bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP25: Targeting Myeloid Cell-Specific Pyruvate Kinase M2 Improves Stroke Outcome following Transient Cerebral Ischemia in the Comorbid Condition of Hyperlipidemia
Authors: Dhanesha Nirav , Jain Manish , Doddapattar Prakash , Nayak Manasa , Bhalla Abhinav , Thedens Dan , Chauhan Anil
Published: January 2019

Background:
Activated leukocytes exhibit a high level of aerobic glycolysis compared to quiescent leukocytes. Dimeric form of pyruvate kinase M2 (PKM2) regulates aerobic glycolysis and transcription of pro-inflammatory mediators. By following the stroke therapy academic industry roundtable (STAIR) guidelines, we tested a novel hypothesis that manipulating metabolic plasticity of myeloid cells, by targeting PKM2, will improve stroke outcome.

Methods:
Using a well-characterized PKM2 activator (ML-265, inhibits PKM2 dimerization and stabilizes tetramer) in standardized neutrophil
in vitro
assays, we evaluated the mechanistic role of PKM2 in modulating post-stroke neutrophil function. Transient cerebral ischemia was induced using the intraluminal filament model of MCAO. Quantitative assessment of stroke outcome was evaluated (up to day 7) by measuring infarct volume, cerebral blood flow, survival rate, neurological/sensorimotor deficits, and thrombo-inflammation.

Results:
Treatment with ML-265 resulted in significantly reduced PKM2 nuclear translocation, IL-1 beta secretion and NETs formation in post-stroke peripheral neutrophils. Myeloid specific

PKM2
-/-

mice (male/female) on wild-type and hyperlipidemic background

(PKM2
fl/fl
LysM
Cre

and

PKM2
fl/fl
LysM
Cre
Apoe
-/-

) exhibited significantly smaller infarcts and improved sensorimotor/neurological outcomes concomitant with enhanced survival rate and reduced post ischemic thrombo-inflammation. Using laser speckle imaging, we found significantly improved post-reperfusion cerebral blood flow in myeloid specific

PKM2
-/-

mice. In microfluidics flow chamber assay, human and mouse whole blood pretreated with ML-265 formed smaller thrombi when perfused over collagen at an arterial shear rate.

Conclusions:
Our data suggest that PKM2 regulates post-stroke neutrophil function and thrombo-inflammation. Targeting PKM2 may be explored as a novel strategy to improve stroke outcome.
Abstract TMP28:
De Novo
Fatty Acid Synthesis In Cd4
+
T Cells After Cerebral Ischemic Stroke - A New Target of Post-stroke Immune Modulation
Authors: Wang Xin , Zhou Yuxi , Zhu Ziyu , Li Yan , Li Peiying , Yu Weifeng
Published: January 2019

Stroke elicits activation and differentiation of CD4
+
T cells into Th17 and Tregs, in which
de novo
fatty acid synthesis plays an important role. Caloric restriction is neuroprotective against cerebral ischemic brain injury, but its impact on post-stroke immune cell metabolism are yet to be explored. We hypothesize that 1) increased
de novo
fatty acid synthesis in peripheral CD4
+
T cells after ischemic stroke could be suppressed by caloric restriction pretreatment, resulting in improved Th17/Treg balance in the peripheral and reduced neuroinflammation; 2) Acetyl-CoA Carboxylase 1 (ACC1), the rate limiting enzyme of
de novo
fatty acid synthesis, might be an important target of pre-stroke caloric restriction. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAO) for 60 minutes in mice. Caloric restriction were performed for 4 weeks before MCAO with 30% reduction of feeds. Each group contains 5 or 6 mice. Mechanistically, ACC1 was either pharmacologically inhibited by Soraphen A at 2 hours after MCAO or genetically depleted by conditional knockout of ACC1 in CD4
+
T cells. The mRNA levels of inflammatory factors were measured by reverse-transcriptase polymerase chain reaction, T cells in the ischemic brain and periphery were evaluated using flow cytometry and immunohistochemistry. Both real-time PCR and flow cytometry confirmed an increased expression of ACC1 in CD4
+
T cells but not in B cells and macrophage after stroke, while inhibiting ACC1 by Soraphen A reduced ischemic brain injury and attenuated neuroinflammation after stroke. Pre-stroke caloric restriction significantly inhibited ACC1 expression in CD4
+
T cells and altered the differentiation of CD4
+
T cells to Th17 or Treg cells and after stroke. Using CD4

cre

ACC1

fl/fl

mice, we showed that ACC1 deficiency in CD4
+
T cells attenuated caloric restriction afforded neuroprotection and preservation of peripheral Th17/Treg balance after stroke. In conclusion,
c
erebral ischemic stroke elicits
de novo
fatty acid synthesis in peripheral CD4
+
T cells and down-regulation of ACC1 might underlie the peripheral mechanism of caloric restriction in combatting neuroinflammation after cerebral ischemic stroke.
Abstract TMP29: Microglia Are Essential for Neuronal Replacement and Improved Functional Recovery Following Cerebral Ischemia
Authors: Rodgers Krista M , Schroeder Christian , Yonchek Joan C , Traystman Richard J , Herson Paco S
Published: January 2019

Introduction:
Microglia are the first responders after stroke, mounting the immune response to CNS injury. While this response has been shown to be both neuroprotective and neurodegenerative following brain injury, it has been generally accepted that activation of microglia during the acute response to stroke is detrimental for neurogenesis and neuronal replacement. The vast majority of studies report that microglial activation reduces the survival of newborn neurons following stoke. However, our findings indicate that proinflammatory signaling is essential for survival of newborn neurons in juveniles. Remarkably, neurogenesis appears to require prolonged activation of microglia during the acute phase of cerebral ischemia. We utilized a juvenile stroke model to study the paracrine signaling triggered by ischemia in activated microglia and its consequence on newborn neuron survival.

Methods:
Electrocorticography (ECoG) was recorded from cortical surface electrodes and striatal depth electrodes implanted prior to middle cerebral artery occlusion (MCAO). Microglia were attenuated with Ibudilast (10 mg/kg), a glial cell activation inhibitor. Neurogenesis and inflammatory markers were examined with immunohistochemistry, and functional outcomes with neurobehavioral measures and ECoG recordings.

Results and Conclusions:
Acute inhibition of microglial activation after stroke resulted in reduced neurogenesis and long-lasting neurodegenerative effects, evidenced by increased astrogliosis, infiltrating macrophages, and glial scarring at 30d post-ischemia in the lateral striatum of MCAO+Ibudilast treated compared to MCAO+Vehicle treated juvenile mice. Behavioral tests and ECoG recordings revealed deficits in affected limb use, general motor functioning, and total ECoG power (μV
2
) in both Ibudilast and vehicle treated MCAO-injured juveniles at 7d post-ischemia, but only MCAO+Vehicle treated juveniles returned to near sham-operated/baseline levels on neurobehavioral tasks and ECoG power in striatum and primary motor cortex at 30d. These surprising and striking findings provide evidence for a novel, supportive role for microglia in neuronal replacement and enhanced functional recovery following stroke in juveniles.
Abstract TMP3: Blood Pressure Variability Within 24 Hours After Mechanical Thrombectomy Correlates With Worse Outcome
Authors: Anadani Mohammad , Orabi Yser , Alawieh Ali , Goyal Nitin , Pandhi Abhi , Mitchell Hunter , Alexandrov Andrei , L. Maier Ilko , Psychogios Marios-Nikos , Liman Jan , Inamullah Ovais , Rahman Shareena , Shah Shreyansh , A Giles James , Allen Michelle , Kansagra Akash , Q.Wolf Stacey , Kan Peter , A. Nascimento Fábio , Chaudry Mohammad Imran , M. Spiotta Alejandro
Published: January 2019

Introduction:
blood pressure variability (BPV) in the acute phase following ischemic stroke is associated with worse outcomes, especially in patients with large vessel occlusions. However, the relationship between BPV and outcome after successful recanalization is not well documented.

Objective:
The aim of this study was to evaluate the association between BPV and outcome after successful recanalization.

Methods:
This was a retrospective multicenter study of patients with anterior circulation large vessel occlusions who achieved successful recanalization with MT. Successful recanalization was defined as TICI≥2b. BP was recorded in hourly intervals for 24 hours post MT. BPV was defined as the difference between maximum and minimum blood pressure within 24 hours. BPV was calculated for mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP). Outcome measures included 90 days mRS, symptomatic ICH (sICH), and mortality. sICH was defined based on ECASS criteria. Good outcome was defined as mRS 0-2.

Results:
A total of 985 patients were included. SBP and MAP variability were higher in poor outcome group (65.2±26 vs. 57± 24.6; p <0.001, and 49.7±21.2 vs. 46.9± 22.3; p=0.048 respectively). Likewise, SBP and MAP variability were higher in sICH group. The association between SBP variability and 90 day mRS, sICH, and mortality remained significant after adjusting for potential confounders.

Conclusion:
Higher blood pressure variability was associated with worse functional outcomes, higher likelihood of symptomatic hemorrhage, and increased mortality.
Abstract TMP30: Mucin is a Novel Target for Gut Protective Immunity in Stroke
Authors: Lee Juneyoung , Quaicoe Victoria , Morales-Scheihing Diego , Ganesh Bhanu P , Venna Venugopal R , McCullough Louise D
Published: January 2019

Introduction:
Infections are a common cause of post-stroke morbidity and mortality. Recent studies suggest that gut microbiota are a major source of post-stroke infection. Gut mucus layers are a major area of communication between gut microbiota and host immune cells. To our knowledge there have been no studies evaluating the role of colonic epithelial mucins, where most of the gut bacteria reside, after ischemic stroke.

Hypothesis:
Epithelial mucin plays a protective role in stroke-induced colonic disruption.

Methods:
Mice were subjected to either sham or 60-minute middle cerebral artery occlusion (MCAO). Neurological deficit score (NDS) and levels of lipopolysaccharide-binding protein (LBP) in plasma were assessed at day 7 after stroke. Mice were sacrificed at day 7 after stroke and colonic epithelial cells (ECs) were isolated for a gene expression study. Tissues were used for histology and bacterial
in situ
hybridization. Fecal samples were collected for 16S sequencing and IgA ELISA.

Results:
Young female mice had lower NDS and LBP levels, with intact colonic structures (n=4/group,
P
<0.05). Young mice ECs significantly increased 1) regenerating islet-derived protein (Reg) family-specific antimicrobial proteins in males (24.3, 21.3 and 2.5 fold change in Reg3β, -γ and -4, respectively) and 2) mucin genes in females (1.8 and 1.4 fold change in Muc2 and -4, respectively, n=4-5/group,
P
<0.05). Young ovariectomized mice switched their protective strategies from enhanced expression of mucin genes to a “male-like” pattern in which Reg genes were increased after stroke (n=3-5/group,
P
<0.05). Aged mice failed to express these sex-specific genes after stroke. Interestingly, after stroke, bacteria from young female but not male mice were found at a farther distance from the colonic epithelium secondary to intact mucus layers. Finally, young female mice increased mucin-regulating
Akkermansia
bacteria and IgA in the feces after stroke (n=4/group,
P
<0.05).

Conclusions:
Our data demonstrates that 1) stroke provokes a colonic epithelial response and 2) mucin is critical for colonic protection in stroke. In conclusion, mucin should be considered as a novel target to improve post-stroke recovery as well as an important element in maintaining colonic structure.
Abstract TMP33: Modulation of Receptor Protein Tyrosine Phosphatase Sigma Promotes Neuroregeneration and Functional Recovery After Ischemic Stroke
Authors: Luo Fucheng , Silver Jerry , Luo Yu
Published: January 2019

Introduction:
Due to the limitation in current treatment window for stroke, the development of delayed stroke treatment is needed. The two main cellular processes of neural repair after stroke are axonal sprouting and neurogenesis. Inhibitory chondroitin sulfate proteoglycans (CSPGs) are increased within the glial scar and perineuronal net after ischemic brain injury, which might play a critical role in blocking neuroblasts migration, axonal regrowth and sprouting. Recently, a novel small peptide memetic of the CSPG receptor (PTP σ) wedge region named ISP (Intracellular Sigma Peptide) is generated and has capabilities to target PTP σ and relieve CSPGs inhibition in the models of spinal cord injury. Here, we aimed to determine whether post-stroke ISP treatment could improve functional recovery in a mouse model of ischemia.

Methods:
Mice were subjected to tMCAO followed by treatment of ISP or vehicle daily for 4 weeks beginning 24h or 7 days post-tMCAO. Motor and sensorimotor functions were measured prior to MCAO and at 1, 2, 3 and 4 weeks post-stroke using locomotion analysis and adhesion removal test. Cognitive function was also assessed with Barnes maze test at 4 weeks post-stroke. Neurogenesis and axonal sprouting was evaluated using genetic labeling and immunohistochemical analysis.

Results:
Our results show that continuous ISP treatment starting at 24 hours post stroke improves both survival and long-term functional recovery after stroke and 7 day post-stroke treatment improves the functional recovery. Correlated with the improved behavior measurements, immunohistochemical analysis revealed that post-stroke ISP treatment increased the total number of newly generated neuroblast cells migrating towards the peri-infarct area as well as a robust sprouting/regeneration of serotonergic axons around the stroke peri-infarct area.

Conclusions:
Our data suggest that inhibition of PTP σ/CSPGs signaling by ISP stimulates functional recovery after stroke via promoting neuroblast migration and axonal growth. Pharmacological targeting of the PTP σ/CSPGs interaction is therefore a potential novel therapeutic strategy for stroke treatment, which may provide a prolonged treatment window for improving functional recovery after stroke.
Abstract TMP34: Identification of New Therapeutic Pathways by Transcriptome Analysis of Electrically Stimulated-Neural Progenitor Cells After Stroke
Authors: Oh Byeongtaek , Swaminathan Vishal , Lam Vivek , Levinson Alexa , George Paul
Published: January 2019

Introduction:
Stem cells have emerged as an exciting stroke therapy but can also serve to determine important pathways for recovery. Utilizing an implantable, electrically conductive polymer scaffold for human progenitor cell (NPC) delivery, we propose the use of transcriptome analysis to determine essential recovery mechanisms.

Materials and Methods:
NPC cDNA (Aruna) was isolated to evaluate transcriptome changes. Furthermore, NPCs were lentiviral modification to reduce (NPC
KD
) or increase (NPC
STC2KI
) STC2 production (with NPC
ScrambleKD
groups as a negative control). Immunocompromised rats underwent a distal middle cerebral artery occlusion stroke. At 1 week post-stroke, implantation surgeries were performed. NPC
Stim
, NPC
KD+Stim
and NPC
ScrambleKD+Stim
received electrical stimulation daily for 3 consecutive days (AC: ±800 mV/100Hz for 1 hr, starting 1 day after implantation, n=10). Blinded, behavior testing was performed for 6 weeks.

Results and Discussion:
Transcriptome analysis confirmed that NPC
Stim
had a distinct upregulation of neurotrophic factors, specifically STC2 (Fig. a, b). If STC2 was knocked-down (NPC
STC2KD
and NPC
STC2KD+Stim
), STC2 was not upregulated with electrical stimulation; and the enhanced stroke recovery observed in animals that received NPCs and stimulation (NPC
Stim
, with NPC
ScrambleKD+Stim
as a positive control) was not seen (Fig. b-c). If NPCs had lentiviral increased STC2 production (NPC
STC2KI
), improved recovery was also observed.

Conclusions:
Our platform enables the manipulation of NPCs
in vivo
to optimize recovery and evaluate the important mechanisms for functional improvement such as STC2 - a protein important in stem cell production.

Figure. a.
Transcriptome analysis of NPCs. Electrical stimulation augmented neurotrophic factors such as STC2.
b.
ELISA analysis of STC2 (**, p < .01 from unstimulated, n=4).
c.
Improved functional recovery in whisker paw (WP) test with NPC
Stim
, NPC
ScrambleKD+Stim
, and NPC
STCKI
(**, p < .01 from unstimulated NPC and other groups, n=10, two-tailed Mann-Whitney U test)
Abstract TMP37: Occurrence of Myasthenia Gravis in Post Stroke Fatigue
Authors: Nambiar Vivek K , Mathai Annamma , Dhanya T S , Ajai Amrutha , Georgy Sharon A , Parvathy K R , Harish Anu , Kannoth Sudheeran
Published: January 2019

Background:
Post stroke fatigue (PSF) is a common cause of poor quality of life after stroke. Mechanism of PSF is related to cortical dysfunction. Post stroke fatigue patients often demonstrate clinical fatigability of muscles.

Objectives:
We intend to study the frequency of seropositive myasthenia in the post stroke fatigue patients.

Materials and methods:
Retrospective analysis of the electronic medical records of follow up stroke patients with documented muscle fatigability and who had serum acetylcholine receptor antibody (AChR Ab)positivity was done. The demographic profile, comorbidities, auto immune disease, type of stroke,interval after stroke onset , muscle groups involved and response to cholinergic therapy were documented and analysed.

Results:
Of the 910 strokes, 132 had significant clinical fatigue after motor recovery, acetylcholine receptor antibody was positive(titre value>0.4 nmol/L) in 48(mean age 64.25
+
10.94, males 68%).Forty four had ischemic stroke rest had intra cerebral bleed. The major risk factors identified in these patients were hypertension (83.3%), diabetes mellitus(52.1%) and dyslipidemia (31.3%). The history of other autoimmune diseases was present in 29.5% (n=14).The major site of fatigability was the proximal muscles of the lower limb (97.8%), followed by shoulder muscles(68.8%), grip(77.1%), neck muscles(58.3%), bulbar(33.3%) and ocular(16.7%).The median time after stroke onset to fatigable weakness was 14.5 months (IQR 22.5).Data regarding thymoma was not available. Neostigmine test was positive for all the patients. Of the 46 patients treated with anticholinergics, all responded except one.Seven patients had mild adverse events and 4 patients discontinued treatment.

Conclusion:
Post stroke fatigue is a common morbidity and myasthenia could be a potentially treatable cause of fatigue after stroke.
Abstract TMP38: Dysregulated Post-Stroke Immune Response is Associated With Cerebral Volume Loss in the Contralateral Non-Ischemic Hemisphere
Authors: Okar Serhat V , Topcuoglu Mehmet A , Yemisci Muge , Oguz Kader K , Arsava Ethem M
Published: January 2019

Background:
There is delicate homeostatic balance between the central nervous system and immune system. Cerebral insults, like ischemia, trigger an immune-depressive state to suppress a potential immune response directed against the neuroglial tissue; however, this supposedly protective reaction inadvertently creates an infection-prone state in the peri-stroke setting. In this study, we assessed the magnitude of cerebral volume loss in the unaffected contralateral hemisphere following stroke, and determined its relationship with the intimate cascades of inflammation, immune-depression and infection.

Methods:
The change in contralateral hemisphere volume was determined by voxel-based morphometry on admission and follow-up MRI’s in a consecutive series of 50 patients with ischemic stroke involving the MCA territory. Information related to clinical features, infectious complications, and markers of inflammation (erythrocyte sedimentation rate, neutrophil/lymphocyte ratio, C-reactive protein) and immunodepression (plasma high mobility group box 1 protein level; HMGB-1) were prospectively collected.

Results:
The contralateral hemisphere volume decreased by a median (interquartile range) of 2.80% (0.70-5.64) after a follow-up duration of 101 (63-123) days (p<0.001); the monthly volume reduction was 0.82% (0.18-1.79). Old age, stroke severity, neutrophil/lymphocyte ratio, and development of infections during hospitalization were significantly associated with monthly volume loss (p<0.05). Stroke severity (NIHSS score or infarct volume) and inflammation related parameters (neutrophil/lymphocyte ratio or systemic infections) remained independently and positively associated with monthly volume loss when assessed in multivariate regression models, while plasma HMGB-1 levels were inversely related to this loss.

Conclusions:
Cerebral tissue damage following stroke is not limited to the ischemic hemisphere. Apart from stroke severity, a pro-inflammatory state and an impaired immune-depressive response contribute to cerebral volume loss in the non-ischemic hemisphere.
Abstract TMP39: The neural and behavioral basis of Transcranial Direct Current Stimulation
Authors: Schlaug Gottfried , Shinde Anant
Published: January 2019

Non-invasive brain-stimulation has been reported to modulate cortical excitability, synaptic plasticity, and interhemispheric interactions of homotop brain regions. All of these processes could play a role in facilitating stroke recovery. Modulation in cortical excitability covaries with changes in regional cerebral blood flow. Our aim was to determine whether varying parameters of transcranially applied direct current stimulation would modulate regional cerebral blood flow and behavioral measures such as motor sequence learning in a differential effect. Twelve right-handed subjects participated in all behavioral and imaging studies. We used three different dose levels (Sham, 2mA and 4mA corresponding current densities: 0mA/cm2, 0.156mA/cm2, and 0.318mA/cm2) and two different electrode montages (unihemispheric or bihemispheric) to examine tDCS effects on a finger sequence learning task and on regional cerebral blood flow (using Arterial Spin Labeling as a Blood Flow MR sequence) using an MR compatible NeuroConn DCMC stimulator. An anodal electrode (diameter of 4 cm) was placed over the right motor region (C4) while the cathodal electrode (diameter of 5 cm) was either placed over the left supraorbital region (unihemispheric montage) or over the left motor region (C3; bihemispheric montage). Each stimulation was of 10 min duration (ON condition) and preceded by 6 minutes of no stimulation and followed by 8 minutes of no stimulation (OFF conditions). A significant difference (p<0.05) in cerebral blood flow between ON and OFF conditions was seen for the group in a region of interest including the perirolandic region on the right (under the anodal electrode) showing an increase in rCBF between sham, 2mA and 4mA. There were trends for stronger bihemispheric blood flow changes for the bihemispheric montage than the unihemispheric montage. In the finger sequence learning task, subjects learned to type a randomly chosen sequence of 7 numbers with digits 2-5 of each hand as accurately and as fast as possible, before and immediately after a 10 minute stimulation phase. Higher numbers of correct finger sequence were seen in the higher current conditions for the unihemispheric condition. Results were more mixed for the bihemispheric montages.
Abstract TMP41: Accuracy of Self-Reported Stroke Subtype and Functional Status Information Submitted by Patients Recruited Online: The Stroke Recovery Initiative
Authors: Kim Anthony S , Zurita Karla G , Toussaint Daniel , Wan Emerald , Farrant Mary
Published: January 2019

Introduction:
An online process for eliciting and assessing information from stroke patients to prescreen for stroke recovery studies holds potential to accelerate enrollment, but the validity of using self-reported information for online pre-screening is uncertain.

Methods:
Among patients in the UCSF Stroke Recovery Initiative, a nationwide, online participant recruitment registry of stroke patients that have expressed an interest in stroke recovery studies (strokerecoveryinitiative.ucsf.edu; NCT03318432), we compared self-reported information on stroke subtype (ischemic vs. hemorrhagic), location (MCA, cerebellar, brainstem), and functional status (modified Rankin Scale) elicited online to final validated responses as determined by follow-up semi-structured telephone interviews. We used descriptive statistics and Cohen’s kappa to evaluate the concordance of self-reported information against validated responses.

Results:
A total of 1,283 of the 3,959 participants in the recruitment registry were selected for semi-structured telephone follow-up (mean age 56; 55% male; average of 2.6 years after the index stroke). There was moderate agreement between self-report and telephone-validated responses for stroke subtype (84.4% agreement, kappa=0.68 for ischemic stroke; 83.0% agreement, 0.70 for hemorrhagic stroke) and similar performance for stroke location (86.1% agreement, kappa=0.75 for MCA location; 81.1% agreement, 0.66 for cerebellar location; 86.9% agreement, 0.78 for brainstem location). Agreement for the modified Rankin Scale for functional status was somewhat lower overall (66.7% agreement, kappa=0.53) but self-reported scores were within 1 point of the validated score 94% of the time.

Conclusion:
Using self-reported information to prescreen patients for stroke recovery studies requires a permissive approach to basic eligibility criteria to flag potentially-eligible candidates for additional follow-up. The efficiency and high-throughput of an online prescreening process would benefit from having studies with eligibility criteria that are developed with an efficient prescreening process in mind as well as high-throughput pre-screening instruments that are optimized for self-report.
Abstract TMP42: Younger Age and Depressive Symptoms Predict Post-Stroke Generalized Anxiety Disorder
Authors: Kapoor Arunima , Si Kevin , Herrmann Nathan , Lanctôt Krista L , Murray Brian J , Swartz Richard H
Published: January 2019

Background:
Depression and anxiety are common post-stroke conditions associated with poor functional outcome and worse quality of life. However, few studies have explored post-stroke generalized anxiety disorder (GAD), especially in patients without comorbid depression.

Hypothesis/Aim:
We aimed to explore the frequency and the predictors of GAD after stroke/TIA. Our secondary aim was to identify the frequency and predictors of GAD in patients without comorbid depression.

Methods:
Consecutive stroke and TIA referrals to the Sunnybrook Stroke Prevention Clinic over a two-year period (April 2012 to April 2014) who spoke English, were not severely aphasic, and who consented to complete neuropsychological testing were included in this analysis. Anxiety and depression were assessed using the Generalized Anxiety Disorder 7-item (GAD-7) scale and Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Scores ≥ 10 on the GAD-7 signified moderate to severe anxiety and ≥16 on CESD indicated moderate to high risk of depression. Clinical depression was assessed using the Structured Clinical Interview for the DSM-IV-Depression Module.

Results:
258 patients completed the GAD-7 scale, of which 56 (22%) had scores ≥ 10. Lower age (p = .004) and greater depressive symptoms (p ≤ .001) were significant predictors of post-stroke GAD, while sex, modified Rankin score, and education did not predict anxiety. Younger patients (≤ 50 years) were significantly more likely to have comorbid depression and anxiety than older patients (30% vs. 12%, p = .001). Our model explained 56% of the variance in GAD after stroke. Anxiety was present in 12% of patients without comorbid clinical depression. In patients without clinical depression (n = 207, 80%), age and symptoms of depression remained the only significant predictors of GAD.

Conclusion:
Anxiety is common after stroke/TIA and is highly correlated with post-stroke depressive symptoms and age, even among those without clinical depression. Given the greater frequency of both anxiety and depression in young survivors, routine screening for depression and further evaluation of anxiety after stroke is warranted. Interventions to improve these conditions could improve quality of life and outcomes following stroke
Abstract TMP43: Fluoxetine May Enhance Visual Recovery After Acute Ischemic Stroke by Cortical Remapping of the Blind Visual Field
Authors: Schneider Colleen L , Busza Ania , Prentiss Emily K , Williams Zoe R , Mahon Bradford Z , Sahin Bogachan
Published: January 2019

Post-stroke homonymous hemianopia is disabling and complete spontaneous recovery is rare (12.5%). Other than acute revascularization, no proven treatments are available to enhance recovery. Compensatory training may lead to modest functional improvements, but does not restore native function. As such, therapies effective beyond the acute stage are desperately needed. In this phase IIa single-center, double-blinded, randomized, placebo-controlled pilot clinical trial, we tested whether fluoxetine (FLX) enhances visual recovery after an ischemic stroke by facilitating cortical remapping as measured by fMRI. We randomized 10 consecutive adults in a 1:1 ratio to 90 days of FLX 20 mg daily
vs
placebo within 5 days of a stroke in the PCA (
n
= 9) or MCA (
n
= 1) territory causing an isolated homonymous field defect. Only one subject was treated with tPA. The primary outcome measure was percent improvement in perimetric mean deviation (PMD) as measured by automated Humphrey perimetry at 6 months. Eight subjects completed the study. Intention-to-treat analysis of the primary outcome measure showed a non-significant benefit of FLX (
n
= 4) over placebo (70.5 ± 21.1%
vs
30.1 ± 23.5%; one-tailed
t
-test,
p
= 0.12). Complete recovery occurred more frequently than expected in both groups (75%
vs
25%), but was significantly greater than 12.5% only in the FLX group (
p
= 0.007
vs p
= 0.41). Percent improvement in PMD significantly correlated with scores on the 25-item Visual Functioning Questionnaire, a vision-targeted measure of health-related quality of life (

r
2

= 0.74;
p
= 0.012). Subjects in both groups who fully recovered showed fMRI evidence of cortical remapping by expansion and shifting of the center of their ipsilesional V1 receptive fields. In those with partial recovery, fMRI showed no cortical remapping, but a return of function in normal retinotopic locations, possibly due to recovery of “stunned” tissue. In conclusion, these results illustrate the feasibility of our approach, suggest a trend in favor of FLX, and have the potential to inform the design of a multi-center trial. Our fMRI analysis raises testable hypotheses about post-stroke recovery and suggests that FLX may improve outcomes by enabling the same kind of plasticity that underlies spontaneous recovery.
Abstract TMP44: Gender and Race/ethnic Disparities in Psychotropic Medication Prescription at Discharge Among TIA and Mild/moderate Stroke Patients in the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) Study
Authors: Goldmann Emily , Ahmadi Ayda , Stein Laura A , Mullen Michael T , Appleton Noa , Parikh Nina S , Boden-Albala Bernadette
Published: January 2019

Depression and anxiety are common after stroke. Little is known about the factors associated with prescription of antidepressants (AD) and anti-anxiety (AA) medications post-stroke. The study used data from DESERVE, a randomized educational trial to reduce vascular risk in a multi-ethnic cohort of TIA and mild/moderate stroke patients in New York City. The study outcome was any AD or AA prescription at discharge, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic and tetracyclic antidepressants, norepinephrine-dopamine reuptake inhibitors, serotonin antagonist and reuptake inhibitors, anxiolytics, and benzodiazepines. Chi-square, Fisher’s exact, and Wilcoxon rank sum tests were used to examine the association between patient characteristics and AD/AA prescription. Factors associated with the outcome at p<0.10 in bivariate analysis were examined using multiple logistic regression. Of the 236 patients with medication information, 21.2% were prescribed an AD or AA, most commonly SSRIs/SNRIs (82.0%) and benzodiazepines (31.4%). In the adjusted model, males (OR=0.37 95% CI: 0.16, 0.84) and Non-Hispanic black/other race patients (OR=0.08, 95% CI: 0.03, 0.24) had significantly lower odds of AD/AA prescription. Probable depression pre-discharge (Center for Epidemiologic Studies-Depression scale ≥ 16) (OR=4.11, 95% CI: 1.46, 11.55) and prior psychiatry history (OR=2.82, 95% CI: 1.02-7.83) were associated with greater odds of AD/AA prescription. Non-significant differences in AD/AA prescription were noted on the basis of stroke severity, modified Rankin scale, and Hispanic ethnicity (Table 1). Prescription of ADs/AAs at stroke discharge was common and associated with gender and race/ethnicity independent of other factors. Further research is needed to better understand disparities in post-stroke psychotropic medication prescription.
Abstract TMP47: Sleep and Endocrine Disturbances Are Associated With Poorer Outcomes During the Post-Acute Phase of Stroke Recovery
Authors: Howell Stefanie N , Robinson Stephanie E , Griesbach Grace S
Published: January 2019

Introduction:
Sleep disturbances, including decreases in slow wave sleep (SWS) are common following stroke. In this study, we sought to identify the implications of decreased slow wave sleep on endocrine function and cognitive/outcome measures in the post-acute phase of stroke recovery.

Methods:
Adult stroke patients (n=44) were assessed via overnight polysomnography (PSG). The mean age was 50 ± 1.8 years and mean latency from stroke was 126 ± 16 days. Sleep measures included total sleep time (TST), sleep and REM latency, percent time in sleep stages, apnea/hypopnea index (AHI), wake after sleep onset (WASO), and arousal index. Hormone levels were analyzed within 10 days of PSG. The primary outcome measures were as follows: California Verbal Learning Test (CVLT), Montreal Cognitive Assessment (MoCA), Trails A and B, Mayo Portland Adaptability Inventory (MPAI), and NeuroQOL. Sex differences were also analyzed.

Results:
Age and BMI were positively correlated with subjective daytime sleepiness using the Epworth Sleepiness Scale (p<.05); however, while BMI was positively correlated with the arousal index (p<.01), it was not correlated with AHI. TST was negatively correlated with subscales of the MPAI (p<.05). Time spent in SWS was associated with decreases in self reported anxiety, fatigue, and sleep disturbances on the NeuroQOL (p<.01). Increases in SWS were also correlated with higher scores on the MoCA (p<.05). Increases in sex hormone binding globulin (SHBG) were associated with decreases in TST (p<.05) and increased percent WASO (p<.01). Additionally, SHBG was negatively associated with the CVLT list B (p<.05). For men, SHBG is positively associated with the number of repetitions on the CVLT (p<.01). As expected, men had a higher arousal index and higher AHI than women.

Conclusion:
Time spent in SWS is associated with better subjective well-being and improved performance on cognitive measures. Hormone levels, especially SHBG, may serve as early biomarkers for sleep disturbances after stroke and are associated with negative performance on some measures of cognition.
Abstract TMP56: Are Depressed Stroke Survivors Less Likely to Be Adherent to Secondary Prevention Therapies?
Authors: Neil William P , Burchette Raoul J , Shiokari Chrislynn E , Ovbiagele Bruce
Published: January 2019

Introduction:
Depression is common after ischemic stroke (IS). Stroke survivors who are depressed are at greater risk for suboptimal recovery, recurrent vascular events, poor quality of life, and mortality. However, how depression leads to poor IS outcomes is unclear and few studies have shown an association between depression after stroke and healthcare use. Objective: To evaluate the impact of depression on medication adherence after stroke.

Methods:
We analyzed the multicenter database comprising information drawn from electronic medical records and pharmacy records (Healthconnect, POINT). All ischemic stroke patients presenting to one of 11 medical centers within a health maintenance organization in California between January 1, 2007 and June 30, 2015 with at least 2 medication fills for a stroke prevention medication and six months of information were evaluated. Adherence was calculated for antihypertensive, hypoglycemic, and lipid lowering medications, but not for antiplatelet or anticoagulant medications as the latter may be obtained over the counter, or with variable daily dosing, which would bias adherence calculations. Adherence was calculated by using the continuous medication gap (CMG) methodology, which determines the cumulative period that no medication was available to the patient. The number of days for which the patient did not have the medication was divided by the number of days in the study window for that patient.

Results:
There were 9933 patients with ischemic stroke during the study period. Of these, 2019 had a diagnosis of depression made after the index stroke. Among the non-clinically depressed patients the CMG adherence was 0.22 (Standard Deviation +/- 0.29), while among clinically depressed patients it was 0.28 (SD +/-0.32, p<0.0001).

Conclusions:
Ischemic stroke survivors diagnosed with depression after an index stroke are overall 26% less likely to be adherent to key secondary prevention drugs than their non-depressant counterparts. Poor medication adherence among depressed stroke patients may be an important contributor to their relatively poorer clinical outcomes.
Abstract TMP59: Recent Trends of Stroke Characteristics and Treatment in Korea: Data From Korean Stroke Registry
Authors: Jeong Han-Yeong , Jung Keun-Hwa , Mo Heejung , Lee Chan-Hyuk , Kim Tae Jung , Kim Chi Kyung , Kim Beom Joon , Kim Joon-Tae , Kim Jinkwon , Seo Woo-Keun , Oh Mi Sun , Lee Jun , Lee Ji Sung , Cha Jae-Kwan , Park Jong-Moo , Yoon Byung-Woo
Published: January 2019

Introduction:
Dynamic changes in lifestyle or healthcare system due to industrialization lead to changes in the pattern of disease. This study investigates the recent trends of acute ischemic stroke characteristics and treatment in Korea, a rapidly developed country.

Methods:
We analyzed individual data of ischemic stroke and transient ischemic attack patients from the Korean Stroke Registry (KSR), a nationwide hospital-based stroke database, between August 2014 and May 2018 (2nd generation KSR). We collected demographic data, risk factors, treatment including thrombolysis, and stroke subtypes. Linear or log-linear Poisson regression analyses were performed to assess the changes. Finally, we compared this data from January 2002 to November 2010 (1st generation KSR).

Results:
A total 39,291 patients of 2nd generation KSR were included in the analysis. The mean±SD age was 68.0±13.0 years, and 58.3% of the patients were male. Over the 5-year period, the mean age of the patients steadily increased by 0.21 year annually (p<0.001). Proportions of hypertension and diabetes remained stable, but frequency of dyslipidemia increased and prior stroke decreased. Proportion of intravenous thrombolysis remained stable (p=0.147), but intra-arterial thrombectomy increased (p<0.001). Relative proportions of stroke subtypes over the 5 years, small vessel occlusion increased, cardioembolism decreased, and large artery atherosclerosis remained stable. Compared with 46,098 patients of 1st generation KSR, the proportion of arrival within 3 hours increased from 25.6% to 33.9%, and any reperfusion therapy increased 6.8% to 15.3%, especially intravenous thrombolysis increased 5.6% to 11.7%. The proportions of stroke subtype also considerably changed compared with 1st generation KSR (large artery atherosclerosis; 36.1% to 32.6%; cardioembolism; 25.4% to 19.9%; small vessel occlusion; 17.1% to 21.3%).

Conclusions:
Stroke characteristics in Korea changed during the first two decades of 21st century. It is likely because of increased lifespan, westernized lifestyle, changed treatment modality and improved public awareness.
Abstract TMP60: Trends in Neurophysiologic Intraoperative Monitoring and Occurrence of Stroke at the Time of Hospitalization for Carotid Endarterectomy
Authors: Vela-Duarte Daniel , Lekoubou Alain , Bishu Kinfe G , Ovbiagele Bruce
Published: January 2019

Background:
intraoperative neurophysiological monitoring (IoNM) is a valuable technique for determining the need for selective intraoperative shunting and prevention of perioperative stroke in patients undergoing carotid endarterectomy (CEA).

Methods:
We aimed to describe the trends of intraoperative monitoring utilization using the US-representative 2006-2015 National Inpatient Sample database. We sought to identify associations of patient’s demographics with outcomes with an adjusted multivariable logistic regression model.

Results:
Between 2006-2014, there were a total of 11003 endarterectomies included in our analysis, most commonly performed in men 6764 (61.5%), and women 4239 (38.5%) mostly older than 65 years old. Intraoperative monitoring was used in 266 cases (2.45%) equally across genders, 168 (2.5%) man, 98 (2.3%) women. Nearly 80.8% undergoing CEA and IoNM were white, 8.7% black, 5.7% Hispanic with no differences of IoNM use across race. No difference between primary payer, location/teaching status or size of the hospital were observed. The use of IoNM during CEA was more frequent in the Midwest region: 32.9% (89), Northeast: 28% (74), South: 21.4% (57), and West: 17.6% (46), p=0.0000. The rate of utilization of IoNM increased across the years, 2006/08 (0.06%), 2009/11 (2.1%) and 2012/14 (4.6%). p=0.0000. Unadjusted rates of in-hospital death were not associated with IoNM. Mean length of stay(LOS) of ECA with IoNM was 8 days (95% CI, 7.36-8.76) and IoNM without ECA was 7.25 (95% CI, 7.10-7.38). Adjusted Mortality did not differ in time. During 2009-2011: aOR 0.60 (95% CI, 0.36-0.98) and 2012-2014: aOR 0.50, (95% CI, 0.29-0.86) were associated with lower odds of using Intraoperative monitoring. The Charlson Comorbidity Index aOR 1.2 (95% CI, 1.09-1.33) and Length of stay aOR 1.06 (95% CI, 1.04-1.08)

Conclusions:
The percent of endarterectomies performed with IoNM has increased over the years; however, this trend does not seem to impact LOS and in-hospital mortality. This might be explained by the overall low rate of utilization, with documentation of its use in only 5.2% of CEA performed in 2014. Despite being a highly specific test in predicting neurological outcomes, the impact on perioperative stroke prevention is perhaps undervalued.
Abstract TMP61: Enrolling Stroke Patients in Prehospital Research During Late Night and Early Morning Times
Authors: Sanossian Nerses , Liebeskind David , Starkman Sidney , Shkirkova Kristina , Kim-Tenser May A , Saver Jeffrey L
Published: January 2019

Background:
Enrolling stroke patients into clinical research studies often necessitates having investigators available to field calls (from paramedics, potential subjects and ED personnel) as well as study nurses available at enrolment sites. Enrolment of patients overnight may thus not be cost effective if there are low numbers. Late night enrolment may have different characteristics such as more severe stroke or greater proportion of intracerebral hemorrhage.

Methods:
The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial enrolled patients 24 hours per day with designated on-call enrolling investigators and study nurses. We compared enrolment in the late night and early morning period defined as 10:00PM through 5:59AM compared to standard hours of 6:00AM through 9:59PM. We also considered implications of changing the late night/early morning definition to Midnight and 8:00AM.

Results:
Of 1700 enrolments, 171 (10%) occurred between 10PM-6AM. There was no significant differences in the late-night enrolments in stroke subtype (27% vs 22% ICH, p=0.268), age, ethnicity, race, vascular risk factors, prehospital stroke severity (LAMS) or hospital arrival stroke severity (NIHSS). Late night enrolments were less likely to be women (35% v 44%, p=0.035). There were 61 enrolments (3.4%) between midnight to 5:59AM. Expanding the early morning period from 6AM to 8AM would lead to 76 (4.4%) less enrollments.

Conclusions:
Late night/early morning enrolments are not clinically or demographically different from those during regular hours and accounted for 10% of overall enrolments. Less than 4% of enrolments occurred between midnight and 6:00AM. Future prehospital stroke trials can consider deferring enrolment in the late night/early morning period to help with resource allocation.
Abstract TMP63: Patient Perceptions of Remotely Delivered Acute Stroke Care
Authors: Lyerly Michael J , Martin Holly A , Plue Laurie , Anderson Jane , Damush Teresa , Graham Glenn D , Martini Sharyl , Williams Linda S
Published: January 2019

Introduction:
Telestroke has been demonstrated to be a cost-effective means to expand access to care and improve outcomes in stroke. However, information on patient perceptions of this system of care delivery are limited. This study seeks to examine patient feedback of a national telestroke system within the Veterans Health Administration.

Methods:
All Veterans receiving a telestroke consultation with a video component were considered for telephone interview 2 weeks post-consult. Those who died within 30 days, who were placed on palliative care/hospice, or who were still hospitalized 30 days after the consult were excluded. If the Veteran could not recall the teleconsult, another person present who could recall it could complete a proxy interview. The interview included 18 standardized questions about technical quality, experience with the telestroke provider, telepresence (the extent to which the consult felt like a face-to-face visit), and overall satisfaction. Open-ended responses were also recorded.

Results:
Over a 9-month period, 174 telestroke consults were completed. Of these, we obtained patient responses from 72 (41%) veterans (56 had a final diagnosis of stroke). Twenty-one responses were completed by a proxy. Veterans reported high levels of satisfaction with technical quality (Figure 1A). While patients felt comfortable with interacting with the telestroke provider, we did identify opportunities for improvement with patient involvement in decision making and communication of treatment recommendations (Figure 1B). Overall, veterans indicated high levels of satisfaction with the telestroke providers and service platform (Figure 1C). Importantly, 91% of respondents indicated that this service allowed them to receive the care that they needed.

Conclusions:
Overall, Veterans report high levels of satisfaction with the technology, expertise, professionalism, and service with a telestroke platform.