20%) no longer had dementia at 1 year; of the 91 who did not have dementia at 4-6 weeks, 13 (14%) had become demented by 1 year. Patients with lacunar stroke had similar risk of cognitive impairment as patients with cortical stroke when adjusted for age, Fazekas score, BDI and NART in multivariable analyses (OR 0.91, 95%CI 0.32-2.13 at 1st assessment & 0.81, 95%CI 0.46-2.27 at 1 year). Previous stroke, low pre-morbid IQ and depression increased risk of dementia at both time points, but not vascular risk factors, sex, NIHSS or Fazekas score.

Conclusion:
Over one third of patients with a non-disabling stroke had dementia at 4-6 weeks post stroke, most of these (80%) remained demented at one year and 13% of those who were cognitively intact ay 4-6 weeks developed dementia by 1 year. Patients with lacunar stroke are equally likely to have dementia as those with cortical stroke, despite the small lesion size and good prognosis. Low pre-morbid IQ increases dementia risk. Future research should account for pre-morbid IQ, age and depression.
Abstract T P106: Sedentary Time During the Acute Hospital Stay is Associated With Functional Performance
Authors: Mattlage Anna , Karcher Sara , Sisante Jason-Flor , Lentz Angela , Rippee Michael , Abraham Michael , Billinger Sandra
Published: March 2022

Purpose:
A few studies have been conducted during in-patient rehabilitation to describe physical activity (PA) levels. Most have been observational and conducted at various time intervals during the day. These studies have shown that during in-patient rehabilitation, stroke survivors participate in minimal therapy as well as spend the majority of their day sedentary. To our knowledge no studies have characterized PA during the acute hospital stay. The purpose of this study was to objectively assess PA levels using tri-axial accelerometers during the acute hospital stay. We will determine whether the duration of sedentary bouts are associated with functional performance at discharge. We hypothesized that shorter bouts of sedentary time will moderately associated with greater performance on walking and functional ability at discharge.

Methods:
Twenty-nine individuals (14 males; average age of 59.17 ± 11.6 years) were enrolled into the study within 48 hours of hospital admission with acute stroke. Tri-axial accelerometers were placed bilaterally on the ankles to monitor activity 24 hours per day. Functional assessments were conducted at baseline and prior to discharge. Walking was assessed using the Timed-Up and Go (TUG) and Six Minute Walk Test (6MWT). Activities of daily living (ADLs) were assessed using the Physical Performance Test (PPT).

Results:
During the acute hospital stay, the average percent time spent in sedentary, light, moderate and vigorous activities was 94.8 ± 3.2%, 4.4 ± 2.1%, 0.5 ± 0.5%, and 0.1 ± 0.3%, respectively. For individuals with functional testing at baseline and discharge (n = 17), average length of sedentary bouts per day was significantly related to 6MWT (r = -0.61, p < 0.006) and PPT (r = -0.76, p < 0.001) at discharge, but not TUG (r = 0.24, p < 0.37) even when controlling for baseline performance.

Conclusion:
Stroke patients spend the majority of the stroke hospital stay sedentary. Stroke patients who had shorter bouts of sedentary time during the hospital stay showed greater performance in the 6-MWT and PPT. Acute stroke patients would benefit from decreasing sedentary time during the acute hospital stay.
Abstract T P108: A Novel Means of Augmenting Motor Recovery After Ischemic Stroke; Vagus Nerve Stimulation (VNS) Paired with Intensive Upper Limb Rehabilitation
Authors: Dawson Jesse , Pierce David , Kilgard Michael , Walters Matthew , Tarver Brent , Engineer Navzer
Published: March 2022

Introduction:
Chronic upper limb impairment is a major predictor of poor functional outcome after stroke. We have developed a rehabilitation intervention to address this isuue. It pairs VNS with intensive upper limb training. Our hypothesis is that short bursts of VNS, specifically timed during therapy, will drive cortical plasticity and improve clinical outcomes via timely release of neuromodulators such as acetylcholine and norepinephrine.

Methods:
Our research includes preclinical and clinical studies. In pre-clinical studies VNS was paired with different types of motor training in a rat Endothelin-1 model of ischemic stroke (n=15). All studies included a sham and intensive therapy control arm (n=17). We also explored the effect of VNS timing through randomizing its timing (n=2 rats). A randomized, controlled clinical trial with blinded endpoint assessment is underway. Twenty patients, at least 6 months after ischaemic stroke with chronic arm impairment will be recruited (10 VNS device plus rehabilitation and 10 rehabilitation only). All participants receive upper limb rehabilitation 3 days a week for six weeks (90-120 minutes per session). The primary endpoint is safety and feasibility and secondary endpoints include measures of upper limb function (such as ARAT, Fugl Meyer score).

Results:
Our animal results demonstrated that VNS resulted in rapid recovery of motor deficits after stroke in rats. This recovery persisted several weeks after the end of therapy. The non-VNS group showed only partial recovery despite the same intensive training. Improvement in motor performance does not appear to depend on precise timing of VNS within a therapy task.

Clinical Study:
Updated interim safety and observational data will be presented. To date (August 2013) 8 subjects are enrolled (4 have received VNS paired therapy and 4 controls). There have been no serious adverse events related to therapy and all participants have adhered to the intensive therapy protocol.

Conclusions:
In the ischemic preclinical models of stroke, VNS paired with physical therapy significantly improved outcomes compared to therapy alone. VNS also appears feasible and safe in adults at least 6 months after stroke and further clinical study of its effect on arm function is warranted.
Abstract T P116: Increased Maintenance of Motor Gains Following a Novel Stroke Therapy
Authors: Falcon M. I , Riley Jeffrey D , Chen E. E , Solodkin Ana
Published: March 2022

Introduction:
Action observation therapy (AOT), a novel approach based on the physiology of the mirror neuron system, uses observation/imitation of movements to facilitate recovery from stroke. We previously showed that AOT confers significant improvement in motor performance. More importantly, these gains are maintained up to 1 year compared to a classic therapy, ND Bobath (NDBT) (Falcon et al 2013). In this study we sought to determine concomitant brain function associated with motor recovery after these therapies and with maintenance of motor gains.

Methods:
Seventeen stroke subjects received either AOT or NDBT for 2 hours/day for 4 weeks. Motor outcome measures and MRI (T1-weighted and fMRI during a bimanual motor task) were acquired pre-treatment (Pre-Tr), post-treatment (Post-Tr) and maintenance after 6-12 months (MiNT). MRI data was processed in AFNI using a general linear model. Network analysis assessing effective connectivity was done via structural equation models (SEM). MRI from 20 healthy controls was included.

Results:

1. fMRI:

Pre-Tr: Compared to controls, all stroke subjects showed increased activation, mainly in parietal and frontal regions.

Post-Tr: Activation decreased in these regions in all stroke subjects.

MiNT: Activation was further decreased in the AOT group, while the NDBT group showed increased activity reminiscent of Pre-Tr levels.

2. SEM:

Pre-Tr: Both group networks involved nodes in parietal and frontal regions with strong connections in both hemispheres.

Post-tr: The weight of connections in the non-dominant hemisphere after AOT decreased compared to Pre-Tr levels. After NDBT, it increased.

MiNT: The weight of connections in the non-dominant hemisphere after AOT continued to decrease.

Conclusions:
Although decreased brain activation in both groups was associated with better motor performance Post-Tr, brain connectivity was discordant; effective connectivity decreased after AOT and increased after NDBT. This indicates differing mechanisms associated with stable (gains maintained) and poor (gains lost) recovery after AOT and NDBT respectively. These results may highlight relevant functional mechanisms for developing potential therapies.
Abstract T P144: Association Between Lipoprotein (a) Levels and Vascular Events in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial
Authors: Pawar Swaroop , Turan Tanya N , Lynn Michael J , Nizam Azhar , Le Ngoc-Anh , Montgomery Jean , Derdeyn Colin P , Fiorella David , Lane Bethany F , Janis Scott , Chimowitz Marc I ,   SAMMPRIS Investigators
Published: March 2022

Background:
Lipoprotein (a) (Lp(a)) has been implicated in atherothrombogenesis and prior studies have suggested its pathogenic role in the development of intracranial atherosclerosis (ICAS).

Objective:
We sought to determine the association between baseline Lp(a) levels and risk of vascular events during follow-up in patients randomized to the medical arm of the SAMMPRIS trial.

Methods:
Baseline Lp(a) data was available for 226 of 227 patients randomized to the medical arm in SAMMPRIS. High Lp(a) was defined as > 65 mg/dL in Blacks and > 35 mg/dL in Whites and Others. The primary outcome was any ischemic stroke and the secondary outcome was a composite of vascular events (ischemic stroke, MI and vascular death). Kaplan-Meier curves for the time to the outcomes were compared between patients with high and low Lp(a) using the log-rank test. Using Lp(a) as a continuous variable, Cox proportional hazards model was used to determine the association between Lp(a) and time to outcomes of interest.

Results:
Overall, 17/92 (18.5%) patients with high Lp(a) levels had an ischemic stroke during follow-up versus 24/134 (17.9%) with normal Lp(a) levels, with no difference between the Kaplan-Meier curves of the groups (p=0.94). In a Cox proportional hazards model relating Lp(a) to time to ischemic stroke, Lp(a) was not statistically significant (p = 0.82). Similarly, 23/92 (25%) patients with high Lp(a) levels had a vascular event during follow-up versus 29/134 (21.6%) with normal Lp(a) levels, with no difference between the Kaplan-Meier curves (p=0.58). In a Cox proportional hazards model relating Lp(a) to time to ischemic stroke, MI, or vascular death, Lp(a) was not statistically significant (p = 0.46).

Conclusion:
Patients with high Lp(a) levels in the SAMMPRIS trial did not have an increased risk of ischemic strokes or vascular events during follow-up. Although prior studies have suggested a pathogenic contribution of high Lp(a) to the development of ICAS, our results do not find an association between high Lp(a) and increased risk of vascular events.
Abstract T P168: Headache and Cerebral Venous Thrombosis
Authors: Cantu Brito Carlos , Chiquete Erwin , Arauz Antonio
Published: March 2022

Background and purpose:
Headache is the most frequent presenting symptom of cerebral venous thrombosis (CVT), but many aspects of its profile are unknown because large scale studies are scarce. We aimed to analyze the headache characteristics in the largest cohort of Hispanic Mestizo patients with CVT.

Methods:
Since 1986 a systematic CVT registry has been carried out in 2 tertiary referral Neurological centers in Mexico City. Herein we examine the headache profile and the association of demographic, clinical and neuroimaging factors with the occurrence of headache in 408 consecutive patients.

Results:
Among 408 patients (82% women) included in this registry, headache occurred in 346 (85%; 86% in women, 79% in men, p NS), being the first neurological manifestation in 309 (76%). Headache onset was acute in 46%, of gradual onset in 51%, and a sudden explosive onset like thunderclap occurred in 3%. A diffuse headache pattern occurred in 56%, bifrontal in 22%, unilateral in 15%, and suboccipital in 8%. It was of pulsatile quality in 73%, and oppressive in 24.3%, and it was mostly deemed as severe (49%) or moderate (47%) in intensity, described as progressive in 19%, and with nausea or vomiting in 52% patients. Headache was the only neurological symptom in 58 patients (14%): as part of an isolated intracranial syndrome in 52 (13%) and as the sole manifestation of CVT in 6 (1.5%). Headache was followed by other neurological symptoms in 70%, appearing within 48 hours of headache onset in 33%, within 3-6 days in 34%, within 7-10 days in 16%, and after 10 days in 18%. CVT diagnosis was significantly delayed in patients with headache, as compared with other neurological presentations (delay >15 days: 30% vs. 8%, respectively; p<0.05). There were not differences in anatomical topography of CVT in patients presenting with headache, as compared with other neurological features.

Conclusions:
There is no identifiable, uniform, recognizable pattern of headache in CVT and often precedes the development of other neurological deficits for days or even weeks delaying the diagnosis of CVT. Interestingly, neither the presence nor the quality of headache is associated with the topography or extension of CTV.
Abstract T P17: Futile Revascularization in Patients With Acute Stroke After Treatment With Mechanical Thrombectomy
Authors: Shi Zhong-Song , Xiang Bin , Ge Sijian Grace , Duckwiler Gary ,   for the MERCI and Multi MERCI Investigators
Published: March 2022

Purpose:
Successful revascularization after endovascular treatment may fail to improve outcome in a subset of acute stroke patients. The purpose of this study was to characterize the frequency and predictors of futile revascularization (FR) in patients treated by mechanical thrombectomy with Merci retriever.

Methods:
We retrospectively analyzed the pooled data of stroke patients from the MERCI and multi MERCI trials. FR was defined as the occurrence of poor outcome (mRS score of ≥3 at 90 days) despite successful revascularization measured by a TIMI score 2 or 3. We evaluated demographic, clinical, angiographic variables and hemorrhage as potential covariates of FR. Variables showing a possible association with FR (p≤0.1) in univariate analysis were considered in multivariate logistic regression modeling.

Results:
Among 305 patients, 197 patients achieved successful revascularization in the pooled trials. A total of 186 patients were included in the outcome analysis. FR was observed in 98 of 186 (52.7%) patients. Patients with FR were older, increased baseline NIHSS score (21 vs. 16; p<0.0001), increased systolic blood pressure (147.8 vs. 140.0 mmHg; p=0.031), increased glucose levels (147 vs. 120 mg/gL; p=0.0001), more often had a history of hypertension and diabetes mellitus, increased number of attempts to remove clot (3.0 vs. 2.0; p=0.033), longer puncture to revascularization time (1.7 vs. 1.4 hours; p=0.049), decreased rate of TIMI 3 revascularization (52.0% vs. 71.6%; p=0.007), higher rate of symptomatic hemorrhage (10.2% vs. 0%; p=0.002). In the multivariate analysis, independent predictors of FR were NIHSS (OR=1.15; p<0.0001), glucose (OR=1.02; p=0.0008), hypertension (OR=2.62; p=0.012), and TIMI 3 revascularization (OR=3.14; p=0.002). Patients with FR had increased NIHSS score at 24 hours post-procedure (23.2 vs. 6.3) and at discharge (23.7 vs. 3.0), and had longer lengths of hospitalization (11.1 vs. 8.1 days).

Conclusion:
Futile revascularization is relatively frequent in patients treated by Merci thrombectomy, particularly among those with severe neurological deficits, hyperglycemia or hypertension. These findings may require validation in a larger sample size of mechanical thrombectomy with Merci and stent retrievers.
Abstract T P177: Cryptogenic Stroke: Frequency and Diagnostic Evaluation Across Different Age Groups
Authors: Razmara Ali , Jindal Jenelle , Ayres Alison , Singhal Aneesh B
Published: March 2022

Introduction:
Stroke etiology differs across the age spectrum, with higher rates of uncommon causes in younger adults, and large-artery atherosclerosis or cardioembolism in older adults. There is little data regarding frequency of cryptogenic stroke (CS) across the age spectrum. Conceivably, CS frequency may differ across age groups because of differences in extent of diagnostic tests, and diagnostic yield (i.e. abnormal result relevant to stroke etiology).

Methods:
We retrospectively analyzed our stroke registry data with consecutive inpatients with imaging-confirmed ischemic stroke/TIA admitted 2007-2010. Stroke etiology was prospectively classified by trained MDs into TOAST categories using an automated algorithm. Patients were grouped according to age, 18-49y, 50-75y and 75+ years.

Results:
As shown in the Table, there were significant differences in NIHSS scores and vascular risk factors across age groups. TOAST subtype distribution was significantly different across age groups (p<0.001, with higher percentage of large-artery and cardio-embolic in older age groups and other well-defined causes in 18-49y age group. Cryptogenic strokes (“undetermined”) were less common in 18-49y group (13% vs 20% vs 21%, p=0.02), possibly because PFO-associated strokes are included under the cardio-embolic category. The rates of diagnostic tests performed were significantly different, as was their diagnostic yield, e.g. toxicology screening was common (63%) in the 18-49y age group with a diagnostic yield of 11%; in the 75+ year age group it was performed in only 38% whereas the yield was not negligible (5%).

Conclusion:
Rates of cryptogenic stroke differ significantly across age groups. This may partly be explained by differences in the extent of diagnostic evaluations. Our results may have implications for stroke management however more research is warranted to determine the cost-effectiveness of diagnostic tests and design appropriate treatment strategies.
Abstract T P179: Atrial Fibrillation Unidentified Prior to Stroke/tia: Background Features, Stroke Severity and Outcome - The Samurai-nvaf Study
Authors: honma kazunari , Toyoda Kazunori , Takizawa Shunya , Todo Kenichi , Kimura Kazumi , Shiokawa Yoshiaki , Kamiyama Kenji , Terasaki Tadashi , Okada Yasushi , Nagakane Yoshinari , Mochizuki Hiroshi , Hasegawa Yasuhiro , Okuda Satoshi , Furui Eisuke , Ito Yasuhiro , Nakashima Takahiro , Kario Kazuomi , Kameda Tomoaki , Takamatsu Kazuhiro , Nishiyama Kazutoshi , Arihiro Shoji , Yamagami Hiroshi , Kobayashi Junpei , Sato Shoichiro , Koga Masatoshi
Published: March 2022

Purpose:
Atrial fibrillation (AF) is often detected after embolic events occur, and it is an obstacle to effective preventive anticoagulation. We aimed to determine a percentage of patients with nonvalvular AF (NVAF) unidentified prior to stroke in the overall stroke patients with NVAF, as well as background features, stroke severity and outcome of such occult NVAF patients.

Methods:
A total of 743 acute ischemic stroke/TIA patients with NVAF (344 women, 78±10 years old) were enrolled between Sep 2011 and Jun 2013 from a multicenter prospective registry (the SAMURAI-NVAF study, NCT01581502). Patients were divided into two groups; those with identified AF before stroke/TIA (Group I) and those with unidentified AF that was documented at emergent visit or later (Group U). Favorable outcome was defined as mRS 0-2 at hospital discharge (for 710 patients, median 23 days) and at 3 months (for 565 patients).

Results:
285 patients belonged to the Group U (38%; 138 women, 78±11 years old). Although both median CHADS
2
(2 vs. 2, p<0.001) and CHA
2
DS
2
-VASc (3 vs. 4, p<0.001) were lower in the Group U than the Group I, patients with the high ischemic risk category (≥2 in each score) accounted for 68% according to CHADS
2
and 91% according to CHA
2
DS
2
-VASc in the Group U. After multivariate adjustment, paroxysmal AF (OR 1.91, 95% CI 1.24-2.75) was more common and congestive heart failure (0.63, 0.40-0.99) and premorbid use of oral anticoagulants (0.08, 0.04-0.13) were less common in the Group U than the Group I. The median initial NIHSS was higher in the Group U (11 [IQR 4-19]) than in the Group I (6 [2-17], p<0.001). Favorable outcome was less common in the Group U than the Group I both at discharge (41% vs. 51%, p=0.011) and at 3 months (46% vs. 56%, p=0.036). Unidentified AF was independently associated with mRS 3-6 after adjustment for sex and age both at discharge (OR 1.57, 95% CI 1.13-2.18) and at 3 months (1.60, 1.10-2.32), but was no longer associated with mRS 3-6 after further adjustment for the initial NIHSS.

Conclusion:
Two fifth of the stroke/TIA patients with NVAF were not diagnosed as having AF prior to the attack, though their ischemia-risk indices were generally high. Patients with such occult NVAF had severer stroke and worse outcome than those with identified AF.
Abstract T P199: Severity-adjusted Re-analysis of the Phase 2 Clear-er Stroke Trial
Authors: Adeoye Opeolu , Sucharew Heidi , Khoury Jane , Schmit Pamela , Hemmen Thomas M , Meyer Brett C , Broderick Joseph , Pancioli Arthur
Published: March 2022

Background:
The proportion of good outcome (modified Rankin score/mRS ≤1 or return to baseline mRS) in the intervention arm of the randomized Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial provided evidence for pursuing a phase 3 trial of IV rt-PA plus eptifibatide versus rt-PA alone in acute ischemic stroke (AIS). However, CLEAR-ER had unanticipated imbalances between groups. Using a sliding dichotomy, we compared the rates of good outcome in CLEAR-ER combinations arm to that in the rt-PA arm of the NINDS stroke trials.

Methods:
CLEAR-ER was a multi-center, double-blind, randomized study. rt-PA eligible AIS patients were randomized to 0.6mg/kg rt-PA plus eptifibatide (135mcg/kg bolus and 0.75mcg/kg/min two-hour infusion) versus standard rt-PA (0.9mg/kg). For this analysis, as previously suggested for acute stroke trials, good outcome was defined as: 90-day mRS 0 if pretreatment NIHSS scores were 1 to 7; 90-day mRS 0-1 if pretreatment NIHSS scores were 8 to 14; 90-day mRS 0-2 if pretreatment NIHSS scores were >14. As in CLEAR-ER, patients who returned to baseline mRS were considered good outcome. To match CLEAR-ER eligibility criteria, NINDS trial rt-PA arm patients aged 18-85 years with a baseline NIHSS score >5 were used for comparison. Logistic regression was used for analyses.

Results:
In the combination therapy arm CLEAR-ER patients, 45% (45 out of 101) had good outcomes compared with 39% (105 out of 266) of the rt-PA arm patients from the NINDS trial (unadjusted odds ratio 1.23, 95%CI 0.77-1.96, p=0.38). After adjusting for baseline NIHSS score, age, gender, pre-existing disability and time to IV rt-PA, the odds ratio was 1.14 (0.69-1.88, p=0.61). When the groups were collapsed by baseline NIH stroke scale <15 versus ≥15, the unadjusted odds ratio was 1.39 (0.88-2.21, p=0.16); after adjustment, the odds ratio was 1.27 (0.75-2.14, p=0.37).

Conclusion:
In this exploratory analysis, severity-adjustment confirmed a direction of effect that justifies a well-designed, adequately powered phase 3 trial to determine the efficacy of rt-PA plus eptifibatide for treatment of AIS.
Abstract T P205: Thrombopoietin Reduces Brain Injury and Cognitive Impairment in Rodent Cerebrovascular Disease Models
Authors: Rosenbaum Daniel M , Zhou Jin , Zhang Haiyan , Li Jie , Zhuang Jiang , Poon Carrie , Poon Carrie , Barone Frank C
Published: March 2022

Objectives:
Thrombopoietin (TPO) reduces brain injury and sensory-motor deficits following stroke in the rat. TPO brain protection is mediated by vascular protection. TPO reduces stroke-induced inflammatory cytokines, matrix metalloproteinase’s and blood brain barrier injury. Here we demonstrate that TPO protects the brain and reduces vascular cognitive impairment in: [1] rat embolic stroke (+/- tissue plasminogen activator; tPA), [2] mouse suture-focal stroke, and [3] mouse chronic carotid stenosis-induced forebrain hypoperfusion.

Methods:
Rats (Wistar) underwent embolic middle cerebral artery occlusion (MCAO). Vehicle, tPA (10 mg/kg, iv), TPO (0.1 μg/kg, iv) or TPO plus tPA were administered 2 hours post-stroke. Mice (C57Bl/6) underwent suture-MCAO or carotid artery stenosis-induced forebrain hypoperfusion and then received Vehicle or TPO (0.3 or 0.1 μg/kg, iv) at 1 hr or 1 day after surgery. Neurological deficits, complex learning and hemispheric infarct size were measured for 1-21 days post-surgery.

Results:
In rat embolic stroke, tPA or TPO plus tPA improved stroke-induced neurological deficits significantly. Significant post-stroke-induced deficits in APA cognitive performance were improved 87.2±16.4% by TPO or 69.4±9.7% by TPO plus tPA, but not by tPA alone. In mouse suture-focal stroke, brain infarcts were reduced by 64.5±7.7% and neurological deficits were reduced by 90.3±6.4%. In mouse carotid artery stenosis-induced forebrain hypoperfusion a single administration of TPO 1 day after surgery improved APA performance 84.8+3.1% 3 weeks later (all p<0.01).

Conclusions:
We have demonstrated TPO long-term protection and safety with and without tPA. TPO exhibits protection in mouse suture-focal and in mouse forebrain hypoperfusion-induced complex learning deficits. These data present multiple model and species work that supports the potential “multiple use” of TPO in the future.
Abstract T P206: Mkp-1 Inhibition Increases Stroke Injury via JNK Pathway Activation
Authors: Liu Lin , Doran Sarah , Xu Yan , McCullough Louise , Li Jun
Published: March 2022

Background:
MKP-1, a negative modulator of several MAP kinases including JNK and p38, is a critical regulator of inflammation and apoptosis in the CNS. Inhibition of MKP-1 worsens stroke outcome in mice, suggesting that MKP-1 is an endogenous protective molecule, although the underlying mechanisms remain unclear. Here we investigated the downstream mediators of MKP-1’s effects in stroke.

Methods:
Stroke was induced by 60 min transient middle cerebral artery occlusion (tMCAO) in male mice. Levels of p-JNK and p-p38 in MKP-1 KO mice and WT littermates 6 hours after stroke were assessed by Western blots. In a second cohort, the selective JNK inhibitor (SP600125) was administered intraperitoneally to both MKP-1 KO and WT mice 30 min before stroke then infarcts were analyzed at 72 hours post ischemia. In a third cohort, WT mice were intraperitoneally administrated the inhibitor or vehicle 30 min before stroke and sacrificed at 6 hours for protein analysis.

Results:
MKP-1 deletion produced significantly higher levels of p-JNK 6 hours after stroke (0.71±0.12 WT vs. 1.32± 0.14 KO, p<0.05, n= 3 p/g); this was not seen for p-p38 (1.06± 0.19 WT vs. 1.30± 0.34 KO, n=3 WT, 2 KO). Furthermore, MKP-1 deletion significantly increased expression of JNK pathway related molecules such as p-c-jun/c-jun (0.57± 0.17 WT vs. 3.65±1.19 KO, p<0.05, n=3 p/g) and cleaved-caspase-3 (0.62 ± 0.09 WT vs. 1.81 ± 0.32 KO, p<0.05, n=3 p/g), with no changes in cleaved-caspase-8 (1.11 ± 0.09 WT vs. 1.02 ± 0.04 KO, p>0.05, n=3 p/g). There was no additive deleterious effects of pharmacological JNK inhibition in MKP-1 KO mice as measured by infarcts at 72 hours (cortex: 25.84±2.44%WT vs. 22.32±1.91%KO, striatum: 33.10±3.61% WT vs. 26.52±1.92% KO, total: 27.85±2.95% WT vs. 26.75±1.61% KO, p>0.05, n=6 p/g). In WT mice, JNK inhibition significantly decreased p-JNK (0.99 ± 0.14 vehicle vs. 0.44 ± 0.13 drug, p<0.05, n=3 p/g) 6 hours after stroke but had no effects on MKP-1 (2.36 ± 0.34 vehicle vs. 3.43 ± 0.45 drug, p>0.05, n=3 p/g).

Conclusions:
JNK is an important downstream mediator of MKP-1’s effects in stroke. In the ischemic brain, activating MKP-1 may restrain JNK activity, thereby producing neuroprotective effects.
Abstract T P211: Reduction of Cerebral Hemorrhage by Dabigatran via Neurovascular Protection after Recanalization with tPA in Ischemic Stroke of Rat
Authors: Kono Syoichiro , Deguchi Kentaro , Omote Yoshio , Yunoki Taijun , Yamashita Toru , Kurata Tomoko , Abe Koji
Published: March 2022

Background & Objectives:
This study aimed to assess the risk and benefit of tPA treatment under oral anticoagulation with dabigatran compared to warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO).

Methods:
After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 h after reperfusion, markers for the neurovascular unit at the periischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography.

Results:
Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group than in the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats.

Conclusions:
The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partly explain the reduction in hemorrhagic complication by dabigatran reported in the clinical study.
Abstract T P219: Customizing the Secretomes of Mesenchymal Stem Cells: Implications for Clinical Trials
Authors: Mir Osman , Parsha Kaushik , Yang Bing , Hanely Patrick , Gee Adrian , Aronowski Jaroslaw , Savitz Sean
Published: March 2022

Background:
Extensive animal data indicate that mesenchymal stem cells (MSCs) improve outcome in stroke models. Systemic delivery either by IV or Intra-arterial(IA) injection of MSCs is a potential therapeutic intervention for stroke based on the broad repertoire of secreted trophic and immunomodulatory cytokines that MSCs produce. We determined if exposure of MSCs to different types of solutions and catheters relevant to IA injections will lead to differential secretion of cytokines and thereby alter the functionality of MSCs.

Methods:
Passage 2 MSCs were derived from human bone marrow donated by a healthy volunteer and tested in the following: 5% albumin(Alb),6% Hexstarch(Hx) or 40% dextran(Dx). Each solution was tested in 3 forms: solution alone, with low dose (5 IU/ml) Heparin, with 10% Omnipaque, or the combination of heparin and omnipaque. 5 million MSCs were suspended in 1ml of respective solution for 5, 30 or 60 mins. At the end of each time point, cells were collected directly or passed through a catheter (PROWLER SELECT LP). Viability and cytokine release profiles were tested under various scenarios.

Results:
Cell viability remained above 90% in all solutions tested, Alb being the highest at 98%, and was not reduced after catheter passage, exposure to heparin or Omnipaque. Catheter passage did not alter MSC cytokine secretion in almost all the cases (Fig). Alb led to increased release of angiogenic factors such as VEGF and IL-8 compared with other solutions while Hx and Dx led to suppression of inflammatory cytokines such as IL-6 and TNF-α.

Conclusions:
Exposure of MSCs to certain types of solutions change the profile of cytokine secretion. The activation patterns of MSCs may therefore be affected by the solutions/vehicles used for these cells. It may thus be possible to customize the profile of MSC secretomes to selectively modify their cytokine expression and individualize stem cell treatment to preferentially enhance or downregulate specific biological effects.