bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2886: Time To Thrombolysis: Does It Make A Difference In Outcome In A Statewide Telestroke Network?
Authors: Yaghi Shadi , Hinduja Archana , Keyrouz Salah G
Published: March 2022

Objective:
to determine whether IV thrombolysis 0-3 hours vs. 3-4.5 hours in a statewide telestroke network result in a difference in outcome.

Background:
The Arkansas SAVES (Stroke Assistance through Virtual Emergency Support) telestroke network provided emergency evaluation and therapy for acute stroke to 22 spoke sites statewide between November 2008 and May 2011. The spoke hospitals range from large to critical access hospitals. Following thrombolysis, patients are cared for at the spoke, or get transferred to one of the hub PSC hospitals. Outcome following IV thrombolysis depends largely on severity of the stroke, and door to needle time, but also on post-thrombolysis care. There is no current data on outcome depending on time window to thrombolysis in a telestroke network.

Methods:
Institutional IRB approval was obtained to review the prospective database of the Arkansas SAVES program. We included all patients who received IV thrombolysis. We divided them into two groups, based on time window to thrombolysis (0-3 hours vs. 3-4.5 hours). Baseline characteristics, time intervals, laboratory data, and post thrombolysis care location (hub vs. spoke) were compared between the groups. For statistical analysis, we used independent T, and fisher’s exact tests. A multivariate regression analysis was performed.

Results:
The cohort included 562 patients receiving a teleconsultation between November 2008 and May 2011, of whom 116 underwent IV thrombolysis and were included in this analysis. Patients who received IV thrombolysis 3-4.5 hours were more likely to be males (OR = 2.64, p = 0.028), younger than 70 years (OR = 2.33, p = 0.047), and to have door to needle time > 90 minutes (OR = 2.22, p = 0.062). Their mean time (minutes) to presentation was significantly longer (45.7 ± 24.0 vs. 105.5 ± 47.5, p < 0.0001). The outcome at 90 days and rate of intracerebral hemorrhage was similar between the groups.

Conclusion:
In a hub and spoke model of a telestroke network, there is no difference in outcome between patients receiving IV thrombolysis 0-3 hours vs. 3-4.5 hours. A longer time to thrombolysis was caused not only by a delay in patients’ presentation, but also by a longer door to needle time, offering an opportunity for improvement in efficiency of those involved in the teleconsultation process.
Abstract 2901: Do working-aged stroke survivors experience economic hardship in Australia? The Psychosocial Outcomes In Stroke (POISE) Study
Authors: Essue Beverley M , Hackett Maree L , Li QIANG , Glozier Nicholas S , Lindley Richard I , Jan Stephen
Published: March 2022

Introduction:
Approximately 12,000 working-aged Australians survive a stroke each year. Most will experience some level of disability during their recovery which can negatively affect the economic well-being of their household. The economic consequences include unemployment, reduction in paid employment and changes in career for both the patient and often a family carer. There are also unbudgeted costs associated with medical care, home modifications, transport and paid care. Thus, recovery from stroke can be associated with substantial household economic hardship. This study is the first to investigate the household economic burden of stroke recovery in working-aged Australians.

Methods:
This was a multi-centre, three year cohort study that recruited a representative sample of younger (< 65 years) stroke survivors to determine the modifiable psychosocial and economic predictors of subsequent return to work. Participants were recruited from the New South Wales Stroke Services network. This paper reports a secondary analysis of the predictors of economic hardship associated with stroke recovery. Hardship was measured using questions about financial stress and financial coping strategies employed.

Results:
A total of 416 participants completed assessments at baseline (pre-stroke) and at six and 12 months after their stroke. At baseline, 36% of participants reported hardship. This increased to 52% at six months and fell to 44% at 12 months and included 137 new cases of hardship post-stroke. The main sources of financial stress reported at 12 months included: utility bills (21%), rent and mortgage payments (15%), medications and medical equipment (10%) and medical care (9%). To maintain expenses at one year, participants most frequently used their savings (40%) and borrowed money (20%). The baseline variables that predicted hardship post-stroke included: gender (females versus males; OR, 2.3; 95% CI, 1.3 to 4.3), level of alcohol consumption (heavy drinker versus not a heavy drinker; OR, 2.3, 95% CI, 1.1 to 5.1) and economic hardship at baseline (OR, 3.1; 95% CI, 1.8 to 5.4).

Conclusion:
Despite strong health and social welfare supports in place in Australia, this study demonstrates that younger stroke survivors experience considerable economic hardship during their recovery. We have identified the main sources of financial stress for this cohort and a sub-group of patients who may be most at risk of experiencing hardship. This research provides a basis to investigate the additional policy supports required to better assist stroke survivors in Australia.
Abstract 2902: Usefulness Of Adenosine Induced Transient Cardiac Arrest For Aneurysm Decompression Without Temporary Clipping In Intracranial Aneurysm Clipping
Authors: Yun Jung-Ho , Kwun Byung Duk , Kwon Do Hoon , Park Eun-Suk
Published: March 2022

Introduction:
Temporary clipping of proximal vessel in intracranial aneurysm clipping can be used in a generalized procedure to reduce flow to the aneurysm, but this method has own disadvantages including postoperative ischemia or the possibility to obscure the surgeon’s view during clipping. On the other hand, adenosine induced transient cardiac arrest facilitated the safe clipping of the aneurysm by producing relaxation of the brain and the aneurysmal sac decompression without temporary clipping. Its action is characterized by a rapid onset, brief duration and rapid spontaneous reversal without associated complications.

Hypothesis:
Aneurysm clipping with adenosine induced cardiac arrest is the safe and brief procedure without any cardio-pulmonary or neurologic complications.

Methods:
We used a retrospectively collected 527 patients’ database which was treated by intracranial aneurysm clipping from January 2010 to June 2011 in our institution and selected 13 patients who had adenosine induced cardiac arrest during aneurysm clip application. Arrest time, arrest frequency, arrest achieving dose and recovery of cardiac arrest recorded on anesthesia record, and the report focuses on outcome data including aneurysm decompression, incidence of successful clipping, perioperative cardio-pulmonary or neurologic complications.

Results:
All of the 13 patients had sinus rhythm and normotension before operation and had been confirmed as good function by cardio-pulmonary consultation and examination. Twelve patients had unruptured intracranial aneurysms and another one patient had a ruptured anterior communicating artery aneurysm. The mean of cardiac arrest achieved dose was 20 mg with ranging from 6 to 63 mg and the mean arrest time was 26 seconds with ranging from 4 to 90 seconds. Satisfactory aneurysm decompression was achieved in all 13 cases, and all aneurysms were clipped successfully without temporary clipping and wide neck dissection although we had two sudden ruptured cases during operation. Also, all patients had no perioperative complications including cardio-pulmonary problems and cerebral infarction within mean follow-up period 5 months (2∼12 months).

Conclusions:
Adenosine induced transient cardiac arrest is a relatively unfamiliar method for aneurysmal sac decompression to facilitate clipping of an aneurysm. But, with preoperative sufficient evaluation of cardio-pulmonary system, accurate monitoring during operation time and intimate co-operation between the surgeon and the anesthesiologist, this method is an excellent procedure with good effectiveness and safe option to facilitate clipping of an aneurysm, especially the following 3 situations: 1) large sized aneurysms with nonvisulization of proximal vessel. 2) paraclinoid aneurysms with impossible proximal neck dissection. 3) sudden aneurysm rupture during operation.
Abstract 2930: Prevalence of Unrecognized Atrial Fibrillation and Stroke Risk in an Otherwise Healthy Population Over 40: A Significant Target for Stroke Prevention
Authors: Deif Bishoy , Freedman Saul Ben
Published: March 2022

About 22% of AF-related ischemic stroke occurs in incidentally documented AF. This prompted us to determine the proportion of the general population that may have unrecognized Atrial Fibrillation (AF) and may therefore be at risk of stroke. We hypothesized that a significant proportion of those with incidentally found AF would have no symptoms and a CHADS2 score high enough to put them at risk of stroke. We reviewed surgical pre-admission ECGs, routinely performed in all patients over 40 years of age and examined medical records of those in AF. Of 1894 ECGs reviewed, 77 (4.1%) showed AF. Medical records of 53/77 (representing 1469 of the 1894 ECGs) were available for review but the study is ongoing. AF was incidentally found in 6/1469 patients (0.4%) and previously diagnosed in 47 (3.2%). The mean age of those in AF was 76 ± 9 and similar in incidental and previously diagnosed AF (74 ± 5 vs. 77 ± 9). Average CHADS2 score was high in both groups: 3.0 ± 1.7 in incidental AF and 2.4 ± 1.2 in previously diagnosed AF. Only 26/37 of those with previously diagnosed AF and CHADS2 score > or = 2 were on Warfarin, consistent with the known evidence-practice gap for thrombo-prophylaxis. The mean resting heart rate was 77 ± 16 in incidental AF, and 78 ± 18/min in previously diagnosed AF. Only 2/6 with incidentally discovered AF reported palpitations. AF is prevalent, and is unrecognized in about 1/200 of a relatively healthy population over 40. Unrecognized AF is generally unassociated with symptoms and resting heart rate is not elevated. Those with unrecognized AF usually have CHADS2 score high enough to warrant anti-coagulation, which suggests that there are appreciable numbers of the well elderly in the community who would benefit from AF recognition through simple detection programs such as feeling the pulse or recording an ECG, followed by thrombo-prophylaxis to prevent future stroke.
Abstract 2938: Decreased Glomerular Filtration Rate Has A Greater Impact On The Outcome In Hemorrhagic Stroke Than In Ischemic Stroke In Acute Stage.
Authors: Ishizaka Shunsuke , Tateishi Youhei , Horie Nobutaka , Hayashi Kentaro , Tsujino Akira , Suyama Kazuhiko , Nagata Izumi
Published: March 2022

Background and Purpose-
Recently, chronic kidney disease: CKD has been focused on the stroke, and decreased glomerular filtration rate (GFR) is reported to be a risk factor for stroke. However, little is known about the difference of impact on the outcome between ischemic stroke and hemorrhagic stroke in acute stage. Here we analyzed the impact of an estimated GFR on prognosis in relation to stroke type.

Methods-
Between July 2007 to July 2010, 433 consecutive patients with acute stroke in our institute were retrospectively analyzed. (Ischemic stroke: N=270, Hemorrhagic stroke: N=163). Estimated GFR (eGFR) was calculated according to the abbreviated modification of diet in renal disease formula in all patients. CKD was categorized by the estimated GFR into severe CKD group (<30), moderate/mild CKD group (30-60) and no CKD group (>60 ml/min/1.73 mm
2
). Patients characteristics, the location and volume of the lesion were analyzed.To examine the relationship between CKD and the outcome assessed with in-hospital mortality and National Institute of Health Stroke Scale (NIHSS), multivariable analyses were conducted.

Results-
In severe and moderate/mild CKD groups, patients with ischemic stroke had a higher age and a lower baseline NIHSS compared to patients with hemorrhagic stroke. (p=0.0001) Among both ischemic and hemorrhagic stroke, groups with poorer eGFR had a significantly higher mortality than groups with better eGFR. (Hemorrhagic stroke: 38%, 14.2% and 5.5% p<0.0001, Ischemic stroke: 15%, 11.1% and 2.2% p<0.0001) A rate of lesion volume expansion after admission was higher in hemorrhagic stroke than in ischemic stroke. (p=0.001) In multivariate analysis, we found a significant stronger correlation between decreased eGFR and in-hospital mortality, a rate of lesion volume expansion in hemorrhagic stroke than in ischemic stroke.

Discussion and Conclusions-
Decreased glomerular filtration rate have a greater impact on the outcome of hemorrhagic stroke than that of ischemic stroke in acute stage. The expansion of the lesion volume might contribute to this result.
Abstract 2941: Wide Variability of Cerebral Blood Volume Response in the Area with Impaired Cerebrovascular Reactivity to Acetazolamide due to Occlusive Carotid Artery Disease
Authors: Ito Masaki , Kuroda Satoshi , Hokari Masaaki , Nakayama Naoki , Hirata Kenji , Shiga Tohru , Houkin Kiyohiro , Tamaki Nagara
Published: March 2022

Background and Purpose -
Recent studies have suggested that hemodynamic and metabolic responses to reduced cerebral perfusion pressure (CPP) are not so simple in patients with occlusive carotid artery disease. Autoregulatory vasodilation reaches maximal and cerebral blood flow (CBF) starts to fall, when CPP critically falls beyond autoregulatory capacity. Theoretically, cerebral blood volume (CBV) is expressed as maximally elevated in the conditions that cerebrovascular reactivity (CVR) to acetazolamide (ACZ) is impaired. However, there are almost no studies that denote whether CBV is maximally elevated in the area with reduced CBF and CVR to ACZ (Kuroda’s Type 3 ischemia). Therefore, this study was aimed to investigate the CBV response to ACZ in the area with reduced CBF and CVR due to occlusive carotid artery disease.

Methods-
This study included totally 24 hemispheres of 20 patients with reduced CBF and CVR on
15
O-gas PET due to occlusive carotid artery disease. There were 8 men and 12 women with a mean age of 57.9 years ranging from 33 to 72 years. All of them were admitted to our hospital between 2004 and 2010. In all 20 patients, CBF, CBV, cerebral metabolic rate for oxygen (CMRO
2
) and oxygen extraction fraction (OEF) were quantitatively measured, using
15
O-gas PET. Subsequently, ACZ was intravenously injected to determine the reactivity of CBF and CBV.

Results-
Both CBF and CVR were reduced in all 24 hemispheres (Type 3). Of these, OEF was elevated in 7 hemispheres (29%). Compared with normal control (3.4 ± 0.5 mL/100g), baseline CBV were significantly elevated both in elevated OEF group (5.2 ± 1.2 mL/100g) and normal OEF group (4.5 ± 0.9 mL/100g). Intravenous administration of ACZ further increased CBV in 4 of 7 hemispheres with elevated OEF and in all 17 hemispheres with normal OEF. %CBV reactivity was 9.5 ± 12% in elevated OEF group, being significantly lower than 22 ± 13% in normal OEF group (P = 0.04, un-paired t). CBV did not increase in patients with steal phenomenon after ACZ injection in elevated OEF group, but increased in normal OEF group.

Conclusion-
These findings strongly suggest that baseline CBV increases, but does not reach maximal in the area with reduced CBF and CVR due to occlusive carotid artery disease, indicating that CBF response to ACZ may imply more complicated mechanisms in the severe ischemic brain.
Abstract 2947: Differentiating Antegrade Flow Across Intravascular Thrombus from Retrograde Collateral Flow in Occluded Cerebral Arteries: Initial Experience Using Time-Resolved CT Angiography
Authors: Frölich Andreas M , Schramm Ramona , Klotz Ernst , Knauth Michael , Schramm Peter
Published: March 2022

Introduction:
In acute stroke patients with occluded cerebral arteries, angiographic demonstration of antegrade opacification distal to an occlusion has been associated with higher rates of vessel recanalization. We sought to determine whether antegrade flow can be demonstrated on near-whole-brain time-resolved four-dimensional CT angiography (4D-CTA) and whether it can be differentiated from retrograde collateral flow.

Methods:
Among 123 consecutive patients with angiographically proven acute intracranial anterior circulation vessel occlusion, thin-section 4D-CTA data obtained as part of a diagnostic multi-modal CT exam were available in 48 cases, 47 of which met inclusion criteria. Pre-treatment thrombolysis in cerebral infarction (TICI) grade, presence of the outline sign (defined as antegrade contrast opacification distal to the thrombus) and presence of retrograde collateral flow extending to the distal thrombus end were assessed on 4D-CTA. Digital subtraction angiograms were reviewed for pre-treatment TICI grade, presence of the outline sign as well as post-intervention TICI grade.

Results:
On 4D-CTA, evidence of antegrade flow was present in 5 of 47 cases (10.6%). Compared to angiography, 4D-CTA correctly classified antegrade flow in 4 cases (80.0%), there was 1 false positive and no false negatives. Recanalization (TICI ≥2a) was achieved in all 5 cases with evidence of antegrade flow on 4D-CTA versus 34 out of the 42 cases (81.0%) without evidence of antegrade flow.

Conclusion:
Using 4D-CTA, it is possible to differentiate antegrade flow across a cerebral artery occlusion from retrograde collateral flow. Further studies, preferably with a larger sample size are needed to confirm our findings and assess whether 4D-CTA can be used to predict success of recanalization procedures in select cases.
Abstract 2948: Ischemic Transient Neurological Events Identified by Immune Response to Cerebral Ischemia
Authors: Jickling Glen , Zhan Xinhua , Stamova Boryana , Ander Bradley P , Tian Yingfang , Liu Dazhi , Sison Shara-Mae , Verro Piero , Johnston S. Claiborne , Sharp Frank R
Published: March 2022

Background and Purpose:
Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE.

Design/Methods:
Analysis of 208 TIAs, ischemic strokes, controls and TNE was performed. RNA from blood was processed on microarray. TIAs (n=26) and ischemic strokes (n=94) were compared to controls (n=44) to identify differentially expressed genes (FDR<0.05, fold change ≥|1.2|). Genes common to TIA and stroke were used predict ischemia in TIA-DWI positive / minor-stroke (n=17), nonischemic TNE (n=13) and TNE of unclear etiology (n=14).

Results:
Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving predominantly granulocytes and B-cells. A prediction model using the common response to ischemia distinguished TIA and strokes from controls with 89% sensitivity and specificity. In the validation cohort, 17/17 TIA-DWI positive / minor-strokes were predicted to be ischemic, and 10/13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD2 scores.

Conclusions:
A common peripheral response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology were identified based upon gene profiles that may be of clinical utility with further development.
Abstract 2962: Recovery from Post-Stroke Visual Impairment: Evidence from a Clinical Trials Resource
Authors: Ali Myzoon , Hazelton Christine , Brady Marian , Lyden Patrick , Pollock Alex
Published: March 2022

Introduction:
Visual impairment after stroke may impact overall disability, but the natural history of recovery from visual impairment (VI) after stroke is poorly characterized. We examined recovery from eye movement disorders and visual field defects after stroke.

Methods:
We extracted anonymised data on age, medical history, modified Rankin Score (mRS), National Institutes of Health Stroke Scale (NIHSS) and European Quality of Life Score (EQ-5D) from the Virtual International Stroke Trials Archive (VISTA). We described eye movement disorders and visual field defects using the Best Gaze and Visual domains of the NIHSS and related these to recovery at 90 days. As visual neglect was not available in our dataset, we used the Extinction domain on the NIHSS to provide a broad measure of neglect of personal, visual, tactile, auditory or spatial stimulation. We used Proportional Odds Modelling, adjusting for age, medical history, vision-unrelated NIHSS domain scores [total baseline NIHSS score - (Best Gaze + Visual Scores)], rt-PA administration and type of stroke to examine associations among VI at baseline, functional outcome (mRS) and quality of life (EQ-5D) at 90 days.

Results:
Eye movement disorders or visual field defects were reported in 7,123/11,623 (61.3%) patients at baseline. By 90 days, these impairments had resolved in 3,177/7,123 (44.6%) patients but persisted in 2,074/7,123 (29.1%); 1,622/7,123 (22.8%) patients had died and 250/7,123 (3.5%) patients were lost to follow up. The total burden of persistent VI at 90 days in all stroke survivors was 2,074/9,384 (22.1%). Complete homonymous hemianopia was most prevalent at both baseline (n=4,165; 35.9%) and at 90 days (n=1,071; 11.5%). Partial gaze palsy (p<0.0001, OR=0.15, 95% CI [0.13, 0.17]), forced deviation (p<0.0001, OR=0.48, 95% CI [0.44, 0.54]) and complete homonymous hemianopia (p<0.0001, OR=0.67, 95% CI [0.61, 0.72]) at baseline were associated with poor functional outcome by mRS at 90 days. Partial gaze palsy and forced deviation at baseline were associated with poorer scores on all domains of EQ-5D except Anxiety/Depression. Thrombolysis was associated with recovery from VI at 90 days (p<0.0001 OR =2.32, 95% CI [2.02, 2.67]).

Conclusions:
VI is arguably a major stroke-related impairment with 22% of all stroke survivors exhibiting persistent visual impairment at 90 days. The extent to which VI causes poor outcome or is simply associated with severe stroke merits further investigation. The consequences of a co-existing VI should be considered in stroke multidisciplinary rehabilitation assessments and interventions.
Abstract 2977: Sex Differences and Hemoglobin Levels in Relation to Stroke Outcomes
Authors: Kimberly William , Lima Fabricio , O'Connor Sydney , Furie Karen
Published: March 2022

Background:
Women have worse outcomes after ischemic stroke compared to men. Several mechanisms are postulated, including older age and a differential effect of sex hormones. We have previously shown that hemoglobin levels are associated with increased stroke volume and infarct expansion. Since women have lower hemoglobin values, we examined whether hemoglobin levels may be associated with poorer stroke outcomes in women.

Methods:
We retrospectively studied 274 patients (N = 121 women, N = 153 men) enrolled in a prospective study. We explored the relationship of hemoglobin with clinical outcome at 6 months, as measured by the modified Rankin Scale. We employed ordinal logistic regression to evaluate the effect of hemoglobin on clinical outcome and to explore the influence of sex on that association.

Results:
Women had a lower hemoglobin level (11.7 +/- 1.8 g/dL) compared to men (13.3 +/- 1.7 g/dL; P < 0.001). Low hemoglobin was correlated with worse 6-month mRS outcome in univariate analysis (P < 0.001). Lower hemoglobin remained independently associated with poorer outcome after adjustment for age, sex, blood glucose, NIH stroke scale score, hypertension, smoking and diabetes mellitus. The inclusion of hemoglobin in the model eliminated the independent effect of sex on outcome.

Conclusions:
Sex differences in stroke outcome may be mediated in part by lower hemoglobin levels, a potentially modifiable predictor. Further examination exploring whether hemoglobin has a causative role is warranted.
Abstract 2978: Size Matters, but so do Broca's Area and Anterior Temporal Cortex, in Recovering from Apraxia of Speech
Authors: Trupe Lydia A , Hillis Argye E , Gottesman Rebecca F
Published: March 2022

Background:
Apraxia of speech (AOS) is considered a deficit of motor planning and programming of speech articulation. In chronic stroke patients, the anterior insula has previously been associated with AOS using lesion overlap studies. However, the anterior insula association with AOS might be due to the typically large areas of infarction in patients with chronic AOS, as insula is infarcted in 94% of patients with stroke due to occlusion of the left middle cerebral artery. We hypothesized that the volume of infarct in chronic stroke patients would be significantly associated with AOS, and we sought to identify other regions that, when damaged, would cause deficits in motor speech programming after controlling for infarct volume.

Methods:
We tested a series of 34 patients at least 6 months post onset of left supratentorial ischemic stroke with the Apraxia Battery for Adults II and obtained concurrent MRI. Patients received scores on 4 apraxia tests: Increasing Word Length Parts A and B, Repeated Trials (which scores errors in the repetition of the same polysyllabic word) and Inventory of Articulation (which scores characteristics of AOS observed during spontaneous speech, reading, and automatic speech). MRI (FLAIR sequences) were analyzed by a technician masked to apraxia results for presence or absence of ischemia in each of 11 Brodmann’s areas (BA) as well as the anterior and posterior insula. The technician also conducted volumetric analysis on each MRI; volumes were recorded (cm3). We identified associations between impaired apraxia measures and both areas of infarct and lesion volumes using age-adjusted linear regression models.

Results:
There was a strong association between lesion volume and AOS, as measured by Inventory of Articulation (coefficient=1.48 more points (worse score) per 10 cc larger infarct; p=0.002) and Repeated Trials (coefficient=-0.91 (worse score) per 10 cc increase; p=0.008). After adjustment for both volume and age, lesions in BA 44 and 45 (Broca’s Area) were significantly associated with AOS, as measured by Inventory of Articulation (coefficient=12.07, p=0.009 for both BA 44 and 45). BA 20 and 38 lesions were also associated with AOS, as measured by Repeated Trials scores (coefficient= -22.7, p=0.008 for both). Additionally, there was a strong association between lesions in the posterior insula and Inventory of Articulation scores (coefficient= 3.23, p=0.007).

Conclusion:
In chronic stroke patients, lesion size is highly correlated with AOS. Chronic damage to Broca’s Area and anterior temporal cortex (BA 38, 20), as well as posterior insula, is also associated with AOS, regardless of lesion size. These areas may be important for recovery of speech planning.
Abstract 3021: Areas of Chronic Infarct Associated with Impaired Verbal Working Memory
Authors: Varma Daniel , Hillis Argye E , Gottesman Rebecca F
Published: March 2022

Background:
Functional imaging studies consistently show activation of Broca's area (Brodmann's area 44 and 45) in verbal working memory (VWM) tasks such as backward digit span, indicating that this area is an important node in the network underlying VWM. We have recently shown acute infarcts in Brodmann’s area (BA) 45 are associated with impaired VWM. However, there is surprising little evidence that chronic lesions of Broca's cause deficits in VWM, although there are case reports and small series of patients with both with normal and impaired VWM. Other areas of the brain might assume this function during recovery. We tested the hypothesis that chronic infarcts in BA 44 and 45 are associated with reduced backward digit span.

Methods:
Patients had tests of backward digit span and MRI at least 6 months after first left supratentorial ischemic stroke. Technicians blinded to digit span results analyzed FLAIR sequences for infarct in BA 4, 6, 10, 11, 19, 20, 21, 22, 37, 38, 39, 40, 44, 45, anterior and posterior insula. Associations between between VWM and ROIs were identified using Fisher's exact tests for dichotomous data. Differences in mean span length between those with and without lesions in each area were identified with t-tests. Additionally, using linear regression analysis (adjusted for age and education level), we determined which areas, when infarcted, predicted backward span length.

Results:
79 patients (mean age 57.2 years; mean education 13.6 years) were included. Reduced VWM (defined as backward digit span <3) was associated with infarct in BA 44 (p=0.002) and BA 45 (p=0.001). Patients with infarct in Broca’s area had significantly shorter backward digit spans than those without (BA 44: 1.3 vs 4.2; p=.003; BA 45: 1.0 vs 4.15; p= 0.006). Using linear regression, infarct in BA 44 was associated with, on average, 2.5 fewer digits on digit span backwards compared to cases without BA 44 infarct (adjusted beta=-2.5; 95% CI -3.4, -1.7), BA 45 (beta=-2.8, 95% CI -3.6, -2.0). BA 39 (adjusted beta=-1.8, 95% CI -2.9, -0.7) or BA 40 (adjusted beta=-2.1, 95% CI -3.0, -1.1) also predicted digit span backwards.

Conclusion:
Left BA 44, 45 (Broca’s area) and 39 and 40 (inferior parietal lobule) are crucial brain regions for recovery of VWM.
Abstract 3034: Does Untreated Peripheral Vascular Disease Create A Remote Ischemic Preconditioning Effect In Human Ischemic Stroke?
Authors: Bilgin-Freiert Arzu , Dusick Joshua R , Gonzalez Nestor
Published: March 2022

Introduction:
Despite promising success in animal models, neuroprotective strategies remain limited in clinical applications. There is a growing interest in endogenous mechanisms of ischemic protection in the human brain and their potential therapeutic application. In this study we investigated if a history of untreated peripheral vascular disease (PVD) could act as a form of “remote ischemic preconditioning” and induce tolerance to cerebral ischemic events in terms of clinical outcomes after ischemic stroke.

Methods:
We performed a retrospective review of a prospectively collected database of 1,473 patients who presented to our institution with ischemic strokes between October 2005 and February 2011. Patients with a history of peripheral vascular disease were identified. A balanced control group within the same database was determined by using a matching algorithm that considered the following characteristics: age, sex, ethnicity, history of hypertension, prior TIA’s, diabetes mellitus, tobacco use, and NIHSS at presentation. The groups were compared in terms of modified Rankin Scale (mRS) at discharge and mortality.

Results:
Forty-five patients were identified to have untreated PVD.
Table 1
summarizes the demographic and risk factor proportions for each group. Age, gender, NIHSS at presentation and past medical history were comparable among the groups. Non-fatal outcomes were not significantly different in the case and control groups. There were 23 patients (51.1%) with a mRS of 3 or less with PVD compared to 22 patients (48.9%) in the control group and 18 patients (39%) with a mRS of 4 or 5 with PVD compared to 14 patients (31.1%) in the control group. However, the mortality rate was significantly different, with 4 deaths (8.9%) in the PVD group versus 10 deaths (22.2%) in the control group (Odds Ratio 0.85, 95% CI 0.7-1.0).

Conclusions:
In a retrospective cohort of patients and case-matched controls with ischemic stroke, a history of untreated peripheral vascular disease (PVD) is associated with a lower mortality rate secondary to stroke. PVD could act as a form of “remote ischemic preconditioning” and induce tolerance to cerebral ischemic events in terms of reduction of stroke-related mortality.
Abstract 3038: Altered Expression Of The Immunomodulatory Proteins Cd200 And Cd200r1 In Lymphoid Tissue Following Ischemic Stroke
Authors: Wesson Winsor , Ritzel Rodney , Doran Sarah , McCullough Louise , Moore Craig
Published: March 2022

Background and Purpose:
Previous studies have demonstrated a rapid activation of peripheral immune responses following experimental stroke, marked by increases in pro-inflammatory cytokines, chemokines, and leukocyte entry into the brain, which may exacerbate tissue damage caused by reperfusion. In the CNS, a consequence of the local immune response to stroke is disruption of the immunosuppressant interaction between CD200 ligand (CD200), expressed by CNS-resident cells, and CD200 receptor (CD200R1) on microglia. Microglia are myeloid-derived cells, which serve as endogenous macrophages within the CNS. In models of CNS injury, disruption of the CD200-CD200R1 interaction leads to changes in intracellular signaling that can increase expression of several pro-inflammatory factors. In the present study, we compared gene expression of CD200 and CD200R1 in the bone marrow, a site of immune cell production, between sham and stroke mice. Additionally, we explored CD200 and CD200R1 protein expression in the primary and secondary lymphoid tissues between sham and stroke mice.

Methods:
Experimental stroke was induced by middle cerebral artery occlusion in male C57BL/6 mice for 90 minutes prior to reperfusion. Mice were sacrificed 5, 24, and 72 hours after stroke. Bone marrow was harvested from femur and RNA was extracted using Trizol®. cDNA was analyzed for CD200 and CD200R1 expression using qPCR. Western blots were performed on protein extracts from spleens and lymph nodes.

Results:
In the 5-hour cohort, a significant increase in CD200R1 and CD200 expression was observed in the bone marrow of stroke mice compared with sham. Expression of CD200 and CD200R1 was also elevated in secondary lymphoid tissue in stroke mice. In the 72-hour cohort, a significant decrease in CD200 expression was observed in stroke mice compared to sham mice. Within lymphoid tissue, similar trends were also observed for CD200R1.

Conclusions:
Immediately following stroke injury, CD200 and CD200R1 gene expression levels are altered in bone marrow, thereby enhancing pro-inflammatory signaling and increasing immune cells in peripheral circulation that can migrate into the brain. The subsequent decrease in expression of these proteins in the 72-hour cohort suggests that CD200- and CD200R-expressing cells are depleted in the bone marrow as a result of their activation, mobilization, and recruitment to the brain. Increased CD200 and CD200R expression in the spleen suggest a similar response by the peripheral immune system as the brain signals for the production of anti-inflammatory components. These results suggest that following stroke, bone marrow activation induces a mobilization signal which targets CD200/R-expressing cells to sites of ischemic brain injury, and is consistent with previous observations showing increased CD200R1 protein levels in the brain following stroke.
Abstract 3046: Co-registration and 3D Comparison Reveal a Variable Trajectory of Intracerebral Hemorrhage Expansion in Relation to Spot Sign Location: Analysis from the PREDICT Study
Authors: Boyko Matthew J , Kosior Robert , Dowlatshahi Dar , Kosior Jayme , Rodriguez-Luna David , Molina Carlos A , Blas Yolanda S , Dzialowski Imanuel , Czlonkowska Anna , Boulanger Jean-Martin , Lum Cheemun , Gubitz Gord , Padma Vasantha , Roy Jayanta , Kase Carlos S , Gladstone David J , Smith Eric , Aviv Richard I , Demchuk Andrew M
Published: March 2022

Background:
Intracerebral hemorrhage (ICH) expansion can have devastating effects for patients. The spot sign, a form of contrast extravasation, has been shown to predict hemorrhage expansion. However, the relationship between the location of the spot sign within the ICH and the direction of hemorrhage expansion has not been defined. We hypothesized that the spot sign can predict the trajectory of ICH expansion.

Methods:
Data from PREDICT, a prospective, observational cohort study coordinated at the University of Calgary, were used to conduct this case series. Non-contrast computed tomography (CT) and CT-angiography data were obtained for each subject. We used segmentation software to outline ICH volume on baseline and follow-up CTs. We then co-registered the scans and volumes in the same space to allow for three-dimensional voxel-to-voxel comparison along the x-, y-, and z-axes. This comparison yielded three points in three-dimensional space: the spot sign center of mass, the baseline ICH center of mass, and the follow-up ICH center of mass. Distances and angles between these points were used to classify four groups of ICH expansion: 1) perpendicular to the spot sign and baseline ICH center of mass; 2) away from the spot sign; 3) toward the spot sign; and, 4) circumferential.

Results:
Eighty-two PREDICT study subjects exhibited spot signs. Forty were multiple spot signs and 42 were single spot signs eligible for this analysis. Seven subjects were excluded because of surgery or incomplete imaging. Sixteen subjects were not co-registered because of head motion or insufficient image quality. Nineteen single spot subjects were successfully co-registered. The radius of these 19 hemorrhages was 1.6±0.4 cm (assuming a sphere). The spot sign was located 1.4±0.6 times the length of the radius away from the baseline ICH center of mass. We classified nine co-registered subjects into the four groups because they showed significant hemorrhage expansion defined as ≥6 mL or ≥33% from baseline to follow-up. Four subjects exhibited hemorrhage expansion away from the spot sign, three exhibited circumferential hemorrhage expansion, and two exhibited hemorrhage expansion toward the spot sign. No hemorrhages expanded perpendicular to the spot sign.

Conclusion:
The spot sign is generally located in the periphery of the ICH. Hemorrhages do not consistently expand in one specific trajectory from the spot sign. This study suggests that the spot sign location may not be useful to predict the direction of hemorrhage expansion.
Abstract 3057: Increased rt-PA Utilization Will Decrease Healthcare Costs in SC
Authors: Kazley Abby S , Simpson Kit , Simpson Annie , Jauch Edward , Adams Robert
Published: March 2022

Recombinant tissue plasminogen activator (rt-PA) has been approved for acute ischemic stroke (AIS) patients since 1996. An early (1998) paper reported net financial and health benefits from its use, but we are aware of no reports of economic impacts of rt-PA use in todays healthcare system. We used a Markov model to estimate the expected current economic and health benefits of rt-PA use for the state of South Carolina.

We compared expected cost for all stroke hospital admission for patients treated with rt-PA at the current rate (3%) of rt-PA use to the stroke costs if the treatment rate increased to 20% of all stroke admissions. We estimated total stroke costs for a five year time period (2012 through 2016). The Markov model used the original rt-PA trial data for estimation of expected outcomes based on the modified Rankin Scale (mRS) of disability at discharge. Health benefits are measured using quality-adjusted life years (QALYs), and the economic impacts are estimated cost to treat a patient based on cost for SC hospital discharges and other stroke care. Costs are reported in 2010 currency. Inflationary factors and economic discounting is not employed for the budget impacts reported here.Assumptions in the model include the rate of recurrent stroke (.052), rate of symptomatic hemorrhage after rt-PA (6.45%), the inclusion of charge for a two hour specialist fee during initial evaluation, patients discharged to a nursing home remain there until death, subsequent strokes do not receive rt-PA, those discharged from rehabilitation went to a nursing home. Patients were assumed to have a median age of 67 years at the time of the stroke. Cost of rt-PA was $2750 for 100mg. A CDC AIS-specific death rate was assumed.

We predicted a total cost of care for stroke in SC for 2012 through 2016 of $2,531,398,032 if rt-PA use continues at a rate of 3%. However, if the rate increases to 20% we will save $16,615,723 in stroke care cost over 5 years. Thus, given the current cost of AIS and the benefits documented for rt-PA treatment, concerted efforts to increase rt-PA use in SC may be expected to save money for payers in addition to improving quality of life for many stroke survivors.
Abstract 3076: Microthrombosis and Microcirculatory Constriction after Experimental Subarachnoid Hemorrhage
Authors: Sabri Mohemmad , Ai Jinglu , Lakovic Katarina , MacDonald Robert L
Published: March 2022

Subarachnoid hemorrhage (SAH) accounts for about 6% of cases of stroke and afflicts more than 50,000 individuals annually in North America. Cerebral angiographic vasospasm has been recognized as being commonly associated with aneurysmal SAH for many years. However, recent studies showed that angiographic vasospasm does not always predict the location of infarction, and alleviation of vasospasm did not result in better outcome in SAH patients. One hypothesis gaining more attention is that separate or interacting pathways may cause delayed cerebral ischemia (DCI) after SAH, and that these, in combination with angiographic vasospasm, lead to poor outcome. Postulated mechanisms include acute brain injury, microcirculatory dysfunction, microthromboembolism, and cortical spreading ischemia. The focus of this study is to determine first, if experimental SAH is associated with microcirculatory constriction and thrombosis, second, to determine if any microthromboemboli are thrombi or emboli and third, to determine if these changes correlate with brain injury.

We used a prechiasmatic cistern injection model of SAH. 15 mice (n = 5 for each group) underwent sham surgery or injection of 100 μl 0.9% NaCl or autologous blood into the prechiasmatic cistern. Mice were sacrificed 2 days later and brains were examined by scanning (SEM) and transmission electron microscopy (TEM) and by immunohistochemistry for fibrinogen and P-selectin. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. Nitric oxide (NO) was measured with 4,5-diaminofluorescein-2-diacetate. TEM and SEM demonstrated that mice with SAH had significantly more arterioles filled with lesions consistent with microthrombi. Quantification of microvessel constriction showed significantly decreased microvessel lumen area but increased micrvessel wall thickness in animals with SAH compared to sham or saline-injected controls (P < 0.01, ANOVA). This was accompanied by decreased concentration of NO in mice with SAH compared to saline and sham mice. There are a significantly increased number of TUNEL positive cells in both cerebral cortex and hippocampus (p < 0.01). Marked increase of fibrinogen positive microvessels are found in both cerebral cortex and hippocampus (p < 0.05 in cortex, p < 0.001 in hippocampus). The number of microthrombi correlates with the number of apoptotic neurons in cerebral cortex (R
2
=0.98). Cell membrane P-selectin is increased in the endothelium of arterioles in mice with SAH. This correlates with decreased NO in the brain.

In conclusion, SAH causes microthrombosis and constriction of arterioles, which correlates with neuronal death. Increased P-selectin and decreased NO suggest a mechanism for microthrombosis and arteriolar constriction.
Abstract 3088: A Systematic Study of Cerebral Hyperperfusion Syndrome after Carotid Endarterectomy
Authors: Maas Matthew B , Kwolek Christopher J , Jaff Michael R , Hirsch Joshua A , MacKay Cheryl , Rosenfield Kenneth , Rordorf Guy A
Published: March 2022

Background:
Cerebral hyperperfusion syndrome (CHS) is a well documented complication of carotid endarterecomy (CEA), yet prior research has been limited to small case series and retrospective analyses, or studies using radiographic rather than clinical definitions.

Methods:
A prospective, independent monitoring system was implemented to monitor CEA outcomes at a major academic medical center. Independent, trained monitors from the neurology department examined all patients undergoing CEA both preoperatively and postoperatively at 24 hours and 30 days. Data were collected on patient demographics, medical history, and procedural and anatomical variables. Clinical variables were analyzed to identify risk factors for CHS, which was defined as cases with postoperative development of a severe headache, new neurological deficits without infarction, seizure or intracerebral hemorrhage.

Results:
Between 2008 and 2010, 832 CEA were monitored and CHS occurred in 14 (1.7%), including seizures in 5 (0.6%) subjects and intracerebral hemorrhage in 4 (0.5%). Univariate analysis identified a history of dyslipidemia, degree of ipsilateral stenosis and urgent CEA (performed during hospitalization for a symptomatic ipsilateral stroke, TIA or amaurosis fugax) as potential risks for CHS (all p<0.2), whereas age, sex, race, hypertension, diabetes, smoking, degree of contralateral stenosis, operative time, presence of intraoperative EEG slowing, history of prior CEA or carotid stent and time from prior carotid interventions were not significant. Multivariable analysis confirmed the risk association between urgent CEA and CHS (p=0.015) but not dyslipidemia (p=0.084) or degree of ipsilateral stenosis (p=0.118). Surgical indications in urgent CEA patients who developed CHS were amaurosis fugax (1), TIA (3) and stroke (5).

Conclusions:
Independent, prospective monitoring of a large cohort of CEA cases identified a brief time interval between ischemic symptoms and endarterectomy as the clearest risk factor for CHS, with dyslipidemia and a high degree of ipsilateral carotid stenosis as possible contributory risks. Occurrence of CHS in patients undergoing urgent CEA does not appear to be limited to those with large strokes.