bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP410: Beneficial Effect in Preventing the Risk of Aspiration Pneumonia in Patients With Acute Ischemic Stroke
Authors: Kim Tae Jung , Kang Min-Kyung , Nam Kiwoong , Mo Heejung , Ko Sang Joon , Ko Sang-Bae , Yoon Byung-Woo
Published: June 2021

Introduction:
Platelet activation is an important mediator in acute thrombosis as well as systemic inflammation. Therefore, modulating P2Y12 receptor, a well-known platelet activation pathway, may influence inflammation process. Clopidogrel, a prototype P2Y12 receptor antagonist, is reported to decrease neutrophil infiltration and decrease inflammation.

Hypothesis:
The aim of this study is to evaluate whether clopidogrel use may decrease the risk of aspiration pneumonia, a common infection, in patients with acute ischemic stroke.

Methods:
A consecutive patients with acute ischemic stroke (within 7 days after onset) were screened between March 2010 and December 2015, and a total of 1,578 patients were included for the analysis. Patients were categorized into two groups (clopidogrel user vs. non-user), and the clinical characteristics and the risk of aspiration pneumonia were compared in two groups.

Results:
Among the included patients (mean age, 67.6 years; men, 60.7%), 642 (40.7%) were clopidogrel user, and 132 (8.2%) patients had aspiration pneumonia. The proportion of patients with aspiration pneumonia was significantly higher in clopidogrel non-user (9.9%) compared to clopidogrel user (6.1%),
(P
= 0.006). Moreover, clopidogrel users had lower proportion of ICU care (12.8 % vs. 38.7 %, P =0.03) and had less chances of having sepsis [defined as quick SOFA (sepsis related organ failure) score of 2 and more) ( 15.4 % vs. 32.4 %,
P=
0.047) compared with clopidogrel non-users. The patients with aspiration pneumonia were more likely to have atrial fibrillation, diabetes mellitus, and higher initial NIHSS. On multivariate analysis with an application of inverse probability of treatment weighting based on a propensity score of clopidogrel use, clopidogrel users had lower risk of aspiration pneumonia [Odds ratio (95% confidence interval); 0.747(0.573-0.974),
P
= 0.007].

Conclusions:
This study suggested that clopidogrel users had lower risk of aspiration pneumonia and less severe infection following acute ischemic stroke. This suggests that clopidogrel may decrease the chances of infection, especially aspiration pneumonia, after stroke.
Abstract TP426: Impact of Electrographic Seizure Activity on Outcomes Among Critically-ill Patients with Stroke
Authors: Dangayach Neha S , Griffiths Stephen A , Melis Marta , Yoo Jiyeoun , Marcuse Lara , Fields Madeline , Gordon Errol , Mayer Stephan A
Published: June 2021

Introduction:
Patients with severe acute stroke can suffer secondary neurological injury due to a variety of causes. The clinical impact of electrographic seizures among critically-ill stroke patients remains unclear.

Methods:
We retrospectively analyzed a cohort of consecutive stroke patients admitted to the Neuroscience Intensive Care Unit (NSICU) at the Mount Sinai Hospital who underwent ≥24 hours of continuous video EEG (cEEG) monitoring for alteration in level of consciousness or suspected non-convulsive seizures between May 2013 and June 2015.

Results:
Of 106 consecutive severe stroke patients admitted to the NSICU who underwent cEEG monitoring, 15 (14%) had clinical or electrographic seizures. The median duration of cEEG monitoring was 1.2 days. Observed seizures included purely electrographic seizures with no clinical correlate in 53%, subtle twitching or altered mental status in 33%, and generalized tonic-clonic seizures with an EEG correlate in 13%. Generalized or lateralized periodic discharges (PEDs) were present in 93% (14/15) of patients in the seizure group, compared to 20% (18/89) in the non-seizure group (P= 0.00). The survival rate at discharge was 53% in the seizure group compared to 73% in the non-seizure group (p = 0.12). Mean ICU length of stay was 16 days in both groups. Of the 11 survivors in the seizure group 100% were severely disabled at discharge (mRS 4 or 5) compared to 75% of the 65 survivors in the non-seizure group.(P=0.06).

Conclusion:
Critically-ill stroke patients with clinical or electrographic seizures in the ICU tend to have higher mortality and worse functional outcome at the time of discharge. PEDS are an important marker of patients at high risk for ictal activity. Careful identification of acute stroke patients that might benefit from seizure prophylaxis is warranted.
Abstract TP429: Association Between Perioperative Management and Outcome in Aged SAH Patients
Authors: Ido Keisuke , Kada Akiko , Nishimura Kunihiro , Kamitani Satoru , Ogasawara Kuniaki , Ono Junichi , Yoshiaki Shiokawa , Aruga Toru , Toyoda Kazunori , Nakagawara Jyoji , Miyachi Shigeru , Yoshimura Shinichi , Okuchi Kazuo , Izumi Nagata , Matsuda Shinya , Matsuda Shinya , Nakamura Fumiaki , Onozuka Daisuke , Hagihara Akihito , Suzuki Akifumi , Kurogi Ryota , Sayama Tetsuro , Arimura Koichi , Nishimura Ataru , Kurogi Ai , Iihara Koji
Published: June 2021

Background and purpose:
The outcomes of subarachnoid hemorrhage (SAH) in aged patients are more severe than those in non-aged patients. There are few reports about the relationship between the age and the effect of perioperative care for SAH patients. We performed a nationwide survey in Japan to determine the relationship between perioperative care and SAH outcomes in aged and non-aged patients.

Methods:
We analyzed 17,343 subarachnoid hemorrhage (SAH) patients treated with clipping or coiling in 579 hospitals who participated in the J-ASPECT study. Data between 2010 and 2013 were obtained from the Japanese Diagnosis Procedure Combination Database. We stratified patients into two groups according to their age (aged group >75 y.o., n=3885; non-aged group < 75 y.o., n=13,458) and analyzed the association between perioperative care and poor outcome (modified Rankin Scale score 3-6 at the time of discharge). With respect to perioperative care, we evaluated time from onset to surgery (days), treatment (clipping or coiling), and drugs delivered after surgery (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, EPA, edaravone).

Results:
In the non-aged group, coiling (OR=0.84; P<0.01) and treatment with fasudil hydrochloride (OR=0.59; P<0.01), statin (OR=0.83; P<0.01), and EPA (OR=0.83; P<0.01) significantly improved the outcomes and cilostazol treatment tended to improve the outcomes (OR=0.91; P=0.07). In both groups, edaravone treatment was associated with poor outcome (aged group: OR=2.34, P<0.01; non-aged group: OR=2.33, P<0.01). Although no factor that could improve outcome in the aged group was identified, JCS scores less than 30, coiling (OR=0.80; P=0.03), and EPA treatment (OR=0.74; P=0.02) were statistically significant prognosis improvement factors.

Conclusion:
Coiling and treatment with fasudil hydrochloride, statins, and EPA improved outcomes of non-aged patients. Although perioperative care did not improve the outcome of aged SAH patients, in cases of relatively mild SAH, perioperative care had the potential to improve the outcome.
Abstract TP441: Fornix Microstructure Correlates with Post-stroke Memory Impairment Independently of Lesion Volume
Authors: Wright Paul , Ray Nicola J , O’Sullivan Michael J
Published: June 2021

Memory impairment is common and a cause of unmet need after stroke. One third of patients recover spontaneously over the first year. Others develop later decline. The mechanism of recovery and the contribution of comorbid neurodegenerative pathology are not well understood. Data from older adults and Mild Cognitive Impairment suggest preserved memory depends on reorganisation of function between the fornix and other temporal lobe white matter tracts. The STRATEGIC study investigates memory over the first year post-stroke. The current analysis uses baseline data to investigate the contributions of initial infarct and white matter status to initial memory impairment. Patients (n = 21; 5 lacunar, 12 MCA, 4 PCA; 11 left hemisphere, 10 right) performed a cognitive battery and had diffusion-weighted MRI at 30-95 days after stroke onset (median = 64 days). Healthy controls (n = 33) provided the same measures. We reconstructed the fornix using HARDI-based deterministic tractography. Lesions were drawn manually on FLAIR images and direct injury of the fornix was excluded. We tested free recall using a delayed verbal memory test and recognition memory using a face recognition test with trialwise confidence ratings. Recall was markedly lower in patients than controls (50% vs 71%, p < 0.001) but did not correlate with age, lesion volume or fornix integrity in patients. Recognition memory was unimpaired in patients. For confidently remembered items, performance correlated with fornix mean diffusivity in both controls (r = -0.344, p < 0.05) and patients (r = -0.544, p < 0.05). Controlling for age eliminated the correlation in controls but in patients there was a correlation independent of age and lesion volume (r = -0.531, p < 0.05). These findings demonstrate that preserved recognition memory after stroke depends on the status of the fornix and is independent of infarct volume. Compromise of fornix structure from pre-existing neurodegeneration may be a predictor of poor cognitive outcome after stroke. Verbal recall in patients was independent of fornix integrity. Investigation of other temporal lobe pathways may reveal reorganisation underpinning partially preserved recall in some patients.
Abstract TP442: Periventricular Not Deep White Matter Hyperintensities Are Associated With Vascular Cognitive Impairment
Authors: Chen Yan , Liu Renyuan , Qiu Shuwei , Xu Yun
Published: June 2021

Introduction:
Cerebral White matter hyperintensities(WMH) are frequent findings on MRI scan. They are well known to correlate with vascular cognitive impairment(VCI). However, controversies still remain about the relationship between WMH locations and cognitive function across studies.

Hypothesis:
Periventricular WMHs(PWH) rather than deep WMHs(DWH) are associated with cognitive decline in VCI.

Methods:
Fifty-nine subjects with WMHs on MRI were divided into three groups, normal control(NC), mild cognitive impairment(MCI) and vascular dementia(VaD), according to clinical manifestation and neuropsychological performance. WMH volumes were evaluated by Fazekas rating scale and segmental volumetric. Correlations between cognitive performance and WMH volumes were determined in virtue of Spearman correlation analysis. Receiver operator characteristic (ROC) curves were generated to define the classification cut-off value of WMH volumes for distinguishing VCI versus normal controls. Multiple linear regression analysis was used to predict cognitive performance with WMH volumes and locations after adjusting for sex ,age and education level.

Results:
Cognitive capacities were gradually declined from NC through MCI to VaD patients while WMH volumes and Fazekas scores altered oppositely. Both PWH and DWH volumes and Fazekas scores were correlated with cognitive performance, and moreover, WMH volumes were correlated with Fazekas scores. ROC analysis showed a cut-off value of PWH rather than DWH to distinguish VCI from NC(AUC=0.745 and 0.635,
p
=0.001 and 0.076, respectively). Linear regression analysis demonstrated that only PWH volumes were associated with cognitive performance(
p
< 0.001).

Conclusion:
Our study demonstrate that PWHs are independent predictors for vascular contribution in white matter lesions and suggest clinicians that PWH should be emphasized on evaluating vascular cognitive impairment related with white matter load.
Abstract TP443: Early Cognitive Decline in Patients with Symptomatic Carotid Stenosis is Related to Plaque Inflammation and Concomitant Intracranial Stenosis
Authors: Wan Yee Shuang , Paliwal Prakash R , Dong Yanhong , Chan Bernard P , Teoh Hock L , Hong Chiew S , Young Heng C , Du Zhengdao , Chen Jin T , Wong Lily Y , Sinha Arvind K , Sharma Vijay K
Published: June 2021

Background and aims:
Symptomatic carotid stenosis is associated with an increased risk of early stroke recurrence. Post-stroke vascular cognitive impairment is highly prevalent with significant functional consequences. However, reliable biomarkers for early prediction of cognitive decline are not well established. We postulated that regional hypoperfusion due to carotid stenosis would impair cognitive performance. Hence, we evaluated the cognitive parameters at baseline and their natural course during 90-days of follow up.

Methods:
This ongoing prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). Data regarding demographics and vascular risk factors were recorded. Cognitive parameters were assessed with the 30-point mini-mental scale (MMSE) and Montreal Cognitive Assessment (MoCA). All patients underwent carotid duplex sonography and 18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) of carotid arteries. Embolic potential of the carotid plaque is estimated by presence of spontaneous microembolic signals (MES) on extended transcranial Doppler monitoring of the middle cerebral arteries. Patients are followed prospectively for change in cognitive parameters.

Results:
Of the 33 patients included in this study, 7 (21%) demonstrated deterioration of their cognitive parameters (MMSE in 4, MOCA in 5 and both in 6) during 90-day follow up. Only high Standard Uptake Value (SUV) on PET (3.62g/ml in cognitive-deterioration group versus 1.72g/ml in the unaffected group; p=0.01) and presence of concomitant intracranial stenosis (p=0.01) were associated with cognitive deterioration. Of the 7 cases who underwent carotid revascularization, 5 (71%) demonstrated improved cognitive performance at day-90.

Conclusions:
Early cognitive decline is common among patients with symptomatic stenosis of the extracranial carotid artery, especially when associated with concomitant intracranial stenosis and plaque inflammation.
Abstract TP447: Edaravone Reduces Hyperperfusion-related Neurological Deficits After Direct Bypass in Adult Moyamoya Disease
Authors: Uchino Haruto , Nakayama Naoki , Kazumata Ken , Houkin Kiyohiro
Published: June 2021

Background and Purpose:
Postoperative hyperperfusion-related transient neurological deficits (TNDs) are frequently observed in adult patients with moyamoya disease (MMD) who undergo direct bypass procedures. The present study evaluated the effect of the free radical scavenger edaravone on postoperative hyperperfusion in adult MMD.

Methods:
This study included 92 hemispheres in 72 adult patients who underwent direct bypass for MMD. Serial measurements of cerebral blood flow were conducted immediately after surgery and on postoperative days 2 and 7. In 40 hemispheres in 36 patients, edaravone (60 mg/day) was administered from the day of surgery until postsurgical day 7. The incidence of postoperative hyperperfusion and associated TNDs were compared with a control group that included 52 hemispheres in 36 patients.

Results:
Radiological hyperperfusion was observed in 28/40 (70.0%) and 39/52 (75.0%) hemispheres in the edaravone and control groups, respectively (P = 0.30). Hyperperfusion-related TNDs incidences were significantly lower in the edaravone group compared with the control group (12.5% vs. 32.7%, P = 0.024). Multivariate analysis demonstrated that edaravone administration (P = 0.009) and left-sided surgery (P = 0.037) were significantly correlated with hyperperfusion-related TNDs (odds ratios, 0.3 and 4.2, respectively).

Conclusions:
Perioperative administration of edaravone reduced the incidence of hyperperfusion-related TNDs after direct bypass procedures in adult patients with MMD.
Abstract TP54: Magnetic Resonance Black-blood Thrombus Imaging Could be a Promising New Tool in the Diagnosis of Cerebral Venous and Sinus Thrombosis
Authors: Yang Qi , Fan Zhaoyang , Duan Jiangang , Ji Xunming , Li Debiao
Published: June 2021

Introduction:
BTI is a novel 3D black-blood imaging technique with isotropic, submillimeter spatial resolution. As opposed to conventional methods that indirectly diagnose CVT by imaging the lumen, BTI directly visualizes the thrombus with suppressed blood signals. We aimed to prospectively evaluate the diagnostic performance of BTItechnique in patients with suspected cerebral venous and sinus thrombosis (CVT) as compared to MR venography.

Materials and Methods:
MR venography and BTI were performed using 3.0 T in consecutive patients suspected of CVT between August 2014 and October 2015. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated for the detected thrombus on BTI. Diagnostic performance of BTI were analyzed on both per-segment and per-patient basis.

Results:
A total of 58 met study criteria Thrombus SNR was 206 ± 95 in acute thrombus and 94 ± 41 in chronic thrombus (P < 0.0001). Thrombus to lumen CNR was 201 ± 94 and 86 ± 40 for acute and chronic thrombus, respectively (P < 0.0001). The sensitivity and specificity rates of BTI in the detection of CVT were 97.3% (36/37, 95% confidence interval [CI] 85.8% to 99.9%) and 95.2% (20/21, 95% CI 76.2% to 99.9%), respectively on per patient level. On per segment level, the sensitivity and specificity were 95.6% (152/159, 95% CI 91.1% to 98.2%) and 98.0% (640/653, 95%CI 96.6% to 98.9%), respectively. The characteristics of the study population are summarized in Table 1. Figure 2 demonstrated thrombus volume quantification in one patient and total volume was 11.8cc.

Conclusions:
BTI allows for selective visualization of acute and chronic thrombus with high sensitivity, specificity and accuracy. Our findings suggest that BTI may emerge as a promising first line diagnostic imaging tool in the diagnosis of CVT.

Figure 1.
BTI images of a 13-year-old female with suspected acute CVT. Sagittal, coronal, and axial images of BTI depict the hyperintense signal of acute thrombi (A, B, and C) in ISS, Galen, SS, RSS, and RTS. Thrombus volume measurement was segmented and total thrombus volume was 11.8cc(D, E, and F).

Table 1. Clinical Characteristics of 58 patients who underwent BTI
Abstract TP59: To Estimate the Time of Stroke Onset by Using Ct Scan and Stroke Severity Scale
Authors: Kamran Saadat , Bhutta Zain , Akhtar Naveed , Bates Vernice , Salam Abdul , Shuaib Ashfaq
Published: June 2021

Purpose:
Thrombolysis in acute stroke is time limited. Onset time is unknown in a large number of patients. We wanted to classify acute stroke patients with unknown time of onset into less than or more than 4.5 hours onset, using CT scan and National Institute of Health Stroke Scale(NIHSS).

Methods:
Acute stroke patients with NIHSS ≥8 and CT within 24 hours of onset were included. The control group included 100 normal CT. Two reviewers blinded to clinical information independently reviewed all images. CT was graded as 0-normal, grade-I poorly-demarcated hypodensity and grade-II well-demarcated hypodensity. Hounsfield unit (HU) calculated in the area of interest using 0.5-1 cm area and compared with the contralateral side (n=44). The diagnosis was confirmed from follow-up scans.

Results:
A total 120 CT-scans were reviewed. There were 65% males, age ranged from 39-90 years.

< 4.5 hour group

:
Sixty-nine CT were graded as <4.5-hours, 87%(n=60) were correctly graded (p<0.0001) and 13%(n=9), false negative) were incorrectly assigned to > 4.5 hours category. Both observers were incorrect on same eight CT-scans. Five of the false negative (assigned to >4.5-hours) were in 2.30-3.0 hours range with average NIHSS of 13. Four patients under two hours developed hypodensity, assigned to >4.5 hour category with average NIHSS of 21. Average NIHSS of the group was 15.

> 4.5 hours group:

Fifty-one CT were over 4.5 hours. Forty-four (86%) were correctly graded as >4.5-hours (p<0.0001) and seven (14%) patients were incorrectly assigned to <4.5 hour category (false positive). Six false positive patients were in 3.30-4.10 time range, average NIHSS of 15. Average NIHSS of >4.5-hour group was 14. Eleven incorrectly categorized scans [false negative (n=5) and positive (n=6)] tend to fall in the 2.45-4.10 hours range. Twenty-five (21%) CT scans were normal, all under three hours except one with NIHSS ≥8 at seven hours. HU were measured in 44 patients. Average HU of patients in <4.5 hour category (n=20) was 3.5 and >4.5 hour category (n=24) was 7.5.

Conclusion:
Acute stroke with unknown time of onset, NIHSS >8 and CT scan changes of grade 0-I indicate <4.5 hours stroke onset. Higher NIHSS patients can develop early hypodensity, incorrectly suggesting >4.5 hours onset (false negative).
Abstract TP60: T1 Rho Magnetic Resonance Imaging Can Detect and Quantify Acute Ischemic Stroke in Humans
Authors: Esenwa Charles , Soun Jennifer , Filippi Christopher , Grinband Jack
Published: June 2021

Introduction:
Establishing a timeline of acute ischemic stroke (AIS) onset is critically important for selecting time-sensitive treatments. However, there is currently no accepted imaging method for reliably dating stroke onset. T1 Rho MR is an investigative imaging modality for quantifying the spin lattice relaxation time constant in a rotating frame. T1 Rho is sensitive to chemical exchange, and in acute stroke, has been shown in animal models to increase linearly in the first 6 hours after onset of cerebral infarction, making it possible to accurately date onset.

Hypothesis:
We hypothesize that a rapid non-contrast T1 Rho MR sequence can be used to detect and quantify AIS in humans.

Methods:
AIS patients (n=11) underwent 3.0T brain MR scans in the late acute to subacute period after onset (mean 56 hours). The infarct volume was identified on DWI and infarct regions of interest (ROIs) were mapped onto the contralateral side to serve as within-subject controls. Infarct and control ROIs were co-registered with T1 Rho maps and compared using a Student t-test.

Results:
T1 Rho infarct volume correlated well to DWI volume and mean T1 Rho intensity values in the infarct, were significantly higher compared to controls (p<0.004, mean difference 37ms, std 19.3). When inter-individual T1rho values were plotted against time from stroke onset, we found that they remained stable.

Conclusion:
T1 Rho MR is feasible, and can detect and quantify AIS in humans. Further, T1 Rho values in the infarct bed were stable in the late acute to early subacute time period, consistent with animal studies that show T1rho values to undergo predictable change only in the first 6 hours after infarct onset. Further studies are needed to determine if T1rho in humans has a predicable rate of change in the early acute phase, that can one day be used as a quantifiable surrogate of stroke onset and thus inform stroke therapy when time of onset is unknown.
Abstract TP66: Laboratory Factors Predisposing to Risk of Intracerebral Hemorrhage After IV Thrombolysis for Acute Ischemic Stroke
Authors: Kamal Haris , Lail Navdeep , Kavak Katelyn , Memon Aurangzeb , Kandel Amit , Ching Marilou , Sawyer Robert N , Mowla Ashkan
Published: June 2021

Background:
Laboratory factors associated with hemorrhagic conversion (HC) after Intravenous thrombolysis with rtPA (IVT) for Acute Ischemic Stroke(AIS) remain nebulous despite advances in our knowledge of AIS. This study aimed to investigate laboratory factors predisposing to HC in AIS patients receiving IVT or IAT.

Methods:
We retrospectively reviewed the medical records of patients who received IV tPA for AIS at our comprehensive stroke center from 01/2006 till 07/2015. Besides age, gender, NIHSS, history of DM, history of atrial fibrillation (Afib), we gathered their laboratory data including INR, lipid panel, serum albumin, serum creatinine, hemoglobin A1c, and admission blood glucose. Post-thrombolysis brain imaging was reviewed to evaluate for any symptomatic ICH (sICH). The mean values of above mentioned laboratory data were compared between the group with sICH and non-bleeders. Univariate and multivariate logistic regression were performed to evaluate the association of the laboratory findings with presence of sICH. sICH was defined as ICH causing an increase in NIHSS ≥4.

Results:
Of the 794 subjects in this study 51 (6.4%) had sICH. In univariate analysis, patients who had sICH had significantly higher NIHSS on admission (14.2±5.4 vs 11.2±6.5, p<.001), LDL (113.3 mg/dl ±36.9 vs. 101.8±38.2, p=.032), HbA1c (6.9 %±2.3 vs. 6.1±1.3, p=.003) and lower levels of Albumin (3.5 mg/dl ±0.4 vs. 3.9±0.5, p<.001) compared to subjects with non-bleeders. Furthermore, a higher prevalence of history of DM (34.8% vs. 22.2%, p=.020) and Afib (19.7% vs. 10.7%, p=.028) was found in subjects presenting with sICH. There were no significant group differences regarding age, sex, total cholesterol, blood glucose on admission, Creatinine or INR levels ( p>.05). After adjusting for covariates , Lower Albumin levels, higher LDL, higher total Cholesterol and higher HbA1c were significantly associated with an increased risk for sICH development. Chance of sICH decreased by 77% for every increase by 1mg/dl towards a normal albumin level (p<0.05).

Conclusion:
Multiple laboratory factors including lower endogenous albumin levels and higher HbA1C have shown to predispose to a higher risk of HC after IV thrombolysis and might be good predictor of of sICH post IV thrombolysis.
Abstract TP67: Safety of Intravenous Alteplase in Chronic Intracranial Hemorrhage: a Five Year Multicenter Study
Authors: Zand Ramin , Tsivgoulis Georgios , Singh Mantinderpreet , McCormack Michael , Goyal Nitin , Noorbakhsh-Sabet Nariman , Alexandrov Andrei V
Published: June 2021

Introduction:
Although, the recently updated tPA label removed a history of intracranial hemorrhage (ICH) as a contraindication, there is very limited data on the safety of intravenous thrombolysis in chronic ICH. The purpose of this study is to evaluate the safety of intravenous tPA among patient with chronic ICH.

Methods:
We analyzed consecutive patients who received intravenous tPA for stroke symptoms at three tertiary stroke centers in a five-year period. Patients without imaging confirmation of the old hemorrhage were excluded from the study. Outcome measures in our study were occurrences of symptomatic ICH and were defined according to European Cooperative Acute Stroke Study (ECASS)-III criteria combined with clinical deterioration of ≥4 points on NIHSS or death.

Results:
Out of 1212 post tPA patients evaluated in this study, seven patients (age 72 ± 11, four men, median NIHSS 5, IQR [2-8], volume ICH 1-21 cm3) had a history and neuroimaging findings consistent with an old ICH. Patients with old ICH did not differ in terms of rates of symptomatic ICH (0%, 95%CI (0-32%) by the adjusted Wald method versus 3.6%, p=0.61) and in-hospital mortality (0% versus 6.0%, p=0.5) when compared with the rest of patients. There was no significance difference between two groups in terms of age and admission NIHSS. Out of seven patients, five patients had ICH in basal ganglia and two patients had ICH in pre-ventricular white matter region.

Discussion:
Our study indicates that administration of intravenous tPA is safe among patients with a history of chronic ICH. More studies are needed to define chronic in such a setting.
Abstract TP84: Comparative Analysis of Genetic and Pharmacological Inhibition of Sirt3 in Post Ischemic Injury
Authors: Verma Rajkumar , Ritzel Rodney , Liang Bruce , McCullough Louise
Published: June 2021

Background:
Sirtuin3 (Sirt3), NAD+-dependent deacetylase, regulates several key proteins in both mitochondria and nucleus. The majority of early studies have shown neuroprotective effects of Sirt3 activation in various models of CNS injury. Recently, it was found that genetic loss of Sirt3 is beneficial in ischemia/reperfusion (I/R) injury. Therefore, this study was designed to explore the effects of both genetic and pharmacological inhibition of Sirt3 in a middle cerebral artery occlusion (MCAo) model of stroke.

Methods:
Focal cerebral ischemia was induced by transient right MCAo for 60min followed by 0, 6, 24 and 72 hrs of reperfusion. A 72hrs post ischemic injury time point was chosen to measure infarction in various treatment groups. The Sirt3 inhibitor AGK7 (sc- 204281 Santa cruz,) that selectively inhibits Sirt3 over Sirt1 and Sirt2, was given as single intraperitoneal injection (0.15, 0.5 and 1.5mg/kg) 3hrs after stroke onset. Activity or expression of Sirt3, was examined with Sirt3 activity kit or western blot using anti-Sirt3, anti-acetylated lysine antibodies.

Results:
Sirt3 knockout mice showed a significant reduction in hemispheric infarct volume compared to WT littermate controls (37.72±5.21 vs 52.8±6.76, p<0.05). In the pharmacological study, a dose of 0.5 mg/kg i.p of inhibitor showed significant reduction in Sirt3 activity and but had no neuroprotective effect. Furthermore, a much higher dose (1.5mg/kg i.p) did not show any additional inhibitory effect on sirt3 activity but unexpectedly increased infarct volume (51.8±6.87 vs. 62.56± 7.89, P<0.05) and hemorrhagic transformation. Expression studies showed no overall change in Sirt3 expression in whole cell lysates at 0, 6, 24 or 72 hrs after reperfusion; however the expression pattern and activity varied with time in different subcellular compartments.

Summary and Conclusions:
Changes in subcellular translocation and activity of Sirt3 after I/R stress suggests it important role in target protein deacetylation in stroke pathophysiology. Surprisingly, genetic deletion but not pharmacological inhibition led to neuroprotection, indicating the need to carefully examine target protein by both genetic and pharmacological approaches.
Abstract TP85: The Kca3.1 Tram-34 Reduces Selective Neuronal Loss, Microglial Activation and Sensorimotor Deficits Following Brief Middle-cerebral Artery Occlusion (mcao) in the Rat
Authors: Baron Jean-Claude , Emmrich Julius , Ejaz Sohail , Williamson David J
Published: June 2021

Introduction:
We have previously shown that 15min distal MCAo in the spontaneously hypertensive rat (SHR) consistently induces isolated selective neuronal loss (SNL) and topographically congruent microglial activation (MA), together with slowly recovering sensori-motor deficit (SMD) (Ejaz et al,
Stroke
, 2015). Whether MA exacerbates SNL in the reperfused penumbra is unclear. We tested whether reducing MA by means of the KCa3.1 blocker TRAM-34 also impacts SNL and SMD in this model.

Methods:
15min microclip distal MCAo was performed in 12 isoflurane-anesthetized adult male SHRs, randomized in two groups of n=6 rats, a control group and a treated group that received TRAM-34 40mg/kg i.p. bd for 1 week starting 12hrs post-MCAo, then od for 3 weeks. To quantify SMD, the sticky label test was administered 3 times a week for 28 days. NeuN and Iba4 immunoflorescence was then performed. Manual delineation of areas of SNL and MA was carried out by two independent assessors on randomly presented IF sections, and volumes of SNL and MA were determined. Both assessments were done blinded to subject’s group.

Results:
Although less so than in controls, SMD was significant in the TRAM-34 group (p<.001 and .01, respectively), with a significant Group x Time interaction (p=0.004, repeated-measures ANOVA) and a trend for faster recovery from day 7 in the latter. On IF, the volume (mm
3
) of MA was lower in the TRAM-34 relative to control group (1.33 ± 1.7 vs 0.27 ± 0.46), which also applied to SNL (1.41 ± 1.79 vs 0.28 ± 0.41) (p = 0.018 and 0.015, respectively; two-sample t-test).

Conclusion:
In this pilot study, the expected marked reduction in MA induced by TRAM34 was associated with concomitant reductions in SNL and faster SMD recovery. Thus, the early administration of an MA blocker following treatment-induced reperfusion in the clinical setting might reduce cell damage in the salvaged penumbra and in turn enhance neurological recovery.
Abstract TP95: Exercise Too Soon After Stroke Exacerbates Hyperglycolysis-mediated Brain Damage
Authors: Huber Mitchell , Shen Jiamei , Ding Yuchuan , Geng Xiaokun
Published: June 2021

Introduction:
Although physical exercise has emerged as a potential therapeutic modality for functional deficits following ischemic stroke, the extent of this effect appears to be contingent upon the time of exercise initiation. In the present study, we assessed how exercise timing affected brain damage through hyperglycolysis associated NADPH oxidase (NOX) activation.

Methods:
Using an intraluminal filament, adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and assigned to one non-exercise and three exercise groups. Exercise on Rota-rod was initiated for 30 min at 6 h (considered very early), at 24 h (early), and at day 3 (relatively late) after reperfusion. Lactate production was measured 30 min after exercise completion, and NOX activity and protein expression of NOX subunits (p47
phox
, gp91
phox
, p22
phox
and p67
phox
) and glucose transporter 1 and 3 (GLUT1 and 3) were measured at 3 and 24 h after exercise. Apoptotic cell death was determined at 24 h after exercise.

Results:
Lactate production and Glut-1 and Glut-3 expression were increased after very early exercise (6 h), but not after late exercise (3days), suggesting hyperglycolysis. NOX activity was increased with the initiation of exercise at 6 h (P<0.05), but not 24 h or 3 days, following stroke. Early (6 and 24 h), but not late (3 days), post-stroke exercise was associated with increased (P<0.05) expression of the NOX protein subunit p47
phox
, gp91
phox
and p67
phox
. This may have led to enhanced apoptosis after early exercise in ischemic rats.

Conclusion:
Hyperglycolysis and NOX activation was associated with an elevation in apoptotic cell death after very early exercise, while the detrimental effect of exercise on stroke recovery began to decrease when exercise was initiated 24 h after reperfusion.
Abstract TP98: Genetic Deletion of Kruppel-Like Factor 11 Aggravates Ischemic Brain Injury
Authors: Tang Xuelian , Liu Kai , Yin Ke-Jie
Published: June 2021

Kruppel-like factors (KLFs) are members of the zinc finger family of transcription factors and the function of the KLFs in the central nervous system is largely unexplored. KLF11 is a member of the KLF family and we have previously demonstrated that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs recruitment of KLF11 as its critical coactivator. In this study we sought to determine the role of KLF11 itself in cerebrovascular function and the pathogenesis of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was performed in KLF11 knockout and wild-type control mice, and brain infarction size was analyzed by TTC staining. BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays. KLF11 KO mice exhibited significantly larger brain infarct volume and worse neurological outcomes in response to ischemic insults. Genetic deficiency of KLF11 in mice also significantly aggravated ischemia-induced BBB disruption by increasing cerebrovascular permeability and edema in comparison with wild-type mice. Mechanistically, KLF11 was found to directly regulate several key inflammatory cytokines in the brains of ischemic mice. These findings suggest that KLF11 acts as a novel protective factor in ischemic stroke. Elucidating the functional importance of KLF11 in ischemic process may lead us to discover novel pharmaceutical targets for the development of effective therapies against ischemic stroke.
Abstract WMP101: The Evolution of Lesions on Diffusion-Weighted MR Imaging in Cerebral Amyloid Angiopathy
Authors: van Veluw Susanne J , Lauer Arne , Ayres Alison , Viswanathan Anand , Greenberg Steven , Vernooij Meike
Published: June 2021

Introduction:
Small hyperintense diffusion-weighted imaging (DWI) lesions are frequent neuroimaging findings in patients with cerebral amyloid angiopathy (CAA). Despite their high occurrence, little is known about the clinical impact of these lesions as well as their evolution over time and potential underlying etiology. Although it is believed that DWI-bright lesions represent acute microinfarcts, it has also been suggested that they are precursors of microbleeds. In this study we assessed DWI lesions in a cohort of CAA patients that underwent multiple imaging sessions. Specifically, we addressed the pathophysiologic nature of DWI lesions by evaluating their appearance on follow-up MRI.

Methods:
Patients (n=79) with probable CAA, as assessed by the Boston criteria, who underwent at least two DWI scans >2 months apart (>2 weeks post-ICH), were included in the study. One experienced neuroradiologist assessed presence and number of DWI lesions at each available time-point. Lesions had to be hyperintense on DWI, hypointense on ADC, and isointense on GRE. Next, on available follow-up images (FLAIR, T1, and GRE scans), lesion visibility and imaging characteristics were assessed by two experienced raters. All ratings were performed on 1.5 T MRI scans.

Results:
A total number of 221 DWI scans were assessed for DWI lesions (39 patients had 2 DWI scans; 40 had ≥3). In total, 57 DWI lesions were found in this dataset (37 in white matter; 16 in grey matter; 4 in cerebellum). For 36/57 lesions >1 imaging sequence was available at follow-up to determine lesion appearance. Twenty-two/36 DWI lesions (61%) were visible on follow-up MRI. Five appeared as lacunar infarcts (of which 4 were located in white matter), 16 were visible as signal change on T1 or FLAIR sequences. Only a single DWI lesion showed evidence of hemosiderin deposition on follow-up, compatible with hemorrhagic transformation / microbleed.

Conclusions:
DWI lesions are common neuroimaging findings in patients with probable CAA. More than 60% of the observed DWI lesions evolve into chronic lesions, but the minority shows cavitation. Their neuroimaging signature strongly suggests that these lesions have an ischemic pathophysiologic nature. We found only one lesion that underwent hemorrhagic transformation.
Abstract WMP104: Associations Between Lobar Microbleed and PiB Negative Intracerebral Hemorrhage.
Authors: Tsai Hsin-Hsi , Tsai Li-Kai , Chen Ya-Fang , Tang Sung-Chun , Yen Ruoh-Fang , Jeng Jiann-Shing
Published: June 2021

Background and Purpose:
Cerebral microbleed (CMB) in the lobar region is regarded as an image marker for cerebral amyloid angiopathy (CAA), but it is sometimes encountered in patients with intracerebral hemorrhage (ICH) owing to hypertension or other small vessel disease (SVD). Recently, enlarged perivascular space (EPVS) in white matter and deep region was suggested to be another potential marker for SVD. Knowledge of CMB location and EPVS in patients with ICH in relation to amyloid deposition might help us understand its heterogeneous pathophysiology.

Methods:
Fifty-seven primary, spontaneous ICH patients underwent magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) to analyze the CMB, the EPVS in basal ganglia (BG) and centrum semiovale (CSO), and the overall white matter hyperintensity (WMH).
11
C-Pittsburgh Compound B (PiB) positron emission tomography was also performed to measure the global amyloid deposition and was quantified as standardized uptake value ratio (SUVR) using cerebellum as the reference.

Results:
Twenty-six patients with lobar ICH and 31 patients with deep ICH were included. Positive PiB scan (SUVR >1.13) was found in 37% of patients (11 lobar ICH, 10 deep ICH). Presence of lobar CMB was found in 65% of patients irrespective of PiB scan status (p=0.084), but PiB (+) had higher number of lobar CMB (14.6 ± 16.9 vs. 5.4± 10.1, p=0.014) compared with PiB (-) patients. In PiB (-) patients, the number of lobar CMB is positively correlated with the number of deep CMB (p<0.001, r=0.773). The presence of lobar CMB in PiB (-) patients is also associated with severe EPVS in BG (70% vs. 31%, p=0.042), but not in CSO (p=0.073).

Conclusions:
Lobar CMB can be found in more than half of ICH patients irrespective of PiB scan status, but higher number of lobar CMB is seen in PiB (+) ICH patients. In PiB (-) patients, the presence of lobar CMB is associated with higher deep CMB number and EPVS in BG, suggesting the contribution of hypertensive angiopathy instead of amyloid angiopathy.
Abstract WMP110: Differentiating Childhood Arterial Ischemic Stroke From Migraine in the Pediatric Emergency Department
Authors: MacKay Mark T , Yock-Corrales Adriana , Churilov Leonid , Donnan Geoffrey A , Babl Franz E , Monagle Paul
Published: June 2021

Objective:
Migraine, a typically benign disorder, is the most common stroke mimic in children presenting with brain attacks. We aimed to identify clinical features which discriminate childhood arterial ischaemic stroke (AIS) from migraine.

Methods:
Fifty-five consecutive children with AIS, presenting to a tertiary pediatric emergency department (ED), prospectively/retrospectively recruited from 2003-2010, were compared to 84 children with migraine, prospectively recruited from 2009-2010.

Results:
Health professional referral, (odds ratio (OR), 5.71, 95% confidence intervals 2.54-12.81), ambulance transport (OR 2.95, 1.45-5.97), high triage category assignment (OR 2.41, 1.06-5.49), sudden onset (OR 2.74, 1.18-6.39), symptoms of focal weakness (OR 6.96, 3.24-14.93), seizures (OR 7.44, 1.99-27.81), speech disturbance (OR 3.06, 1.48-6.32), and ataxia (OR 4.88, 1.63-14.65) were significantly associated with increased odds of AIS diagnosis. Signs of face (OR 155.37, 20.03-1205.33), arm (OR 15.58, 6.41-37.84), or leg weakness (OR 15.40, 5.75-41.27), inability to walk (OR 14.18, 3.07-65.41), dysarthria (OR 47.21, 6.07-367.13), dysphasia (OR 12.76, 1.52-106.97) and altered consciousness (OR 2.45, 1.03-5.85) were also significantly associated with increased odds of AIS diagnosis, In contrast, vomiting (OR 0.23, 0.10-0.53), visual symptoms (OR 0.24, 0.10-0.57), other symptoms (OR 0.06, 0.01-0.48) and absence of neurological signs on ED physician assessment (OR 0.05, 0.01-0.17) were associated with decreased odds of AIS diagnosis.

Conclusion:
Differing presenting symptoms and signs allow discrimination of childhood AIS from migraine. These findings can inform decisions about urgency and type of diagnostic neuroimaging in the ED for children presenting with brain attack symptoms.
Abstract WMP12: Does IV tPA Improve Outcomes in Stroke Patients with Large Vessel Occlusions Treated with Intra-arterial Therapy?
Authors: Ho Joseph T , Tarpley Jason W , Li Hsin-Fang
Published: June 2021

Introduction:
The benefit of endovascular therapy (IAT) for the treatment of emergent large vessel occlusion (ELVO) in stroke patients has been established. However, it is not known whether administration of IV tPA prior to IAT is beneficial in these patients.

Methods:
A retrospective review of ischemic stroke patients in the Providence Health & Services Get with the Guidelines (GWTG) database was performed from 01/2012 to 05/2016. The analysis was limited to patients who presented within 4.5 hours of last known well time (LKWT) and treatment included any form of IAT. End points were limited to data available in the GWTG database, including discharge mRS, discharge NIHSS, change in NIHSS from admission to discharge, and length of stay. Continuous variables were summarized using means and standard deviation while categorical variables were summarized using frequencies and percentages. To yield a more robust estimate against outliers for the time-related variables, medians and interquartile range (IQR) were computed and assessed using Wilcoxon rank sum tests. Chi-square tests and independent two-sample t-tests were used to evaluate the demographic and outcome differences for categorical and continuous variables, respectively.

Results:
A total of 10,868 patients with an ischemic stroke diagnosis were found in the specified time frame and presented within 4.5 hours of LKWT. Of these, 461 patients were treated with some form of IAT, 235 received IV tPA prior to IAT, 226 had IAT alone due to contraindication to IV tPA. There was no statistical difference in patient demographics, complication rates, TICI score, discharge NIHSS or mRS at discharge. There was a significantly higher NIHSS on admission (18.3 vs 16.7, p = 0.026), greater improvement in NIHSS (11.6 vs. 7.9, p=0.012), longer door to IAT (146 vs 101.5 min, p < 0.0001), and shorter length of stay (5 vs 6 days, p = 0.016) in the IV tPA group.

Conclusions:
These data suggest that IV tPA, when administered to eligible patients with ELVO, provided some benefit over IAT alone, even though it delayed IAT. Future prospective randomized trials are planned that may better address this question, but these results underscore the need for retrospective analysis of existing data.
Abstract WMP18: Assessment of Perfusion Pattern Can be Useful for Predicting the Progression of Lacunar Infartion
Authors: Shin Dong Hoon
Published: June 2021

Background and Purpose:
The pathomechanism of a single subcortical infarct (SSI) may be better determined by assessing the perfusion status between parent artery and ischemic lesion. We aimed to compare the classifications into branch atheromatous disease (BAD) versus non-BAD based on DWI or CTP and to test whether a CTP-based classification improves the predicting power for progression in SSI (PSSI) compared to that by DWI.

Methods:
We enrolled 93 consecutive patients with SSI examined by whole-supratentorial brain CTP and follow-up DWI. Time-to-drain (TTD) maps were calculated from 1-mm dynamic CTP data. BAD was assumed when either the ischemic lesion extended to the basal surface of the parent artery on axial DWI or the hypoperfused area (TTD≥5 sec) was <5mm apart from the CSF-perforators interface on both coronal and sagittal CTP. We tested the relationship between DWI and CTP for determining BAD, and compared demographics, imaging, and the frequency of PSSI between the BAD and non-BAD based on CTP. Multivariate regression analysis was performed to determine predicting factors for PSSI.

Results:
On DWI, 57 of 93 patients (61.3%) were classified as BAD; on CTP 28 patients (30.1%), showing significant difference (
P
<0.0001). PSSI was significantly different between BAD versus non-BAD by CTP (35.7% versus 12.3%,
P
=0.020), but not different by DWI (22.8% versus 13.9%,
P
=0.289). BAD-type perfusion was the only independent predictor for PSSI (OR, 5.242; 95% CI, 1.372-20.021;
P
=0.015).

Conclusion:
The classifications of SSI with and without BAD by CTP and DWI are significantly different. CTP may help to predict PSSI.