bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2840: Aspect Score: DWI or CT Scan, Which One Is Better Marker For Stroke Morbidity And Outcome?
Authors: Mittal Manoj , Seet Raymond , Yi Zhang , Rabinstein Alejandro
Published: July 2021

Background and Objective
The Alberta Stroke Program Early CT Score (ASPECTS) is a validated grading system to assess ischemic changes on CT in acute ischemic stroke. Magnetic resonance imaging with diffusion weighted imaging (DWI) sequence is commonly used to identify the final ischemic changes. We examined the difference between the relationship of NIHSS at admission and ASPECT score calculated using CT scan versus MRI DWI sequence.

Methods
We conducted a retrospective analysis of prospectively collected data from 99 cases of acute ischemic stroke treated with IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. CT head at 24 hours and MRI DWI sequence were used to assign ASPECT score. We dichotomized ASPECTS (categorized as 0 to 7 versus 8 to 10) and favorable patient outcome at 3 month (modified Rankin score less than equal to 2 and more than 2). Univariate analysis including t-test, Chi-square, and Fisher Exact test was used when appropriate.

Results
Mean age was 70±14 years. Mean admission NIHSS score was 8±4. DWI ASPECTS (p<0.001) and CT ASPECTS (p=0.127) were inversely associated with admission NIHSS. Higher (8-10) CT ASPECTS (p=0.001) or DWI ASPECTS (p=0.002) were associated with good outcome (mRS ≤2) at 3 months. Sensitivity, specificity, positive predictive value and negative predictive value for good outcome identified by CT ASPECTS versus DWI ASPECTS were 81% vs 52%, 54% vs 54%, 83% vs 59% and 50% vs 47% respectively.

Conclusion
CT and MRI DWI are comparably useful to calculate the ASPECTS for estimation of functional outcome, but CT scan at 24 hours may be more sensitive for the prediction of good recovery.
Abstract 2855: The Application of Time-of-Flight MR Source Images in Predicting Hemorrhagic Transformation in Ischemic stroke
Authors: Shang Ty T , Katsnelson Michael , Ortiz Gustavo , Wright Clinton , Koch Sebastian , Romano Jose , Rundek Tatjana , Sacco Ralph
Published: July 2021

Introduction:
Hemorrhagic transformation (HT) is a feared complication in ischemic stroke. Its prediction has remained a challenge. It is more common among patients with worse stroke severity, early infarct signs, hyperdense artery sign, and hyperglycemia. Increased blood brain barrier permeability within the ischemic area is also associated with HT. Bleeding probably occurs from damaged vessels within the necrotic or edematous brain tissue. Time-of-Flight MR (TOF) source images provide parenchymal and vascular information relevant to HT: they are sensitive to T1 relaxation time and can detect hypointense areas that represent edema or necrosis which are early infract changes, and can also detect vessels with slow flow.

Methods:
We sought to define “
v
essels
i
n hy
p
ointensity
s
ign” (VIPS), hyperintense signals of vessels within the hypointense area of necrotic or edematous tissues, on TOF source images. We hypothesized that VIPS would be associated with an increased risk of HT if identified on early MRI. We retrospectively reviewed our consecutive ischemic stroke patient registry from January 2009 to April 2011. We included patients with ischemic strokes in middle cerebral artery (MCA) or posterior cerebral artery territory and MR TOF obtained within 12 hours after symptom onset, who had inpatient follow-up CT scans. Patients with lacunar infarction, malignant infarction, endovascular acute treatment, HT limited to petechial hemorrhage on MRI, or poor quality images were excluded. The HT was recorded according to the ECASS morphologic definitions. Participation in the ethical review board-approved database requires informed consent.

Results:
A total of 35 patients met the inclusion criteria from 787 patients. VIPS was seen in 14 (40%) patients (age 65 years, women 43%, NIHSS median 14.5). The prevalence of HT was greater in patients with VIPS than those without (78% vs. 19%, p<0.001). PH2 type of HT was also more common in patients with VIPS than those without (64% vs. 25%, but not statistical significant due to small number of patients). The figure illustrates a VIPS in the right MCA territory and subsequent HT in that area. Patients with VIPS were younger than those without (65 vs. 75 years, p<0.05), but there were no statistical differences in sex, IV thrombolysis, proximal vessel occlusion, and admission NIHSS, blood pressure, glucose, and lipid level.

Conclusion:
VIPS may be a risk factor for HT in ischemic stroke if seen within 12 hours on MRI after symptom onset. Further studies are needed to confirm these findings.
Abstract 2884: Angiographic Lumen Changes From Oversized Neuroform Stent Implantation
Authors: Lazzaro Marc A , Katib Omar , Golshani Behrad , Zaidat Osama O
Published: July 2021

Introduction:
The effect of oversized intracranial stent implantation, and the potential for excessive neointimal hyperplasia from the resulting chronic outward radial force, has not been previously reported. We sought to compare the angiographic narrowing associated with implantation of oversized Neuroform stents overlapping vessels of different diameters.

Methods:
We reviewed an aneurysm database and identified patients treated with stent-assisted coil embolization involving stent placement overlapping a vessel size transition. Patient demographics and lesion characteristics were extracted from chart review. A submillimeter digital caliper was used for angiogram measurement of lumen diameter at four sites (
figure
). The relationship between lumen diameter and stent oversizing was compared with student’s t-test and Pearson’s correlation.

Results:
Twenty vessels were identified in 18 patients, providing 80 paired data points. Mean age was 52 years (SD 12), with mean follow-up time of 8 months (SD 6). The distribution of vessel transitions included BA to PCA (n = 8), A1 to A2 or M1 to M2 (n = 8), ICA to ACA or MCA (n = 3), and Vertebral artery to PICA (n = 1). Stent diameter ranged from 3 mm to 4.5 mm, and the average oversizing in the smaller diameter parent vessel landing-zone was 1.75 mm (range 0.8 to 2.9 mm) greater than the vessel diameter. The mean change in lumen size from pre-stent implantation to follow-up was not significantly different for any of the four sites; the proximal end-stent decreased by 5.5% (SD 19.7), proximal mid-stent increased by 7.3% (SD 18.8), distal mid-stent increased by 14.7% (SD 13.8), and the distal end-stent decreased by 0.9% (SD 13.1). Stent oversizing by less than a factor of 1.65 resulted in a mean lumen loss of 4.1% (SD 15.6), while oversizing by greater than a factor of 1.65 resulted in a mean lumen gain of 11.1% (SD = 17.2), (p = 0.006).

Conclusions:
These data suggest oversized Neuroform stent implantation within the intracranial vasculature does not lead to increased stenosis. Stent oversizing by a factor of 1.65 or more leads to significant persistent luminal gain. The non-significant trend toward lumen loss at the stent tines suggests diminished radial force or greater neointimal hyperplasia at these sites, however persistent luminal gain from the oversized stent radial force likely predominates over any neointimal hyperplasia.
Figure
. A NF stent overlapping the M1 and M2 segments (A, tines indicated by white arrows). Four points of measurement (B), proximal tines (1.), mid-stent in proximal landing zone (2.), mid-stent in distal landing zone (3.), and distal tines (4.).
Abstract 2903: Nutritional Access of Dysphagic Patients 3 Months after Onset of Acute Stroke -From Database of 5,000 Patients in a Single Stroke Center-
Authors: Nakajima Makoto , Inatomi Yuichiro , Yonehara Toshiro , Hashimoto Yoichiro , Hirano Teruyuki
Published: July 2021

Background and purpose:
Prediction of swallowing function in dysphagic patients with acute stroke is indispensable for discussing percutaneous endoscopic gastrostomy (PEG) placement. We performed a retrospective study using database of a large number of acute ischemic stroke patients to clarify predictors for acquisition of oral intake in chronic phase.

Methods:
A total 4,972 consecutive acute stroke patients were admitted to our stroke center during 8.5 years; a questionnaire was sent to all the survivors after 3 months of onset. We investigated nutritional access after 3 months of onset in 588 patients who could not eat orally 10 days after admission, and analyzed predictive factors for their acquisition of oral intake. Continuous variables were dichotomized to identify the most sensitive predictors; the cutoff values were investigated by receiver operating characteristics curve analysis.

Results:
Out of 588 dysphagic patients, 75 died during the 3 months, and 143 (28%) of the residual 513 achieved oral intake after 3 months. In logistic-regression models, age ≤80 years, absence of hyperlipidemia, absence of atrial fibrillation, modified Rankin Scale score 0 before onset, and low National Institutes of Health Stroke Scale (NIHSS) score independently predicted oral intake 3 months after onset. From two different model analyses, NIHSS score ≤17 on day 10 (OR 3.63, 95% CI 2.37-5.56) was found to be a stronger predictor for oral intake than NIHSS score ≤17 on admission (OR 2.34, 95% CI 1.52-3.59). At 3 months, 17/143 (12%) patients with oral intake were living at home, while only 1/370 (0.3%) patients without oral intake were.

Conclusion:
A quarter of dysphagic patients with acute stroke obtained oral intake 3 months after onset. Clinicians should be cautious about PEG placement for stroke patients with severe dysphagia who were independent prior to the stroke, aged ≤80 years, and show NIHSS score ≤17 on day 10, because their swallowing dysfunction may improve in a few months.
Abstract 2933: Combined Clinical, CT, And CTA-SI Scale To Expect The Presence Of Large Infarct Volume On DWI In Acute Stroke Patients Within 8h Of Onset.
Authors: Aoki Junya , Tateishi Yohei , Cummings Chirs , Hussain Muhammad S , Uchino Ken
Published: July 2021

Background and Purpose:
Large ischemic volume (>70-80ml) on diffusion-weighted imaging (DWI) has been associated with a lack of response to early recanalization therapy of acute ischemic stroke. We investigated whether a scale that combines clinical, conventional computed tomography (CT) and CT angiography source imaging (CTA-SI) information can estimate large infarct of >80ml seen on early DWI.

Methods:
Acute anterior circulation stroke patients within 8h of onset and examined with CT and CTA were prospectively enrolled. Only imaging findings evaluated within 1.5h interval among CT, CTA and DWI were analyzed. NIH Stroke Scale (NIHSS) score was assessed on admission. The Alberta Stroke Programme Early CT Score (ASPECTS) was scored on CT and CTA-SI. To devise the early infarct volume estimation scale, NIHSS score, CT and CTA-SI ASPECTSs were scored as 1, if the NIHSS score was greater than or equal to, and, CT and CTA-SI ASPECTS was smaller than or equal to the cut-off value to distinguish the DWI volume of >80ml from others. Collateralization was also defined as score of 1 if collateral filling was limited <50% on CTA-SI. We compared the DWI volume based on the scale, score of 0, 1, 2, 3 and 4. After that, we calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the score to estimate the DWI volume of >80ml were calculated.

Result:
Fifty-seven subjects (median age [quartiles]; 74 [56-82], male; 28 [49%]) were enrolled from May 2010 to July 2011. DWI volume of >80ml was seen in 10 (18%) patients. Using ROC curve, the cut-off value of NIHSS score to predict DWI of >80ml was 20 (sensitivity of 0.70 and specificity of 0.70, area under curve [AUC] 0.761, p=0.010), that of CT ASPECTS was 6 (sensitivity of 0.98 and specificity of 0.68, AUC 0.887, p<0.001), that of CTA-SI ASPECTS was 6 (sensitivity of 0.87 and specificity of 0.80, AUC 0.952, p<0.001), respectively. Based on the scale, DWI volume was 14 (8-23) ml in patients with score of 0, 22 (11-36) ml with of 1, 67 (36-88) ml with of 2, 127 (71-147) ml with of 3, and 177 (131-191) ml with of 4 (p<0.001). All of those with score of 0 or 1 had DWI volume of ≤80ml (sensitivity of 1.00, specificity of 0.87 PPV of 1.00, and NPV of 0.62 (p<0.001). Seven (54%) of the 13 patients with score of 2 or 3 had DWI volume of >80ml (sensitivity of 0.70, specificity of 0.87, PPV of 0.54, and NPV of 0.93, p<0.001), and all of the 3 patients with score of 4 had DWI volume of >80ml (sensitivity of 0.30, specificity of 1.00, PPV of 1.00, and NPV of 0.87, p=0.004).

Conclusion:
Clinical and CT based radiological examinations may estimate the large ischemic volume on early DWI.
Abstract 2981: Neuroprotective Effect Of Acute Ethanol Administration In Rat With Transient Cerebral Ischemia
Authors: Geng Xiaokun , Ji Xunming , Wang Fei , Wang Yu , ASMARO Karam , Ding Yuchuan
Published: July 2021

Background and Purpose
_ Despite a focus on the pathological effects of alcohol abuse, numerous studies published over the past several decades also demonstrate beneficial effects of light-to-moderate consumption of alcoholic beverages. Recent studies have demonstrated that elevated serum ethanol levels are associated with increased survival in patients with traumatic brain injury (TBI), suggesting that an acute exposure to alcohol exerts a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified administration of ethanol as a possible treatment for acute ischemic stroke.

Methods
_Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for two hours. Five sets of experiments were conducted: 1) to determine the dose-response effect of ethanol (0.5, 1.0 and 1.5g/kg) on brain infarction and functional outcome; 2) to determine whether combining ethanol (1.5g/kg) and hypothermia produces synergistic neuroprotection; 3) to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage (ICH) in hemorrhagic or ischemic stroke, or after administration of thrombolytics in ischemic stroke; and 5) to test the affect of ethanol on HIF-1α protein expression.

Results
—Ethanol at 1.5 g/kg, which produce blood levels (89mg/dL) within the legally intoxicated range for driving (80-100 g/dL), most effectively reduced infarct volume and behavioral dysfunction when administered at 2, 3 or 4 hours after MCAO. We find that ethanol and moderate hypothermia (32-34 °C) exert neuroprotective effects of similar magnitude at both the lesion volume and functional levels, but do not exert a synergistic effect in this model. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue plasminogen activator (rt-PA) or urokinase (UK). Up-regulation of HIF-1α protein levels was enhanced by ethanol, in association with reduced brain infarct volume and improved functional recovery in rats subjected to stroke using the same dose (1.5 g/kg).

Conclusions
—Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, and does not promote ICH when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke.
Abstract 2997: The Severity of Intracranial Stenosis in Anterior Circulation Correlates with Asymmetrical Hemispheric Cerebral Volume on Magnetic Resonance Imaging
Authors: Watanabe Masaki , Majidi Shahram , Chaudhry Saqib A , Suri M. Fareed K , Qureshi Adnan I
Published: July 2021

Background and Purpose:
Chronic hypoperfusion associated with high grade intracranial atherosclerosis may results in regional atrophy. This study was performed to determine the effect of intracranial stenosis on ipsilateral regional cerebral volume.

Methods:
We included patients with intracranial stenosis >50% in the anterior circulation who underwent brain magnetic resonance image (MRI) who were admitted to a University hospital. The severity of intracranial atherosclerosis was evaluated by angiography and degree of stenosis was calculated using the WASID criteria. MRI images were acquired with a 1.5-T MR scanner and fluid attenuated inversion recovery (FLAIR) images were used for volumetric analysis. Volumetric analysis was performed by a single observer with the ANALYZE 9.0 software package. Hemispheric supratentorial volume was defined as hemispheric volume (HV) and included a cumulative value of grey and white matter volumes in frontal, parietal, and occipital lobes.

Results:
A total 42 hemispheres in 21 patients (12 men, mean age±standard deviation 56.4±16.2 years) with intracranial stenosis were studied. There was no statistical difference of HV in between non-stenotic and stenotic side (491.7±62.6 vs 486.7±57.8 cm3, p=0.3953, t-test). There was no statistical difference of HV in between moderate stenosis (50∼75%) and severe stenosis (>75%) (480.6±56.7 vs 490.5±60.4 cm3, p=0.3657, t-test). However, in regression analysis, difference between both HV (non stenotic-side - stenotic side HV) within individuals significantly correlated with degree of stenosis (R2=0.27, P=0.0152).

Conclusion:
The patients with intracranial stenosis of anterior circulation appear to have an asymmetry in regional cerebral volume directly related to the severity of stenosis. This observation supports the concept that regional cerebral atrophy may be seen with intracranial stenosis.
Abstract 3: Restenosis following Carotid Artery Stenting and Endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial
Authors: Lal Brajesh K , Beach Kirk W , Roubin Gary S , Lutsep Helmi L , Moore Wesley S , Malas Mahmoud B , Chiu David , Gonzales Nicole R , Burke James L , Rinaldi Michael , Elmore James R , Weaver Fred A , Narins Craig R , Foster Malcolm , Hodgson Kim , Shepard Alexander D , Meschia James F , Bergelin Robert O , Voeks Jenifer H , Howard George , Brott Thomas G
Published: July 2021

Objectives
The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) showed no difference in the composite endpoint of stroke, myocardial infarction, or death between carotid artery stenting (CAS) and carotid endarterectomy (CEA) in patients with symptomatic or asymptomatic carotid stenosis (CS). We compared restenosis or occlusion, and repeat revascularization, between CAS and CEA over 2 years of follow-up.

Methods
Restenosis, occlusion, and repeat revascularization were assessed at 1, 6, 12 and 24 months post-randomization. Hemodynamically significant restenosis (≥70% diameter reduction) was defined by a peak systolic velocity (PSV) ≥300 cm/second on standardized duplex ultrasonography (DUS), occlusion by an absence of flow within the target artery on DUS, and repeat revascularization by any additional procedure (CEA, angioplasty or CAS) performed on the index artery. Studies were performed in CREST-certified laboratories and interpreted in the CREST Ultrasound Core Lab. Patients included in this report were those who received their assigned treatment within 30 days of randomization and had an ultrasound reviewed at the Core Lab (n=2191). Treatment differences were assessed using proportional hazards models adjusting for age, sex, and symptomatic status.

Results
In the analytic cohort, 1086 patients received CAS and 1105 received CEA. Over 2 years 113 patients developed restenosis, 56 (rate 5.8%) in the CAS group and 57 (rate 5.8%) in the CEA group; and 8 developed an occlusion, 3 (rate 0.3 %) in the CAS group and 5 (rate 0.5%) in the CEA group. The combined restenosis-occlusion rate was 6.0% (n=58) for CAS and 6.3% (n=62) for CEA (HR=0.90, 95% CI=0.63-1.29, p=0.58). Forty-three patients of the 2191 underwent repeat revascularization (20 CAS, 23 CEA, p=0.69) of which 28 had restenosis by our criteria and so were included (
Figure
). Stroke occurred in 13 (4 CAS; 9 CEA) of the 120 patients with restenosis or occlusion; 1 of the 4 CAS strokes occurred after restenosis was detected, and 5 of 9 CEA strokes occurred after restenosis was detected.

Conclusions
This analysis of carotid restenosis is the largest reported to date from any randomized clinical trial. Restenosis and occlusion were infrequent and similar up to 2 years following CAS or CEA among 2191 patients. The rates of revascularization likewise did not differ between CAS and CEA. Follow-up out to 10 years is ongoing.

Figure.

Kaplan-Meier curves of restenosis and occlusion over 2 years.
Abstract 3007: What Perfusion Parameters Best Define Ischemic Penumbra in Patients with TIA and Minor Stroke; Data from the VISION study
Authors: Asdaghi Negar , Coulter Jonathan I , Stewart Teri S , Goyal Mayank , Demchuk Andrew M , Butcher Ken S , Hill Michael D , Coutts Shelagh B
Published: July 2021

Background:
Patients with TIA and minor ischemic (MIS) stroke are at high risk for clinical and radiographic deterioration. Acute Perfusion-Diffusion (PWI-DWI) mismatch have been used to identify those at risk for early deterioration. However, optimal perfusion thresholds for ischemic penumbra have not been defined in TIA/MIS patients. We aimed to determine the interrater reliability of different perfusion measurements and the optimal values that predict DWI lesion expansion in patients with TIA/MIS.

Methods:
Patients with minor stroke (NIH Stroke Scale ≤3) and TIA were prospectively enrolled and imaged within 24 hours of symptom onset. All patients had follow-up imaging at day 30. Raw perfusion images were used to generate maps of time to peak of the impulse response (Tmax), cerebral blood flow (CBF) and cerebral blood volume (CBV). DWI and PWI volumes were measured with planimetric and thresholding techniques by two independent groups of readers (1 group with a single experienced rater and a second group with 2 inexperienced raters) and 95% confidence intervals were calculated. Infarct progression (FLAIR 30 vol-DWI Acute vol) was a priori defined as growth of at least 2.5 ml.

Results:
At baseline 55.2% of the 116 patients included had DWI lesions and 42.2% had PWI deficits. The inter-rater reliability for assessment of hypoperfused regions was excellent for all Tmax thresholds (Tmax+2s (Intraclass Correlation Coefficient (ICC)=0.996 [0.994, 0.997], Tmax+4s(0.99 [0.985, 0.993], Tmax+6s (0.998 [0.998, 0.999] and Tmax+8s(0.996 [0.994, 0.997]). The interrater agreement was very good for assessment of regions with reduced CBF (ICC=0.84[0.78-0.89] and moderate for evaluation of regions with low CBV (ICC=0.43 [0.27, 0.57]). 18.1% of patients had evidence of radiographic progression on follow-up. Mismatch volumes (PWI-DWI) calculated using Tmax+4s predicted infarct expansion (R=0.8, [0.21-0.28], P<0.001). In contrast, mismatch volumes calculated with CBF did not predict infarct expansion (R=0.04, [-0.31,0.50] P=0.66). A mismatch volume (Tmax+4s-DWI) of ≥10 ml predicted infarct progression with 81% sensitivity and 92% specificity (AUC =0.85, [0.74-0.97]).

Conclusion:
In patients with TIA/MIS, penumbral patterns are common. Application of perfusion thresholds produced Tmax maps with excellent intra-rater reliability. Mismatch volume calculated as Tmax+4s-DWI volume reliably predicted infarct expansion. Objective PWI-DWI mismatch definitions such as these may be useful for acute reperfusion treatment decision making in patients with minor ischemic symptoms
Abstract 3012: Significant Genome Wide Association Identified Between the Glycine N-Methyltransferase Gene (GNMT) and Post-Methionine Load Test Homocysteine Levels in the Vitamin Intervention for Stroke Prevention (VISP) Cohort
Authors: Williams Stephen R , Chen Fang , Keene Keith , Chen Wei-Min , Hsu Fang-Chi , Wang Liewei , Doheny Kimberly F , Zilka Michelle , Worrall Bradford B , Sale Michèle M
Published: July 2021

The Vitamin Intervention for Stroke Prevention (VISP) trial was a multi-center, controlled, double blinded clinical trial, designed to determine whether the daily intake of high dose folic acid, vitamins B6 and B12 reduced recurrent cerebral infarction. Baseline post-methionine load homocysteine levels were predictive of recurrent stroke risk in VISP. We have conducted a genome-wide association study (GWAS), investigating 2100 VISP stroke cases required to have homocysteine levels greater than the 25th percentile at enrolment. Using imputation with 1000 genomes and principal component analysis, we were able to detect an association of p≤6.70x10-17 for SNPs within, or flanking, the glycine N-methyltransferase (GNMT) gene and post-methionine load test homocysteine level. Change in homocysteine levels pre and post-methionine load test also resulted in significant GWAS scores in the chromosome 6 region (p = 2.54x10-23, rs7760250). GNMT catalyzes the conversion of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine and sarcosine via the folate one-carbon metabolism pathway. In addition to being an essential component in the conversion of methionine to homocysteine, GNMT plays a significant role in the global epigenetic state as homocysteine is an important methyl donor. This region displays significant linkage disequilibrium, warranting close analysis of the entire GNMT locus in search of both rare and common variants. Cases who carry the minor allele haplotype at associated loci had a higher level of post-methionine load homocysteine (37.69µM/L) than those who carry the major allele haplotype (27.33µM/L), inferring functional differences due to GNMT variants. Taken together these data suggest a clear and important role for GNMT in post-methionine load test homocysteine level, epigenetic state and stroke risk.
Abstract 3022: Image-Guided Endoscopic Evacuation of Spontaneous Intracerebral Hemorrhage
Authors: Dusick Joshua R , Dye Justin , Gonzalez Nestor , Varma Jennifer , Frazee John , Vespa Paul M , Martin Neil A
Published: July 2021

Introduction:
Spontaneous intracerebral hemorrhage (ICH) is associated with a high morbidity and mortality rate despite current medical management. The benefits of open surgical evacuation for ICH remain controversial. Here we present initial results of the effectiveness of stereotactic image-guided endoscopic evacuation of ICH.

Methods:
Over 9-years, 41 patients with ICH (age 65+−14 years, 66% male, average admission GCS 10 & ICH Score 2, 46% with concurrent intraventricular hemorrhage) were treated. The current technique, which evolved from using direct endoscopic visualization, uses frameless stereotactic guidance alone to aspirate at two specified locations within the hematoma. An endoscope sheath is introduced through a bur hole into the hematoma along its long axis. Suction is applied to the sheath, without endoscopic viewing, at two locations, 1/3 and 2/3 of the way through the long-axis of the ICH. Endoscopic visualization of the cavity is then performed to ensure hemostasis. ICH volume was calculated using pre- and postoperative CT measurements ((length x width x height)/2).

Results:
Pre- and postoperative ICH volumes averaged 56.5 and 15.9cc, respectively, a reduction of 67.6+−41.9% (p<0.0001) with greater than 50% reduction in 78% of patients. Within 30 days, two patients (5%) developed rebleeding, one with acutely increased hematoma volume on postop CT. Average preop modified Rankin Score (mRS) decreased from 4.4 to 4.1 at follow-up (p=0.17). Seven-day and 30-day mortality occurred in 5 (12%) and 1 (2.4%) patients, respectively. This 30-day mortality compares favorably with the predicted rate of 26% based on average ICH score of 2 for the series. There were 2 surgical complications including ipsilateral ischemic stroke and subdural hematoma. Comparing the current aspiration technique to the previous technique, there were trends towards greater average reduction in hematoma volume (81.7% versus 58.5%, respectively, p=0.08) and greater improvement in clinical outcome (average mRS improvement 0.75 points versus 0 points, respectively, p=0.08).

Conclusions:
Image-guided endoscopic evacuation is a minimally-invasive approach to reduce ICH volume. Greater than 50% reduction in hematoma volume was achieved in the large majority of patients. Further study is required to evaluate the impact of endoscopic ICH evacuation on clinical outcomes compared to other treatments.
Abstract 3092: Does Pre-existing Antiplatelet Treatment Influence Post-thrombolysis Intracranial Hemorrhage In Community Treated Ischemic Stroke Patients?
Authors: Meurer William J , Skolarus Lesli E , Adelman Eric E , Frederiksen Shirley M , Kade Allison M , Kalbfleisch Jack D , Scott Phillip A
Published: July 2021

Background:
Post-thrombolysis ICH is associated with poor outcomes. Previous investigations have attempted to determine the relationship between pre-existing anti-platelet (AP) use and the safety of intravenous thrombolysis, but have been limited by low event rates thus decreasing the precision of estimates. Our objective was to determine whether pre-existing AP therapy increases the risk of ICH following thrombolysis.

Methods:
Consecutive cases of ED treated thrombolysis patients were identified using multiple methods, including active and passive surveillance. Retrospective data were collected from 4 hospitals from 1996-2005, and 24 distinct hospitals from 2007-2010 as part of a cluster randomized trial. The same chart abstraction tool was used during both time periods and data was subjected to numerous quality control checks. Hemorrhages were classified using a pre-specified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow up imaging (primary outcome). Symptomatic ICH (secondary outcome) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to post-thrombolysis ICH. The models included: pre-existing AP use, age*, NIHSS*, pre-treatment systolic blood pressure, onset to treatment interval, pre-treatment blood glucose*, tobacco use, presence of post-treatment protocol violations (*variable classified by quartile). As there were fewer SICH events, the multivariable model was constructed similarly, except that variables divided into quartiles in the primary analysis were dichotomized at the median.

Results:
There were 830 patients included, with 47% having documented pre-existing AP treatment. The mean age was 69 years, the cohort was 53% male, and the median NIHSS was 12. The unadjusted proportion of patients with any ICH was 15.1% without AP and 19.3% with AP (difference 4.2% [95% CI: -1.2% - 9.6%]); for SICH this was 6.1% without AP and 9% with AP (difference 3.1% [95%CI: -1-6.7%]). No significant association between pre-existing AP treatment with radiographic or symptomatic ICH was observed (
table
).

Conclusions:
We did not find that AP treatment was associated with post-thrombolysis ICH or SICH in this cohort of community treated patients. Pre-existing tobacco use, younger age, and lower severity were associated with lower odds of SICH. An association between AP therapy and SICH may still exist - further research with larger sample sizes is warranted in order to detect smaller effect sizes.
Abstract 3094: Diffusion-Positive Cerebral Ischemia with Transient Symptoms - Is it Transient Ischemic Attack or Minor Ischemic Stroke? A Formal Analysis of Demographics, Risk Factors, and Prognosis
Authors: Lee Yongseok , Liebeskind David S , Ali Latisha , Starkman Sidney , Kim Doojin , Raychev Radoslav , Abcede Hermalinda , Adamczyk Peter , Salamon Noriko , Saver Jeffery L
Published: July 2021

Background:
The classification of patients with minor cerebral ischemic events is evolving. Under the classical time-based definition of TIA, cerebral infarcts with transient symptoms (CITS) were classified as TIA, while it is classified as minor ischemic stroke (MIS) under the modern tissue-based definition. However, arguments for this reclassification have been largely based on pathologic principles rather than formal analysis of whether CITS patients clinically more resemble DWI-negative TIA patients or MIS patients in demographics, clinical features, and prognosis.

Methods:
We analyzed consecutive patients recorded in a prospectively maintained database with symptoms of presumed focal ischemic origin either lasting less than 24 hours or with minor neurologic deficits (NIHSS≤5) lasting more than 24 hours. Patients had to present within 48 hours of symptom onset and have undergone acute DWI. Patients were excluded if ischemia occurred immediate after carotid endarterectomy or stenting. Clinical variables, ABCD
2
score, presence of DWI abnormality, relevant large artery disease (≥ 50% stenosis or occlusion of ipsilateral intracranial or extracranial vessels), and stroke recurrence within 90 days were recorded for analysis.

Results:
Among 416 patients meeting inclusion criteria (mean age 67 years, female 47.1%), 108 (26.0%) were CITS, 149 (35.8%) were DWI-negative TIA, and 159 (38.2%) were MIS. Compared with DWI-negative TIA patients, CITS patients were younger (65 vs. 70 years, p=0.017), had more coronary artery disease (25.9% vs. 14.1%, p=0.024) and relevant large artery disease (45.2% vs. 20.8%, p<0.001). In contrast, only diabetes differed between CITS and MIS patients (16.7% vs. 29.7%, p=0.027). The frequency of recurrent stroke was not different between MIS and CITS patients (16.0% vs. 12.3%, p>0.05), however, both were substantially higher than in DWI-negative TIA patients (2.5%). In multivariate logistic regression analysis performed across the entire cohort, the independent predictors of recurrent stroke were presence of DWI lesion (OR 4.95, 95% CI 1.11-22.09) and relevant large artery disease (OR 3.58, 95% CI 1.47-8.73).

Conclusion:
DWI-positive cerebral ischemia with transient symptoms more resembles MIS than DWI-negative TIA in risk factor profile and prognosis of patients. DWI abnormality and large artery disease, rather than clinical variables, are the predominant determinants of early stroke recurrence. These results emphasize the utility of urgent MR imaging in patients with minor cerebral ischemic episodes and support the rationale of tissue-based definition of TIA over time-based definition.
Abstract 3123: Toolkit for Return to Work after Stroke
Authors: Gilmore Paula , Barry John , Blanchard Jeff , Howson Shannon , Korzycki Martha
Published: July 2021

Background:
The Southwestern Ontario (SWO) Stroke Network completed community engagement forums with stroke survivors, their loved ones and community service providers to determine barriers to living fully in the community after stroke. One of the priorities identified in the forums was the need for "return to work" services. Currently, 10 % of stroke survivors are people under the age of 50 and in the prime of their working life. Research indicates that return to work rates after stroke are as low as 7%. However, employment is one of the most important social roles that a person fulfills and not working has negative impacts on one’s overall quality of life, health, finances, social isolation and self-efficacy. Stroke survivors and health care professionals need to be aware of how to navigate the process of return to work after stroke.

Purpose:
A toolkit of resources has been developed to assist stroke survivors and health care professionals navigate the process of return to work after stroke.

Methods:
A working group comprised of experts in vocational rehabilitation and stroke care developed a toolkit of resources to educate and assist stroke survivors and health care professionals navigate the complex system of return to work. The resources have undergone an external review by health care professionals and stroke survivors.

Results:
Resources developed include a self assessment guide. It assesses five critical areas to return to work by evaluating the stroke survivor’s current abilities against the demands of the job and is designed to help focus the individual’s recovery efforts. Algorithms on how to navigate the system of return to work, including how to traverse the system of financial benefits and questions to ask employers and information on community financial supports were developed. A literature review and inventories outlining services for persons with stroke, who are preparing to re-enter the workforce, are part of the toolkit. Health care providers and stroke survivors have confirmed the face to face validity of the resources.

Conclusions:
Research indicates that stroke survivors should be encouraged to evaluate their potential of returning to work and should receive support from knowledgeable professionals regarding return to work as soon as possible after stroke. This toolkit is intended to support stroke survivors and their health care professionals to navigate the system for a successful return to work. Next steps include the development of a website to assist with return to work.
Abstract 3130: A 101 cm
3
Diffusion-Weighted Imaging (DWI) Cerebral Infarct Volume is the Maximum Volume Compatible with Good 30- Day Functional Outcome
Authors: Cheng-Ching Esteban , Aoki Junya , Tateishi Yohei , Wisco Dolora , Toth Gabor , Uchino Ken , Gebel James , Hussain Muhammad S
Published: July 2021

Background:
Several predictors of clinical outcome have been identified in acute ischemic stroke patients, including age, National Institutes of Health Stroke Scale scores (NIHSS), and large vessel occlusion. Predicted infarct volumes are thought to generally correlate with clinical outcome, however, to date, mostly small studies have failed to demonstrate a convincing relationship between Diffusion-weighted imaging (DWI) volumes and clinical outcome, and this correlation is controversial.

Hypothesis:
We hypothesized that final DWI infarction volumes would correlate with 30-day modified Rankin Score (mRS). We also sought to describe the maximum cerebral infarct volume compatible with a favorable 30 day (mRS of 0-2) outcome.

Methods:
We retrospectively reviewed a prospectively collected database of acute stroke patients with large vessel occlusion who were potential intra-arterial therapy candidate, which recently incorporated systematically collected imaging data at our large academic medical center. Additional inclusion criteria were MRI on admission as per our hyperacute stroke treatment protocol, and available 30-day mRS (n=91). Final DWI volume was obtained from the last MRI the patient had during their stroke treatment admission. Differences between final DWI volume and 30-day mRS were analyzed using the Kruskal-Wallis test.

Results:
See
Table 1
for DWI volumes by individual mRS. There was a strong overall positive relationship between final DWI volume and 30-day mRS [Kruskall Wallis p= .0047]. No patient with an mRS of 0 had a DWI volume >12.1 cm
3
. No patients with an mRS of ≤1 had an DWI volume over 85 cm
3
, and no patient with a mRS of ≤2 had a DWI volume over 101 cm
3
.

Conclusions:
Cerebral infarct volumes strongly correlate with 30-day functional outcome, but there is great individual variability. The maximum infarct volume compatible with survival and mild or less disability at 30 days was 101 cm
3
. In this study, the maximum cerebral infarct volume compatible with zero clinical symptoms or disability at 30 days was 12.1 cm
3
.
Abstract 3137: Significant Impairment in Gait Coordination Consistency at Two Self-Selected Walking Speeds in Chronic Stroke
Authors: Daly Janis J , Roenigk Kristen , Litinas Krisanne , McCabe Jessica , Pundik Svetlana
Published: July 2021

Background/Objectives:
Gait coordination is not well-studied nor well-described in chronic stroke. Gait coordination can be defined as the simultaneous consideration of spatial and temporal movement characteristics. One aspect of gait coordination is the consistency of relative movements of hip/knee, hip/ankle, and knee/ankle across the gait cycle. Without consistency of relative joint movement from step to step, safety of gait is compromised and function is reduced. Therefore, the hypothesis of this study was that in chronic stroke survivors with persistent gait deficits, consistency of gait coordination is impaired, according to a measure of inter-joint coordination consistency (hip/knee; hip/ankle; and knee/ankle) of movement excursion and timing across the gait cycle from step to step.

Methods:
Ten healthy adults and thirty-eight subjects with persistnet gait deficits were enrolled (>6mos after stroke). In terms of gait speed, stroke subjects were either household ambulators (HA; <.4m/s; n=28) or limited community ambulators (CA; .41-.9m/s; n=10). Control subjects’ gait variables were measured at each of these two speeds imposed during testing. Gait kinematics were measure using Vicon MX (Oxford Metrics, UK) and modified Helen Hayes model of marker placement. The average consistency coefficient (ACC, range 0 - 1) was calculated for hip/knee (H/K ACC), hip/ankle (H/A ACC), and knee/ankle (K/A AC) for both controls and stroke. ACC=1, indicated perfect consistency from step-to-step in terms of relative inter-limb joint movement. T-test was employed to compare stroke versus controls for each coordination consistency measure. Findings: Within the HA-speed group, there was a significant difference between stroke and HA-speed controls in terms of H/K ACC, H/A ACC, and K/A ACC (p = .0001). Also within the CA-speed group, there was a significant difference between stroke and CA-speed controls for all three measures of coordination consistency (p=.0001). Control subject ACC’s ranged from .85 - .95; whereas, stroke ACC’s ranged from .7063 - .8638 (1=perfect consistency).

Conclusions:
Inconsistent relative joint movement between hip, knee, and ankle across the gait cycle, could be a source of falls, poor walking endurance, and dysfunction. The presence of this impairment should be noted in assessment and targeted during treatment.
Abstract 3144: Neuroglobin Inhibits Oxygen-Glucose Deprivation-induced Mitochondrial Permeability Transition Pore Opening in Primary Cultured Mouse Cortical Neurons
Authors: Yu Zhanyang , Liu Ning , Wang Xiaoying
Published: July 2021

Background:
Accumulating evidences from our laboratory and others have demonstrated that neuroglobin (Ngb) is protective against hypoxic/ischemic brain injury, thus targeting Ngb may be a novel approach for endogenous neuroprotection, but the molecular mechanisms remain undefined. Mitochondrial permeability transition pore (mPTP) opening is a key mitochondrial response to hypoxia/ischemia, followed by release of mitochondrial factors such as Cyt c and activation of Caspase-dependent apoptosis pathways. In this study, we test our hypothesis that Ngb inhibits OGD-induced mPTP opening in primary neurons.

Method:
Primary mouse cortical neurons were transduced with AAV-Ngb to achieve Ngb over-expression and Ngb-shRNA to achieve Ngb knockdown. At day 9 of culture, primary neurons were subjected to 4 hr OGD followed by reoxygenation. Neurotoxicity was measured after 20 hr reoxygenation by LDH release assay. mPTP opening was measured at 4 hr after reoxygenation by testing mitochondria swelling, NAD release and Cyt c release. NAD release was also measured using isolated mitochondria treated with OGD after incubation with recombinant Ngb protein.

Results:
(1) Four hour OGD followed by 20 hr reoxygenation caused 40±4.5% neuron death; Ngb overexpression significantly reduced the death rate to 18±5.2% (n=5, p<0.05). (2) Ngb-overexpression significantly reduced OGD-induced mitochondria swelling, and rescued OGD-induced mitochondrial NAD release (mitochondrial NAD content 4±0.56 nmol/mg protein at normoxia, 2.1±0.35 nmol/mg prot. after OGD, 3.4±0.46 nmol/mg prot. in Ngb-overexpressing group after OGD) (n=4, p<0.05). (3) Ngb-overexpression significantly reduced OGD-induced Cyt c release from mitochondria to 0.43±0.08 fold (n=3, p<0.05). (4) Incubation with recombinant Ngb significantly reduced OGD-induced mitochondria NAD release in isolated mitochondria (mitochondrial NAD content 3.5±0.46 nmol/mg protein at normoxia, 1.8±0.32 nmol/mg prot. after OGD, 3.0±0.45 nmol/mg prot. in Ngb-overexpressing group after OGD) (n=4, p<0.05). (5) Ngb knockdown significantly increased OGD-induced neuron death from 40±4.5% to 56.4± 7.2%, and worsened OGD-induced mitochondria NAD release, but these changes were rescued by CsA, an mPTP inhibitor (n=3, p<0.05). (6) Co-IP detected protein interaction between Ngb and VDAC, an mPTP component, and the interaction was increased after OGD.
Abstract 3165: Influence Of Hypertension On Cognition Is Mediated By Brain Injury
Authors: Kuo Julie , Lee Anne , Fletcher Evan , Singh Baljeet , Martinez Oliver , Haan Mary , Beckett Laurel , DeCarli Charles
Published: July 2021

Background
Substantial evidence indicates that hypertension is a major risk factor for cognitive decline and incident dementia. Unfortunately, community based, longitudinal studies examining this association are limited. In addition, while it is assumed that vascular brain injury likely mediates this association, these studies are similarly limited.

Methods
The Sacramento Area Latino Study of Aging is a community based longitudinal study of life-style factors and cognitive performance among individuals 65 years and older. Comprehensive assessment including blood pressure measures and yearly cognitive testing was performed. In addition, a subgroup of 207 subjects received brain MRI with quantitative analysis of gray matter, hippocampus and white matter hyperintensity (WMH) volumes. We analyzed the relationship between baseline measures of blood pressure (systolic (SBP), diastolic (DBP) and pulse pressure (PP)), MRI measures and longitudinal cognitive performance over an average of six visits as measured by the 3MMSE using random mixed models regression analysis.

Results
On average, subject performance improved slightly during the first two visits after baseline measurement, but then began to deteriorate in a fashion best estimated by a quadratic term (trial*trial). 3MMSE performance was significantly and inversely associated with increased baseline SBP and PP, as well as linear (BP*trial) and quadratic (BP*trial*trial) declines over time (p<0.03 for all comparisons). Similarly, baseline 3MMSE performance was associated with gray matter and hippocampal volumes (p < 0.01 for all comparisons). Hippocampal and WMH volumes were also associated with change in 3MMSE performance over time (p <0.002 for all comparisons). In a multivariate model that included blood pressure and MRI measures, the MRI associations remained significant predictors of 3MMSE performance at baseline and over time, whereas blood pressure measures were no longer significant.

Conclusion
The impact of elevated blood pressure on cognition is mediated through measures of brain injury. This has implications for clinical trials of blood pressure modification designed to improve cognitive health in our aging society.