bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 204: High Framingham Cardiovascular Risk Scores are of Prognostic Value in Recent Ischemic Stroke Patients without known Coronary Heart Disease
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: March 2022

Background:
Stroke and myocardial infarction (MI) share similar risk factors and pathophysiological mechanisms. Ischemic stroke (IS) patients often harbor asymptomatic coronary heart disease (CHD); furthermore, beyond one month after the index stroke, they are at a higher risk of death from MI than recurrent stroke. Framingham Cardiovascular Risk Score (FCRS) is a simple, widely recognized tool for estimating 10-year risk for “hard” CHD outcomes, but its role as a prognosticator after recent stroke has not been assessed.

Objectives:
To determine the prevalence, predictors, and prognosis of high FCRS (≥ 20%) among recent IS patients.

Methods:
Analysis of a trial dataset involving 3680 recent (≤120 days) IS patients aged ≥ 35 years, recruited from 56 centers between 1996 and 2003, and followed for 2 years. We determined prevalence of high FCRS among subjects without known CHD. Association between baseline vascular risk factors and high FCRS were assessed using multivariable logistic regression. Cox models with and without competing risks were used to determine the associations between high FCRS vs. primary (stroke, MI, vascular death) and secondary (stroke) outcomes.

Results:
Of 2547 subjects (∼70% of cohort) who met study criteria, 37% had a high FCRS. Prior carotid endarterectomy (CEA), hypertension, and higher NIHSS, BMI, triglyceride, and LDL levels were associated with high FCRS. After adjusting for age and sex, BMI ≥30 kg/m
2
(HR 1.66, 95% CI 1.25–2.20), triglyceride level >150 mg/dL (OR 2.86, 95% CI 2.29–3.56), LDL level >100 mg/dL (OR 2.62, 95% CI 2.04–3.36), black vs. white race (OR 1.72, 95% CI 1.08–2.72) and other vs. white race (OR 1.78, 95% CI 1.31–2.43) were associated with higher odds of high FCRS, while alcohol use in the past year was associated with lower odds of high FCRS (OR 0.73, 95% CI 0.59–0.92). After adjusting for sociodemographic characteristics, vascular risk factors, stroke severity, and medication use at baseline, high FCRS was associated with a higher risk of stroke, MI or vascular death (HR 1.43, 95% CI 1.14–1.81)(
Figure
). The adjusted association between high FCRS and recurrent stroke followed a similar trend, but was weaker and not significant.

Conclusions:
Over 1/3 of recent IS patients without known CHD have a high FCRS. High FCRS among such patients independently confers a higher risk of a major vascular event within 2 years. Using available information on history/risk profile, FCRS could be a cheap, practical, and sustainable way for clinicians to identify IS patients who may benefit from add-on CHD-specific therapies and to assess progress of major vascular risk modification.
Abstract 2128: Development and Impementation of a Nursing Swallow Screen
Authors: Ware James , Mil Elizabeth , Sanfilipo Geri , Townsend Helene , Leatherman Kristine , Littig Scott , Weber Cheri , Stein Sandra J
Published: March 2022

Development and Implementation of a Nursing Swallow Screen Timely and safe administration of medications and PO intake for patients is essential. The goal of Capital Health (CH) was to develop and implement a standard swallowing screen completed by nursing for all patients admitted to a comprehensive stroke center with the confirmed or potential diagnosis of CVA or TIA. A review of literature and communication with other hospitals and the American Speech Language and Hearing Association uncovered a limited amount of information about swallowing screens. The CH Swallowing Screen was designed by the Stroke Team using information from other hospitals and input from the Nursing and Speech Pathology Departments at CH. The Swallowing Screen, comprised of 3 distinct sections, was designed to be sensitive to aspiration and determine the safety of gross swallowing skills or the need for a complete swallowing assessment by a certified Speech Language Pathologist (SLP). An added benefit of this screen was more rapid access to oral medications and PO intake. After screen development and nursing staff education, the form became a standard part of the admission process for all patients admitted to CH with a confirmed or potential diagnosis of CVA/Stroke or TIA. The following variables were selected as key components of the program: - If the patient passed the Swallowing Screen but was referred for a full evaluation, were the findings of the full assessment in agreement with those of the screening? - If a patient failed the Swallowing Screen, was s/he referred for a full evaluation by the SLP? - If the patient passed the Swallowing Screen, was s/he then placed on a diet? Data was collected from January 2008 to December 2010. Results indicate that the CH Swallowing Screen is being used both accurately and effectively. Agreement between the initial screening and full assessment (variable #1) improved from 91% in 2008 to 100% in 2010. During the same time period, effectiveness of the process (variable #2 and #3) improved from 83-98% and 87% to 92% respectively. Patients who pass the screen are now receiving oral medications and an oral diet in a more timely fashion. Patients who do not pass the screen are being referred to the SLP for a full assessment, while maintaining NPO status until that assessment is completed. Finally, the nursing staff has demonstrated proficiency to assess gross swallowing skills, as evidenced by agreement when patients who passed the screen were also evaluated by the SLP and no diet modifications were necessary. The development and implementation of the swallowing screen at CH has enhanced the timeliness and quality of treatment provided to CVA/stroke patients. Finally, use of this screen has fostered increased awareness and facilitated collaboration between Nursing and the Speech Pathology Department, thus improving the effectiveness of patient care and becoming part of the culture at CH.
Abstract 22: Increased Cerebral Perfusion Pressure Delays the Microvascular Shunting and Tissue Hypoxia in the Rat Brain at High ICP in a Time Dependent Manner
Authors: Bragin Denis E , Bush Rachel C , Nemoto Edwin M
Published: March 2022

Background:
We reported earlier that high intracranial pressure (ICP) in rats is associated with tissue hypoxia and brain edema due to a transition from capillary (CAP) to thoroughfare channel (TFC) non-nutritive shunt flow. Recently we showed that increasing cerebral perfusion pressure (CPP) shifts the transition threshold to a higher ICP. Here we studied the time dependence of the transition to TFC shunt flow at high ICP to determine how long the increased CPP could delay the transition from CAP to TFC shunting

Methods:
ICP was increased and maintained at 20, 40 or 60 mmHg for three hours by raising an artificial cerebrospinal fluid reservoir connected to a catheter in the cisterna magna while MAP was elevated by i.v. dopamine infusion to keep CPP at 60 or 80 mmHg. Using
in vivo
2-photon laser scanning microscopy through a cranial window over the rat parietal cortex, we measured microvascular red blood cells flow velocity (by fluorescein dye) and tissue oxygenation (NADH fluorescence). CAP flow = microvessel flow velocities < 1.0 and TFC shunt flow = microvessel flow velocities >1.0 mm/sec. Doppler flow, rectal and cranial temperatures, ICP, arterial blood pressure and arterial blood gases were monitored.

Results:
Maintenance of CPP at 60 mmHg even at a moderate ICP of 20 mmHg did not prevent a gradual increase in microvascular shunting and tissue hypoxia over 3 hours. However, a CPP of 80 mmHg prevented the transition from CAP to TFC shunting at an ICP of 20 mmHg (
Fig. 1
, p<0.05). At ICP of 40 and 60 mmHg and CPP of 60 and 80 mmHg there was a gradual decrease in the CAP/TFC ratio (increased microvascular TFC shunting) and rise in NADH with time. However at a CPP of 80 mmHg, the gradual increase occurred at later time points and was less detrimental than at CPP of 60 mmHg (
Fig. 1
, p<0.05).

Conclusions:
Increasing CPP with raised ICP could prevent the transition from CAP to TFC shunt flow and tissue hypoxia for a duration that depends upon the level of CPP. Thus, the transition to shunt flow at a given raised ICP and sustained CPP is time dependent. Our data suggest that increasing CPP above the clinical guideline of 50 to 60 mmHg may be beneficial at high ICP.
Abstract 2200: Altered Mental Status “Code Strokes” Rarely Result in Ischemic Diagnosis
Authors: Bruce Nhu , Raman Rema , Ernstrom Karin , Meyer Brett , Hemmen Thomas
Published: March 2022

Background:
The clinical diagnosis of acute ischemic stroke remains challenging, especially with many diagnoses mimicking ischemia. Frequently, Code Stroke activations are initiated in patients who are found not to have focal brain ischemia. To better understand the frequency, diagnoses and outcomes of mimics, we analyzed our Code Stroke population for patients with altered mental status (AMS) but without focal neurological deficits.

Methods:
We analyzed all patients from the University of California San Diego (UCSD) Code Stroke database, in whom scoring of the entire NIHSS upon admission was available, from 2004 to 2010. Patients with AMS but without focal neurological deficit were defined by initial NIHSS score: On questions 1a or 1b or 1c: ≥ 1; and 5a=5b (motor arm) and 6a=6b (motor leg) and 9=0 (aphasia). The final diagnosis was based on Code Stroke review by a panel of cerebro-vascular subspecialty trained physicians. Univariate logistic regression was used to examine the association between outcomes (90 day mRS, discharge disposition and death) and age, gender, race, ethnicity, baseline NIHSS, pre-stroke modified Rankin score, prior stroke, hypertension and diabetes. Good outcome was defined at mRS (0-1) at 90 days. Good discharge disposition was defined as discharge home or to acute rehabilitation.

Results:
We identified 108 patients who met our inclusion criteria. Of those, 18 (17%) had a diagnosis of acute ischemic stroke, 10 (9%) TIA and 75 (69%) were categorized as other. Of those “other” patients, 14/75 (19%) were diagnosed with seizure post-ictal, 15 (20%) with toxic-metabolic encephalopathy, 6 (8%) somatization and 7 (9%) intoxication. Only 5/108 patients were treated with thrombolysis. Discharge dispositions were known in 107/108 (99%). 73/107 (68%) of all patients and 56 out of the 75 (75%) patients diagnosed with “other” had good outcomes. Only baseline NIHSS was associated with discharge disposition with p=0.0025.

Conclusion:
Only 1 in 4 (26%) Code Stroke patients that presented with AMS and no signs of focal neurological impairment were noted to have a cerebral ischemia diagnosis. Alteplase was rarely used (none in the non-ischemic patients) and most of the “other” non-ischemic patients (75%) had good discharge disposition and clinical outcome. In this cohort, most patients who presented with AMS but without lateralizing signs on their neurological exam were not diagnosed with acute ischemic event. Therefore perhaps more common etiologies should be explored prior to initiating a code stroke solely for the presentation of AMS.
Abstract 2207: Racial Disparities in Ischemic Stroke Mortality
Authors: McKinney James S , Deng Yingzi , Paolucci Ugo , Kostis John B
Published: March 2022

Introduction---
Stroke is more prevalent in blacks than whites. CDC data suggest age-adjusted mortality may be 3-fold higher in blacks. However, an analysis of the Get With The Guidelines-Stroke registry found a lower risk of in-hospital death in blacks. We hypothesized that black and white stroke patients differed in both in-hospital and longer term mortality, as well as in cause of death.

Methods---
We used the Myocardial Infarction Data Acquisition System (MIDAS) database, which includes demographic and clinical data on patients discharged with a primary diagnosis of cerebral infarction from all non-federal acute care hospitals in New Jersey between 1996 and 2007. Out-of-hospital deaths were assessed by matching MIDAS records with New Jersey death registration files. In-hospital, 1-year, and interval (discharge to 1-year) mortality were calculated. Total, cardiovascular disease (CVD), and non-CVD mortality were calculated. Multivariate logistic regression models were used to measure the effect of race on in-hospital, 1-year, and interval mortality after adjusting for demographics, comorbid conditions, hospital type, year of admission, and treatment. Statistical significance was defined as a
P
-value ≤ 0.05.

Results---
123,326 patients were admitted with a primary diagnosis of cerebral infarction during the study period. Significant baseline differences existed between black and white stroke patients (
Table
). Intravenous tPA rates were low overall, but no difference existed between races (Black 1.29% versus White 1.39%, p=0.3) Overall, in-hospital and 1-year mortality rates were 6.5% and 18.9% for blacks and 9.3% and 26.9% for whites. After adjusting for available covariates, no significant difference was observed between races for in-hospital (OR = 1.00; 95% CI = 0.93 to 1.06), 1-year (OR = 0.99; 95% CI = 0.95 to 1.03), or interval (OR = 0.98; 95% CI = 0.93 to 1.03) mortality. Blacks were less likely to die in the hospital from CVD causes (OR = 0.66; 95% CI = 0.58 to 0.76). However, this racial disparity was no longer observed in deaths occurring in the year after discharge (OR = 0.94; 95% CI 0.86 to 1.03).

Conclusion---
Black stroke patients in New Jersey are on average almost 10 years younger, more likely to be female, and have more comorbid conditions than their white counterparts. No difference was observed for adjusted in-hospital or 1-year mortality. Black patients are more likely to die from non-CVD related conditions during the initial hospitalization.
Abstract 2247: A Very Early Neurological Improvement After Intravenous Thrombolysis For Acute Cerebral Ischemia Does Not Necessarily Predict A Favorable Outcome.
Authors: Bodenant Marie , Debette Stéphanie , Cordonnier Charlotte , Dumont Fréderic , Girot Marie , Hénon Hilde , Lucas Christian , Bordet Régis , Leys Didier
Published: March 2022

Background:
in patients treated by intravenous (i.v.) thrombolytic therapy after cerebral ischemia, a very early neurological improvement (VENI) (National Institutes of Health Stroke Scale score [NIHSSS] 0, or early improvement >5 points), predicts a favorable outcome. VENI patients are therefore usually excluded from trials testing complementary strategies. However, a few of them have bad outcomes.

Objective:
to determine why VENI patients may have bad outcomes

Methods:
we analyzed the reasons for bad outcomes (modified Rankin scale [mRS] score 2 to 6 at month-3) in consecutive VENI patients.

Results:
of 365 consecutive patients with a pre-stroke mRS 0-1 (185 men; median age 69 years; median NIHSSS 12; median onset-to-needle time 147 min), 71 (19.5%) had VENI. They were more likely to have had recent transient ischemic attacks (OR: 3.64; 95% CI: 1.08-12.27), higher baseline NIHSSS (median 14 vs. 11; p=0.003), and shorter onset-to-needle times (median 135 min vs. 151; p=0.01), and less likely to develop pneumonia (OR: 0.27; 95% CI: 0.09-0.76) or malignant infarction (p=0.045). In the 21 VENI patients (29.6%) with a mRS 2 to 6 at month-3 , bad outcomes were due to the residual deficit in 14, secondary worsening of ischemia in 4, intracranial hemorrhage in 2, and death from cancer in 1.

Conclusion:
one-third of VENI patients have bad outcomes, due to the residual neurological deficit in most of them. This finding suggests that VENI patients who still have a significant neurological deficit one hour after thrombolysis should not be excluded from trials testing complementary strategies.
Abstract 2258: Ambulance Directed Care for Acute Stroke Patients at Cedars-Sinai Medical Center
Authors: Steiner Nili E , Guerra Sonia , Paletz Laurie , Robertson Betty , Rosenfield Paula , Wolber Nicole
Published: March 2022

Quality Improvement Study: Background:
Advances over the last decade highlight the important role of Emergency Medical Services (EMS) agencies in optimizing stroke care. Los Angeles County’s Department of Health Services (LA County DHS) Stroke Patient Policy was instituted on November 16, 2009. As a result, ambulances now transport suspected stroke patients directly to approved Stroke Centers. In a single institution-TJC certified as a PSC since 2008, we studied the effect of the Stroke Patient Destination Policy and ambulance-directed care on the percentage of ischemic stroke patients receiving acute stroke treatments (IV tPA, intra-arterial thrombolysis or clot-retrieval, or bridge therapy).

Methods:
2, 156 patient charts were retrospectively reviewed from the 16 months prior to the implementation of ambulance-directed care compared to a 16-month period between after implementation of ambulance-directed stroke care.

Results:
In the pre-policy period, 344 suspected stroke patients arrived by EMS versus 491 suspected stroke patients arriving by EMS in the post-policy period - a 30% increase. (Chi
2
p=0.07). Of 344 patients, 34 (9.9%) received acute stroke treatment in the pre-policy period, compared to 63 of 491 patients receiving acute stroke treatments in the post-policy period (12.8%, NS). The median age of patients pre and post policy change was 69.5 years old. The median gender distribution was 46% male and 54% female. Neither age nor gender differed before or after the policy change.

Conclusions:
Implementation of the LA County DHS Stroke Patient Destination Policy appeared to cause a higher volume of acute stroke patients receiving treatment at one Joint Commission certified academic medical center. The data suggests that 29 additional patients were treated with acute stroke treatments due to ambulance directed care. Additional confirmatory data is needed from other centers.
Abstract 2261: Presence of Large Deep White Matter Lesion May Predict Futile Recanalization in Endovascular Therapy for Acute Ischemic Stroke
Authors: Tateishi Yohei , Wisco Dolora , Cummings Christopher , Ammar Tamer , Bhalla Tarun , George Pravin , Katzan Irene , Gebel James , Toth Gabor , Hui Ferdinand , Hussain Muhammad S , Uchino Ken
Published: March 2022

Background:
A subset of stroke patients treated with endovascular recanalization therapy suffers poor outcome despite good arterial recanalization. The aim of this study is to identify whether large ischemic lesion in deep white matter (DWM) on diffusion weighted imaging (DWI) prior to therapy predicts futile recanalization.

Method:
Consecutive acute stroke patients with anterior circulation ischemia whose artery had been recanalized at Thrombolysis in Myocardial Infarct (TIMI) flow grade 2 or 3 following endovascular therapy were included. All patients underwent CT and MRI before endovascular therapy. We defined large DWI - DWM lesion if DWI showed the hyperintense lesion in the DWM which mostly extended between anterior and posterior horn of the lateral ventricle. We identified Alberta Stroke Program Early CT Scores (ASPECTS) of CT and DWI, and volumes measured on initial DWI and mean transit time of perfusion weighted images. We assessed the prevalence of TIMI grade 3 recanalization and parenchymal hemorrhage type 2, and final ischemic lesion volume after endovascular therapy. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Futile recanalization was defined as a 30-day modified Rankin Scale score 3 to 6 despite recanalization at TIMI grade 2 or 3. Univariate and multivariate regression analyses were performed to identify predictors of futile recanalization.

Results:
Partial or complete recanalization (TIMI grade 2 or 3) was observed in 35 of 46 patients (76 %). Of the 35 patients, futile recanalization was observed in 20 patients (57 %). Patients with futile recanalization had older age (median, 74 versus 58 years old, p = 0.053), higher initial NIHSS score (median, 17 versus 9, p = 0.042), pre-treatment large DWI - DWM lesion (45 versus 9 %, p = 0.022), and larger final ischemic lesion volume (median, 37 versus 9 ml, p = 0.003). ASPECTS of CT (median, 9 versus 9, p = 0.527) and DWI (median, 8 versus 8, p = 0.943) and initial ischemic lesion volumes on DWI (median, 21 versus 14 ml, p = 0.230) and on mean transit time (median, 189 versus 192 ml, p = 0.976) did not demonstrate statistically significance between patients with and without futile recanalization. There were also no significant differences between the outcome groups in times from stroke onset to imaging or endovascular therapy. Logistic regression analysis demonstrated that large DWI - DWM lesion was an independent predictor of futile recanalization (OR 10.40, 95 % CI 1.03 to 105.21, p = 0.047).

Conclusion:
Patients who have large pre-treatment DWI - DWM lesion may be poor candidates for endovascular therapy.
Abstract 2283: Relative Deficiency of Vascular Endothelial Growth Factor (VEGF) in Subarachnoid Hemorrhage.
Authors: Testai Fernando D , Aiyagari Venkatesh , Hillmann Maureen , Amin-Hanjani Sepideh , Max Joann , Dawson Glyn , Gorelick Philip B
Published: March 2022

Cerebral vasospasm (VS) after subarachnoid hemorrhage (SAH) is associated with delayed cerebral ischemia and poor neurological outcome. We have recently reported that shortly after SAH, there is a dramatic elevation in the levels of the endogenous VEGF-antagonist soluble
fms-
like tyrosine kinase-1 (sFlt1), particularly among individuals that will later develop symptomatic VS (sVS). Based on this observation we have proposed that an imbalance in the levels of endogenous angiogenic and anti-angiogenic factors occurs in SAH. In this study we examined the association of cerebrospinal fluid (CSF) levels of VEGF, sFlt1, and VEGF/sFlt1 ratio with vasospasm in SAH patients. We studied seventeen patients with Fisher Grade 3 aneurysmal SAH and five controls with no prior history of neurological disorders who underwent lumbar puncture for headache and had normal CSF studies. Demographics and medical history were documented. Patients were followed prospectively and samples of CSF were obtained within 48-hours of symptoms onset. VEGF and sFlt1 levels were determined using commercially available ELISA tests (R&D Systems). SAH subjects were subcategorized into those with sVS and those who did not develop symptomatic VS (noVS). sVS was defined as the occurrence of neurological deterioration in the setting of angiographically proven VS and in the absence of other conditions that could explain the neurological decline. Ratios and levels of the compounds of interest in the different groups were compared using the nonparametric Mann-Whitney U test. Age, history of hypertension, exposure to elicit drugs, RBC count in the CSF and proteinorrachia were not statistically different between sVS and noVS groups. Similar to what has been described by others, compared to controls, SAH patients showed a trend towards having higher VEGF levels in the CSF (106±53 vs. 180±172 pg/mL); this, however, did not reach statistical significance (p>0.05). The CSF levels of sFlt1 were 46±23 pg/mL in the control group and 598±423 pg/mL in the SAH group (p=0.01). Among patients with SAH, sFlt1 levels were 1018±797 pg/mL in the sVS group and 304±184 pg/mL in the noVS group (p=0.01). The mean VEGF/sFlt1 ratios were 2.27±0.25 in controls, 0.39±0.25 in SAH patients, 0.23±0.10 in the sVs group, and 0.61±26 in the noVS group (p=0.02). An early elevation in sFlt1 levels and a relative deficiency of VEGF occur in the CSF of SAH patients, particularly in those with sVS. These results suggest that an imbalance in the production of angiogenic and anti-angiogenic factors may be part of the pathogenesis of VS and that analysis of these molecules might potentially have a role in predicting sVS in SAH patients.
Abstract 2287: Treatment of Acute Stroke in Patients on Dabigatran: A Survey of US Stroke Specialists
Authors: Rybinnik Igor , Mullen Michael T , Messe Steve , Kasner Scott E , Cucchiara Brett
Published: March 2022

Background and Purpose:
There are no guidelines for the use of thrombolytic therapy in acute stroke patients taking dabigatran (DBT), or DBT reversal strategies in patients with ICH. We assessed how stroke neurologists plan to care for these patients.

Methods:
An internet-based questionnaire was sent to all US board-certified stroke neurologists. Case scenarios for patients on DBT with acute ischemic stroke were presented with varying stroke severity, time from symptom onset and last DBT dose, and activated partial thromboplastin time (PTT), and questions assessed whether and when IV and/or catheter-based thrombolysis would be used. Questions also assessed treatment of patients with DBT-associated ICH. Open-ended comments on the cases were also solicited.

Results:
Responses were available from 221/809 stroke neurologists surveyed. Of these, 88% reported that they were somewhat or very familiar with DBT. For an ischemic stroke patient 2 hours post onset and eligible for IV tPA except for use of DBT (time of last dose unknown), 49% would not treat with IV tPA regardless of PTT, 28% would treat if the PTT was normal, 9% if PTT <40 sec, and 4% regardless of PTT. Stroke severity did not appear to greatly modify the decision to treat. When time of last DBT dose was known and the PTT was normal, 21% would treat regardless of time since last dose, 14% would treat only if last dose > 12 hours, 15% only if > 24 hrs, 13% if >48 hrs, 5% if > 4 days, and 15% would not treat regardless of the time from last dose; 10% wanted additional information such as creatinine clearance. For the 3-4.5 hour window, 26% indicated they would be equally likely to treat as within 3 hours, 26% would be less likely to treat, 17% would not treat, and 24% would not treat in < 3 or 3-4.5 hours. Between 8-14% of respondents answered the above questions by saying they were not sure what they would do. For catheter-based lysis, 25% indicated they would treat with IV tPA but would prefer catheter lysis if available, 30% indicated they would use IV tPA and consider catheter lysis as they would for any patient not on DBT, 36% would only use catheter lysis, and 9% would not use IV tPA or catheter lysis. For a patient with DBT associated ICH, 73% said they would attempt reversal of DBT. The following reversal strategies were chosen (more than one could be selected): FFP -53%; factor VIIa - 24%; prothrombin complex concentrates - 61%; platelet transfusion - 7%; hemodialysis - 24%. Some respondents commented that they would use thrombin time and not PTT to select patients on DBT for lysis, and many requested guidance on what should be done in these scenarios.

Conclusions:
There is a remarkable lack of consensus amongst stroke neurologists regarding the assessment and treatment of acute stroke patients on DBT. More data on the evaluation and treatment of these patients is urgently needed.
Abstract 2292: Dipyridamole Induced Headache Indicates Lower Recurrence Risk in Secondary Prevention of Ischemic Stroke
Authors: Diener Hans-Christoph , Sacco Ralph , Yusuf Salim , Cotton Dan , Gorelick Philip B , Bath Philip , Lipton Richard B , Davidai Giora
Published: March 2022

Background
Headache is a common adverse event in patients treated with dipyridamole (DP) for secondary stroke prevention. The headache resembles migraine, possibly indicating that vessel walls and endothelium of cerebral vessels are still intact and able to dilate.

Purpose
We hypothesized that patients who develop headache on DP will have a lower risk of recurrent stroke compared to patients without headache.

Methods
We analysed data from PROFESS (N=20,332) comparing aspirin plus DP with clopidogrel. Prospective data on headache as an adverse event within 7 days of start of medication or reason for discontinuation of study drug and recurrent stroke incidence were collected. We compared the relative risk of recurrent stroke in patients who did and did not get headache and who did or did not discontinue study medication due to headache. Analyses were repeated in the smaller ESPS 2 study (N=6,602) investigating aspirin, aspirin plus DP, DP or placebo in secondary stroke prevention.

Results
In PROFESS 3067 patients taking aspirin plus DP complained of headache in the first 7 days while 6988 did not. In the aspirin plus DP group, the recurrent stroke risk after 2.5 years was 8.2% in patients with and 9.4% in patients without headache resulting in a RR of 0.90 (95% CI 0.81-1.01, p= 0.07). In the clopidogrel treated group there was no difference in stroke risk between patients with and without headache RR = 1.00 (95% CI 0.82-1.23). In PROFESS, 518 patients taking aspirin plus DP discontinued treatment due to headache in the first 90 days. Their risk of recurrent stroke was 5.0%. In patients who did not discontinue aspirin plus DP due to headache in the first 90 days, the recurrent stroke risk was 9.2% resulting in a RR of 0.53 (95% CI 0.36-0.79, p=0.001). In the clopidogrel treated patients the RR was 0.89(95% CI 0.36-2.20); 7.9% of 63 clopidogrel patients who discontinued due to headache within 90 days of randomization had stroke vs. 8.9% in all other patients. In ESPS 2, 129 patients taking aspirin plus DP discontinued treatment due to headache in the first 90 days. Their rate of recurrent stroke was 6.2%. In patients who did not discontinue aspirin plus DP due to headache in the first 90 days, the recurrent stroke rate was 9.8% resulting in a RR of 0.63 (95% CI 0.31-1.26, p=0.18).

Conclusions
In PROFESS patients who developed headache on aspirin plus DP for secondary stroke prevention had a reduced risk of stroke recurrence in comparison with those who did not or were treated with clopidogrel. These results are directionally supported by similar but non-significant findings on treatment discontinuation of aspirin plus DP in ESPS 2. Headache in clopidogrel treated patients did not demonstrate any protective effects, suggesting specificity. These results suggest that DP-induced headache may be a marker for more reactive vessel walls in cerebral arteries.
Abstract 2324: Translational Stroke Research: Identification Of A Novel Family Of Natural Product Derived Flavonoid-Based Polyphenols With Potent Pleiotropic Neuroprotective Activity.
Authors: Lapchak Paul A , Schubert Dave , Maher Pamela
Published: March 2022

Multiple plant (fruits, vegetables) and spice (turmeric)-derived natural products, which have pleiotropic activities (anti-inflammatory, antioxidant, anti-apoptotic, neurogenic) are also neuroprotective in vitro against numerous chemical insults and promote behavioral recovery in vivo following embolic strokes. We have focused on 2 types of natural products: 1) curcumin-based compounds such as CNB-001 and 2) flavone-based compounds such as fisetin and baicalein. We have synthesized a new library of flavonoid molecules to improve their pharmacological characteristics and have selected candidates using a battery of vitro screening assays with stringent criteria: 1) HT22 hippocampal cell survival (in vitro ischemia model using 20µM iodoacetic acid); 2) primary mouse cortical neurons cell survival (in vitro excitotoxicity assay using 10µM glutamate); 3) HT22 hippocampal cell survival assay (oxytosis using 5 mM glutamate to induce non-NMDA mediated cell death due to the absence of NMDA receptors on HT22 cells). EC50 ≤ 100 nM and survival ≥80% in the IAA assay, ≥35% survival in the cortical neuron assay and EC
50
≤ 300 nM and ≥50% survival in the oxytosis assay. All compounds were screened in triplicate using concentrations up to 10 µM. We chemically modified fisetin to improve its potency, increase blood brain barrier penetration (CLogP, an indicator of blood brain barrier penetration) and reduce tPSA (topographical polar surface area). We have developed a structure activity relationship (SAR) indicating that the absence of a hydroxyl group on the A ring of fisetin enhances its potency. Two compounds PM-001 and PM-004) are 6 fold more potent than fisetin. Altering a hydroxyl group at the 3-position of the B ring has no impact on activity. The addition of multiple hydrophobic groups to various positions on the A ring, such as the addition of methyl groups at the 6 and/or 7 position improved potency ∼10-100 fold over fisetin (e.g. compound PM-010) while the addition of a more hydrophobic naphthalene group (PM-002) and (PM-003) improved the potency ∼40 fold over fisetin and increased the ClogP and reduced the tPSA. SAR studies on the C ring suggested that hydrogen bond accepting groups such as a methoxy at the 4' position and a hydrogen bond donating group such as a hydroxyl at the 3' position further enhanced potency. For example compound CMS-064, CMS-069 and CMS-092 are some of the most potent compounds, with EC
50
s below 40 nM. These compounds also have CLogPs and tPSAs consistent with enhanced brain penetration. In conclusion, we have used a rational medicinal chemistry approach in combination with in vitro screening analysis to identify new flavonoid molecules to optimally promote neuroprotection. The molecules which will be discussed in detail are being further characterized and de-risked to treat stroke.
Abstract 2342: Sphingosine Kinase & Sphingosine 1-phosphate Modulation On Microglia And Brain Derived Endothelial Cells
Authors: Kacimi Rachid , KARLINER Joel S , YENARI Midori A
Published: March 2022

Sphingolipid metabolites, have emerged as a new class of potent bioactive molecules, implicated in a variety of cellular processes. In particular, sphingosine-1-phosphate (S1P) the product of sphingosine phosphorylation, through transactivation of five cognate G protein-coupled receptors namely endothelial cell differentiation gene receptors (EDGs/S1P1-5), promotes proliferation, differentiation, enhances cell survival and inhibits apoptosis in different cellular systems. Modulation of sphingolipids and their receptors has been shown in some stroke models to be neuroprotective and anti-inflammatory. We undertook this study to elucidate the role of S1P receptor subtypes and sphinosine kinase (SPHK) in models of brain derived endothelial cells and microglia. We studied mono and co-cultures where endotoxin (LPS) activated microglia stimulate endothelial cell death. After documenting SPHK1/ 2 expression in microglia by immunofluorescence, we found that an agonist of SPHK ((2-(p-Hydrozyanilino)-4(p-chlorophenyl) tiazole, SKI) preserved microvascular endothelial cells, and markedly prevented microglia-induced endothelial cell injury. Furthermore, SKI inhibited iNOS and NO generation in microglia by both endotoxin as well as a second TLR4 agonist (Kdo2-Lipid (ADi[3-deoxy-D-manno-octulosonyl]-lipid A) (*P<0.01). S1P (1) agonists SEW-1 and FTY720 and endogenous ligand S1P had no significant effect in on microglia-mediated cell injury or NO induction by LPS. However, preincubation with the S1P (3) antagonist (
CAY10444
) dose dependently prevented NO accumulation, while JTE-013 (S1P2 antagonist) &
VPC23019
(S1P1 antagonist) were effective in preventing NO release. Our findings indicate that sphingosine phosphorylation promotes immune responses in microglia and its blockade, especially SPHK1 and to lesser extent S1P (3) attenuated these responses. This inhibition also led to decreased cell death due to immune cell activation. Our data suggests that targeting aspects of the sphingolipid pathway may be a new strategy to inhibit microglia activation and preserving endothelial cell integrity in relevant cerebrovascular pathologies such as stroke, trauma, or sepsis
Abstract 2354: Prospective Determination of %NODS (Not consistent with Organic Deficit of Stroke) Likelihood with Resultant rt-PA Safety and Functional Outcome
Authors: Sodhi Ajeet , Raman Rema , Ernstrom Karin , Meyer Dawn M , Guzik Amy K , Ovbiagele Bruce , Hemmen Thomas M , Meyer Brett C
Published: March 2022

Objective:
To assess safety and functional outcomes of rt-PA patients prospectively assigned a high %NODS score. NODS include mimics, functional overlay and complex presentations of mild symptoms. Background: Evidence exists that mimics may be safe to treat but the act of giving rt-PA often results in a stroke diagnosis. Additionally, patients with ICH are unlikely to be coded as non-strokes. Attempts to assess mimics are usually done retrospectively, however after treatment there is often uncertainty in classification of patients as ‘NODS’ or ‘True Stroke.’ Prospective designations of such may not be recorded. To our knowledge, this is the first outcome study for patients prospectively labeled with a high %NODS score prior to rt-PA treatment.

Methods:
We reviewed the UCSD SPOTRIAS database, (8/09-Present) for patients prospectively defined as NODS (% likelihood that deficits are Not consistent with Organic Deficits of Stroke) ≥75% and NODS≥50%. Baseline characteristics, safety (SxICH), and outcome (90-day mRS(0-2)) were compared to ‘True Strokes’ (NODS≤25%). Continuous variables were compared using Wilcoxon-Rank Sum. Categorical variables were compared with Fisher's Exact.

Results:
There were 114 'True Strokes', 7 NODS≥75%, and 12 NODS≥50%. Mean age was 70.7, 51.9 (p=0.0064) and 51.1 years (p<0.001) respectively. Pre-stroke mRS(0-2) was 85.1%, 100% (p=0.59) and 91.7% (p>0.999). Baseline NIHSS was 11.5, 7.7 (p=0.36) and 6.6 (p=0.08). Outcomes were adjusted for baseline mRS. Home d/c was 40.95%, 71.4% and 66.7%. 90-day mRS(0-2) was 50%, 66.7% and 70%. Ambulance use was 85.1%, 57.1% and 58.3%. SxICH was 6.2%, 0%, 0%. Timelines were similar except for “Onset to Arrival” (74min, 42min, 61min), and “CT to decision” (22min, 43min, 38min).

Conclusions:
Small numbers precluded statistical significance, but absolute numbers were of clinical interest. NODS patients were younger, had less prior deficit, had milder strokes, activated EMS less frequently (possibly due to mild or less “real” deficit), had better 90-day mRS, less ICH, shorter 'onset-arrival' (perhaps arriving earlier due to improved recognition, increased fear of true or perceived deficit, or even EMS issues) but longer 'CT-decision' (perhaps requiring more time to consider pros and cons of rt-PA therapy). This intriguing exploratory analysis serves to generate hypotheses for our subsequent larger studies. If verified, high %NODS score patients may be considered safe for rt-PA therapy.
Abstract 2356: Predicting Factors Of Developing The Malignant Middle Cerebral Artery (MCA) Infarction For An Acute Mca Infarction With Main Mca Occlusion
Authors: Bae Hyo-jin , Cha Jae Kwan , kim Dae Hyun
Published: March 2022

Background :
Malignant middle cerebral artery (MCA) infarction is leading cause of death for acute MCA infarction patients. Early detection of patients who can develop the malignant MCA infarction (MMI) is important for timely decision for life-saving treatment such as an decompressive surgery. So we studied to figure out a reliable predicting parameters for developing MMI using acute stroke magnetic resonance imaging (MRI) such as diffusion and perfusion images.

Methods :
We included 209 MCA infarction patients with main MCA occlusion within 6 hours of symptom onset between January 2007 and December 2010 in Dong-A University Stroke center. All patients were performed brain MRI including diffusion and perfusion images. Vessel occlusion was diagnosed by MR angiography. We used regional cerebral blood volume (rCBV) ratio as a representing parameters of perfusion image. The rCBV ratio was calculated by comparing the blood volume of the ischemic lesion with that of the corresponding unaffected contralateral region.Definition of the malignanat MCA infarction was as following : 1) deterioration of neurological and consciousness with clinical signs of uncal herniation and mass effect, 2) large space-occupying MCA infarction or at least two-third of the MCA territory with compression of ventricles of midline shifting. We observed any changes of neurological deterioration within 7 days of symptom onset. Severity of neurological symptom and clinical outcome were assessed by using National Institute Stroke Severity Scale (NIHSS) and the modified Rankin Scale (mRS).

Results :
Among 209 pts, 84 (40.2%) developed MMI, and 125 (59.8%) did not (non-MMI). In a univariate analysis, MMI group was more older (69.08 vs 63.54), more additional lesion in ACA or PCA territory (13.1% vs 1.6%), higher NIHSS score. In MMI group, MCA with ipsilateral ICA occlusion was more frequent (76.2% vs 40.0%), and larger diffusion volume (99.13 vs 21.57), lower rCBV ratio (0.53 vs 0.87). Also, the presence of diffusion-perfusion mismatch (DPM) was more common in non-MMI group (80.8% vs 46.4%). In MMI group, large portion of patients were included in mRS 5-6 group (61.4%) compared with non-MMI group (15.8%). In a multivariate analysis, these parameters were identified as a predicting factors of MMI : larger diffusion volume (OR :1.02, 1.01-1.04, p<0.001), lower rCBV ratio (OR :0.97, 0.95-0.99, p<0.001), higher NIHSS on admission (OR: 1.31, 1.16-1.47, p<0.001). The cutoff value of diffusion volume, NIHSS on admission and rCBV ratio were 69ml, 15 point and 0.66 respectively.

Conclusion :
Brain MRI including diffusion and perfusion image, especially diffusion volume and rCBV ratio can predict malignant course in MCA infarction with main MCA occlusion patients within 6 hours of symptom onset.
Abstract 2372: Error Rate Estimates for the modified Rankin Score “Shift Analysis” Using Information Theory Modeling
Authors: Krumpelman Chase S , Mandava Pitchaiah , Kent Thomas A
Published: March 2022

Background:
There remains debate as to the most appropriate functional outcome measurement in acute stroke trials. One approach is to use the whole range of ordinal/categorical variables of the modified Rankin Score (mRS), often termed “Shift Analysis”. Here we consider one of its main theoretical bases, Shannon’s information theory. Noise in Shannon’s model assumes the signal transmitted is uniform. However, van Swieten (Stroke 1988), and others show that the errors (noise), in the mRS are predominantly in the mid-range values of 2-4. In order to test the applicability of Shannon’s concept to shift analysis, we used entropy models to quantify errors with the primary noise considered in this range.

Methods:
We identified 16 randomized stroke trials that reported the full range of mRS. A custom Matlab® program was written to simulate Shannon’s model both when the whole range of mRS was used and with commonly used dichotomous cut-points of mRS0-1 or mRS0-2 and mRS 6. Each stroke trial’s mRS distribution was multiplied with the “confusion matrix” from Table 1 of van Swieten’s mRS inter-rater variability. This matrix is equivalent to a band-limited noise in the signal-processing sense. The output of this step produced a misclassification/error percentage for each mRS category both from the full range of mRS or with specified cut-points. Error rates were compared by ANOVA.

Results:
If the full range of mRS is considered, error rates ranged from 22 to 32% (Mean ± SD: 26% ± 2.8). If mRS 0-1 and mRS 6 were cut-points, then error ranged from 2.6 to 13.4% (7.5% ± 2.5). Error rates for mRS 0-2 and mRS 6 were 6.9 to 14.3% (8.8% ± 1.8; overall p<0.001).

Conclusion:
We show from an information theory perspective that when the uncertainty in the midrange mRS is considered, there are relatively high error rates if the full range is used. Lower error rates were found with specified cut off dichotomization. Federov et al (2009) contend there is loss of information with dichotomization. However, this view does not consider the non-random distribution of noise and it assumes a Poisson distribution of mRS values. As seen in the left
figure
, none of the 16 trials had a Poisson distribution (compare to right panel modeling different Poisson distributions). We conclude that while use of entire mRS range is conceptually appealing, even if these were Poisson distributions, any potential gain of information with considering the complete scale is accompanied by a decrease in fidelity, hence more uncertainty regarding the validity of the outcome compared to dichotomization.
Abstract 2382: Self-rated Health is an Independent Predictor of Incident Stroke: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study
Authors: Singh Jasvinder A , Howard Virginia , Cushman Mary , Safford Monica , Howard George , Muntner Paul
Published: March 2022

Objective:
Self assessments of health contain important information on factors that influence outcomes that are not routinely captured in traditional risk factors. Few data are available on whether they are associated with incident stroke independent of traditional risk factors.

Methods:
We evaluated the association between self-rated health and incident stroke using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national, population-based cohort study of 30,239 African-American and white adults aged ≥ 45 years. Framingham stroke risk factors (current smoking, systolic blood pressure, antihypertensive medication use, diabetes, atrial fibrillation, coronary artery disease and left ventricular hypertrophy) and self-rated health were collected during a baseline examination. Participants reported self-rated health on a single question “In general, how would you rate your health?” with response options of excellent, very good, good, fair or poor. Similar to previous studies, excellent and very good self-rated health was grouped for analysis.

Results:
Of 24,708 REGARDS study participants without a history of stroke at baseline and included in this analysis, 534 had an incident stroke over a median of 5.1 years of follow-up. Compared to participants reporting excellent/very good health, the unadjusted hazard ratios (95% confidence intervals [CI]) for incident stroke associated with good, fair and poor health were 1.41 (1.17 - 1.70), 1.98 (1.56 - 2.51), and 3.21 (2.21 - 4.67), respectively (p-trend<0.001). After adjustment for age, race, sex and Framingham risk factors, the respective hazard ratios (95% CI) for stroke were 1.14 (0.94 - 1.39), 1.39 (1.08 - 1.80), and 2.09 (1.41 - 3.10) (p-trend<0.001).

Conclusion:
Self-rated health is an independent predictor of incident stroke even after adjusting for traditional stroke risk factors.
Abstract 2394: A Systematic Review of Respiratory Muscle Training in Stroke and Neurological Diseases
Authors: Pollock Ross , Rafferty Ged , Moxham John , Kalra Lalit
Published: March 2022

Background:
Respiratory muscle weakness in stroke patients may contribute to increased risk of pneumonias. We undertook a meta-analysis of randomised controlled trials (RCT) of respiratory muscle training (RMT) to investigate their benefit in stroke patients.

Method:
A literature search for relevant articles was performed on Medline, EMBASE, ISI web of knowledge and the Cochrane Central Register for Controlled Trials. Key words searched were
stroke, cerebrovascular accident, multiple sclerosis, Parkinson’s disease, motor neurone disease
and
neurolog*
in combination with
inspiratory, expiratory, respiratory
or
ventilatory
and
training, loading
and
muscle
. Studies were assessed for quality and analyses were undertaken following Cochrane guidelines. The primary outcome measure of muscle strength was the maximum inspiratory mouth pressure (PImax).

Results:
The search identified 1140 articles of which 34 remained after screening aganist pre-defined criteria and removal of duplicates. Of these 25 were excluded because 17 were not RCTs, 1 did not assess PI max and 7 investigated children. A total of 103 patients were included in the 9 eligible studies (2 stroke, 7 other neurological diseases). PImax was greater in patients receiving respiratory muscle training compared with controls at the end of training (WMD 6.94 cmH
2
O, 95% CI 2.84 - 11.04, P = 0.0009). The 2 studies in stroke patients included only 24 patients but showed a definite benefit in improving respiratory muscle strength (WMD for PI max 6.93 cmH
2
O, 95% CI 1.76 12.09, P = 0.009). (
Fig 1
)

Conclusion:
Large trials of RMT in stroke are lacking but there is a suggestion that stroke patients have a potential to benefit. Large well designed studies are needed to evaluate the effectiveness of RMT for improving respiratory muscle strength and clinical outcomes in stroke patients.