bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P194: Improved Efficacy of ICM Detection of Atrial Fibrillation in Cryptogenic Stroke Patients with MRI-Defined Infarcts: Preliminary Results from the SPIDER Registry
Authors: Joseph Kelley , Wanjiku Stephen , Jumaa Mohammed , Richards Mark
Published: July 2021

Introduction:
Recent trials have demonstrated the efficacy of the implantable cardiac monitor (ICM) in detecting atrial fibrillation (AF) in cryptogenic stroke (CS) patients. However, these trials have included patients with TIAs or no CT or MRI imaging of the brain. We hypothesized that the AF detection rate in CS patients would be improved by requiring the presence of an embolic-appearing infarct on MRI.

Methods:
All CS patients within the Promedica Stroke Network were considered for inclusion in the SPIDER (Stroke Prevention through the Improved Detection of AF) registry. All patients were monitored by inpatient telemetry for AF for a minimum of 48 hours, and received brain MRI with or without angiography. Patients with no AF, a negative transesophageal echo for ASD/PFO, and an embolic-appearing MRI infarct (wedge infarct, multiple vascular distributions) were offered an ICM (Reveal or Reveal LINQ™) for AF detection (minimum of 10 seconds).

Results:
64 patients have been enrolled to date and followed for 223 days. Mean age was 66.9 ± 12.8 years and 40.6% were female with a median NIH stroke score of 5.2 on presentation. AF episodes were detected in 11 patients, resulting in an AF detection rate of 17.2% and a median time to AF detection of 35 days. While both mean follow-up and time to AF detection were comparable to the data from CRYSTAL-AF (6 months, 41 days), AF detection rate was increased nearly two-fold.

Conclusions:
Here we show that restricting ICM implantation for AF detection in CS patients to those with MRI-defined embolic-appearing infarcts improves efficacy, with an increase of 8.3% in detection at six months, when adjusted for follow-up time. Explanations for this higher detection rate might include a slightly higher age (66.9 vs 61.5 years of age), a more liberal cutoff for AF (10 vs 30 seconds), and, likely, a more highly selected patient population. Such an approach might both improve access to this important technology and help preserve health care resources.
Abstract W P209: Trends in Hospital Certification and EMS Utilization of Primary Stroke Centers
Authors: Pajerowski William , Messe Steven R , Jia Judy , Abboud Michael , David Guy , Mechem Crawford , Band Roger , Kasner Scott E , Carr Brendan G , Mullen Michael T
Published: July 2021

Objective:
In December 2003, the Joint Commission began certifying primary stroke centers (PSCs). Preferential routing of suspected stroke cases by Emergency Medical Services (EMS) to PSCs is recommended by the American Heart Association and Philadelphia EMS officially enacted such a policy in October 2011. We assessed trends in hospital bypass over time and estimated the time cost of bypassing the nearest hospital.

Methods:
Data from the Philadelphia EMS database was used to identify patients with a prehospital impression of stroke, defined by EMS provider impression, between January 2004 and December 2013. PSC status and date of initial certification was determined for each of the 22 hospitals in the region. Travel distances and estimated transport times from the scene to all area hospitals were calculated.

Results:
The number of PSCs increased over time from 1 hospital in 2004 to 17 in 2013. There were a total of 15,034 cases. The proportion of cases arriving at PSCs increased from 6.3% in 2004 to 87.6% in 2013. There was an increase in the total proportion of cases in which EMS bypassed the closest hospital, 36.9% in 2004 to 41.4% in 2013, p=.006. As more hospitals became PSCs, bypass of the closest hospital to arrive at non-PSCs decreased while bypass of the closest hospital to arrive at PSCs increased (Figure 1). Hospitals that would eventually become certified as PSCs received 79.8% of stroke cases in 2004 and 87.6% in 2013, p<.001. Patients who bypassed the closest hospital for a PSC had longer mean transport times than patients transported to the closest, non-PSC, 9.0 vs. 5.0 minutes, p<0.001.

Conclusions:
EMS bypass of the closest hospital was common before there was an official destination policy and has only modestly increased over the study period. Increasing numbers of patients were treated at PSCs over time, primarily due to increasing numbers of PSCs.
Abstract W P216: Recognition Of Stroke By EMS Is Associated With Improved Emergency Department Quality Of Care
Authors: Abboud Michael , Jia Judy , Pajerowski William , Guo Michelle , David Guy , Messe Steven R , Band Roger , Carr Brendan G , Mullen Michael T
Published: July 2021

Objective:
Hospital arrival via Emergency Medical Services (EMS) has been associated with faster evaluation and treatment of stroke. Among stroke cases presenting via EMS, we sought to determine if accurate recognition of stroke by prehospital providers was associated with increased quality of care in the Emergency Department (ED).

Methods:
Single center retrospective study of patients presenting via EMS between September 2009 and October 2012 with a discharge diagnosis of transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH). Hospital and EMS databases were used to determine dispatcher and EMS provider impression, pre-hospital and in-hospital time intervals, EMS prenotification, NIH stroke scale (NIHSS), symptom duration and use of tissue plasminogen activator (tPA). Multivariable models were constructed to determine independent associations.

Results:
There were 399 cases identified: 14.5% TIA, 67.2% IS, and 18.3% ICH. Dispatchers correctly identified 58.2% of cases and EMS providers correctly recognized 57.6% of cases. Compared to cases missed by EMS, strokes that were correctly recognized had longer median on-scene time (17 vs. 15 min, p=0.01) but shorter transport times (12 vs. 15 min, p=0.001). Cases correctly recognized by EMS had shorter door-to-physician time (4 vs. 11 min, p<0.001) and shorter door to CT time (23 vs. 48 min, p<0.001). These associations were independent of age, NIHSS, symptom duration, and EMS prenotification (Door to Physician β = -4.42, p=0.027; Door to CT β= -18.81, p<0.001). Among the 268 ischemic stroke patients, 155 (57.8%) were correctly recognized by EMS. Cases correctly recognized by EMS were more likely to receive tPA (15.7% vs. 3.6%, p<0.001). This remained significant after adjusting for age, NIHSS, symptom duration and EMS prenotification (OR=5.54, p=0.006).

Conclusion:
Recognition of stroke by EMS providers was independently associated with faster door to physician time, faster door to CT time, and greater odds of receiving tPA. Quality initiatives to increase EMS recognition of stroke have the potential to improve hospital based quality of care and outcomes after stroke.
Abstract W P243: Multiple Therapeutic Effects of Progranulin on Experimental Acute Ischemic Stroke
Authors: Kanazawa Masato , Kawamura Kunio , Takahashi Tetsuya , Miura Minami , Tanaka Yoshinori , Koyama Misaki , Toriyabe Masafumi , Igarashi Hironaka , Nakada Tsutomu , Nishihara Masasugi , Nishizawa Masatoyo , Shimohata Takayoshi
Published: July 2021

Introduction:
In central nervous system, progranulin (PGRN), a glycoprotein growth factor, is considered to play crucial roles in maintaining physiological functions, and mutations in PGRN gene cause TAR DNA-binding protein-43 (TDP-43)-positive frontotemporal lobar degeneration. Although several studies reported that PGRN plays protective roles against ischemic brain injury, it remains unknown the precise mechanisms by which PGRN exerts protective effects on the ischemic brain injury.

Methods:
We determined the temporal changes of expression and localization of PGRN after ischemia as well as therapeutic effects of PGRN on ischemic brain injury using in vitro and in vivo models.

Results:
First, we demonstrated a dynamic change of PGRN expression in ischemic Sprague-Dawley rats, including increased levels of PGRN expression in microglia within the ischemic core, and increased level of PGRN expression in survived neurons as well as induction of PGRN expression in endothelial cells within the ischemic penumbra. Second, we demonstrated that PGRN could protect against acute focal cerebral ischemia by variety of mechanisms including via attenuation of blood-brain barrier disruption, suppression of neuroinflammation, and neuroprotection: we found that PGRN may regulate vascular permeability via vascular endothelial growth factor (VEGF), that PGRN may suppress neuroinflammation after ischemia via anti-inflammatory interleukin-10 (IL-10) in microglia, and that neuroprotective effect of PGRN may be explained in part by inhibition of cytoplasmic redistribution of TDP-43 using PGRN knock-out mice (C57Bl/6 background). Finally, we demonstrated the therapeutic potential of PGRN against acute focal cerebral ischemia using a rat autologous thromboembolic model with delayed tissue plasminogen activator (tPA) treatment. Intravenously administered recombinant PGRN reduced volumes of cerebral infarct and edema, suppressed hemorrhagic transformation, and improved motor outcome (P = 0.007, 0.038, 0.007, and 0.004, respectively).

Conclusions:
PGRN may be a novel therapeutic target that provides vascular protection, anti-neuroinflammation, and neuroprotection related in part to VEGF, IL-10, and TDP-43, respectively.
Abstract W P270: Quality of In-Hospital Stroke Care in Veterans Affairs Hospitals
Authors: Lyerly Michael J , Sager Danielle , Coffing Jessica , Damush Theresa , Cutter Gary , King Peter H , Williams Linda
Published: July 2021

Introduction:
Increasing focus is being placed on quality metrics for stroke care in an effort to improve outcomes. This study aims to examine if quality of stroke care is the same for Veterans experiencing an in-hospital stroke compared to patients presenting through the emergency department (ED).

Methods:
We analyzed data from an 11-site VA quality improvement study, where 30 months of ICD-9 defined stroke admissions were chart reviewed by a central, trained group of abstractors to assess stroke diagnosis, clinical data, and eligibility and passing for 11 stroke quality indicators (QIs; 8 Joint Commission and 3 others). Stroke severity was determined by retrospective NIHSS scoring of the admission exam. Strokes were classified as presenting to the ED or in-hospital (already admitted for another diagnosis). Transfers (N = 362) were excluded. We compared clinical and QI data between the in-hospital and ER groups using Student’s t-tests and Chi-square tests.

Results:
There were 35 in-hospital and 1788 ED strokes. The two groups did not differ with respect to age, race or sex, however in-hospital strokes had higher stroke severity (mean 11.1 vs 5.1, p=0.002), increased length of stay (12.8 vs 7.3, p=0.003), and were less likely to be discharged home (34.3% vs 63.8%, p<0.001). QI results are shown in the Table; those with in-hospital stroke were more likely to be eligible for tPA, but received less dysphagia screening.

Conclusions:
Veterans who develop an in-hospital stroke receive similar quality of care as patients presenting to the ED although fewer in-hospital patients had dysphagia screening. Interestingly, tPA eligibility and utilization were higher for in-hospital strokes although utilization did not reach significance. While it is reassuring that in-hospital strokes are receiving similar quality of care, there is still room for improvement in all patient care settings and in-hospital stroke patients should be included in future QI processes.
Abstract W P289: Cost Burden of Stroke Mimics and Transient Ischemic Attacks Following Intravenous Tissue Plasminogen Activator Treatment
Authors: Goyal Nitin , Male Shailesh , Bellamkonda Sushma , Zand Ramin
Published: July 2021

Objective:
The decision to treat a patient with acute stroke symptoms is based on pertinent history, brief neurological examination, urgent labs, and head CT. In this setting, patients with stroke mimic (SM) may mistakenly receive IV-tPA. The main goal of this study was to investigate the excess direct and indirect hospital costs among patients who received IV-tPA when the final diagnosis was not ischemic stroke.

Method:
We reviewed the records of 538 IV-tPA treated patients who presented to our primary stroke centers. The excess cost analysis compared the actual direct and indirect hospital costs of an individual patient to what their direct and indirect hospital costs would have been had they primarily been diagnosed with SM or TIA. We obtained the actual and itemized direct and indirect hospital costs of each patient who had a diagnosis of SM or TIA. We determined the ‘calculated cost’ for each patient based on the projected direct and indirect hospital costs associated with each patient’s actual diagnosis, symptoms, severity of disease, other active clinical problems, and hospital course.

Results:
Seventy-four of 538 post IV-tPA patients had final diagnosis of SM and 21 had TIA. The excess direct and indirect hospital costs for SM was $257,975 and $152,813, respectively. The median excess cost was $5,401 per admission. The excess total cost for TIA was $85,026 with a median of $3,407 per admission. Considering the 2013 Wage Index report for Memphis, TN (WI: ∿ 0.93), and a 42% rate of direct personnel cost in our direct cost analysis, we can estimate that, in the United States, the excess direct hospital cost associated with administration of IV-tPA to patients with SM is approximately 15 million dollars per year with an average hospital direct cost of $3600 per admission.

Conclusion:
Our study reveals that administration of IV-tPA to patients with SM is associated with significant excess cost; mainly from the cost of unnecessary hospital admission, IV-tPA, and higher level of care.
Abstract W P29: Tissue Plasminogen Activator Mediated Reperfusion, and Subsequent Improvement in Resting State Connectivity Correlates with Functional Outcome in Acute Ischemic Stroke Patients
Authors: Sen Souvik , Fridriksson Johann , Hanayik Taylor , Rorden Christopher , Hubbard Isabel , Burdine Joselyn , Herath Priyantha , Fridriksson Julius
Published: July 2021

Background:
Intravenous Tissue Plasminogen Activator (TPA) is the only FDA approved medical therapy for acute ischemic stroke (AIS). Prior study suggests that early recanalization is associated with better stroke outcome. Our aim was to correlate task-negative and task-positive (TN/TP) resting state network activity with tissue perfusion and functional outcome, in stroke patients who received TPA.

Method:
AIS patients were consented and underwent NIH stroke scale (NIHSS) assessment and magnetic resonance imaging (MRI) scans during TPA infusion (baseline) and six hours post stroke. The MRI sequences include contrast-enhanced perfusion weighted image (PWI) and resting state Blood Oxygen Level-Dependent or BOLD (RSB) images acquired using a Siemens Treo 3T MRI scanner. Additionally, the RSB scan and the NIHSS were obtained at a 30-day follow up visit.

Results:
Fourteen patients (mean age ± SD=63 ±14, 50% male, 50% white, 43% black and 7% others) who qualified for TPA completed the study at baseline and 6 hours post stroke. Of these, 6 patients had valid follow up data at 30 days. Three patients without cerebral ischemia were excluded. A paired samples t-test comparing baseline and 6h post stroke showed a significantly improved TP network t(10)= -4.24 p< 0.05. The resting network connectivity improved from 6 hours post stroke to 30-days follow up, t(5)= -5.35 p< 0.01. Similarly, NIHSS, at 6h post stroke t(10)= 3.62 p< 0.01 and at 30-days follow up t(5)= -3.4 p< 0.01 were significantly better than the NIHSS at baseline. The 6-hours post-stroke perfusion correlated with the resting network connectivity in both the damaged (r=-0.56 p= 0.07) and intact hemispheres (r= -0.57 p= 0.06). Differences in functional connectivity and NIHSS scores from baseline to 6 h were positively correlated (r= 0.56 p=0.07).

Conclusion:
In this pilot study we found that TPA led to changes in MRI based resting state networks and associated functional outcome. Correlations were found between perfusion, functional connectivity and NIHSS. This suggests that the improvement of resting state network means improved efficiency of brain activity indicated by functional outcome and may be a potential predictive MRI biomarker for TPA response. A larger study is needed to verify this finding.
Abstract W P313: Risk of Rebleed with Resumption of Anticoagulation after Intracranial Hemorrhage
Authors: Weimer Jonathan M , Gordon Errol , Frontera Jennifer A
Published: July 2021

Introduction:
Rebleed after resumption of anticoagulation following intracranial hemorrhage (ICH) remains a substantial concern, but little data is available describing the occurrence of such events.

Methods:
Prospectively collected data from 2008-2011 was reviewed in patients with intraparencymal (IPH), subdural (SDH), and subarachnoid (SAH) hemorrhage. Patients with anticoagulant use prior to ictus were identified, as were patients started on full anticoagulation during hospitalization. In hospital rates of ischemic events, major and minor hemorrhages were collected. Univariate analyses were performed using either Fisher’s exact or Mann-Whitney U tests.

Results:
387 total ICH patients were identified, including 132 (34.1%) SAH, 134 (34.6%) SDH, and 121 (31.3%) IPH. At time of ictus, 67 (17.3%) were anticoagulated and underwent reversal of coagulopathy. Of these 67 patients, ischemic complications including myocardial infarction (MI), pulmonary embolism (PE), and deep vein thrombosis (DVT) occurred in 8 (11.9%) during hospitalization. 6 of 67 (9.0%) patients resumed full anticoagulation at a median of 14.5 days from ictus. 14 additional patients were started on full anticoagulation de novo at a median of 12 days from ictus. Significant indications for anticoagulation after ICH included: 4 (20%) history of valvular heart disease, 7 (35%) DVT, 1 (5%) PE, 7 (35%) arrhythmia, and 1 (5%) coronary artery disease. Of the 20 patients fully anticoagulated after ICH, 2 (10%) experienced a major hemorrhagic complication. 1 new ICH occurred 36 days from ictus on the day anticoagulation was restarted, and 1 SDH expansion occurred 56 days from ictus and 47 days from resuming anticoagulation. 1 patient experienced a minor hemorrhagic complication (retroperitoneal hematoma).

Conclusions:
Ischemic complications occurred in 11.9% of ICH patients who underwent coagulopathy reversal. It remains unclear if coagulopathy reversal or delay to resuming anticoagulation is the cause of ischemic events. Initiation of anticoagulation after a median of 14 days from ictus was associated with major hemorrhage in 10% of patients. Reversal of anticoagulation and initiation of anticoagulation after a median of 14 days is associated with an acceptable risk profile.
Abstract W P325: Hematoma Volumes Are Independent of Elevated Prehospital Blood Pressure in Patients with Intracerebral Hemorrhage
Authors: Zewude Rahel T , Gioia Laura C , Kate Mahesh P , Liss Kim , Lowe Brian R , Butcher Kenneth
Published: July 2021

INTRODUCTION:
In a recent prehospital interventional trial, it was observed that high prehospital BP in intracerebral hemorrhage (ICH) patients is associated with larger ICH volumes. We tested the hypotheses that higher prehospital BP is associated with larger baseline ICH volumes outside a clinical trial setting.

METHODS:
We conducted a retrospective analysis of a prospectively-maintained centralized database of electronic patient health care reports (ePCR), including serial BP measurements, of all patients transported by Emergency Medical Services (EMS) to the Emergency Department (ED) of a single hospital with acute stroke symptoms during an 18-month period. All patients with an EMS dispatch code for suspected stroke were included. Hospital charts and neuroimaging were reviewed. Hematoma and intraventricular hemorrhage (IVH) volumes were measured planimetrically.

RESULTS:
A total of 877 patients were transported by EMS for suspected stroke. ICH was diagnosed in 50 (5.7%) patients. Median (IQR) time from symptom onset to first BP measurement was 82 (362) minutes. Mean prehospital SBP was 173 ± 32 mmHg. Median baseline hematoma volume was 31.8 (53.2) ml and median total ICH volume was 33.4 (58.1) ml. Mean prehospital BP was unrelated to hematoma volume (R=0.12, p=0.42) and total ICH volume (R=0.14, p=0.34). Mean prehospital SBP in patients with hematoma volumes <33 ml (169 ± 32 mmHg) was similar to those ≥33 ml (177 ± 32 mmHg, p=0.45). Similar results were found with 15 ml (p=0.82), 45 ml (p=0.52), and 60 ml (p=0.50) hematoma volume cutoffs. Mean prehospital SBP in patients with total ICH volume <33 ml was similar (168 ± 33 mmHg) to those ≥33 ml (177 ± 31 mmHg, p=0.39). IVH was present in 16 (32%) patients. The mean prehospital BP did not differ in patients with IVH (180 ± 27 mmHg) when compared to those without IVH (169 ± 34 mmHg, p=0.10).

CONCLUSION:
Prehospital BP is consistently high across different ICH volumes. Hematoma and total ICH volumes are independent of prehospital BP. These findings do not preclude a prehospital BP treatment effect.
Abstract W P326: Comparison of Spontaneous Intracerebral Hemorrhage Outcomes in Patients with Warfarin and Antiplatelet Medication Use
Authors: Murthy Santosh , Moradiya Yogesh , Dawson Jesse , Lees Kennedy , Hanley Daniel F , Ziai Wendy C
Published: July 2021

Background:
Use of antiplatelet medications and warfarin has been associated with poor clinical outcomes in spontaneous intracerebral hemorrhage (ICH). However, a head to head comparison between these groups has not been performed. We compared ICH outcomes among patients on these medications.

Methods:
In this cohort study, we analyzed 987 patients with ICH from the Virtual International Stroke Trials Archive. Patients with ICH presented within six-hours of symptom onset had baseline clinical, radiological data, and computed tomographic scan at 72 hours. Hematoma expansion was defined as interval increase in size by >33%. Main outcome variables were 90-day mortality, and modified Rankin Score (mRS) at 90 days dichotomized into 0-3 vs 4-6.

Results:
Of 987 ICH patients 154 had prior antiplatelet use, 30 had warfarin, and 803 had neither of the two medications. The warfarin group had significantly higher age (p<0.001) and higher prevalence of atrial fibrillation (p<0.001). Of the ICH characteristics, comparing warfarin, antiplatelet and no warfarin/antiplatelet cohorts, the warfarin group had lower Glasgow coma scale (GCS) scores (p=0.049), higher intraventricular hemorrhage (IVH) rate (p=0.010), and more hydrocephalus (p<0.001). Hematoma expansion at 72 hours was significantly higher with warfarin use (p=0.003), while the ratio of perihematomal edema volume to hematoma volume at 72 hours was lowest with warfarin use (p<0.001). In the logistic regression model adjusted for age, sex, race, hematoma volume, perihematomal edema, GCS, IVH and hydrocephalus; warfarin patients had significantly lower odds of achieving mRS 0-3 (OR: 0.23, 95% CI: 0.06-0.83, p=0.025), while the antiplatelet group had similar functional outcomes compared to no warfarin/antiplatelet use (OR: 0.75, 95% CI: 0.46-1.23, p=0.260). The 90-day mortality outcomes were not significantly different across the three groups (18.7% to 40.3%, p=0.520).

Conclusion:
Warfarin use is associated with a higher incidence of hydrocephalus, intraventricular hemorrhage and hematoma expansion, but lesser perihematomal edema relative to the hematoma volume. Warfarin associated ICH appears to be independently associated with worse functional outcomes but not with 90-day mortality in ICH.
Abstract W P332: Ratio of Blood Urea Nitrogen to Serum Creatinine Predicts Primary Intracerebral Hemorrhage Volume
Authors: Shiue Harn , Albright Karen C , Sands Kara A , Gadpaille Alissa , Boehme Amelia K , Khawaja Ayaz , Sisson April , Shahripour Reza Bavarsad , Harrigan Mark
Published: July 2021

Background&Purpose:
Dehydration is associated with poor outcomes in stroke patients. A common marker of hydration status is the calculated blood urea nitrogen (BUN) to serum creatinine (SCr) ratio. Few studies in primary ICH patients have focused on intravascular volume depletion and ICH volume. We examined if dehydration (BUN/SCr > 15) predicted admission ICH volume.

Subjects&Methods:
Consecutive patients (2008 – 2013) who presented with a spontaneous ICH to our academic stroke center in the Southeast US were retrospectively analyzed. Demographics, initial lab values, ICH volumes, and ICH scores were recorded. Patients with INR <= 1.5 were divided into two groups: BUN/SCr <= 15 and > 15. ICH volumes were compared between groups. Statistical significance was determined using linear regression adjusting for admission systolic blood pressure (SBP) and ICH score.
Results:
We identified 326 patients who met inclusion criteria (mean age 63; SD=15, 43% women, 45% black). Patients with ratio >15 were older (68 vs.60 years, p<0.001). In addition, a higher proportion were white (63% vs.40%, p <0.001) and female (56% vs. 36%, p<0.001). The average SBP on arrival was similar between groups (176 vs.181 mmHg, p=0.159). The average initial ICH volumes for those with BUN/SCr > 15 were higher than patients with BUN/SCr <= 15 (29.6 mL vs. 20.6 mL, p = 0.022). After adjusting for SBP and ICH score, patients with elevated BUN/SCr had an average of 9 mL larger ICH volumes on admission.

Conclusions:
Elevated BUN/SCr ratio is linked to larger initial ICH volumes even after controlling for ICH score and SBP. This simple ratio is an independent predictor of ICH volume, may reflect poor hydration status, and can potentially be used in the early evaluation and treatment of ICH patients. Future studies to determine if correction impacts functional outcomes are warranted.
Abstract W P333: Seizure as the Presenting Symptom of ICH Patient Characteristics and EEG Utilization
Authors: Arora Kanika , Gadpaille Alyssa , Albright Karen C. , Alvi Muhammad , Khawaja Ayaz , Shiue Harn , Sands Kara , Harrigan Mark
Published: July 2021

Background and Purpose:
Seizures are the presenting symptom in a significant number of patients with spontaneous ICH. The role of EEG in the routine evaluation patients, with or without clinical evidence of seizures, is unclear. This study was undertaken to better understand seizures and the use of EEG in patients with ICH.

Methods:
Retrospective review of consecutive spontaneous ICH patients at our institution from 2008-2013. Patients were considered to have a seizure on presentation if a clinical evidence of a seizure was documented in the medical record; EEG data was not required to confirm seizure on presentation. Demographics, vascular risk factors, ICH score, and EEG findings were assessed.

Results:
Of 402 spontaneous ICH patients (mean age 63, 42% black, 43% female), 10% presented with seizure. Patients presenting with seizure were younger (mean age 65 vs. 54, p<.001). Compared to patients with ICH presenting without a seizure, blacks presented more frequently with seizure (62% vs. 40%, p=.009). A higher proportion of patients who presented with seizure had a history of alcohol use (50% vs. 27%, p=.008) and substance abuse (23% vs. 10%, p=.025). Patients who presented with seizure more frequently had cortical ICH (54% vs. 32%, p=.007). EEGs were performed more frequently in ICH patients that presented with seizure (66% vs. 19%, p<.001). Among patients with an EEG, epileptiform discharges or rhythmic pattern was more common in patients who presented with seizure (30% vs. 10%, p=.040) and with a cortical ICH (29% vs. 9%, p=.036). There were no significant differences in the proportion of patients that received EEG based on race, history of alcohol abuse, or history of substance abuse.

Conclusions:
Patients who presented with seizure were younger, black, and a higher proportion had a history of alcohol and substance abuse compared to patients with ICH who did not present with a seizure. Only 66% of those presenting with clinical seizure underwent EEG. Despite the prevalence of subclinical seizures in ICH patients, only 19% of patients who did not present with a seizure underwent EEG. Our study suggests that there may be room for improvement on the part of stroke neurologists in the diagnosis and management seizure of ICH patients.
Abstract W P336: Sepsis in Intracranial Hemorrhage - Should We Be Bugged?
Authors: Rajagopalan Swarna , Ronca Richard , Azizi Ausim
Published: July 2021

INTRODUCTION:
Intracerebral hemorrhage (ICH) has the highest mortality rate of all stroke subtypes and accounts for 10-40% of all strokes. ICH patients are known to be at higher risk for infection and subsequent complications, however there is sparse data regarding the incidence of sepsis in critically ill patients with ICH. We hypothesize that the incidence of sepsis is high in ICH patients with terminal outcomes, and type of ICH would impact risk of developing sepsis.

METHODOLOGY:
A retrospective review was done of 200 patients with ICH admitted to an inner city hospital between June 1, 2013 and June 30, 2014. Inclusion criteria included patients with ICH and a terminal outcome, defined as death or comfort care as a result of their immediate condition. Exclusion criteria included patients with hemorrhagic infarcts, pre-existing conditions contributing to terminal outcomes, or conditions where ICH was a direct result of sepsis. ICH was subdivided into types: Spontaneous ICH (SICH), Subarachnoid Hemorrhage (SAH), Subdural Hematoma (SDH) and Intraventricular Hemorrhage (IVH). We collected age, sex, history of hypertension, location of ICH, evidence of sepsis, sever sepsis or septic shock, presence of intra-ventricular extension, volume of ICH, GCS, and calculated ICH score where applicable.

RESULTS:
Of 200 patients admitted with ICH, 22 patients had terminal outcomes (11.5%). Of the 22 patients, 8 had or were suspected of having sepsis (36.6%) of which three (37.8%) were due to pneumonia and in five, a source was not identified. Two of the patients had septic shock. Non-septic patients had worse ICH scores (3.42 vs. 2.88) than septic patients but this was not statistically significant. Non-septic patients had shorter lengths of stay (3.29 vs. 5.9, p=0.07). Sepsis was distributed evenly throughout various ICH types.

CONCLUSION:
The incidence of sepsis in ICH patients with terminal outcomes is high (36.6%) and increased to 50% in patients with a length of stay of at least 4 days. The primary source of sepsis was pneumonia; this can be used to target sepsis prevention in ICH patients in the future. Future studies need to be performed analyzing a larger sample size.
Abstract W P37: Accuracy Of CT Angiography In The Localization Of Carotid Occlusion Sites In Acute Ischemic Stroke
Authors: Rocha Marcelo , Delfyett William T , Aghaebrahim Amin , Jadhav Ashutosh , Jovin Tudor
Published: July 2021

Background and Purpose:
CT angiography yields rapid detection of a major cerebral vessel occlusion during the evaluation of patients with acute ischemic stroke leading to its widespread use in rapidly triaging for IA trial enrollment. In such trials, patients who have an extracranial carotid occlusion in tandem to the intracranial target lesion are typically excluded. However, ICA terminus occlusions may be misidentified as cervical carotid occlusions on CTA. The goal of this study is to determine the accuracy of CTA in identifying ICA terminus occlusions from tandem carotid occlusions (cervical and intracranial segments).

Methods:
Retrospective review of a prospectively maintained database containing patients treated at our comprehensive stroke center between 1996 and 2014 in whom catheter angiogram and CT angiogram were available on PACS. A Neuroradiologist, blinded to catheter angiographic results reviewed the CT angiography identifying the presence of intracranial stenoses and concomitant cervical carotid occlusions.

Results:
Of 196 patients presenting with intracranial carotid occlusions on catheter based angiogram, 101 patients were identified with good quality CT angiography and subsequent catheter angiograms. Mean ages for identified patients was 65 +/- 14, of which 52% women and 48% men. Forty-four percent of patients had an ASPECT score of 9-10. The overall rate of agreement between retrospective CTA and conventional angiography readings was 77%. Of 72 isolated intracranial occlusions on conventional angiography, CT angiography misidentified 23 cervical carotid occlusions. The sensitivity of CTA for detecting isolated carotid terminus occlusion was 68% in this cohort. Specific factors associated with CT and catheter based angiographic discrepancy are reviewed.

Conclusions:
The study raises systematic considerations for maximizing inclusion of patients with target arterial occlusions who are most likely to benefit from intra-arterial therapy in future clinical trials. Future steps will include determination of specificity, predictive value of CTA for localization of specific carotid occlusion sites. Clinical variables associated with lower CTA accuracy will also be examined.
Abstract W P40: Predicting Tissue at Risk for Infarction Within an Optimal Arterial Spin Labeling Cerebral Blood Flow Threshold in Patients with Acute Stroke
Authors: Niibo Takeya , Ohta Hajine , Yonenaga Kazuchika , Ikushima Ichirou , Miyata Shirou , Takeshima Hideo
Published: July 2021

Background:
and Purpose: The aim of this study was to investigate whether pseudo-continuous arterial spin-labeling (ASL) in combination with an appropriate cerebral blood flow (CBF) threshold can reliably detect tissue at-risk for infarction.

Methods:
The retrospective study included 50 patients with acute stroke in the middle cerebral artery (MCA) territory who underwent perfusion-weighted magnetic resonance imaging (PW-MRI) within 24 hr of symptom onset and again in the subacute phase. After image co-registration the core and mismatch were segmented on ASL maps. Receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal ASL-CBF threshold. Volumes on PW-MRI were recorded based on their ASL-CBF threshold (≧19-, 20-, 21-, 22-, 23-, 24- and 25 sec). Then the correlation between the penumbral salvage area and infarct growth, defined as the size difference between the lesion on baseline PWI- and the baseline diffusion-weighted images, and the final infarct volume were determined.

Results:
ROC analysis showed that the optimal threshold was 21.2 mL/100 g/min (area under the curve 0.88). The correlation between infarct growth and the penumbra salvage volume was significantly better for PWI lesions defined by ASL≦21 mL/100 g/min (r=-0.66; p<0.001). In 9 patients without recanalization on MRI obtained in the subacute phase, the ASL≦21 mL/100 g/min threshold more closely predicted the final infarct volume (r=0.82; p=0.006).

Conclusion:
PWI (ASL≧21 ml/100 g/min) volumes may provide an approximation of the volume of tissue at-risk for infarction in patients with acute stroke in the MCA territory.
Abstract W P400: Headache at the Onset of Anterior versus Posterior Circulation Ischemic Stroke
Authors: Cahill Caroline , Espaillat Kiersten , Gilchrist Emily , Froehler Michael
Published: July 2021

Background:
Past evidence suggests that there is a higher incidence of onset headache with posterior rather than anterior circulation stroke. We sought to further explore this connection in order to better understand the mechanisms underlying onset headache and to examine this symptom in relation to ischemic stroke.

Methods:
A retrospective chart review was conducted of 253 patients who presented to Vanderbilt University Medical Center in 2013 with ischemic stroke in either the anterior or posterior circulation. The significant difference between the incidence of onset headache in the anterior and posterior circulation territories was analyzed using a chi-squared test of independence. The frequency of onset headache was compared between the two groups, as well as between more specific locations within the posterior circulation and the middle cerebral artery (MCA).

Results:
A total of 48 (19%) of patients reported experiencing onset headache. Of those, 12 (25%) suffered a stroke in the anterior circulation, while 28 (58%) suffered a stroke in the posterior circulation (The remaining 8 were excluded due to multiple infarcts or poorly defined territories). Analysis was done comparing the MCA, the posterior cerebral artery (PCA), and the vertebrobasilar territories. The frequency of onset headache was 21% for vertebrobasilar stroke, 6.1% for MCA stroke, and 33% for PCA stroke. Compared to the other areas, PCA stroke showed a significantly higher rate of headache as a symptom at onset (χ
2
= 18.60, p < 0.001, ϕc = 0.312). Furthermore, 20 (42%) of the 48 patients in this study who had reported onset headache were found to have suffered ischemia of the thalamus.

Conclusions:
Patients who suffered a stroke in the PCA territory were more likely to have experienced a headache at stroke onset. Given the rich blood supply to the thalamus from the posterior circulation, an additional mechanism linking ischemic stroke in the PCA to thalamic pain pathways should be further scrutinized as a possible cause for onset headache.
Abstract W P407: Shear Stress and Co-culture with Astrocytes Determine Brain Microvascular Endothelial Cell Phenotype
Authors: Salehi Omran Sina , Garcia Polite Fernando , Edelman Elazer , Balcells-Camps Mercedes
Published: July 2021

Introduction:
Dementia has classically been identified to be of either vascular or neural origin. These domains overlap and are complementary, thus we consider dementia a disease of the single cerebrovascular unit. Our objective was to generate a modular platform for co-culture of brain microvascular endothelial cells and astrocytes that also incorporates mechanical stresses, and to then use this model of the cerebrovascular unit microenvironment to study the unit
in vitro
.

Hypothesis:
We assessed the hypothesis that endothelial health and blood-brain barrier integrity are modulated by shear stress and co-culture with astrocytes.

Methods:
We lithographed polydimethylsiloxane substrate on Teflon negative molds with subjacent rectangular channels of 0.45 and 2 mm depth for seeding of human brain microvascular cells and astrocytes, respectively, separated by a polytetrafluoroethylene (0.45 μm pore size) membrane under no flow or physiologic flow (6.2 dynes/cm
2
) for one week. Immunocytochemical staining for glial fibrillary acidic protein and CD31 was simultaneously visualized by confocal microscopy. Cells from each channel were detached via trypsinization, and expression of transport proteins P-glycoprotein (P-gp) and glucose transporter-1 (GLUT-1), in addition to junction proteins zona occludens-1 (ZO-1) and CD31, was measured by Western Blot.

Results:
We stably co-cultured brain microvascular endothelial cells and astrocytes with no chamber leakage or mixing. CD31 staining revealed endothelial cell alignment to direction of flow. Expression of ZO-1 by endothelial cells increased in presence of flow and co-culture independently, by 1.6-fold in combined conditions relative to static monoculture (p<0.05). For P-gp, the increase in combined conditions was 5.5-fold (p<0.05). GLUT-1 and CD31 levels did not change significantly with co-culture or flow.

Conclusion:
Cell biology devoid of microenvironmental cues provides limited insight, especially when considering whole tissues, on the impact of disease. A co-culture system that introduces multiple cells, flow, controlled stress and independent visualization and sampling of each cell domain adds deeper understanding and greater value to
in vitro
biological models and tissue biology.
Abstract W P415: A Comparison between Fasudil and Simvastatin Treatment in Two Murine Models with Cerebral Cavernous Malformation
Authors: Shenkar Robert , Shi Changbin , McDonald David , Austin Cecilia , Rorrer Autumn , Gallione Carol , Zhang Lingjiao , Marchuk Douglas , Awad Issam
Published: July 2021

Objective:
To compare therapeutic effect on cerebral cavernous malformation (CCM) genesis and maturation of fasudil (specific RhoA kinase inhibitor) and simvastatin (with pleiotropic effects including Rho inhibition) in two heterozygous murine models.

Methods:
The murine models

Ccm1
+/-
Msh2
-/-

and

Ccm2
+/-
Trp53
-/-

were treated from weaning to 5 months of age with fasudil (100 mg/kg/day administered in drinking water), simvastatin (40 mg/kg/day administered in chow) or with placebo. Brains were removed, fixed, embedded and blindly analyzed for lesion count and size, and for iron leak by Perls staining.

Results:
Fasudil, but not simvastatin, improved survival in

Ccm1
+/-
Msh2
-/-

mice (
P
=0.05). Both drugs did not affect attrition in

Ccm2
+/-
Trp53
-/-

mice. Fasudil decreased mature CCM lesion burden and total lesional area per animal in

Ccm1
+/-
Msh2
-/-

mice (
P
=0.007,
P
=0.18, respectively), more in males (
P
=0.04,
P
=0.05, respectively) than in females (
P
=0.10,
P
=0.81, respectively) when compared to mice given placebo. In the same model, simvastatin decreased total lesion count less significantly (
P
=0.09), with no decrease in lesional area. Integrated iron density per area of CCM lesions was decreased in mice treated with fasudil (
P
<0.01) or simvastatin (
P
=0.09) compared to mice given placebo. In contrast, both fasudil and simvastatin treatment of

Ccm2
+/-
Trp53
-/-

mice (with less aggressive phenotype) did not significantly affect attrition, lesion count or lesional area. No decrease in iron density was observed in

Ccm2
+/-
Trp53
-/-

mice given fasudil.

Conclusions:
The ROCK inhibitor fasudil was more efficacious than simvastatin in the longitudinal treatment of

Ccm1
+/-
Msh2
-/-

mice, decreasing lesion formation, maturation, and iron leak. The favorable, although weaker benefit of simvastatin, including decreased iron leak, would suggest a need for higher statin dose to accomplish a same effect as fasudil. There was no effect by either drug in

Ccm2
+/-
Trp53
-/-

mice, likely in part because of milder phenotype in this model. Treatment with higher statin dose and effects on more aggressive

Ccm3
+/ -

models are being assessed in ongoing research.
Abstract W P416: Outcomes following Microsurgical Resection of Intracranial Arteriovenous Malformations previously treated with Stereotactic Radiosurgery
Authors: Choudhri Omar , Gupta Mihir , Chang Steven , Levy Richard , Do Huy , Marks Michael , Steinberg Gary
Published: July 2021

INTRODUCTION:
Large and complex intracranial AVMs can be challenging to treat and may require a multimodality strategy. The success rates of stereotactic radiosurgery alone for large and deep intracranial AVMs is only 25-50%. Many of these previously irradiated AVMs, with or without embolization may require additional treatment. This study hypothesizes that prior remote radiation therapy can aid microsurgical resection of lesions to achieve cure.

METHODOLOGY:
This retrospective study utilized the Stanford AVM database, to identify 92 patients treated with microsurgery after prior radiation between 1990-2014. A total of 84 patients with complete data were used for this study.

RESULTS:
Patients were 7 to 64 years old (mean 33), and underwent microsurgical resection 6 mos-11 yrs after radiosurgery. Sixty-nine patients (82%) underwent endovascular embolization prior to surgery. Initial AVM volumes were 0.6-117 cm3 (mean 21). Radiation doses were 4.6-45 GyE (mean 21.5). Seventy-three AVMs (87%) were located in eloquent or critical areas. Venous drainage was deep in 28, superficial in 32 or both in 20 lesions. Spetzler-Martin grades were I (4%), II (12%), III (31%), IV (39%) and V (14%). Prior to surgery, twenty-one patients (25%) experienced hemorrhage in a delayed fashion following radiation or embolization, while 14 (17%) developed radiation necrosis. At surgery AVMs were partially thrombosed, markedly less vascular, and more easily resected than if the patient had not received radiosurgery. Blood loss was minimal and the radiosurgery transformed difficult AVMs into easily resectable ones. Despite persistent angiographic AVM filling, much of the small-vessel component was obliterated by the radiosurgery. Complete AVM resection was achieved in 71 (85%) of cases. Five patients (6%) died of delayed re-bleeding from residual AVM following deliberate subtotal surgical resection. Over a mean follow-up of 24 months, clinical outcome was excellent in 33%, good in 48% and poor in 11%.

CONCLUSIONS:
Stereotactic radiosurgery several years prior to microsurgical resection is a useful adjunct for treating large and complex intracranial AVMs. Excellent or good clinical outcome can be achieved in most patients using this multimodal therapy.
Abstract W P48: Flair Vessel Hyper-intensities Could Predict Target Mismatch Signs in Acute Stroke Patients
Authors: Inoue Manabu , Mlynash Michael , Cerada Carlo W , Mishra Nishant K , Christensen Soren , Straka Matus , Kemp Stephanie M , Ichikawa Hiroo , Bammer Roland , Lansberg Maarten G , Albers Gregory W
Published: July 2021

Background and purpose:
Fluid-attenuated inversion recovery (FLAIR) vessel hyper-intensities (FVH) have been hypothesized to have a positive correlation with good collaterals and more favorable clinical outcomes in acute stroke patients. We assessed if FVH predict the Target mismatch profile (TMM) and clinical outcomes in the DEFUSE studies.

Methods:
Patients with technically adequate baseline diffusion weighted images (DWI), perfusion images (PWI), and FLAIR images were included in this pooled analysis of the DEFUSE 1 and 2 studies. The FVH sign was defined as visible hyper-intense vessels on FLAIR images and assessed at basal ganglia levels by two independent raters. Clinical outcomes were assessed using modified Rankin Scale (mRS) at 90 days. The Target mismatch profile was based on baseline DWI and PWI volumes using automated software (RAPID).

Results:
Seventy seven patients met the inclusion criteria. Median time (IQR) from symptom onset to baseline MRI was 4.6 hours (3.9 - 5.4) and median (IQR) DWI lesion was 13.1 (5.0 - 32.0) ml. Of these, 66 patients (86%) had the FVH sign. Kappa score for inter-rater agreement was 0.621 (95CI: 0.33 - 0.91). Seventy (74%) cases with FVH had TMM profile vs. 33% of No FVH patients (p=0.023). Good clinical outcome (mRS 0-2) did not differ (50% with FVH vs. 73% without FVH, p=0.203). Only 38% of the patients with FVH had good angiographic collaterals and the rate of early reperfusion did not differ (45% with FVH vs. 25% without FVH, p=0.45).

Conclusions:
FVH is common in acute stroke patients (86%) and is associated with the Target Mismatch profile. However, FVH was not associated with favorable angiographic collaterals, good clinical outcome or early reperfusion in the DEFUSE 1 and 2 cohorts.