bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3665: COL4A1 and COL4A2 Mutations cause Genetically Modifiable Cerebrovascular Diseases
Authors: Jeanne Marion , Weng Yi-Chinn , de Leau Michelle , Labelle-Dumais Cassandre , Kauffman Berkeley W , Greenberg Steven M , Rosand Jonathan , Gould Douglas B
Published: July 2021

Mutations in the type IV collagen alpha 1 gene (COL4A1) cause Cerebrovascular Diseases (CVDs) in mice and human patients. Patients with COL4A1 mutations suffer from a broad range of CVDs, from infantile porencephaly to debilitating or fatal intracerebral hemorrhage (ICH), to subclinical cerebral microbleeds, suggesting that environmental and other genetic factors may influence their phenotypes. COL4A1 is one of the most abundant proteins in basement membranes and forms heterotrimers with COL4A2. Among possible pathogenic mechanisms are cellular stress due to the toxic intracellular aggregation of the COL4A1 and COL4A2 proteins and/or their absence in the basement membrane. Our first goal is to identify the relative contributions of COL4A1 and COL4A2 mutations to sporadic ICH and to understand the cellular mechanisms and genetic complexity underlying the disease. We identified novel COL4A1 mutations and for the first time, we discovered COL4A2 mutations in a cohort of 96 patients with sporadic ICH. Using a cell-based assay we determined that the mutations impair COL4A1 and COL4A2 secretion. We showed that mutant COL4A1 or COL4A2 proteins accumulate within the cell where they titrate normal COL4A1 and COL4A2 proteins. Interestingly, we found that some of the mutations can ultimately result in endoplasmic reticulum (ER) stress and activation of the Unfolded Protein Response. Our second goal was to test the hypothesis that differences in genetic context could contribute to phenotypic variability in human patients. Thus, we characterized CVD in Col4a1 mutant mice with two different genetic backgrounds. Using cerebral magnetic resonance imaging and histological analysis, we show that one or more genetic modifiers from the CAST/EiJ strain significantly reduce the size and frequency of ICHs detected in Col4a1 mutant mice on a C57BL/6J background. In conclusion, we found that both COL4A1 and COL4A2 mutations cause ICH in human patients, our results support that ER stress could be involved in the pathogenesis and we showed that genetic context is crucial for expressivity and severity of the CVD. We predict that ongoing experiments to better understand the cell biology of COL4A1 and COL4A2 mutations and the mechanisms of genetic modification could lead to targeted therapeutics to reduce the risk of CVD in patients with COL4A1 or COL4A2 mutations.
Abstract 3670: Lean Manufacturing Process Improvement Methods Accelerate and Simplify Transfer of Patients to a Comprehensive Stroke Center
Authors: Spencer Mary , Van Stavern Renee B , Panagos Peter , Ford Adrienne , Hoff Brian , Glovers Gwendolyn , Adams-Robinson Mae , Ray Zack , Bucelli Robert , Ushe Mwiza , Zipfel Gregory , Lee Jin-Moo
Published: July 2021

Background and Purpose:
Acute therapies offered at comprehensive stroke centers require the rapid transfer of stroke patients from outlying hospitals. Here, we describe the application of Lean manufacturing process improvement methods to stroke care in order to accelerate the transfer of patients from outlying hospitals.

Methods:
A multidisciplinary team of Stroke Neurologists, Vascular Neurosurgeons, ED Physician, Call Center staff and Lean Performance Management Engineers critically evaluated the chain of events required to accept a patient for transfer from outlying hospitals. Barriers and inefficiencies were identified in a “current state” Value Stream Map (VSM). A “future state” VSM created a new process for stroke patient transfer by overcoming the identified barriers and was implemented in March, 2011. Metrics were prospectively collected for a 4-month period prior to (7/1/10-10/30/10) and after implementation of the “future state” VSM (3/1/11-6/30/11), and included: mean time from call start to physician acceptance, percent of calls resulting in acceptance of patients within 15 minutes, total number of patients accepted within 15 minutes over 4 months, and total number of calls. Student’s T-test was used to compare means, while Chi-square test was used to compare ratios.

Results:
Identified barriers to rapid acceptance of patients included: 1) inefficient distribution of cases between services (neurology vs. neurosurgery); 2) calls frequently transferred from one physician to another on other services; and 3) lack of available beds resulting in acceptance delays. To overcome these inefficiencies, a new process was created with the following changes: 1) alternating call coverage shared between neurology and neurosurgery; 2) immediate acceptance of the patient with behind the scenes patient allocation to appropriate service; 3) direct involvement of patient placement services in transfer process. Mean time to acceptance decreased significantly from 14 min prior to new protocol implementation to 9 minutes (p< 0.03). The total number patients accepted within 15 minutes increased from 186 to 307 during this 4-month period. Percent accepted within 15 minutes also increased from 73% to 92% (p<0.0002). In addition, the rate of patient calls (#calls/month) increased after new protocol implementation (see
table
).

Conclusions:
Lean manufacturing process improvement tools are effective in designing hospital and physician work flow to help improve stroke care. Such practices require a collaborative approach including all parties involved in the process.
Abstract 3725: Contrast Enhanced MRI with a Reduced Dose of Gadolinium for Measurement of Blood to Brain Influx Rate in Cerebrovascular Diseases
Authors: Taheri Saeid , Rosenberg Gary A
Published: July 2021

Dynamic Contrast-Enhanced MRI with a Reduced Dose of Gd-DTPA for Measurement of Blood-to-Brain Influx Rate in Cerebrovascular Diseases
In vivo
quantification of blood-to-brain transfer rate is of immense importance in diagnosis and monitoring cerebrovascular damages after stroke. Dynamic contrast-enhanced (DCE) methods in CT and MR have been used to collect data about the health of blood-brain barrier (BBB). However high dose of radiation in CT and high dose of contrast agent and long protocol time in MR limit the application of DCE methods in acute stroke imaging. The goal of this study was to investigate DCEMRI with a reduced dose of Gd-DTPA and reduced acquisition time for BBB quantification. Fifteen healthy subjects (23-85 years, 9M, 6F) were randomly divided into 4 groups. Each group received one of 4 different doses of Gd-DTPA (group I, 0.1mmol/Kg, n=4; group II, 0.05 mmol/Kg, n=4; group III, 0.025mmol/Kg, n=4; and group IV, 0.0125 mmol/kg, n=3) for DCEMRI. The MRI data acquisition was performed using a 1.5-Tesla Siemens whole-body scanner with a standard eight-channel array headcoil. Fast T1 sequence, TAPIR, was used to estimate the time-concentration of different doses of Gd-DTPA after IV bolus injection. In addition clinical laboratory data of time-dependent concentration of Gd-DTPA in plasma was obtained from contrast agent manufacturer. Clinical and MR-based data were analyzed for 1) nonlinearity effect of contrast on MR signal and 2) evaluate the percentage of MR sampling error. The reduced dose of Gd-DTPA was used to quantify the BBB transfer rate in 14 MS and 9 cerebral cavernous malformation patients recruited from other studies. Comparison of pharmaco dynamics of Gd-DTPA over a range of different initial doses (less than 0.1 mmol/Kg) shows that 1/4 of the standard dose renders less error in T1 sampling and provides a sufficient dynamics in the intensity of MR signal to achieve a shorter DCEMRI experiment. In comparison to the regular Gd-DTPA-enhanced images, the reduced dose of Gd-DTPA used in DCEMRI is more sensitive in BBB abnormality detection. Comparison of 4 different doses of Gd-DTPA showed that a dose of 25% of 0.1 mmol/Kg, when using a fast T1 mapping protocol, is optimal for BBB permeability quantification in patients. DCEMRI-based BBB influx rate measurements with reduced dose of contrast agent may offer a suitable and less risky biomarker for disease progression and drug trials. Imaging stroke; Left panel represent FLAIR anatomical image of patient with stroke. Right panel represents BBB transfer rate map.
Abstract 3736: Applying the Carotid Atherosclerosis Score in a Clinical Environment: a Feasibility Study
Authors: Xu Dongxiang , Sun Jie , Song Yan , Hippe Daniel S , Chen Min , Zhou Cheng , Yuan Chun
Published: July 2021

Background
Carotid atherosclerosis is a leading cause of stoke. Recent studies have shown that its severity can be stratified by the Carotid Atherosclerosis Score (CAS) as measured by MRI. However, these studies were performed using customized imaging sequences, coils and comprehensive plaque analysis by specialized human reviewers, which are not generally available in a clinical environment. Whether CAS can be applied for clinical risk assessment is unknown. In this study, we used clinically collected MRI data to compute CAS. We investigated the correlation between CAS and the prevalence of neurological symptoms and disrupted luminal surface (DLS), an indicator of plaque instability, to evaluate the feasibility of translating CAS for clinical use.

Methods
Seventy six patients with either symptomatic or asymptomatic carotid disease detected by ultrasound were recruited. All patients underwent a multi-contrast MRI with clinical sequences and a commercially available coil. The lumen and outer wall boundaries and DLS were outlined manually and the plaque components were identified automatically using histologically validated image analysis software. The maximum wall thickness (MWT) and maximum % area (100 x area/[wall area]) of lipid-rich necrotic core (LRNC) were outputted by the software to compute CAS as follows: CAS=1 with MWT<2.0mm, CAS=2 with LRNC<20%, CAS=3 with LRNC between 20% and 40% and CAS=4 with LRNC>40%. Trend analysis was done to evaluate the associations between CAS and prevalence of symptoms and DLS. The area under the receiver operating characteristic (ROC) curve was used to evaluate the classification performance of CAS.

Results
Of the 76 patients, there was a significant increasing trend (p=0.01) between CAS scores and neurological symptom status. The presence of DLS also demonstrated a significant increasing trend (p<0.001) versus CAS with rates 0% (0/7), 7% (2/27), 35% (7/20) and 59% (13/22). ROC analysis of CAS also showed it was a good classifier of symptom status (AUC = 0.67, p=0.01) and DLS (AUC = 0.80, p<0.001)

Conclusion
In this study, we conclude that the CAS computed from clinically collected MRI data can stratify the severity of carotid atherosclerotic disease as indicated by neurological symptom status and DLS, both of which are important in monitoring patients and evaluating treatment options. Further study is needed to assess how a fully automated CAS analysis affects the quality of the score and how well the score can stratify the risk of future outcomes.
Abstract 3742: Downstream Toll-like Receptor (TLR) Signaling Modulates The Acute Stress Response To Focal Cerebral Ischemia
Authors: Famakin Bolanle M , Mou Yongshan , Johnson Kory R , Hallenbeck John M
Published: July 2021

Background:
The Toll-like receptor (TLR) signaling pathway plays an important role in the innate immune response to a number of inflammatory conditions and in the innate immune response to ischemia. However, the downstream TLR signaling events that occur during focal ischemia remain poorly understood. We thereby sought to determine the gene expression profile in the brains of MyD88-/- and TRIF mutant mice following focal cerebral ischemia.

Methods:
Wild type (WT) mice and mice with disruptions of either MyD88 (MyD88-/-) or TRIF (TRIF mutant) were subjected to permanent Middle Cerebral Artery Occlusion (pMCAO). Total RNA was extracted from brain homogenates from 9 mice per group;3 mice per baseline (without surgery),3 and 24h following focal ischemia. Gene profiling of baseline and ischemic brain cortices was assessed by Affymetrix microarrays and confirmed by Real-time Polymerase Chain Reaction (RT-PCR). Ingenuity Pathway Analysis (IPA) was used for functional analyses of microarray data.

Results:
A total of 1,833 gene fragments, representing 754 known genes, were significantly differentially regulated following ischemia. IPA functional analyses suggested the association of differentially expressed genes with the acute stress response. RT-PCR confirmed the differential expression of acute stress response genes such as NR4A1 (Nur77), Activity-related Cytoskeleton-associated protein (ARC) and zinc finger transcription factors such as Early Growth Response (EGR) 1 and 2, following focal cerebral ischemia. Expression of these acute stress response elements was increased in the brains of WT mice, but were either unchanged, non-significantly increased or decreased with ischemia, in mice with disruptions of either MyD88 or TRIF. Importantly, these findings were associated with significantly increased expression, at baseline, of these acute stress response elements, such as EGR2, in mice with disruptions of MyD88 (9.7-fold; p=0.027) and TRIF (8.3-fold; p=0.015), compared to baseline WT mice. Interestingly, levels of zinc metallopeptidases such as Insulin-degrading enzyme (IDE), important in clearing of amyloid in the brain, known to be modulated by ischemia, were significantly decreased from baseline following focal ischemia in mice with disruptions of MyD88 or TRIF compared to WT mice.

Conclusions:
We describe a novel role of the MyD88 and TRIF TLR signaling pathways in modulating the acute stress response to ischemia. These downstream elements may also be involved in regulating the expression of enzymes such as IDE, thereby linking these downstream TLR pathways to the clearance of amyloid in the brain. Finally, the aberrant up-regulation, at baseline, of elements related to the acute stress response in mice with disruptions of MyD88 and TRIF, implicates these downstream TLR pathways in the optimal response to ischemic stress and probably also to other types of cellular stress.
Abstract 3763: Impact Of Race And Ethnicity On Stroke Risk Factors And Care: Echocardiographic Risk Stratification And Discharge Disposition
Authors: Lee Jessica D , Upreti Bhim , Pezzullo John C , Hodics Timea
Published: July 2021

Background:
Hispanic Americans (HA) and African Americans (AA) are known to have greater incidence of stroke and may have more severe deficits than non-Hispanic whites (NHW). AA and HA are known to have higher incidences of hypertension compared to NHW. Little has been published on the use of echocardiography to determine racial and ethnic distribution of risk factors Recently published information indicates that while minorities have equal access to rehabilitative services, minorities with stroke have longer hospital stays and poorer functional outcomes compared to NHW, leading to potential increased healthcare needs post-discharge.

Hypothesis:
We hypothesize that HA and AA are more likely than NHW to have evidence of hypertensive pathology on echocardiographic evaluation. We further hypothesize that HA, due to social and cultural differences, are more likely to discharge home and less likely than AA and NHW to utilize skilled nursing facilities (SNF) or long term acute care facilities (LTAC).

Methods:
We conducted a retrospective chart review of patients at a single institution with a diagnosis of TIA, ischemic or hemorrhagic stroke admitted from January 2004 to January 2007 (N=1480). Demographic information, co-morbid conditions, diagnostic test results, and information regarding discharge were collected. We used descriptive statistics to characterize the groups, and association between ethnicity and echocardiogram evaluation and discharge disposition was tested by Chi-square analysis.

Results:
TTE and TEE were used equally across ethnic groups. AA had more evidence of hypertensive pathology on echocardiographic imaging compared to NHW and HA (95% vs. 43% and 40%, respectively, p<.001). Unexpectedly, HA were more likely to have potential embolic sources found on echocardiographic studies compared to NHW or AA (68% vs. 38% and 44% respectively, p<.001). HA were less likely to discharge to SNF or LTAC compared to NHW or AA (2% vs. 7% for both NHW and AA, p<.001). There was no difference in the likelihood of discharge to SNF or LTAC between AA and NHW.

Conclusions:
HA have more embolic sources as a potential cause for stroke compared to either NHW or AA. This may have impact on the diagnostic utilization of TTE and TEE. Hypertensive echochardiographic changes are common in AA, emphasizing the need for primary prevention. HA are more likely to discharge home, rather than to a SNF or LTAC facility. This finding may indicate a need for additional home care services and education regarding home care of stroke patients for this population.
Abstract 3775: Education to Reduce Stroke Risk in Prediabetic Patients
Authors: Jackson Nancy , Ruhmann Christy
Published: July 2021

Background:
Diabetes is a known risk factor for stroke. We sought to assess the reduction of secondary complications of diabetes in stroke patients through an education initiative. We identified prediabetic pts as a group not receiving any instruction in glucose control to prevent diabetes.

Methods:
At our private, community health center, we introduced a pilot education program for all ischemic stroke and transient ischemic attack patients from March to July 2011. Patients were included if they tolerated oral diet and were placed on the stroke protocol at our center. Patients were identified by a certified dietician and divided into two groups: HbA1c ≤ 6.4% and HbA1c > 6.4%. Patients with an HbA1c of 5.8 -6.4% (prediabetics) were placed on a calorie controlled diet and received diet and activity education from the dietician. Meters were available for them to take home if they desired. Patients with an HbA1c greater than 6.4% received diet and activity education, and also met with the diabetes nurse educator for more in depth education on controlling their diabetes. Our endpoint was to increase the number of patients receiving diabetic education.

Results:
The program saw 214 patients, and education was provided to 81 prediabetics and 51 diabetics. In the first 4 months of the pilot program, 76% of prediabetics and 71% of diabetics received education. Limitations to education included pts not on stroke protocol so HbA1c was not ordered, difficulty getting orders for calorie controlled diet, and difficulty placing order for Diabetes Educator. By month 5 only 1 pt did not receive education and 5 had not had HbA1c drawn to assess need for education.

Conclusion:
Education of glucose control strategies for prediabetic and diabetic stroke pts has been effectively initiated. The large population of prediabetic pts has received education to begin to reduce their risk of developing diabetes in the next 3-5 years. Patient feedback has been entirely positive at this time. Future evaluation to determine if pts with prediabetes were able to delay onset of diabetes and reduce development of future stroke would be beneficial.
Abstract 3807: Threshold Effects on Language Lateralization
Authors: Young Brittany M , Nair Veena A , Radtke Andy , Pankratz Joshua , Holdsworth Ryan , Baniulus Dovile , Konder Nicole , Voss Jed , Gallagher Tom A , Moritz Chad , Meyerand Beth , Prabhakaran Vivek
Published: July 2021

Background:
Vascular lesion patients may have atypical language networks (Vikingstad et al. 2000). When evaluating language function in vascular lesion patients, the threshold of significance at which functional activations are analyzed may lead to differences in the lateralization index (LI) calculated. We examine the effect of various thresholds on language LIs in vascular lesion patients and control subjects. We further aim to compare language LIs in these two groups and to analyze patient LIs for correlations with lesion activation distance (LAD).

Methods:
Structural and functional images were collected from 29 vascular lesion patients and 14 normal controls while they performed language tasks in the scanner such as word generation and text comprehension. Left Hemisphere, frontal lobe (Broca’s), and temporal lobe (Wernicke’s) masks as well as masks of their homologous counterparts were created based on the language network identified in a meta-analysis of language studies by Vigneau et al. 2006. LI was calculated for each subject for each task on which data was acquired using each of the six masks at four different thresholds of statistical significance. Patient LIs were further analyzed for correlations with LAD to Broca’s and Wernicke’s areas.

Results:
Vascular lesion patients tend to display bilateral or left-lateralized language functions. At the group level, increasing threshold value tended to shift LIs toward left-lateralization. Relative to controls, patients with vascular lesions appear to lateralize language functions necessary for word generation to a lesser degree, which was trending toward significance. Pooled data from visual receptive language tasks shows association between computed LI values for the frontal lobe and Wernicke's LAD, which was significant at lower thresholds.

Conclusions:
Variable thresholding may cause reclassification of some patients based on LI, and higher thresholds tend to shift LI towards left-lateralization. The association observed between frontal lobe LI values and LAD to Wernicke’s area suggest that for these patients LAD to Wernicke’s may be a significant factor in lateralization at lower thresholds. These factors may be important if using LI in presurgical planning. Differences in the degree of lateralization between vascular lesion patients and controls may be due to long-term brain reorganization.
Abstract 3815: Relationship Between Sleep Duration And Functional Outcomes In Patients With Ischemic Stroke - A New Factor To Think About
Authors: Katzan Irene , Bae Charles , Uchino Ken , Gebel James , Thompson Nicholas
Published: July 2021

Introduction:
Sleep duration has been associated with an increased risk of mortality, but there is little data on the impact of sleep duration on functional status and health-related quality of life (hrQoL) in the stroke population. We explored the relationship of sleep duration with hr-QoL and functional status in ischemic stroke patients being seen in cerebrovascular outpatient clinics.

Methods:
The Cleveland Clinic Cerebrovascular Center collects patient-reported and provider collected clinical information in all patients seen in the ambulatory clinic beginning Jan 2009 and included the EuroQol (EQ-5D) (generic hrQOL scale) - the Patient Health Questionnaire 9 PHQ9 (depression screen) and the Stroke Impact Scale 16 (disability scale), NIHSS, and Rankin. Sleep time categories were defined as: short sleep - 9 hours per night, normal sleep - 6-9 hours per night. We analyzed data from the first visits of patients with diagnosis of ischemic stroke seen between Dec 13, 2010 to June 30, 2011. Factors associated with sleep duration were assessed using multinomial regression with sleep duration category serving as the dependent variable. To explore the relationship of sleep duration with functional status, sleep duration was entered as a covariate in linear regression analyses along with demographics, stroke mechanism, days since stroke, marital status and NIHSS score.

Results:
Mean age of the 1,246 patients was 59.1 yrs (SD 14.6) and 54.6% were female. Black race was associated with short sleep duration (p=.0053). Several factors were associated with long sleep duration including: black race (p<0.0001), single status (0=0.0058), mechanism small vessel occlusions (<0.0001) and cryptogenic embolism (p <0.0001). Short and long sleepers had significantly greater depression severity and lower quality of life compared to those with normal sleep duration, as indicated by higher scores on the PHQ-9 ( 7.0 short, 12.1 long vs 4.3 normal, p<0.0001) , and lower scores on the EQ-5D (0.71 short, 0.65 long, 0.80 normal, p< 0.0001). Similarly, short and long sleepers had higher disability as defined by SIS16 (78.7 short , 70.5 long vs 83.8 normal, p=0.0002) than those in the 6-9 hr rage. This remained significant in the long sleeper group after adjustment for multiple factors.

Conclusion:
Short and long sleepers have a lower quality of life and higher rates of disability. Sleep duration, especially longer sleep times, may be a relevant factor in outcomes after stroke and merits further evaluation.
Abstract 3818: Reasons To Withhold Anticoagulation In Atrial Fibrillation Subjects After Ischemic Stroke
Authors: Kiernan Terri E , Coull Jesse D , Lendzion Nadine , Lee-Iannotti Joyce , Capampangan Dan J , Demaerschalk Bart M , Dodick David W , Ingall Timothy J , Vargas Bert B , Aguilar Maria I
Published: July 2021

Background:
Atrial fibrillation (AF) is an important modifiable and independent risk factor for stroke. AF is associated with 2-4% annual risk for first time stroke and about 8% annually for recurrent stroke. Anticoagulant therapy reduces the risk by 60%, while the relative risk reduction (RRR) obtained from antiplatelet therapy is only 20%. The effect is more robust for secondary than for primary prevention. Risk stratification schemes are utilized to assess an individual’s risk of future stroke and to determine the optimal antithrombotic or anticoagulation regimen for stroke prevention. Despite Warfarin’s superiority over antiplatelet therapy to reduce the risk of AF related systemic embolism, Warfarin is largely underutilized. The aim of this study was to determine the frequency and reasons behind withholding anticoagulation in patient with AF related cardioembolic stroke in our institution.

Method:
We extracted patients from our Get With The Guideline’s (GWTG) database who were admitted to Mayo Clinic AZ between January 2004 and December 2009. Two authors (TK and NL) independently identified all patients with the diagnosis of atrial fibrillation who were not prescribed Warfarin therapy upon discharge, then reviewed to identify the reason(s) why anticoagulation was not initiated. Factors such as discharge disposition (home, acute rehabilitation, long term nursing facility, hospice, other) and functional status (able to ambulate independently, with assistance, unable to ambulate, or not documented) were also assessed to help support the decision process.

Results:
From a total of 1295 patients, 305 with AF were identified. Patients who expired 48 (3.7%) from un-related causes were excluded. Of the 257 patients, 206 (80.2%) were anticoagulated and 51 (19.8%) were not anticoagulated. We found that in the anticoagulated group, patients discharged home were more likely to receive anticoagulation (89.2%), followed by those discharged to acute rehabilitation and skilled nursing facilities (77%). Those discharged to hospice were the least likely to receive anticoagulation (6.4%). In addition, patients with greater functional ability were also more likely to receive anticoagulation (independent 89.8%, vs. assisted 76.7%, vs. non-ambulatory 33.3%; p<0.0001). Reasons to withhold anticoagulation therapy at discharge included terminal illness/comfort measures only (40.0%); risk/discomfort due to bleeding (24%); risk of falls (13.0%); and patient refusal (9.0%).

Discussion:
Based on the results, we conclude that functional status and disposition at discharge are significant factors influencing the decision to anticoagulate after cardioembolic stroke attributed to AF.
Abstract 3839: Obtaining Systematic Neurologic Follow-up after Stroke Discharge - Is it possible?
Authors: Katzan Irene , McNeil Julie , Morton Johanna , Winfield Michelle , Dopler Chris , Speck Micheal
Published: July 2021

Background:
Systematic follow-up after hospital discharge for stroke is an important part of optimizing transitions of care, although its feasibility is not well known. Advances in healthcare technology provide a means to accomplish this.

Methods:
The Cleveland Clinic Neurological Institute implemented a technology-based follow-up system for patients hospitalized on the Stroke service. The system includes two major components to assist with follow-up: an electronic health record-based method for physicians to order a 30 day follow-up appointment electronically during patients’ admissions (similar to ordering a lab test), and system-generated messages that are sent to a nursing pool in cases where patients either do not have a scheduled appointment or their appointment was not kept. These activities are also monitored with standard reports. In addition, structured templates were developed to allow discrete capture of clinical data at the time of follow-up. Data on stroke patients from the first 15 months were analyzed after excluding patients who died prior to discharge or were discharged to hospice care.

Results:
Of the 574 patients in the study, from 3/2010 - 6/2011, 42.9% were discharged to home and 57.1% were discharged to other facilities. The rate of scheduled follow-up appointments within 45 days of discharge was 31.6% at baseline, although many of those were scheduled post-discharge. Successfully completed follow-up appointments within 45 days occurred in 10.5% at baseline and increased steadily over the 15 month period to 58.1% in June 2011 (see Table). Patients discharged to home had higher rates of completed follow-up compared to patients discharged to other facilities (63.6% vs 33.1%, p<0.01).

Conclusion:
Implementation of systematic, electronic processes for establishing post discharge follow-up in stroke patients is associated with a progressive increase in rate of successfully completed appointments. There were lower rates of successful follow-up in patients not discharged to home, and coordinated efforts across facilities may be required for full implementation of follow-up care. Informatics technology will play an increasingly important role in systems-based care for the stroke patient population.
Abstract 3854: Family History Of Cervical Artery Dissection In A Large Multicenter Cohort: The CADISP Study
Authors: Debette Stephanie , Martin Juan Jose , Kloss Manja , Engelter Stefan , Metso Tiina , Pezzini Alessandro , Thijs Vincent , Touze Emmanuel , Paolucci Stefano , Samson Yves , Bejot Yannick , Altintas Ayse , Metso Antti , Lichy Christoph , Lamy Chantal , Grau Armin , Caso Valeria , Lyrer Philippe , Tatlisumak Turgut , Grond-Ginsbach Caspar , Leys Didier , Dallongeville Jean , Bersano Anna
Published: July 2021

Background:
Little data is available on familial occurrence of cervical artery dissection (CEAD), a major cause of ischemic stroke in young adults. We aimed to examine the prevalence of family history of CEAD in a large multicenter cohort of CEAD patients and compare characteristics of CEAD patients with and without such a family history.

Methods:
Across 18 neurological departments in 8 countries, consecutive patients with a diagnosis of CEAD were included in the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) cohort study following a standardized protocol and using the same questionnaire.

Results:
Among 921 consecutive CEAD patients, 11 patients (1.2%, 95%CI:0.5-1.9%) from 9 families (1.0%, 0.3-1.6%) had a family history of CEAD, mostly in a first degree relative (64%). One patient without family history of CEAD had biologically confirmed vascular Ehlers-Danlos syndrome, while none of the patients with a family history of CEAD had a diagnosis of known inherited connective tissue disorder. Risk factors, baseline features, and 3-month outcome did not differ significantly between CEAD patients with and without a family history of CEAD.

Conclusion:
In the largest series of CEAD patients to date, family history of CEAD was very rare, although slightly higher than expected by chance given the low disease incidence.
Abstract 3856: Adoptive Transfer Of Regulatory T Cells Confers Long Term Neuroprotection Against Cerebral Ischemic Stroke
Authors: Li Peiying , Hu Xiaoming , Gan Yu , Zhang Feng , Gao Yanqin , Liang Weimin , Chen Jun
Published: July 2021

Stroke is the leading cause of serious long-term disability in adults. Activation and mobilization of CD4+CD25+ regulatory T cells (Tregs) is an intrinsic mechanism the body uses to restrict pro-inflammatory response, one of the well-established contributing factors for secondary neuronal injury and long-term neurological deficits after stroke. The current study explores the protective effect of Tregs adoptive therapy against post-ischemic brain damage and investigated the mechanisms underlying the action of Tregs. Using a mouse model of focal transient ischemia, we found that intravenous injections of Tregs (2 x 10
6
/animal) within 24 hours (2, 6, and 24 hours) after ischemia resulted in marked reduction of brain infarct. The maximal protection occurred upon earlier Tregs transfer with 2-hour delay after MCAO, which resulted in approximately 30% reduction of infarct volume. Post-ischemic sensorimotor dysfunction significantly improved during both the acute and late recovery after MCAO in Treg-treated mice as assessed by corner test, forelimb placing and cylinder test up to 28 days after ischemic stroke. Furthermore, Tregs treatment inhibited the up-regulation of IL-6, IL-1β, IL-17 and TNF-α in the ischemic brain and mitigated the cerebral infiltration of peripheral immune cells, including neutrophil, macrophage and T cells early after MCAO. Taken together, our study demonstrates that adoptive therapy with Tregs is a novel and potent cell-based therapy targeting post-stroke inflammatory dysregulation.
Abstract 3867: Robust Infiltration of Inflammatory Monocytes 12 Hours After Experimental Intracerebral Hemorrhage
Authors: Hammond Matthew D , Alander Cynthia B , Sansing Lauren H
Published: July 2021

Background and Purpose:
Inflammation is a key component of injury in the initial hours following intracerebral hemorrhage (ICH). Neutrophils are thought to be the earliest cells infiltrating into brain, but traditional methods to identify leukocytes are unable to differentiate between infiltrating monocyte populations and resident microglia. We used flow cytometry on brains 12 hours after ICH to quantify the specific infiltrating leukocyte populations. This is an early timepoint when neurobehavioral deficit is maximal and treatment could realistically be initiated.

Methods:
ICH was modeled by injecting 15μ l of blood from a C57BL/6 mouse (carrying leukocyte marker CD45.2) into the right striatum of a B6Ly5.2 mouse (which expresses CD45.1). The different CD45 isoforms allowed infiltrating leukocytes from the recipient mouse to be distinguished from the blood that was injected to model the ICH. Brains were harvested 12 hours later, dissociated mechanically and enzymatically, and cells collected from the interphase of a 30%/70% percoll gradient. Cells were then stained for CD45.1, CD45.2, CD3, CD11b, CD11c, Ly6G, and GR-1 and analyzed on a BD LSRII flow cytometer. Blood-derived leukocytes were identified as CD45.1hi, neutrophils as CD45.1hiCD11b+Ly6G+, inflammatory monocytes as CD45.1hiCD11b+Ly6G-CD11c-Gr1+, monocytes as CD45.1hiCD11b+Ly6G-CD11c-Gr1-, and dendritic cells as CD45.1hiCD11b+Ly6G-CD11c+. Mean cell counts in the ipsilateral hemisphere were compared to the contralateral hemisphere by t-test.

Results:
At 12 hours after ICH, we observed a significant increase in blood-derived leukocytes within the ipsilateral hemisphere (p<0.01, see
figure
). Less than 4% of total leukocytes were CD45.2. Surprisingly, we noticed a robust inflammatory monocyte population in the ipsilateral hemisphere (p<0.05,
figure
). Significant changes were not observed in monocyte, dendritic, or T cell populations, although there was a trend towards an increase in neutrophils (p=.055,
figure
).

Conclusions:
Using a CD45.1/CD45.2 blood transfer model, we determined that the cells injected into the striatum as part of the modeled hemorrhage are no longer detectable 12 hours later. Infiltrating inflammatory monocytes outnumbered neutrophils at 12 hours. This challenges conventional thought regarding the time course of invading immune cell populations following ICH, and suggests that future studies are needed to determine the contribution of inflammatory monocytes to early injury after ICH.
Abstract 3872: Transgenic HuR in Astrocytes Increases Ischemic Lesion Size in Mice
Authors: Carpenter Randall S , Hinkson Cyrus L , King Peter H , Ardelt Agnieszka A
Published: July 2021

Introduction:
Stroke is a serious neurological disorder that affects more than 800,000 Americans each year. HuR, an mRNA binding protein, regulates gene expression by modulating the stability and translational efficiency of mRNAs containing adenine-uridine rich elements in the 3’ untranslated region. Genes implicated in neuroprotection and post-ischemic repair may be regulated by HuR. The current investigation utilizes transgenic mice engineered to express Flag-HuR in astrocytes using the glial fibrillary acidic protein (GFAP) promoter. We hypothesized that modulation of mRNA stability in astrocytes would change the outcome from transient cerebral ischemia.

Methods:
Four mouse cohorts were studied: male or female and transgenic (TG) or wild-type (WT). Mice underwent 30-minute transient right middle cerebral artery occlusion (MCAO) and survived for 24 or 72h. Neurological scores were recorded after ischemia and prior to euthanasia, and brain tissue was sectioned for histology and immunolabeling. In a blinded fashion, Flag-HuR expressing nuclei were counted in peri-lesional regions of interest (ROI) and contralateral mirror ROIs, and ischemic/contralateral indices were calculated. Representative lesion size was determined in hematoxylin-eosin sections at the level of Bregma 1.10 mm.

Results:HuR-Flag expression:
The transgene was expressed in peri-lesional astrocytes. 24h after MCAO, hormonally intact female mice had higher levels of Flag-HuR expression: Flag-HuR index was 5.9 ± 1.9 in females (n = 7) vs. 2.0 ± 0.7 in males (n = 6), p = 0.002, Mann-Whitney rank sum test. 72h after MCAO, TG expression declined in females to levels comparable to those of males.

Lesion size:
There was no difference in lesion size between sex-matched TG and WT mice 24h post-MCAO, but at 72h lesion size was larger in TG females than WT females: 47% ± 12 (n = 10) vs. 22% ± 11 (n = 5), respectively, p = 0.002, t-test. Analysis of neurological scores, sex hormone levels, and long term survival is ongoing.

Discussion:
We hypothesized that altering mRNA stability in ischemic astrocytes would change outcome from cerebral ischemia. Initial characterization of TG mice in which HuR was expressed under control of the GFAP promoter showed that ischemia results in peri-lesional upregulation of the transgene, which is more robust in females than males 24h after MCAO and comparable to males 72h after MCAO. Transgene expression correlated with increased lesion size in females 72h after MCAO. While the mechanism of this effect requires elucidation, our results suggest that HuR is a viable novel target for further investigation in cerebral ischemia.
Abstract 3889: Diagnosis of Transient Ischemic Attack Varies by Neurologist
Authors: Bhupali Deepa P , Sheikh Huma U , Labovitz Daniel L
Published: July 2021

Introduction:
The short duration of symptoms and multitude of non-vascular mimics make diagnosis of transient ischemic attack (TIA) subjective and challenging. Physician practice may influence whether a patient receives the diagnosis of TIA. Pathophysiology is the same for TIA and ischemic stroke (IS). Therefore, the proportion of TIA versus IS diagnoses should be the same across demographic and clinical strata and theoretically should not vary between physicians.

Hypothesis:
The TIA-IS ratio, defined as the proportion of TIA among all TIA and IS cases, varies between medicine and neurology services and between board-certified vascular and other neurologists.

Methods:
TIA and IS cases were identified using primary ICD9 discharge codes at Montefiore Medical Center from January 2009 through June 2011. Each TIA diagnosis was confirmed by chart review, excluding cases with acute IS on brain imaging, duration >24 hours or a clearly non-vascular syndrome. The TIA-IS ratio was assessed based on the primary ICD9 code and again on the diagnosis by chart review for discharges from the neurology versus the medicine service and also individually for each board-certified neurologist with more than 25 IS or TIA discharges during the study period. Mantel-Hantsel chi-square was used for univariate statistical comparison between groups.

Results:
There were 659 cases of TIA and 1927 cases of IS by primary ICD9 discharge code, for an overall TIA-IS ratio of 25.5 %. The ratio was higher for discharges from medicine (28.6%) than neurology services (23.8%, p=0.009). The ratio was higher for 12 non-vascular neurologists (27.0%, range 17.9-44.4%, 904 cases), than 5 vascular neurologists (20.0%, range 18.7-23.0, 715 cases, p=0.001). Chart review reduced the overall TIA-IS ratio to 16.3% and the difference between medicine and neurology discharges became non-significant but non-vascular neurologists still had a higher TIA-IS ratio (20.7%) than vascular neurologists (14.4%, p=0.001).

Conclusions:
The TIA-IS ratio is different on medicine and neurology services and varies widely among board-certified neurologists, with vascular neurologists less likely to assign the diagnosis of TIA than other neurologists even after excluding obvious non-TIA cases. The ABCD2 score, assessing patients’ symptoms and vascular risk factors, is promoted as a criterion for admission; however, these data suggest that physician training and perspective affect the diagnosis, and thus assessment of future stroke risk, as well.
Abstract 3956: Outcomes of Patients Undergoing Endovascular Treatment for Mycotic Intracranial Aneurysms
Authors: Hassan Ameer E , Chaudhry Saqib A , Suri M Fareed K , Qureshi Adnan I
Published: July 2021

Background:
Mycotic intracranial aneurysms are rare with primary treatment focusing on underlying infection to reduce the high mortality rates. Treating these aneurysms remains challenging and obliteration procedures without sacrificing the parent artery often fail due to the fusiform and fragile aneurysm wall.

Objective:
To determine the outcomes associated with endovascular embolization in patients with mycotic intracranial aneurysms using a large nationally representative sample.

Methods:
We determined the frequency of endovascular and surgical procedures performed in patients with mycotic intracranial aneurysms and associated in-hospital outcomes using data from the Nationwide Inpatient Survey (NIS) data files from 2002 to 2009. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate logistic regression analysis.

Results:
Of the 1,915 patients admitted with the diagnosis of infected “mycotic” aneurysms, 83 (4.3%) underwent endovascular embolization, and 59 (3.1%) underwent surgical treatment. In mycotic aneurysms treated with endovascular treatment compared to surgical treatment, discharge outcomes were better with higher rates of minimal disability self-care (40% vs. 23.7% p=0.2436), and lower rates of moderate-severe disability (36% vs. 40% p=0.7874), and in-hospital deaths death (22.9 vs. 35.2 p= 0.3608). After adjusting for age, gender, and hospital teaching status, discharge mortality after endovascular treatment was not inferior to surgical treatment (odds ratio [OR] 1.58, 95% confidence interval [CI] 0.14 - 17.9) or those treated medically (OR 0.56, 95% CI 0.132 - 2.36).

Conclusion:
Endovascular embolization for mycotic intracranial aneurysms provides comparable outcomes to surgical treatment and should be considered whenever feasible when aneurysm obliteration is indicated.
Abstract 3967: Interdisciplinary Emergency Department (ED) Acute Stroke Case Review Decreases Door to Needle (DTN) Times
Authors: Fritz Melissa T , Fritzlar Sandy
Published: July 2021

Background:
Stroke is one of the leading causes of death and the leading cause of disability in the United States. Previous studies suggest that the quicker that intravenous tissue plasminogen activator (IV tPA) is administered, the safer and more effective it is, thus lowering the odds of in hospital mortality and symptomatic intracranial hemorrhage.

Objective:
To investigate whether implementing a process oriented, interdisciplinary bimonthly review of acute ischemic stroke cases would decrease DTN times and ultimately lead to the consistent administration of IV tPA within 60 minutes of arrival to the ED.

Methods:
To decrease the IV tPA DTN times, the stroke team at United Hospital in St. Paul, Minnesota developed a new ED stroke review process in July 2010 to analyze each acute ischemic stroke case. The cases were compiled into a document that contained time specific goals for each step of the acute stroke code process. Members of the stroke team would review the data prior to the meeting and if there was a delay (ie outside of the timed goal for lab result) in their department they would investigate the cause. At the meeting, the team would identify best practice efficiencies and barriers, leading to changes in the process. Formal follow up with each department and key learnings were sent to staff on a monthly basis.

Results:
In 2010, there were 82 patients admitted with an
acute
ischemic stroke, within 3.5 hours from time last known well, and 28 patients received IV tPA 34% (28/82). From January to June, 2011 there have been 46 acute ischemic stroke patients and 18 patients received IV tPA (18/46) 39%. The mean DTN time was 88 minutes in 2010 vs. 70 minutes in 2011; mean age was 64 vs. 66.5; % female was 46% (13/28) vs. 67% (12/18); median NIH Stroke Scale was 6 vs. 6. The percentage of patients treated with IV tPA within 60 minutes of hospital arrival increased from 21.4% (6/28) in 2010 to 50% (9/18) from January to June 2011 (p=0.022).

Conclusions:
The DTN times significantly decreased after the implementation of a process oriented, interdisciplinary ED acute stroke case review. The percentage of patients receiving IV tPA within 60 minutes increased from 21.4% to 50% over a 18 month period.
Abstract 3994: Obese Patients Receiving Intravenous Thrombolysis in Acute Ischemic Stroke Have lower Rates of Intracerebral hemorrhage and Mortality
Authors: Hassan Ameer , Grigoryan Mikayel , Chaudhry Saqib , Qureshi Adnan
Published: July 2021

Background:
The current recommended dose of intravenous tissue plasminogen activator (IV rt-PA) for ischemic stroke patients weighing >100 kg is fixed at 90 mg and thus obese patients receive less than the recommend 0.9mg/kg dosage. We hypothesized that obese patients receive a lower dose of thrombolytics and they will have a lower rates of intracerebral hemorrhages (ICH), but lower rates of clinical benefit from IV rt-PA.

Objective:
To determine the relationship between obesity and clinical outcomes among acute ischemic stroke patients receiving IV rt-PA.

Methods:
Data were obtained from all states within the United States that contributed to the Nationwide Inpatient Sample. All patients admitted to US hospitals between 2002 and 2009 with a primary discharge diagnosis of stroke treated with IV thrombolysis (identified by the International Classification of Diseases, Ninth Revision procedure codes) were included. We analyzed whether the presence of obesity was associated with clinical outcome and ICH with multivariate logistic regression analysis after adjusting for potential confounders.

Results:
Of the 84,727 patients with ischemic stroke treated with IV rt-PA, 5,437 (6.4%) had concurrent obesity. The ICH rates between obese and non-obese patients was 4.3% versus 6.1% (p=0.005). After adjusting for age, sex, hypertension, diabetes mellitus, renal failure, hospital teaching status, and ICH, the presence of obesity was not associated with increased rates of self-care (odds ratio [OR] 0.929, 95% confidence interval [CI] 0.815-1.063, p=0.27), but was associated with decreased rates of mortality (OR 0.78, 95% CI 0.61 - 0.94, p=0.045) at discharge.

Conclusion:
Obese patients undergoing IV t-PA treatment for acute ischemic stroke appear to have lower rates of ICHs and mortality presumably due to lower weight adjusted thrombolytic dose.