bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract T P221: Anti-amyloid Immunotherapy Results in Exacerbation of Cerebrovascular Disease Through Activation of Matrix Metalloproteinases
Authors: Weekman Erica M , Sudduth Tiffany L , Wilcock Donna M 
Published: March 2022

Cerebrovascular disease is frequently co-morbid with Alzheimer’s disease (AD) and we hypothesize this co-morbidity could complicate the development of disease-modifying therapies. The amyloid-beta (Aβ) peptide has been the intense focus of therapeutic development for the treatment of AD. One therapeutic approach uses passive immunization against Aβ using anti-Aβ antibodies. We further hypothesize that inflammation mediated activation of MMP9 and MMP2 lead to the exacerbation of cerebrovascular pathologies following immunotherapy. To test our hypothesis we took aged 21 month old APP transgenic mice (PDAPP mice) that have cerebral amyloid angiopathy (CAA) and disruptions of the blood-brain barrier and administered anti-Aβ antibody or control IgG2a for 8 weeks at a dose of 12.5mg/kg. Expression of the MMP2 and MMP9 families were measured by qPCR and Western blot, total Aβ, CAA and albumin for vasogenic edema were measured using immunohistochemistry, and finally, microhemorrhages were assessed with Prussian blue staining.
Treatment with the anti-Aβ antibody resulted in significantly decreased Aβ in the frontal cortex and hippocampus. Further, we found increased microhemorrhage associated with increased gene expression of MMP9, MMP2 and MMP14 (the activator of MMP2). Assessment of vasogenic edema, as well as CAA and inflammatory states is currently ongoing.
Overall, while anti-Aβ treatment leads to decreased Aβ, cerebrovascular pathologies, most notably microhemorrhages, are increased by immunotherapy. This increased microhemorrhage is associated with increased MMP2 and MMP9 expression. These data suggest that co-morbidity of cerebrovascular pathologies with AD will significantly impair efficacy of therapeutics for AD and could potentially lead to adverse events.
Abstract T P272: Improvement in Door to Thrombolytic Time in a Rural Community Hospital
Authors: Siwiec Elaine , Gerard Daniel , Moriarty-Smith Toni , Levy Robert 
Published: March 2022

Background:
Receiving thrombolytic therapy as soon as possible from stroke onset improves chance of complete or near complete neurologic recovery and reduces risk of bleeding. McLaren Northern Michigan (MNM) is a 213 bed nonacademic, regional referral hospital servicing 22 counties. The decision to give thrombolytic therapy at MNM has been the responsibility of the on-site neurologist. Neurological assessment, completion of inclusion/exclusion checklist and verification of stroke onset time were the responsibilities of the Code Stroke neurologist after arrival from home or office.

Hypothesis:
In a rural community hospital door to thrombolytic time can be reduced by using telephone neurology consultation and a revised multidisciplinary approach to treatment.

Methods:
Reviewed select Code Stroke data from 2012 to 2013 by a multidisciplinary team:

Notification to neurologist arrival in ED
Neurologist arrival to decision to treat
Decision to treat to start of thrombolytic bolus
Door to start of thrombolytic bolus

Results:
Identified delays:

Neurology travel from home or office to ED
Completed inclusion exclusion checklist, verification of onset time and neuro assessment by on-site neurologist
Mixing of thrombolytic agent by nursing
Revised the Code Stroke protocol to shift responsibilities from on-site neurologist to onsite ED nurses and ED physician. Provided with phone consultation with neurology:
Documentation and verification ”Last Known Well” time
Initial NIH Stroke Scale score and major deficits
Results of Inclusion / Exclusion checklist
Revised Code Stroke protocol to include a pharmacist at bedside to mix thrombolytic.

Conclusion:
Door to thrombolytic time was significantly decreased by shifting Code Stroke responsibilities and incorporating a pharmacist at the bedside. There were no major bleeds or adverse events
Abstract T P345: Knowledge Translation in Stroke Care in Toronto: Impact of member informed improvements to a Virtual Community of Practice
Authors: Donald Michelle , Skrabka Krystyna , Avinoam Gail , Willems Jacqueline , Sharp Shelley , Linkewich Elizabeth 
Published: March 2022

Background:
The Toronto Stroke Networks Virtual Community of Practice (VCoP) is a secure social media platform, part of an evidence-informed knowledge translation (KT) approach to bridge identified gaps in knowledge for successful implementation of stroke best practices. In 2014, a formative developmental evaluation examined members’ perspectives about the value of the VCoP. Key themes emerged: networking, response time, validation of practice, and prioritization of best practices. Themes informed subsequent improvements: enhanced search functions, ability to share documents within a discussion forum, and formal facilitation.

Objective:
To examine the impact of VCoP enhancements on KT using value cycles 1-5 of the

Wenger (2011) model:
1.immediate value: activity / interactions
2.potential value: knowledge capital
3.applied value: changes in practice
4.realized value: performance improvement
5.reframing value: redefining success

Methods:
Each theme was explored to identify potential improvement opportunities. Discussion with developers informed feasibility. Three priorities were identified: enhanced search functions, ability to share documents within discussion forums, and formal facilitation to prompt discussion. VCoP members were informed of improvements. Qualitative (members’ narratives) and quantitative indicators (e.g. response times, number of discussion threads) were examined.

Results:
Preliminary results indicate that formal facilitation supports increased value in activity and interaction (Cycle 1) on the VCoP. Within the first month of formal facilitation, posts in discussion forums increased from 3.75/month (FY13/14) to 11; average response times decreased from 18 to 8 days. Early examination of narratives indicates themes aligning with Cycle 2: members express value in VCoP information. Further evaluation, in progress, examines the impact of improved search functions and document upload capabilities including analysis of themes aligning with the Wenger Cycles, number of uploaded documents, and search effectiveness.

Conclusions:
Member informed enhancements to the VCoP contribute to KT through enhanced activity, member interactions, and knowledge capital.
Abstract T P368: High Risk of Mortality in Congenital Heart Disease Patients Who Suffer Strokes
Authors: Cheng Henry H , Rajagopal Satish , McDavitt Erica , Esch Jesse , Williams Kathryn , Thiagarajan Ravi , Grant Ellen , Rivkin Michael J 
Published: March 2022

Introduction:
Congenital heart disease (CHD) patients have many risk factors for stroke. Our goal was to describe CHD patients who suffered strokes and determine factors associated with in-hospital mortality.

Methods:
Patients with acquired or CHD who suffered a stroke (radiologic evidence of arterial/venous infarct; subdural, subarachnoid, parenchymal or epidural hemorrhage) from 1/2010-5/2014 at our hospital were identified. Patient charts were retrospectively reviewed.

Results:
Seventy-five stroke patients were identified. Median age at diagnosis was 5.7 months (IQR 0.6, 33.2), and 26 (35%) were neonates. Twenty-six patients (35%) had single ventricle CHD, and 9 (12%) had Fontan circulations.

Seven patients (9%) presented with neurologic symptoms at home. The remainder developed neurologic findings after being hospitalized for a median duration of 9.5 days (IQR 4.0, 21.8). Thirty-four patients (45%) presented with clinically evident neurologic deficits (e.g. weakness, seizures). Forty-seven patients (63%) had arterial infarcts, and 14 (19%) had parenchymal hemorrhages.
At diagnosis, 49 patients (65%) were on inotropes, 48 (64%) were intubated, and 18 (24%) were on ECMO. Twenty-seven patients (36%) had CPR within 30 days of diagnosis. Twenty-four patients (32%) had ≥3 cardiac procedures (surgical or catheter based) during their hospitalization before stroke diagnosis with a median duration of 3 days (IQR 1, 9) between their last procedure and diagnosis.
Forty-eight patients (64%) survived to hospital discharge. Survivors had a median total hospital length of stay of 1.1 months (IQR 0.5, 2.7). Factors associated with in-hospital mortality were: inotropes (p<0.01), intubation (p<0.01), and ECMO (p=0.03) at time of stroke diagnosis; and ≥3 cardiac procedures before stroke diagnosis (p=0.02). Recent CPR (p=0.06) and stroke type (p=0.09) were not associated with in-hospital mortality.
Of 37 surviving patients with neurologic follow-up, 21 (57%) had chronic neurologic deficits due to their strokes (median follow-up: 6.0 months, IQR 2.5-22.8).

Conclusions:
A majority of CHD stroke patients present while hospitalized and without focal neurologic findings. In-hospital mortality is high and associated with severity of illness.
Abstract T P369: Increased Prevalence of Potential Right-to-Left Shunting in Children with Sickle Cell Anemia and Stroke
Authors: Dowling Michael M , Ramaciotti Claudio , Kanter Julie , Osunkwo Ifeyinwa , Inusa Baba , Iyer Rathy , Kwiatkowski Janet , Johnson Clarissa , Rhodes Melissa M , Owen William , Strouse John J , Quinn Charles , Panepinto Julie A , Neumayr Lynne , Sarnaik Sharada , Hynan Linda S , Plumb Patricia , Kirkham Fenella 
Published: March 2022

Children with sickle cell anemia (SCA; HbSS and HgbSβ
0
thalassemia) suffer stroke at a rate 220x higher than other children, but are typically less extensively investigated for modifiable risk factors. In patients without SCA, “paradoxical embolization” via intracardiac or intrapulmonary "right-to-left" shunting is a recognized stroke risk factor. Hypercoagulable states and increased right heart pressures predispose to paradoxical embolization and both occur in SCA. We hypothesized that children with SCA and overt stroke have an increased prevalence of potential right-to-left shunting compared to controls.

We performed contrasted transthoracic echocardiograms (conventional 2D, color Doppler, and 4 contrast injections with agitated saline, including 2 during Valsalva) on children (ages 2-19y) with SCA and history of overt stroke, and a control group of children with neither SCA nor stroke, at 14 institutions in the US and UK. Potential right-to-left shunting was defined as any potential shunt detected by any method, including “late bubbles” (contrast appearing in the left heart >5 cardiac cycles following injection). Echocardiograms were reviewed locally and centrally, with adjudication of conflicts.
We enrolled 153 children with SCA and stroke and 129 controls. There were no significant differences in age or gender between the groups. The prevalence of potential right-to-left shunting was significantly higher in the SCA and stroke group (43.1% vs. 20.0% in controls (p<0.001). There was no significant difference in intracardiac shunting (22.9% vs. 16.2%, p=0.157) but there was a higher proportion with intrapulmonary shunting (“late bubbles” only) in the SCA and stroke group (27.5% vs. 5.5% in controls, p<0.001).
Our findings suggest that intracardiac and intrapulmonary shunting could be an independent, potentially modifiable risk factor for stroke or stroke recurrence in children with SCA. Additional therapeutic interventions in patients at risk of stroke or stroke recurrence via paradoxical embolization, including antiplatelet agents or shunt closure, should be evaluated in children with SCA.
Abstract W MP24: Improving Collateral Circulation Evaluation Accuracy: Multiphase CTA on Acute Stroke
Authors: Rubiera Marta , Carvalho Vanessa , Bonet Sandra , Flores Alan , Carcamo Daniel , Lemus Miguel , Coscojuela Pilar , de Bonadona David , Ponciano Rafael , Muchada Marian , Rodriguez-Luna David , Pagola Jorge , Sero Laia , Tomasello Alejandro , Menon Bijoy K , Goyal Mayank , Ribo Marc , Molina Carlos A 
Published: March 2022

Good collateral circulation (CC) associates favourable outcomes on acute stroke patients, but which is the best technique to evaluate it is controversial. Single-phase CTA (sCTA) is widely used, but lacks of temporal resolution, and may mislabel CC. We aim to evaluate a new, quick (not post processing), time resolved technique to evaluate CC: multiphase CTA (mCTA).

METHODS:
Consecutive <4.5h stroke patients evaluated for reperfusion therapies with confirmed M1-MCA or TICA occlusion by sCTA were included. Two more cerebral CTA acquisitions with 10 and 20 seconds delay were performed for mCTA. CC evaluation is described in the Table. sCTA and mCTA were compared as predictors of clinical, radiological and functional endpoints. Recanalization (REC) was assessed by TCD at 24h.

RESULTS:
78 patients were included. Mean age: 66.3±13.6y, median NIHSS 17.5 (IQR 6.3), 52 (66.7%) M1- and 26 (33.3%) TICA-occlusions. Mean time from onset to CTA: 2:32±1:31h. On sCTA, 61.8% patients presented good CC whereas on mCTA, 54.7%. Only on mCTA good CC was an independent predictor of low infarct volume at 24h (OR 3.6, CI 95% 1.3-10.5, p=0.017).

Moreover, only mCTA-CC status was associated with lower 24h median NIHSS (good CC:5 vs poor CC:17, p<0.001), and 3 months favourable outcome (mRS0-2: good CC 57.1% vs poor CC 11.5%, p<0.001).
Association with outcome was especially significant in patients without REC: among poor CC patients, mRS0-2: 0% in non REC Vs 50% in REC (p<0.01).
In a logistic regression model including age, NIHSS, ASPECTS and REC, only good CC on mCTA predicted favourable outcome (OR 6.8, CI 95% 1.6-29.2, p=0.009).

CONCLUSION:
CC evaluation on mCTA improves accuracy of clinical and radiological endpoints as compared with sCTA. Good CC on mCTA is an independent predictor of low infarct volume and good outcome, especially if REC is not achieved.
Abstract W MP44: Investigations Using a Combination of Computational Fluid Dynamics Technique and an Animal Model of Experimentally Induced Cerebral Aneurysms Suggest Important Roles of Wall Shear Stress on the Cerebral Aneurysm Development
Authors: Fukuda Shunichi , Shimogonya Yuji , Fukuda Miyuki , Hasegawa Koji 
Published: March 2022

We have a series of reports suggesting that an increase in hemodynamic factors, especially wall shear stress, plays a central role in cerebral aneurysm development. We show here the effect of wall shear stress on the cerebral aneurysm growth, using computational fluid dynamics (CFD) analyses and an animal model of experimentally induced cerebral aneurysms.
3-dimentional CT angiographic images of 34 human cerebral aneurysms were used for CFD analyses. Measured flow rates derived from physiological data of individual patients, but not theoretically assumed rates, were used as inlet boundary conditions because there exists a significant influence of inlet boundary conditions between measured and theoretically assumed values on hemodynamics in human cerebral aneurysms as we reported previously. CFD analyses in human cerebral aneurysms frequently indicated an increase in wall shear stress at the aneurysm orifice. Moreover, if the arterial geometry around the aneurysm is virtually reconstructed just before the aneurysm induction by artificial removal of the aneurysm, the enhanced magnitude of wall shear stress and gradient oscillatory number was observed near the apex of arterial bifurcation where the aneurysm was removed.
In animal experiments, we examined the effect of blockage in the P2X4 purinoceptor, the vascular endothelial shear-sensor, on the frequency of aneurysm induction after aneurysm-inducing surgery, using P2X4 knockout mice (n=19) and wild type mice (n=21). The incidence of induced aneurysm formation in P2X4 knockout mice was significantly lower than in wild types (p<0.02). Immunohistochemical examinations indicated that the immunoreactivity of MCP-1, which is closely associated with inflammatory responses during aneurysm formation, was weaker in P2X4 knockout mice than in wild types.
These data suggest that during aneurysm formation, vascular endothelial cells might sense excessively high levels of wall shear stress over physiological limit, which may initiate damage to vascular components, leading to aneurysm development. A combination of CFD simulation in the human cerebral aneurysm and an animal model of experimentally induced cerebral aneurysms may be a good tool for the study of cerebral aneurysm formation.
Abstract W P16: Comparing Outcome Prediction Scoring Systems in the Interventional Management of Stroke (IMS) III Trial: No Clear Winner
Authors: de los Ríos la Rosa Felipe , Seiffge David J , Fan Liqiong , Yeatts Sharon D , Khatri Pooja , Engelter Stefan 
Published: March 2022

Introduction:
Several prognostic scores have been developed to predict patient outcome after ischemic stroke. We aimed to compare eight scores in the IMS -III dataset.

Hypothesis:
Prediction of good and poor outcome using different scores is possible in IMS-III.

Methods:
We retrospectively calculated area under the curve (AUC), sensitivity, and specificity for poor (mRS 4-6) and good (mRS 0-2) 90-day outcome in all IMS-III participants with complete data. The scoring systems analyzed were: Houston Intra-arterial Therapy 2 (HIAT2), Ischemic Stroke Predictive Risk Score (iScore), Totaled Health Risks in Vascular Events (THRIVE), DRAGON, Hemorrhage after Thrombolysis (HAT), Alberta Stroke Programme Early CT Score (ASPECTS), Stroke-Thrombolytic Predictive Instrument (TPI), and Simple Variables Model (SVM). Those receiving IV rtPA followed by endovascular therapy (treatment) and those receiving IV rtPA only (control) were analyzed separately.

Results:
Among 656 IMS III subjects, 651 had complete data, including 429 treatment and 222 control subjects. Overall, all scoring systems showed good prediction abilities (AUC range 0.60 to 0.78). AUC comparisons did not clearly favor a single scoring system.

Treatment group: For predicting poor outcome, the TPI score outperformed ASPECTS (AUC 0.73 vs 0.61; P <0.05). For predicting good outcome, the HAT score was significantly better than ASPECTS (0.73 vs. 0.64; P <0.05).
Control group: For poor outcome, the TPI score was significantly better than ASPECTS and THRIVE (0.78 vs. 0.62 and 0.71, respectively; P <0.05). For good outcome, TPI performed better than ASPECTS and THRIVE (0.73 vs. 0.61 and 0.67, respectively; P <0.05).

Conclusions:
Outcome prediction using different scores in IMS III is possible. HIAT2, iSCORE, DRAGON, HAT, TPI, and SVM all performed comparably. Prognostic performances were comparable in both treatment arms.
Abstract 152: Complications and Outcomes From Thrombolysis in Stroke Patients With Significant Pre-stroke Disability: Data From the UK National Stroke Registry
Authors: Paley Lizz , Bray Benjamin , James Martin , Tyrrell Pippa , Hoffman Alex , Cloud Geoffrey , Rudd Anthony ,   On behalf of the SSNAP Collaboration
Published: March 2022

Introduction:
National clinical guidelines in England and Wales recommend that intravenous thrombolysis is provided regardless of pre-stroke disability, but thrombolysis trials have included very few patients with a modified Rankin scale (mRS) score of more than 2. We therefore analysed data from the national stroke register of England and Wales of over 100,000 records to determine the safety and outcomes of thrombolysis in patients with varying levels of pre-stroke disability.

Methods:
Data were extracted from the national stroke register (Sentinel Stroke National Audit Programme (SSNAP)) of adults with acute ischemic stroke treated in all hospitals in England and Wales from April 2013-March 2015.

Results:
Of 128826 adults with acute ischemic stroke admitted to 202 hospitals, 23850 (18.5%) were dependent in some activities of daily living before stroke (mRS of more than 2). Of these, 1926 (8.1%) were treated with intravenous alteplase (iv-tPA).

Of the patients with an mRS greater than 2 who were treated with iv-tPA, 1239 (64.3%) were female, 120 (6.2%) had an onset whilst already an inpatient, and 1395 (72.4%) were fully conscious upon arrival at hospital. The median age was 84 years (IQR 78-89); the median NIHSS score 15 (IQR 9-21).
Of the 1320 patients (68.5%) with a fully completed NIHSS at arrival and at 24h after thrombolysis, the median change in NIHSS was a 3 point improvement (IQR 0-7).
A total of 214 patients (11.1%) had complications from thrombolysis; 104 (5.4%) had symptomatic intracranial hemorrhage, 10 (0.5%) had angioedema, 21 (1.1%) had extracranial bleeds and 82 (4.3%) had some other type of thrombolysis complication.
Inpatient case fatality rate was 29.2%, and 10.2% were newly institutionalised in a care home (14.4% of those discharged alive).

Conclusions:
Patients treated with iv-tPA who were not independent before stroke have similar rates of complications as reported for independent patients in national registries and clinical trials. However stroke for patients with pre-stroke disability carries a high risk of mortality and a high proportion of survivors are discharged to long term care for the first time.
Abstract 32: Radiographic and Clinical Outcomes Demonstrate Long-term Efficacy of Indirect Revascularization 20 Years After Surgery for Pediatric Moyamoya
Authors: Storey Armide D , Smith Edward R , Scott R. Michael 
Published: March 2022

Introduction:
Pediatric moyamoya patients have little long-term data to inform them about what to expect after revascularization beyond a 5-year window. Here we present a series of pediatric patients treated with indirect revascularization with long-term clinical and radiographic follow-up.

Hypothesis:
We assessed the hypothesis that indirect revascularization, such as pial synangiosis, provides durable clinical and radiographic protection from stroke in pediatric moyamoya patients.

Methods:
Retrospective case series. Records of all children with moyamoya surgically revascularized by the senior author prior to 1996 (20 years ago) were analyzed.

Results:
37 patients (27F/12M) were identified, all diagnosed under age 22 years. Most common presentations included ischemic symptoms and 30 patients (81%) had a radiographic stroke prior to surgery. Bilateral disease existed in 36 patients; 1 unilateral. Average age at surgery was 8 years (range=1-22 yr.). Surgery consisted of 25 EDAS (encephalo-duro-arterio-synangiosis) and 48 pial synangiosis.

Average follow-up=16 years (range=5.5-31.8 years). Only one stroke occurred during this period (2.7% of patients). Two deaths occurred, 1 from a malignant meningioma at age 27 and the other from aneurysmal hemorrhage after intracranial radiation for tumor at age 40. In all other patients, mRS scores were stable or improved at most recent follow-up.
Descriptive data less amenable to analysis but subjectively helpful to patients includes information on patient life experiences. A total of 91% completed high school, 90% are employed, 56% completed college and 3 patients have graduate degrees. Four of the female patients had successful vaginal child births.

Conclusions:
Revascularization confers durable protection from stroke for pediatric patients on long-term follow up. These data suggest that pediatric patients do very well after treatment and support the use of interventions such as pial synangiosis.