bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 30: Transcranial Direct Current Stimulation for Children With Perinatal Stroke and Hemiparesis: a Randomized, Controlled Trial
Authors: Kirton Adam , Ciechanski Patrick , Zewdie Ephrem , Andersen John , Carsolio Lisa , Herrero Mia , Quigley Jillian , Nettel-Aguirre Alberto , Hodge Jacquie , Hill Michael
Published: March 2022

Background:
Perinatal stroke causes hemiparetic cerebral palsy. Brain stimulation may enhance motor function in adult stroke. We demonstrated that rTMS enhances motor learning therapy in children with perinatal stroke. Transcranial direct current stimulation (tDCS) may have similar capacity but is unstudied.

Hypothesis:
tDCS increases motor function in hemiparetic children undergoing 2 weeks of motor learning therapy.

Methods:
Randomized, controlled, double blind clinical trial. Subjects were recruited from a population-based cohort with MRI-classified unilateral perinatal stroke, age 6-18 years, and disabling hemiparesis. All completed a goal-directed, peer-supported, 2 week “after school” motor learning camp (32 hours of therapy). Subjects were randomized 1:1 to 1mA cathodal tDCS over the contralesional primary motor cortex for the initial 20 minutes of daily therapy or sham. Primary subjective (Canadian Occupational Performance Measure, COPM), objective (Assisting Hand Assessment, AHA), safety, and secondary outcomes were measured at 1 week and 2 months. Analysis was intention-to-treat.

Results:
Twenty-four subjects were randomized (median 11.8+/-2.7 years, range 6.7-17.8). COPM performance and satisfaction scores more than doubled at 1 week with sustained gains at 2 months (p<0.001). Both COPM scores increased more with tDCS compared to sham (p=0.004). AHA scores demonstrated only mild increases at both time points with no tDCS effects. Procedures were safe and well tolerated with no decrease in either arm function or serious adverse events.

Conclusion:
tDCS trials appear feasible and safe in hemiparetic children. Lack of change in objective motor function may reflect under-dosing of therapy and/or modest sample size. Greater gains in subjective function with tDCS warrant further study.
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.
Abstract 37: Novel Oral Anticoagulants for the Secondary Prevention of Cerebral Ischemia: A Network Meta-analysis
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Mavridis Dimitrios , Frogoudaki Alexandra , Vrettou Agathi-Rosa , Ikonomidis Ignatios , Paraskevaidis Ioannis , Parissis John , Voumvourakis Konstantinos , Alexandrov Anne W , Alexandrov Andrei V
Published: March 2022

Background & Purpose:
There are no randomized clinical trial (RCT) data regarding direct comparisons between different novel oral anticoagulants (NOACs). We conducted a network meta-analysis using published data from secondary prevention subgroups of different phase III RCTs comparing individual NOACs to warfarin.

Methods:
We performed a comprehensive literature search in Medline, SCOPUS and the Cochrane Central Register of Controlled Trials to identify available RCTs. The primary efficacy outcome was stroke or systemic embolism and the primary safety outcome was the occurrence of a major bleeding event during the follow-up period. We performed a Bayesian-framework, multiple-treatments meta-analysis and ranked the comparative effects of all NOACs against warfarin with the surface under the cumulative ranking (SUCRA) probabilities.

Results:
We identified 4 RCTs (including 15,302 patients) comparing individual NOACs (Apixaban, Dabigatran, Rivaroxaban) to warfarin. In indirect comparison analysis Dabigatran was related to a significantly lower risk of hemorrhagic stroke compared to Rivaroxaban (RR=0.28; 95%CI: 0.11-0.75), while Rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared to Dabigatran (RR=0.14; 95%CI: 0.03-0.74). Clustered ranking plot for the primary efficacy and safety endpoints highlighted Apixaban as the treatment with the probably best benefit-to-risk ratio profile among NOACs followed by Dabigatran and Rivaroxaban (Figure).

Conclusion:
The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention. These findings serve only for hypothesis generation and require independent confirmation in head to head RCTs.

Figure legend:
Corresponding SUCRA Probabilities for different NOACs to be ranked as the most effective treatment for the prevention of Stroke/systemic embolism (y axis) and Major bleeding (x axis)
Abstract 38: Comparison of Gastrointestinal Bleeding Risk Among Different Statin Exposures With Warfarin: An Electronic Health Record-based Retrospective Cohort Study
Authors: Lee Jin Soo
Published: March 2022

Introduction:
Patients who require both warfarin and statin are frequently seen in vascular clinics. Gastrointestinal bleeding (GIB) is one of the most frequently occurring complications when a patient is administered warfarin, and this complication hinders continuous administration of warfarin.

Hypothesis:
GIB risk may differ among different statin exposures with warfarin.

Methods:
We observed patients who were exposed to one of four statins (pravastatin, simvastatin, atorvastatin, or rosuvastatin) and warfarin concomitantly for up to 2 years (730 days). Observation was ended when GIB occurred or observation was censored. To evaluate the risk of co-administration of different statins and warfarin on GIB, within-class comparison was used. We performed 1:1 matching using a propensity score for comparison of each single statin and others. Kaplan-Meier analysis with log-rank test and Cox proportional hazard regression were conducted for comparison.

Results:
We identified 1,686 patients who were administered statin concomitantly with warfarin. The patients were classified by each statin: 287 patients were exposed to pravastatin, 317 to simvastatin, 716 to atorvastatin, and 366 to rosuvastatin. Mean levels of total cholesterol during the observation period were 167 ± 44, 155 ± 36, 145 ± 35, and 139 ± 37 mg/dl, respectively (p<0.001). On Kaplan-Meier curve analyses, GIB was less frequent in the pravastatin group than in others (p<0.05). It was more frequent in the rosuvastatin group than in others (p=0.009). In the Cox proportional hazard regression analysis, age, sex, Charlson comorbidity index, nonsteroidal anti-inflammatory drug exposure, steroid exposure, antiplatelet exposure, and the proportion of time in the therapeutic range of warfarin international normalized ratio were adjusted. Hazard ratio (HR) of GIB on statin exposure in the rosuvastatin group was significantly high (HR, 5.0 [95% confidence interval, 1. 1-23.3], p=0.038) while the ratio in the pravastatin group tended to low (0.3 [0.1-1.0], p=0.051).

Conclusions:
Rosuvastatin administration has a relatively high risk of GIB among patients who are concomitantly administered warfarin, whereas pravastatin administration appears to carry a low risk.
Abstract 43: Dementia After Spontaneous Intra-cerebral Hemorrhage
Authors: Moulin Solène , Labreuche Julien , Rossi Costanza , Boulouis Gregoire , Bombois Stéphanie , Hénon Hilde , Leys Didier , Cordonnier Charlotte
Published: March 2022

Background:
Stroke and dementia are closely related but no prospective study ever focused on dementia in patients with intracerebral hemorrhage (ICH).

Objective:
To determine incidence, prognostic factors and possible mechanisms of post-ICH dementia in a large population of non-demented ICH patients over a long period of follow-up.

Methods:
Prospective cohort of consecutive adults with spontaneous ICH. Patients free of dementia and alive at 6 months were included. We studied clinical and neuroradiological (MRI) biomarkers with a prespecified subgroup analysis according to ICH location. Age-adjusted analyses were used to select variables (p<0.1) included in multivariable models that took into account death as competing risk.

Results:
In a cohort of 218 ICH patients (108 males; median age 67.5, interquartile range (IQR) 55-76), 63 patients developed new onset dementia during a median follow-up of 5.4 years (IQR, 4.2-5.8). At 1 year after ICH, the overall incidence of dementia was 20% (95% CI 15-25). It differed between lobar ICH (n=77, 30% 95% CI 20-40) and non lobar ICH (n=141, 16% 95% CI 10-22). Prognostic factors of new onset dementia were lobar Iocation (Hazard Ratio (HR): 2.21; 95% CI 1.30-3.79), older age (HR: 1.06 per year; 95% CI 1.03-1.09), history of previous stroke or transient ischemic attack (HR: 2.56; 95% CI 1.42-4.61), higher NIHSS (HR: 1.03 per year; 95% CI 1.01-1.06), severe leucoaraïosis (HR: 2.87; 95% CI 1.63-5.07) and recurrent stroke during follow-up (HR: 3.22; 95% CI 1.27-8.15). Prognostic neuroradiological biomarkers were increasing cortical atrophy (HR: 2.7; 95% CI 1.7-4.3), presence of disseminated superficial siderosis (HR: 7.10; 95% CI 3.93-12.83), higher number of lobar cerebral microbleeds (HR: 3.40; 95%CI 1.87-6.18). Among lobar ICH, superficial siderosis was a strong predictor (HR: 6.74; 95% CI 3.32-13.68).

Conclusion:
The incidence of new onset dementia is high after ICH with a strong influence of lobar location. Among patients with lobar ICH, prognostic factors suggested a strong implication of underlying cerebral amyloid angiopathy that might predict future risk of dementia. Results of our study suggest that all prognostic factors of dementia are already present before the ICH occurs.
Abstract 45: Cerebral Microbleeds and Cognitive Function in a Community-based Study
Authors: Chung Chih-Ping , Wang Pei-Ning , Lin Ching-Po , Chen Liang-Kung
Published: March 2022

Introduction and Objective:
Cerebral microbleeds (CMBs) have been acknowledged as a manifestation of age-related cerebral small vessel diseases. The prevalence of CMBs has been reported around 4.5%-15.3% in the general population, and could reach as high as 35.7% in people >80 years old. Studies have evaluated the effects of CMBs on cognitive functions, however, the results about the influence of CMB location (e.g. deep/infratentorial or lobar) are inconsistent. Besides, there are scanty CMB studies of the Asian community-based population and even fewer have investigated in the impacts of CMBs on different cognitive domains. The present study aimed to evaluate the correlations between the CMBs and cognitive functions in a Taiwan community-based population. We determined whether the number and location of CMB had impacts on a variety of cognitive functions.

Methods:
Study subjects were from the community-based I-Lan Longitudinal Aging Study. Subjects with dementia and stroke were excluded. The cognitive domains including verbal memory, language, visuospatial executive, and verbal executive functions were evaluated. The number and location of CMBs were revealed by the 3T susceptibility weighted imaging MRI.

Results:
There were 401 subjects [63.87(8.82) years, 193(48.1%) men] included. CMBs were found in 11.7% of population. The results showed that lobar CMBs were significantly associated with poorer visuospatial instead of verbal executive function independent of age, gender, education, hypertension and the other markers of cerebral small vessel diseases. The presence of CMBs in the temporal and frontal lobes determined worse neuropsychological tests involving the visuospatial executive functions, the complex figure test [temporal CMBs: regression coefficient (95% confidence interval) = -4.59 (-9.46 - -0.35), p = 0.035; frontal CMBs: -2.13 (-6.91 - 2.65), 0.381] and clock drawing test [temporal CMBs: -1.55 (-3.17 - 0.10), p = 0.063; frontal CMBs: -1.48 (-3.15 - 0.18), 0.082].

Conclusion:
The location is more important than amounts regarding the CMB effects on cognitive functions in non-demented non-stroke healthy subjects. Lobar CMBs, particular in the temporal and frontal lobe, are associated with poorer visuospatial executive function.
Abstract 46: Adherence to Ideal Cardiovascular Health Guidelines Prevents Stroke and Preserves Cognitive Function
Authors: Pase Matthew P , Beiser Alexa , Enserro Danielle , Xanthakis Vanessa , Aparicio Hugo , Satizabal Claudia , Kase Carlos , Ramachandran Vasan , DeCarli Charles , Himali Jayandra , Seshadri Sudha
Published: March 2022

Introduction:
The American Heart Association (AHA) has proposed a 7-point Cardiovascular Health (CVH) score as a way of quantifying and promoting ideal CVH. Despite awareness that vascular risk is associated with cognitive decline, this index is yet to be examined with respect to vascular cognitive impairment (VCI) or subclinical brain injury.

Hypothesis:
We hypothesize that ideal CVH is associated with a lower risk of VCI, stroke and vascular brain injury on MRI.

Methods:
We studied 2,750 stroke- and dementia-free Framingham Offspring Cohort participants (mean age 61±9y; 55%F). Ideal CVH was calculated for participants who attended the 7th exam (1998-2001) by combining 4 ideal health behaviors (nonsmoking, optimal body mass index plus both physical activity and dietary habits at current recommendations) and 3 ideal health factors (total cholesterol, blood pressure and fasting blood glucose all untreated and at optimal levels). We related CVH scores to change in neuropsychological and MRI data over approximately 7 years, and to the incidence of stroke over a median follow-up of 11 years.

Results:
In adjusted models, higher ideal CVH predicted a lower risk of incident stroke (HR = 0.83, 95% CI 0.71-0.97), less cognitive decline on tasks measuring visual memory (visual reproductions delayed; β±SE =0.02±0.01, p=0.012) and reasoning (Similarities; β±SE =0.02±0.01, p=0.044) and less decline in frontal brain volume (β±SE = 0.32±0.10, p=0.002). A 1-point higher CVH score reduced the rate of decline in frontal brain volume to that of someone 3.4 years younger. Ideal CVH was not associated with silent brain infarcts or verbal memory.

Conclusion:
Ideal CVH predicted stroke and a vascular pattern of cognitive decline. Adherence to the AHA’s ideal health factors and behaviors may protect against vascular cognitive impairment.
Abstract 48: Cerebral Amyloid Angiopathy in Asymptomatic Community-Dwelling Older Adults
Authors: Gurol M. Edip , Schultz Aaron P , Fotiadis Panagiotis , Hedden Trey , Becker J. Alex , Sperling Reisa A , Greenberg Steven M , Johnson Keith A
Published: March 2022

Background:
Cerebral amyloid angiopathy (CAA), characterized by accumulation of β-amyloid in cortical vessels, is an established cause of hemorrhagic and ischemic brain damage. Although Boston criteria can accurately diagnose CAA in patients who had lobar intracerebral hemorrhage (ICH), its value in asymptomatic older adults is unknown.

Objective:
We aimed to compare the amyloid load, structural MRI measures and risk factors between asymptomatic subjects who would qualify for a diagnosis of probable CAA based on lobar microbleeds (LMB) and superficial siderosis (SS) to subjects without these MRI findings.

Methods:
Healthy older adults (n=181) prospectively enrolled in Harvard Aging Brain study had research MRIs and Pittsburgh Compound B (PiB) PET scans. Probable CAA was diagnosed based on presence of 2 or more LMBs or a combination of LMB/SS. Distribution volume ratio (DVR) of PiB-retention, white matter hyperintensity (WMH) and hippocampal volume (HV) were calculated. Demographics, APOE status, risk factors, and imaging markers were compared between subjects with and without probable CAA diagnosed based on LMB/SS.

Results:
Participants had mean age 74.5±5.8 and 56% were female. Forty-six (25%) subjects had lobar MBs, 11(6%) had deep and 4(2%) cerebellar MBs. The 22 subjects diagnosed with probable CAA had higher occipital DVR (1.35 vs 1.28, p=0.004) and higher WMH (0.51 vs 0.16, p=0.005) when compared to persons without MB. These associations remained significant after adjustment for age and gender. Age, HV, ApoE status and vascular risk factors were similar between probable CAA and no MB/SS subjects (all p>0.2).

Conclusions:
Probable CAA diagnosis based on presence of lobar MBs and/or SS on MRI of healthy elderly volunteers is associated with other radiologic markers of CAA (posterior amyloid load, WMH) but not with vascular risk factors or markers of Alzheimer’s Disease (HV, ApoE 4). Boston criteria and amyloid imaging thus may allow early diagnosis of CAA even in asymptomatic subjects without ICH or dementia.
Abstract 6: Patient Selection is a Better Predictor of Good Outcome Than Time to Reperfusion in Acute Ischemic Stroke
Authors: Tsai Jenny P , Mlynash Michael , Christensen Soren , Kemp Stephanie , Mishra Nishant , Federau Christian , Kim Sun , Frankel Michael , Dehkharghani Seena , Devlin Thomas G , Yavagal Dileep R , Akhtar Naveed , Jovin Tudor , Nogueira Raul G , Bammer Roland , Straka Matus , Zaharchuk Gregory , Albers Gregory W , Marks Michael P , Lansberg Maarten G
Published: March 2022

Introduction:
Intra-arterial therapy has become standard-of-care for stroke patients with large vessel occlusions presenting within 6 hours of symptom onset. Treatment effectiveness at later times is currently unknown. Using data from the CT Perfusion (CTP) to predict Response to recanalization in Ischemic Stroke Project (CRISP), we assessed the effect of time to treatment on the probability of good outcomes.

Hypothesis:
Symptom onset-to-reperfusion time is not associated with probability of favorable outcomes in patients with target mismatch who achieve reperfusion.

Methods:
All patients enrolled underwent baseline CTP. For this analysis, we included data from patients with target mismatch (ratio of Tmax>6s lesion to core volume of >1.8) who achieved endovascular reperfusion. We determined reperfusion status by early follow-up MRI or CTP, or final TICI score 2b-3 if early follow-up perfusion imaging is unavailable. We defined good functional outcome (GFO) as mRS 0-2 at day 90. We assessed the probability of good outcome as a function of onset-to-reperfusion time using logistic regression, with prespecified adjustment for age and baseline NIHSS.

Results:
Following intra-arterial intervention performed within 18 hours, 102 patients with target mismatch achieved reperfusion. Median onset-to-reperfusion time was 6.6 hours (IQR 5.2-9.5). In univariate analysis, onset-to-reperfusion time was not associated with GFO (p=0.19), whereas age and NIHSS were. Similarly, in multivariate analysis, age and NIHSS were associated with GFO, while onset-to-reperfusion time was not. The adjusted relative risk per hour of delay is 0.994 (95% CI 0.97-1.02). GFO was achieved in 71.4% of patients treated within 6 hours, and in 61.7% of patients treated after 6 hours.

Conclusion:
The lack of significant association between onset-to-reperfusion time and GFO, and the high proportion of patients achieving good outcomes at 6-18 hours, suggest that endovascular interventions may be beneficial beyond 6 hours with a CTP target mismatch profile, supporting randomized controlled trials of endovascular therapy in the extended time window in selected patients.
Abstract 70: Neurogenesis in the Pediatric Brain Following Ischemic Stroke: a Potential Target for Endogenous Regeneration and Repair
Authors: Rodgers Krista M , Ahrendsen Jared T , Strnad Frank A , Yonchek Joan C , Macklin Wendy B , Traystman Richard J , Herson Paco S
Published: March 2022

Introduction:
Following stroke, neurons are seriously damaged or die, impairing local brain function and contributing to long-term disability. Mounting evidence suggests that stroke recovery in children is enhanced compared to adults. Neurogenesis, a process involving the generation of functionally integrated neurons from progenitor cells, may play a role in enhanced plasticity and neuronal repair. Stroke-induced neurogenesis in adults involves massive proliferation and migration of newborn neurons, however these newborn neurons go on to die, never repopulating areas of damage. We tested the hypothesis that neurogenesis in the young brain effectively repopulates injured regions following ischemia.

Methods:
Stroke was induced in adult (2-3 mo, n=21) and pediatric (P20-25, n=21) mice by 45-min right middle cerebral artery occlusion (MCAo). Bromodeoxyuridine (BrdU) was injected on days 3 and 4, and mice sacrificed at 24 hr, 7 d or 30 d after recovery from MCAo. Immunohistochemistry was performed to assess cellular proliferation and neurogenesis.

Results:
The results revealed extensive neuronal cell death in the striatum of both pediatric and adult mice at 24 hr and 7 d after stroke. Remarkably, significant numbers of healthy, mature neurons (NeuN+) were observed in the striatum of pediatric mice at 30 d post-injury. Birth-dating with BrdU demonstrated robust, ischemia-induced proliferation of neural progenitor cells in both adult and pediatric brain. Consistent with previous reports, we observed very few mature NeuN+ neurons double labeled with BrdU in the injured adult brain. In contrast, significant numbers of BrdU+NeuN cells were observed in the pediatric brain 30 d after MCAo, indicative of mature neurons and most importantly, with COUP-TF1-interacting protein 2 (Ctip2) expression, a marker of medium spiny striatal neurons.

Conclusion:
Our results indicate that cerebral ischemia in pediatric mice increases neurogenesis and migration to sites of damage, and supports the possibility of true neuronal replacement in the pediatric brain. These findings have exciting implications for heightened restorative processes in the pediatric brain microenvironment.
Abstract 71: Final Results of the B01-02 Phase 2 Trial Testing the Safety and Efficacy of MultiStem® in Treatment of Ischemic Stroke
Authors: Hess David C , Auchus Alexander P , Uchino Ken , Sila Cathy , Clark Wayne M , Chiu David , Wechsler Lawrence R ,   B01-02 Investigators, Mays Robert W
Published: March 2022

Introduction:
MultiStem is an adult, adherent, stem cell product, having shown safety and efficacy in other clinical indications and pre-clinical models of stroke. We assessed whether it was safe and improved outcomes in patients with ischemic stroke.

Methods:
B01-02 was a double-blind, placebo-controlled study of ischemic stroke patients (NIHSS 8-20, inclusive) treated within 24-48 hours of symptoms at 33 sites in the U.S. and U.K. Patients were randomized 1:1 and received infusion of 1.2 billion cells or placebo. Efficacy endpoints included Global Recovery (mRS ≤2, NIHSS Δ ≥75% and BI ≥95) and Excellent Outcome between groups (mRS ≤1, NIHSS ≤1, BI ≥95) at Day 90, among others. Safety end points included neurologic worsening, secondary infections, adverse events and mortality.

Results:
126 patients formed the Intention-To-Treat (ITT) population, 65 receiving MultiStem, 61 placebo. The cell therapy did not show a significant benefit relative to placebo for the primary and secondary endpoints. However, MultiStem treatment was associated with lower rates of infections and pulmonary events, a reduction in hospitalization, and a reduction in life threatening adverse events and death. A higher proportion of patients receiving MultiStem treatment achieved an Excellent Outcome (p=0.10) compared to placebo. Post-hoc analyses indicate that, compared to placebo subjects (n=52), patients who received cell treatment earlier in the treatment window (≤36 hrs, n=27) had better Global Recovery (41.9% vs. 17.3%, p<0.01) and Excellent Outcome (18.5% v. 3.8%, p=0.03), had significantly better recovery by mRS shift analysis (p=0.03) and significantly reduced hospitalization (6.7d vs. 10.3 d, p<0.01).

Conclusions:
Administration of MultiStem is safe and well tolerated in ischemic stroke patients within 48 hours of onset and reduces adverse events and death. Post-hoc analyses suggest that earlier administration of MultiStem may provide therapeutic benefit. Additional clinical studies exploring the optimal time frame for MultiStem administration are warranted.
Abstract 79: Pre-hospital Diagnosis in Mobile Stroke Treatment Unit
Authors: Ramanathan Rsmnath Santosh , Wisco Dolora , Vela-Duarte Daniel , Zafar Atif , Taqui Ather , Winners Stacey , Buletko Andrew Blake , Organek Natalie , Hustey Fredrick , Reimer Andrew , Hussain Shahzam , Uchino Ken ,   On behalf of the Cleveland Pre-Hosp Acute Stroke Treatment (PHAST) Study Group
Published: March 2022

Introduction:
Mobile stroke treatment unit (MSTU) has been shown to be able to provide pre-hospital thrombolysis in acute ischemic stroke (AIS). MSTU can also be used for early pre-hospital diagnosis and treatment of other neurological diseases.

Hypothesis:
MSTU encounters neurological disorders other than AIS that needs emergent treatment.

Methods:
We obtained pre-hospital diagnosis and treatment data from the prospectively collected dataset on 231 consecutive MSTU encounters. Based on initial clinical evaluation and neuroimaging obtained on MSTU, the stroke physician made the diagnosis of AIS (definite, probable, and possible AIS, transient ischemic attack), intracranial hemorrhage, and unlikely AIS. Non-stroke diagnosis made by MSTU physician was compared with final hospital discharge diagnosis.

Results:
From July 2014 to May 2015, 231 patients were treated on MSTU of which 84 (36%) had clinical diagnosis of definite/probable AIS, 70 (31%) had possible AIS, while 14 (6%) patients had intracranial hemorrhage. Sixty-three (27%) were diagnosed as unlikely AIS including 23 (10%) metabolic encephalopathy, 19 (8%) seizures (including 1 partial status epilepticus), 16 (7%) migraines, 16 (7%) substance abuse, 6 (3%) CNS tumor, 5 (2%) infectious etiology and 3 (1%) hypoglycemia. Thirty-three (14%) patients received non-thrombolytic treatments on MSTU including anti-hypertensives (24), anti-epileptic medications (7), coagulopathy reversal (1), and mannitol (1). In patients with initial diagnosis of possible AIS, final diagnoses were 29 AIS and 25 non-strokes, while in patients initially diagnosed with unlikely AIS, 5 were AIS and 38 were non-strokes in the final discharge diagnosis.

Conclusion:
About a third of MSTU encounters were deemed not AIS initially, including intra cranial hemorrhage and seizure. MSTU can also be utilized to provide early pre-hospital treatments in emergent neurological conditions other than AIS.
Abstract 8: The Pipeline Embolization Device: Midterm Results and Predictors of Outcomes in 335 Consecutive Patients
Authors: Chalouhi Nohra , Daou Badih , Starke Robert M , Barros Guilherme , Tjoumakaris Stavropoula , Rosenwasser Robert , Hasan David , Jabbour Pascal
Published: March 2022

Introduction:
Flow diversion has emerged as a promising treatment for intracranial aneurysms. The safety and efficacy of this new technology is under investigation. We present the largest single-center experience to date with the pipeline embolization device (PED) and identify several predictors of outcomes.

Methods:
The study includes 335 consecutive patients who underwent PED treatment at our institution between 2011-2015. Safety data was prospectively recorded both peri-operatively and through follow-up. Angiographic images were independently reviewed and aneurysm occlusion classified as complete (100%), near-complete (95-99%), or incomplete (<95%).

Results:
Mean Aneurysm size was 9.4 mm. Aneurysms were saccular in 84% and fusiform/dissecting in 16%. Seventeen patients (5%) were treated in the setting of subarachnoid hemorrhage (SAH). The mean number of PEDs used was 1.2, and this number significantly decreased from 1.9 early in the study to 1.1 in the last year (p<0.05). Complications occurred in 5% which included a 3.0% hemorrhagic complication rate, 1.5% thromboembolic complication rate, and 0.5% rate of PED migration. Predictors of complications were increasing aneurysm size, early discontinuation of dual antiplatelet therapy, and treatment in the setting of SAH. At follow-up (mean, 14 months), aneurysm occlusion was complete in 77.6%, near-complete in 9.1%, and incomplete in 13.3%. No patient had aneurysm recurrence. Predictors of incomplete occlusion were older patients, previously coiled/stented aneurysms, and MCA and posterior circulation aneurysms. At the latest follow-up, favorable outcomes (mRS 0-2) were noted in 95.7%. Neurologic mortality was 1.7% and neurologic morbidity was 1.2%. Multivariate predictors of poor outcome were early discontinuation of antiplatelet therapy, increasing aneurysm size, and increasing number of PEDs deployed.

Conclusion:
Treatment with the PED has an excellent safety-efficacy profile at large cerebrovascular centers. Several key factors associated with outcomes are discussed. Prolonged dual antiplatelet therapy is crucial for avoidance of complications. Off label locations are associated with lower occlusion rates. A single PED should be used whenever possible.
Abstract 80: Drive-Time Proximity to Certified Stroke Centers in California, 2015
Authors: Reynen David J , Darsie Brendan , Kamigaki Alisa , Bates Janet
Published: March 2022

Introduction:
As access to timely, optimal treatment for acute stroke is associated with lower stroke mortality, understanding the relative access to acute stroke care at a certified primary and/or comprehensive stroke center (CPCSC) is essential for the development of a statewide system of care. The present study aims to describe this access, in relation to the relative burden of stroke mortality in California.

Hypothesis:
It is hypothesized that: (1) Overall, in California, access to CPCSCs is relatively high; and (2) Californians who reside in areas with the highest stroke mortality rates have less access to CPCSCs than do those who reside in areas with the lowest stroke mortality rates.

Methods:
Using ArcView, a map was created, showing the location of each of the 171 Joint Commission CPCSCs in California, the geographic area within a 40 minute drive-time of each center, and the underlying relative stroke mortality rate in each service area.

Results:
Overall, 92% of Californians live within a 40 minute drive of a CPCSC. Further, while 98% of those who live in the least burdensome areas (in terms of stroke mortality) have access to such a center, only 65% of those who live in the most burdensome areas have this kind of access. Two geographic examples of this latter situation include California’s Central Valley and the most northern counties.

Conclusions:
It is incumbent upon California’s public health and emergency medical systems to ensure that all Californians have access to high quality acute stroke care at CPCSCs, especially as clinical standards of care advance. Utilizing GIS technology can help identify potential service gaps and inform ongoing and future efforts to ensure this access.
Abstract 81: Safety and Efficacy of Intravenous Thrombolysis in Telestroke Networks: a Systematic Review and Meta-analysis
Authors: Kepplinger Jessica , Barlinn Kristian , Deckert Stefanie , Scheibe Madlen , Bodechtel Ulf , Schmitt Jochen
Published: March 2022

Introduction:
The aim of the present systematic review and meta-analysis was to evaluate the safety and efficacy of intravenous thrombolysis with tissue plasminogen activator (tPA) delivered through telestroke networks in patients with acute cerebral ischemia.

Methods:
We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available randomized controlled and prospective non-randomized studies that compared telemedicine-guided thrombolysis to either phone-guided or on-site thrombolysis. Outcomes of interest were mortality and favorable functional outcome (i.e., modified Rankin scale 0-1) at 90-days and any tPA-associated intracerebral hemorrhage. Fixed-effect model was used to compute pooled effect estimates and the I2 statistic was used to assess heterogeneity.

Results:
Of 529 records identified through database searching, only five studies with a total of 1,562 patients fulfilled our eligibility criteria. Intracerebral hemorrhage rates were similar between patients subjected to telemedicine-guided thrombolysis and those receiving tPA after phone consultation or on-site at a stroke center (odds ratio=0.68, 95%CI: 0.36-1.26; p=0.216) with no evidence of heterogeneity (I2=0%). Neither there was a difference in mortality (odds ratio=1.17, 95%CI: 0.85-1.61; p=0.328) nor in favorable functional outcome (odds ratio=1.24, 95%CI: 0.83-1.86; p=0.291) at 90-days between telemedicine-guided thrombolysis and phone-guided or on-site thrombolysis. There was evidence of low heterogeneity (I2=29% and 37%, respectively; p>0.1). No evidence of publication bias (p>0.1, Egger statistical test) was detected.

Conclusions:
Our findings indicate that intravenous tPA delivery through telestroke networks is safe and effective. Lack of prospective trials, however, emphasize the need to further substantiate these findings in studies with sound methodological quality.
Abstract 83: Field Validation of Prehospital LAMS Score to Identify Large Vessel Occlusion Ischemic Stroke Patients for Direct Routing to Emergency Neuroendovascular Centers
Authors: Noorian Alireza , Sanossian Nerses , Liebeskind David S , Starkman Sidney , Eckstein Marc , Stratton Samuel , Woolf Graham G , Chatfield Fiona , Conwit Robin , Saver Jeffrey L
Published: March 2022

Background:
As endovascular (EV) thrombectomy is a proven highly effective treatment for acute ischemic stroke due to large vessel occlusion (LVO), there is an urgent need for validated tools for paramedic use to identify likely LVO patients for direct routing to EV-capable centers. A deficit score ≥4 on the Los Angeles Motor Scale (LAMS) performed well in identifying such patients when administered by physicians in the ED. We now report a prospective validation with LAMS performed by paramedics in the field.

Methods:
We analyzed all acute cerebral ischemia patients in the NIH FAST-MAG prehospital treatment trial who had LVO on first vessel imaging (CTA, MRA, or cath angio) done within 6h of last known well and prior to start of IV tPA. Prehospital LAMS was performed by paramedics prior to field enrollment. Hospital arrival (HA) LAMS and NIHSS were subsequently done by trained study nurses after ED arrival. LVO in a proximal cerebral artery (ICA, MCA M1 & M2, Basilar) was determined by 3 vascular neurologists with expertise in neuroimaging.

Results:
Among 190 patients, age was 68 (±13), 45% female. Paramedic (PM) prehospital LAMS were done 21 (IQR 14-38) mins after last known well (LKW), and 33 (27-39) mins before ED arrival. The HA LAMS and HA NIHSS were done 154 (121-180) mins after LKW. On PM LAMS, median score was 4 (3-5) and 57% had score ≥4. Vessel imaging was done 41 (SD 97) mins after ED arrival. Overall, 95 (50%) patients had LVO, including MCA (n=62), ICA (29) and basilar (4). PM LAMS scores were higher in LVO patients, 5 vs. 3, p<0.001. When performed simultaneously with the NIHSS, HA LAMS ≥ 4 showed similar accuracy to HA NIHSS ≥ 10 in identifying LVO, c statistics 0.73 vs 0.77. The PM LAMS showed similar accuracy (c statistic 0.70) (slightly less discrimination is expected because of dynamic stroke evolution in the first 60 mins). For LVO, prehospital PM LAMS≥4 showed sensitivity 74%, specificity 58%, positive likelihood ratio 1.76 and negative LR 0.46.

Conclusions:
The Los Angeles Motor Scale score identifies LVO in acute cerebral ischemia patients as well as the current gold standard NIHSS. In prospective field validation testing, a positive paramedic LAMS increased the likelihood of LVO by 76% and a negative cut the chance of LVO by more than half.
Abstract 85: Small Vessel Disease and Stroke During Sleep
Authors: Lauer Arne , Ay Hakan , Charidimou Andreas , Bianchi Matt , Ayres Alison , Schwab Kristin , Viswanathan Anand , Rosand Jonathan , Greenberg Steven , Gurol Edip M
Published: March 2022

Introduction/Hypothesis:
Stroke onset during sleep is common and sleep related pathologies have been associated with increased stroke risk. Based on available preliminary data, we tested the hypothesis that stroke during sleep is associated with small vessel disease (SVD).

Methods:
Prospectively collected data from patients consecutively enrolled after an intracerebral hemorrhage (ICH) related to SVD or after an ischemic stroke (IS) were analyzed. Symptom onset was recorded in relation to sleep vs. awake. Etiology of ICH was coded as cerebral amyloid angiopathy (CAA, per Boston criteria) and hypertensive deep ICH (HTN-ICH). The IS cohort was characterized based on the Causative Classification of Stroke system (5 subtype CCS). We compared frequencies of stroke onset during sleep between the SVD-related ICH and IS cohorts. Event rates, proportions of strokes during sleep and its associations (etiology, risk factors and stroke characteristics) were also analyzed within each cohort.

Results:
We analyzed 1,038 ICH (mean age: 72.5y +/- 13.0y, 45.4% female) and 1,812 IS patients (mean age: 67.9y +/- 15.9y, 46.4% female). Stroke while asleep was significantly more common among ICH patients (n=282, 26.6%) when compared to IS (n=363, 20.0%, p<0.001). This association between SVD-related ICH and stroke during sleep remained significant after controlling for age, gender and other risk factors (p<0.001). CAA-related ICH and small artery occlusion (SAA) related IS were etiologic subtypes more common among patients who had a stroke during sleep within their respective cohorts (asleep vs awake for CAA within ICH: 57.2% vs. 48.0%, p=0.008 and for SAA within IS: 19.3% vs. 9.1%, p<0.001). CAA and SAA etiologic types remained independent predictors of ICH and IS during sleep in respective multivariate models including other clinical features and risk factors (p=0.019 and p=0.011).

Conclusions:
Stroke during sleep was strongly associated with SVD-related ICH when compared to all IS. CAA within ICH group and SAA etiology within IS cohort were related to stroke during sleep in univariate and multivariate models. Presence of SVD can interact with sleep pathologies and/or sleep related hemodynamic changes to cause ischemic and hemorrhagic stroke.
Abstract 90: Cerebral Microbleeds in CADASIL: Influence of APOE Genotype and Hypertension
Authors: Lee Jungseok , Kang Chul-hoo , Oh Jung-Hwan , Park Joon Hyuk , Fisher Mark
Published: March 2022

Introduction:
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a genetic disorder with an important predisposition for development of cerebral microbleeds (CMB). However, the relative impact of the two most common risk factors for CMB, hypertension and cerebral amyloid angiopathy, in CADASIL is uncertain.

Hypothesis:
We hypothesized that APOE (apolipoprotein E, an important predictor and correlate of cerebral amyloid angiopathy) genotype and hypertension influenced the presence and distribution of CMB in patients with CADASIL.

Methods:
CMB were identified as small (up to 10 mm) areas of signal void seen on 3.0T MRI susceptibility-weighted images. The locations of CMB were characterized as lobar, deep, and infra-tentorial.

Results:
In 83 patients with CADASIL (mean age 62.5 years), CMB were observed in 69.9% (58/83) of the total patient population. The most common areas of CMB were deep (57.8%, 48/83), lobar (50.6%, 42/83), and infra-tentorial location (38.4%, 33/83). Hypertension was found in 59% (49/83) of patients. APOE genotype frequencies were: ε2/ε3 9.6% (8/83); ε2/ε4 2.4% (2/83); ε3/ε3 57.8% (48/83); ε3/ε4 30.1% (25/83). Hypertension was associated with presence of CMB in lobar (p<0.001), deep (p=0.035), and infra-tentorial locations (p=0.012). However, no significant associations were found between APOE genotype and presence of CMB in any location.

Conclusions:
In this cohort of CADASIL patients, hypertension but not APOE genotype predicted presence of CMB in all locations. These findings suggest that hypertension may amplify the arteriopathy of CADASIL in the development of CMB.
Abstract 95: MRI Description of an Adult Primary Angiitis of the Central Nervous System in the French COVAC Cohort
Authors: Boulouis Gregoire , de Boysson Hubert , Zuber Mathieu , Guillevin Loic , Meary Eric , Pagnoux Christian , Naggara Olivier
Published: March 2022

Introduction:
Primary angiitis of the central nervous system (PACNS) is a potentially severe inflammatory disease of central nervous system vessels and despite its extreme sparsity, knowledge has improved within past decades. PACNS diagnosis, however, remains challenging, mainly because of the multiple mimickers and possible differential diagnoses. Previous MRI/MR Angiography descriptions of PACNS adult patients might have become outdated

Hypothesis:
To report an updated overview and pictural review of MR/MRA findings in adult PACNS, determine type/distribution of parenchymal, meningeal and vascular lesions in an independent multicentric inception cohort.

Methods:
Patients from the French mutlicentric COVAC cohort, adults with biopsy/angiographically proven PACNS were included if they had MRI/MRA available imaging upon diagnosis for retrospective review. Systematic imaging review was performed blinded to clinical data.

Results:
Among the 91 enrolled patients in cohort, 60 met inclusion criteria for this study. Mean age was 45yo (±12.9). Patients presented initially with focal deficit(s) (83%), headaches (53%), cognitive disorder (40%) or seizures (38.3%). MRI was abnormal in all patients, most common finding being ischemic stroke following a small arteries distribution with multi-territorial lesions (50% of evaluated patients), with a predominant anterior distribution. 57% of parenchymal hemorrhagic lesions were hemorrhagic transformation of ischemic strokes. 26% of patients had otherwise subarachnoid hemorrhage. 42% of patients demonstrated preeminent leptomeningeal enhancement. Seven had tumor like presentation. 77% of MRA studies were abnormal revealing proximal/distal stenoses in respectively 57% and 61% of patients. Only 11 patients demonstrated a typical beading aspect on MRA. DSA unmasked distal stenotic lesions in <10% of patients with normal MRA.

Discussion:
We present the largest to date MRI/MRA systematically assessed cohort of adult PACNS patients, extend our current knowledge of this rare and heterogeneous disease and present an extensive analysis of MRI and MR Angiography characteristics of PACNS in adults.
Abstract 97: Association between Non-Stenosing Carotid Artery Plaque and Acute Ischemic Stroke
Authors: Gupta Ajay , Gialdini Gino , Giambrone Ashley , Lerario Michael P , Baradaran Hediyeh , Navi Babak B , Marshall Randolph S , Iadecola Costantino , Kamel Hooman
Published: March 2022

Introduction:
It is unknown whether stroke risk is increased in the setting of large-artery atherosclerotic plaque that does not cause significant luminal stenosis.

Hypothesis:
We hypothesized that the prevalence of vulnerable, non-stenosing carotid artery plaque on the side ipsilateral to an acute brain infarction would be higher than on the contralateral side.

Methods:
Using a prospective stroke registry, we identified patients with acute infarction limited to the vascular territory of one internal carotid artery (ICA) and no large-vessel atherosclerosis based on the common criterion of greater than or equal to 50% luminal stenosis. We used magnetic resonance angiography to ascertain vulnerable ICA plaque, as defined by the presence of intraplaque high-intensity signal (IHIS). We used McNemar’s test for correlated proportions to compare the prevalence of IHIS on the side ipsilateral to acute infarction versus the contralateral side within individual subjects.

Results:
We analyzed 218 arteries in 109 unique patients. IHIS-positive ICA plaque was found in 31 arteries (14.2%), with 22 IHIS-positive lesions occurring ipsilateral to the side of the patient’s infarction versus 9 IHIS-positive lesions contralateral to the side of infarction (P = 0.01). When stratified by stroke subtype (See Figure which includes representative MRA images), IHIS was associated with infarctions that were classified as of unknown etiology (P < 0.001), but not in those due to cardioembolism (P = 0.76) or small-vessel occlusion (P = 0.49).

Conclusion:
We found an association between vulnerable, non-hemodynamically-significant ICA plaque and acute brain infarction. This association held true only in the subset of patients with stroke of undetermined etiology, suggesting that non-stenosing large-artery atherosclerotic lesions may explain some proportion of cryptogenic strokes.