bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P9: SAMMPRIS, WASID, and the Non-Linearity of Stroke Risk: Is There Room for Further Trials of Intervention for Intracranial Stenosis?
Authors: Kung Nancy T , Damania Dushyant , Jain Minal , Jain Anunaya , Koch George E , Benesch Curtis , Jahromi Babak S
Published: July 2021

Background:
SAMMPRIS concluded that aggressive medical management (AMM) was superior to early percutaneous transluminal angioplasty and stenting (PTAS) plus AMM for patients with symptomatic severe intracranial stenosis. WASID and SAMMPRIS have shown that the risk of recurrent stroke after the initial event is early, non-linear, and markedly diminishes over one year irrespective of treatment. We therefore investigated the feasibility of demonstrating benefit for a new endovascular intervention (nEI) for these patients within this narrow time window.

Methods:
We compared 1-year stroke/death rates in patients treated with AMM versus a hypothesized nEI. The 1-year stroke/death rate for AMM was derived from the SAMMPRIS trial. A minimal 30-day stroke/death rate for a nEI was set to 3% using data from endovascular treatment of unruptured intracranial aneurysms. The subsequent stroke/death rate over the ensuing 11 months was varied above and below the rates achieved in SAMMPRIS, and the sample size for a future 1-sided superiority trial was calculated at 0.05 alpha and 80% power.

Results:
For a nEI with the same 31-365 days stroke/death rate as SAMMPRIS AMM (5.3%) but an improved 30-day stroke/death rate of 3%, a total of 1,484 subjects would be required to show significant benefit over AMM. At the SAMMPRIS recruitment rate of 187 patients/year, it would take 7.9 years to recruit 1,484 patients. Varying the 31-365 days stroke/death rate for nEI from 3% to 8%, and keeping 0-30 days stroke/death rate constant at 3%, (1 year total nEI stroke/death rate ranging from 6% to 11%), the total sample size required to show significant benefit at 1 year over AMM (1 year stroke/death rate of 12.2%) would be 518 and 17,600 respectively. This trial would take approximately 2.8 years and 94.1 years to recruit the eligible subjects at the SAMMPRIS rate, respectively.

Conclusion:
Identification of higher-risk subgroups, demonstration of decreased 30-day endovascular complication rates, and enhanced recruitment strategies will be necessary before institution of trials of new endovascular interventions for symptomatic intracranial stenosis.
Abstract W P95: Assessment of the Optimal Cell Number for the Trans-arterial Transplantation after Stroke in Rat
Authors: Fukuda Yutaka , Horie Nobutaka , Satoh Katsuya , Ishizaka Shunsuke , Hiu Takeshi , Nishida Noriyuki , Nagata Izumi
Published: July 2021

Introduction and Purpose:
Recently, cell transplantation have emerged as a promising treatment option for cerebral infarction in various kinds of animal models. However, optimal conditions (cell number, timing of cell transplantation, optimal route of delivery, best source of cells) remain unknown. The aim of this study was to clarify the optimal cell number for trans-arterial transplantation after stroke.

Methods:
Male Sprague-Dawley rats were subjected to an intraluminal occlusion of the middle cerebral artery (75 min.). At 24 hours post-stroke, we transplanted human mesenchymal stem cells (hMSCs) via carotid artery. The animals were divided into three groups, 1х10
6
hMSCs transplantation (n=8), 1х10
6
hMSCs transplantation (n=8) , and vehicle (n=8). Neurological recovery was assessed using modified neurological severity score (mNSS) and cylinder tests at day 0, 1, 2, 5 and 9 post-stroke in addition to body weight, lesion size, immune response, and hMSC distribution.

Results:
Rats treated with 1х10
6
hMSCs improved neurological recovery at day 5 (P<0.05), and day 9 post-stroke (P<0.05). Moreover, rats treated with 1х10
6
hMSCs cells showed further improvement at day 5 (P<0.01), and day 9 (P<0.05) compared with vehicle group. Transplantation of hMSCs (1х10
4
,1х10
6
) significantly showed less body weight loss at day 8 and 9 post-stroke (P<0.01), and revealed smaller lesion size at day 9 post-stroke (P<0.05). Interestingly, hMSC treated (1х10
4
, 1х10
6
) animals showed better engraftment of cells in the peri-infarct area, where immune response was significantly supressed (P<0.05).

Conclusion:
We found that trans-arterial transplantation with small amount of hMSCs could be sufficient to show functional recovery after stroke. These findings provide new information about optimizing cell number in trans-arterial transplantation after stroke, which is much beneficial especially for autologous transplantation.
Abstract W P98: Activation of α7 Nicotinic Acetylcholine Receptor Reduces Pro-Inflammatory Macrophage and Improves Ischemic Stroke Recovery
Authors: Han Zhenying , Shen Fanxia , He Yue , Degos Vincent , Camus Marine , Wankhede Mamta , Maze Mervyn , Young William L. , Su Hua
Published: July 2021

Background and Purpose:
Inflammation influences stroke recovery. Activation of α7 nicotinic acetylcholine receptor (α7 nAchR) attenuates inflammation. We hypothesize that α7 nAchR agonist treatment reduces pro-inflammatory macrophages (M1) and improves ischemic stroke recovery.

Methods:
C57BL/6 mice underwent permanent distal middle cerebral artery occlusion (pMCAO). They were randomly assigned to 7 groups: injected intraperitoneally with 0.4 or 0.8 mg/Kg PHA568487 (PHA, α7 nAchR agonist), 4 or 6 mg/Kg methyllycaconitine (MLA, α7 nAchR antagonist), or saline immediately after pMCAO, or with 0.8 mg/Kg PHA or 6 mg/kg MLA immediately and 24 hours after pMCAO. Behavior was assessed by corner and adhesive removal tests at 3, 7, and 14 days after pMCAO (n=12). Atrophic volume (n=7) and the percentage of total (CD68
+
) and M1 (CD11b
+
/Iba1
+
) macrophages (n=6) among total cells in the peri-infarct region were quantified 14 days after pMCAO. The expression of M1 (CD11b and iNOS) and M2 marker (CD206) were quantified using real-time RT-PCR (n=4).

Results:
Compared to the saline-treated mice, those treated with two doses of 0.8 mg/kg PHA performed better in both behavioral tests at 3 (adhesive: p=0.01, corner: p=0.02) and 7 (adhesive: p=0.005, corner: p=0.03) days, and in the adhesive removal test at 14 days (p=0.004) after pMCAO. They had smaller atrophic volume (16±7 mm
3
vs
26±5 mm
3
, p=0.008), and fewer total (9±2.5% vs 15.8±1.7%, p<0.001) and M1 (14±2.3% vs 20.6±4.2%, p=0.005) macrophages. Mice treated with two doses of 6 mg/kg MLA performed worse in the behavioral tests at all times (p<0.05), had larger atrophic volume (48±20 mm
3
, p=0.03), and more total (25±4.2%, p=0.0003) and M1 macrophages (28±4.5%, p=0.01). The expression of CD11b and iNOS decreased (p<0.05) in the PHA group, and increased (p=0.01) in the MLA group. CD206 expression increased (p=0.04) in the PHA group and did not change in the MLA group. One-dose treatment had no effect.

Conclusions:
Activation of α7 nAchR reduces pro-inflammatory macrophages in the peri-infarct region, which is associated with reduction of atrophic volume and improvement of behavioral recovery.
Abstract 10: The PROMIS Physical Function Scale- a Promising Scale for use in Stroke
Authors: Katzan Irene , Griffith Sandra , Fan Youran
Published: July 2021

Background:
Functional status is a critically important outcome measure after stroke. The ability to electronically capture this through self-report is increasing. The Patient Reported Outcomes Measurement Information System (PROMIS) uses computer adaptive testing (CAT), which can increase score precision and reduce patient burden. The number of questions depends on the patient’s responses. The objective of this study was to evaluate the performance of the PROMIS physical function scale (PROMIS PF) compared to the validated Stroke Impact Scale 16 (SIS16) in an ambulatory stroke clinic.

Methods:
Patient-reported PROMIS PF (CAT version) and SIS16 were electronically collected on patients seen in the stroke clinic using the Knowledge Program platform. Patient completion rates were > 70%. Distribution of scores was compared to assess ceiling/floor effects. Internal consistency was assessed by calculating the SEM for PROMIS PF and Cronbach’s alpha for SIS16. Correlations with NIHSS were performed to assess convergent validity.

Results:
The PROMIS PF and SIS16 were collected on 5,691 patients from Jan 2010 - May 2014. Mean SIS16 score = 81.4 (SD 21.5), mean PROMIS PF score = 42.8 (SD 11.2). The SIS16 had a22% ceiling effect, <1 % ceiling effect was seen with PROMIS PF (Figure). Patients completed 16 SIS16 items and a median of 4 [IQR 4, 5] PROMIS PF items. Cronbach’s alpha for SIS16 = 0.959, SEM for PROMIS PF = 2.3; both values suggest excellent internal consistency. Test-retest correlation was 0.867 for SIS16 and 0.87 for PROMIS PF. Correlations between NIHS and the 2 scales were -0.461 (p<0.001) for PROMIS PF and -0.559 (p<0.0001) for SIS16.

Conclusion:
The use of the PROMIS system to obtain electronic patient-reported functional status in ambulatory stroke clinic is feasible. PROMIS PF is an option for measurement of physical function in patients with stroke. It had similar test characteristics as the SIS16 but with lower patient burden and no ceiling effect.
Abstract 105: Time for Collaterals? Evidence from 695 Endovascular Therapy Cases for Acute Stroke in ENDOSTROKE
Authors: Liebeskind David S , Berkefeld Joachim , Nolte Christian H , Bohner Georg , Niederkorn Kurt , Deutschmann Hannes , Gröschel Klaus , Boor Stephan , Neumann-Haefelin Tobias , Hofmann Erich , Reich Arno , Wiesmann Martin , Stoll Anett , Bormann Albrecht , Weimar Christian , Schlamann Marc U , Haring Hans-Peter , Trenkler Johannes , Bussmeyer Matthias , Mpotsaris Anastasios , Scalzo Fabien , Jander Sebastian , Turowski Bernd , Singer Oliver C ,   for the ENDOSTROKE Study Group
Published: July 2021

Background:
Recent stroke clinical trials demonstrate the profound impact of collaterals, yet time constraints are often cited as rationale for not evaluating or imaging collaterals prior to endovascular therapy (EVT). We examined the role of collaterals on patient outcomes in a large registry of EVT, analyzing actual time required to obtain such data before treatment of various occlusion sites and monitoring for potential harm.

Methods:
ENDOSTROKE is an industry-independent, centrally-monitored multicenter registry evaluating EVT in routine clinical practice. Central reading of angiographic data blinded to clinical information was performed by the core lab in 695 patients assessing TICI scores, ASITN collateral grade and detailed procedural time metrics.

Results:
75% had anterior circulation strokes (including 270 proximal MCA, 106 ICAT, 90 cICA occlusions) and 25% posterior circulation strokes (including 148 basilar artery occlusions). Assessment of ASITN collateral grade was possible in 511 (73%) of patients; in 184 (27%) collateral status was not obtained prior to therapeutic intervention. Median time from initial angiography and first evidence of TICI 2A reperfusion was only one minute longer in patients with available ASITN scores than in those without (38 min (23, 61) vs. 37 (22, 55), p=0.552) and time-differences were even smaller in anterior circulation strokes (median time 37 min in both groups). In vertebrobasilar occlusion, this time metric was 5 minutes longer in those with available ASITN scores (39 min (24, 39)) than in those without (34 min (23, 52), p=0.357). Of those with ASITN available, patients with grade 3-4 had much better outcomes (48% 0-2 90-day mRS) than patients with grade 0-2 (30%, p<0.0001). No excess in complication rate (i.e. dissection, thrombemboli) was noted in the cohort with available ASITN.

Conclusions:
Collaterals have a dramatic association with clinical outcomes in the largest endovascular study to date. In routine practice, EVT outcomes across various occlusion sites are strongly influenced by collateral grade. Negligible time of only a few minutes is typically required to obtain such essential data prior to treatment with no cost of incremental harm.
Abstract 112: Hydrocoils Reduce Recurrence Rates in Recently Ruptured Medium Sized Intracranial Aneurysms: A Subgroup Analysis of the HELPS Trial
Authors: Brinjikji Waleed , White Phil M , Cloft Harry J , Kallmes David F
Published: July 2021

Background and Purpose:
The Hydrocoil Endovascular aneurysm occlusion and Packing Study (HELPS) was a randomized controlled trial comparing Hydrocoil to bare platinum coils . We performed a subgroup analysis of angiographic and clinical outcomes of medium sized aneurysms in the HELPS trial.

Methods:
We selected all patients with medium sized aneurysms (5mm-9.9mm) in the HELPS trial. The following outcomes were compared between the HydroCoil and control groups: 1) any recurrence, 2) major recurrence, 3) retreatment and 4) good neurological outcome defined as mRS≤2. Outcomes of recently ruptured and non-recently ruptured aneurysms were compared separately. Comparisons between groups were performed using Fisher’s exact test. A multivariate logistic regression analysis adjusting for aneurysm neck size, shape, use of adjunctive device and rupture status was performed.

Results:
A total of 288 patients with medium sized aneurysms were randomized (144 in each group). At 15-18 months post-treatment, major recurrence rate was significantly lower in the HydroCoil group than the control group (18.6% versus 30.8%, P=0.03, respectively). For recently ruptured aneurysm patients, major recurrence rate was significantly lower for HydroCoil than controls (20.3% versus 47.5%, P=0.003), while rates were similar between coil types for unruptured aneurysms (16.7% versus 14.8%, P=0.80). On multivariate analysis for patients with recently ruptured aneurysms, HydroCoil was associated with lower odds of any recurrence as compared to bare platinum (OR=0.37, 95%CI=0.18-0.76, P=0.006) and major recurrence (OR=0.27, 95%CI=0.12-0.58, P=0.0007). There was a trend towards lower retreatment rates in the recently ruptured group treated with HydroCoil (OR=0.00, 95%CI=0.00-2.01, P=0.12).

Conclusion:
For recently ruptured, medium sized aneurysms, as compared to bare platinum coils HydroCoils were associated with lower rates of major recurrence that were both statistically significant and clinically relevant. These findings suggest that HydroCoils should be the preferred treatment for this subset of patients.
Abstract 119: Apoe-ɛ4 Is Associated With Cerebrovascular Insufficiency, Increased Susceptibility to White Matter Injury and Cognitive Dysfunction
Authors: Koizumi Kenzo , Park Laibaik , Zhao Lingzhi , Luo Wenjie , Paul Steven M , Iadecola Costantino
Published: July 2021

ApoE-ɛ4 (apoE4) is a risk factor for white matter ischemic lesions (Neurology 81:292, 2013) and Alzheimer’s disease (Neuron 63:287, 2009). However, the underlying mechanisms remain to be defined. We tested the hypothesis that the apoE4 allele is associated with alterations in the regulation of the cerebral circulation and increased white matter susceptibility to ischemic injury. To this end, we used human ApoE targeted replacement mice (Sullivan et al., JBC, 272:17972, 1997) in which cerebral blood flow (CBF) was measured by laser-Doppler flowmetry in the somatosensory cortex under anesthesia (n=5/group; age 4 mo.). In apoE4 mice, the increase in CBF produced by whisker stimulation (WS) or by topical application of the endothelium-dependent vasodilator acetylcholine (ACh) was attenuated (WS, -48%; ACh, -39%; p<0.05; mean±SE). Next, we asked if this neurovascular dysfunction increases the propensity of apoE4 mice to develop white matter ischemic lesions. White matter hypoperfusion was induced in the corpus callosum by bilateral carotid artery stenosis (BCAS) with microcoils for 4 weeks. BCAS led to more severe white matter injury in apoE4 than in apoE3 mice. Thus, BCAS reduced myelin density more in apoE4 (10±1 relative fluorescence units) than in apoE3 mice (15±1), a reduction of 33% (p<0.05). Furthermore, the axonal nodal structure, assessed by the NaV1.6/caspr index, was disrupted in apoE4 mice (normal index 0.5; BCAS apoE3: 0.58±0.13; BCAS apoE4: 1.05±0.13; p<0.05 from apoE3). BCAS induced impairments in spatial memory in the Y-maze test (arm alternation rate), an effect worse in apoE4 (43±3%) than apoE3 mice (52±3) (p<0.05). These findings suggest that the apoE4 allele is associated with cerebrovascular dysfunction, which leads to more severe white matter damage and cognitive deficits following exposure to chronic cerebral hypoperfusion. Cerebrovascular alterations in apoE4 carriers may play a role in the cognitive impairment associated with vascular risk factors and in the ischemic pathology associated with Alzheimer's disease.
Abstract 123: Door To Needle 60, Creative Solutions in Academia
Authors: Ruff Ilana M , Liberman Ava L , Caprio Fan Z , Sachdeva Kapil , Bergman Deborah L , Bernstein Richard A , Curran Yvonne , Patel Paras , Khare Rahul K , Malik Sanjeev , Prabhakaran Shyam
Published: July 2021

Introduction:
National guidelines endorse that eligible acute ischemic stroke (AIS) patients should be treated with intravenous tissue plasminogen activator (IV tPA) within 60 minutes of arrival to an emergency department (ED). We participated in the American Heart Association’s Target: Stroke program which successfully reduced door to needle (DTN) times through 10 best practices, but academic hospitals face a unique challenge as junior residents evaluate and manage AIS patients. We hypothesized that a “stroke boot camp” could improve resident efficiency during stroke codes and shorten DTN times through faster stroke code to tPA times.

Methods:
A neurology resident educational protocol was developed and implemented in April 2013 using a Socratic case-based discussion to emphasize focused history and exam, medication history, and tPA exclusion criteria. We distributed cards with IV tPA risks/benefits and a checklist for tPA exclusion criteria. We compared pre-intervention (January 2010-April 2013) to post-intervention (April 2013-April 2014) patient demographics, comorbidities, resident level, relevant times, and outcomes using appropriate tests.

Results:
We analyzed 122 consecutive AIS patients treated with IV tPA in our ED during the study period. Pre and post intervention groups did not differ by demographics except gender (p = 0.005). There were no difference in comorbidities, baseline NIHSS, or resident post graduate year (PGY). After the intervention, stroke-code-to-tPA was significantly reduced (75 min vs. 45 min; p < 0.001), whereas door-to-stroke-code (7 min vs. 6 min, p = 0.56) and door-to-CT (18 min vs. 19 min, p = 0.44) did not change. The proportion of patients treated within 60 minutes increased (16.4% vs. 51.4%, P < 0.001) and median DTN time decreased (81 min vs. 60 min P < 0.001) significantly after the intervention. Time reductions were consistent across PGY levels without increased adverse outcomes.

Conclusion:
Reduction in stroke code-to-tPA times after implementation of a “stroke boot camp” led to a significant reduction in DTN time. Focused neurology resident acute stroke education should be implemented at academic institutions to improve rapid IV tPA administration
Abstract 131: MR-based Selection for Endovascular Therapy in Acute Ischemic Stroke With ICA or MCA Occlusion : Propensity Score Matched Analysis From RESCUE-Japan Registry
Authors: Miyazaki Yuichi , Yamagami Hiroshi , Toyoda Kazunori , Enomoto Yukiko , Okada Yasushi , Kitagawa Kazuo , Kimura Kazumi , Tanahashi Norio , Hyogo Toshio , Sakai Nobuyuki , Yosimura Shinichi
Published: July 2021

Objective:
To identify optimal criteria for MR-based endovascular therapy (EVT) in acute ischemic stroke with the internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion.

Materials and methods:
From RESCUE-Japan registry, a prospective nation-wide survey of acute ischemic stroke with large vessel occlusion, 996 patients diagnosed with ICA or MCA occlusion by initial MRA and assessed with DWI-ASPECTS were included in the present study. We used a propensity score matching method to create a well-balanced cohort to reduce confounding by indication of EVT. Propensity score was calculated using the following variables: sex, age, initial NIHSS score, Onset-to-Door time, DWI-ASPECTS, occluded site on MRA (categorized into four groups, ICA/proximal M1/distal M1/M2 or distal) and IV-tPA. Favorable outcome defined as modified Rankin Scale of 0 to 2 at 90 days after stroke onset was compared between the propensity score-matched groups.

Results:
Propensity score matching yielded a well-balanced cohort of 528 patients (264 pairs with and without EVT). In this cohort, there was no significant difference in favorable outcome between the patients with and without EVT (33.7% vs 29.2%, OR 1.25, 95% CI 0.855 - 1.81, p=0.25). However, in the subgroup with ICA/proximal M1 occlusion, the patients with EVT more often achieved favorable outcome than the patients without EVT (33.5% vs 17.7%, OR 2.35, 95% CI 1.41 - 3.97), and there was a significant interaction between the cohorts with ICA/proximal M1 occlusion and distal M1/M2 or distal occlusion (p for interaction < 0.001). Further subgroup investigations showed that this effect was concentrated in the patients with NIHSS of 8 to 29 and DWI-ASPECTS of 4 or more (OR 3.28, 95%CI 1.74 - 6.48, p for interaction=0.066). With respect to Onset-to-Door time, optimal threshold was not obtained.

Conclusions:
MR-based EVT did not show clinical benefit in the overall study population, but significant increase in favorable outcome in the patients with ICA or proximal M1 segment of MCA occlusion. NIHSS of 8 to 29 and DWI-ASPECTS of 4 or more were thought to be optimal thresholds as additional inclusion criteria.
Abstract 137: Noninvasive Fractional Flow on MRA and Recurrent Stroke: SPS3 Trial
Authors: Nakajima Makoto , Ohara Nobuyuki , Pearce Lesly A , Feldmann Edward , Bazan Carlos , Liebeskind David S , Hart Robert G , Benavente Oscar R
Published: July 2021

Background and Purpose:
Noninvasive fractional flow reserve (FFR) on time-of-flight magnetic resonance angiography (TOF-MRA) may be used to identify high-risk intracranial lesions. We tested whether FFR was associated with vascular territory of the qualifying lacunar stroke in participants of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and the utility of FFR for predicting recurrent stroke during the trial.

Methods:
SPS3 was a randomized trial investigating optimal blood pressure target and antiplatelet regimen in patients with recent, symptomatic, MRI-confirmed lacunar stroke patients TOF-MRA proximate to study entry was adequate and available for 2169 of 3020 study patients. Signal intensity (SI) was measured in the background, and proximal and distal aspects of 7 intracranial arteries (internal carotid, middle cerebral, basilar, and vertebral). Adjusted FFR was then calculated in each artery: FFR = [distal SI - background SI] / [proximal SI - background SI] and divided into quartiles by artery. Associations between the vascular territory of the qualifying infarct and the FFR quartile of the relevant artery were investigated using contingency tables and chi-square tests. Risks for recurrent stroke associated with FFR quartiles were evaluated using Cox Proportional Hazards models (model adjusted for assigned treatment groups).

Results:
Mean age of the 2169 patients included was 63 yr with 63% male; hypertension, diabetes, and prior lacunar stroke were present in 75%, 36%, and 10% respectively. Median FFRs varied by artery with the lowest in the basilar (0.793) and highest in the middle cerebral arteries (left 1.154; right 1.176). A recurrent stroke occurred in 195 patients during a mean follow-up of 3.5 years (annualized rate 2.5% per patient-year).No significant association was found between the FFR tertiles and the vascular territory of the qualifying infarct. Quartiles of adjusted FFR in any of the 7 arteries were not found to be predictive of recurrent stroke.

Conclusion:
In this large well-characterized cohort of lacunar stroke patients, FFR was not associated with the location of the qualifying subcortical infarct and did not predict the risk of recurrent stroke.
Abstract 138: Perfusion Imaging of Intracranial Atherosclerotic Disease in SAMMPRIS
Authors: Liebeskind David S , Derdeyn Colin P , Sanossian Nerses , Cotsonis George A , Scalzo Fabien , Prabhakaran Shyam , Romano Jose G , Turan Tanya N , Johnson Mark S , Lynn Michael J , Fiorella David J , Hess David C , Chimowitz Marc I , Feldmann Edward ,   on behalf of the SAMMPRIS Investigators
Published: July 2021

Background:
Noninvasive perfusion imaging with CT (CTP) or MRI (PWI) provides key physiologic data regarding hemodynamics of intracranial atherosclerotic disease (ICAD). Parameters of delayed perfusion such as Tmax, time to peak (TTP), mean transit time (MTT) and cerebral blood volume (CBV) or flow (CBF) may disclose important mechanisms of stroke in ICAD. We analyzed CTP and PWI acquired in SAMMPRIS to identify the principal perfusion patterns, correlation with conventional angiography and potential links with clinical outcome.

Methods:
CTP and PWI were identified in the SAMMPRIS imaging archive. Perfusion datasets were processed with Olea Sphere® to yield Tmax, TTP, MTT, CBV and CBF maps graded by 2 expert readers to identify markers of decreased, normal, or increased perfusion in the symptomatic territory. The resultant multiparametric perfusion patterns were correlated with clinical and angiographic variables, using Fisher’s exact test and Kaplan-Meier methods followed by log-rank tests.

Results:
Perfusion imaging was available in 59 subjects at baseline and 42 at follow-up. Baseline perfusion included Tmax (decreased in 2, normal in 18, increased in 39); TTP (decreased in 2, normal in 18, increased in 39); MTT (decreased in 2, normal in 27, increased in 30); CBV (decreased in 5, normal in 42, increased in 12); CBF (decreased in 7, normal in 48, increased in 4). The baseline Tmax increases in 66% of subjects were associated with the combined (TICI and collaterals) diminished angiographic flow patterns (p=0.016) and with increased 30-day SIT (p=0.015). Baseline CBV changes were associated with stroke as a qualifying event (p=0.007), NIHSS (p=0.039), presenting symptoms of hypoperfusion (p=0.071), severity of stenosis (p=0.015), and angiographic flow patterns (p=0.009). Follow-up CTP or PWI revealed similar patterns to baseline, although delay maps normalized in patients after stenting.

Conclusions:
Noninvasive perfusion imaging with CT or MRI discloses delayed flow caused by ICAD, often compensated by autoregulatory vasodilation (increased CBV) to maintain CBF in the downstream territory. Perfusion imaging parameters may reflect angiographic collateral flow patterns in ICAD, warranting further investigation as predictors of stroke risk.
Abstract 139: Future Clinical Tools: Carotid Plaque Characterization via Shear Wave Elastography - A Phantom Study
Authors: Widman Erik , Maksuti Elira , Urban Matthew , Caidahl Kenneth , Larsson Matilda
Published: July 2021

Introduction:
Shear Wave Elastography (SWE) is a recently developed noninvasive method for elastography assessment using ultrasound. The technique consists of sending an acoustic radiation force into the tissue that in turn generates an orthogonal low frequency propagating shear wave. The shear wave propagation speed, which is calculated from B-mode images, is correlated to the tissues mechanical properties. Currently, SWE is primarily used in breast and liver to detect tumors easily missed with normal B-mode ultrasound. SWE could potentially aid in the characterization of plaques in the carotid artery, which is critical for the prevention of ischemic stroke.

Methods:
Six polyvinyl alcohol (PVA) phantoms were created with soft and hard plaque mimicking inclusions. The plaques were excited with acoustic radiation force and the shear wave was measured using high speed B-mode imaging. The data was post-processed with a custom in-house algorithm fitting a model of a Lamb wave propagating through a plate to the shear wave dispersion curve, which allowed the shear modulus to be estimated. The results were validated by measuring the phantom plaque shear modulus with mechanical testing.

Results:
SWE measured a mean shear modulus of 6 ± 1 kPa and 106 ± 17 kPa versus 3 kPa and 95 kPa measured by mechanical testing in the soft and hard plaques respectively. The results show good agreement between the shear modulus measured with SWE and mechanical testing. In this study simplified homogenous phantom plaque models were examined in a static experimental setup with results validated by mechanical testing. Algorithm improvements for measurements in a dynamic environment are being developed for a future in vivo pilot study.

Conclusion:
The results show good agreement between the shear modulus measured with SWE and mechanical testing and indicate the possibility for an in vivo application.
Abstract 151: Vascular Events Occur More Frequently In Stroke Patients With Lower Concentrations of Vitamin D: A Prospective Cohort Analysis
Authors: Khoo Sebastian K , Tan Jayne Y , Yeo Leonard Y , Paliwal Prakash , Teoh Hock L , Chan Bernard P , Sharma Vijay K , Chan Yiong Huak , Seet Raymond C
Published: July 2021

Introduction:
Vitamin D deficiency has been implicated in vascular dysfunction and the risk of recurrent vascular events. Previous studies, limited by a small sample size and lack of comparisons with long-term events, have yielded discordant results. To assess the hypothesis that low vitamin D levels predict long-term vascular events in patients with ischemic stroke, we conducted a large hospital-based study to compare the association between baseline vitamin D levels and the subsequent risk of vascular events.

Methods:
Between January 2010 and July 2011, 590 participants (mean age, 60.7 years; 69% men) diagnosed with ischemic stroke and transient ischemic attack at the National University Hospital, Singapore, were prospectively followed for vascular events (recurrent stroke, myocardial infarction and vascular death). Serum 25-hydroxyvitamin D levels were determined using the Roche Cobas e411 analyzer. Cox proportional hazards models were used to assess the associations between quartiles of serum 25-hydroxyvitamin D and the risk of vascular events, which were adjusted for demographic, stroke severity and subtype, and vascular risk factor covariates.

Results:
During a mean follow-up of 3.2 years (1,190 person-year), 116 participants developed a recurrent vascular event (recurrent stroke, n=63; myocardial infarction, n=30; vascular death, n=23). Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval) for recurrent vascular events in participants with lower levels of serum 25-hydroxyvitamin D (<14.9 mmol/l, 14.9-21.4 mmol/l and 21.5-28.9 mmol/l) were 1.43 (0.81-2.55), 1.70 (0.97-2.91) and 2.09 (1.22-3.58) compared to participants with higher concentrations (>28.9 mmol/l). Kaplan-Meier plots for unadjusted rates of vascular events show clear differences in risk by quartiles of serum 25-hydroxyvitamin D after a year of follow-up.

Conclusions:
Our results support the association between vitamin D deficiency and increased risk of recurrent vascular events in patients with ischemic stroke. Clinical trials are needed to ascertain whether correcting for this deficiency could indeed reduce the burden of vascular events in these individuals.
Abstract 159: Treatment with Intravenous Tissue Plasminogen Activator in the “Golden Hour” in the National US Get With The Guidelines-Stroke Population
Authors: Saver Jeffrey L , Fonarow Gregg C , Smith Eric E , Reeves Mathew J , Navalkele Digvijaya , Grotta James C , Grau-Sepulveda Maria , Hernandez Adrain F , Peterson Eric D , Schwamm Lee H
Published: July 2021

Background:
Innovations in prehospital and Emergency Department systems of care increasingly enable IV tissue plasminogen activator (tPA) delivery in the first 60 minutes after onset, a time window not tested in placebo-controlled clinical trials. We sought to characterize efficacy and safety outcomes when tPA is delivered in the “golden hour.”

Methods:
We analyzed 65,384 acute ischemic stroke patients treated with tPA within 4.5 hours of symptom onset in 1456 hospitals participating in GWTG-Stroke from Jan 2009 to Sept 2013. Multivariable logistic regression modeling was employed to evaluate the independent impact of treatment within 60 minutes of onset on outcome.

Results:
878 patients (1.3%) received lytic therapy within 60 minutes of onset, versus 6490 (9.9%) in 61-90m, 46,457 (71.1%) in 91-180m, and 11,559 (17.7%) in 181-270m. Independent patient-level factors associated with treatment in the golden hour were older age (aOR 1.15 per 5 years over age 65), higher NIHSS (aOR, 1.04 per scale point), non-EMS arrival (aOR 1.59), and arrival during on hours (aOR 1.61). Hospital level predictors were higher tPA volume (aOR 1.08 per 5 cases), non-PSC (aOR 1.27), and Western region (aOR 1.38 vs Northeast). Compared with the 61-270m window, treatment within 0-60m was associated with increased independent ambulation at d/c, aOR 1.22 (95% CI 1.03-1.45); discharge to home, aOR 1.25 (1.07-1.45); and being disability-free at d/c, aOR 1.72 (95% CI 1.21-2.46, mRS 0-1). No differences were noted in in-hospital mortality or SICH. Considering all discharge mRS transitions, golden hour treatment showed greatest impact at mRS 0-1 vs 2-6 (Figure).

Conclusions:
Ischemic stroke treatment with IV tPA in the golden hour is associated with more frequent independent ambulation at discharge, discharge to home, and, especially, being disability free at discharge. These findings support intensive efforts, including Target: Stroke and prehospital thrombolysis, to speed treatment initiation.
Abstract 170: Luminal Neovascular Sprouting with Inflammation Contributes to Symptomatic Intraplaque Hemorrhage in Carotid Stenosis
Authors: Horie Nobutaka , Morofuji Yoichi , Morikawa Minoru , Yamaguchi Susumu , Tateishi Yohei , Izumo Tsuyoshi , Hayashi Kentaro , Tsujino Akira , Nagata Izumi
Published: July 2021

Background and Purpose:
Neovascularization of carotid plaques is associated with plaque vulnerability. However, the role of neovascularization in the development of intraplaque hemorrhage (IPH) and the clinical contribution of neovascularization to IPH and symptomatic presentation remain undetermined.

Methods:
Consecutive patients with moderate to severe carotid atherosclerosis who underwent carotid endarterectomy were prospectively analyzed from 2010 to 2014. The neovessel appearance was categorized into three groups based on dynamic intraoperative indocyanine green videoangiography: neovessels derived from the endothelium (NVe), neovessels derived from the vasa vasorum (NVv), and no neovessels. Each neovessel pattern was evaluated with respect to clinical, radiological, and pathological findings.

Results:
Of 57 patients, 13 exhibited NVe, 33 exhibited NVv, and 11 exhibited no neovessels. There were no significant differences in baseline characteristics among the three groups with the exception of a higher percentage of symptomatic presentations among patients with NVe. Moreover, patients with NVe exhibited larger infarctions than did those with NVv (P=0.04). Pathologically, patients with NVe had more severe IPH (P=0.002), hemosiderin spots (P=0.04), neovessels (P=0.11) and inflammation (P=0.26), all of which were correlated with hyperintensity on time-of-flight magnetic resonance imaging. Interestingly, inflammation was significantly correlated with neovessel formation (R=0.43, P=0.008), hemosiderin spots (R=0.62, P<0.0001), and IPH (R=0.349, P=0.0097), suggesting that inflammation may be a key factor in plaque vulnerability.

Conclusions:
Luminal neovascular sprouting with inflammation and lumen communication could clinically contribute to IPH and symptomatic presentation in patients with carotid stenosis. This condition may thus be a key therapeutic target against neovessel formation and inflammation.
Abstract 179: International Survey of Clinical Case Vignettes in Acute Ischemic Stroke
Authors: Luby Marie , Warach Steven J , Albers Gregory W , Cognard Christophe , Donnan Geoffrey A , Fiebach Jochen B , Hacke Werner , Lansberg Maarten G , Liebeskind David S , Mattle Heinrich P , Oppenheim Catherine , Schellinger Peter D , Wardlaw Joanna M , Bornstein Natan , Dávalos Antoni , Kang Dong-Wha , Kaste Markku , Michel Patrik , Parsons Mark W , Sasaki Makoto , Wintermark Max
Published: July 2021

Background and Purpose:
To quantify consistency across stroke centers worldwide in the typical imaging and treatment decisions made when presented with independent clinical case vignettes including various imaging findings across specific time from onset intervals.

Methods:
Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA)-Imaging circulated an online survey of clinical case vignettes through its website, through the websites of national professional societies from multiple countries as well as through email distribution lists from STIR and participating societies. Vignettes varied in terms of patient’s age, time from onset, neurological symptoms and NIHSS. The survey displayed the imaging findings offered by the imaging strategy selected, and the responders selected the appropriate therapy considering time from onset, clinical presentation and imaging findings.

Results:
We received responses from 30 countries including 260 centers. The specific onset interval presented: 0-3 hours, 6 hours, 10 hours or wake-up, influenced the type of imaging work-up selected rather than the clinical scenario. CT was used more often than MRI across all time intervals. For cases with M1 occlusion and large penumbra, vascular imaging was most common (36%) in 0-3 hours and perfusion imaging more frequently used in 6 hours (62%) and wake-up stroke (65%). For large penumbra cases with M1 or ICA occlusion, combination, IV tPA thrombolysis followed by endovascular\IA, treatment (81%) was most common in 0-3 hours. Endovascular treatment was selected the most at 6 hours (43%) for M1 occlusion and large penumbra cases but still selected in 27% of patients up to 10 hours for ICA occlusion and large penumbra cases. For M1 occlusion and large penumbra cases imaged with MRI only, treatment of wake-up stroke increased to 89% from 58% cases imaged with CT alone. Sites that obtained more imaging tended to be more aggressive in terms of revascularization treatment, particularly endovascular therapy.

Conclusions:
Adding vascular and\or perfusion imaging increased the likelihood of thrombolysis across all time intervals. Usage of MRI perfusion imaging was associated with an increased likelihood of enrollment into a randomized trial up to 83%.
Abstract 186: Poor Leptomeningeal Collateral Circulation Baseline Status Is a Predictor of Malignant Infarction in Patients Treated With tPA
Authors: van Eendenburg Cecile , Puig Josep , Blasco Gerard , Serena Joaquín , Pedraza Salvador , Silva Yolanda , Terceño Mikel , Castellanos Mar
Published: July 2021

Background and Purpose:
Malignant infarction (MI) is a life-threatening complication in patients with hemispheric stroke. Although few biochemical and neuroimaging markers have been published to be useful for the prediction of MI development, information about predictors of this complication is scarce. Leptomeningeal collateral circulation (LMC) has been associated in few studies with poor clinical outcome and infarct growth in patients with acute ischemic stroke, but no data have been reported about the possible association about LMC and MI. In this study, we investigated wether LMC baseline status can be a predictor of MI in patients treated with tissue plasminogen activator (tPA).

Methods:
One hundred and thirty-six patients with hemispheric stroke treated with tPA and angio-CT perfusion before tPA administration were evaluated. MI was diagnosed following Schwab et al. criteria (complete space-occupying MCA infarction with midline shift and compression of the basal cisterns on follow-up CT and further neurological deterioration consisting of a decrease in the level of consciousness to somnolence or stupor compared with baseline clinical status at admission). ASPECTS score was evaluated on CT at admission. LMC baseline status was also scored on CT angiography maps before tPA and classified as good or poor according to Tan et al. criteria and Lima et al. criteria

Results:
Sixty-six patients (48.2%) had good LMC and 70 patients (51.1%) had poor LMC, regardless of the classification used. Patients with poor LMC had a significantly higher NIHSS at admission and ASPECTS score < 7 was also found more frequently in this group. With regards to LMC, 14 patients (93%) developed MI in the group with poor LMC whereas just 1 patient (6.7%) had MI in the group with good LMC (p<0.001). In the multivariate analysis, only poor LMC at admission remained as an independent predictor of this complication (OR 12.8; CI 95%, 1.58-104.13; p=0.017).

Conclusions:
Poor LMC at admission is a predictor of MI in patients treated with tPA and, so this neuroimaging finding might be useful to identify those patients at higher risk to develop this fatal complication.
Abstract 188: Safety of Stroke Thrombolysis During Pregnancy: A Population-Based Analysis
Authors: Mainali Shraddha , Cool Josephine A , Navi Babak , Fink Matthew , Kamel Hooman
Published: July 2021

Background:
Use of tissue plasminogen activator (TPA) during pregnancy is controversial given potential risks of placental and fetal complications. Since knowledge on this topic is limited, we assessed rates of TPA use during pregnancy and the associated patient characteristics and outcomes in a population-based sample of patients.

Methods:
We used administrative claims data on all discharges from nonfederal emergency departments and acute care hospitals in California, Florida, and New York between 2005 and 2012. Pregnancy was defined as the 40 weeks prior to delivery or abortive outcome. Using a validated ICD-9-CM diagnosis code algorithm, we identified cases of ischemic stroke, as well as cases of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) since these may represent hemorrhagic transformation of an infarct. We included only the first recorded stroke to focus on incident cases. TPA use was identified by ICD-9-CM procedure code 99.10, which has been validated as 98% specific in this population. Comparisons between groups were made using Fisher’s exact test and t-test or rank-sum test as appropriate.

Results:
Among 428,564 women with stroke, 599 cases occurred during pregnancy. The rate of TPA use for stroke was significantly lower during pregnancy (1.2%; 95% CI, 0.4-2.4%) than otherwise (3.5%; 95% CI, 3.4-3.6%; P = 0.001). Among pregnant stroke patients, we found few notable differences in the baseline characteristics of the 7 who received TPA versus the 592 who did not: those receiving TPA had higher rates of heart failure (28.6% versus 2.2%; P = 0.01) and pneumonia (14.3% versus 1.2%; P = 0.09) and lower rates of of pre-eclampsia (0.0% versus 29.1%; P = 0.09). There were no notable differences between pregnant stroke patients who did or did not receive TPA in terms of length of hospital stay, discharge disposition, and in-hospital mortality rate. However, we noted a significantly higher rate of abortive pregnancy outcomes during stroke hospitalization in those who received TPA than those who did not (28.6% versus 4.6%; P = 0.04).

Conclusion:
We found a significantly higher rate of abortive pregnancy outcomes in patients who received TPA. This suggests the need for caution and further research regarding TPA use for stroke in pregnancy.
Abstract 190: Hemorrhage of Cerebral Arteriovenous Malformations Significantly Alters Stereotactic Radiosurgery Outcomes
Authors: Ding Dale , Yen Chun-Po , Starke Robert M , Xu Zhiyuan , Sheehan Jason P
Published: July 2021

Introduction:
Intracranial hemorrhage is simultaneously the most frequent and most debilitating manifestation of cerebral arteriovenous malformations (AVM), but its impact on success and complications of radiosurgery has not been rigorously assessed. In this case-control study, we define the effect of prior hemorrhage on AVM radiosurgery outcomes.

Methods:
From a prospective, institutional database of 1400 AVM patients treated with Gamma Knife radiosurgery, unruptured and ruptured AVMs were matched in a 1:1 fashion, blinded to outcome, based on patient demographics, prior embolization, AVM size (mean volume of unruptured AVMs 3.7 cm3 versus ruptured AVMs 3.5 cm3, P=0.195), Spetzler-Martin grade and radiosurgical treatment parameters (mean prescription dose for unruptured AVMs 20.9 Gy versus ruptured AVMs 21.0 Gy, P=0.837). There were 270 patients in each cohort. Matched statistical analyses were used to compare the baseline characteristics, obliteration rates, post-radiosurgery latency period hemorrhage risks, and incidences of radiation-induced changes (RIC) between the two cohorts.

Results:
The actuarial obliteration rates of the two cohorts were similar (unruptured AVMs: 38%, 58%, 76% at 3, 5, 10 years, respectively; ruptured AVMs: 40%, 60%, 73% at 3, 5, 10 years, respectively; P=0.592). However, for embolized AVMs, complete obliteration was more likely to be achieved in unruptured lesions (unruptured AVMs: 25%, 32%, 54% at 3, 5, 10 years, respectively; ruptured AVMs: 18%, 27%, 42% at 3, 5, 10 years, respectively; P=0.038). Prior AVM rupture resulted in a higher annual risk of post-radiosurgery latency period hemorrhage (ruptured AVMs 2.3% versus unruptured AVMs 1.1%, P=0.025) but a lower rate of cumulative and symptomatic RIC (cumulative RIC: ruptured AVMs 30.4% versus unruptured AVMs 48.9%, P<0.0001; symptomatic RIC: ruptured AVMs 7.0% versus unruptured AVMs 12.2%, P=0.041, respectively). The rates of permanent RIC were similar between the unruptured (2.2%) and ruptured (1.9%) AVM cohorts (P=0.761).

Conclusion:
Prior AVM rupture significantly alters the risk of latency period hemorrhage and RIC following radiosurgery. These effects should be taken into consideration with the multidisciplinary management of AVM patients.
Abstract 192: Axonal Guidance Factors as Potential Pediatric AVM Urinary Biomarker
Authors: Pricola Katie , Smith Edward
Published: July 2021

Introduction:
Development of noninvasive biomarkers for pediatric arteriovenous malformations (AVMs) could improve diagnosis and identify potential therapeutic targets. The axonal guidance factor, EphrinB2, and its cognate receptor EphB4 have been implicated in AVM development. Here we report our initial experience with urinary EphrinB2 as a novel AVM-specific urinary biomarker.

Hypothesis:
We hypothesize that urinary and tissue levels of EphrinB2 will be elevated in patients with AVM and distinguish AVM from other cerebrovascular disease.

Methods:
Specimens were collected from 45 pediatric patients (0-21 years of age) including unruptured AVM (n=15), moyamoya (n=15) and age- and sex-matched controls (n=15), per an IRB-approved protocol. ELISA quantified levels of urinary EphrinB2. Matched AVM tissue from the same patient was subjected to immunohistochemistry to correlate source tissue expression with biomarker levels.

Results:
Statistical analysis revealed a statistically significant increase in EphrinB2 and AVM-specific biomarker fingerprints capable of discerning AVM both from controls and also from other types of vascular neurosurgical disease. Compared to controls, EphrinB2 was elevated with mean EphrinB2 (0.10 pg/ug vs. 0.019 pg/ug, p<0.01) and compared to moyamoya patients mean EphrinB2 (0.10 pg/ug vs. 0.014, p<0.01). Similarly, EphrinB2 and EphB4 staining was significantly increased in AVM tissue vs. normal blood vessels matched as controls.

Conclusion:
In conclusion, these data suggests potential utility of urinary biomarkers, specifically EphrinB2, as diagnostic tools for clinicians treating children with AVMs and demonstrates proof-of- principle results supporting the concept of hypothesis-driven biomarker “fingerprinting” for unique cerebrovascular disease, differentiating AVM from other vascular pathology. For the first time, these data correlate known aspects of AVM molecular biology with clinically relevant diagnostics.