bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 107: Flow-Diversion for Ophthalmic Segment Aneurysms. Clinical/Angiographic Outcomes and the Fate of the Ophthalmic Artery
Authors: Chalouhi Nohra , Zanaty Mario , Tjoumakaris Stavropoula , Starke Robert M , Hasan David , Rosenwasser Robert , Jabbour Pascal
Published: March 2022

Introduction:
Flow diverters have emerged as an important tool in the management of intracranial aneurysms. This study aims to assess the visual outcomes, the obliteration rate and the need for retreatment of ophthalmic segment aneurysms (OSA) treated by the pipeline embolization device (PED). The study also systematically assesses a crucial issue with the use of flow diverters namely the patency of the ophthalmic artery (OA).

Methods:
Forty-one patients harboring 44 OSA treated by flow-diversion and 95 patients with internal carotid artery (ICA) aneurysms who had one or more PEDs covering the OA and in whom angiographic follow-up was available were identified. Complication rates, the need for re-treatment, aneurysm occlusion rates, the evolution of visual symptoms, and the evolution of headache/retro-orbital pain were registered. The patency of the OA at follow-up was systematically evaluated by two investigators.

Results:
The technical success rate was 100% for OSA. The complication rate was 2.27% and the mortality rate was 0%. At final angiographic follow-up, 77.27% of patients with OSA had complete occlusion, 6.81% had near-complete occlusion, and 15.90% had incomplete occlusion. Of symptomatic OSA, complete resolution or significant improvement was noted in 72.72%, while worsening of symptoms occurred in 4.54%. Also, 22% of patients had no significant changes in their symptoms. Of 95 patients with ICA aneurysms, the OA was covered by 1 PED in 81 patients (85%) and by 2 PEDs in 14 patients (15%). Mean angiographic follow-up time was 7.5 months. At the latest follow-up, the OA remained patient in 85 patients (89%), showed diminished flow in 4 patients (4%), and was occluded in 6 patients (7%). Only one patient (1%) had clinical symptoms related to OA occlusion. In multivariable analysis, younger age, larger aneurysm size and coverage by more than 1 device predicted OA occlusion.

Conclusion:
Flow-diversion appears to be an appealing option for OSA. The PED also preserves the patency of the OA in most cases. The occlusion of the OA in the few cases where it occurs is usually a clinically irrelevant event. Minimizing the number of PEDs across the OA is a crucial factor to preserve its patency.
Abstract 113: Nuclear Translocation of Neuronal Histone Deacetylase 4 (HDAC4) is Detrimental in Stroke
Authors: Yuan Hui , Benashski Sharon , Denton Kyle , Li Xue-jun , McCullough Louise , Li Jun
Published: March 2022

HDAC4 has been identified as a transcriptional corepressor that catalyzes local histone deacetylation. It is highly expressed in neurons and usually trapped in cytosol. In vitro, translocation of HDAC4 from cytosol into nucleus induced neuronal death in response to glutamate toxicity. Here we assessed the hypothesis that accumulation of nuclear HDAC4 occurs after stroke, this translocation is detrimental in stroke outcome and regulated by calcium/calmodulin-dependent protein kinase IV (CaMK IV).

Wild type (WT) and CaMK IV knockout (KO) mice were subjected to transient middle cerebral artery occlusion and were sacrificed 6 hours for molecule assessments or 72 hours post stroke for outcome assessments. Primary cortical neurons underwent oxygen-glucose deprivation (OGD) and viability was measured 24 hours after OGD. Lentiviral vectors were utilized in culture and mice.

Stroke induced HDAC4 nuclear translocation in WT mice as assessed by both Western blots and immunohistochemistry. Knockdown of HDAC4 improved cell viability after OGD (HDAC4 SiRNA: 87.19±7.57% vs. control: 68.09±3.83%, p<0.05, n=6). Expression of a nuclear restricted HDAC4 mutant (Nuc) reduced cell viability after OGD (p<0.05), in contrast, no effect was seen for a cytoplasmic mutant HDAC4 (Cyto) (Nuc: 50.32±1.36% and Cyto: 68.95±2.17% vs. GFP control: 73.25±1.28%, n=6). In vivo nuclear HDAC4 mutant expression increased hemispheric infarcts (Nuc: 57.54±1.67% vs. Cyto: 36.98±3.26%) and worsened mice performance in rotarod test (Nuc: 12.38±3.50 seconds vs. Cyto: 33.65±2.98 seconds) compared with expression of cytoplasmic HDAC4 mutant after stroke (p<0.05, n=8-10). Percentage of nuclear HDAC4 positive neurons in penumbra was increased in CaMK IV KO mice (KO: 66.28±4.28% vs. WT: 37.08±2.44%, p<0.05, n=4) when compared to WT after stroke. Finally, overexpression of CaMK IV increased neuronal viability after OGD; however, this effect was lost when HDAC4 was inhibited by SiRNA.

In conclusion, we showed that ischemia induces HDAC4 nuclear shuttling in neurons and this translocation is deleterious in stroke outcome. Our data suggested CaMK IV inhibits HDAC4 nuclear accumulation in stroke.
Abstract 116: Matrix Metalloproteinase-9 Deletion Attenuates Blood-Brain Barrier Disruption and Consequent Injury in White Matter After Subarachnoid Hemorrhage
Authors: Egashira Yusuke , Hua Ya , Keep Richard F , Xi Guohua
Published: March 2022

Objective:
The detailed mechanism of white matter injury after subarachnoid hemorrhage (SAH) remains unclear. We hypothesized that blood-brain barrier (BBB) disruption occurs in white matter after SAH and it leads to consequent injury. In this study, we investigated the potential role of matrix metalloproteinase-9 (MMP9) in SAH-induced white matter injury.

Methods:
SAH was induced by endovascular perforation in male wild-type (WT) C57BL/6 and MMP9 knockout (MMP9-/-) mice. The following three experiments were devised: 1) to determine BBB disruption and MMP9 activation/expression in white matter, mice underwent MRI at 24 h after SAH. They were then euthanized for immunostaining, transmission electron microscopy and MMP zymography; 2) to investigate the role of MMP9 in BBB disruption, lesion volumes on MRI were compared between WT and MMP9-/- mice at 24 h after SAH; 3) WT and MMP9-/- mice underwent MRI at 1 and 8 days after SAH induction to detect time-dependent changes, and were euthanized at 8 days after SAH. Removed brains were used to investigate myelin integrity and axonal damage in the white matter.

Results:
In WT mice with SAH, albumin leakage along the white matter was increased (p<0.05; vs. sham) and was consistent with T2-hyperintensity on MRI (r=0.97, p<0.01). In microvessels, tight junction detachment and swollen astrocyte endfeet were demonstrated by electron microscopy. MMP9 activity was elevated in white matter at 24 h after SAH (vs. sham; p<0.05), and MMP9 was mainly expressed in astrocytes and oligodendrocyte precursors. The volume of T2-hyperintensity in the white matter in WT mice with SAH was 6.2 ± 3.0 mm3 (p<0.001; vs. WT sham), while that in MMP9-/- mice with SAH was significantly smaller (1.0 ± 1.4 mm3; p<0.01). At 8 days after SAH, decreased myelin integrity and an increased density of damaged axons were observed in WT with SAH mice compared to normal control mice (p<0.05; for each), while T2-hyperintensity on MRI in the white matter almost disappeared. MMP9-/- mice developed less of those injuries than WT mice at 8 days after SAH (p<0.05; for each).

Conclusions:
SAH causes BBB disruption and consequent injury in the white matter, and MMP9 plays an important role for those pathologies. MMP9 could be a therapeutic target for SAH-induced white matter injury.
Abstract 130: Impact of Time to Reperfusion in Endovascular Stroke Therapy on Outcome over the Entire Range of Disability
Authors: Sheth Sunil , Jahan Reza , Gralla Jan , Pereira Vitor M , Nogueira Raul , Zaidat Osama , Saver Jeffrey L
Published: March 2022

BACKGROUND:
Faster time from onset to recanalization (TTR) in acute ischemic stroke using endovascular therapy (ET) has been associated with better outcome. However, prior studies have analyzed only dichotomized disability outcomes, which may underestimate the full effect of treatment.

METHODS:
In the combined databases of the SWIFT and STAR trials, we identified patients treated with the Solitaire FR stent retriever with achievement of substantial reperfusion (TICI 2b-3). A multivariate linear regression model was used to assess factors associated with TTR.

RESULTS:
Among 195 patients treated with ET with TICI2b-3 reperfusion, average age was 68, 62% were female, NIHSS was 16, and premorbid mRS was 0 in 71% and 1 in 16%. Target occlusion location was ICA in 14% and M1 in 71%, and 56% received IV tPA. Median TTR was 304 min (IQR 198-436). Shorter TTR was associated with improved median 90-day mRS (1.4 vs. 2.3 vs. 3.3, for TTR groups of 124-240 vs. 241-360 vs. 361-648, p<0.001). Increased NIHSS was associated with increased likelihood of longer TTR (18 min delay per 5 point increase in NIHSS, p<0.05). Adjusted 90 days mRS outcomes for TTR time intervals ranging from 180 to 480 minutes showed reductions in disability across the entire outcome range (Figure). The number of patients identified as benefitting from therapy with shorter TTR were 3-fold (range 1.6-5.1) higher on ordinal compared with dichotomized analysis. For every 15 minute acceleration of TTR, 31 per 1000 treated patients had improvement in outcome by at least one mRS health state.

CONCLUSIONS:
Analysis of disability over the entire outcome range demonstrates a marked effect of shorter time to reperfusion upon improved clinical outcome, substantially higher than simple binary metrics. These findings emphasize the importance of accelerating endovascular reperfusion therapy.
Abstract 133: FACET: Fractal Angiography for Continuous Revascularization Evaluation during Thrombectomy
Authors: Scalzo Fabien , Thorenfeldt Christian , Sheth Sunil , Liang Conrad , Duckwiler Gary R , Liebeskind David S
Published: March 2022

Introduction:
The technical success of endovascular therapies in stroke may be visually evaluated with the Thrombolysis in Cerebral Ischemia score (0,1, 2A, 2B, 3), ranging from absent to complete downstream reperfusion. Subtle but possibly relevant reperfusion differences may not be detected with the observer dependent TICI score. The development of a quantitative and continuous measure to assess revascularization would provide a powerful tool to evaluate efficacy of clot retrieval. We present FACET, a fractal-based computational framework that can infer a continuous measure of revascularization from DSA.

Methods:
The DSA dataset used in this study was established retrospectively from patients treated with endovascular therapy for acute stroke. An expert reader manually delineated the MCA territory on the AP view of the angiogram using a region of interest (ROI) and TICI scores were obtained by consensus between 3 readers. The computational framework then processed each ROI to first extract the vessels using a vessel detector, followed by a skeletonization of the output responses that was used to compute the fractal dimension (FD). Evaluation was performed using nonlinear regression model to test the ability of the model in predicting degree of revascularization.

Results:
Among 97 patients included, 61 (63%) were female, mean age was 65.8 (range 22-93). TICI scores were distributed as [0:14, 1:5, 2a:31, 2b:40, 3:7]. FACET responses strongly correlated with TICI (r=.66, p <0.001) mapped to a continuous scale. In multivariate analysis, TICI 0 did not differ significantly from TICI 1 (p=.94) and 2a (p=.32), but did differ from group 2b (p<.0001) and 3 (p<.0001). Similarly, TICI 1 did not differ from TICI 2a (p=.46), but 2b (p<.0001) and 3 (p<.0001). Significant difference was found between TICI 2a and 2b, 3; but not between 2b and 3. Despite strong correlation, multivariate analysis of variance between TICI groups indicate non-strict equivalence between the TICI and FACET.

Conclusions:
FACET, or fractal analysis of DSA provides a continuous and objective measure that mirrors the TICI score and enables semi-automated high-throughput analysis of angiographic reperfusion.
Abstract 141: Leukoaraiosis is Associated with Impaired Functional Recovery and Outcome after Mild Ischemic Stroke
Authors: Onteddu Sanjeeva Reddy , Minaeian Artin , Goddeau Richard , Henninger Nils
Published: March 2022

OBJECTIVE:
To determine whether leukoaraiosis (LA) severity is an independent risk factor for impaired functional recovery and outcome after mild ischemic stroke.

METHODS:
We retrospectively analyzed data from 185 consecutive patients admitted to a single tertiary care stroke center with mild ischemic stroke (National Institutes of Health Scale [NIHSS] score ≤5). LA severity was graded from 0 (absent) to 4 (severe) using the van Swieten scale (VSS). LA was also dichotomized in 0-2 (absent to moderate) vs. 3-4 (severe). NIHSS was assessed at admission, discharge, and 90 days. Lastly, infarct volumes were measured in a subset of patients with available MRI (n=153). Multivariable ordinal logistic regression analyses were used to identify independent predictors of an excellent 90 days outcome (modified Rankin Score [mRS] ≤1).

RESULTS:
Severe leukoaraiosis was independently associated with a poor outcome in patients with mild ischemic stroke (OR 3.1, 95% CI 1.5-6.4; p=0.003; Figure 1A). Interestingly, patients with severe LA had smaller infarct volumes than those with absent to moderate LA (Figure 1B). Further, at the time of admission, NIHSS did not differ between LA-severities (Figure 1C). However, patients with severe LA had less complete improvement by 90-days as assessed by the NIHSS.

CONCLUSIONS:
Among patients with minor stroke sever LA is independently associated with a poor 90-day outcome despite having smaller infarct volumes and similar deficits at the time of presentation as patients with absent-to-moderate LA. Together with the observed less complete NIHSS-improvement these results indicate that LA negatively affects cerebral plasticity and recovery.
Abstract 147: Perceived Social Support is Related to Initial Severity of Post-Stroke Depression, but Not to Depression Improvement
Authors: Kammeyer Ryan , Daggy Joanne K , Schmid Arlen A , Williams Linda
Published: March 2022

Background:
Post-stroke depression (PSD) is a common occurrence after stroke, with multiple associated co-morbidities, and is often undermanaged. Perceived social support has been shown to be related to the presence of PSD; however, little is known about the relationship of social support and its specific dimensions to baseline PSD severity and depression improvement.

Methods:
We conducted a secondary analysis of data collected as part of a PSD cohort study in which depressed and non-depressed patients were matched 1:1 and enrolled at approximately one month post-stroke. PSD presence was assessed by a structured clinical interview, and PSD severity by the total PHQ-9 score. PSD improvement was measured at 12 weeks, and was defined as a PHQ-9 score < 5 or a decrease by at least 50% from baseline. We constructed multivariable regression models to assess the relationships between social support, as measured by the Medical Outcomes Study Social Support Survey (MOS-SSS) and its subscales, clinical and demographic covariates, and PSD presence, severity, and improvement.

Results:
Among 385 ischemic stroke patients (203 non-depressed and 182 depressed), baseline MOS-SSS scores were associated with initial PSD presence (OR: 0.987, 95% CI = [0.976, 0.998]), but were not predictive of PSD improvement at 12 weeks (OR: 0.997, 95% CI = [0. 983, 1.011]). The positive social interaction dimension of social support was a significant contributor to variance in baseline PSD severity in all study participants (semi-partial R2: 8.65E-3, p=0.03), especially in the depressed cohort (semi-partial R2: 2.66E-2, p=0.02).

Conclusions:
Self-reported social support was independently associated with the presence and severity of PSD one month post-stroke. However, we did not find a relationship between baseline social support and subsequent depression improvement independent of other clinical and demographic factors. This suggests that depression interventions may be effective even in patients with low initial social support. Positive social interactions, in the form of leisure or recreational activities, may help to prevent or attenuate initial PSD severity.
Abstract 160: Final Results of the Thrombolysis for Minor Ischemic Stroke With Proven Acute Symptomatic Occlusion Using TNK-tPA (TEMPO-1) Trial
Authors: Coutts Shelagh B , Dubuc Veronique , Mandzia Jennifer L , Kenney Carol , Patil Shivanand , Goyal Mayank , Hill Michael D ,   for the TEMPO-1 Investigators
Published: March 2022

Background:
Minor stroke and TIA with an intracranial occlusion are associated with a 20-30% risk of neurological deterioration and subsequent disability. TNK-tPA compared to alteplase is easier to administer, has a longer half-life, higher fibrin specificity and possibly a lower rate of intracranial hemorrhage. Therefore, it may be an ideal thrombolytic agent for recanalization in this population.

Methods:
TEMPO-1 was a multi-centre, prospective cohort, TNK-tPA dose-escalation, safety and feasibility trial. Patients with an NIHSS < 6, intracranial arterial occlusion on CTA, with no sign of well-evolved infarction who were treated within a 12h treatment window were enrolled. 50 patients were enrolled. The first 25 patients were treated at a dose of 0.1 mg/kg, and a second cohort of 25 patients treated at a dose of 0.25 mg/kg. Primary outcome was the rate of symptomatic intracranial (SICH) and extracranial hemorrhage. SICH was defined as a new ICH with ≥ 2 points worsening on the NIHSS. SITS-MOST definition of SICH was also assessed. Secondary outcomes include complete neurological (NIHSS 0-1) and functional (mRS 0-1) recovery at 90 days, recanalization at 4-8 h on CTA and minor bleeding.

Results:
Median baseline NIHSS was 2 (SD 1.24) and median age was 71 years (SD 18). Site of intracranial occlusions were: MCA-M1 (13), MCA-M2 (21), MCA-M3 (8), PCA-P1 (1), PCA-P2 (1) branches, vertebral artery/PICA (3) and undetermined (3). There was one SICH seen [2% (1/50), CI95 0.5%-10.6%], which was in the 0.25mg/Kg dose tier. There were no SICH by the SITS-MOST definition. For the 0.1mg/Kg dose tier recanalization between 4-8 hours post drug was complete in 21.7%, partial in 26.1% and no recanalization was seen in 52.2%. For the 0.25mg/Kg dose tier recanalization between 4-8 hours post drug was complete in 56.6%, partial in 13% and no recanalization was seen in 30.4%. 90-day disability and neurological outcome assessment will be available at the time of the International Stroke Conference.

Conclusion:
We have shown the safety and feasibility of thrombolysis with TNK-tPA in a minor stroke with intracranial occlusion population. Rates of recanalization are high in the 0.25mg/Kg tier and we have chosen this dose to proceed with a randomized controlled trial in this population.
Abstract 165: Microrna-126 Contributes to Human Umbilicus Cord Blood Cell Induced Neurorestorative Effects in Type Two Diabetes Mice
Authors: Chen Jieli , Ning Ruizhuo , Zacharek Alex , Cui Yicheng , Yan Tao , Roberts Cynthia , Kuzmin-Nichols Nicole , Sanberg Cyndy D , Chopp Michael
Published: March 2022

Introduction:
Human umbilical cord blood cell (HUCBC) treatment of stroke induces neurorestorative effects in non-diabetic rats. Whether HUCBC induces neurorestorative effects in type two diabetes (T2DM) has not been investigated. In this study, we tested the neurorestorative therapeutic effects and underlying mechanisms of action of HUCBC treatment of stroke in T2DM mice.

Methods:
BKS.Cg-m+/+Lepr
db
/J (db/db)-T2DM mice were subjected to extraluminal permanent distal MCAo (
dMCAo
) and were treated with: 1) PBS control; 2) HUCBC (1x10
6
) at 3 days after dMCAo. A battery of functional tests was performed. Mice were sacrificed at 14 days after dMCAo. Vascular and white matter (WM) changes and microRNA were measured.

Results:
HUCBC treatment of stroke in T2DM mice does not decrease lesion volume (12.7±3.0% vs control: 14.5±3.2%), but significantly improves functional outcome, increases axon (Bielschowsky silver), myelin (Luxol fast blue) and arteriolar (a-SMA) density in the ischemic boundary zone (IBZ) compared to T2DM-dMCAo control mice (p<0.05). To test the mechanisms of HUCBC induced neurorestorative effects, serum and ischemic brain miR-126 expression were measured. T2DM mice exhibit significantly decreased miR-126 expression in serum and in the IBZ compared to db+ (no-DM) control mice (p<0.05). While HUCBC treatment in T2DM mice significantly increased miR-126 expression compared to non-treatment T2DM mice. In vitro, we found that HUCBC secretes miR-126 enriched exosomes and also stimulates brain endothelial cell miR-126 expression. Co-culture of brain endothelial cells (BECs) with primary cortical neurons (PCNs) increases PCN axon outgrowth. Knockdown of miR-126 in BECs not only decreases capillary tube formation, but also decreases PCN axonal outgrowth compared to miR-126-/-Con-BECs (p<0.05). Knockdown miR-126 in HUCBC (miR-126-/-HUCBC) treatment of stroke in T2DM mice significantly decreases miR-126 expression in blood serum and attenuates HUCBC induced functional outcome after stroke in T2DM mice.

Conclusion:
HUCBC treatment initiated 3 days after stroke improves functional outcome, increases WM and vascular remodeling in T2DM mice. Increasing miR-126 contribute to HUCBC induced neurorestorative effects in T2DM.
Abstract 168: Intra-arterial Stem Cell Treatment Reduces Ischemic Brain Injury In Reproductively Senescent Female Rats
Authors: Yavagal Dileep R , Bhattacharya Pallab , Zhao Weizhao , Khan Aisha , Hare Joshua M , Perez-Pinzon Miguel A , Raval Ami P
Published: March 2022

Background:
Cell therapy is emerging as a promising treatment for stroke. We recently we demonstrated the efficacy of intra-arterial delivery of MSCs (IA MSCs) at 24h after a reversible middle cerebral artery occlusion (MCAo). Our study also identified a maximum tolerated dose of MSCs that could be delivered IA without compromising middle cerebral artery flow. The IA approach avoids first-pass trapping of MSCs in the lungs and liver as seen with intravenous delivery. Intra-arterial treatment is also minimally invasive and widely available in clinical practice and thus appealing for clinical translation. Since majority of ischemic strokes in women occur after onset of menopause it is crucial that we test the efficacy of IA MSCs in reproductively senescent females consistent with STAIR recommendations. We aimed to validate the efficacy of IA MSCs in reproductively senescent female rats. Methods: Retired breeder female (9-11 months; 280-350 g) Sprague-Dawley rats showing estrous acyclicity were exposed to MCAo (90 min). A day later, rats were treated with IA MSCs (1x10^5 cells) or phosphate-buffered saline (PBS). MSCs or PBS treated rats were sacrificed at 28-30 days for infarct volume measurement using histology. To test motor function, the rotarod test was performed. Rats were trained for 3 consecutive days for the rotarod test before undergoing the MCAo procedure. The mean duration (in seconds) on the device was recorded from 3 rotarod measurements 1 day before surgery. The rats were tested at 1, 7, 15 and 28-30 days after MCAo. Results: We observed significantly lower mean infarct volume in the MSC-treated group (12 ± 3 mm3; n=6) compared to the PBS-treated group (29 ± 7 mm3; Mean ± SEM; n=4, p<0.05). Treatment at 1 day after MCAO with MSCs significantly improved functional recovery, as evidenced by improved rotarod test results and neurological scores at 7, 15 and 30 days (P<0.05) compared with the PBS-treated group. Conclusions: Intra-arterial stem cell treatment reduces ischemic brain injury and improves functional outcomes in reproductively senescent female rats. Validating the efficacy of IA MSC treatment using a reproductively senescent animal stroke model suggests high potential for future clinical translation in a population at high risk for stroke.
Abstract 17: Development of High Risk TCD in Sickle Cell Disease
Authors: Adams Robert , Fullerton Heather , Kwiatkowski Janet , Voeks Jenifer
Published: March 2022

Background:
The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) as standard of care. Some information on conversion from low to high risk was derived from the STOP/2 studies but information is needed from “real world” practice to improve TCD screening guidelines.

Subjects and Methods:
During STOP and STOP2, 3,837 children, ages 2 to 16 y with SCD-SS or SCD-SBeta-0-thalassemia, underwent screening TCD. The POST-STOP study was designed to follow-up all children who participated in one or both of these trials. 19 of the 26 original study sites participated in POST-STOP, contributing a total of 3,541 (92%) of STOP/STOP2 subjects. Data abstractors visited the clinical sites to extract TCD, neuroimaging and neurological outcome information.

Results:
Of the 3,541 subjects, follow-up data were available for 2834 (80%). The mean age at the last TCD STOP/2study was 9.5 years, the mean age at last follow-up in POST-STOP was 19.6 years and the mean duration of follow-up after exiting STOP/STOP2 was 9.2 years. STOP TCD risk stratification was used: normal < 170 cm/sec; conditional 170-199 cm/sec; abnormal >200 cm/sec. Subjects were classified by their highest risk TCD in STOP/STOP 2. The population was divided on this basis into normal (1813 --64%), conditional (478 --17%), abnormal (357-- 13%) or inadequate (186 --7%). Among the 478 with conditional TCD studies in STOP/STOP2, the mean age at last follow-up in POST-STOP was 19.2 years (range 4.9-33.1) and follow-up TCD was obtained on 252 (53%) from 11 months to 16 years after STOP/2 (median 10.4) . Forty three of these had an abnormal TCD (mean age at abnormal was 8.5 years from 3 months to 8.4 years after STOP/2 (median 1.97 years).

Conclusions:

1) We could find evidence of follow up TCD for about of half of these children indicating that more needs to be done to insure regular and consistent surveillance of these children who have some elevated risk.

2) Conversions to abnormal TCD were documented. Treatment decisions as well as stroke outcomes for all the 479 with conditional TCD will be derived from adjudication of the complete data set (in progress).
Abstract 176: Perfusion Instability Impacts Tissue Outcome Beyond 6 Hours After Ischemic Stroke Onset
Authors: An Hongyu , Ford Andria L , Eldeniz Cihat , Chen Yasheng , Vo Katie D , Powers William J , Lee Jin-Moo , Lin Weili
Published: March 2022

Background:
During the first 24 hours after stroke, brain perfusion is highly dynamic. While early reperfusion can salvage tissue, it is unclear if late perfusion changes affect tissue fate. We examined perfusion changes between 6 and 24h after stroke onset and its impact on tissue outcome using a voxel-based approach.

Methods:
Mean transit time (MTT) and FLAIR maps were obtained in 27 ischemic stroke patients (median NIHSS: 14) at 3, 6, and 24h after onset to measure perfusion change; and at 1mo to assess tissue fate (dead or alive). MTT prolongation (pMTT) was calculated as: MTT - (median MTT of the non-ischemic hemisphere). At 2 time intervals (3-6h and 6-24h), perfusion change was classified into 3 categories: stable (|pMTT t1-t2| ≤ 2s), improved (|pMTT t1-t2| < -2s), or worsened (|pMTT t1-t2|>2s), pooling voxels from all patients. Infarct probability was plotted as a function of pMTT at 3h and 6h for stable, improved, or worsened perfusion.

Results:
Across the range of pMTT (0-22s), perfusion change was observed in a median of 76% (57% improved; 19% worsened) of tissue for 3-6h and 83% (66% improved; 17% worsened) of tissue for 6-24h. To determine the impact of dynamic perfusion on tissue fate, 3 infarct probability curves were plotted for improved (green), stable (blue), and worsened (red) perfusion between 3-6h (Fig A) and 6-24h (Fig B). As expected, early (3-6h) perfusion improvement or worsening impacted tissue fate for pMTT values 2-18s (yellow and purple region), likely representing penumbral tissue. Surprisingly, late perfusion change (6-24h) also influenced infarct probability, though its influence was restricted to milder pMTT of 2-14s (yellow region), suggestive of a closing therapeutic window.

Conclusions:
Late perfusion changes impacted tissue fate for pMTT 2-14s suggesting that regions of milder ischemia may have a longer therapeutic window than regions of more severe ischemia. Such tissue could be targeted for intervention beyond current treatment windows.
Abstract 180: Time and Tissue: Imaging of Early Ischemia in FAST-MAG
Authors: Liebeskind David S , Sanossian Nerses , Starkman Sidney , Villablanca Pablo , Burgos Adrian M , Scalzo Fabien , Johnson Mark S , Eckstein Marc , Stratton Sam , Pratt Frank , Conwit Robin , Hamilton Scott , Saver Jeffrey L ,   on behalf of the FAST-MAG Investigators
Published: March 2022

Background:
The NINDS FAST-MAG prehospital stroke trial treated patients in the field, providing unique perspective on the timecourse and tissue effects of ischemia. We characterized the presence of early ischemic changes (EIC) on initial imaging and the relationship with time in FAST-MAG.

Methods:
All subjects enrolled in FAST-MAG with a final diagnosis of TIA or stroke were included in our imaging analyses. Clinical and imaging variables in the final dataset were analyzed to establish the extent of EIC and the relationship of ASPECTS total and regional scores with respect to time.

Results:
Among 1245 cases of cerebral ischemia (mean age 69 (SD 13), median NIHSS 7 (IQR 2-15), 45% women), first brain imaging was obtained a median of 93 minutes (74-121) after last known well, 28 minutes (19-41.5) after arrival in the ED. EIC included loss of grey-white (27.1%), insular ribbon sign (19.6%), lentiform hypodensity (16.8%) and sulcal effacement (16.0%). ASPECTS score (mean 8.58 (SD 2.4), median 10 (IQR 8-10)) was calculated in 1240. Total ASPECTS exhibited a wide range (1-10), with regional involvement of caudate (2.3%), lentiform (14.7%), insula (23.1%), internal capsule (1.4%), M1 (21.4%), M2 (21.5%), M3 (14.1%), M4 (17.3%), M5 (16.2%) and M6 (9.8%). ASPECTS score was unrelated to time from symptom onset (r=0.008, p=0.77) across this relatively narrow early time period.

Conclusions:
Even in the earliest epochs after stroke symptom onset, a wide range of ischemic changes may be evident at imaging. Specific patterns of ischemia or regional predilection may be noted, but the timecourse of tissue changes may vary with each stroke patient.
Abstract 184: Clinical Outcomes According to Previous Intracranial Hemorrhage in Patients Receiving Intravenous Thrombolysis
Authors: Lee Sanghwa , Park Tai Hwan , Park Sang-Soon , Lee Soo Joo , Ko Youngchai , Lee Kyung Bok , Lee Jun , Park Jong-Moo , Kang Kyusik , Choi Jay Chol , Kim Dong-Eog , Ryu Wi Sun , Kim Joon-Tae , Choi Kangho , Cha Jae-Kwan , Kim Dae-Hyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi Sun , Cho Yong-Jin , Hong Keun-Sik , Kim Wook-Joo , Lee Juneyoung , Lee Ji sung , Shin Dong-Ick , Yeo Minju , Kim Beom Joon , Han Moon-Ku , Bae Hee-Joon
Published: March 2022

Objective:
This study aimed to describe clinical outcomes in patients treated with intravenous (IV) tPA according to evidence of previous Intracranial hemorrhage (ICH) and investigate the associations between previous ICH and clinical outcomes.

Methods:
Using a prospective multicenter stroke registry database, we identified acute ischemic stroke patients who were hospitalized to the 14 participating centers between January 2011 and July 2013 and were treated with IV tPA within 4.5 h of onset. Presence of previous ICH was screened using the formal radiologic reports or the clinical history of ICH from the registry database. If suspected, previous ICH was confirmed through direct review of brain MRI. As clinical outcomes, modified Rankin scale (mRS) 0-1 at discharge, mortality during hospitalization and symptomatic hemorrhagic transformation (sHT) were collected. sHT was defined according to the definition of SITS-MOST trial.

Results:
Among 1495 patients who were treated with IV tPA, 70 (4.7%) had evidence of previous ICH. sHT developed in 69 (4.6%) of all subjects; 7.1% (n=5) of 70 patients with previous ICH and 4.5% (n=64) of 1425 without previous ICH (p=0.25 on Fisher’s exact test). Hospital Mortality and mRS 0-1 at discharge was observed in 5.6% and 26.6% of all subjects and in 8.6% and 22.9% of those with previous ICH and 5.4% and 26.7% in those without it (p=0.28 on Fisher’s exact test and p=0.47 on Pearson’s chi-squared test, respectively). Multivariable logistic regression analysis with adjustment for age, initial National Institute of Health Stroke Scale, initial glucose and tPA dose showed that previous ICH was not associated with sHT, mortality during hospitalization and having discharge mRS 0-1 (p’s >0.4). Review of MRI on 5 patients who had previous ICH and developed sHT after IV tPA demonstrated that, in 4 cases, location of sHT was different from where previous ICH had developed, but in 1 case sHT occurred exactly where previous ICH had developed.

Conclusions:
This study shows that previous ICH may not increase the risk of sHT and death and aggravate functional outcome at discharge. However, it should be noted that the retrospective nature and small sample size of this study limit the generalization of its results.
Abstract 193: Cerebral Cavernous Malformation Location and Mode of Presentation Predict the Risk of Hemorrhage During Their Untreated Clinical Course: Individual Patient Data Meta-Analysis
Authors: Horne Margaret A , Flemming Kelly D , Su I-Chang , Stapf Christian , Brown Robert D , Christianson Teresa J , Agid Ronit , terBrugge Karel , Willinsky Robert , Maxwell Susanne , Murray Gordon D , Al-Shahi Salman Rustam ,   Cerebral Cavernous Malformation Individual PatientData Meta-Analysis Collaborators
Published: March 2022

INTRODUCTION:
Cerebral cavernous malformations (CCM) are the second commonest incidental finding on brain MRI and may cause symptomatic intracranial hemorrhage (ICH). However, the risk and predictors of ICH from CCM remain uncertain.

HYPOTHESIS:
Presentation with ICH or non-hemorrhagic focal neurological deficit (FND) attributable to CCM, brainstem CCM location, female sex, increasing age and multiple CCM predict ICH occurrence during follow-up without CCM treatment.

METHODS:
Three hospital-based cohorts and two cohorts from a population-based study provided individual patient data on clinical course from CCM diagnosis until either first CCM treatment or last available follow-up. We used survival analysis of each cohort to estimate the 5-year risk of symptomatic ICH or new FND, multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in meta-analysis.

RESULTS:
Among 988 adults who experienced 62 ICHs during 3,232 person-years of follow-up, clinical presentation with ICH or FND (hazard ratio [HR] 7.4, 95% confidence interval [CI] 2.9-19.2) and brainstem CCM location (HR 5.7, 95% CI 3.2-10.3) were associated with a higher risk of a first ICH within five years of CCM diagnosis, but age, sex and CCM multiplicity were not. The 5-year estimated risk of ICH during untreated follow-up was 2.4% (95% CI 1.0-3.8) for 566 adults without ICH/FND from CCM outside the brainstem, 5.5% (95% CI 0-12.9) for 51 adults without ICH/FND from brainstem CCM, 10.6% (95% CI 5.1-16.1) for 198 adults with ICH/FND from CCM outside the brainstem, and 25.7% (95% CI 18.3-33.1) for 173 adults with ICH/FND from brainstem CCM. In secondary analyses of first ICH or FND, event rates increased but predictors remained unchanged.

CONCLUSION:
Mode of clinical presentation and CCM location are independently associated with ICH or FND within five years of CCM diagnosis, which can inform decisions about CCM treatment.
Abstract 195: The Natural History and Predictive Factors of Hemorrhage from Choroidal (Intraventricular) Brain Arteriovenous Malformations
Authors: Sacho Raphael H , Saliou Guilaume , Tymianski Michael , Krings Timo , Terbrugge Karel
Published: March 2022

Background:
The natural history and risk of hemorrhage for patients harbouring choroidal/ intraventricular AVMs is poorly understood. We examined the impact of demographic and angiographic features on the likelihood of future hemorrhage.

Methods:
A prospectively maintained database from the Toronto Western Hospital was analyzed. Inclusion criteria were AVMS that were entirely intraventricular and supplied predominantly from choroidal arteries (anterior/ posterior). The rate of hemorrhage over long term follow up was calculated. The impact of baseline clinical and angio-architectural on time to hemorrhage were analyzed using survival analysis and compared with the total AVM population (n = 1018).

Results:
44 patients (median age 27, range 2 - 72 years) identified with choroidal AVMs (4.4% of all AVMs) were followed for 151 patient years. 36 patients (82%) presented with hemorrhage (vs 39% for all AVMs), 28 (77%) of which were predominantly intraventricular. Hemorrhage rates were 7.3%/ year (vs 1.7%/year for all AVMs, HR 2.3, p<0.001). The presence of venous reflux into thalamostriate or cortical veins was a significant independent risk factor for future hemorrhage (HR 1.80, p =0.047) with intranidal aneurysms not significantly associated with future hemorrhage risk (HR = 1.3, p =0.18).

Conclusion:
Choroidal AVMs are more likely to present with hemorrhage, particularly of the intraventricular type and are associated with approximately 2-fold greater likelihood of future hemorrhage, especially in the presence of venous reflux.
Abstract 198: Relationship Between 24 Hour Infarct Volume And Clinical Outcomes In IMS 3
Authors: Jovin Tudor G , Goyal Mayank , Modi Jayesh , Demchuck Andrew , Hill Michael , Idrif Sherief , Mahajan Aakash , von Kummer Ruediger , Khatri Pooja , Liebeskind David , Tomsick Thomas , Broderick Joseph
Published: March 2022

Background:
Prospective, core lab adjudication of 24 hour post randomization head CT in IMS3 enabled analysis of the association between 24 hour infarct volume (24HRIV) and clinical outcomes in patients randomized to IV tPA alone or IV/IA approach.

Methods:
Manually calculated volumes of hypodense areas deemed acute and found within the affected territory on the IMS 3 follow-up CT scans expressed in cc were termed 24HRIV. These were correlated with several variables of interest in the IMS3 database including clinical outcomes expressed as modified Rankin score (mRS), baseline NIHSS (bNIHSS), follow-up NIHSS at 24 hours (fNIHSS), treatment allocation and occlusion location assessed on baseline CTA.

Results:
Of the 656 randomized patients, 502 (76.5%) had available 24HRIV’s and were included in the analysis. Good outcomes (defined as mRS 0-2) were noted in 197 (39.2%) of patients. Mean (median) 24HRIV in patients with favorable outcomes was 24.2 (12.2) cc vs. 115 (75.11) cc in those with unfavorable outcomes (p< 0.00001). A strong correlation was noted between the 24HRIV and clinical outcomes across the entire spectrum of the mRS scale (Figure1). Mean (median) 24HRIV’s were not significantly different in the IV vs IV/IA group 76.8 (34.5) vs 84.8 (37.8) cc, p= 0.38. No differences in 24HRIV were noted between IV and IV/IA groups in patients with ICA occlusion on baseline CTA (mean 24HRIV 125.8 vs 123.8 cc's respectively, p=0.9) or MCA occlusion (mean 24HRIV 54.4 vs 54.6 cc's respectively, p=0.9). A strong correlation was found between 24HRIV and fNIHSS (spearman rho=0.7, p<0.0001).

Conclusions:
In IMS 3, a significant correlation between 24 hour infarct volume on CT and clinical outcomes both at 24 hours and at 90 days was demonstrated. No significant differences in 24 hour infarct volumes were noted between the IV and the IV/IA group, suggesting that endovascular reperfusion strategies utilized during IMS3 overall lacked added effectiveness compared to IV t-PA alone.
Abstract 2: Structural Integrity of the Corpus Callosum Correlates with Sensorimotor Impairment after Stroke
Authors: Dewanjee Pritha , Tran George , Stewart Jill C , Quinlan Erin B , Dodakian Lucy , McKenzie Alison , See Jill , Cramer Steven C
Published: March 2022

Introduction:
Responsiveness to motor rehabilitation varies greatly after stroke. Improved knowledge of the brain correlates of motor function are needed to assist in the development of more effective and personalized rehabilitation protocols. Changes in the integrity of the ipsilesional corticospinal tract after stroke have been well documented, but less is known about changes in the corpus callosum (CC). The purpose of this study was to determine if structural integrity of the motor and sensory portions of the CC change after stroke and whether any such changes are related to clinical measures of sensorimotor impairment and function.

Methods:
Fifty-five individuals with chronic stroke (age 60.5±13.2; days post-stroke 351.9±560; UE Fugl-Meyer (FM) motor score 38.5±14.6, no lesion in the CC) and 16 age-matched controls underwent diffusion tensor imaging (DTI) and behavioral assessments. Mean fractional anisotropy (FA) values for the motor and sensory regions of the CC were extracted and examined in relation to motor system behavioral measures including the UEFM, Box & Blocks (BB), Nottingham sensory score, and Stroke Impact Scale (SIS) hand subsection.

Results:
Participants with stroke had significantly lower FA values compared to controls in both the motor and sensory CC regions (
p
<0.02) despite their strokes sparing the CC. In the CC motor region, FA was related to UEFM, BB, and SIS scores, such that higher structural integrity correlated with better motor status (
ρ
>0.30,
p
<0.03 across comparisons). In the CC sensory region, FA was related to UEFM and SIS scores (
ρ
>0.31,
p
<0.02) as well as Nottingham sensory scores (ρ=0.33, p<0.05). CC motor and sensory FA did not correlate with FA in the ipsilesional peduncle (
ρ
<0.12,
p
>0.40), suggesting that the magnitude of change in each region of the motor system was distinct.

Conclusions:
Decreased structural connectivity between the sensorimotor regions of the two hemispheres is related to motor impairment in chronic stroke in a manner that is distinct from corticospinal tract injury. Interventions that target the communication between hemispheres during motor rehabilitation may be warranted.
Abstract 201: Effect of Endovascular Reperfusion in Relation to Site of Arterial Occlusion: A Pooled Analysis of Individual Patient Data
Authors: Lemmens Robin , Hamilton Scott , Liebeskind David , Tomsick Thomas , Demchuk Andrew , Nogueira Raul , Marks Michael , Jahan Reza , Tran Jennifer , Gralla Jan , Nonato James , Uppuluri Nagesh , Yoo Albert , Palesch Yuko , Mendes Pereira Vitor , Broderick Joseph , Saver Jeffrey L , Albers Gregory W , Lansberg Maarten G
Published: March 2022

Background:
Previous studies have shown an association between reperfusion and good clinical outcome, but it is unknown if this association differs depending on the site of the arterial occlusive lesion (AOL). We pooled individual patient data from prospective endovascular stroke studies to assess this.

Methods:
We included data from the endovascular arm of IMS III, a trial of intravenous (IV) thrombolysis alone versus IV thrombolysis and endovascular treatment; SWIFT, a trial comparing the Solitaire with the Merci device; STAR, a cohort study of patients treated with the Solitaire device; and DEFUSE 2, a cohort study of patients who received endovascular therapy. We compared the strength of the associations between reperfusion and clinical outcomes in patients with ICA, M1 and M2/3/4 (M2+) occlusions. The primary outcome was good functional outcome at day 90 defined as a modified Rankin Scale 0-2. Secondary outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH).

Results:
710 Patients were included in the analysis. The site of the AOL was ICA in 161, M1 in 389, and M2+ in 160 patients (M2=131, M3=23 and M4=6). The association between reperfusion and good functional outcome was stronger for patients with ICA occlusions (45% vs 19%; OR 3.5, 95%CI 1.7-7.2) and M1 occlusions (58% vs 18%; OR 6.2, 95%CI 3.8-10.2) than for patients with M2+ occlusions (53% vs 45%; OR 1.4, 95%CI 0.8-2.6) (p for difference in ORs=0.003). Mortality was reduced with reperfusion in patients with ICA (39% vs 18%; OR 0.4, 95%CI 0.2-0.7) and M1 occlusions (30% vs 10%; OR 0.3, 95%CI 0.2-0.5), but not in patients with M2+ occlusions (15% vs 15%; OR 1.0, 95%CI 0.4-2.3). Reperfusion was associated with fewer incidences of sICH without evidence of an interaction with AOL (OR 0.3, 95%CI 0.2-0.6).

Conclusion:
The association between endovascular reperfusion and improved clinical outcomes is more profound in patients with ICA and M1 occlusions than in patients with M2+ occlusions. This differential response to reperfusion has important implications for the design and power calculations of endovascular stroke trials.
Abstract 207: Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: The CRYSTAL-AF Study
Authors: Bernstein Richard A , Di Lazzaro Vincenzo , Rymer Marilyn M , Passman Rod S , Brachmann Johannes , Morillo Carlos A , Sanna Tommaso , Rogers Tyson , Ziegler Paul D , Diener Hans-Christof
Published: March 2022

Introduction:
The Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) trial showed that continuous cardiac monitoring with an insertable cardiac monitor (ICM) detected atrial fibrillation (AF) in patients (pts) with cryptogenic ischemic stroke (CS) at a rate approximately 7 times greater than standard monitoring, with AF detection rates of 12.4% at one yearand 30.0% at three years in the ICM arm. We hypothesized that among the CS pts who underwent continuous monitoring there would be a radiographic pattern of infarction (acute and/or chronic) associated with an increased likelihood of subsequent AF detection by 12 months.

Methods:
In this trial, 221 pts with recent CS confirmed by brain imaging were randomized to long-term continuous cardiac monitoring. The brain images, including 86 CT scans and 166 MRI scans, from 212 pts were available for review by a core lab to determine the distribution of acute and chronic lesions. Hazard ratios (HR) comparing pts with and without AF detected at 12 months were calculated for the imaging characteristics reviewed, and the log-rank test was used to determine significance.

Results:
Index infarctions (pts could have >1 infarction as their index event) were cortical (41.6%); subcortical (18.1%); both cortical and subcortical (21.7%); lacunar (24.4%); posterior circulation (8.1%); and internal border zone (0.9%). Old ischemic infarctions were found in 106 pts (48.0%), including leukoaraiosis in 31.7%. No acute lesion pattern was significantly associated with AF detection at 12 months. However, detection of AF was more frequent in pts having chronic infarcts (HR 2.84 [95% CI 1.13-7.15], p=0.02), with territorial old infarctions (HR 2.37 [95% CI 0.98-5.72], p=0.05) or leukoaraiosis (HR 2.94 [95% CI 1.28-6.71], p <0.01) contributing most to increased AF detection.

Conclusions:
In pts with CS who underwent continuous cardiac monitoring, no acute infarction pattern predicted detection of AF at 12 months. The presence of old infarcts was associated with detection of AF but the effect size was small. This suggests that long-term monitoring should be considered in all pts with CS as defined in CRYSTAL AF.