bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3794: Investigating Gender Differences in Secondary Stroke Prevention Care in Ontario
Authors: Khan Ferhana , Hodwitz Kathryn , Hall Ruth , Fang Jiming , Kapral Moira , Silver Frank
Published: March 2022

Introduction:
In Ontario, more women than men (51% vs. 49% in 2009/10) are admitted for stroke or transient ischemic attack (TIA). Women are also older when they experience stroke or TIA (78 vs. 72 median years) and have strokes resulting in greater disability. Best practice stroke care indicates secondary stroke prevention is essential to reducing the likelihood of recurrent vascular events following stroke or TIA. There is currently limited information about whether or not gender differences exist in the type of care delivered at Secondary Stroke Prevention Clinics (SPCs). This study examined whether or not gender differences in the quality of care exist at SPCs across Ontario.

Methods:
Subjects included all consecutive stroke/TIA patients seen at 21 of 33 designated SPCs in Ontario participating in the Registry of the Canadian Stroke Network’s Stroke Performance Indicators for Reporting Improvement & Translation (SPIRIT-SPC) web-based data collection. Patients with presumed stroke/TIA referred to SPCs between January 2007 and April 2011 were identified for this study. We excluded referrals not initiated as a direct result of an acute stroke/TIA event within the past 3 months, non-strokes, and incomplete referrals/visits. We compare the performance rate for seven quality of care indicators related to secondary prevention between men and women.

Results:
Of the 14,966 stroke/TIA patients with at least one SPC visit, 47.2% were female and the mean age in years was 69 for women and 67 for men. Significant gender differences were found in referral reason and source, risk factors, and final diagnosis made after the first SPC visit. Women were more likely to be referred for query stroke (61.1% vs. 57.7%) and referred by an emergency or family physician (82.5% vs. 79.6%) compared to men. In terms of risk factors associated with stroke, compared to men, fewer women had a history of smoking; dyslipidemia, diabetes, and previous stroke, however, more females were obese. A higher percentage of women were diagnosed with TIA or query stroke after the first SPC visit (33.2% vs. 26.3%). Significant gender differences were observed in 3 of 7 performance indicators. Women had lower rates of neuroimaging (F=91.5%, M=92.6%, p<0.05), carotid imaging (F=87.4%, M=89.2%, p<0.05) and antithrombotics (F=91.2%, M=92.5%, p<0.05). No significant differences were found in access, time to assessment, and prescriptions for anticoagulants among patients with atrial fibrillation.

Conclusion:
Women are less likely to receive diagnostic imaging and antithrombotic prescriptions at or prior to a SPC visit compared to males. As best practice stroke care recommends all patients with presumed stroke/TIA should receive appropriate diagnostic evaluation and treatment, there is a need to eliminate gender gaps in secondary prevention care.
Abstract 3821: Achieving the Recertification as Primary Stroke Center in Brazil.
Authors: Alves Monique B , Coelho Fernando M , Barros Claudia G , Lopes Tania O , Cendoroglo-Neto Miguel , Silva Gisele S ,   Albert Einstein Hosp Quality Dept,   Albert Einstein Stroke Cntr
Published: March 2022

Certification programs for Primary Stroke Centers (PSC) became a possibility after the publication of the recommendations for the establishment of PSC from the Brain Attack Coalition. The Joint Commission Organization (JCO), with the support of the AHA and ASA, launched a certification program in Dec-03. In Jan-11, more than 800 PSC were recognized in the USA. Albert Einstein Hospital in São Paulo, Brazil was the first hospital in the world to achieve the hospital accreditation quality program by Joint Commission International (JCI) outside the USA in 1999 and also was the second institution outside the USA that achieved the certification as PSC in March 2007. Albert Einstein Hospital still continues as the only certified PSC in Latin America. Our aim was to describe the actions implemented from March 2007 to March 2010 in order to obtain the recertification as PSC.

Methods/Results:
We used the first version of the manual of the JCI “Disease Specific Programs” translated to Portuguese. The main actions implemented to achieve the standards required for recertification were: 1) Program management- we adopted the “Disease and the Case Management Strategies” to include the patients in the program. All patients admitted with stroke were followed by a case manager nurse since admission. A physician coordinator was hired to manage the stroke program. Neurologists were made available at the ED around the clock. 2) Delivering or facilitating clinical care: all the staff received different training programs: basic, intermediate, advanced and core stroke team. Our protocols were developed using ASA and the Brazilian Stroke guidelines. 3) Clinical information management: all the patients were prospectively evaluated and data were collected during stroke admission. 4) Supporting self-management: clinical pathways were used according to the targets of the rehabilitation program. All the risk factors were screened for and patients and families were educated and encouraged for life style changes. Education about stroke was given during admission. Educational folders and information sheets were also distributed. For smokers, we used a dedicated educational program. 5) Performance improvement and measurement: the quality indicators followed were the same as JCO and Get with the Guidelines Stroke Program. All of the 10 quality indicators used by the JCO in addition to door-image and door-needle time were also evaluated and followed since January since 2005. Monthly, quality indicators were discussed in clinical meetings and reported on the internet annually. The quality program involved tools like Lean Six Sigma and PDCA to improve the results.

Conclusion:
We achieved the recertification as PSC in March 2010. We believe that the certification contributed to engage the clinical staff in offering a better assistance for all patients with stroke admitted to our service.
Abstract 3828: Cerebrovascular Disease And Risk Of Stroke In Patients With ACTA2 R179H And R179L Mutations
Authors: Regalado Ellen , Ostergaard John R , Ganesan Vijeya , Guo Dong-chuan , Milewicz Dianna M
Published: March 2022

Cerebrovascular disease and risk of stroke in patients with
ACTA2
R179H and R179L mutations

Ellen S. Regalado
1
, John R. Østergaard
2
, Vijeya Ganesan
3
, Dong-chuan Guo
1
, and Dianna M. Milewicz
1
1
Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA;
2
Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital, Skejby, Denmark;
3
Neurosciences Unit, Institute of Child Health, University College London, London, UK Mutations in the
ACTA2
gene, which codes for the smooth muscle specific isoform of alpha actin, predispose to a variety of vascular diseases, including thoracic aortic aneurysm and dissection, early onset stroke, and coronary artery disease. Recently we reported a severe de novo
ACTA2
p.R179H mutation that causes a syndromic smooth muscle dysfunction resulting in aortic aneurysms, patent ductus arteriosus, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut, and pulmonary hypertension. Additionally, childhood onset of cerebrovascular disease is a prominent feature of this syndrome. To understand the extent of cerebrovascular disease and risk of stroke in these patients, we examined the clinical data of 9 patients recruited worldwide (8 Caucasians, 1 Asian; female to male ratio, 5:4; 8 with p.R179H mutation, 1 with p.R179L mutation). These patients ranged in age from 1 to 27 years old at the time of diagnosis of the
ACTA2
mutation. All of these patients demonstrated multiple areas of narrowing of the intracranial vessels and increased T2 signal intensity in the periventricular white matter. Eight patients had bilateral stenosis of the distal internal carotid arteries and ectasia of the internal carotid arteries involving the petrous, cavernous and clinoidal segments and one patient had occlusion of the basilar artery only. Of these 9 patients, 5 have presented with ischemic stroke or recurrent transient ischemic attacks (age range, 2-27 years old; female to male ratio, 4:1), 4 of whom demonstrated cerebral infarction on MR imaging (age range, 2-16 years old). Two patients underwent bilateral revascularization procedures at age 9 and 6 years; the 9 year old patient developed an acute ischemic stroke within a year of surgery whereas the 6 year old remains stroke free 10 years after surgery. These data demonstrates the severity of cerebrovascular disease presentation in this subset of patients with the
ACTA2
mutation and underlines the need for early diagnosis and careful surveillance and management in order to prevent ischemic strokes.
Abstract 3873: Relationship Between Alberta Stroke Program Early CT Score (ASPECTS) And Outcomes In Intra-arterial Treatment Of Acute Ischemic Stroke
Authors: Jadhav Ashutosh P , Zaidi Syed , Jumaa Mouhammad , Reddy Vivek , Hammer Maxim , Wechsler Lawrence , Jovin Tudor
Published: March 2022

Background and Purpose:
Identification of early ischemic stroke is instrumental in rapidly triaging patients who may benefit from revascularization. We sought to understand the relationship between baseline ASPECT scores and outcomes in patients who underwent intra-arterial thrombolysis.

Methods:
Retrospective review of a prospectively maintained database of acute ischemic strokes at the University of Pittsburgh Medical Center during the time period of 2001-2011. CT-ASPECT scores were prospectively scored by treating physicians. The following additional factors were considered: age, NIHSS, time from last seen well (TLSW) to angiography, good vascular flow (TIMI score of 2 or 3), parenchymal hematoma (PH) formation and good clinical outcome (mRS score of 0-2 at 90 days).

Results:
Of 322 patients included in the study, there was a significant correlation between ASPECT score and good clinical outcome when good vascular flow was achieved.
Table
1 and
graph
1 summarizes the distribution of ASPECTS scores and corresponding rate of good TIMI flow and good clinical outcome along with other variables of interest.

Conclusions:
A baseline ASPECT score of 7 or greater is predictive of a good clinical outcome, particularly when adequate recanalization is achieved. In contrast, patients with an ASPECT score of 6 or less had poor clinical outcomes, particularly when recanalization was not achieved. These data support a paradigm in which CT ASPECT scores are used to define patients appropriate for endovascular treatement.
Abstract 3879: Symptomatic Cerebral Vasospasm and Cerebral Infarct do not significantly contribute to In-Hospital Mortality after Subarachnoid Hemorrhage
Authors: Lee Vivien , Conners James J , John Sayona , Temes Richard E , Garg Rajeev K , Bleck Thomas P , Prabhakaran Shyam
Published: March 2022

Background:
The International Cooperative Study on the Timing of Aneurysm Surgery suggested that delayed cerebral vasospasm is a significant contributor to mortality (at 6 months) after subarachnoid hemorrhage (SAH). However, the Cincinnati population based study did not find cerebral vasospasm to be a significant contributor to short-term mortality.

Methods:
We reviewed 350 consecutive non-traumatic SAH patients who were hospitalized at our institution from August 1, 2006 to June 30, 2010. Data were collected on demographics, Hunt and Hess grade, presence of cerebral infarct, symptomatic vasospasm, and in-hospital mortality. Symptomatic vasospasm was defined as cerebral vasospasm that required intra-arterial therapy (pharmacologic vasodilators or angioplasty). Cerebral infarct was defined as any new radiographic infarct seen on CT or MRI (of any cause).

Results:
Among 350 patients with non-traumatic SAH, the mean age was 56.7 years (range, 21.5 to 89.1) and 68% were aneurysmal. The overall in-hospital mortality rate was 20.2% (71 patients). The causes of in-hospital mortality were withdrawal of support in 53 (75%), brain death in 14 (20%), and cardiopulmonary death in 4 (8%). The mean time to death was 8.1 (range 0 to 31) days, with 36% of deaths occurring within the first 2 days of hospitalization. Among patients with symptomatic cerebral vasospasm or cerebral infarct , 19% (26/139) died. In univariate and multivariate analyses, symptomatic cerebral vasospasm and cerebral infarct were not associated with in-hospital mortality. When the analysis was restricted to patients with aneurysmal SAH, cerebral vasospasm and cerebral infarct were still not predictive of in-hospital mortality. In multivariable analysis, the variables most associated with in-hospital mortality were Hunt and Hess score (HH) (p <0.0001), rebleed (p <0.0001), and age ≥ 80 (p 0.0017).

Conclusions:
In-hospital mortality after SAH is associated with initial severity of hemorrhage, rebleeding, and age. Symptomatic cerebral vasospasm and cerebral infarct were not significant contributors of overall in-hospital mortality, and approximately one-third of in-hospital mortality after SAH occurs within the first 2 days of hospitalization. By design, studies that exclude patients with severe SAH tend to over-estimate the contribution of cerebral vasospasm on short-term mortality.
Abstract 39: Timing Of Infection And Risk Of Arterial Ischemic Stroke In Children
Authors: Hills Nancy K , Johnston S.Claiborne , Sidney Stephen , Fullerton Heather
Published: March 2022

Background.
Minor acute infections have been associated with arterial ischemic stroke (AIS) in both adults and children, and exposure to multiple infections over time is thought to contribute to atherosclerosis in adults. Our goal was to examine the association between infection and stroke, and assess whether timing or burden of infection is a stronger predictor of childhood AIS.

Methods.
We performed a case-control study nested in a cohort of 2.5 million children (<20y) enrolled in a large integrated health care plan (1993-2007). Non-neonatal AIS cases were identified from searches of diagnostic and radiology databases, and confirmed through independent chart review; 3 controls per case were randomly selected from the cohort, matched by age and primary care facility. A medical records analyst abstracted data on all out-patient visits for infection during the 2 years prior to the stroke, or index date in controls (stroke date for the paired case). The proportion of subjects who had an infectious visit in each period: from 0-2 days, 3-7 days, 8-28 days, 1-3 months, 3-6 months, 6-12 months, and 12-24 months prior to stroke was determined. Cases were compared to controls using conditional logistic regression and the Kaplan-Meier method.

Results.
We identified 126 cases (median age 10.5 years) and 378 controls. Infectious visits within the prior 2 years were documented in 79% of cases and 62% of controls. A striking disparity in number of cases and controls with an infectious visit was observed in the first 2 days prior to stroke: 29% of cases vs. 1% of controls (p<0.0001). From 3-7 days prior, 13% of cases and 2% of controls had a visit for infection (p<0.0001). Analysis with Kaplan-Meier methods, defining time-to-event as days prior to stroke/index date of most proximate infection, yielded a significant difference between survival functions for cases vs. controls (p<0.0001). In conditional logistic regression adjusted for gender, and hematologic, autoimmune, and cardiac disease, a visit with infection in the 2 days prior to stroke was associated with a relative hazard of 182 (p<0.0001), which dropped to 10 (p<0.0001) and 2 (p=0.046) for periods of 3-7 and 8-28 days prior.

Conclusions.
The risk of stroke is substantially elevated among children in the week after a visit for infection. The risk was greatest in the first 2 days after infection but remained elevated for the first month, even after adjustment for the presence of chronic disease. After the first month, infectious burden was not significantly different between cases and controls, and does not appear to be associated with an increased risk of childhood AIS.
Abstract 3903: Dynamin-related Protein 1 Independent Apoptosis In Neurons Following Oxygen-glucose Deprivation
Authors: Wappler Edina A , Institoris Adam , Katakam Prasad V , Busija David W
Published: March 2022

Background and purpose:
Previous studies showed that mitochondrial (mito) fission occurs prior to apoptosis and that a key initiator is the mito fission protein dynamin-related protein 1 (Drp1). However, little information is available concerning mito dynamics in neurons due to OGD. Therefore, we investigated mito fission and mito fusion responses in cultured neurons in an
in vitro
model of brain ischemia.

Methods:
Primary rat cortical neurons were isolated from E18 Sprague Dawley fetuses. Neurons were exposed to OGD 9 days after culturing for 3 hr followed by up to 24 hr of reoxygenation. Mito dynamics were investigated by measuring the expression of: 1) mito fission [Drp1; mito fission 1 (Fis1)] and mito fusion [mitofusin-2 (Mfn2); optic atrophy-1 (OPA1)] proteins; 2) electron transport chain proteins (complex II 70 kDa subunit, complex IV subunit I, complex V alpha subunit); 3) mito DNA; and 4) apoptosis protein Bax. We also examined neuronal and mito morphology using transmission electron microscopy. The effects of the Drp1 inhibitors 15d-Prostaglandin J
2
(2.5-20 µM) (15d-PGJ
2
) and Mdivi-1 (2.5-250 µM) were also investigated.

Results:
3hr OGD followed by 3-24 hr recovery resulted in an increase in the level of mito DNA and enhanced expression of complex IV and V proteins. During this time, abnormal morphology, including enlarged and/or swollen mitochondria, was often observed. However, many mitochondria still retained normal morphology. Drp1 levels decreased before virtually disappearing by 6 hr of reoxygenation following OGD while Fis1 expression did not change. Bax expression increased with an increasing number of apoptotic cells during this time. Mfn2 decreased after OGD while OPA1 did not change significantly. 15d-PGJ
2
treatment dose-dependently increased cell death both in control and OGD-exposed neurons. Furthermore, 15d-PGJ
2
treatment surprisingly increased Drp1 both in controls and in OGD-exposed cells, and also increased the mito DNA. Additionally, 15d-PGJ
2
treatment itself increased the number of larger mitochondria in the neurons. However, Mdivi-1 did not have any effects.

Conclusions:
Despite a lower fission/fusion protein ratio, the increase in mitochondrial size indicates a shift to enhanced fusion in neurons following OGD. In addition, apoptosis induction seems to be Drp1 independent in this model. Additionally, 15d-PGJ
2
treatment appears to decrease survival in neurons following OGD. Thus, mito dynamics are affected by OGD and 15d-PGJ
2
treatment and play a role in cell survival/death.
Abstract 3946: Determinants and Outcomes Associated with Withdrawal of Care following Endovascular Treatment in Acute Ischemic Stroke Patients.
Authors: Hassan Ameer , Rostambeigi Nassir , Chaudhry Saqib , Khatri Rakesh , Rodriguez Gustavo , Suri Fareed , Qureshi Adnan
Published: March 2022

Background:
Withdrawal of care although frequently used may prematurely reduce the odds of recovery in patients with acute ischemic stroke. We performed this study to provide a better understanding of physician practices in withdrawal of care following endovascular treatment in acute ischemic stroke patients.

Objective:
Our goal was to identify frequency and factors associated with endovascular treatment that increase the odds of withdrawal of care in consecutive series of acute ischemic stroke patients.

Methods:
We reviewed consecutive acute ischemic stroke patients treated with endovascular treatment over a 5-year period. Demographics characteristics, National Institute of Health Stroke Scale (NIHSS) score before and after the procedure, and modified Rankin scale (mRS) at discharge were collected. The Qureshi grading scale was used to evaluate angiographic recanalization. We analyzed whether the presence of successful recanalization, or post-procedure intracerebral hemorrhage (ICH), was associated with withdrawal of care after age and 24 hr NIHSS score adjustment. The effect of withdrawal of care on poor outcome (mRS 3-6) at discharge was determined after adjusting for age and admission NIHSS score.

Results:
A total of 186 patients underwent endovascular treatment, mean age + SD: 65 (±17) years, 100 (54%) men, and mean NIHSS score ± SD: 15.5+ 7. Sixty four patients received intra-arterial thrombolytic only, 28 mechanical thrombectomy only, and 75 combined lytic/mechanical thrombectomy. Among all, 142 patients (77%) had vessel recanalization. Of these, 17 (9%) underwent withdrawal of care. 14% of the patients with recanalization versus 8% without recanalization underwent withdrawal of care (p=NS). Overall there were 37 patients who developed post-procedure ICH, but this occurrence was not associated with withdrawal of care status (p=NS). After adjusting for age and admission NIHSSS, there was no relationship between angiographic recanalization with withdrawal of care (OR=0.5, p=0.3). Patients who underwent mechanical thrombectomy during endovascular treatment had significant correlation with withdrawal of care compared to intra-arterial thrombolytic therapy alone (OR=10, p=0.02).

Conclusion:
Withdrawal of care, although infrequent, contributes to poor outcome at discharge in patients undergoing endovascular procedure for acute ischemic stroke. However, the choice of withdrawal of care is not related to angiographic recanalization or post-procedural ICH.
Abstract 3957: Do Men And Women Undergoing Carotid Endarterectomy Or Carotid Stent Placement In General Practice Have Different Outcomes
Authors: Khatri Rakesh , Chaudhry Saqib A , Jadhav Vikram , Hassan Ameer E , Rodriguez Gustavo J , Suri M. Fareed K , Qureshi Adnan I
Published: March 2022

Background:
Data derived from Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) suggested differential comparative periprocedural benefit between carotid angioplasty and stent placement (CAS) and carotid endarterectomy (CEA) on basis of gender. We sought to investigate the impact of gender on post-procedural outcomes of CAS and CEA in general practice at a national level.

Methods:
We analyzed the data from the Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States from 2005-2009. The primary end point was occurrence of stroke, cardiac complications, or death during the post procedural period. Outcomes of interest were compared between men and women, undergoing CEA and CAS. Multivariate logistic regression was performed to determine the effect of gender on occurrence of post-operative stroke, cardiac complications, or death for CAS and CEA separately. Covariates included in the logistic regression were patient’s age, gender, co-morbid conditions including hypertension, diabetes mellitus, chronic lung disease, coronary artery disease, congestive heart failure, and renal failure; symptom status (symptomatic versus asymptomatic status), and hospital characteristics.

Results:
Of the total 673,170 estimated patients, who received CEA or CAS for carotid artery disease during the study period, 591,543 (88%) underwent CEA and the remaining 81627 (12%) underwent CAS. Out of a total of 282,632 (42%) women, 250,502 (89%) women underwent CEA compared to 32130 (11%) women who underwent CAS procedures. There was no difference between men and women in post-operative stroke, cardiac complications, or death for women undergoing CAS for both symptomatic and asymptomatic status as well as symptomatic women undergoing CEA. Post operative strokes (0.99% vs 0.84%, p= 0.01) were higher in asymptomatic women however cardiac complications were higher for asymptomatic men (2.0% vs 1.64%, p= 0.0001) and composite end points was lower in women (2.80% vs 3.00%, p= 0.02) undergoing CEA. In multivariate analysis, gender was not a significant factor for composite end points among patients undergoing either CAS (RR, 95% CI) or CEA (RR, 95% CI) after adjusting for potential confounders.

Conclusion:
Our analysis suggests that postprocedural rate of events are not significantly different between men and women undergoing either CAS or CEA in general practice and should not be used to determine eligibility for either procedure .
Abstract 3980: Early Results of Stenting for Acute Stroke Intervention Following Full Dose IV Alteplase (SASI-1 Study)
Authors: Kirmani Jawad F , Moussavi Mohammad , Bitra Karuna , Siddique Usama , Channapragada Theja , Carlowicz Cecilia , Ibrahim Mohammad , Gizzi Martin
Published: March 2022

Background and Purpose:
Strategies for rapid restoration of flow using fibrinolytic therapy followed by acute stenting have been well studied for myocardial infarction. Previously reported data, on older stent designs, suggested that there may be an unacceptably high risk of Intracerebral Hemorrhage (ICH). Also reported were high rates of technical failure when using this strategy for ischemic stroke treatment. The SAS-1 study was designed to address this safety concern and look into the technical feasibility of the procedure.

Methods:
Patients were enrolled prospectively at a university-affiliated community hospital for this phase I trial from November 2009 to June 2011. Standard angiographic techniques, self expanding stents (SES) and anti-GIIb-IIIa were used following lack of improvement after administration of IV Alteplase. Angiographic recannalization (R) was recorded using modified TIMI and Qureshi grading scales. CT scans were performed immediate post procedure and at 24 hours. Clinical evaluations were performed at presentation, 24 hours, 7 to 10 days and/or at discharge, and 3 months after the treatment. All adverse events were noted. Safety stopping rules were prespecified. Results were analyzed using SPSS (11.0) software.

Results:
Of the 1012 ischemic stroke patients 64 were screened for the study. Nineteen patients met the study criteria (Mean Age 68.9, Range 38-93, Males = 7(36.84%), Females - 12(63.16%)). For this early analysis primary outcomes of interest were: (1) Technical feasibility (2) Recannalization Rates (Complete and Partial); and (3) serious adverse events within 72 hours (4) neurologic outcome within the first week. Fifteen patients had intracranial stenting (MCA n=12, basilar n=1, IC n=1) and 5 had extracranial carotid stents. There were no technical failures. In 2 patients stents were retrieved following complete recannalization. Comparison with historical studies suggests high recannalization rates (Complete Recannalization - 47.37%, Partial Recannalization - 47.37%), low occurrence of symptomatic ICH (n=1, 5%) and asymptomatic ICH (n=3, 15%). No other serious adverse events were noted. Early Neurological Improvement was seen in 63.16% (n=19). Three month follow-up are still not complete for all patients.

Conclusion:
The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds. There were no technical failures. The results form the basis of a larger randomized trial addressing the efficacy of full dose intravenous alteplase followed by acute stenting.
Abstract 40: Updating White Matter Hyperintensity Visual Scoring: Incorporating Research Advances, Improving Reproducibility and Correlation with Automated Volumes
Authors: King Kevin , Alhilali Lea , Whittemore Anthony , McColl Roderick , Hulsey Keith , Peshock Ron
Published: March 2022

Introduction:
White Matter Hyperintensities (WMH) have been implicated as a risk factor for motor and cognitive decline, dementia and stroke. A standard for use in clinical settings is needed to identify which cases are advanced or meet thresholds with implications for degree of impairment. The system of Fazekas is a promising candidate due to its simplicity and strong correlation with outcomes. The original Fazekas categorized deep and periventricular WMH separately. Advanced periventricular and deep WMH were later shown to have equivalent pathology and etiology. Subsequent work by De Carli showed the classification of deep and periventricular WMH on axial images to be arbitrary and suggested a common etiology for lesser degrees of WMH as well. We therefore adapted the Fazekas criteria to consider deep and periventricular WMH jointly. Questions persist about low reproducibility of grading systems. In a preliminary analysis we found frequent disagreement classifying lesions less than 3mm in diameter and decided to incorporate this threshold into our criteria to determine the effect on reproducibility and correlation of our final model with automated volumes.

Hypothesis:
Modification of the Fazekas grading system to consider deep and periventricular WMH jointly is less arbitrary. Simple modifications of such a system will result in a high degree of reproducibility and high correlation with automated WMH volumes.

Methods:
Axial 3T FLAIR MR images of the brain were obtained from community dwelling subjects. Grading measurements were applied to diameter of deep WMH and thickness of periventricular WMH. The initial system defined Grade 0 as no WMH, Grade 1 as < 10mm, Grade 2 as >=10mm but <20mm and Grade 3 as >=20mm. 52 studies were read separately by 2 reviewers. We then revised grade 0 to include intensities < 3mm and grade 1 as >=3mm but <10mm. 40 additional studies were then read and level of agreement was re-assessed. 563 studies were read for correlation with automated volumes.

Results:
After modifications, inter-rater agreement for Fazekas white matter score increased from 72% to 89% with kappa increased from 0.45 to 0.78. There was good correlation of grade and automated volume (ANOVA R-Square: 0.52 P <.0001).

Conclusion:
Advances in understanding of White Matter Hyperintensities suggest periventricular and deep lesions should be rated jointly. This modification was applied to the Fazekas system with excellent reproducibility after implementation of a 3mm size threshold as well as high agreement with automated volumes ammong community dwelling subjects.
Abstract 4002: Vulnerability to Contralateral Pneumonia in Patients with Hemispheric Strokes
Authors: Franc Daniel , Chaudhry Saqib , Hassan Ameer E , Rizvi Ashter , Rodriguez Gustavo J , Suri M. F , Qureshi Adnan I
Published: March 2022

Background:
Stroke is associated with contralateral focal motor, visual, and sensory deficits. It remains unclear whether there is laterality to muscle deficits involved in upper airway and respiration. We hypothesized that there is laterality in motor deficits and coordination of muscles involved in upper airway and respiration in acute stroke resulting in greater vulnerability to contralateral pneumonia in supratentorial stroke patients.

Methods:
We reviewed medical records, chest radiographs, and laboratory testing to identify patients with pneumonia among a study population of 1033 adults (239 with intracerebral hemorrhage (ICH), and 794 with ischemic stroke) admitted to two University affiliated hospitals from 2008-2010. Hospital-acquired pneumonia was defined by new or progressive radiographic infiltrate and at least two clinical features (fever, leukocytosis, or purulent tracheal secretions) based on definitions used in previous studies.

Results:
Overall, 76 patients (7.36%) were diagnosed with pneumonia during their hospitalization; 24 patients with bilateral pneumonia at the time of diagnosis were excluded. In all stroke patients with a unilateral stroke, a higher number of unilateral pneumonias were found in the contralateral lung (40) as compared to the ipsilateral lung (12) (OR 3.33, 95% confidence interval [CI] 1.43-7.75) after correction for endotrachial and nasogastric tube placement. The relationship was more prominent in patients with ischemic stroke patients (OR 5.20, 95% CI 1.57-17.18) as compared with patients with ICH ( OR 2.00, 95% 0.57-7.06).

Conclusions:
Unilateral vulnerability to pneumonia in patients with hemispheric stroke supports targeted chest percussions and postural drainage therapies to reduce the rate of such events and associated morbidity.
Abstract 4034: Aspirin And Cilostazol Increase Cerebral Blood Flow In Acute Ischemic Stroke Patients Compared To Clopidogrel - A Single Center, Randomized, Open, Blinided-endpoint Pilot Study
Authors: Lee Si Baek , Koo Jaseong , Kim Yeong-In , Chung Yong-An
Published: March 2022

Introduction & Hypothesis :
Antiplatelet drugs are widely used in the treatment and prevention of ischemic stroke. The key effect of antiplatelet drugs is inhibition of platelet aggregation, which may prolong bleeding time and increase bleeding complications. Improving cerebral blood flow (CBF) is important in recovery after ischemic stroke. Cilostazol is a phosphodiesterase III inhibitor and has a vasodilatory effect as well as antiplatelet effect. Previous report showed that cilostazol did not increase bleeding time despite comparable effect on platelet aggregation compared to aspirin or clopidogrel. Cilostazol is also known to increase CBF. We conducted a single center, prospective, randomised, open-label blinded-endpoint pilot study to assess the hypothesis that aspirin plus cilostazol may increase CBF compared to clopidogrel in patients with acute ischemic stroke.

Methods :
We enrolled consecutive 24 acute ischemic stroke patients who visited our clinic within 72 hours of symptom onset. Patients were randomly assigned to aspirin (100 mg/d) and cilostazol (200 mg/d) (n=11) or clopidogrel (75 mg/d, n=13) and treated for 12 weeks. Measurement of platelet aggregation (ADP, collagen, epinephrine, and ristocetin), bleeding time and CBF were done at baseline (before taking study medication) and at 12 weeks. CBF was measured by use of 99mTc HMPAO SPECT and the results were analyzed by use of statistical parametric mapping 2 (SPM 2) with aid of MATLAB 6.1 software.

Results :
Demographic and clinical features of the patients of each treatment group were not significantly different. Degree of platelet aggregation and bleeding time at baseline and 12 weeks were not significantly different between the treatment groups. The change of CBF between baseline and at 12 weeks were significantly different and CBF were more increased in patients treated with aspirin and cilostazol compared to clopidogrel only. Two patients taking clopidogrel had serious adverse events; one with angina pectoris and the other duodenal ulcer.

Conclusion :
In ischemic stroke patients, aspirin plus cilostazol increased CBF significantly more than clopidogrel only with similar effect on platelet aggregation and bleeding time.
Abstract 4036: Collateral Status And Stroke Severity Is Important In Thrombolytic Therapy Of Internal Carotid Artery Occlusion
Authors: Nam Hyo Suk , Kim Jinkwon , Song Tae Jin , Kim Young Dae , Heo Ji Hoe
Published: March 2022

Background:
Despite the poor prognosis in patient with internal carotid artery occlusion (ICAO), optimal management is uncertain. However, mechanical thrombectomy showed promising results in recanalization of ICAO, the prognosis of patients with ICAO after thrombolytic therapy is still unsatisfactory. The futile recanalization of ICAO might be related from the initial poor collateral flow and severe stroke. We performed a retrospective analysis of clinical and imaging data of patients who received endovascular treatments due to acute symptomatic ICAO to reveal the factors associated with good outcome at 3 months.

Methods:
From the stroke database, patients with ICAO were recruited. Inclusion criteria were 1) acute symptomatic ICAO within 6 hours of symptom onset, 2) attempted endovascular revascularization, and 3) enabled 3 months follow-up. Factor associated good outcome (modified Rankin scale score 0-2) at 3 months were evaluated including collateral grading, which was assessed with the ASITN/SIR Collateral Flow Grading System on pre-treatment angiography. A score of grade 0-1 was designated as poor, grade 2-3 as good collateral flow (no patients with ICAO showed grade 4 collateral).

Results:
During 8 year study period, total 80 patients were enrolled , good collateral flow was shown in 35 patients (44%) and poor collateral in 45 (56%). The patients with good collateral had lower National Institute of Health Stroke Scale (NIHSS) score comparing with poor collateral (15 ± 5 vs. 18 ± 4, p = 0.008) and less frequently suffered symptomatic intracranial hemorrhage (14% vs. 40%, p = 0.02). Multivariate analysis revealed that good collateral flow before treatments [OR 6.77, 95% CI, 1.12-41.05] and complete recanalization after treatments [OR 9.18, 95% CI, 1.13-74.04] were independent predictors of good outcome at 3 months. Whereas, higher NIHSS score were strong predictor of poor outcome [OR 0.74, 95% CI, 0.577-0.95] after adjusting age, sex, onset-to-treatment time, parenchymal hematoma, initial glucose and systolic blood pressure.

Conclusions:
In acute symptomatic carotid artery occlusion, the patient with initial good collateral flow with less severe neurological deficit and subsequent complete recanalization had higher chance of good outcome. To avoid futile recanalization in ICAO, collateral assessment and achieving complete recanalization might be important.
Abstract 42: Impact Of White Matter Hyperintensities Extension On Rate Of Cognitive Decline
Authors: Maillard Pauline , Carmichael Owen , Fletcher Evan , Reed Bruce , Mungas Dan , DeCarli Charles
Published: March 2022

Background:
Characterizing the impact of cerebral white matter (WM) damage in age related cognitive decline is of growing interest. Recently, we used DTI to show that White Matter Hyperintensities (WMH) are surrounded by a penumbra of subtly-injured WM. Because this finding supported the view that WMH may result from a continuous WM degeneration process rather than a sudden event, longitudinal studies are needed to determine whether development of WMH may determine subsequent change in cognitive performances.

Methods:
This study examined the strength of association between longitudinally measured WMH and longitudinally measured cognition in a sample of 153 individuals. The sample included AD, MCI, and cognitively normal (CN) who completed cognitive evaluation and MRI scans on two dates (mean delay: 4.0 years). Psychometrically matched measures of cognition were used to assess episodic memory and executive function at both dates. WMHs were repeatedly measured, and incident WMH dissociated into two categories: WMH Extension (extension of existing baseline WMH) and WMH Emergence (newly formed WMH). We used a stepwise approach to investigate the effects of Baseline WMH and rates of WMH Extension and Emergence on the rate of change in episodic memory and executive functions including gender, years of education, ethnicity, BV and the baseline corresponding cognitive score as covariates.

Results:
Analyses revealed significant increases in total WMH burden over time. In addition, baseline WMH volume and rate of WMH Extension, but not Emergence, were significantly associated with rates of change in cognitive measures with larger baseline WMH and higher rate of WMH Extension being associated with steeper rate of decline in executive functions and episodic memory (see
Figure1
).

Discussion:
This work provides evidence that the extension over time of WMH, but not newly formed WMH, is a predictor of the rate of cognitive decline. This result is of importance as the extension of WMH accounted for about 80% of the overall WMH.
Abstract 49: Diagnostic Yield of Catheter Angiography in Patients with Subarachnoid Hemorrhage and Negative Initial Non-Invasive Neurovascular Examinations
Authors: Delgado Almandoz Josser E , Crandall Benjamin M , Fease Jennifer L , Scholz Jill M , Anderson Ruth E , Tubman David E
Published: March 2022

Purpose:
To determine the yield of catheter angiography for the detection of causative vascular lesions in patients with subarachnoid hemorrhage (SAH) who have a negative initial non-invasive neurovascular examination.

Methods:
Between January 1st, 2006 and August 1st, 2011, we instituted a prospective protocol by which patients who presented to our institution with SAH and had a negative initial non-invasive neurovascular examination (CT or MR angiogram [CTA, MRA]) were examined with catheter angiography to detect causative vascular lesions. Two experienced neuroradiologists evaluated the NCCTs to determine the pattern of SAH (diffuse, perimesencephalic or peripheral) and the catheter angiograms to assess for the presence of a causative vascular lesion. All differences in reader interpretation were resolved by consensus.

Results:
Forty-eight patients were included in our study, with a mean age of 58 years (median 59 years, range 25-84 years). Twenty-six patients were male (54.2%) and 22 female (45.8%). Twenty-eight patients had diffuse SAH (58.3%), 11 peripheral SAH (22.9%) and 9 perimesencephalic SAH (18.8%). The initial non-invasive neurovascular examination was a CTA in 41 patients (85.4%) and an MRA in 7 patients (14.6%). A second catheter angiogram was performed in 30 patients (62.5%). Mean time interval between the initial non-invasive neurovascular examination and the first catheter angiogram was 0.9 days (median 1 day, range 0-7 days) and the second catheter angiogram was 12.2 days (median 8.5 days, range 4-69 days). Catheter angiography demonstrated a causative vascular lesion in 4 patients (8.3%), 3 of which had diffuse SAH (yield of 10.7%) and 1 had peripheral SAH (yield of 9.1%). Of note, 1 of the causative vascular lesions was identified in a second catheter angiogram performed 8 days after the CTA in a patient with diffuse SAH. The vascular lesions identified were 2 dural arteriovenous fistulas, 1 pial cerebellopontine angle arteriovenous malformation with a 2-mm feeding artery aneurysm located in the internal auditory canal (
Figure
), and a 3-mm anterior communicating artery aneurysm. Two of the vascular lesions underwent endovascular embolization, 1 radiosurgery and 1 endovascular embolization followed by radiosurgery. In retrospect, the vascular lesion could be seen in the initial examination in 2 patients.

Conclusion:
Catheter angiography is a valuable tool in the evaluation of patients with diffuse and peripheral SAH who have a negative initial non-invasive neurovascular examination, demonstrating a causative vascular lesion in 10.7% and 9.1% of patients, respectively.
Abstract 50: A Novel Method for Quantification of Brain Edema in Ischemic Stroke
Authors: Tipirneni Aaryani , Straka Matus , Lansberg Maarten G , Mlynash Michael , Bammer Roland , Albers Gregory W
Published: March 2022

Background:
Measurement of final infarct volumes are typically done on MRI or CT scans obtained at 30 or 90 days after symptom onset. At these delayed time points, true infarct volume is often underestimated because of atrophy. Moreover, late imaging leads to a high percentage of missing data due to early mortality and poor compliance with late imaging. Obtaining an early assessment of infarct volume avoids these limitations; however, it overestimates the true infarct volume because of vasogenic edema. The aim of this study was to develop a novel approach to quantify brain edema so that final infarct volumes can be approximated on day 5 scans.

Method:
We analyzed MRI scans from 15 acute stroke patients enrolled in the DEFUSE 2 study. The edema volume was determined by comparing spatially-coregistered ADC maps obtained at baseline and at day 5. Edema displaces CSF from the sulci and the ventricles. We therefore estimated the edema volume as the change in CSF volume between baseline and follow-up. CSF displacement was determined by analyzing ADC maps; a voxel by voxel comparison was performed and voxels with ADC values that shifted from the CSF range (2.0-4.4 x 10
-3
mm
2
/s) to the parenchymal range (0.60-1.05 x 10
-3
mm
2
/s) were considered to represent edema (yellow region in
figure
). The analysis was performed on 5 control patients with no or very small lesions (2.4±2.0 mL on FLAIR) and 10 patients with large lesions (240±115 mL on FLAIR).

Results:
The mean volume of CSF displacement in the control group was 1.6±2.4 mL. CSF displacement (edema volume) in the large infarct group ranged from 33 to 152 mL. The estimated edema volume, as a percentage of the overall day 5 FLAIR lesion volume, ranged from 15% to 52%. Linear regression analysis performed between day 5 FLAIR lesion volumes and the estimated edema volumes produced a correlation coefficient (r)of 0.78 (P< 0.01) with a slope of 0.31.

Conclusion:
Vasogenic edema can be measured based on assessment of CSF displacement. Using this novel technique we determined that the day 5 FLAIR lesion volume, on average, overestimates the final infarct volume by 31%. These findings suggest that the final infarct volume can be accurately estimated from an MRI scan obtained during the vasogenic edema phase. Validation of this technique, using data sets that have infarct volume determinations at multiple time points, is in progress and results will be presented.
Abstract 55: Correlation Of Carotid Intraplaque Hemorrhage With Acute Territorial Cerebral Ischemic Events Using Magnetic Resonance Imaging
Authors: McNally Joseph S , Kim Seong-Eun , Yoon Hyo-Chun , Findeiss Laura , Roberts John , Daniel Nightingale , Krishna Narra , Dennis Parker , Gerald Treiman
Published: March 2022

Background:
Carotid intraplaque hemorrhage has been associated with clinical stroke symptoms and can be detected with MPRAGE (Magnetization-Prepared Rapid Acquisition with Gradient-Echo). Currently, there are no studies correlating carotid intraplaque hemorrhage (IPH) concurrent with acute territorial ischemic events defined by brain diffusion weighted imaging (DWI). Our aim was to determine the association of carotid intraplaque hemorrhage with acute territorial ischemic events using carotid MPRAGE and brain DWI.

Methods and Results:
Carotid IPH was defined as at least 2-fold higher carotid MPRAGE signal intensity compared to adjacent sternocleidomastoid muscle. Using the MPRAGE sequence, IPH was identified with an accuracy of 91.2%, sensitivity of 91.3%, and specificity of 90.9% as compared to histology in 91 slides from 10 endarterectomy subjects. The Kappa values for interobserver and intraobserver agreement on MPRAGE signal were 0.806 and 0.818 respectively (very good agreement). After the addition of the MPRAGE sequence to the neck MRA protocol, 131 consecutive patients with suspected acute stroke were evaluated with both brain DWI and carotid MPRAGE sequences over the course of 1.5 years, providing 262 carotid artery and paired brain images for analysis. 34 arteries were excluded due to an extracarotid etiology of brain ischemia and 4 were excluded due to carotid occlusion. 224 arteries were eligible for data analysis. Carotid IPH was associated with acute territorial ischemic events with a relative risk of 4.1 (p<0.05). This is demonstrated by the representative image below depicting left carotid IPH as hyperintense MPRAGE signal (left) and an acute ischemic event in the left middle cerebral artery distribution with diffusion restriction on brain DWI (right). The relative risk of an ischemic event with carotid IPH was increased in mild, moderate and severe stenosis categories (5.1, 2.9, and 1.8, p<0.05).

Conclusion:
In the workup of acute stroke, carotid IPH increased the risk of simultaneous territorial cerebral ischemic events in all carotid stenosis categories. By using objective data from brain DWI, accurate risk assessment of vulnerable plaque components can be obtained.