bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P289: Genetic Variation in the Sulfonylurea Receptor 1 (Sur1)-regulated NCCa-ATP Channel and Stroke Outcome: The Genetics of Early Onset Stroke Study
Authors: Cole John W , Ryan Kathleen A , Cheng Yu-Ching , Koontz Deborah , Bean Christopher J , Gallagher Margaret , Hooper W C , McArdle Patrick , O’Connell Jeffrey R , Stine O. C , Wozniak Marcella A , Stern Barney J , Mitchell Braxton D , Kittner Steven J , Simard J M
Published: March 2022

Background and Purpose:
Recent evidence indicates that the sulfonylurea receptor 1 (Sur1)-regulated NCCa-ATP channel is transcriptionally upregulated de novo in cells of the neurovascular unit in response to cerebral ischemia and plays a key role in the development of cerebral edema. We hypothesized that polymorphisms in the genes coding for the proteins associated with this channel may play a role in outcome following ischemic stroke.

Methods:
From a biracial population-based study we identified 856 cases of first-ever ischemic stroke in women and men ages 15 to 49 years. 44 SNPs were genotyped in ABCC8, 16 SNPs in TRMP4, and 6 SNPs in SP1. Cases with diabetes were excluded since glyburide is known to block the Sur-1 NCCa-ATP channel. Lacunar strokes were excluded since edema is not hypothesized to contribute to outcome in this stroke subtype. Following exclusions the final population included 235 African-American and 342 Caucasian cases. Utilizing the modified Rankin Score at hospital discharge (0 to 3 and 4/5 combined), ethnicity-stratified regression analyses were performed against genotype in an additive model, controlling for age and gender.

Results:
Among Caucasians there were 6 significantly associated TRMP4 SNPs (all with MAF~0.32; p=0.02-0.05) that were in strong linkage disequilibrium (D’>0.80). Among African-Americans there were 3 significantly associated TRMP4 SNPs (p=0.02-0.04). Notably, 2 of these 3 SNPs were also among those identified the Caucasians, rs909010 and rs1175791 (both AA SNPs with MAF~0.45). In ABCC8 there was 1 significant SNP (rs2299640; MAF=0.30; p=0.01) among African-Americans and none among Caucasians. SP1 analyses demonstrated no associated SNPs in either ethnicity.

Conclusions:
Genetic variation in TRMP4 may play a role in outcome following ischemic stroke. Confirmatory studies are needed.
Abstract T P29: Arterial-Spin Labeled MRI After Endovascular Stroke Therapy: Validation of a Novel Scale to Quantify the Degree and Heterogeneity of Reperfusion
Authors: Liebeskind David S , Sanossian Nerses , Alger Jeffry R , Qiao Joe X , Scalzo Fabien , Johnson Mark S , Starkman Sidney , Ali Latisha K , Kim Doojin , Rao Neal M , Hinman Jason D , Tansy Aaron P , Calderon-Arnulphi Mateo , Modir Royya F , Vespa Paul M , Blanco Manuel B , Jahan Reza , Tateshima Satoshi , Gonzalez Nestor R , Duckwiler Gary R , Viñuela Fernando , Saver Jeffrey L , Yoo Bryan , Salamon Noriko , Wang Danny J ,   for the UCLA Stroke Reperfusion Therapy Investigators
Published: March 2022

Background:
The degree of reperfusion in acute stroke is a key predictor of clinical outcome, yet validation of a noninvasive imaging technique such as arterial spin-labeled MRI (ASL) that can quantify both hypo- and hyperperfusion is needed.

Methods:
Consecutive series of endovascular therapy for acute stroke and ASL-MRI within 36 hours after treatment start during a 3-year period were analyzed. Reperfusion on DSA was scored with TICI and mTICI (2b definitions of 2/3 and ½, respectively). ASL cerebral blood flow was graded with a scale analogous to mTICI (0=none, 1=< ½, 2=>½, 3=complete) separately for hypo- and hyperperfusion based on occlusion site, yet blinded to TICI/mTICI results.

Results:
64 patients (mean age 67.7 ± 13.9 years; 53% women; median baseline NIHSS 15 (2-38)) had ASL acquired within 36 hours (median 7.07 hours (2.69-33.08)) from start of IV thrombolysis or thrombectomy over a 3-year period. 31/64 (48%) patients received IV tPA before endovascular therapy. DSA revealed 32 M1, 18 ICA, 10 M2, and 4 basilar occlusions. After endovascular treatment, TICI0/mTICI0 (6%), TICI1/mTICI1 (2%), TICI2a/mTICI2a (30%), TICI2a/mTICI2b (22%), TICI2b/mTICI2b (39%) and TICI3/mTICI3 (2%) results were noted. ASL revealed hypoperfusion (0 (19%); 1 (59%); 2 (14%); 3 (8%)) and hyperperfusion (0 (69%); 1 (27%); 3 (5%)). 7 combined patterns of hypo- and hyperperfusion were noted on ASL, all unrelated to baseline clinical variables. ASL mTICI hypoperfusion strongly correlated with DSA mTICI (R=-0.77, p<0.001) and TICI (R=-0.71, p<0.001). ASL hyperperfusion was noted only with TICI2a/mTICI2a (9%), TICI2a/mTICI2b (14%), TICI2b/mTICI2b (9%) and was more common with increased time from DSA to ASL (p=0.017).

Conclusions:
ASL hypoperfusion within 36 hours of acute stroke therapy strongly correlates with reperfusion scores on DSA, providing a novel means to accurately quantify degree of reperfusion. ASL hyperperfusion, concomitant with hypoperfusion, affects a substantial number of cases, predominantly affecting the TICI2a/mTICI2b reperfusion category on DSA.
Abstract T P294: Systematic Implementation of a Multi-Hospital Rapid TIA Evaluation Protocol Reduces Unnecessary Admissions
Authors: Bakhadirov Khamid , Razmara Ali , Ali Syed F , Hand Laura B , Elias Josephine S , Feske Steven K , Almozlino Avraham , Schwamm Lee H
Published: March 2022

Intro:
Rapid management of TIA patients is a cost-effective intervention to reduce stroke incidence. We evaluated the effect of an ED-based rapid TIA evaluation protocol on the provision of care concordant with a system-wide TIA guideline that was developed in a multi-hospital collaborative QI project.

Method:
We included 89 consecutive patients in pre-intervention (2012) and 72 in post-intervention (2013) phases from 2 tertiary and 1 large community hospitals. Patient evaluations and disposition were compared to an evidence-based TIA protocol which determined ED discharge vs. inpatient admission based on imaging results, ability to comply with follow-up, and ABCD2 score (admit if 6-7; outpatient follow-up within 5d if 2-5, or within 7d if 0-1). Univariate and multivariable models explored factors associated with concordant care.

Result:
Patient characteristics were comparable in the pre- and postintervention phases (Table 1). Neuro-imaging findings determined disposition more often post-intervention. There was no difference pre vs. post in the recommended disposition to discharge (71.9% vs.73.6%, p 0.86), but the intervention more than doubled the proportion of patients who were actually discharged among those for whom discharge was recommended (22.5% vs. 52.8%, p<0.001). Guideline-concordant care increased significantly from pre-intervention to post (48% to 75%, p=0.001) with all three centers showing improvement (range: Pre 37-62%; Post 68-81%). In univariate analysis, factors associated with concordant care were younger age, medical instability, and post-intervention, while only medical instability [OR 9.95 (CI 1.21 - 82.12) p=0.033] and post-intervention [OR 3.30 (CI 1.64 - 6.65), p=0.001] were independently associated in multivariable analyses.

Conclusion:
Implementation of a rapid TIA evaluation protocol increased care concordant with system-wide guidelines, particularly decreasing the percent of patients admitted unnecessarily.
Abstract T P3: The Impact of Mechanical Thrombectomy in Patients Over 80 Years of Age
Authors: Villwock Mark R , Singla Amit , Padalino David J , Deshaies Eric M
Published: March 2022

Many physicians debate the efficacy of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), but most agree that to establish the true benefit there needs to be improved patient selection. The elderly are the fastest growing age group in the USA and present a growing population of AIS patients. The benefit of MT for these patients may be greatly reduced due to diminishing neuroplasticity and a larger number of medical co-morbidities at the time of intervention. The paucity of data on this intervention in the elderly limits the physician’s ability to adequately counsel patients and their families regarding any potential benefit from this emergent intervention. To address this knowledge gap, our objective was to examine clinical and economic outcomes after MT in the AIS population from the Nationwide Inpatient Sample (2008-2010). Our hypothesis was that patients > 80 years of age would fare worse at discharge in comparison to their younger counterpart. Independent samples t-tests and chi-squared tests were used to make comparisons. Multivariable models, adjusted for confounding factors, investigated outcomes. Less than 1% of all AIS cases were treated with MT. Of these, 18% (9300 cases) involved patients > 80 years. The odds of mortality in elderly patients treated with MT were more than double that of younger patients (OR:2.11, P<.001) and there was a significant reduction in the odds of being discharged home (OR:0.30, P<.001). Although univariate analysis depicted a significant difference in hospital charges and length of stay, multivariate analysis revealed no significant differences. In conclusion, patients > 80 years experienced worse clinical outcomes than their younger counterpart. Studies to better identify specific subpopulations of patients, in all age groups, that would benefit from mechanical thrombectomy are needed urgently.
Abstract T P30: Novel Algorithm for the Prediction of Motor Recovery of Upper Limb and Finger Using Diffusion Tensor Imaging after Stroke
Authors: Ishizaka Shunsuke , Nakashima Akira , Hamaue Yohhei , Koizumi Tetsuji , Shimizu Tadashi , Ryu Nobutoshi
Published: March 2022

Introduction:
Prediction of the outcome of upper limb and finger disability is critical for the rehabilitation in the acute stage of stroke. Here, we show a novel algorithm for the prediction of the recovery patterns by using diffusion tensor imaging (DTI).

Methods:
42 supratentorial stroke patients, including both ischemic and hemorrhagic types, with upper limb and finger paralysis were prospectively recruited from May 2012. DTI was performed with a 1.5-T MRI during 14-16 days after onset. Fractional anisotropy (FA) within the cerebral peduncle were measured and the ratios between FA values in the affected and unaffected side (rFA) were calculated. Fiber-tracking was also constructed by the one ROI method using same ROI as the FA measurement in the affected side. DTI findings were categorized into 3 types according to rFA and fiber-tracking (Fig. 1). Brunnstrom stage (BRS, upper limb + finger) was assessed at 2 weeks, 1 month, and 3 months after onset. Recovery patterns were also categorized into 3 groups according to the phase of recovery and final BRS (early recovery: BRS achieved 9-12pt. within 1 month, late recovery: BRS achieved 9-12pt. during 1-3 months, poor recovery: BRS had never achieved 9pt. within 3 months). We statically analyzed the correlation between DTI types and recovery patterns.

Results:
Positive correlation was found between rFA and final BRS.(p<0.01, Spearman r=0.52) Furthermore, extremely strong correlation was also found between recovery patterns and DTI types.(p<0.0001, Spearman r=0.91) Based on these results, we created a simple algorithm, which can predict the patterns of upper limb and finger recovery during 3 months after stroke with high accuracy. (Fig. 1, early recovery; 73%, late recovery; 85% and poor recovery; 95%)

Conclusions:
Our algorithm is novel in terms of taking advantages of both FA and fiber-tracking. This method allows us to predict not only final outcome, but also the phase of recovery, which are critical for the rehabilitation.
Abstract T P303: Recent Rise in Stroke-Related Emergency Department Visits by Young and Middle-aged Adults in the United States
Authors: Sun Wenyu , boan andrea , Ovbiagele Bruce , Adams Robert J , Ellis Charles , Lackland Daniel , Feng Wuwei (Wayne)
Published: March 2022

Background:
Population-based studies suggest increasing rates of stroke among young/middle-aged adults. However, the qualitative and quantitative aspects of this surge in young/middle-aged adults on utilization of emergency department (ED) services in the US have not been previously characterized.

Methods:
Data from the 2002-2010 National Hospital Ambulatory Medical Care Survey were analyzed to identify ED visits among young/middle-aged adult patients (25-64 year old) with a diagnosis of stroke. Diagnosis of stroke was identified using ICD-9-CM codes and analyses were completed by combining 3 years of data (2002-2004, 2005-2007, and 2008-2010). All estimates were adjusted using weights provided by the National Center for Health Statistics to generate nationally representative estimates.

Results:
An estimated annual average of 581,000 adult patients were diagnosed with stroke in U.S. ED from 2002 to 2010, representing ~0.5% of all ED visits. Among stroke-related ED visits, 36% were by patients aged 25-64. ED visit rates per 100,000 population for young/middle-aged stroke patients during 2002-2004, 2005-2007 and 2008-2010 were 127 (95% CI 110-144), 125 (95% CI 103-147) and 148 (95% CI 112-185), respectively. Visit rates per 1,000 ED visits were 3.6 (95% CI 3.1-4.1) during 2002-2004, 3.4 (95% CI 2.7-4.1) during 2005-2007 and 3.7 (95% CI 2.6-4.7) during 2008-2010, respectively. The overall rate per 1,000 ED visits for young black patients was similar to whites (3.6 vs. 3.5), however Blacks had a higher rate of stroke-related ED visits per 100,000 population compared to Whites counterparts for each successive three year period; 2002-2004 (245 vs. 113); 2005-2007 (267 vs. 106) and 2008-2010 (299 vs. 132).

Conclusion:
Visits to the ED by young/middle-aged adults diagnosed with stroke has risen progressively over the last decade in the US, with a higher rate of these visits by Blacks. These findings may have implications for healthy policy makers and medical providers.
Abstract T P31: Microembolus (MES) Detection by TCD in Acute Stroke Service
Authors: Ahmad Aftab , Derksen Carol , Ghrooda Esseddeeg , Basir Ghazala , Khan Khurshid , Shuaib Ashfaq , Saqqur Maher
Published: March 2022

Background and purpose:
One of the main applications of TCD in acute stroke is microembolic signal (MES) detection. Both Spectral display and M-mode can be used to detect MES using validated criteria published previously. MES is reported to be an independent risk factor for stroke. Our study’s aim is to evaluate the yield of TCD MES in an acute stroke service and if this correlate with stroke’s mechanism and recurrence of stroke.

Methods:
We did analysis of all stroke and TIA patients who were evaluated in the University of Alberta Hospital between jan2006- July 2013. The clinical information was collected from charts and TCD studies for MES detection were reviewed by Neurologists certified by American Society of Neuroimaging using validated criteria. All cases had bilateral TCD monitoring of MCA /ACA or PCA vessels. The positive emboli on spectrogram was defined based on the consensus criteria and the M mode one based on our previous published criteria. Positive MES TCD monitoring was defined by the presence of ≥1 MES on either hemisphere.

RESULTS:
49 /455 patients(10.7%) were MES positive. Mean age was 54.7(StD ±20), Gender: 33/49( 67.3%)were male, Median duration of monitoring was 50minutes( interquartile range 27.5-60), the indication was TIA in 16/49( 32.7%) acute ischemic stroke in 32/49(65.3%) subarachnoid hemorrhage in 1/49(2%), 36/49( 73.5%) presented with motor weakness 4/49( 8.2%) with isolated vision disturbances, 45/49(91.9%) patients had anterior circulation related symptoms, whereas 4/49(8.2%) had posterior circulation related symptoms,17/49(34.7%) showed acute infarct on imaging 6/49(12.2%) showed both acute and chronic infarcts and 3/49(6.1%) showed chronic infarcts only, 12/49(24.5%) showed infarcts in multiple vessels territories, TOAST: 20/49(40.8%) had large vessel atherosclerosis(LVA), 14/49(28.6%)had cardioembolic(CE) cause, 8/49(16.3%) had other determined etiology and 7/49(14.3%) had cryptogenic stroke, 7/49(14.3%) had recurrent stroke and 1/49(2%) had recurrent TIA. Total no of MES in anterior circulation were 324.

CONCLUSION:
Our study showed that 1 out of every 10 patients with acute ischemic stroke or TIA showed positive micro embolic signal on TCD monitoring. The high yield was mainly seen in LVA and CE stroke.
Abstract T P312: The Addition of the Post Stroke Checklist to Standard Outcome Measures Provides Unique Information Relevant to Stroke Recovery
Authors: Reichwein Raymond K , Morrison Kathy J , Chinchilli Vernon M , Graybeal John M , Vonhauser Julie M , Feng Xue , Good David C
Published: March 2022

Background:
The Post Stroke Checklist (PSC) is an easily administered, recently developed clinical tool to identify unmet needs in stroke patients. The relative value of the PSC compared to other outcome measures has yet to be determined.

Method:
We evaluated 126 ischemic stroke patients (median age 68, range 31-97) 30 days following discharge in the outpatient clinic of our Comprehensive Stroke Center. Items were originally scored by a nurse and reviewed with a stroke physician. The PSC was administered to all patients as well as the Barthel Index (BI) and modified Rankin Scale (mRS). We stratified each scale according to severity and identified actionable PSC items in each severity group. Using Fisher’s Exact Test we searched for correlation between the total number of PSC items scored positively and the total score of other outcome measures. We also looked for correlations between individual PSC items and other outcome scores.

Results:
The median (range) BI was 100 (10-100) and mRS was 1 (0-4). We stratified each outcome measure into 2 groups: BI-S (more severe) 0-89 (n=23) and BI-L (less severe) 90-100 (n=103); mRS-S (more severe) 3-5 (n=23) and mRS-L (less severe) 0-2 (n=103). 79 patients responded positively to one or more items in the PSC. There was no difference in total positive scores for any of the stratified groups, mRS (p=0.69) and BI (p=0.28). The frequency of positive responses for individual patients ranged from 1 to 6. The most common items identified are listed in the table below. No significant differences were noted.

Conclusion:
The PSC is simple to administer and was well accepted by clinicians and patients. Depression/Anxiety, Cognitive Dysfunction, Instrumental ADL’s, and New Onset Pain are not included in the BI and mRS but are easily identified using the PSC. Our results suggest that the PSC provides important information about these unmet needs in stroke patients independent of stroke severity.
Abstract T P326: Additive Neuroprotection of a 20-hete Inhibitor with Delayed Therapeutic Hypothermia after Asphyxic Cardiac Arrest in Neonatal Piglets
Authors: Zhu Junchao , Wang Bing , Lee Jeong-Hoo , Armstrong Jillian S , Bhalala Utpal S , Yang Zeng-Jin , Martin Lee J , Koehler Raymond C
Published: March 2022

The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) has been found to contribute to neurodegeneration after asphyxic cardiac arrest in neonatal piglets. Current therapy involving hypothermia is only partially effective, in part, because initiation of hypothermia is often delayed. Therefore, an unmet need is to find a neuroprotective drug that can be safely given early after resuscitation and that provides additional protection compared to delayed hypothermia alone. Here, we tested whether administration of the 20-HETE-synthesis inhibitor HET0016 (1 mg/kg) at 5 min after return of spontaneous circulation (ROSC) combined with whole body cooling initiated at 3 h of ROSC enhances the neuroprotection compared to delayed hypothermia alone. Anesthetized piglets (3-4-day-old) were subjected to 45 min ventilation with 10% O2, 7 min of airway occlusion, and CPR. In hypothermic groups, cooling started at 3 h ROSC and rewarming occurred over 4 h starting at 20 h ROSC. The density of viable neurons at 10 days ROSC was significantly increased with delayed hypothermia alone (n=12) compared to normothermic recovery (n=6) in sensorimotor cortex (63±5% to 71±6%; % of sham; ±SD), ventral posterolateral thalamus (41±6% to 57±8%), putamen (23±2% to 61±75%), caudate nucleus (58±5% to 72±6%), and CA3 hippocampus (59±3% to 71±5%). Further significant increases occurred with HET0016+hypothermia (n=12) in cortex (86±6%), thalamus (73±8%), and putamen (70±6%), but values remained less than in the sham group (n=6). Neurologic deficits with combined treatment were less than in the normothermic group through 6 days ROSC. Early treatment with the 20-HETE inhibitor HET0016 enhances the therapeutic benefit of delayed hypothermia in protecting regionally vulnerable neurons from asphyxic arrest.
Abstract T P33: Collateral Grade on MRI - Validation With Conventional Angiography is Key
Authors: Ng Kwan L , Saver Jeffrey L , Alger Jeffry R , Scalzo Fabien , Salamon Noriko , Yoo Bryan , Starkman Sidney , Ali Latisha K , Rao Neal , Hinman Jason , Calderon-Arnulphi Mateo , Modir Royya , Tansy Aaron , Liang Conrad W , Sheth Sunil A , Noorian Alireza R , Vespa Paul , Blanco Manuel B , Jahan Reza , Vinuela Fernando , Duckwiler Gary R , Tateshima Satoshi , Gonzalez Nestor , Liebeskind David S
Published: March 2022

Introduction:
Collateral status may predict outcomes after endovascular therapy, yet a reliable noninvasive technique prior to angiography is needed. We developed a novel method for projection of perfusion imaging data and validated it with respect to DSA acquired immediately afterwards.

Methods:
Consecutive acute ischemic stroke patients with M1 MCA occlusions with perfusion MR imaging prior to endovascular revascularization therapy were included. Collateral status on DSA was graded with the ASITN/SIR scale (0-4). 4-D dynamic susceptibility contrast concentration time images were constructed and projected in 2-D axial and sagittal planes at each time point. Independent review of the resulting MRI-based collateral sequences was conducted to generate a score analogous to the ASITN/SIR scale, followed by correlation studies between the two techniques.

Results:
47 patients were included with mean age 68.5 ± 16.3, 76.5% were female, baseline NIHSS was median 14 (range 3-31), and mean time from MRI to groin puncture was 109 min ± 95.5. DSA collateral grade was (0 (n=3); 1 (n=9); 2 (n=12); 3 (n=21); 4 (n=2)) with MRI collateral grade (0 (n=2); 1 (n=11); 2 (n=13); 3 (n=18); 4 (n=2)). MRI and DSA collateral scores were closely correlated, Spearman's rho = 0.91, weighted kappa = 0.82 (P <0.00001). Poor collateral status on MRI showed correlations with moderate to severe NIHSS (Spearman's rho = -0.31 (p< 0.039)). Figure depicts a panel version of MRI-based collateral sequences from a patient with a left M1 occlusion with a MR collateral grade of 1.

Conclusions:
Novel post-processing of noninvasive MRI perfusion data based on routine acquisitions can reliably measure the degree of collaterals on DSA.
Abstract T P333: Impact of Secondary Prevention Therapy on Mortality after a First Ischemic Stroke in Puerto Rico
Authors: Rojas Maria E , Marsh Wallace , Felici Marcos , Acuña Juan , Rodriguez Rosa J , Zevallos Juan C
Published: March 2022

Background:
Stroke is the fourth leading cause of death and the most prevalent cause of long-term disability in Puerto Rico. Prompt implementation of evidence-based clinical practice guidelines by physicians is crucial to reduce morbidity and mortality in patients with a first ischemic stroke.

Purpose:
The purpose of this study is to evaluate the impact of prescription of secondary prevention therapies on mortality in Puerto Rican patients hospitalized with a first ischemic stroke.

Methods:
This was a retrospective secondary data analysis of 2007 and 2009 Puerto Rico Stroke Registry electronic database. Information was obtained from the medical charts of patients discharged with ICD-9 codes 434 and 436 from 20 hospitals located in Puerto Rico. Descriptive analyses were conducted for demographics and comorbidities. Chi2 statistics compared the proportion of patients prescribed secondary prevention therapy and the proportion of patients not prescribed secondary prevention therapy. Lastly, survival rates were calculated to December 2010.

Results:
The mean age of 3,965 patients was 70 years (+/-13.8) and 64% were females older than 84 years. The most frequent comorbidities were hypertension (85%), diabetes (52%), and hyperlipidemia (25%). Secondary prevention therapy was prescribed to 11% of the patients. The case-fatality-rate for patients prescribed secondary prevention therapy was 16% compared to 26% for patients not prescribed secondary prevention therapy (P< 0.01). The mean survival for stroke patients prescribed secondary preventions was 450 days, (95% CI,182-718) compared to 266 days, (95% CI, 244-287) for those not prescribed secondary prevention therapy (p= 0.175).

Conclusion:
A low percentage of patients with first ischemic stroke were prescribed secondary prevention therapy. Although our findings suggest that secondary prevention therapy decreased mortality in patients with stroke, the difference did not reach statistical significance.
Abstract T P342: Impact of the Type of Prior Antithrombotic Agents on Secondary Hemorrhagic Stroke: Location, Severity and Outcome
Authors: Horie Nobutaka , Kaminogo Makio , Hirao Tomohito , Fukushima Masaaki , Izaki Akira , Mori Katsuharu , Shibayama Akira , Haraguchi Wataru , Shirakawa Kiyoshi , Hirose Makoto , Takahata Hideaki , Tsujino Akira , So Gouhei , Izumo Tsuyoshi , Nagasato Kunihiko , Nagata Izumi
Published: March 2022

Introduction:
Randomized trials and meta-analyses have shown the efficacy of antithrombotic therapies to prevent secondary ischemic stroke. However, hemorrhagic event is a major complication of long-term antithrombotic therapy affecting poor outcomes and increased mortality, which has not been fully investigated. Here, we examined the impact of the type of prior antithrombotic agents on secondary hemorrhagic stroke.

Methods:
Using multicenter retrospective study of stroke risk in antithrombotic therapy (RESTATE) database, 1067 consecutive patients who presented secondary stroke during antithrombotic therapy were registered. Among them, patients showing secondary hemorrhagic stroke were analyzed in detail regarding the type of antithrombotic agent; aspirin, ticlopidine, clopidogrel, cilostazol and warfarin.

Results:
Two hundred and fifty seven patients presented secondary hemorrhagic stroke; 144 patients in aspirin (20.5%), 15 patients in ticlopidine (16.3%), 17 patients in clopidogrel (13.7%), 23 patients in cilostazol (16.0%) and 58 patients in warfarin (21.8%). Thalamus was the most common location (27.7%) following putamen (24.4%), cerebral cortex (24.4%), cerebellum (12.2%), and brain stem (4.7%). Multivariate analysis found that male sex (OR: 0.73, 95% CI: 0.54-0.98, P=0.04), INR >1.4 (OR: 2.72, 95% CI: 1.77-4.19, P<0.001) and antihypertensive therapy (OR: 0.64, 95% CI: 0.45-0.91, P=0.01) were independently associated with secondary hemorrhagic stroke. Interestingly, only the presence of cilostazol significantly affected lower hemorrhage volume compared with other agents in basal ganglia hemorrhage (P=0.03), and only the presence of clopidogrel significantly affected higher hemorrhage volume compared with other agents in subcortical hemorrhage (P<0.001). Finally, only the patients taking cilostazol had significantly higher favorable outcome (mRS 0-2) at 3 months after the secondary hemorrhagic stroke.

Conclusions:
We first provide the evidence that female sex, INR>1.4 and non-antihypertensive therapy could be risk factors for the secondary hemorrhagic stroke. Location and hemorrhage volume could be different depending on the type of antithrombotic agent, which affect outcome of secondary stroke.
Abstract T P344: Clopidogrel Resistance in Stroke Patients (The CRISP Trial)
Authors: Manoj Aravindakshan L , Fitzsimmons Paul R , Sharma Nikhil , Menezes Brian , Thachil Jecko , Greenhalf William , Oates Melanie , Lopez Paula , Fletcher Glyn , Cox Penelope
Published: March 2022

Background:
Clopidogrel is a thienopyridine with ADP antagonising effects that is widely used in the secondary prevention of ischemic strokes and transient ischemic attacks (TIAs). Despite this some patients will go on to have recurrent strokes or TIAs.

Cardiology trials have identified patients with clopidogrel resistance, defined as a vasodilator-stimulated phosphoprotein (VASP) index of >50% after at least 7 days of clopidogrel treatment. This was associated with recurrent cardiac events.

The VASP-index measures phosphorylation of VASP in the resting state and activated states using flow cytometry techniques. As phosphorylation of VASP is dependent upon activation of the platelet P2Y12 receptor that is targeted by clopidogrel the difference in phosphorylation between the two states provides an indirect measure of platelet inhibition.

Previous trials have shown a prevalence of clopidogrel resistance in stroke patients of between 8 and 18%, but no study to date has shown whether this is associated with significantly more recurrent cerebrovascular events.

We are testing the hypothesis that amongst patients treated with clopidogrel for secondary prevention of cerebrovascular disease, those with resistance are more likely to have recurrent Strokes or TIAs.

Should this hypothesis be confirmed, then further research would be needed to identify treatment strategies that may minimise this risk.

Design A prospective cohort study recruiting 120 patients from the acute stroke unit at the Royal Liverpool hospital with a diagnosis of stroke or TIA that will be commenced on clopidogrel therapy and expected to continue it for at least one year. We will compare outcomes between those found to be 'clopidogrel responders' and 'clopidogrel resistant'.

A sample size of 120 patients was chosen based on the concept of 'reproducibility probability', taking into account the number of patients needed for similar studies in cardiology patients, the prevalence of 'clopidogrel resistance' amongst stroke patients and the potential for patients to later be excluded.

Outcome Recurrent cerebrovascular event within 6 months of entering trial.

Trial Status Recruitment ongoing.
Abstract T P347: Metabolomic Analysis of PFO-Related Stroke Shows Immediate and Persistent Decrease of Homocysteine Post PFO Closure
Authors: Ning MingMing , Deng Wenjun , Beecher Chris , Burant Charles , Lopez Mary , De Jong F , Palacios Igor , Inglessis Ignacio , Silverman Scott , Feeney K , Thayer M , Elia M , Wickham T , McMullin D , Dec GW , Buonanno Ferdinando S , Lo Eng H
Published: March 2022

Background:
PFO, an independent stroke risk factor, enables direct mixing of venous and arterial circulation. As we have found previously, PFO serves not only as a conduit for venous clots, but also enables harmful factors such as serotonin (5HT) to avoid pulmonary filtration to remain within circulation at elevated levels, potentially contributing to a prothrombotic state. We hypothesize that in addition to 5HT, other factors may also be involved. In the context of endovascular PFO closure, a bedside model to understand PFO circulatory signaling, we performed a full metabolomic profile of mediators that may respond to PFO closure.

Method:
Non-migraine stroke patients were recruited in accordance with IRB approval, plasma was sampled from left and right atria pre and post closure and also from venous blood 3 months post PFO closure. A discovery metabolite screening was performed in 14 patients who underwent PFO closure, and analysis was performed using one-way ANOVA.

Result:
After stringent data filtering (537 metabolites, one-way ANOVA, p-value <0.01), we identified significant changes in a panel of small molecules after PFO closure - the most prominent change being in homocysteine (HCY). While relative HCY levels (expressed as peak area) in the left atrium (LA) and right atrium (RA) were comparable pre-closure (pre-LA: 5.61 ± 0.09; pre-RA: 5.30 ± 0.48), HCY immediately decreased in LA post PFO closure (post-LA: 4.56 ± 0.04) and HCY level remained low in peripheral venous blood at 3-month follow-up (4.57 ± 0.06; p = 0.0036).

Conclusion:
We found PFO closure to lower HYC immediately in left atrial (arterial) blood, and this effect persists in peripheral venous circulation at 3 months post procedure. Since high level of HYC is independently associated with stroke and heart disease, our results suggest that mechanical PFO repair may improve circulatory profile of PFO stroke patients. Studies in a larger patient cohort and validation of other important metabolites are ongoing.
Abstract T P349: Long Term Survival and Hospital Re-Admission Rates in Elderly Patients With Subarachnoid Hemorrhage Treated With Surgical or Endovascular Treatment
Authors: Chaudhry Saqib A , Georgiadis Alexanderos L , Qureshi Adnan I
Published: March 2022

Background:
In International subarachnoid aneurysm trial (ISAT), the 7 year survival was higher among those treated with endovascular treatment compared with surgical treatment.

Objective:
To determine the long-term survival in elderly patients with subarachnoid hemorrhage who underwent either surgical or endovascular treatment.

Methods:
The study cohort included a representative sample of fee-for-service Medicare beneficiaries aged ≥65 years who underwent endovascular or surgical treatment for ruptured intracranial aneurysms with post-procedure follow-up of 2.87 (±2.2) years. Cox proportional hazards analysis was used to assess the relative risk (RR) of all-cause mortality for patients treated with endovascular treatment compared with those treated with surgical treatment after adjusting for potential confounders. The 5 year survival was estimated for both treatment groups using Kaplan Meir survival methods. We also determined the annual rate of hospital re-admission for both groups during the follow-up period.

Results:
A total of 724 patients with subarachnoid hemorrhage were treated with either endovascular (n=277) or surgical treatment (n=447). The rate of immediate post-procedural neurological complications (6.3% vs. 2.9%, p=0.04) was higher among patients treated with surgery compared with those treated with endovascular treatment. The estimated 5 year survival was 64.6% and 61.7% in patients treated with surgical and endovascular treatments, respectively. After adjusting for age, gender, and race/ethnicity, relative risks of all-cause mortality (RR 0.97, 95% confidence interval [CI] 0.75 - 1.23) was significantly was similar in two groups.
Abstract T P35: Baseline Diffusion Weighted Imaging Lesion Volume Predicts Disappearance of Infarct on Fluid Attenuated Inverse Recovery Sequences Within 30 Days of TIA/Minor Stroke
Authors: Riaz Parnian , Kate Mahesh , Sivakumar Leka , Emery Derek , Butcher Kenneth
Published: March 2022

Introduction:
Evidence of infarction on MRI is predictive of early stroke recurrence after TIA/minor stroke. It has recently been reported that diffusion-weighted imaging (DWI) changes are not associated with evidence of infarction on Fluid Attenuated Inverse Recovery (FLAIR) sequences 90 days later in 30% of patients. We completed a serial MRI study to determine the time course of infarct resolution. We tested the hypothesis that acute DWI lesion volume predicts infarct disappearance by 30 days.

Methods:
Acute TIA/minor stroke patients (NIHSS≤3) were prospectively imaged at baseline, 7 and 30 days after symptom onset. Lesion volumes were measured planimetrically by a blinded rater at each time point on DWI and FLAIR sequences. Mean and relative (to contralateral tissue) Apparent Diffusion Coefficient ((r)ADC) values were also calculated.

Results:
Acute DWI lesions were found in 94/172 patients. Median time between symptom onset and baseline MRI was 20.9(19.3) h. DWI volume decreased from baseline (1.51 ml (4.36)) at 7 days (1.13 ml (2.96),
P
=0.001) and at 30 days (0.40 ml (0.97),
P
<0.0001). DWI lesions at 7 days pseudo-normalized (infarct visible on FLAIR) in 3.4% and resolved without evidence of infarction in 8% of patients. Seventy-seven (82%) patients had persistent lesions on FLAIR at 30 days (FLAIR+). Baseline NIHSS scores were similar between FLAIR+ (1.40±1.21) and FLAIR– patients (1.18±1.19,
P
=0.64). Baseline rADC was similar in FLAIR+ (0.84(0.17)) and FLAIR– patients (0.89(0.21),
P
=0.155). Baseline DWI volumes were larger in FLAIR+ (2.08 ml (6.9)) than FLAIR– patients (0.69 ml (0.95),
P
=0.007). ROC analysis indicated that a baseline DWI volume <2.04 ml predicted absence of FLAIR lesion at 30 days with a specificity of 100% and sensitivity of 50.6%. Good functional outcome (modified Rankin Score ≤2) at 90 days was similar in FLAIR+ (54/62, 87%) and FLAIR– patients (12/12, 100%,
P
=0.339).

Conclusion:
Acute DWI lesions are transient and not always associated with visible infarction on FLAIR, even as early as 7 days after symptom onset. Delaying MRI results in a failure to demonstrate evidence of infarction in the majority of patients, particularly those with DWI lesion volumes below 2 ml.
Abstract T P353: Positive Fluid Balance Predicts Poor Clinical Outcomes in Aneurysmal Subarachnoid Hemorrhage
Authors: Kissoon Narayan R , Fugate Jennifer E , Mandrekar Jay N , Rabinstein Alejandro A
Published: March 2022

Background and Purpose:
Strict maintenance of normovolemia is standard of care in treatment of aneurysmal subarachnoid hemorrhage (aSAH) and induced hypervolemia is used to treat delayed cerebral ischemia (DCI) from vasospasm. Fluid-related complications are not uncommon. We tested the hypothesis that fluid balance affected clinical outcomes in aSAH.

Methods:
We reviewed 307 patients with aSAH admitted to the Neuroscience Intensive Care Unit (NICU) from October 2001 to June 2011. We collected data on fluid balance during NICU stay, clinical and radiographic evidence of vasospasm, cardiopulmonary complications, and functional outcomes by modified Rankin scale (mRS) upon follow-up (mean 8 ± 8 months). Poor functional outcome was defined as mRS 3-6. Associations of variables of interest with outcome were assessed using univariable and multivariable logistic regression. Propensity scores were estimated to account for imbalances between patients with positive versus negative fluid balance and were included in multivariable models.

Results:
Average net fluid balance was 1153 ± 5586 mL. Results of univariate analysis are shown on the Table. On multivariate analysis, WFNS grade at nadir (p<0.001, OR=3.09, 95%CI 2.38-4.02) and positive fluid balance per liter increase (p=0.0005, OR=1.12, 95%CI 1.05-1.20) were associated with poor functional outcome. For every liter increase in positive net fluid balance, there was a 12% increased risk of a poor functional outcome on adjusted analysis (Area under ROC Curve 0.868). The association between positive net fluid balance and poor functional outcomes was confirmed using propensity score analysis to control for multiple confounding variables.

Conclusions:
Greater positive net fluid balance is independently associated with poorer functional outcome in patients with aSAH. This association does not appear to be solely explained by an excess of cardiopulmonary complications.
Abstract T P356: Predictors of Depression 6 Months After Aneurysmal Subarachnoid Hemorrhage
Authors: Fukuda Keiko A , Higashida Randall T , Lawton Michael T , Smith Wade S , Ko Nerissa U
Published: March 2022

Background:
Functional outcome is of increasing importance among survivors of aneurysmal subarachnoid hemorrhage (SAH). Depression is commonly reported after stroke and may play a significant role in functional recovery after SAH. Our goal was to determine the prevalence and predictors of depression among survivors of SAH at 6 months.

Methods:
Six-month follow up data was analyzed from a cohort study of SAH patients at a tertiary care center. With IRB approval and consent, patients completed serial 6-month outcome assessments including the Modified Rankin Scale (mRS) and the Hospital Anxiety and Depression Scale (HADS). Independent predictors of poor functional (mRS>2) and mood outcomes (HADS≥10) were determined using univariate and multivariate statistics.

Results:
Of 247 subjects (74% female, mean age 55), 7% had poor functional outcome. Depression was reported in 17%. Poor functional outcome was significantly associated with a longer hospitalization (mean 26 days, p=0.02), placement of an EVD and VP shunt (p=0.008 & 0.02) and antibiotic use (p=0.001). Depression was significantly associated with poor functional outcome, prior history of depression, and vasospasm (p=0.001, 0.004 & 0.05). Depression showed a trend in those who received an EVD, ventilator, and antibiotics. Depression was not significantly associated with treatment modality. Multivariate logistic analyses demonstrated that poor functional outcome (OR=5.25, CI=1.44-19.10, p=0.01), history of depression (OR=7.66, CI=1.87-31.45, p=0.005), and vasospasm (OR=2.65, CI=1.04-6.75, p=0.04) remain significant predictors of depression, however, EVD, ventilator, antibiotics, and Hunt Hess Grade are not significant.

Conclusion:
Depression is not uncommon after SAH, and highly associated with poor neurological recovery at 6 months. Risk factors for development of depression include prior history of depression and cerebral vasospasm. Based on these results, we recommend screening for depression and consideration for early treatment for patients at highest risk after SAH.
Abstract T P36: Classification of Hemorrhagic Transformation by ECASS II Criteria More Severe on MRI Than CT
Authors: Hsia Amie W , Luby Marie , Farber Jordan , Merino José G , Nadareishvili Zurab , Warach Steven , Latour Lawrence L
Published: March 2022

Background and Purpose:
ECASS II criteria for hemorrhagic transformation (HT) are based on CT, and no similar scoring system has been applied to MRI. Validation of MRI HT classification has implications for future MRI-based clinical trials and for clinical management. The purpose of our study was to apply and compare HT classification using T2*-weighted MRI and CT.

Methods:
We reviewed the scans of consecutive stroke patients treated with IV thrombolytic therapy from 2002 to 2012 who had post-treatment scans with CT bracketed by MRIs within 72h of CT, or CT and MRI within 24h of each other. Separately for both CT and MRI, the same 2 independent readers blinded to clinical information assigned HT classification using ECASS II criteria. A third reader adjudicated discrepancies. Inter-rater and inter-modality reliability were determined. For the inter-modality comparison, final readings were included for CT-MRI pairs obtained within 3 hours and cases with consistent MRI reads obtained before and after CT.

Results:
Of the 121 patients included, 79 had bracketed MRIs with CT and 42 had a CT-MRI pair (CT before MRI in all cases). Inter-rater agreement was similar for CT and MRI HT classifications between the 2 raters (CT: 80% agreement, Cohen’s κ=0.692, n=119; MRI: 85% agreement, Cohen’s κ=0.739, n=187). Between CT and MRI there was good agreement across the 5 ECASS HT categories (82%, Cohen’s κ=0.65), and for combined hemorrhagic infarction (HI) vs. parenchymal hematoma (PH) (88%; Cohen’s κ=0.754). For those patients identified as having HT on either modality (n=24), HT was rated as more severe using MRI compared to CT (p=0.026) (Figure).

Conclusions:
ECASS II classification of HT by MRI has good inter-rater and inter-modality agreement overall compared to CT, but for those with hemorrhage, HT is rated as more severe using MRI. Therefore, MRI classification of HT should not be equated to that of CT.
Abstract T P361: Reduced Brain and Cerebellar Volumes Correlate With Cognitive Deficits in Chagas Disease
Authors: Oliveira-Filho Jamary , Reis Carolina C , Fernandes Rodrigo D , Jesus Adriano A , Fonseca Luana F , Muller Mila C , Lordelo Morgana J , Ventura Laís M , Barreto-Neto Nestor J , Ferreira Isadora L , Resende Lucas L , Andrade Alisson L , Gonçalves Beatriz M , Jesus Pedro A , Abbehusen Cristiane B , Furie Karen L
Published: March 2022

Background:
Chagas disease (CD) is a major cause of stroke and cardiomyopathy in Latin America. Brain atrophy has been associated with CD independently of stroke or cardiac disease, but cognitive effects of this finding has not been explored. Our objective was to compare cognitive impairment in patients with CD and non-CD cardiomyopathy; and to correlate these findings with quantification of brain and cerebellar volumes.

Methods:
Consecutive patients from a cardiomyopathy clinic without a history of stroke were submitted to a structured interview including clinical information and cognitive tests (Mini Mental State Exam - MMSE, digit span, clock drawing test, delayed memory test). Brain MRI was performed and brain and cerebellar volumes quantified by ITK-SNAP software. MR spectroscopy quantified N-acetylaspartate (NAA)-, choline- and myoinositol-to-creatine ratios.

Results:
118 patients were recruited; mean age 54 +/- 12 years, 53% female, 49% with CD. Despite a better systolic cardiac function by echocardiography (ejection fraction 45 vs 38%, P=0.006), patients with CD performed worse on various cognitive tests (MMSE, delayed memory test and clock drawing test, P<0.01). Cerebellar volumes, but not brain volumes, were significantly smaller in CD vs non-CD cardiomyopathy (125 vs 136ml, P=0.035) and correlated with clock drawing test results (rS=0.219, P=0.024). In a multivariable analysis, delayed memory impairment, NAA/creatine ratio and cerebellar volumes were independently associated with Chagas disease.

Conclusions:
Cognitive dysfunction in CD occurred independently of cardiac disease severity and was associated with cerebellar atrophy.
Abstract T P367: Influence of Patient Age on Angioarchitecture of Brain Arteriovenous Malformations
Authors: Hetts Steven W , Cooke Daniel L , Nelson Jeffrey , Gupta Nalin , Dowd Christopher F , Halbach Van V , Higashida Randall T , Lawton Michael T , Kim Helen
Published: March 2022

Background and Purpose:
To determine if clinical and angioarchitectural features of brain AVMs differ between children and adults.

Materials and Methods:
A prospectively collected institutional database of all patients diagnosed with brain AVMs since 2001 was queried. Demographic, clinical, and angioarchitecture information was summarized and analyzed with univariable and multivariable models.

Results:
Results often differed when age was treated as a continuous variable as opposed to dividing subjects into children (≤18 years) versus adults (>18 years). Children were more likely to present with AVM hemorrhage than adults (59% vs. 41%, p=0.001). Although AVMs with a larger nidus presented at younger ages (mean of 26.8 years for greater than 6 cm compared to 37.1 years for less than 3 cm), this was not significantly different between children and adults (p=0.069). Exclusively deep venous drainage was more common in younger subjects both when age was treated continuously (p=0.04), or dichotomized (p<0.001). Venous ectasia was more common with increasing age (mean, 39.4 years with ectasia compared to 31.1 years without ectasia) and when adults were compared to children (52% vs. 35%, p<0.001). Patients with feeding artery aneurysms presented at later average age (44.1 years) than those without such aneurysms (31.6 years); this observation persisted when comparing children to adults (13% vs. 29%, p<0.001).

Conclusion:
Although children with brain AVMs were more likely to come to clinical attention due to hemorrhage than adults, venous ectasia and feeding artery aneurysms were underrepresented in children, suggesting that these particular high risk features take time to develop.