bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP99: Proteomics Study Of Stroke In Young Adults
Authors: Zhu William , Xu Huichun , Gaynor Brady , Mitchell Braxton D , Kittner Steven J , Stanne Tara M , Jern Christina , Malik Rainer , Dichgans Martin , Pare Guillaume , Chong Michael ,   Early-Onset Stroke Consortium
Published: February 2022

Introduction:
A prior systematic Mendelian randomization screen of 653 circulating proteins in a predominantly older ischemic stroke (IS) population identified a causal role for several established and novel biomarkers for IS and IS subtypes. We contrasted the magnitude of genetically determined levels of 6 of these biomarkers between early- and late-onset IS.

Methods:
We constructed genetic risk scores (GRS) for these 6 protein biomarkers from previously published GWAS analyses carried out in European populations. Using regression analysis, we evaluated associations of these GRS with IS and IS subtypes in 10,549 early onset (ages 18-59) and 9,272 late onset (ages 60 and older) IS cases and associated controls. The Wald test was used to test for heterogeneity in the odds ratios between the two groups.

Results:
Of the 6 biomarkers, only genetically determined protein levels of histo-blood group ABO system transferase were more strongly associated with early compared to late onset stroke (p < 0.002). Higher genetically determined levels of F11 and LPA and lower genetically determined levels of MMP12 were associated with both early and late onset IS with no evidence for differential effect sizes, while genetically determined levels of CD40 and SCARA5 showed no association with either early or late onset stroke. In subtype-specific analyses, increasing levels of genetically determined F11 were correlated with increased risk of all strokes in both groups. Higher genetically determined LPA levels were associated with large artery atherosclerotic (LAA) strokes in both groups, while lower genetically determined MMP12 levels were associated with LAA strokes in both groups.

Conclusions:
Genetically determined histo-blood group ABO system transferase levels are more strongly associated with all strokes in early than in late onset stroke. Genetically determined blood protein levels of F11, LPA, and MMP12 were associated with both early and late onset stroke. Lack of association for CD40 and SCARA5 may be due to a smaller sample size than the initial discovery study.
Abstract WP10: Automated Methods Of Aneurysm Growth Detection Compared With Clinical Assessment And Follow-up
Authors: Chien Aichi , Bizjak Ziga , Špiclin Žiga , Vinuela Fernando
Published: February 2022

Introduction:
In cases where the risk of intracranial aneurysms (IA) rupture is low or secondary to other patient health concerns, unruptured IA may be monitored through imaging. In this work, we applied different computational methods to detect IA growth and compared the results to clinical findings.

Hypothesis:
We hypothesize that automated methods of IA growth detection are comparable to clinical assessment.

Methods:
The study cohort consisted of 20 female patients with saccular IA diagnosed between 2005-2011 in UCLA Medical Center. 6 were located at the PcoA, 10 at the superior hypophyseal artery, and 4 at the ophthalmic artery. 8 IA were determined to be growing. Baseline IA size was 3.85±4.30 mm. For each case, initial and first follow-up CTA image studies (interval 2.50±2.75 yrs) were analyzed. Cohort follow-up continued for an average of 8.5±5.75 yrs. Automated methods to detect IA growth included maximum diameter (HMAX), surface area (SA), volume (V), and a novel 2-stage morphing approach which deforms the baseline IA surface mesh to that of the subsequent scan and yields a set of characteristics that describe the changes: dMPL, dSA, dV, and dICDD. Statistical methods used included the Mann-Whitney U test and Chi-Square Test with significance set at p <0.01, and ROC AUC analysis.

Results:
The stable and growth groups did not significantly differ with respect to case details and medical history, including IA size, location, imaging interval, age, family history, stroke, hypertension, thyroid disease, cancer, and atherosclerosis. Clinically determined change in IA diameter (p=0.007, AUC=0.927), computed HMAX (p=0.0002, AUC=0.958), SA (p=0.001, AUC=0.917), V (p=0.001, AUC=0.927), and dSA (p=0.005, AUC=0.865) were significantly different between the groups. The duration of follow-up significantly differed between the groups (p<0.01), largely due to treatment of growing IA. During follow-up only one IA changing from stable to growing, and 5 of 6 subsequently treated IA were from within the initial growth group.

Conclusion:
Several automated measures provided comparable performance to clinical size when assessing IA growth. HMAX in particular may be useful to assist clinical evaluation, as it was slightly more effective than recorded clinical size alone.
Abstract WP101: Clinical Utility Of Simultaneous Multislice Diffusion MRI In Acute Stroke Workup
Authors: Culleton Sinead , HashemizadehKolowri SeyyedKazem , Sharma Anuja , Roberts John , de Havenon Adam , Dibella Edward , McNally Joseph
Published: February 2022

Purpose:
Rapid and accurate ischemic stroke detection is essential for optimal management. Diffusion tensor imaging (DTI) trace sequences are highly accurate for acute stroke detection but require long acquisition times. This study aimed to assess the impact of simultaneous-multislice (SMS) acceleration on scan time, image quality, and diagnostic accuracy.

Methods:
In this IRB-approved study, MRI brain imaging was performed during stroke workup on Siemens 1.5T scanners with a 16-channel head coil. DTI (20 directions, b-value of 2000 sec/mm
2
) was acquired without and with slice acceleration factor 2 (SMS-2). DTI trace-positivity (stroke or other) was independently assessed by two neuroradiologists, blinded to sequence parameters and clinical data. Average image quality (5-point scale, 5=excellent) was measured between the radiologists for each MRI. Differences in signal-to-noise ratio (SNR), coefficient of variation (CV), repetition time (TR), interrater agreement (Kappa), and receiver operating characteristic (ROC) areas were determined using a p<0.05 significance threshold.

Results:
SMS-2 significantly reduced TR, equivalent to 45.0% reduced scan time. Image quality and SNR were slightly but significantly reduced in SMS-2-DTI compared to standard (STD)-DTI (N=41, see
table
and
figure
). Interrater agreement for DTI-positivity was ‘excellent’ on both STD-DTI and SMS-2-DTI without significant difference. ROC areas of each observer were also not significantly different between STD-DTI and SMS-2-DTI.

Conclusion:
SMS-2 reduces scan time. Image quality was slightly reduced, however, satisfactory diagnostic accuracy for stroke detection was maintained.
Abstract WP108: Is Infarct Core Growth Truly Linear? Follow-up Infarct Volume Estimation By Rapid Baseline Infarct Growth Rate And Linear Model
Authors: Suomalainen Olli P , Abou Elseoud Ahmed , Martinez-Majander Nicolas , Tiainen Marjaana , Valkonen Kati , Virtanen Pekka , Forss Nina , Curtze Sami
Published: February 2022

Background:
Current guidelines for recanalization treatment are based on the time window between symptom onset and treatment in addition to ischemic core and perfusion lesion volumes by computed tomography perfusion imaging (CTP). Linear growth of infarction is commonly assumed.The aim was to test, whether measured follow-up infract volume (FIV) could be approximated from the linear growth model (eFIV) based on CTP baseline infarct growth rate.We assumed the infarct growth to stop, when recanalization was achieved or when the eFIV reached the volume of the perfusion lesion (T
max
>6s volume).

Methods:
All consecutive stroke code patients from 11/2015-9/2019 transferred to Helsinki University Hospital as candidates for endovascular treatment (EVT) were screened; patients with large vessel occlusion (LVO), EVT, CTP and known time of symptom onset were included to study.The infarct growth rate was calculated by dividing the CTP
core
by the time from symptom onset to baseline imaging.eFIV was calculated by infarct growth rate multiplied with the time from baseline imaging to recanalization or follow-up imaging. We assumed a performance of +/- 19% for the accuracy of the CTP
core
assessment. FIV was measured from the 24h non-enhanced computed tomography images. Recanalization was defined as modified Treatment in Cerebral Infarction (mTICI) scale as successful (TICI 2b or 3) or futile (TICI 0,1,2a).

Results:
Out of 5234 patients, 48 had LVO and EVT, CTP imaging and known time of symptom onset (Figure 1). In 40/48 (83%) patients, infarct growth was not within the 19% margins of linear growth. eFIV exceeded FIV in 25/42 patients with successful recanalization (median absolute difference 25 mL,7-73).

Conclusions:
eFIV from linearly approximated growth model did not support linear growth of the infarct.
Abstract WP11: The Impact Of Dual Antiplatelet Therapy Duration On Unruptured Aneurysm Occlusion Following Flow Diversion
Authors: Vranic Justin , Harker Pablo , Stapleton Christopher , Regenhardt Robert W , Alotaibi Naif , Leslie-mazwi Thabele M , Gupta Rajiv , Tan Can Ozan , Koch Matthew J , Dmytriw Adam A , Raymond Scott B , Mascitelli Justin , Patterson Tyler , Seinfeld Joshua , White Andrew , Case David , Roark Christopher , Gandhi Chirag D , Al-Mufti Fawaz , Cooper Jared , Matouk Charles , Sujijantarat Nanthiya , Devia Diego A , Villamizar-Torres Daniel E , Ocampo-Navia Maria A , Puentes Juan C , Patel Aman B
Published: February 2022

Objective:
The objective of this study is to assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications following endoluminal flow diversion with a single flow diverting stent.

Methods:
A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and >12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure.

Results:
A total of 205 patients underwent flow diversion with a single pipeline embolization device. During the study period, 12.7% of treated aneurysms remained non-occluded. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and non-occluded groups. Non-occluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 mo, p=0.016) with ANOVA demonstrating a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202)=4.2, p=0.016). An exploratory analysis demonstrated the optimum DAPT discontinuation time to minimize aneurysm non-occlusion rates was 7.9 months (95% CI: 6-11 months). There was no significant difference in the rate of complications or delayed ischemic strokes observed between patients receiving short (<6 mo) and prolonged duration (>6 mo) DAPT (7.9% vs 9.3%, p=0.76).

Conclusions:
Following endovascular flow-diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing delayed thromboembolic complications.
Abstract WP115: Venous Thromboembolism Readmission In Acute Ischemic Stroke
Authors: Shu Liqi , de Havenon Adam H , Liberman Ava L , Cutting Shawna M , Stretz Christoph , Burton Tina , Goldstein Eric , Perelstein Elizabeth , Reznik Michael , Mahta Ali , El JAMAL SLEIMAN , Kala Narendra , Al-Mufti Fawaz , Xiao Han , Furie Karen L , Yaghi Shadi
Published: February 2022

Introduction:
Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication of acute ischemic stroke (AIS). We performed a nationwide analysis to evaluate rate and risk factors for VTE readmission in patients with AIS.

Methods:
Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included adult patients with a principal discharge diagnosis of AIS from 2016 to 2018. AIS, pulmonary embolism, deep vein thrombosis and other diagnosis were identified based on standard ICD-10 CM codes. Patients who had VTE diagnosis during the index admission were excluded. We determined 90-day VTE readmission rates and trends in patients with a principal diagnosis of AIS stratified by 30-day epochs. We then constructed a stepwise binary logistic regression model to determine odds ratios (OR) of demographic and clinical factors associated with VTE readmission rates.

Results:
Of the 1,023,478 patients with AIS, 8378 (0.82%) had VTE during readmission and 2906 (0.28%) had VTE as principal diagnosis for readmission within 90 days of discharge. Among them, more than half (4557, 54.39% and 1581, 54.40%, respectively) of patients were readmitted within 30 days of discharge. The rate of VTE readmission decreased further away from index event (P < 0.001). In the Cox regression model, obesity (OR 1.48, 95% CI 1.24-1.76, P < 0.001), plegia of at least one limb (OR 1.24, 95% CI 1.08-1.43, P = 0.003), longer hospital length of stay (OR 1.02, 95% CI 1.01-1.02, P < 0.001), higher NIHSS (OR 1.04, 95% CI 1.03-1.05, P < 0.001) were associated with VTE readmission. Conversely, VTE readmission rates were lower in patients with a history of atrial fibrillation/flutter (OR 0.72, 95% CI 0.62-0.84, P < 0.001).

Conclusion:
Patients with obesity, paralysis, higher NIHSS score, or prolonged hospital length of stay are at higher risk for VTE readmission. AF strokes are less likely to have DVT/PE, perhaps due to anticoagulant use in such patients. Studies are needed to determine whether early mobilization and mechanical and/or chemical prophylaxis reduces VTE risk in high-risk patients.
Abstract WP117: Post-procedural Screening With ROTEM For Risk Of Hemorrhage Following Revascularization Therapy For Acute Ischemic Stroke
Authors: Nguyen Andrew M , Williamson Craig A , pandey aditya S , Sheehan Kyle M , Smith Aaron , Rajajee Venkatakrishna
Published: February 2022

Introduction:
Hyperfibrinolysis is associated with intracerebral hemorrhage (ICH) after the use of tPA for acute ischemic stroke (AIS). Point-of-care Rotational ThromboElastoMetry (ROTEM) testing may rapidly detect hyperfibrinolysis and identify AIS patients at high risk for hemorrhage.

Hypothesis:
Evidence of fibrinogen depletion on ROTEM will accurately predict bleeding following revascularization therapy for AIS.

Methods:
We reviewed medical records of AIS patients who underwent revascularization therapy between 2019-2020. All patients underwent ROTEM testing post-procedure to facilitate targeted blood product transfusion should hemorrhage occur. However, transfusion was not performed prophylactically. Repeat imaging with dual-energy CT was performed within 24 hours. A quality control registry of all AIS patients who undergo revascularization is maintained for purposes of Joint Commission certification. All variables, including ROTEM values and occurrence of intra- and extracranial hemorrhage, were entered prospectively. We examined the predictive value of a FIBTEM-A10 <10mm for post-procedural hemorrhage.

Results:
A total of 52 patients were included. Median age was 68 years (Interquartile Range, IQR 60-83), and median admission NIHSS was 16 (IQR 10-20). Thirty-four patients (65%) received tPA, 46 (88%) received mechanical thrombectomy, and 28 (54%) received both. Median post-procedure FIBTEM-A10 was 16mm (IQR 14-22); 5 patients had values <10mm. Overall, 19 (37%) suffered radiographic ICH, 5 (10%) symptomatic ICH, and 3 (6%) extracranial hemorrhage. FIBTEM-A10 <10mm had sensitivity 17% and specificity 97% for any post-procedural hemorrhage. For symptomatic ICH, sensitivity was 0% and specificity 89%.

Conclusions:
The use of ROTEM to identify hyperfibrinolysis following AIS revascularization therapy achieved poor sensitivity and high specificity for prediction of any post-procedural hemorrhage, but was inaccurate for the prediction of symptomatic ICH.
Abstract WP120: Can Early Transcranial Doppler Ultrasound Predict Early Neurological Deterioration And Risk Of Hemorrhagic Transformation After Endovascular Treatment?
Authors: Bavarsad Shahripour Reza , Azarpazhooh M. Reza , Tarpley Jason W , Agrawal Kunal , Modir Royya F , Meyer Brett C , Hemmen Thomas M , Meyer Dawn M
Published: February 2022

Background:
Recent advances in endovascular therapy (EVT) have led to a significant improvement in functional outcomes of patients with stroke. However, early neurological deterioration (END) after EVT has still remained a concerning issue. Reasons for END include reocclusion, hyperperfusion after recanalization, and hemorrhagic transformation. The current study was designed to assess the feasibility of early transcranial Doppler (TCD) after EVT, to identify association between TCD findings and END.

Methods:
This is a pilot study to assess the feasibility of TCD prior and early (within 60 minutes) after EVT. For all selected arteries, we measured peak systolic velocity, end diastolic velocity, mean flow velocity and pulsatility index. Patients were followed for three months after the intervention and disability was measured using modified Rankin scale (mRS). We examined the possible association between active leptomeningeal collateral flow after EVT and END.

Results:
Between October 16, 2020, and March 28, 2021, we recruited 20 acute ischemic stroke patients with large vessel occlusion who underwent EVT. Five patients were excluded because of a poor temporal window; two had an unsuccessful intervention. Four patients had END and all of them had active leptomeningeal flow with elevated blood pressure after EVT. In cases without END, we did not observe any flow diversion or active leptomeningeal collateral after EVT.In those without significant post-stroke disability (mRS<2), we did not observe any active leptomeningeal flow or flow diversion with blood pressure of ≤ 155/85. Most patients with post-stroke disability (mRS ≥ 2) had either flow diversion or active leptomeningeal flow in the presence of blood pressure ≥ 170/93. Hyperemia was associated with hemorrhagic transformation, particularly in the presence of elevated blood pressure. All cases with symptomatic hemorrhagic transformation had hyperemia.

Conclusion:
TCD is a feasible approach early after EVT. It has clinical implications in identifying those with END and risk for sICH. Early TCD after EVT may provide personalized BP management based on individualized cerebral flow and the presence of active collateral flow after EVT. Studies with larger sample size are warranted.
Abstract WP123: Comparison Of Surgical Versus Medical Therapy In Malignant Posterior Circulation Infarction: A Systematic Review And Meta-analysis
Authors: Lim Nicole-Ann , Lin Hong-Yi , Lim Mervyn J , Tan Choon Han , Yeo Tseng Tsai , Nga Vincent, Diong Weng , Tan Benjamin Y , Yeo Leonard L
Published: February 2022

Introduction:
Whilst surgical decompression in malignant middle cerebral artery infarction is well established, its role in malignant posterior circulation infarction (MPCI) is unclear. Recent small cohort studies suggest that neurosurgery in this group may be beneficial. This systematic review and meta-analysis aims to compare outcomes of MPCI patients undergoing surgical intervention versus medical therapy.

Methods:
Medline, Embase and Cochrane were searched from inception until 2 April 2021. Studies were included if they evaluated patients with posterior circulation stroke treated with neurosurgical intervention. Observational cohort studies and case series with death and functional outcome data were included. Death was defined as Glasgow Outcome Scale (GOS) 1 and modified Rankin scale (mRS) 6, or extracted from the text. Favourable functional outcome was defined as mRS 0-2, GOS 4-5, Barthel Index 91-100 or extracted from text at the latest follow-up period. 6673 studies were filtered, with 31 studies included for data extraction, of which 8 studies included both a surgical and medical therapy group. Random effects meta-analysis, analysis of proportions and meta-regression were performed.

Results:
The medical therapy cohort (n=235) had significantly better odds of good functional outcome (GFO) than the surgical cohort. There was no significant difference in odds of death between the two groups (Figure 1). Amongst surgical patients (n=184), 18% died and 55% had GFO. On meta-regression, the proportion of patients with atrial fibrillation and hydrocephalus was negatively associated with odds of death and GFO respectively (both p<0.05).

Conclusion:
In patients with MPCI, neurosurgery did not improve functional outcome or mortality in comparison with medical therapy. Larger cohort studies are warranted to resolve this clinical equipoise.
Abstract WP132: National Trends In Utilization And Outcomes Of Acute Ischemic Stroke And Intracerebral Hemorrhage Patients Undergoing Gastrostomy Tube Placement
Authors: Chaudhry Mohammad Rauf , Kherani Danish , Fadah Kahtan , Chaudhry Saqib A , Singh Baljinder , Kausar Naila , Ghatali Mohammad , Vellipuram Anantha Ramana R , Piriyawat Paisith , Maud Alberto , Sheriff Faheem , Rodriguez Gustavo , Cruz-Flores Salvador , Qureshi Adnan I
Published: February 2022

Background and Purpose:
Persistent dysphagia requiring gastrostomy tube placement continues to be a major issue for stroke patients. We performed analysis to evaluate trends in utilization of gastrostomy tube placement and associated rates of death among acute ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients over a 10-year period.

Methods:
We obtained data for patients admitted to hospitals in United States from 2009 to 2018 with a primary diagnosis of IS or ICH using a large national database. We determined rate and pattern of utilization and associated in-hospital outcomes of gastrostomy tube placement among IS and ICH patients.

Results:
A total of 50551 (7.05%) and 136922 (2.45%) patients underwent gastrostomy tube placement among the 716777and 5567538patients admitted with ICH and IS, respectively. There was a 3.2-fold decrease in patients who gastrostomy tube placement among patients with IS (2.3% in 2009 vs 0.7% in 2018; P<0.001), and by a 1.5-fold decrease for those with ICH (7.8% in 2009 vs 5.3% in 2018; P<0.001). The rates of in-hospital mortality among patients undergoing gastrostomy tube placement remained unchanged throughout the 10 years for patients with IS (5.2% in 2009 vs 4.9% in 2018; p = 0.54) but decreased by fold for those with ICH (7.58% in 2009 vs 2.7% in 2010; p = 0.01). The length of hospitalization remained significantly higher in patients undergoing gastrostomy tube placement compared with those who did not for both patients with IS (16.2 ±15.7versus 3.6±4.3, p<.0001) and those with ICH (24.4±22.1 versus 6.0±7.5, p<.0001). The cost of hospitalization remained significantly higher in patients undergoing gastrostomy tube placement compared with those who did not for both patients with IS ($140563± 172413 versus $ 37950.2± 45101.6, p<.0001) and those with ICH ($254519± 251973 versus $ 62133.3± 90833.9, p<.0001).

Conclusions:
Between 2009 and 2018, there has been a significant reduction in the proportion of IS and ICH patients who underwent gastrostomy tube placement. However, the length and cost of hospitalization remained significantly higher among patients who underwent gastrostomy tube placement.
Abstract WP133: Sex Differences In The Human Intracerebral Hemorrhage Peripheral Blood Transcriptome Implicate Differential Immune And Inflammatory Responses
Authors: Knepp Bodie , Rodriguez Fernando , Yee Alan H , Ng Kwan , Jickling Glen , Zhan Xinhua , Amini Hajar , Carmona Paulina , Hull Heather , Alomar Noor , Hakoupian Marisa , Sharp Frank R , Ander Bradley , Stamova Boryana
Published: February 2022

Sex differences in immune and inflammatory pathways have been shown in health and disease. However, little research has been done on sex differences following human Intracerebral Hemorrhage (ICH). We sought to unveil transcriptome differences in blood between Male (M) and Female (F) ICH responses. We evaluated 33 ICH patients and 33 vascular risk factor matched controls (VRFC), 9F and 24M each. Peripheral blood expression of 21,175 genes was analyzed at the co-expression network level with WGCNA - separate F (F-ICH and F-VRFC) and M (M-ICH and M-VRFC) networks generated; and per gene level (ANCOVA: Age, Time, and Sex*Dx (Diagnosis)). Five F (F-6, F-20, F-21, F-19, F-5) and 2 M (M-32, M-26) WGCNA modules were significant to Dx (p < 0.05) (Fig 1A). 105 genes were significant for the direct comparison (F-ICH vs M-ICH p < 0.05, |FC| > 1.2; Sex*Dx FDR < 0.2), which separated Sex*Dx groups (Fig 1B). 1,425 genes were differentially expressed in F-ICH (F-ICH vs F-VRFC p < 0.05, |FC| > 1.2; Sex*Dx FDR < 0.2) and 421 in M-ICH (M-ICH vs M-VRFC p < 0.05, |FC| > 1.2; Sex*Dx FDR < 0.2) (Fig 1C). F-ICH response was enriched in Monocyte and T Cell Specific genes and M-ICH in B Cell and Erythroblast specific genes; both were enriched in Neutrophil specific genes (Fig 1A). Overall, F modules and gene lists were significantly enriched in 236 GO terms (FDR < 0.1) and M modules in 55; 20 were common (Fig 1D). The ICH response unique to F-ICH included Inflammatory Response, T Cell Activation, Autophagy, Apoptotic Process, and RNA Splicing. M-ICH unique included B Cell Receptor Signaling, Immunoglobulin Receptor Binding, Antigen Binding, Complement Activation, and Receptor Mediated Endocytosis. Common responses included Innate Immune Response, Blood Coagulation, and Fc-ã Receptor Signaling Involved in Phagocytosis (Fig 1E). We found sex differences in ICH transcriptome responses in human peripheral blood. These implicate specific cell types in each sex that could represent novel sex-specific treatment targets.
Abstract WP137: Mirna 206 Expression Is Associated With Perihematomal Edema Volume And Functional Outcomes After Intracerebral Hemorrhage
Authors: Saeed Rula , Dennis Savannah , azizi Elham , nguyen doan , Lindsay Michael , Gastanaduy Mariella , Iwuchukwu Ifeanyi O
Published: February 2022

Introduction:
Circulating micro-RNAs (miR) are reported in the pathophysiology of intracerebral hemorrhage. Previous reports suggested that miR-206, miR-486, miR-150 and miR-146a are associated with ICH outcomes. In this, study we explored the associated of miRNA expression with radiological predictors of outcome hematoma expansion (HE) and perihematomal edema volume (PHEV) and functional outcomes.

Methods:
Patients (n=96) with acute spontaneous ICH were consented and blood samples were collected within 48 hours of ICH onset. Plasma miR were used to screen 752 well-characterized miR using locked nucleic acid (LNA) probe-based real-time PCR (ver3.3.5). Cycle threshold data were obtained using the regression method and global mean normalization to a universally expressed miR-92a was applied. Significance levels were assessed using the Mann-Whitney’s U-test and the Welch’s t-test (GenEx). Demographic, clinical data and Modified Rankin Score (MRS) were collected with follow-up calls at 30, 90, and 365-days from ICH onset. Hematoma and perihematomal edema volumes were calculated based on the ABC/2 formula at presentation, 24hrs, and 96hrs from ICH onset. Spearman’s rank correlation was used to determine the association of miRNA expression with HE (>30% increase in volume) and PHEV at onset, 24hrs and 96hrs. Simple logistic regression was used to determine the odds of survival at 30-days and favorable outcome at 90- and 365-days, defined as MRS
<
3.

Results:
Overall, cohort mean age 60.2years (IQR 52-73), 57.1% were deep nuclei (thalamic and basal ganglia ICH), mean ICH vol. 38.4 (SD23.2). We observed a positive correlation with miR-206 and PHEV at 48-96hrs (rho 0.451, p=0.003). Expression of miR-206 was associated with a higher odds of survival at 30-days (OR 1.149 95% CI 1.016-1.299 p=0.0266) and a favorable outcome at 365-days (OR 1.135 95% CI 1.007-1.278 p=0.038). There was no association of miR-206 expression with HE. miR-486, miR-150, and miR-146a were not associated with radiological or functional outcomes.

Conclusion:
In our cohort, miR-206 was associated with PHEV at 96hrs, survival at 30days and favorable outcome at 1 year. Further studies are ongoing to further delineate the role of miR206 in ICH related biological mechanisms.
Abstract WP140: Environment Matters: Neighborhood Socioeconomic Disadvantage And Cerebral Small Vessel Disease Are Associated With Poor Outcomes Among Patients With Intracerebral Hemorrhage
Authors: Potter Thomas , Bako Abdulaziz T , Meeks Jennifer , Tannous Jonika , Pan Alan , Vasileios-Arsenios Lioutas , Dubey Prachi , MCCANE Charles D , Garg Tanu , GADHIA RAJAN R , Misra Vivek , Volpi John J , Chiu David , Vahidy Farhaan S
Published: February 2022

Background:
Only 20-30% of Intracerebral Hemorrhage (ICH) survivors achieve functional independence. We investigated if neighborhood socioeconomic disadvantage (NSD) mediated by cerebral small vessel disease (CSVD) is associated with post-ICH functional outcomes.

Methods:
Clinical and imaging data were extracted from electronic medical records and 90-day modified Rankin Score (mRS) was obtained from prospectively collected stroke registry at a large hospital system. CSVD was assessed based on MRI markers from 1-year before to 30 days after the ICH event and was scored from 0-4 with severe CSVD (S-CSVD) ≥ 2. Exact patient addresses were geocoded, and state-level Area Deprivation Index (ADI) was calculated, with high NSD (H-NSD) categorized as the top 15% of ADI scores. The outcome was severe disability or death (SDD) categorized as 90-day mRS score ≥4. Multivariate logistic regression models were fitted, and mediation was evaluated by structural equation modeling. Odds ratios (OR) and 95% confidence intervals (CI) are reported.

Results:
Final analysis included 367 patients (mean age: 65 years, 49.7% female, median presentation ICH Score: 1) with complete data. We found significant associations between older age, Black race, S-CSVD, H-NSD, hematoma volume, presence of ventricular hemorrhage, presentation systolic blood pressure (SBP), and ICH score with SDD (P<0.05). In a multivariate model adjusted for age, SBP, ICH score and other important clinical co-variates, SDD was significantly and independently associated with both H-NSD (OR, CI: 2.03, 1.05 - 4.23) and S-CSVD (OR, CI: 1.93, 1.12 - 3.35). Our data did not demonstrate an association between CSVD and NSD; and S-CSVD did not mediate the relationship between H-NSD and SDD.

Discussion:
In addition to known clinical factors, NSD, as measured by the ADI, and CSVD were independently associated with poor ICH outcomes. Potential causal pathways between H-NSD and poor ICH outcomes need to be further evaluated.
Abstract WP141: Effect Of Non-invasive Vagus Nerve Stimulation In Hemorrhagic Brain Injury And Permanent Ischemic Stroke In Rats
Authors: Ay Ilknur , Liebler Eric , Ay Hakan
Published: February 2022

Introduction:
Non-invasive vagus nerve stimulation (nVNS) reduces infarct volume after transient ischemia in rats. Here, we tested the effect of nVNS in intracerebral hemorrhage (ICH) and permanent ischemic brain injury models.

Methods:
ICH was induced by whole blood (n=24) or collagenase (n=24) injection into the striatum of adult male and female Wistar rats. 1-hour sham stimulation (n=16) or nVNS (n=32) was initiated 30 minutes after injection. Spontaneous circling, hindlimb retraction, and grasp ability were tested at 24 hours to measure functional deficit. Rats were euthanized 24 hours or one week after injury, and brain tissue was processed for water content analysis (n=24) and histology (n=24), respectively. Permanent ischemia was induced by filament occlusion of the right middle cerebral artery in adult male Wistar rats (n=18). Sham stimulation and nVNS initiated 30 minutes after the induction of ischemia were applied for 1 hour and 3 hours (n=6 per group). Rats were euthanized 24 hours later to measure infarct volume.

Results:
1-hour nVNS was associated with a non-significant reduction in hematoma volume in both models of ICH (Fig). Animals treated with nVNS demonstrated better functional outcome at 24 hours after ICH (
p
=0.042). There was no difference in brain edema between control and active treatment arms in both models of ICH. 3-hour nVNS reduced infarct volume by 21% in permanent ischemia (
p
=0.047, Fig).

Conclusion:
The results of this study support prior evidence that nVNS may have a therapeutic potential in ischemic stroke. nVNS is currently being evaluated in two clinical studies (NCT03733431 and NCT04050501) for the treatment of acute ischemic stroke. The lack of adverse events in two different models of ICH in this study suggests that nVNS could be safely administered as early as an ambulatory setting before the stroke etiology (ischemic vs. hemorrhagic) has been determined.
Abstract WP148: Magnetically Enhanced Diffusion (MED) Of Intravenous Thrombolytics Decreases Thrombus Leading To Accelerated Reperfusion
Authors: Abendschein Dana R , Swaminathan Sohaan , Rethmeyer Aimee , Recinella Dan , Morris Sean , Derdeyn Colin P
Published: February 2022

Whether systemic fibrinolysis alone or, more recently, combined with thrombectomy are used to re-establish blood flow in cerebral arteries occluded with thrombus, a shower of fragments often plugs more distal arterial branches leading to continued infarction, resulting in some loss of brain function. We hypothesized that magnetite MicroBeads injected intra-arterially near a thrombus and exposed to a rotating magnetic field after IV administration of plasminogen activators (lytics) would accelerate fibrinolysis leading to decreased distal thrombus burden, increased blood flow, and less brain infarction and loss of function. Clots formed
in vitro
from recalcified citrated rabbit blood were weighed (ave = 100mg) and injected into both common carotid arteries with blood flow occluded at the level of C3/4 in anesthetized male and female rabbits. rtPA (Activase, 1mg/kg, Genentech) was infused IV over 1h or Tenecteplase (TNK, 0.3-0.9mg/kg, Genentech) was injected IV as a bolus. After 30 min, magnetite MicroBeads were injected (300ug) as a bolus every 5 min over 30min (6 doses, 1,800mg) through a 5F angiocatheter placed within 2-3cm of the clot in one carotid, while the other carotid received the lytic alone by diffusion. The clots were removed after 1h and reweighed. MED increased the rate of fibrinolysis of clots leading to >95% reduction in clot weight vs 83% with Activase alone (p<0.0001 for paired testing, n=8). Clot lysis was also increased with MED + TNK (p<0.05, n=6) compared to TNK alone. Thus significant acceleration of lysis and reduction in clot weight occurs after treatment with MicroBeads plus lytic compared to lytic alone. This approach may enhance reperfusion and decrease infarction during stroke treated by either lytic alone or lytic + thrombectomy leading to improved outcomes.
Abstract WP155: Relationship Between Nonstenotic Plaque, Left Atrial Enlargement, And Age In Patients With Embolic Stroke Of Undetermined Source: A Multi-center Observational Cohort Study
Authors: Oak Solomon , Thau Lauren , Nguyen Thanh N , Sathya Anvitha , Reyes-Esteves Sahily , Cucchiara Brett L , Vigilante Nicholas , Kamen Scott , Hall Jillian , Patel Parth , Thon Jesse M , Siegler James E
Published: February 2022

Background:
Nonstenotic internal carotid artery (ICA) plaque as a mechanism of embolic stroke of undetermined source (ESUS) is controversial. Studies show an inverse relationship between cardioembolic stroke risk and nonstenotic plaque in ESUS patients. We explored this relationship using left atrial enlargement (LAE) as a marker of cardioembolic stroke predisposition.

Methods:
A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried. ESUS diagnosis was based on an embolic stroke pattern without an identifiable source on imaging and ≥24hrs of telemetry. Descriptive statistics were used to differentiate clinical, laboratory, and imaging predictors of sex adjusted LAE.

Results:
Of the 4155 patients screened, 273 (7%) met the inclusion criteria. Compared to patients without LAE, those with LAE were older (68y vs 62y, p<0.01), and had more frequent hypertension (83.7% vs 66.9%, p<0.01) and coronary artery disease (22.8% vs 11.3%, p=0.02). All had greater ipsilateral than contralateral ICA plaque (median 1.9cm [IQR 0-3] vs 1.5cm [IQR 0-2.6], p<0.01) without any difference in stenosis (median 0% [IQR 0-0] vs. 0% [IQR 0-0], p=0.19). Patients under 70 had greater plaque ipsilateral versus contralateral than patients 70 or older (mean difference 0.42cm [±1.24] vs 0.08cm [±1.54], p=0.047), and were less likely to have any LAE (28.6% vs 42.9%, p=0.02) or moderate-to-severe LAE (6.3% vs 15.3%, p=0.02). The probability of finding more ipsilateral than contralateral plaque in ESUS patients exceeded chance (50%) for patients under 70 (Figure).

Discussion:
Clinically relevant ipsilateral ICA plaque was more frequent in this ESUS cohort, regardless of LAE. When stratified by age, younger patients had greater ipsilateral ICA plaque burden and less LAE. While nonstenotic plaque and LAE frequently co-exist, younger ESUS patients were at greater risk of nonstenotic plaque than the elderly, who were at greater risk of LAE.
Abstract WP158: Trends In Utilization Of IV Thrombolysis And Mechanical Thrombectomy In Patients With Stroke And Malignancy.
Authors: Otite Fadar , Somani Sana , Chaturvedi Seemant , Mehndiratta Prachi
Published: February 2022

Background and Purpose:
Existing data shows that IV thrombolysis (tPA) and mechanical thrombectomy (MT) use in acute ischemic stroke (AIS) patients and malignancy is <2%. Our aim was to determine whether utilization of recanalization therapies has increased in AIS patients with cancer since publication of pivotal MT trials.

Methods:
All admissions with a primary diagnosis of AIS (weighted n=5,554,161) were identified from the 2007-2018 Nationwide Inpatient Sample. Cancer-associated strokes (CAS) were categorized into hematologic (hem), solid and metastatic (met) cancers. Joint point regression and multivariable-adjusted logistic regression models with interaction terms were used to evaluate rate of change in t-PA and MT use in CAS compared to non-CAS admissions.

Results:
Across this period, 4.0% of AIS admissions had comorbid CAS. The proportion of AIS hospitalizations with CAS increased from 3.8% in 2007 to 4.4% in 2018. Mean age of CAS was 72.9 (47.6% women) vs. 70.6 years (51.8% women) among non-CAS. CAS patients had fewer vascular risk factors. Highest t-PA usage was in non-CAS pts (7.8%) and lowest use in met-CAS pts (3.8%) and this difference was significant. In contrast MT usage was highest in met-CAS (2.0%) vs non-CAS (1.6%) and hem-CAS (1.2%). A race-by-time interaction revealed an increase in utilization of both therapies in all CAS groups. Pace of the increase was slower in met CAS (OR 0.97, 95%CI 0.95-0.99) per unit increase in year. MT use increased at a faster pace in met-CAS patients (OR 1.07, 95%CI 1.02-1.12) compared to non-CAS. Although overall mortality rates for patients with cancer has decreased for all cancer types, CAS had significantly higher in hospital mortality as compared to NCS (8.9% vs 4.4%, p <0.001).

Conclusions:
Utilization of both t-PA and MT has increased over the last decade. Contrary to prior studies, the current frequency and pace of increase in MT use is greater in met-CAS admissions compared to non-CAS. Patients with CAS have fewer traditional vascular risk factors and significantly higher in hospital mortality. Future studies should address longer term outcomes in CAS versus non-cancer strokes.
Abstract WP167: Machine Learning Modelling To Predict 90 Day Home Time In Patients Undergoing Endovascular Thrombectomy
Authors: Singh Nishita , Kashani Nima , McDonough Rosalie , Bala Fouzi , Horn MacKenzie , Stang Jillian , Stang Jillian , Demchuk Andrew M , Hill Michael D , Almekhlafi Mohammed , Holodinsky Jessalyn K
Published: February 2022

Background:
90-day home-time, the number of days a patient is back at their premorbid living situation without an increase in level of care in the first 90 days post stroke, is routinely collected in administrative data. We evaluated the prediction of 90-day home-time using machine learning modelling in patients undergoing endovascular treatment (EVT).

Methods:
We used the QuICR provincial stroke registry and administrative data from Southern Alberta from Jan 2015-Dec 2019 to identify patients who underwent EVT. Imaging data were scored by 2-physician consensus. The primary outcome was 90 day home-time, which has a highly non-normal distribution with excess zero’s. We modelled using generalized boosting machine model with Gaussian distribution. Contribution of different covariates to hometime was determined using partial dependence plots.

Results:
We identified 659 EVT patients from Jan 2015 to Dec 2019 treated in Calgary, Alberta. Overall,median predicted 90d home-time was 41days (IQR 5.5 to 77.8) with good model accuracy (Root mean square error 6.96). Holding other covariates constant, factors predicting lower 90d-hometime were diabetes mellitus(-14.1d), hypertension (-7d), low baseline ASPECTS (≤5) (-5.6d) and symptomatic intracerebral hemorrhage (sICH) on follow up scan (-13.8d). There was a consistent improvement in the predicted home-time over the last 5 years. There was no meaningful difference in predicted 90d-home-time by age, baseline NIHSS, sex, atrial fibrillation, occlusion site, tandem occlusion, thrombolysis, or successful reperfusion (Figure 1)

Conclusions:
Predicting 90-d hometime using boosting machine learning modelling is useful to assess complex relationships between predictors and home-time. Hypertension, diabetes, low ASPECTS and sICH were predictors of lower 90-d home-time in this registry.
Abstract WP171: Incidence And Outcomes Of Pseudoaneurysm In Pediatric Patients With Blunt Cerebrovascular Injury
Authors: Pabst Lisa , Chung Melissa G , Sribnick Eric
Published: February 2022

Objective:
Pseudoaneurysm is a rare manifestation of blunt cerebrovascular injury (BCVI) in pediatric patients and carries a high risk of both ischemic stroke and rupture. There is a paucity of data regarding the incidence, prognosis and best practice in management in children. The aim of this study is to describe the history and outcomes of children with traumatic cerebrovascular pseudoaneurysm.

Methods:
Patients between the ages of 0 and 18 years were identified from the prospectively enrolled trauma registry at a tertiary care pediatric hospital between January 1, 2011 and July 1, 2021 who presented with head and/or neck blunt trauma, had available cerebrovascular imaging and a diagnosis consistent with BCVI. Retrospective chart review was performed to identify patients with pseudoaneurysm formation.

Results:
Twenty patients were identified with diagnosis of BCVI and of those, six developed pseudoaneurysm. Twelve of the fourteen other BCVIs included the internal carotid artery, while two involved vertebral arteries. All pseudoaneurysms were of the internal carotid artery. Pseudoaneurysm was diagnosed at a median interval of 5 days from initial injury (range 1 day to 6 weeks). Other BCVIs were all diagnosed within the first 2 days of hospitalization. Treatment for pseudoaneurysm included a course of antiplatelet therapy in all. Three patients were initially treated with anticoagulation with subsequent transition to antiplatelet therapy. Endovascular intervention was performed in two patients. 2 patients suffered arterial ischemic stroke. All 6 patients were living and discharged home with favorable neurologic outcomes based on Glasgow Outcome Scale with median follow-up time of 7 months.

Conclusions:
In this retrospective cohort, pseudoaneurysm was observed in 30% of pediatric patients with BCVI, which is higher than previously reported. Treatment of pseudoaneurysm was variable, but all patients had favorable neurologic outcomes. Compared to other forms of BCVI, pseudoaneurysm was identified following a longer period of time from initial injury. Further studies are needed to identify risk factors for pseudoaneurysm and to inform the need and timing for serial imaging in identifying pseudoaneurysms given potential treatment implications.
Abstract WP178: Biological Age Influences Clinically-evident And Asymptomatic Cerebrovascular Disease: Combined Analysis In The Uk Biobank And All Of Us
Authors: Rivier Cyprien , Szejko Natalia , Acosta Julian , Both Cameron , Leasure Audrey C , Torres Lopez Victor , Gill Thomas M , Sheth Kevin N , Falcone Guido J
Published: February 2022

Background:
While chronological age is defined by time, biological age (also known as phenotypic age) is defined by biological variables that summarize the status of key physiological processes. Mounting evidence indicates that biological age is a crucial determinant of longevity and other aging-related traits. We hypothesize that biological age influences clinically-evident and asymptomatic cerebrovascular disease.

Methods:
We analyzed data from the UK Biobank (discovery) and All of Us (replication) studies. We ascertained ischemic and hemorrhagic stroke using questionnaires and EHR data. In the UK Biobank we also evaluated MRI-defined white matter hyperintensity (WMH) volume and brain volume (BV). We estimated biological age using PhenoAge, a validated tool that integrates information on albumin, creatinine, glucose, C reactive protein, lymphocyte percentage, mean corpuscular volume, red blood cell distribution width, alkaline phosphatase and white blood cell count. Biological age was divided into tertiles and entered in multivariate Cox and linear regression models adjusting for chronological age and vascular risk factors.

Results:
The discovery phase included 416,415 UK Biobank participants. Compared to the biologically youngest tertile, the risk of stroke was 17% (HR 1.17, 95%CI 1.04-1.32) and 61% (HR 1.61, 95%CI 1.40-1.86) higher in tertiles 2 and 3 of biological age, respectively (test-for-trend p<0.001). All results were replicated on 56,513 All of Us participants (all associations p<0.05). In 34,095 UK Biobank participants with MRI data, compared to the biologically youngest tertile, those in tertile 2 had 83% (beta 0.003, se 0.014) higher WMH volume and 3.3% (beta -0.012, se 0.013) lower BV, whereas those in tertile 3 had 177% (beta 0.041, se 0.02) higher WMH volume and 5.6% (beta -0.049, se 0.019) lower BV (test-for-trend p<0.001).

Conclusion:
Biological age is a significant contributor to clinically evident and silent cerebrovascular disease. Combined interventions targeting the biological processes that determine biological age could result in important synergistic effects for primary and secondary prevention. Further research is needed to determine the role of biological age in stroke outcome and recurrence.