bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP100: Thymosin β4 for the Treatment of Sub-Acute Stroke in Aged Rats
Authors: Morris Daniel , Chopp Michael , Cheung Wing Lee , Cui Yischeng , Zhang Talan , Lu Mei , Zhang Li , Zhang Zheng G
Published: March 2022

Introduction:
Thymosin β4 (Tβ4) is a 5K peptide which influences cellular migration by inhibiting organization of the actin-cytoskeleton. Tβ4 has neurorestorative properties and is a potential candidate for the treatment of sub-acute stroke. Previous research demonstrated that Tβ4 improved neurological outcome in a young (3 months) rat model of embolic stroke.

Hypothesis:
We hypothesized that Tβ4 would improve neurological outcome in an aged rat model of embolic stroke when administered 24 hours after embolic stroke.

Methods:
Aged Male Wistar rats (Charles River, France 18-21 months) were subjected to embolic middle cerebral artery occlusion (MCAo). Rats were randomized to receive Tβ4 (12 mg/kg, Regenerx Biopharmaceuticals, Inc.) or control 24 hrs after MCAo and then every 3 days for 4 additional doses. The dose of 12 mg/kg was the maximal dose of Tβ4 that showed functional improvement in a young rat model of embolic stroke. Functional tests were performed weekly. The rats were sacrificed 56 days after MCAo and lesion volumes measured. Generalized Estimating Equations were used to compare the treatment effect on functional recovery and t-test for lesion volumes.

Results and Conclusions:
Twenty-three rats were included in the study: control group (n=12) and Tβ4 group (n=11). After randomization, there were three deaths in both the control and Tβ4 groups. The Tβ4 treatment reduced infarct volume by more than 50% (12.8% ± 9.3%, mean ± SE, p<0.05) compared to the control group (26.0% ± 4.3%). However, Tβ4 did not show improvement in functional outcome compared to control. Lesion volumes in the treated group showed a correlation to functional testing of (R=0.85, p<0.05), whereas no correlation was observed in the control group (R=0.19).

Conclusions:
The Tβ4 treatment of stroke aged animals significantly reduces infarct volume compared to vehicle treated stroke. Dissociation between infarct volume and functional outcome in the control group suggests, a ceiling effect of these functional tests in aged animals may obscure proper evaluation of functional outcome between the Tβ4 and control groups. Additional studies and more sensitive behavioral tests are needed to examine the dissociation between infarct volume and functional outcomes in aged ischemic rats.
Abstract WP105: Therapeutic Time Window for Conivaptan Treatment of Cerebral Edema and Blood-Brain Barrier Breakdown in Mice
Authors: Zeynalov Emil , Jones Susan M , Elliott J.Paul
Published: March 2022

Introduction:
Stroke is complicated by brain edema, blood-brain barrier (BBB) disruption, and is often accompanied by increased release of arginine-vasopressin (AVP). AVP, acting through V1a and V2 receptors can trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. We recently reported that conivaptan, V1a and V2 receptor blocker, reduces stroke-evoked brain edema and blood-brain barrier (BBB) disruption in mice when administered immediately after reperfusion. However, these pre-clinical results can be translated into clinical applications if the therapeutic time window for conivaptan is explored.

Hypothesis:
We hypothesized that conivaptan will alleviate brain edema and BBB disruption even if the treatment is delayed.

Methods:
Mice underwent the filament model of middle cerebral artery occlusion (MCAO) with reperfusion. After 60 minutes occlusion, mice were recovered and randomly allocated into the following groups: conivaptan or vehicle-treated at 3 or 5 hours after MCAO. Treatments were administered via a jugular catheter and continued for 48 hours. Physiological variables, plasma and urine sodium and osmolality, brain water content (BWC) and Evans Blue (EB) extravasation were evaluated at the end point.

Results:
Conivaptan produced aquaresis as indicated by changes in plasma and urine sodium and osmolality. Conivaptan treatment, when initiated at 3 hours after MCAO reduced BWC in the ipsilateral hemisphere from 80.2 ± 0.2% (vehicle) to 78.1 ± 0.1% (p < 0.05 vs vehicle, n=10), and attenuated the EB extravasation index from 1.3 ± 0.2 (vehicle) to 1.01 ± 0.1 (p < 0.05, n=5-7). However, a 5-hour delay of conivaptan treatment after MCAO did not affect ipsilateral BWC (n=10).

Conclusion:
A 3-hour delay of conivaptan treatment after experimental stroke is effective at reducing brain edema and protecting BBB integrity. Further delay of treatment up to 5 hours after stroke abolishes the beneficial effect of conivaptan on postischemic brain edema. In conclusion, these results present an opportunity for potential use of conivaptan to treat post-ischemic brain edema in ICU patients.
Abstract WP106: Optogenetic Neuronal Stimulation Reduces Neuronal Nitric Oxide Synthase After Stroke
Authors: Cheng Michelle Y , Gonzales Lorenzo , Wang Eric H , Wang Stephanie , Ishizaka Shunsuke , Sun Guohua , Steinberg Gary K
Published: March 2022

Objective:
Nitric oxide (NO) is a gaseous messenger that mediates many physiological functions, including neuronal excitability, vascular tone and angiogenesis. Nitric oxide synthases are a family of enzymes that catalyzes the production of NO. While activation of endothelial NOS (eNOS) has been shown to be neuroprotective, activation of neuronal NOS (nNOS) and inducible NOS (iNOS) worsens ischemic damage. Although the role of NOS in acute stroke is well-established, their contribution in stroke recovery is less clear. Our lab recently demonstrated that optogenetic neuronal stimulation can enhance post-stroke recovery. As NOS mediates many physiological processes important for stroke recovery, we investigate whether NOS is involved in stimulation-enhanced recovery. We hypothesize that neuronal stimulations promote recovery by altering NOS expression.

Methods:
Thy-1-ChR2-YFP line-18 transgenic male mice were used. Mice underwent experimental stroke induced by an intraluminal middle cerebral artery suture occlusion. Repeated optogenetic stimulations in the contralesional cerebellar dentate nucleus (cLCN) were administered from post-stroke day5-14. Functional recovery was evaluated by sensory-motor behavior tests. Mice were sacrificed at post-stroke day15, ipsilesional and contralesional motor and sensory cortices were dissected. qPCR was performed to examine expression of nNOS, iNOS and eNOS.

Results:
Our data showed that stimulated stroke mice recovered quickly, with significantly faster rotating beam speed at day14 post-stroke (p<0.001). Quantitative PCR revealed that stimulations significantly reduced nNOS expression, while no change was detected for eNOS and iNOS. Interestingly, nNOS was significantly reduced in the contralesional primary motor cortex in cLCN-stimulated stroke mice (p<0.001), suggesting the involvement of nNOS in the contralesional cortex in stroke recovery.

Conclusion:
Optogenetic stimulations promote post-stroke recovery and selectively reduced nNOS expression in the contralesional motor cortex. Current ongoing studies examine the nNOS signaling pathway after stimulation and the effect of manipulating nNOS expression in stroke recovery.
Abstract WP109: Repairing the Brain by Hematopoietic Stem Cell Factors 6 Months Post-experimental Stroke: a Causal Link Between Functional Improvement and Neurovascular Remodeling in the Peri-infarct Cavity Cortex
Authors: Zhao Li-Ru , Cui Lili , Wang Dandan
Published: March 2022

Stroke, a leading cause of adult disability in the world, is a severe medical condition with limited treatment. Chronic stroke represents the phase beyond 3 months after stroke onset. Physical therapy, the only treatment available for stroke rehabilitation, appears to be effective within 6 months post-stroke. Here we have mechanistically determined the efficacy of combined two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) (SCF+G-CSF) in brain repair 6 months after cortical infarct induction in the transgenic mice carrying yellow fluorescent protein in layer V pyramidal neurons (Thy1-YFP-H). Using a combination of live brain imaging, whole brain imaging, molecular manipulation, synaptic and vascular assessments, and motor function examination, we found that SCF+G-CSF promoted mushroom spine formation, enlarged postsynaptic membrane size, and increased postsynaptic PSD-95 accumulation and blood vessel density in the peri-infarct cavity cortex through NF-κB. Once the SCF+G-CSF-enhanced synaptogenesis and angiogenesis in the peri-infarct cavity cortex were blocked by an NF-κB inhibitor, the SCF+G-CSF-induced motor function improvement was eliminated. These data suggest that a stroke-damaged brain is repairable by SCF+G-CSF even 6 months after the lesion occurs. This study provides novel insights into the development of new restorative strategies for stroke recovery.

This work was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS)(R01 NS060911) in the United States.
Abstract WP113: Dose-response and Therapeutic Time-window of Compound 21: a Randomized Preclinical Trial in Rat Model of Thromboembolic Stroke
Authors: Ishrat Tauheed , Fouda Abdelrahman Y , Pillai Bindu , Eldahshan Wael , Ahmed Heba , Waller Jennifer L , Ergul Adviye , Fagan Susan C
Published: March 2022

Background:
We and others have previously shown promising results with the use of the angiotensin type 2 receptor agonist, compound 21 (C21), in experimental stroke. Here we aimed to determine the best dose and time window for C21 in a clinically relevant embolic stroke model.

Methods:
This study was conducted as a translational, randomized, controlled, blinded preclinical trial with the guidance of our biostatistician. Male Wistar rats (8-9 weeks old) were subjected to embolic middle cerebral artery occlusion (eMCAO). For the dose-response study, animals received C21 (0.01, 0.03 and 0.06 mg/kg/d) or saline (orally) for 5 days, with the first dose given IV at 3 h post-eMCAO. For the time-window study, the optimal dose of C21 was initiated at 3, 6 or 24 h post-eMCAO and daily thereafter, for 5 days. Behavioral outcomes (Bederson, paw grasp and grip strength) were blindly assessed at days, 1, 3, 5 and 7. Rats were then sacrificed and their brains collected for infarct size and vascular density analyses. Results (Table): In the dose-response study, repeated-measures ANOVA showed significant (p < 0.05) behavioral improvement with the low dose (0.01 mg/kg). This dose was associated with higher vascularity in the ischemic penumbra, detected by laminin staining, compared to saline treated controls (65±6 vs 46±7 p < 0.05). In the time-window study, the 0.01 mg/kg dose displayed non-statistically significant improvements when given 3 h and 6 h after eMCAO. There were no differences between doses or time-windows for either % infarct size or tissue loss.

Conclusions:
C21 given at 0.01 mg/kg/d was effective in improving behavioral dysfunction after embolic stroke when administered within 6 h. Compound C21 shows promise as a potential therapeutic agent and should be examined for safety and efficacy in clinical trials for ischemic stroke.
Abstract WP115: Atrial Fibrillation and Acute Stroke Recurrence in Minor Stroke Patients With Carotid Stenosis
Authors: Fujimoto Shigeru , Osaki Masato , Tagawa Naoki , Kanazawa Makoto , Oya Yuichiro , Kitazono Takanari
Published: March 2022

Background & Purpose:
Carotid stenosis (CS) and atrial fibrillation (AF) can be associated with a bad outcome even in minor stroke. We investigated acute stroke recurrence and short-term outcome in Japanese minor stroke patients with CS with or without AF.

Subjects & Methods:
Among the consecutive 6246 stroke patients who were admitted to the 7 stroke centers within 48 hurs after the onset, 429 patients with acute ischemic stroke with extracranial carotid stenosis (50% or more in diameter measured by using MR angiography or carotid ultrasonography), the initial NIH stroke scale (NIHSS) score of 7 or less, and prior modified Rankin scale (mRS) of 0 or 1 were included in the present study. Patients who were planned for carotid endarterectomy within 3 weeks were excluded. We observed a stroke recurrence and outcome during 3 months. Stroke recurrence was defined as a neurological deterioration (NIHSS score worsening of ≥1 point) with a new ischemic lesion on diffusion weighted image. Good outcome was defined as a mRS score of 0 or 1 at 3 months.

Results:
AF was observed in 94 (22%) patients at hospital discharge. The acute stroke recurrence rate was not different between patients with (11%) and without AF (12%), however, good outcome was less frequent in patients with (39%) than without AF (66%). The Degree of carotid stenosis in NASCET method was more severe in patients with than without acute stroke recurrence (66% vs 59%). The initial diastolic blood pressure, pulse rate, NIHSS Score, WBC, TG, glucose, HbA1c, CRP, and D-dimer values were lower in patients with than without good outcome at 3 months. On the multivariate analysis, AF was negatively associated with good outcome (OR 0.36, 95%CI 0.20-0.0.64). The initial D-dimer value (OR 0.84, 95%CI 0.75-0.94) was also negatively associated with good outcome. Among 94 patients with both CS and AF, combined treatment with both antiplatelet and anticoagulant agents was more frequent in patients with than without good outcome.

Conclusions:
AF and the initial D-dimer value were significant negative predictors for good outcome in patients with CS. Optimal antithrombotic treatment in patients with both CS and AF should be investigated.
Abstract WP123: Changes of Signal Intensities Across Intracranial Arterial Stenosis on Magnetic Resonance Angiography Are Associated With Ipsilateral Cerebral Perfusion.
Authors: Lan Linfang , Leng Xinyi , Abrigo Jill , Ip Vincent , Leung Thomas , Yu Simon , Wong Ka Sing
Published: March 2022

Background:
Intracranial arterial stenosis (ICAS) is a predominant cause of ischemic stroke in Asia. Changes of the signal intensities across ICAS lesions on time-of-flight magnetic resonance angiography (MRA) have been indicated to partially reflect the hemodynamic significance of the lesions, which we aimed to verify by correlating with cerebral perfusion features provided by CT perfusion imaging.

Methods:
Ischemic stroke or transient ischemic attack patients with unilateral symptomatic stenosis (≥50%) of intracranial internal carotid artery or middle cerebral artery were included in this study. Change of signal intensities across an ICAS lesion on time-of-flight MRA was calculated by the distal and proximal signal intensity ratio (SIR). Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) within the middle cerebral artery territory of ipsilateral and contralateral hemispheres were evaluated on the CT perfusion images at the basal ganglia level. Relative CBV, CBF and MTT were defined as the ratios of the parameters obtained from ipsilateral and contralateral hemispheres. The relationships between SIR and CT perfusion parameters were analyzed.

Results:
Fifty subjects (74% male, mean age 62.84) were recruited. Overall, mean SIR was 0.77 ± 0.17. SIR of ICAS significantly, linearly and negatively correlated with ipsilateral CBV (r = -0.335, P = 0.017), CBF (r = -0.312, P = 0.028), and MTT (r = -0.301, P = 0.034), and relative MTT (r = -0.443, P = 0.001).

Conclusions:
Changes of the signal intensities across ICAS lesions on time-of-flight MRA may be a simple marker to reflect cerebral perfusion changes in patients with symptomatic ICAS.
Abstract WP125: Plaque Inflammation Imaging in Carotid Stenosis and Recurrent Cerebral Ischemia
Authors: Sharma Vijay K , Kulkarni Amit , Paliwal Prakash R , Teoh Hock-Luen , Chan Bernard P , Hong Chiew S , Chen Jin-Tao , Chee Young-Heng , Du Zhengdao , Seow Philip A , Wong Lily Y , Chandra Bhartendu , Yeo Leonard L , Sinha Arvind K
Published: March 2022

Background and aims:
Symptomatic carotid stenosis is associated with an increased risk of early stroke recurrence. Currently, therapeutic decisions are largely based on the luminal narrowing, which mainly explain the cerebral ischemia related to regional hypoperfusion. Plaque inflammation, the initiating event for plaque rupture and thromboembolism (artery-to-artery embolism), is not evaluated routinely in patients with carotid stenosis. Using combined 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT), we investigated the role of plaque inflammation and stroke recurrence in our cohort of stroke patients with recently symptomatic carotid stenosis.

Methods:
This ongoing prospective study aims to include consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake is quantified as mean standardized uptake values (SUV, g/ml). Patients are followed prospectively for stroke recurrence. Embolic potential of the carotid plaque is estimated by presence of spontaneous microembolic signals (MES) on continuous transcranial Doppler monitoring of the middle cerebral arteries (MCA) for 40 minutes.

Results:
Of the 22 patients included in the study, 5 suffered from recurrent cerebral ischemic event in the same vascular territory within 90 days. In patients with recurrent cerebral ischemia, the mean SUV value in the carotid plaque on the side of symptomatic carotid stenosis was higher (3.46g/ml) as compared to the patients without stroke recurrence (1.72g/ml; p=0.03). MES were noted in 3/5 cases with recurrent cerebral ischemia as compared to 2/17 cases (p=0.001)

Conclusions:
FDG-PET/CT aids in the imaging of plaque inflammation and identification of patients with higher risk of subsequent cerebral ischemic events. This ongoing study intends to develop a robust prediction model for risk stratification based on luminal stenosis and plaque characteristics for better therapeutic decision-making.
Abstract WP126: Impaired Dynamic Cerebral Autoregulation Predicts Cerebral Hyperperfusion Syndrome After Carotid Angioplasty and Stenting
Authors: Chi Nai-Fang , Chen Yen-Ting , Ku Hsiao-Lun , Chan Lung , Hu Chaur-Jong
Published: March 2022

Introduction:
Cerebral hyperperfusion syndrome (CHS) is a devastating complication after carotid revascularization procedure such as carotid angioplasty and stenting (CAS). Although there is no reliable predictor of CHS after CAS, it is believed CHS is caused by impaired cerebral autoregulation (CA). However, there is no study using CA assessment as a predictor of the occurrence of CHS after CAS.

Hypothesis:
Impaired preoperative CA index is associated with occurrence of CHS after CAS.

Methods:
17 patients with 70-95% stenosis of internal carotid artery who were scheduled to have CAS were enrolled. All patients had dynamic CA assessment 1 day before CAS by analyzing the relationship between the blood pressure of peripheral artery and the flow of stenotic internal carotid artery. Two dynamic CA indexes were measured: time domain analysis (mean pressure-flow correlation coefficient index, Mx) and frequency domain analysis (phase difference at 0.05-0.15Hz measured by a nonlinear analytic method based on Hilbert-Huang transform). In addition, magnetic resonance perfusion image with arterial spin labeling (MR-ASL) was done at 1 day before CAS as baseline, and was followed at 1 and 3 days after CAS to assess the temporal change of cerebral blood flow (CBF). The definition of hyperperfusion is 100% increase of CBF in MR-ASL compared to baseline.

Results:
1 patient developed CHS after CAS, whose Mx is 0.68; and 1 patient was found to have asymptomatic hyperperfusion after CAS, whose Mx is 0.58. The other 15 patients have no hyperperfusion after CAS, and their CBF after CAS did not change significantly compared to baseline (P=0.312 and 0.286 on day 1 and day 3 after CAS, respectively) The average Mx between patients with and without hyperperfusion are significant different (0.16±0.24 vs. 0.63±0.07, p=0.025). The average phase difference between patients with and without hyperperfusion are not different (32.5±11.1 vs. 28.2±19.8, p=0.307).

Conclusions:
Impaired preoperative dynamic CA using time domain analysis (Mx) is associated with cerebral hyperperfusion status after CAS. Therefore, preoperative dynamic CA is a potential screening tool to improve the safety of CAS.
Abstract WP139: Pathological Study of Intracranial Artery Atherosclerosis in 7307 Autopsy Cases
Authors: Kimura Hiroaki , Takao Masaki , Mihara Ban , Kanemaru Kazutomi , Suzuki Norihiro , Murayama Shigeo
Published: March 2022

Introduction:
It has not been analyzed whether atherosclerotic changes in the major cerebral arteries differ with age or with era of birth.

Hypothesis:
To examine our hypothesis that such changes would vary with age at death and era of birth, we studied chronological changes in intracranial artery atherosclerosis in consecutive autopsy cases.

Methods:
We analyzed 7307 autopsy cases of our brain bank from 1972 to 2014. Severity of atherosclerosis was classified on the following semi-quantitative scale based on pathological observation of each artery after formalin fixation: 0 = no stenosis; 0.5 = fatty streaks but no stenosis; 1 = less than 50% stenosis; 2 = 50% to 90% stenosis; 3 = 90% or more stenosis. We scored the cerebral arteries (anterior, middle, and posterior) and vertebral arteries bilaterally and the basilar artery. Then we summed the scores in each patient and defined the sum as the atherosclerosis score. We compared atherosclerosis scores by age at death and era of birth.

Results:
Atherosclerosis scores increased with age at death, as follows: age 50s, 1.9 ± 3.8; 60s, 4.6 ± 5.2; 70s, 6.1 ± 5.3; 80s, 7.6 ± 5.4; 90s, 8.2 ± 5.3; and 100s, 9.2 ± 5.3 (mean ± SD, P < 0.0001). The percentage of cases with a score of 2 or 3 in each artery also increased with age (P < 0.0001). Interestingly, in each age group (from the 60s to 90s) at the time of death, the score declined as the birth year became later (Figure. P < 0.0001, box plots for each group showing atherosclerosis score).

Conclusions:
Our analysis from a brain bank cohort showed that intracranial artery atherosclerosis 1) advanced with age, and 2) was more severe in subjects born earlier.
Abstract WP144: Predictors of In-hospital Speech Therapy Referral in Aphasic Acute Ischemic Stroke Patients Within a Population
Authors: Coleman Elisheva R , Sucharew Heidi , Alwell Kathleen , Moomaw Charles J , Kissela Brett M , Woo Daniel , Flaherty Matthew L , Martini Sharyl R , Mackey Jason , Adeoye Opeolu , Ferioli Simona , De Los Rios La Rosa Felipe , Kleindorfer Dawn
Published: March 2022

Background:
Aphasia is a major cause of disability following ischemic stroke (IS). We sought to determine clinical characteristics of patients with aphasia that are associated with speech therapy evaluation (STE) in the acute setting within a large, biracial population.

Methods:
Adult IS patients in 2010 in the Greater Cincinnati/Northern KY region (population 1.3 million) were ascertained from all local hospitals via ICD-9 codes 430-436, using retrospective chart review. Aphasia was defined by symptoms or examination documented in the medical record. Demented patients were excluded. Logistic regression was used to determine associations between STE and clinical characteristics. We ran our model twice, including and excluding patients who died in-hospital or shifted to comfort/hospice care. Age and NIHSS were evaluated for potential nonlinear effects using spline functions.

Results:
In 2010, there were 1997 non-demented IS subjects, with 21% black, 54% female, and mean age of 68 (SD 15) years. Of these, 728 (36%) presented with aphasia, of whom 514 (71%) were assessed by ST. Age, race, gender, and academic hospital were not significantly associated with STE. In-hospital death and hospice referral were negative predictors (OR 0.12 and OR 0.19; both p<0.01); excluding these 202, 463 (79%) of the remainder were assessed. Factors predictive of STE in both models were stroke/neurology consult (OR 2.56 (95% CI 1.55, 4.21), p<0.01), dysarthria (OR 2.34 (1.46, 3.75), p<0.01), and NIHSS. NIHSS had a non-linear relationship, with moderate strokes most likely to be evaluated and mild and severe strokes less likely (Figure).

Discussion:
Of non-moribund IS patients presenting with aphasia, 1 in 5 did not receive STE during acute hospitalization. While moderate stroke patients had a high rate of STE, mild and severe strokes showed a bias towards less consultation. Our results suggest that limited ST resources are not always directed at those with potentially the greatest need.
Abstract WP145: Intra-arterial Stem Cell Therapy for a Persistent Vegetative State Patient: A DTI Analysis of Recovery
Authors: Ramdas Kevin N , Guada Luis , Pafford Ryan , Haussen Diogo , Pattany Pradip , Yavagal Dileep R
Published: March 2022

Background:
Cell therapy is promising in pre-clinical studies of global ischemia. The aim of this pilot study is to describe the first intra-arterial (IA) delivery of bone marrow derived ALD-401 cells in a persistent vegetative state (PVS) patient in the U.S. & findings on MRI Diffusion Tensor Imaging (DTI) and Diffusion Tensor Tractography (DTT).

Material:
A 51-yr. woman developed PVS due to cardiac arrest. At 2 years post PVS state, experimental cell therapy was requested by the family. The FDA approved a one-time compassionate use IA delivery of ALD-401 cells. Bone marrow harvest from the patient, followed by processing with flow cytometry was completed to separate ALD-401 cells. Intra-arterial infusion of cells was done bilaterally into each supra-clinoid carotid. Post-infusion neurological assessments- National Institute of Health Stroke Scale (NIHSS), JFKr coma recovery scale, brainstem reflexes, modified Rankin Scores (mRS) and MRI DTI imaging were collected at 1-, 3-, 6-, 9-mo & 1 year

Result:
The patient had no adverse events peri-operatively. Over 1-year follow-up the patient had 1 hospitalization for UTI and postmenopausal bleeding. No other adverse events occurred. Minor clinical improvement was shown on assessment scales above. However, DTI-DTT analysis of Fractional Anisotropy (FA) showed improvement in the FA and ADC of white matter tracts starting 7 months post injection for the Cortical Spinal Tract (CST) and starting 4 months post injection for the Corpus Callosum (CC) months (see figure). Diffusion Tensor Tractography also showed qualitative improvement in organization and caliber of CC & CST over follow-up post intervention (see figure)

Conclusion:
Assessing minor neurological improvements in this severe PVS patient remains challenging; DTI-DTT MRI imaging detects changes in white mater tracts that could serve as biomarkers for recovery. Further follow-up clinical assessments and imaging will continue in this patient to define further recovery.
Abstract WP147: Advancing Rehabilitation in Ischemic Stroke Using Early Neurostimulants
Authors: Reznik Michael E , Ojha Ajitesh , Durkin Joseph , Reddy Vivek K , Shutter Lori A , Molyneaux Bradley J
Published: March 2022

Objective:
To determine if the use of neurostimulant medications enables more patients with acute ischemic stroke to qualify for inpatient rehabilitation at hospital discharge.

Methods:
Seventy-eight patients with ischemic stroke, admitted between 2011 and 2014 to an academic tertiary care stroke center, received neurostimulants during their admission and were retrospectively reviewed. A group of 78 controls from our institution’s stroke registry was matched 1:1 by sex, NIHSS, and age. The proportion of patients who were initially not candidates for an inpatient rehabilitation facility (IRF) but who subsequently became eligible, either after receiving neurostimulants or with standard care, was then compared between the two groups.

Results:
There were 78 patients treated with neurostimulants, 46 of whom did not initially qualify for IRF; of these, 39.1% subsequently converted and qualified for IRF after initiating a neurostimulant medication. In comparison, only 12.5% of patients in the matched cohort converted after initially not qualifying for IRF (Fisher exact test, p=0.028). Mean time to initiation of neurostimulant was 5.5 days in patients who successfully converted to IRF status, compared to 7.3 days in those who did not (Student’s t-test, p=0.16).

Conclusions:
In patients with acute ischemic stroke, early administration of neurostimulants may enable more to qualify for inpatient rehabilitation at hospital discharge.
Abstract WP148: Tactile-enhanced Motor Practice Improves Manual Dexterity Over Visually-guided Practice
Authors: Geed Shashwati , Silva Gabriela G , Rodrigues Maira D , Kukke Sahana N
Published: March 2022

Introduction:
Manual dexterity requires multi-sensory (e.g., vision and touch) integration with movement, and is often impaired due to sensorimotor deficits in stroke survivors. Currently, neurorehabilitation involves repetitive visually-guided motor practice without particular emphasis on tactile feedback for movement. As a first step to improve post-stroke hand function, we studied the effects of providing enhanced tactile feedback during motor practice on dexterity of the non-dominant hand in healthy volunteers.

Hypothesis:
We hypothesized that 2, 45-minute sessions of enhanced tactile-motor practice would improve non-dominant hand dexterity more than the same duration of visuo-motor practice.

Methods:
Twenty healthy adults (8 males; mean age = 27.7 ± 22 years) were randomized to an enhanced tactile-motor (TM) or visuo-motor (VM) group. Volunteers performed 3, 15-minute blocks of motor practice that required 1) sorting small (< 2.5 cm) wood-chips, 2) completing 3-D puzzles using small (<1.25 cm) cubes, and 3) copying patterns using 3.6 cm3 interlocking building bricks. Motor practice was either based on tactile cues of textured objects with vision partially obscured by a blurry screen (TM) or visual cues of smooth colored objects (VM). Motor practice occurred twice, seven days apart, with the non-dominant hand. Nine-hole peg test (9HPT) was the primary outcome to measure manual dexterity of non-dominant hand. Scores on the 9HPT were measured at 4 times: T1) pre-practice day 1, T2) post-practice day 1, T3) pre-practice day 2, and T4) post-practice day 2. A mixed-methods ANOVA was used to test the effect of motor practice (TM, VM), and time (T1, T2, T3, T4) on manual dexterity (9HPT).

Results:
The 2x4 mixed ANOVA showed a significant interaction between time and motor practice (F (3, 51) = 2.96, p = 0.04, partial η2 = .148), revealing that the change in 9HPT scores over time was different for the 2 groups. The TM group significantly improved on 9HPT from T1 to T4 (Mean difference = 2.7 s, SE = 0.53, p = 0.001), but the VM group did not improve.

Conclusions:
Tactile enhancement during 2 motor practice sessions can significantly improve dexterity. Future work will translate these methods to stroke rehabilitation.
Abstract WP150: The Effects of Chronic Stroke on Brain Function While Driving
Authors: Churchill Nathan , Vesely Kristin , Hird Megan , Tam Fred , Saposnik Gustavo , Graham Simon , Schweizer Tom
Published: March 2022

Introduction:
Chronic stroke may lead to persistent cognitive deficits in multiple domains. Despite this issue, there are no clear guidelines about post-stroke fitness to drive, due to a limited understanding of how stroke impairs brain networks essential for driving. We hypothesize reduced activity in driving-related brain regions, for more cognitively demanding tasks (e.g. left turns with traffic, distraction) and individuals with poorer neurocognitive test scores.

Methods:
we tested 7 adults with prior ischemic stroke (44-71 yrs.) and imaged brain function using functional Magnetic Resonance Imaging (fMRI) while they performed simulated driving scenarios, using our novel MRI-compatible simulator system. Performance was compared to 10 healthy age-matched controls (56-75 yrs.).

Results:
chronic stroke patients showed similar posterior brain activations as controls (e.g. visual and prefrontal lobes, precuneus). However, individuals with lower neurocognitive test scores (e.g. Montreal Cognitive Assessment, Trail-Making Test) had greater posterior activation during turning tasks, potentially due to increased cognitive effort. They also showed greater reductions in activity during distraction tasks, indicating brain function is more sensitive to distracting stimuli. Functional abnormalities were not proximal to infarcts, indicating non-focal alterations of brain networks following stroke.

Conclusions:
This is the first demonstration of systematic changes in brain function for stroke patients, and relation to clinical measures. This may have implications in our understanding of how stroke affects brain function during integrative, real-world tasks.
Abstract WP154: Bihemispheric Modulation of the Motor Cortex by Single-session Transcranial Direct Current Stimulation During Training in Subacute Stroke Patients
Authors: Kuo I-Ju , Tang Chih-Wei , Tsai Yun-An , Juan Chi-Hung , Lee I-Hui
Published: March 2022

Introduction:
Non-invasive transcranial direct current stimulation (tDCS) can induce polarity-specific changes in cortical excitability. Compared to unilateral anodal tDCS over the non-dominant motor cortex (M1), dual-hemispheric tDCS to the M1 may further accelerate motor reaction of the target hand and alter excitability of the corticospinal tract (CST). However, the effects and individual variability of bi-hemispheric tDCS to the M1 during motor training remain largely unclear in healthy and stroke subjects.

Purpose:
We assessed the hypothesis that bi-hemispheric tDCS during single-session motor training alter inter-hemispheric inhibition, CST excitability and bilateral cortical oscillations.

Methods:
We enrolled first-time, unilateral ischemic stroke patients between two and four weeks after stroke and matched healthy controls. They were subjected to two 20 min-sessions of dual-hemispheric tDCS (anode over non-dominant or ipsilesional M1, cathode over dominant or contralesional M1; 2mA for 20 mins) and sham tDCS (2mA for 2 mins) in a randomized crossover design during repetitive extension of the non-dominant or paretic extensor carpi radialis muscle. We compared the post-stimulation changes of motor evoked potentials (MEPs), ipsilateral silent period (iSP), short interval intracoritcal inhibition (SICI), as well as resting and unilateral finger lifting-related cortical oscillations by magnetoencephalography (MEG).

Results:
Compared to the sham tDCS, the dual-hemispheric tDCS significantly increased MEP amplitudes and reduced SICI at the anodal-stimulated M1, as well as decreased inter-hemispheric inhibition from the cathodal-stimulated M1 with shortened iSP for about 30 mins in healthy controls (n=8). In contrast, reduced MEP amplitudes were observed at the cathodal-stimulated M1. The tDCS effects on cortical oscillations and in stroke patients are currently under investigation.

Conclusions:
Task-concurrent dual tDCS may enhance activity-dependent motor plasticity in subacute stroke.
Abstract WP157: Stroke Risk Factors for Women With Preeclampsia in New York State, 2008-2012: a Case Control Study
Authors: Miller Eliza C , Gatollari Hajere J , Too Gloria , Boehme Amelia K , Colello Anna , Elkind Mitchell S , Willey Joshua Z
Published: March 2022

Introduction:
Pregnancy-associated stroke (PAS) remains among the leading causes of maternal morbidity and mortality. Up to 20% of women with PAS have preeclampsia or eclampsia (PEC). However, PEC is relatively common (∼3.4% of pregnancies), while PAS is rare (∼20 per 100,000 deliveries). It is not clear what risk factors differentiate women with PEC who develop PAS.

Hypothesis:
Identifying risk factors for stroke in women with PEC could help identify women at highest risk for PAS.

Methods:
We used the 2008-2012 New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS) inpatient sample database to identify pregnant or postpartum women (APR MDC 14) aged 12-50 with mild to severe preeclampsia (642.4x-642.5x) or eclampsia (642.6x). We compared non-stroke PEC patients (controls) to those with ischemic (ICD-9 433.xx, 434.xx, 436), ICH (ICD-9 431), SAH (ICD-9 430), and non-specified pregnancy-related strokes, including post-partum stroke (ICD-9 671.7, 674.0-674.4). Risk factors included delivery type (C-section vs vaginal), age, multigravida, primary hypercoagulable state, pre-existing diabetes, obesity and migraine. The associations between risk factors and stroke were evaluated using generalized estimating equation logistic regression adjusting for patients’ re-hospitalizations to calculate odds ratios and 95% confidence intervals (OR, 95%CI) for stroke .

Results:
There were 85 stroke cases and 41,634 PEC controls without stroke. A majority of strokes in PEC patients occurred postpartum (n=76, 89.4%). Stroke patients were more likely to have eclampsia (OR: 24.7, 95%CI: 15.6-39.3) or severe pre-eclampsia (OR: 1.6, 95%CI: 1.0-2.5) compared to non-stroke patients. In multivariable analyses, being multigravida (OR: 1.4, 95%CI 1.3-1.6), primary hypercoagulable state (OR:2.1, 95%CI 1.8-2.4) and migraine (OR 2.3, 95%CI 2.1-2.5) were also risk factors for stroke.

Conclusions:
Women with eclampsia were at at the highest risk for pregnancy-associated stroke. Several other risk factors for stroke in women with preeclampsia may also help identify women who warrant closer monitoring for neurological symptoms in the peripartum period.
Abstract WP16: Endovascular Recanalization Therapy in Acute Ischemic Stroke: Updated Meta-analysis of Randomized Controlled Trials
Authors: Rha Joung-ho , Hong Keun-Sik , Ko Sang-Bae , Lee Ji-Sung , Yu Kyung-Ho
Published: March 2022

Background:
Recent randomized clinical trials (RCTs) using stent-retriever thrombectomy demonstrated clear and consistent benefit of endovascular recanalization therapy (ERT) in contrast to the negative result of earlier trials. We aimed to calculate the pooled estimate of the ERT benefit added to standard therapy in AIS.

Methods:
We systematically searched Pubmed and EMBASE until 31 Apr 2015. Inclusion criteria were 1) RCT, 2) the active arm receiving ERT, 3) the control arm receiving standard therapy including intravenous TPA, but not treated with ERT, and 4) mRS score reported at 90 days or at the end of the trial. Using a random-effect model, we generated a pooled estimate as an odds ratio (OR) with 95% CI for the effect of ERT regarding the efficacy and safety outcomes for all trials, stent-retriever trials, and RCTs comparing ERT and intravenous TPA.

Results:
We identified 15 relevant RCTs involving 2,899 patients. For all trials, ERT compared to control was associated with increased good outcome (OR [95% CI], 1.79 [1.34, 2.40]; P<0.0001; number needed-to-treat [NNT]=9). ERT also increased outcomes of no or minimal disability, good neurological recovery, good activity of daily living, and recanalization. ERT was not associated with increased risks of symptomatic intracranial hemorrhage (SICH) (1.19 [0.83, 1.69]; P=0.3453; number needed-to-harm [NNH]=88) and death (0.87 [0.71, 1.05]; P=0.1508; NNT=55). On the contrary, ERT significantly reduced extreme disability or death (0.77 [0.61, 0.97]; P=0.0246; NNT=21). When restricting 5 stent-retriever RCTs which generally compared ERT added to intravenous TPA versus intravenous TPA alone, the benefit was even greater: 2.39 [1.88, 3.04], P<0.0001, NNT=5 for good outcome; 0.57 [0.41, 0.78], P=0.0006, NNT=9 for extreme disability or death. Analysis restricting 8 RCTs comparing ERT (added to intravenous TPA in 6 RCTs) with intravenous TPA alone also showed similar efficacy and safety.

Conclusions:
This updated meta-analysis shows that ERT compared to the current standard therapy substantially improves good outcome and reduces extreme disability or death without significantly increasing SICH. Now, we are facing a new challenge how to provide ERT more and faster to eligible patients.
Abstract WP160: Inflammatory Markers and Outcomes After Lacunar Stroke: the Levels of Inflammatory Markers in Treatment of Stroke Study
Authors: Boehme Amelia , McClure Leslie A , Luna Jorge M , Del Brutto Oscar H , Benavente Oscar R , Elkind Mitchell
Published: March 2022

Background:
C-reactive protein predicts prognosis after stroke, but relationships of other inflammatory biomarkers to prognosis is uncertain. We hypothesized that concentrations of interleukin 6 (IL6), serum amyloid A, tumor necrosis factor-α receptor 1 (TNFR1), CD40 ligand, and monocyte chemoattractant protein 1 predict recurrent major vascular events (MVE) after lacunar stroke.

Methods:
Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) Phase 3 trial in patients with recent lacunar stroke. Patients were randomized to aspirin versus aspirin/clopidogrel. Blood samples were collected at enrollment, and markers measured centrally using ELISA. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (HR, 95% CI) for risk of MVE (stroke, myocardial infarction, vascular death) after adjusting for demographics, comorbidities, and statin use.

Results:
Among 1244 lacunar stroke patients (mean age 63.3 ± 10.8 years), there were 115 MVE. Risk increased with concentrations of both TNFR1 (adj HR per standard deviation [SD] 1.21, 95% CI 1.05-1.41) and IL6 (adj HR per SD 1.10, 95% CI 1.02-1.19). Compared with the bottom quartile of TNFR1, those in the top quartile had twice the risk after adjusting for demographics (HR 1.98, 95% CI 1.11-3.52), though this attenuated after adjusting for other risk factors (adjusted HR 1.68, 95% CI 0.93-3.04). There was an interaction between antiplatelet assignment and TNFR1 (p=0.008; figure) and IL6 quartiles (p=0.035); as biomarker concentrations increased, dual antiplatelets became less effective than aspirin alone. Other markers were not associated with prognosis.

Conclusions:
Among recent lacunar stroke patients, IL6 and TNF receptor concentrations predict risk of recurrent vascular events and efficacy of antiplatelet therapies.
Abstract WP161: Accessibility of Current Stroke Education Brochures: Linguistic Analysis of Written Style and Readability Measures
Authors: Froeschke Laura L , Nelson Nickola W , Lagerwey Mary , Campbell Evvy H
Published: March 2022

Background/Purpose:
Existing guidelines for disease education require that written materials not exceed 6th grade reading level. Evidence shows that 90% of cardiovascular educational literature is written at or above the 8th grade level. Moreover, evidence points to variations in linguistic style, also called register, as important to lay understanding and response to disease education. The purpose of the current study was to: a) provide a description of linguistic register of current stroke education brochures; b) assess the degree to which lexical, syntactic, and discourse register features relate to Flesch-Kincaid measures; and c) provide an expanded framework for assessment of stroke literature accessibility.

Method:
Framed by critical discourse analysis and guided by Biber’s conceptual model of linguistic register, nine brochures originating from five national organizations yielding a sample of 9,903 words comprising 820 lines of text were analyzed for syntactic, lexical and discourse characteristics. Descriptive data on features were analyzed within and across brochures using linguistic analysis software. Flesch-Kincaid readability scores for each brochure permitted correlational analysis against quantitative linguistic data.

Results:
Flesch-Kincaid readability scores for stroke brochures ranged from 38.60 to 75.0 with a sample median of 63.20, or grade level 7.2. Linguistic register was found to vary within and across the body of brochures, and included features of biomedical, everyday, and advertising registers, with a predominance of biomedical register. Syntactic and lexical features used in analysis of register variation were found to vary independent of Flesch Kincaid measures. These included nominalization (Spearman’s rho = -.02, p = .97), lexical density (Spearman’s rho = -.57, p - .13), and specialized/technical vocabulary (Spearman’s rho = -.317, p = .41).

Conclusion and Discussion:
Flesch Kincaid scores obtained in this sample reinforced prior concerns of reading levels which exceed current guidelines in stroke brochures. Quantitative and qualitative linguistic analyses identified numerous features consistent with biomedical and advertising registers which varied independent of Flesch Kincaid measures.
Abstract WP162: Shared Biological Pathways Among Genetic Variants Associated With White Matter Hyperintensity in CADASIL
Authors: Giese Anne-Katrin , Zhang Cathy R , Cloonan Lisa , Rost Natalia S
Published: March 2022

Introduction:
White matter hyperintensity (WMH) is a prominent neuroimaging phenotype commonly detected in patients with stroke as well as genetic disorders like cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL). We sought to identify biologically connected pathways between the genetic loci associated with WMH burden in patients with CADASIL.

Methods:
We investigated a published polygenetic risk score for WMH burden in 466 CADASIL patients. Sixty-one single nucleotide polymorphisms (SNPs) with p-values of p<10
-4
comprised the score. We applied GRAIL (Gene Relationships Among Implicated Loci), a statistical text-mining software to assess shared biological pathways among these SNPs. The degree of relatedness to other genes was evaluated by mining PubMed abstracts. Identified related genes were ranked and scored based on inferred functional connections and investigated for association with WMH burden in 804 ischemic stroke patients.

Results:
We identified four loci (CADM1, DPP6, GCNT1 and GCNT3) which were significantly more related to other genes in the network than expected by chance (p<0.05, Figure 1). There were 304 SNPs within these loci associated with WMH burden at p<0.05 in a meta-analysis of 804 patients with ischemic stroke. Among the identified keywords were: tyrosine, core, phosphorylation, cathepsin, channels, kinase, cancer, peptidase, suppressor, activated, tumor, fragile, channel, activation, mucin, adhesion, cell and domain.

Conclusion:
Biological relationships between the four identified loci suggest putative molecular pathways associated with metabolic, enzymatic, and membrane channel-based activity mediating the effect of WMH burden in CADASIL. The role of biological pathways shared between CADASIL and ischemic stroke related WMH requires further investigation.