bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP84: A Prediction Score for Hematoma Expansion Following Acute Intracerebral Hemorrhage
Authors: Brouwers H. B , Chang Yuchiao , Falcone Guido J , Ayres Alison M , McNamara Kristen A , Vashkevich Anastasia , Battey Thomas W , Valant Valerie , Schwab Kristin , Rost Natalia S , Romero Javier M , Viswanathan Anand , Greenberg Steven M , Rosand Jonathan , Goldstein Joshua N
Published: March 2022

Purpose:
Hematoma expansion (HE) following acute intracerebral hemorrhage (ICH) is common and associated with poor outcome. Ongoing clinical trials therefore focus on restricting HE. In order to provide treatment options to the patients at highest risk of HE, we aimed to develop a prediction score for HE.

Methods:
We performed a prospective cohort study of consecutive primary ICH patients presenting to a single center over a 12-year period, with available baseline and follow-up CTs. HE was assessed using semi-automated software and defined as 6 mL or 33% growth. Our cohort was randomly divided in a 2/3 development and 1/3 validation cohort. Uni- and multivariate logistic regression was performed to assess clinical and neuroimaging covariates for relationship with HE. A prediction model was derived based on regression estimates, and this model was subsequently tested in the validation cohort.

Results:
817 ICH patients were included: 544 in the development cohort and 273 in the validation cohort. Overall, HE occurred in 156 patients (19%). In multivariate analysis, warfarin use (OR 2.09 [95%CI 1.24-3.52],
p
= 0.006), shorter time to CT (≤6 vs. >6 hours; OR 2.14 [95%CI 1.18-3.90],
p
= 0.013), baseline ICH volume (<30, 30-60, >60 mL; OR 1.90 [95%CI 1.01-3.55],
p
= 0.045), and the CT angiography spot sign (OR 3.59 [95%CI 1.77-7.29],
p
= 0.0004) were predictive of HE. The derived prediction score (0-9) showed a linear relation with the probability of HE and mortality (at discharge and 90 days), in both the development and the validation cohorts. The probability of HE in the validation cohort was 0%, 10%, 39%, and 54% for categorized scores 0, 1-3, 4-6, and 7-9, respectively. The c statistics were 0.69 for the development cohort and 0.78 for the validation cohort.

Conclusion:
Warfarin use, presentation within 6 hours after ICH, larger ICH volumes at baseline, and the CT angiography spot sign are independent predictors of HE and mortality. Based on these findings, we developed a prediction score for HE. Since no therapy has demonstrated benefit in a randomized trial, our results open a path for individualized treatment and trial design in ICH, aimed at patients at highest risk of HE.
Abstract TMP85: Enhancing Stroke Nursing Education Through Simulation
Authors: Grace Melissa
Published: March 2022

BACKGROUND:
During a Primary Stroke Center recertification survey by The Joint Commission at this 504 bed community hospital a knowledge gap was discovered in applying the National Institutes of Health Stroke Scale (NIHSS) at the bedside and correlating it with clinical findings. Since 2009, this stroke program has required nurses caring for acute stroke patients to complete NIHSS certification annually. The purpose of this simulated educational competency program was to verify performance of the NIHSS and provide education correlating symptoms with brain physiology.

METHODS:
Nurses caring for acute stroke patients attended this mandatory educational program which included a review of anatomy, NIHSS application and scoring on a simulated patient, and a debriefing discussion. The simulated patients were assigned specific deficits to portray. Immediate feedback was provided to participants upon completion. Symptoms of each patient were correlated with the affected brain physiology during a group debriefing discussion. Participants evaluated their perceived competency performing the NIHSS and associating brain physiology before and after the session using a four point Likert-type scale with 1 being strongly disagree and 4 being strongly agree.

RESULTS:
Competency was demonstrated by 196 nurses with 174 completing evaluations expressing high satisfaction with the material and mode of learning. Evaluation data was analyzed using descriptive statistics and a paired
t
test showing improvements in self perceived NIHSS competency and ability to correlate the affected brain physiology. The mean self perceived NIHSS competency prior to the session was 3.28 compared to 3.90 post session (
t
(172) = 13.99,
p
< 0.01). The mean self perceived ability to correlate the affected brain physiology prior to the session was 2.61 compared to 3.57 post session (
t
(173) = 18.09,
p
< 0.01).

CONCLUSION:
The current NIHSS certification examination has known limitations. Integrating simulated learning experiences together with NIHSS certification resulted in perceived improvement in understanding and competency. Follow up is necessary to determine if this translates into improved bedside clinical practice.
Abstract TMP90: Caregiver Task Difficulty, Depressive Symptoms, and Life Changes among Stroke Family Caregivers: Does Type of Relationship Matter?
Authors: Jessup Nenette M. , McLennon Susan M. , Weaver Michael T. , Bakas Tamilyn
Published: March 2022

Background/Purpose:
The high incidence of stroke creates greater need for caregivers than can be met solely by immediate family members. However, little research has explored how caregiver relationship to the stroke survivor may affect caregiver experiences. The purpose of this study is to explore differences in caregiver task difficulty, depressive symptoms, and life changes based on type of relationship to the stroke survivor.

Methods:
Stroke caregivers (N=175) recruited into an ongoing stroke caregiver intervention trial were categorized by relationship to survivor as spouse (n =79), adult child/in-law (n = 57), and other (n =39). Baseline data for task difficulty (Oberst Caregiving Burden Scale: OCBS); depressive symptoms (PHQ-9); and life changes (Bakas Caregiving Outcomes Scale: BCOS) comprised the dependent variables. Differences in means between relationship groups were analyzed using separate ANOVA models for each dependent variable.

Results:
Means for the 3 relationship groups were similar for all dependent measures. Task difficulty [F(2,172) = 1.00; p =.37], depressive symptoms [F(2,172) = .04; p =.96], and life changes [F(2,172) = .06; p =.94] all had non-statistically significant results.

Conclusions:
The type of caregiver relationship to the stroke survivor did not differ with respect to mean task difficulty, depressive symptoms, or life changes scores. While these groups were similar at baseline, evaluating whether relationship moderates response to intervention at later time points may provide further implications for targeted interventions based on type of relationship.
Abstract TMP93: Level of Renal Function and Short-term Risk of Recurrent Stroke
Authors: Thomas Abraham , Poisson Sharon , Johnston S. C. , Ovbiagele Bruce , Klingman Jeff , Sidney Steve , Nguyen-Huynh Mai
Published: March 2022

Introduction:
Renal insufficiency is an established risk factor for first-time vascular events including stroke. There is a paucity of data on the relation of renal function to recurrent stroke risk, especially in a population-based setting. We evaluated the associations of different levels of renal function with short-term recurrent stroke risk.

Methods:
Our cohort included patients admitted to 12 hospitals in a Northern California healthcare network with acute ischemic stroke between 2004 and 2007. Records from the index hospitalization and for 6 month follow ups were reviewed. Estimated Glomerular Filtration Rate (eGFR) in mL/min/1.73 m
2
, calculated using the MDRD equation, was categorized by modified National Kidney Foundation stage: 1 (≥90), 2(60-90), 3(30-60), 4 (<30). Multivariate analyses, using generalized estimating equations to adjust for within and between hospital variances, were adjusted for age, race, sex, hypertension, diabetes, and hyperlipidemia.

Results:
Of 2,882 patients with eGFR, mean age was 73±13 ; 66% were Caucasian, 14% African-American, 11% Asian and 52% were female. On admission, renal function was stage 1 in 693 (24%), 2 in 1341 (47%), 3 in 706 (25%), and 4 in 142 (5%). An inverse relationship between age and eGFR was observed (p<0.001). African Americans were most likely to have stage 1 and stage 4 renal function (p<0.001) and Caucasians were more likely to have stage 2 and 3 renal function (p<0.001). Hypertension was most common among those with stage 3 renal function (p<0.001), and diabetes and hyperlipidemia were most common among those with stage 4 renal function (p<0.001 for both). In multivariate analysis, blood pressure control at 6 month follow up was less likely with stage 4 renal function compared with lower stages (OR 0.47, p<0.001), but there was no difference between stages 1, 2 and 3. There was a direct relationship between stage of renal function and risk of recurrent stroke (stage 1 REF, stage 2 OR 1.6, stage 3 OR 1.7, stage 4 OR 1.8, p<0.01 for all).

Conclusions:
Decreased renal function is an independent predictor of short-term recurrent stroke in a graded dose-dependent manner. Even among those with “normal” renal function (eGFR 60-90), recurrent stroke risk was 60% greater than in those with higher eGFR.
Abstract TMP95: A Prospective Quality Initiative to Maximize Dysphagia Screening Prevents Stroke Associated Pneumonia
Authors: Titsworth William L , Abram Justine , Fullerton Amy , Hester Jeannette , Guin Peggy , Waters Michael F , Mocco J
Published: March 2022

BACKGROUND AND PURPOSE:
Dysphagia can lead to pneumonia and subsequent death following acute stroke. However, no prospective study has demonstrated reduces pneumonia rates after implementation of a dysphagia screen.

METHODS:
This was a single-center prospective interrupted time series trial of a dysphagia screening quality initiative. Subjects included all ischemic or hemorrhagic strokes over a 42-month period with a 31-month (n=1686) pre-intervention period and an 11-month (n=648) post intervention period. The multifaceted interdepartmental quality improvement initiative centered on a nurse-administered dysphagia screen with rapid speech pathology evaluation.

RESULTS:
The dysphagia screening initiative increased the percentage of stroke patients screened from 39.3% to 74.2% (p<0.001). Increased screening correlated with a drop in stroke-associated pneumonia from 6.5% to 2.8% (p<0.001). Patients admitted post-initiative had 53% lower odds of pneumonia, after controlling for multiple confounds (OR=0.43, CI=[0.255, 0.711], p=.0011). The best predictors of pneumonia were stroke type (p<.0001), NPO status (p<0.0001), dysphagia screening status (p=.0037), and hospitalization prior to the initiative (p=.0449). By using a nurse-administered bedside screen and streamlining of protocols 11.5% of speech pathology referrals came directly from nurses without a physician order.

CONCLUSION:
A quality improvement initiative utilizing a nurse-administered bedside screen improves screening rates and is associated with decrease pneumonia among stroke patients.
Abstract TMP98: Transient Ischemic Attack in Children and Its Relationship to Cerebral Infarction Identified by MRI
Authors: Lehman Laura L , Danehy Amy R , Rivkin Michael J
Published: March 2022

Objectives:
Recent definition of transient ischemic attack (TIA) in adults includes negative neuroimaging for ischemic injury. Among children, TIA has not been well characterized. Further, the extent to which TIA symptoms are associated with MRI evidence of new cerebral injury has not been investigated. We present a cohort of 68 children with TIA symptoms and associated neuroimaging (MRI).

Methods:
We searched the patient medical record database at Boston Children’s Hospital using the search terms “transient ischemic attack” or “TIA” in the year 2010. We examined cases of TIAs in children 18 years of age or younger whose TIA occurred between 2009 to 2011. TIA was defined as a focal neurologic deficit that resolved completely. We only included children who had an MRI done close to the time of the event. A blinded neuroradiologist evaluated all MRIs.

Results:
Diffusion weighted imaging was done in 82% of cases in the cohort. Time from TIA to MRI varied from the day of TIA to 122 days after TIA with 68% scanned within 10 days of TIA presentation. Following TIA, nine of the 68 patients (13%) sustained a stroke verified by evidence of new ischemic injury in a vascular territory on neuroimaging. Time from initial TIA to stroke occurrence varied from hours to 3 years. Acute stroke was documented within one week of TIA in 56% of children who developed stroke following TIA. Further, 67% of the children who had a stroke after TIA demonstrated neuroimaging evidence of arteriopathy as compared to only 10% of children who did not have a stroke. Recurrent TIA was more common in children who eventually had a stroke (78%) than in children who did not have a stroke (59%).

Conclusion:
In our cohort of 68 children who presented with TIA symptoms, 13% subsequently demonstrated evidence of acute cerebral infarction by neuroimaging, some as early as the first week following TIA. Like adults, TIA symptoms may herald stroke in children. Clinical evidence of cerebral arteriopathy and multiple TIAs may identify children at high risk for stroke after presentation with TIA symptoms. Additional inquiry to identify features of TIAs in children that impart high risk for stroke and their treatment is warranted.
Abstract TP101: Gene Expression Profile After Repetitive Transcranial Magnetic Stimulation
Authors: Oh Byung-Mo , Beom Jaewon , Choi Joong Kyung , Lee Seung Ah , Bang Moon Suk , Park Woong Yang , Han Tai Ryoon
Published: March 2022

Introduction:
Although repetitive transcranial magnetic stimulation (rTMS) has been getting attention as a new therapeutic tool in stroke rehabilitation, little is known about its molecular mechanisms.

Objectives:
We have performed microarray mRNA and miRNA analysis as well as miRNA-mRNA integrated analysis to investigate of rTMS-induced molecular changes at a genome-wide scale.

Methods:
Eight adult male Sprague-Dawley rats were subjected to a single session of unilateral rTMS with 1 Hz (n=4) or sham (n=4) protocol to explore the immediate effect after rTMS. Additional 8 rats were assigned to receive either 1-Hz (n=4) or sham (n=4) rTMS for 5 consecutive days to the left hemisphere using the same protocol. The Illumina HumanHT-12 v3 Expression BeadChip microarray was used for mRNA expression analysis. Agilent Rat microRNA Microarrays (mirBASE 15.0) (Agilent Technologies, Inc. Santa Clara, CA) was used for additional analysis of miRNA.

Results:
Microarray analysis reveals differentially expressed genes in the rat cortex after real or sham rTMS. Overrepresented gene ontology categories include positive regulation of axon extension, axonogenesis, intracellular transport, and synaptic plasticity after repetitive sessions of rTMS. A single session of rTMS, however, induced changes primarily in immediate early genes. In addition, several miRNAs showed significant inverse relationship with mRNAs.

Conclusion:
We explored potential mechanisms of rTMS in a small animal model of unilateral hemispheric rTMS and confirmed its differential molecular effects on the stimulated cortices. Future study will be required to validate the functional significance of selected genes and to refine therapeutic use of rTMS. Figure 1. Cluster analysis for 200 probes of high fold-change did not show clear distinction between groups immediately after rTMS (A). Repetitive stimulation for 5 consecutive days shows, however, obvious difference of gene expression between groups (B).
Abstract TP104: Candesartan Increases Matrix Metalloproteinase Activation but Still Provides Benefit When in Combination with Tissue Plasminogen Activator in Experimental Embolic Stroke
Authors: Ishrat Tauheed , Pillai Bindu , Ergul Adviye , Fagan Susan C
Published: March 2022

Background & Objective:
Recently, combination therapy with tissue plasminogen activator (tPA) has been shown to worsen stroke outcome in experimental and clinical studies (Erythropoietin). Candesartan increases matrix metalloproteinase (MMP) activation and exhibits vascular protection in experimental stroke. It is imperative to test for interactions with tPA. The present study evaluated the effect of candesartan in combination with tPA in a rat model of embolic stroke.

Methods:
Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO) and treated with either candesartan (1mg/kg) alone early at 3h, tPA (10mg/kg) alone at 6h, the combination of candesartan (early 3h and delayed 24h) and tPA (6h), or saline control. A battery of functional outcome test was performed before sacrifice at 24 and 48h after eMCAO and infarct sizes, hemoglobin content (Hb) and tissue MMP activity analyzed.

Results:
The combination therapy of candesartan (3h) and tPA (6h) after MCAO reduced the brain hemorrhage in terms of Hb content and improved functional outcome compared with rats treated with tPA alone. However, when the candesartan therapy was delayed to 24 h (tPA at 6h) after MCAO, the benefit was lost. Furthermore, candesartan (3h) alone and also in combination with tPA increased MMP activation compared with respective controls.

Conclusions:
Acute administration of candesartan, despite increasing MMP activation, reduces bleeding associated with tPA use in the rat embolic model. MMP activation alone is insufficient to cause increased hemorrhagic transformation. Table 1. Summary of experimental stroke data. SE are shown in parentheses. P<0.05 was considered significant.
Abstract TP105: Increaed GABA
A
Mediated Synaptic Activity and Structural Remodeling in Peri-infarct Cortex Layer 5 in the Post-stroke Rodent Brain.
Authors: Hiu Takeshi , Bliss Tonya M , Farzampour Zoya , Paz Jeanne T , Olson Andrew , Micheva Kristina D , Wang Eric H , Wang Gordon , Manley Nathan , Nishiyama Yasuhiro , Arac Ahmet , O’Rourke Nancy , Huguenard John R , Smith Stephen J , Steinberg Gary K , Tran Kevin
Published: March 2022

Introduction:
The mechanisms of functional recovery after stroke are thought to be based on structural and functional changes in brain circuits adjacent to or connected with the stroke site. Deciphering these changes at the synaptic level is key to understanding the re-organization of the synaptic circuitry. Here we use a combined approach of i) array tomography to determine the composition of GABA synapses in the post-stroke mouse brain, with ii) electrophysiology to determine whether stroke leads to functional changes in GABA
A
receptor-mediated neurotransmission.

Methods:
A cortical lesion was induced in 12-week-old C57BL/6J male mice using the distal middle cerebral artery occlusion model of ischemia. For array tomography, small tissue was removed from the peri-infarct cortex and ribbons of serial ultrathin sections were obtained. Ribbons were stained with antibodies for synaptic markers. Analysis of the resultant staining pattern was used to quantify GABAergic synapses. In addition, whole-cell patch clamp recordings from acute neocortical brain slices were performed to evaluate GABA-mediated synaptic signaling in the peri-infarct cortex. Behavior was evaluated weekly.

Results:
At 1 week post-stroke, the array tomography data revealed an increase in the density and proportion of alpha1 subunit-containing GABAergic synapses in layer 5 of the peri-infarct cortex (Density: 0.064 vs 0.036 synapses/μm3. Proportion: 15.3 vs 9.1 %, p<0.05, n=6); no changes were observed in layer2/3. Changes in GABA synapses were transient and returned to basal levels by 1 month. Electrophysiological recordings at 1 week post-stroke showed that GABA
A
receptor-mediated currents were enhanced in layer 5, but not in layer 2/3. These changes were specific to the pyramidal neurons. Behavioral impairment after stroke was observed only at 1 week compared to sham mice (p<0.05, n=10).

Conclusion:
Our results suggest that stroke leads to an increased expression of functional GABA
A
receptors in peri-infarct neocortex and that these changes are layer- and cell type-specific. These synaptic changes may represent a mechanism of post-stroke functional recovery and remapping of surviving circuits.
Abstract TP118: Dizziness Rule Out Posterior Circulation Stroke
Authors: Nalleballe krishna C , Garg Ravi , Jasti Madhu S , Katz Paul M
Published: March 2022

Objective:
Dizziness is the 3rd most common major medical symptom reported and accounts for 3-5% of visits across care settings. In the United States, this translates to 10 million visits per year because of dizziness with roughly 25% of these visits to emergency departments. In this study we tried to evaluate the incidence of posterior circulation strokes in patients presenting to the emergency department with symptoms of isolated dizziness (dizziness, vertigo or imbalance).

Methods:
A retrospective review of patients admitted with symptoms of isolated dizziness to the Neurology department at our hospital from May 2010 to May 2012. Inclusion Criteria were all patients had to be seen by a neurologist and have Magnetic Resonance Imaging (MRI). Exclusion Criteria were having long track signs, cranial nerve findings, known metastatic cancer, or history of Menieres disease.

Results:
During the study period, among 450 patients 101 patients met the criteria, 60 were admitted for Dizziness, 34 for Vertigo, and 7 for imbalance. Four out of 101 (3.96%) had positive findings on the MRI. Among these 4 patients one was a 28 year old patient who was found to have T2 hyper intensity in the left cerebral peduncle (indicating glioma versus demyelinating disease) which remained stable on repeat scan after a year. Two out of the other 3 patients had acute stroke on Computed Tomography (CT), while the third patient had an age indeterminate lacunar infarct in the brain stem. All 3 patients who had a posterior circulation stroke in our study( 3 out of 101 which is 2.97%) were greater than 45yrs of age and had greater than 2 vascular risk factors for stroke.

Conclusions:
Less than 4% (3.96%) of the patients who presented with symptoms of isolated dizziness had posterior circulation strokes or lesions on MRI. The incidence of cerebrovascular events in patients presenting with isolated dizziness without long track signs, cranial nerve findings, or vascular risk factors for stroke is very low.
Abstract TP121: Predictors of Ischemic Stroke in Patients with Atherosclerotic Vascular Disease: Observations from the TRA 2°P-TIMI 50 Trial
Authors: Bonaca Marc P , Ameriso Sebastian F , Alberts Mark J , Mohr Jay P , Hankey Graeme J , Murphy Sabina A , Scirica Benjamin M , Braunwald Euegene , Morrow David A
Published: March 2022

Risk factors for ischemic stroke broadly overlap with predictors of atherosclerotic vascular disease. Few studies have examined this risk in patients with different types of symptomatic atherosclerotic disease.

Methods:
TRA 2°P-TIMI 50 was a multinational, randomized, trial of 26449 patients with atherothrombosis randomized to vorapaxar or placebo added to standard therapy. Patients qualified with a history of myocardial infarction (MI), symptomatic peripheral arterial disease (PAD), or recent ischemic stroke (CVD, 2 wks to 12 mo.). Stroke was adjudicated by an independent CEC. Correlates of stroke were determined in placebo patients (N=13,169)

Results:
A total of 294 ischemic strokes occurred during follow up. Overall age, hypertension, diabetes mellitus, PAD, prior ischemic stroke, renal dysfunction, atrial fibrillation/flutter, and carotid stenosis ≥ 50% were associated with new ischemic stroke during follow up (Figure A). After adjustment age, hypertension, diabetes, prior ischemic stroke, and atrial fibrillation/flutter remained significantly associated with ischemic stroke with a history of ischemic stroke associated with the greatest hazard (adj HR 5.15, 95% CI 4.02 - 6.61, p<0.001). When stratified by qualifying event, traditional risk factors and distant ischemic stroke were associated with new stroke in the MI/PAD group (Figure B). In contrast, only diabetes and prior myocardial infarction were associated with recurrent stroke in the CVD group (Figure C).

Conclusions:
Predictors of ischemic stroke in patients with atherosclerotic vascular disease vary by the primary symptomatic bed. In patients with recent MI or PAD, prior stroke is the strongest predictor while traditional risk factors are also associated with recurrent events. In patients with recent stroke only prior MI and diabetes predict recurrent stroke.
Abstract TP122: Identifying Predictors of Seizure Recurrence After Nonconvulsive Seizures Recorded on Continuous Electroencephalogram (cEEG) in Ischemic Stroke
Authors: Newey Christopher R , Hantus Stephen
Published: March 2022

INTRODUCTION:
Seizures are well-recognized complications of ischemic strokes (IS). The risk of subsequent development of epilepsy has been shown to be 2-4% in acute IS and much higher in remote IS. However, the risk of epilepsy in IS who have nonconvulsive seizures on cEEG is not well characterized. We present here a five-year retrospective study of IS patients who have nonconvulsive seizures on cEEG identifying risk factors for the development of epilepsy.

METHODS:
We retrospectively reviewed prospectively collected cEEG and clinical data on consecutive patients monitored from January 1, 2007, to December 31, 2011. We identified those patients with cEEG seizures that were secondary to either acute (<30 days) or remote (>30 days) ischemic stroke (IS; n=109) and then included in this study only those patients with follow-up encounters. Statistical analyses were performed with JMP 9.0.

RESULTS:
Sixty-five (41.5% acute IS, 58.5% remote IS) patients met inclusion criteria for this study. All patients were discharged on at least one antiepileptic. Nineteen (29.2%) patients were found to have seizure recurrence (i.e., epilepsy) with 84.2% being remote IS (p=0.0116). Periodic lateralized epileptiform discharges (PLEDs) were seen on cEEG in 21.5% (22.2% acute IS, 21.1% remote IS). 15.8% with PLEDs on initial cEEG developed epilepsy (p=0.74). 33.3% of patients classified as stupor/coma at the time of nonconvulsive seizures were found to have seizure recurrence compared to 24.1% of patients classified as awake/lethargy (p=0.5841). On follow up EEG (mean (SEM) 384.4 (59.1) days), the finding of sharp wave/spike (12.1%) significantly correlated with seizure recurrence (p=0.0175).

DISCUSSION:
This retrospective study found that patients with remote IS are at a higher risk of developing epilepsy when nonconvulsive seizures are recorded on cEEG in the hospital. Additionally, the finding of sharp waves on follow-up routine EEG further identifies those at risk for recurrence. This study highlights the usefulness of cEEG in patients in patients with acute or remote strokes and provides guidance on utility of follow-up EEG.
Abstract TP126: The Ketones Acetoacetate And Beta-hydroxybutyrate Alleviate Ischemic Injury Following Occlusion Of The Middle Cerebral Artery
Authors: Maalouf Marwan , Yin Junxiang
Published: March 2022

Acute ischemic stroke is treated with thrombolysis but therapeutic benefits are modest. One potential reason for the limited clinical improvement is the apoptotic, delayed cell death that occurs prominently in the periphery of the ischemic core, the penumbra, despite successful reperfusion. Apoptotic cell death has been attributed to glutamate excitotoxicity, a consequence of ischemic energy depletion as well as a cause of persistent mitochondrial dysfunction that perpetuates energetic failure. We have previously shown that glutamate excitotoxicity and mitochondrial dysfunction are alleviated by the ketones acetoacetate and beta-hydroxybutyrate, a combination of physiological compounds produced by liver during calorie restriction to sustain cellular energy requirements. Ketones enhance mitochondrial respiration driven by complex I of the electron transport chain, decrease oxidative stress and increase ATP synthesis. Here, we investigated the effects of ketones in 3 month-old mice subjected to middle cerebral artery (MCA) occlusion with a filament for 90 min. Ketones (50 mg/kg) were administered intraperitoneally 30 min after the onset of ischemia and significantly improved outcomes. MCA occlusion caused significant neuronal loss 24 hours later in the subcortical and cortical regions of the ipsilateral hemisphere. Damage was most severe in the subcortical region and was quite evident on a 7 Tesla MRI. The results were confirmed by non-invasive imaging of apoptosis with the fluorescent indicator Annexin Vivo 750 using a Xenogen IVIS Spectrum (Caliper). Treating mice with ketones significantly decreased neuronal damage based on histology, MRI and fluorescence imaging of apoptosis with Annexin Vivo 750. Furthermore, ketones improved motor activity on the Rotarod and Open Field tests. Untreated mice exhibited evident decreases in the times they remained on the rods whereas ketone-treated mice were almost back to baseline. Consistently, untreated animals were less active in the open field. In sum, our data show that a combination of physiological ketones previously shown to enhance mitochondrial activity and alleviate glutamate excitotoxicity decreases cellular loss and improves motor function in a mouse model of ischemic stroke.
Abstract TP130: Age-Adjusted Normative Blood Flow in Major Cerebral Vessels: Implications for Assessment of Cerebrovascular Occlusive Disease
Authors: Amin-Hanjani Sepideh , Du Xinjian , Pandey Dilip K , Thulborn Keith R , Charbel Fady T
Published: March 2022

Objective:
We have previously demonstrated an effect of age and Circle of Willis anatomic variants on individual major cerebral vessel flow rates, using quantitative magnetic resonance angiography (QMRA). We have now sought to establish normative flow ranges which could serve as clinically useful benchmarks for evaluating the hemodynamics of large vessel cerebrovascular occlusive disease.

Methods:
326 healthy adult volunteers with no history of cerebrovascular disease underwent QMRA of cerebral vessels. Flows were measured bilaterally in the internal carotid artery (ICA), middle cerebral artery (MCA), anterior cerebral artery (ACA) A1 and A2 segments, posterior cerebral artery (PCA), basilar artery (BA), and vertebral artery (VA). Both individual vessel flow in ml/min, and indexed to total cerebral flow (TCBF=ICAs + VAs) was examined in relation to age and vascular anatomy, and percentile thresholds for normative flow were determined.

Results:
The volunteers ranged from 18 to 84 (mean 48) years old, with 48% female. All individual vessel flows declined with age (P<0.01), with TCBF on average 3ml/min/year lower. When individual vessel flow was indexed to TCBF, the age effect was neutralized (as demonstrated for left MCA flow in figure). Although anatomic variations, such as fetal PCA or hypoplastic A1 continued to have a significant impact on indexed flow in vessels proximal to the circle of Willis (ICA and BA), distal vessels revealed less variability, allowing percentile distributions of normative flow to be created.

Conclusions:
Indexing individual flows to TCBF allows age-adjusted normative ranges to be defined by percentile categories. Definition of these ranges may allow examination of the hemodynamic effect of cerebrovascular occlusive disease, although it remains to be examined if specific percentile thresholds for individual distal vessel flow will be a useful predictor of increased hemodynamic stroke risk.
Abstract TP132: Decompressive Hemicraniectomy Improves Survival in Malignant Middle Cerebral Artery Stroke Patients with Hemorhagic Conversion Admitted with a High Glasgow Coma Scale
Authors: Ojeda Chris , Chitravanshi Nitya , Reid Patrick C , Prestigiacomo Charles J , Duffis Ennis J , Gandhi Chirag D
Published: March 2022

Decompressive hemicraniectomy (DHC) has been shown to improve clinical outcome in cases of malignant infarct but its indications have not been well classified. This study focuses on patients who suffered malignant middle cerebral artery (MMCA) infarct with subsequent hemorrhagic conversion and were admitted with mild brain injury (initial Glasgow Coma Scale≥13). Survival rates of MMCA infarct patients with hemorrhagic conversion who underwent DHC were compared with those treated with medical management only.

Hypothesis:
Patients admitted for MMCA infarct with a Glasgow Coma Scale ≥13 who develop hemorrhagic conversion have improved survivability when DHC is performed.

Methods:
Retrospective review was performed on all cases consulted for neurological surgery from 2007-2012 at University Hospital. Patients were selected on the criteria of MMCA infarct on admission with subsequent development of hemorrhage conversion. Patients who underwent DHC had to have the hemorrhagic conversion prior to surgery for inclusion. The primary endpoint was mortality. Fisher’s Exact Test and odds ratio were performed on patients with MMCA infarct and hemorrhagic conversion comparing patient mortality with DHC to that without.

Results:
In total, 91 MMCA infarct patients were referred to neurological surgery, 33 with an initial Glasgow Coma Scale >13. Of those, 36% (12/33) had hemorrhagic conversion. Six patients underwent DHC with a survival rate of 6/6. Patients treated medically had a survival rate of 33%. The Fisher’s Exact Test showed statistical significance (p<0.05) for improved survival rate and Odds ratio confirmed reduced mortality within a 95% confidence interval of hemorrhagic conversion following MMCA infarct when DHC was performed using GraphPad InStat 3.10.

Conclusion:
A statistically significant increase in survival has been found with use of DHC for MMCA infarct with subsequent hemorrhagic conversion in patients with a high admission Glasgow Coma Scale.
Abstract TP139: Usefulness of Staged Angioplasty for Carotid Artery Stenting
Authors: Kidani Naoya , Sugiu Kenji , Tokunaga Koji , Hishikawa Tomohito , Hiramatsu Masafumi , Toyoshima Atsuhiko , Okuma Yu , Shimizu Tomohisa , Haruma Jun , Date Isao
Published: March 2022

Introduction:
Hyperperfusion syndrome is one of the most serious complications after carotid revascularization. We report the efficacy of staged angioplasty (SAP) for patients with severely impaired cerebral vasoreactivity.

Methods:
From April 2008 to March 2012, seventeen of 83 patients with high-grade internal carotid artery stenosis were considered at high risk of postoperative hyperperfusion based on the results of preoperative single-photon emission computed tomography (SPECT) with acetazolamide. They were treated with SAP which consists of mild balloon angioplasty (1st stage) and carotid artery stenting one month later (2nd stage). Rest 123I-IMP SPECT was performed to evaluate hyperperfusion just after the procedure of each stage.

Results:
Before we induced SAP procedure, 1.9%(3 of 158) of patients treated with CAS had a hemorrhagic complication due to hyperperfusion. None of 17 patients treated with SAP had hyperperfusion phenomenon on SPECT, and a hemorrhagic complication. The mean rate of stenosis was 91% before treatment, 70% after 1st stage, 21% after 2nd stage. Although stenosis had been worsened during the period between 1st and 2nd stages in four patients, all patients showed satisfactory recovery of cerebral blood flow after 2nd stage.

Conclusions:
In selected patients, SAP is effective and relatively safe to decrease hyperperfusion syndrome after procedures. However, method to choose high-risk patient for postoperative hyperperfusion and protocol of treatment are still controversial.
Abstract TP14: Simultaneous Endovenous Hypothermia and Intra-Arterial Thrombectomy for Acute Ischemic Stroke is Safe, Feasible and Does Not Require General Anesthesia
Authors: Linares Guillermo , Polderman Kees H , Wechsler Lawrence R , Ortega-Gutierrez Santiago , Jankowitz Brian , Horowitz Michael B , Reddy Vivek , Hammer Maxim D , Jadhav Ashutosh P , Grandhi Ramesh , Oakley Jennifer , Koehler Steven A , Jovin Tudor G
Published: March 2022

Background:
Hypothermia is a promising neuroprotectant. Amelioration of reperfusion injury after recanalization is a potential benefit. Due to easy access to the femoral vein, endovenous hypothermia can be combined with intra-arterial therapy. Hypothermia and shivering control is possible without mechanical ventilation, deep sedation or paralytic agents.

Methods:
Consecutive patients with acute ischemic stroke and receiving intra-arterial therapy were studied. An arterial sheath and an endovenous hypothermia catheter were placed into the femoral artery and vein. Hypothermia induction was performed with cold saline infusion. Goal temperature prior to recanalization was 35° or lower. Hypothermia was continued to a goal of 32° for 24 hrs. Controlled rewarming at 0.2°/hr was carried out. Shivering was controlled with skin counter warming, magnesium, dexmedetomidine, and meperidine. The BSAS scale was used to monitor shivering.

Results:
A total of 10 patients were studied, five women. Two patients with brainstem infarction were intubated, eight recieved sedation. Median age was 65 (range 49 - 80), NIHSS 16 (12 - 27), time from last known well 4 hrs (1 - 10) and ASPECTS 7 (6 - 10). Median door to venous needle time was 37 minutes (26 - 67) and arterial 40 minutes (30 - 70). Median time to reach 35° was 23 minutes (13 - 45). Eight patients reached 35° prior to recanalization. Median time to reach 32° was 171 minutes (122 - 235). Median BSAS was 1 (1-2). Median dose of dexmedetomidine infusion was 0.5 mcg/kg (0.2 - 0.8) meperidine 25mg (0 - 75) and magnesium 4gr (4-6). Two patients were treated for pneumonia prior to discharge. One DVT and one PE were diagnosed. No groin complications were recorded. Three patients died, two after withdrawal of care. Five patients were discharged to a rehabilitation facility and two to a skilled nursing facility.

Conclusions:
Combined endovenous hypothermia and intra-arterial therapy for acute ischemic stroke is feasible. In non-intubated patients shivering is well controlled and does not necessitate deep sedation or paralytic agents. Hypothermia catheter insertion does not delay intra-arterial recanalization. These data support the planning of a phase 2 trial to assess safety and optimum temperature goals.
Abstract TP141: Blood Pharmacokinetics of the Intravenous Neuroprotectant Dodecafluoropentane Emulsion in Rabbits
Authors: Ricca Aaron M , Skinner Robert D , Woods Sean D , Winter Melissa L , Hamilton Eric , Borrelli Michael J , Hendrickson Howard P , Lay Jack O , Johnson Jennifer L , Unger Evan C , Culp William C
Published: March 2022

Introduction:
Intravenous dodecafluoropentane emulsion (DDFPe) has proven ability to transport oxygen in ischemic and anemic animal models. Therapeutic effects in rabbits and pigs last at least 90 minutes, although in human studies dodecafluoropentane (DDFP) is eliminated rapidly from the blood through respiration. DDFPe neuroprotection reduces infarct volumes >80% in our rabbit embolic stroke model. Since little is known about DDFPe activity in rabbits, blood pharmacokinetics were investigated in healthy rabbits to determine dosing regimens.

Hypothesis:
We hypothesize that DDFP pharmacokinetics in the rabbit are similar to those in humans, with blood half-life values near 2.2±1.2 min, and clearance values near 49.6±10.8 mL/min/kg.

Methods:
Bilateral ear catheters, one intravenous and one intraarterial, were introduced into New Zealand White rabbits (N=8, 4.2±0.9 kg) for DDFPe administration and blood sampling, respectively. Rabbits were divided into 3 DDFPe dosage groups: 1) single bolus (0.6 mL/kg) with blood sampling for 4 hrs (N=4), 2) 15 doses (0.1 mL/kg) with sampling for 24 hrs (N=2), 3) 5 doses (0.6 mL/kg) with sampling for 7 hrs (N=2). Repeated doses of 2% w/v DDFPe were administered every 90 min. All samples were kept frozen until thawed before analysis by headspace gas chromatography-mass spectrometry.

Results:
An exponential regression closely approximated the blood concentration vs. time plot of single bolus sampling with an average R
2
of 0.96±0.02, thus compartmental modeling was used for pharmacokinetic analysis. The blood half-life was 1.9±0.6 min, with a clearance of 90.1±45.3 mL/min/kg. In all multi-dose rabbits, blood concentration of DDFP did not reach a steady state. The concentration vs. time data exhibited a repeated sequence of individual bolus data, with DDFP reaching undetectable levels 10 min after each dose.

Conclusion:
Blood elimination half-life and clearance rates of DDFPe in rabbits are comparable to humans, further indicating that the rabbit stroke model is appropriate for investigation of the neuroprotective potential of DDFPe. The time disparity between blood levels and therapeutic oxygen transport ability of DDFPe suggests multiple compartments and merits further investigation.
Abstract TP151: Stenting of Symptomatic Intracranial Stenosis Using Balloon Mounted Coronary Stents: A Single Center Experience
Authors: Geraghty Scott , Southerland Andrew , Conant Patricia , Jensen Mary , Evans Avery
Published: March 2022

Introduction:
The SAMMPRIS trial demonstrated that stenting for symptomatic intracranial stenosis (ICS) (70-99%) with the Wingspan system is significantly more dangerous than best medical management. The Wingspan involves a complicated four step deployment procedure; when conversely, the balloon mounted coronary stent (BMCS) is a single step process without the need for an exchange maneuver. Based on our experience, we hypothesize that intracranial stenting with BMCS is a less complicated, clinically viable alternative for patients with symptomatic ICS.

Methods:
We performed a retrospective chart review of all patients at our center with symptomatic ICS (defined as >70%) and attempted placement of BMCS (n=37) between 12/2005-6/2012. Pretreatment ICS was measured by conventional cerebral angiography in all cases. Clinical outcomes included peri-procedural stroke or death prior to hospital discharge and all cause stroke or mortality within serial follow-up. Procedural outcomes included complications of stent placement and long-term stent patency. Follow-up was obtained up to 48 months with a mean follow-up of 18.5 months.

Results:
BMCS was attempted in 37 patients (14 women, 23 men; age range 30-80 years, mean 60.8 years). There was a 97% technical success rate for the procedure with one patient suffering an asymptomatic MCA dissection. Two patients (5.4%) had small peri-procedural infarcts. There were no peri-procedural deaths. At one year follow-up, there were three non-stroke related deaths (8%), one asymptomatic stent occlusion at three months follow-up and five patients requiring angioplasty for restenosis. There were two late infarcts, one not in distribution of the stent, and one in a patient who was taken off antiplatelet regimen. Angiography in these patients demonstrated stent patency.

Conclusion:
This small single center experience suggests that BMCS may be a safer, less complicated, and clinically viable alternative to the Wingspan stent for patients with symptomatic ICS who fail best medical therapy. Further prospective comparative studies of BMCS for symptomatic ICS would be required to verify this experience.
Abstract TP17: Magnetically Enhanced Diffusion (MED) for Improved Efficacy of Thrombolytic Therapy in Acute Ischemic Stroke_A Prospective First in Man Clinical Study
Authors: Bladin Christopher , Levi Christopher , Parsons Mark
Published: March 2022

BACKGROUND:
Preclinical studies have shown that the MED system developed by Pulse Therapeutics, Inc. appears efficient in delivering co-administered agents by affecting the fluid dynamics in targeted occluded arteries. The system is an adjunct to IV rt-PA, and is composed of biologically-safe magnetic particles and a portable magnet system for use in the ED. Preclinical studies support strong efficacy and safety of the MED technology. The primary objective of this feasibility study is to establish the safety (sICH at 24 hours post onset) of the technology when used as an adjunct to IV rt-PA for moderate-to-large (10≤NIHSSS≤24, occlusion confirmed by CTA) ischemic strokes within three hours of acute onset.

METHODS:
10 subjects with moderate-to-large ischemic strokes between ages 18-80 will be enrolled at 2 centers in Australia (Box Hill and John Hunter hospitals). All candidates must possess an intracranial arterial occlusion of the middle cerebral, anterior cerebral, internal carotid, posterior cerebral or distal basilar artery confirmed by CTA or MRA, and must be administered rt-PA within 3 hours of acute onset. Artery selection is input into the MED system and the magnet energized for the entirety of the rt-PA infusion, plus 30min. The primary endpoint is safety as assessed by incidence and evaluation of any adverse effects associated with the investigational procedure compared with historical controls treated with rt-PA alone. The secondary endpoint is the degree of recanalization (partial and complete) and reperfusion as measured by CTA at 2-4hrs and MRI at 24±6hrs post MED therapy. TIMI Grade Flow of 2 or 3 will be considered responsive to treatment.

CONCLUSIONS:
This feasibility trial will attempt to establish the safety (sICH) and recanalization efficacy of the MED technology as an adjunctive therapy to standard-dose IV rt-PA. As of August 2012, Box Hill and John Hunter hospitals have enrolled 2 patients.
Abstract TP177: Discharge to Skilled Nursing Facility May Explain the Association Between Neighborhood Disadvantage and Mortality after Stroke: the Cardiovascular Health Study
Authors: Brown Arleen F , Vassar Stefanie D , Liang Li-Jung , Merkin Sharon S , Escarce Jose J , Obviagele Bruce , Longstreth W, T
Published: March 2022

Background:
Older adults who reside in disadvantaged communities have higher mortality after stroke. We examined whether hospital discharge disposition contributed to neighborhood differences in post-stroke mortality.

Methods:
We used data from the Cardiovascular Health Study, a population-based, longitudinal study of adults ≥65 years. The outcome was death after stroke. Neighborhood socioeconomic status (NSES) was a composite of 6 census variables. Post stroke discharge status, assessed using linked Center for Medicare and Medicaid Services (CMS) data, was classified into no hospitalization, discharge home, or discharge to a skilled nursing facility (SNF)/other subacute care. Multilevel Cox proportional hazard models adjusted for age, sex, race, and stroke type were constructed to examine the association of post-stroke discharge status to mortality at 1 year.

Results:
Among the 592 participants (93% matched to CMS data) with a stroke during the mean 11.5 year follow up, mortality at 1-year post stroke was higher among those discharged to SNF/other care than those discharged home (HR=3.85, 95% CI 2.49-5.93). Participants with no hospitalization did not differ in mortality from those discharged home (HR = 1.08, 0.59-1.99). There was higher mortality in the most disadvantaged neighborhoods among those discharged to SNF/other care, but no differences for those who were discharged home or never hospitalized (Figure).

Conclusions:
The association between lower neighborhood socioeconomic disadvantage and higher post-stroke mortality may be due to characteristics of the SNFs/other facilities where residents of lower SES communities receive care after stroke.