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Abdominal aortic aneurysm (AAA) is a progressive dilatation of the aorta that can lead to aortic rupture. The pathophysiology of the disease is not well characterized but is known to be caused by the general breakdown of the extracellular matrix within the aortic wall. In this comprehensive literature review, all current research on proteins that have been investigated for their potential prognostic capabilities in patients with AAA was included. A total of 45 proteins were found to be potential prognostic biomarkers for AAA, predicting incidence of AAA, AAA rupture, AAA growth, endoleak, and post-surgical mortality. The 45 proteins fell into the following seven general categories based on their primary function: (1) cardiovascular health, (2) hemostasis, (3) transport proteins, (4) inflammation and immunity, (5) kidney function, (6) cellular structure, (7) and hormones and growth factors. This is the most up-to-date literature review on current prognostic markers for AAA and their functions. This review outlines the wide pathophysiological processes that are implicated in AAA disease progression.

Abstract Background Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. Methods Five hundred thirteen participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. Results Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson’s disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. Conclusions In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.

Introduction: MRI-visible perivascular spaces (PVS) are a neuroimaging feature of cerebral small vessel disease and are commonly observed in patients with cerebrovascular and neurodegenerative disease. However, it is unclear whether PVS burden is associated with cognition. The aim of this study was to investigate the potential associations between PVS volumes, brain atrophy, white matter hyperintensities (WMH), and speeded executive function, in patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Methods: ONDRI participants (n=333) clinically diagnosed with Alzheimer's disease/mild cognitive impairment (ADMCI), frontotemporal dementia (FTD), and cerebrovascular diseases (CVD), with clinical, neuropsychological, MRI, plasma biomarkers (glial fibrillary acidic protein (GFAP); neurofilament light, (NfL); p-tau181; Aβ42/40), and available apolipoprotein E epsilon 4 (APOE E4) status, were included in this analysis. MRI-based measurements for brain parenchymal fraction (BPF), lacunes, PVS and WMH were extracted using the ONDRI imaging pipeline. The neuropsychological test scores were standardized (z-transformed), speeded executive function z- scores were computed as the mean of digit symbol modalities test and trail making test part B timed z-scores. The variables selected in bivariate analysis (p

Abstract Introduction The current therapeutic landscape of Alzheimer's disease (AD) is evolving rapidly. Our treatment options include new anti-amyloid-β protein disease-modifying therapies (DMTs) that decrease cognitive decline in patients with early AD (prodromal and mild AD dementia). Despite these advances, we have limited information on how neurologists would apply the results of recent DMT trials to make treatment decisions. Our goal is to identify factors associated with the use of new AD DMTs among neurologists applying concepts from behavioral economics. Methods This non-interventional, cross-sectional, web-based study will assess 400 neurologists with expertise in AD from across Spain. Participants will start by completing demographic information, practice settings, and a behavioral battery to address their tolerance to uncertainty and risk preferences. Participants will then be presented with 10 simulated case scenarios or vignettes of common encounters in patients with early AD to evaluate treatment initiation with anti-amyloid-β DMTs (e.g., aducanumab, lecanemab, etc.). The primary outcomes will be therapeutic inertia and suboptimal decisions. Discrete choice experiments will be used to determine the weight of factors influencing treatment choices. Results The results of this study will provide new insights into a better understanding of the most relevant factors associated with therapeutic decisions on the use of DMTs, assessing how neurologists handle uncertainty when making treatment choices, and identifying the prevalence of therapeutic inertia in the management of early AD.

Background: Differences in ischemic stroke outcomes occur in those with limited English proficiency. These health disparities might arise when a patient's spoken language is discordant from the primary language utilized by the health system. Language concordance is an understudied concept. We examined whether language concordance is associated with differences in vascular risk or post-stroke functional outcomes, depression, obstructive sleep apnea and cognitive impairment. Methods: This was a multi-center observational cross-sectional cohort study. Patients with ischemic stroke/transient ischemic attack (TIA) were consecutively recruited across eight regional stroke centers in Ontario, Canada (2012 – 2018). Participants were language concordant (LC) if they spoke English as their native language, ESL if they used English as a second language, or language discordant (LD) if non-English speaking and requiring translation. Results: 8156 screened patients. 6,556 met inclusion criteria: 5067 LC, 1207 ESL and 282 LD. Compared to LC patients: (i) ESL had increased odds of diabetes (OR = 1.28, p = 0.002), dyslipidemia (OR = 1.20, p = 0.007), and hypertension (OR = 1.37, p

Background Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion. Methods We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios. Results There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P

Background Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra‐high‐performance liquid chromatography–mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13‐DiHOME/12(13)‐EpOME ratio (β=0.251, P=0.023). The 12,13‐DiHOME/12(13)‐EpOME ratio was associated with more lacunes (β=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13‐DiHOME/12(13)‐EpOME and 9,10‐DiHOME/9(10)‐EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, P

Abstract Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson’s disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.

BackgroundThe current management of patients with Dementia, primarily with Alzheimer's Disease (AD) is rapidly evolving. However, limited information is available about the current gaps and decision-making in primary care.ObjectivesTo evaluate factors associated with gaps, risk preferences regarding diagnostic and therapeutic choices in the management of patients with AD by primary care physicians (PCP) from across Canada.MethodsWe propose a non-interventional, cross-sectional pilot study involving 120 primary care physicians referred from the College of Family Physicians of Canada to assess diagnostic and therapeutic decisions in the management of ten simulated AD-related case-scenarios commonly encountered in clinical practice. We initially describe the current landscape and gaps regarding diagnostic and therapeutic challenges in the management of patients with AD in primary care. Then, we provide concepts from behavioral economics and neuroeconomics applied to medical decision-making. Specifically, we include standardized tests to measure risk aversion, physicians' reactions to uncertainty, and questions related to risk preferences in different domains. Finally, we summarize the protocol to be implemented to address our goals. The primary study outcome is the proportion of participants that elect to defer initial investigations to the specialist and the associated factors. Secondary outcomes include the proportion of PCP willing to order cerebral spinal fluid studies, PET scans, or initiate treatment according to the simulated case-scenarios. The study will be conducted in English and French.ConclusionsThe study findings will contribute a better understanding of relevant factors associated with diagnostic and therapeutic decisions of PCP in the management of AD, identifying participant's preferences and evaluating the role of behavioral aspects such tolerance to uncertainty, aversion to ambiguity, and therapeutic inertia.

Background The best management of basilar artery occlusion (BAO) remains uncertain. The BASICS (Basilar Artery International Cooperation Study) and the BEST (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) trials reported neutral results. We sought to understand physicians’ approaches to BAOs and whether further BAO randomized controlled trials were warranted. Methods We conducted an online international survey from January to March 2022 to stroke neurologists and neurointerventionalists. Survey questions were designed to examine clinical and imaging parameters under which clinicians would offer (or rescind) a patient with BAO to endovascular therapy (EVT) or best medical management versus enrollment into a randomized clinical trial. Results Of >3002 invited participants, 1245 responded (41.4% response rate) from 73 countries, including 54.7% stroke neurologists and 43.6% neurointerventionalists. More than 95% of respondents would offer EVT to patients with BAO, albeit in various clinical circumstances. There were 70.0% of respondents who indicated that the BASICS and BEST trials did not change their practice. Only 22.1% of respondents would perform EVT according to anterior circulation occlusion criteria. The selection of patients for BAO EVT by clinical severity, timing, and imaging modality differed according to geography, specialty, and country income level. Over 80% of respondents agreed that further randomized clinical trials for BAO were warranted. Moreover, 45.6% of respondents indicated they would find it acceptable to enroll all trial‐eligible patients into the medical arm of a BAO trial, whereas 26.3% would not enroll. Conclusion Most stroke physicians continue to believe in the efficacy of EVT in selected patients with BAO in spite of BEST and BASICS. There is no consensus on which selection criteria to use, and few clinicians would use anterior circulation occlusion criteria for BAOs. Further randomized clinical trials for BAO are warranted.

Carotid artery stenosis (CAS), an atherosclerotic disease of the carotid artery, is one of the leading causes of transient ischemic attacks (TIA) and cerebrovascular attacks (CVA). The atherogenic process of CAS affects a wide range of physiological processes, such as inflammation, endothelial cell function, smooth muscle cell migration and many more. The current gold-standard test for CAS is Doppler ultrasound; however, there is yet to be determined a strong, clinically validated biomarker in the blood that can diagnose patients with CAS and/or predict adverse outcomes in such patients. In this comprehensive literature review, we evaluated all of the current research on plasma and serum proteins that are current contenders for biomarkers for CAS. In this literature review, 36 proteins found as potential biomarkers for CAS were categorized in to the following nine categories based on protein function: (1) Inflammation and Immunity, (2) Lipid Metabolism, (3) Haemostasis, (4) Cardiovascular Markers, (5) Markers of Kidney Function, (6) Bone Health, (7) Cellular Structure, (8) Growth Factors, and (9) Hormones. This literature review is the most up-to-date and current comprehensive review of research on biomarkers of CAS, and the only review that demonstrated the several pathways that contribute to the initiation and progression of the disease. With this review, future studies can determine if any new markers, or a panel of the proteins explored in this study, may be contenders as diagnostic or prognostic markers for CAS.

Abstract Background Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. Methods Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). Results In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer's disease participant; (2) a duplication of exons 1–5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of >3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7–11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. Conclusion The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.

Abstract Crucial elements for achieving optimal long-term outcomes in multiple sclerosis (MS) are patient confidence and effective physician–patient communication. Patient-reported instruments may provide the means to fill the gap in currently available clinician-rated measures. The SymptoMScreen (SMSS) is a brief self-assessment tool for measuring symptom severity in 12 neurologic domains commonly affected by MS. We conducted a non-interventional study to assess the dimensional structure and item characteristics of the SMSS. A total of 218 patients with relapsing–remitting MS and mild disability (median Expanded Disability Status Scale score 2.0) were studied. Symptom severity was low (SMSS score 13.5, interquartile range 4.2–27), fatigue being the domain with the highest impact. A non-parametric item response theory, i.e., Mokken analysis, found that the SMSS is a robust one-dimensional scale (overall scalability index H 0.60) with high reliability (Cronbach’s alpha 0.94). The confirmatory factor analysis model confirmed the unidimensional structure (comparative fit index 1.0, root-mean-square error of approximation 0.001). Samejima’s model fitted well an unconstrained model with different item difficulties. The SMSS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement addition to measure the symptom severity in clinical practice.

Background The therapeutic landscape for spinal muscular atrophy has changed in the last few years, encompassing respiratory/motor function and life expectancy benefits. However, physicians still have the challenge of tailoring individuals’ treatment to therapeutic goals, disease progression, patient/caregiver’s preferences, and personal experience to achieve an optimal risk/benefit balance. This study aims to provide insight into the preferred treatment choices of pediatric neurologists managing spinal muscular atrophy in their daily practice and to recognize behavioral factors that may influence decision-making. Methods This is a noninterventional, cross-sectional pilot study involving 50 pediatric neurologists managing spinal muscular atrophy in Spain. We designed an online platform that contains 13 simulated case scenarios of common presentations of patients with spinal muscular atrophy. The primary study outcome will be treatment preferences according to the percentages of participants who select treatment initiation when recommended, switch therapies when there is evidence of disease progression, and select treatment discontinuation when disease progression puts patients outside treatment recommendation (11 case scenarios). Secondary outcomes include therapeutic inertia prevalence (11 case scenarios), herding phenomenon prevalence (2 case scenarios), care-related regret prevalence (specific questions) and intensity (10-item Regret Intensity Scale), occupational burnout prevalence (nonproprietary single-item measure), and risk preferences (uncertainty test and risk aversion assessment). Conclusions The study findings will contribute to better understand relevant factors associated with therapeutic decisions of pediatric neurologists in spinal muscular atrophy, identifying treatment preferences and evaluating the role of behavioral aspects such as therapeutic inertia, herding, regret, and workplace burnout.

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.

Background: Decisions based on erroneous assessments may result in unrealistic patient and family expectations, suboptimal advice, incorrect treatment, or costly medical errors. Regret is a common emotion in daily life that involves counterfactual thinking when considering alternative choices. Limited information is available on care-related regret affecting healthcare professionals managing patients with multiple sclerosis (MS).Methods: We reviewed identified gaps in the literature by searching for the combination of the following keywords in Pubmed: “regret and decision,” “regret and physicians,” and “regret and nurses.” An expert panel of neurologists, a nurse, a psychiatrist, a pharmacist, and a psychometrics specialist participated in the study design. Care-related regret will be assessed by a behavioral battery including the standardized questionnaire Regret Intensity Scale (RIS-10) and 15 new specific items. Six items will evaluate regret in the most common social domains affecting individuals (financial, driving, sports—recreation, work, own health, and confidence in people). Another nine items will explore past and recent regret experiences in common situations experienced by healthcare professionals caring for patients with MS. We will also assess concomitant behavioral characteristics of healthcare professionals that could be associated with regret: coping strategies, life satisfaction, mood, positive social behaviors, occupational burnout, and tolerance to uncertainty.Planned Outcomes: This is the first comprehensive and standardized protocol to assess care-related regret and associated behavioral factors among healthcare professionals managing MS. These results will allow to understand and ameliorate regret in healthcare professionals.Spanish National Register (SL42129-20/598-E).

Background Nurse practitioners (NPs) play a critical role in the multidisciplinary management of patients with multiple sclerosis (MS). Neurologists´ behavioral characteristics have been associated with suboptimal clinical decisions. However, limited information is available on their impact among NPs involved in MS care. The aim of this study was to assess nurses´ therapeutic choices to understand behavioral factors influencing their decision making process. Methods A non-interventional, cross-sectional, web-based study was conducted. NPs actively involved in the care of patients with MS were invited to participate in the study by the Spanish Society of Neurology Nursing. Participants answered questions regarding their standard practice and therapeutic management of seven simulated relapsing-remitting MS (RRMS) case scenarios. A behavioral battery was used to measure participants´ life satisfaction, mood, positive social behaviors, feeling of helpfulness, attitudes toward adoption of evidence-based innovations, occupational burnout, and healthcare-related regret. The outcome of interest was therapeutic inertia (TI), defined as the lack of treatment escalation when there is clinical and radiological evidence of disease activity. A score to quantify TI was created based on the number of simulated scenarios where treatment intensification was warranted. Results Overall, 331 NPs were invited to participate, 130 initiated the study, and 96 (29%) completed the study. The mean age (SD) was 44.6 (9.8) years and 91.7% were female. Seventy-three participants (76.0%) felt their opinions had a significant influence on neurologists´ therapeutic decisions. Sixteen NPs (16.5%) showed severe emotional exhaustion related to work and 13 (13.5%) had depressive symptoms. The mean (SD) TI score was 0.97 (1.1). Fifty-six of NPs showed TI in at least one case scenario. Higher years of nursing experience (p = 0.014), feeling of helpfulness (p = 0.014), positive attitudes toward innovations (p = 0.046), and a higher intensity of care-related regret (p = 0.021) were associated with a lower risk of TI (adjusted R2 = 0.28). Burnout was associated with higher risk of TI (p = 0.001). Conclusions Although NPs cannot prescribe MS treatments in Spain, their behavioral characteristics may influence the management of patients with RRMS. Continuing education and specific strategies for reducing occupational burnout may lead to better management skills and improve MS care.

BackgroundRegional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases (CVD) can be estimated using specialized neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misclassification errors and segmentation failures.PurposeThe main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer’s (FS’s) cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and CVD, with varying degrees of neurovascular lesions and brain atrophy.MethodsIn 155 CVD participants enrolled in the Ontario Neurodegenerative Disease Research Initiative (ONDRI), FS outputs were compared between a fully automated, unmodified procedure and a corrected procedure that accounted for potential sources of error due to atrophy and neurovascular lesions. Quality control (QC) measures were obtained from both procedures. Association between cortical thickness and global cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) score was also investigated from both procedures.ResultsCorrected procedures increased “Acceptable” QC ratings from 18 to 76% for the cortical ribbon and from 38 to 92% for tissue segmentation. Corrected procedures reduced “Fail” ratings from 11 to 0% for the cortical ribbon and 62 to 8% for tissue segmentation. FS-based segmentation of T1-weighted white matter hypointensities were significantly greater in the corrected procedure (5.8 mL vs. 15.9 mL, p < 0.001). The unmodified procedure yielded no significant associations with global cognitive status, whereas the corrected procedure yielded positive associations between MoCA total score and clusters of cortical thickness in the left superior parietal (p = 0.018) and left insula (p = 0.04) regions. Further analyses with the corrected cortical thickness results and MoCA subscores showed a positive association between left superior parietal cortical thickness and Attention (p < 0.001).ConclusionThese findings suggest that correction procedures which account for brain atrophy and neurovascular lesions can significantly improve FS’s segmentation results and reduce failure rates, thus maximizing power by preventing the loss of our important study participants. Future work will examine relationships between cortical thickness, cerebral small vessel disease, and cognitive dysfunction due to neurodegenerative disease in the ONDRI study.

Background: Therapeutic inertia (TI) is a common phenomenon among physicians who care for patients with chronic conditions. We evaluated the efficacy of the traffic light system (TLS) educational intervention to reduce TI among neurologists with MS expertise. Methods: In this randomised, controlled trial, 90 neurologists who provide care to MS patients were randomly assigned to the TLS intervention ( n = 45) or to the control group ( n = 45). The educational intervention employed the TLS, a behavioral strategy that facilitates therapeutic choices by facilitating reflective decisions. The TLS consisted in a short, structured, single session intervention of 5-7 min duration. Participants made therapeutic choices of 10 simulated case-scenarios. The primary outcome was a reduction in TI based on a published TI score (case-scenarios in which a participant showed TI divided by the total number of scenarios where TI was possible ranging from 0 to 8). Results: All participants completed the study and were included in the primary analysis. TI was lower in the TLS group (1.47, 95% CI 1.32-1.61) compared to controls (1.93; 95% CI 1.79-2.08). The TLS group had a lower prevalence of TI compared to controls (0.67, 95% CI 0.62-0.71 vs. 0.82, 95% CI 0.78-0.86; p = 0.001). The multivariate analysis, adjusted for age, specialty, years of practice, and risk preference showed a 70% reduction in TI for the TLS intervention compared to controls (OR 0.30; 95% CI 0.10-0.89). Conclusions: In this randomized trial, the TLS strategy decreases the incidence of TI in MS care irrespective of age, expertise, years for training, and risk preference of participants, which would lead to better patient outcomes.

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF).Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groupsResults: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1–17)], followed by the warfarin withdrawal group [11, IQR (1–14, 18)], the no antithrombotic group [5, IQR (1–13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1–10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384–8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group.Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes.

Stroke is one of the leading causes of death and morbidity worldwide. The occurrence of stroke is strongly dependent on well-known vascular risk factors. After rapid modernization, urbanization, and mechanization, East Asian countries have experienced growth in their aged populations, as well as changes in lifestyle and diet. This phenomenon has increased the prevalence of vascular risk factors among Asian populations, which are susceptible to developing cardiovascular risk factors. However, differing patterns of stroke risk factor profiles have been noted in East Asian countries over the past decades. Even though the prevalence of vascular risk factors has changed, hypertension is still prevalent and the burden of diabetes and hypercholesterolemia will continue to increase. Asia remains a high tobacco-consuming area. Although indicators of awareness and management of vascular risk factors have increased in many East Asian countries, their rates still remain low. Here we review the burdens of traditional risk factors, such as hypertension, diabetes, hypercholesterolemia, and smoking in East Asia. We will also discuss the different associations between these vascular risk factors and stroke in Asian and non-Asian populations.

Importance: The prescription of generic (non-proprietary) compared to brand-name drugs is increasing worldwide. In many developing and emerging countries, generics companies market products at similar costs as brand-name competitors benefiting from more flexible compliance rules and regulations for marketing their products in the health system. Together, this phenomenon may influence prescriber's behavior (e.g., maintaining the same treatment despite guideline's recommendations or despite evidence of disease progression).Objectives: To compare the prevalence of therapeutic inertia (TI) between primary prescription of brand-name vs. generic drugs in the management of MS in Argentina.Design: We conducted a population-based online study comprising 117 neurologists with expertise in MS. Participants answered questions regarding their clinical practice, most commonly prescribed disease modifying agents, and therapeutic choices of 10 simulated case-scenarios that assessed TI. Inertia was defined as the lack of treatment initiation or escalation despite evidence of clinical and radiological activity (8 case-scenarios, 720 individual responses). We created the generic-brand name score (GBS) according to the 5 most frequently prescribed generic (n = 16) vs. brand-name (n = 9) drugs for MS, where scores higher than 1 indicated higher prescription of generic drugs and scores lower than 1 indicated higher prescription of brand-name agents. Candidate predictors of prescribing generic drugs included demographic data, MS specialist vs. general neurologist, practice setting, years of practice, volume of MS patients, risk preferences, costs of annual treatment.Participants and setting: population-based prospective study using including neurologists who care for patients with multiple sclerosis across Argentina.Exposure: prescription of generic vs. brand-name MS drugsMain outcome of interest: Therapeutic inertia (TI), defined as lack of treatment escalation when goals are unmet. Secondary outcomes included factors associated with generic drug prescription and costs of MS treatment.Results: Ninety participants completed the study (completion rate 76.9%). TI was observed in 153 (21.3%) of participants' responses. The evaluation of aggregate responses revealed a mean GBS score (SD) of 3.44 (2.1), with 46 (51.1%) participants having a GBS equal to or higher than 1. Older age (OR 1.19; 95% CI 1.00–1.42), being a general neurologist (OR 3.91; 95% CI 1.19–12.8), and being more willing to take risks in multiple domains (SOEP score OR 1.06, 95% CI 1.01–1.12) were associated with higher prescription of generic drugs in MS care. Costs of treatment were not associated with prescribing generic drugs. There was no difference in the annual costs of MS treatment for primary prescribers of brand-name vs. generic drugs (67,500 US$ vs. 67,496 US$; p = 0.99).The evaluation of individual responses revealed that participants with higher prescription of generics—reflected by a higher GBS—had higher incident risk of TI (mean GBS 3.61 for TI vs. 2.96 for no TI; p < 0.001). Multivariate analysis revealed that a prescription of generic agents was associated with an increased incident risk of TI (OR 1.56; 95%CI 1.07–2.29). There was no difference in the annual costs of MS treatment for participants that exhibited TI vs. those without TI (67,426 US$ vs. 67,704 US$; p = 0.66).Conclusions: General neurologist, older age, and willingness to take risks were associated with increased prescription of generic drugs despite similar costs compared to brand-name agents. In our study, the prescription of generic-MS drugs was associated with a higher incident risk of therapeutic inertia.

Introduction: According to previous studies, therapeutic inertia (TI) may affect 7 out of 10 physicians who care for MS patients, particularly in countries where clinical guidelines are not widely used. Limited information is available on the prevalence of TI and its associated factors across Canada.Objectives: (i) To evaluate factors associated with TI amongst neurologists caring for MS patients across Canada; (ii) to compare the prevalence of TI observed in Canadian neurologists to the prevalence of TI observed in Argentinean, Chilean, and Spanish neurologists (historical controls from prior studies).Design: One hundred and eight neurologists with expertise in MS were invited to participate in an online study in Canada. Participants answered questions regarding their clinical practice, risk preferences, management of 10 simulated case-scenarios. The design of that study was similar to that of the prior studies completed in Argentina and Chile (n = 115). TI was defined as lack of treatment initiation or escalation when there was clear evidence of clinical and radiological disease activity (8 case-scenarios, 440 individual responses). A TI score was created & defined as the number of case-scenarios that fit the TI criteria over the total number of presented cases (score range from 0 to 8), with a higher score corresponding to a higher TI. TI scores observed in the Canadian study were compared with those observed in Argentina and Chile, as both studies followed the same design, case-scenarios and methodologies. Predictors of TI included demographic data, MS specialist vs. general neurologist, practice setting, years of practice, volume of MS patients and risk preferences.Results: Fifty-five Canadian neurologists completed the study (completion rate: 50.9%). The mean age (±SD) was 38.3 (±15) years; 47.3% of the participants were female and 56.4% self-identified as MS specialists. Overall, 54 of 440 (12.3%) individual responses were classified as TI. 60% of participants displayed TI in at least one case-scenario. The mean TI score across Canada [0.98 (SD = 1.15)] was significantly lower than the TI score observed in the Argentinean-Chilean [1.82 (SD = 1.47); p < 0.001] study. The multivariable analysis revealed that older age (p = 0.018), years of experience (p = 0.04) and willingness to risk further disease progression by avoiding treatment initiation or treatment change (p = 0.043) were independent predictors of TI.Conclusions: TI in Canada was observed in 6 out of 10 neurologists, affecting on average 1 in 8 therapeutic decisions in MS care. TI in Canada is significantly lower than in the other studied countries. Factors associated with TI include older age, lower years of experience, and willingness to risk disease progression by avoiding treatment initiation or treatment change. Differences in clinical practice patterns and adherence/access to accepted MS guidelines may explain how TI in Canada differs significantly from TI in Argentina-Chile.

Background Statins are commonly used for the prevention of cardiovascular events; however, statins are underutilized in patients with noncoronary atherosclerosis. We sought to establish the rates of statin use in patients with carotid artery disease and to examine the association between statin therapy and outcomes after carotid revascularization. Methods and Results In this population‐level retrospective cohort study, we identified all individuals aged ≥66 years who underwent carotid endarterectomy or stenting in Ontario, Canada (2002–2014). The primary outcome was a composite of 1‐year stroke, myocardial infarction, or death (major adverse cardiac and cerebrovascular events). Five‐year risks were also examined. Adjusted hazard ratios were computed using inverse probability of treatment weighting based on propensity scores. A total of 7893 of 10 723 patients (73.6%) who underwent carotid revascularization were on preprocedural statin therapy; moderate‐ or high‐dose therapy was utilized by 7384 patients (68.9%). The composite rate of 1‐year major adverse cardiac and cerebrovascular events was lower among statin users (adjusted hazard ratio: 0.76; 95% confidence interval, 0.70–0.83). Patients who were on persistent long‐term statin therapy after the carotid procedure continued to experience significantly lower risk of major adverse cardiac and cerebrovascular events at 5 years (adjusted hazard ratio: 0.75, 95% confidence interval, 0.71–0.80). The beneficial associations with statin use were observed regardless of type of carotid revascularization procedure, carotid artery symptom status, or statin dose. Conclusions Continuous statin therapy was associated with a 25% lower risk of long‐term adverse cardiovascular events in patients with significant carotid disease. Along with other supportive evidence, statins should be considered in patients undergoing carotid revascularization, and efforts are required to increase statin use in this undertreated population.

Background: Educational interventions are needed to overcome knowledge-to-action gaps in clinical care. We previously tested the feasibility and potential efficacy of an educational intervention that facilitates treatment decisions in multiple sclerosis care. A demonstration of the usability of such an intervention is crucial prior to demonstration of efficacy in a large trial.Objectives: To evaluate the usability of a novel, pilot-tested intervention aimed at neurologists to improve therapeutic decisions in multiple sclerosis (MS) care.Methods: We surveyed 50 neurologists from Chile, Argentina, and Canada randomized to an educational intervention arm of a pilot feasibility study using the System Usability Score (SUS) to assess the usability of a traffic light system (TLS)-based educational intervention. The TLS facilitates therapeutic decisions, allowing participants to easily recognize high-risk scenarios requiring treatment escalation. The SUS is a validated 10-item questionnaire with five response options. The primary outcome was the average and 95% confidence interval (CI) of the SUS score. Values above 68 are considered highly usable.Results: Of 50 neurologists invited to be part of the study, all completed the SUS scale and the study. For the primary outcome, the average usability score was 74.7 (95%CI 70.1–79.2). There was one outlier with a score of 35. The usability score excluding the outlier was 76.8 (95%CI 72.7–80.8). Multivariate analysis revealed no association between participants' characteristics and the SUS score.Conclusions: Our educational intervention has shown high usability among neurologists. The next step is to evaluate the effectiveness of this educational intervention in facilitating treatment decisions for the management of multiple sclerosis in a large trial.

The landscape of multiple sclerosis (MS) treatment is constantly changing. Significant heterogeneity exists in the efficacy and risks associated with these therapies. Therefore, clinicians have the challenge to tailor treatment based on several factors (disease activity level, risk of progression, individual patient preferences and characteristics, personal expertise, etc.), to identify the optimal balance between safety and efficacy. However, most clinicians have limited education in decision-making and formal training in risk management. Together, these factors may lead to therapeutic inertia (TI); defined as the absence of treatment initiation or intensification when therapeutic goals are unmet. TI may lead to suboptimal treatments choices, worse clinical outcomes, and more disability. This article provides a succinct overview on factors influencing TI in MS care.

BackgroundStroke can affect a variety of cognitive, perceptual, and motor abilities that are important for safe driving. Results of studies assessing post-stroke driving ability are quite variable in the areas and degree of driving impairment among patients. This highlights the need to consider clinical characteristics, including stroke subtype, when assessing driving performance.MethodsWe compared the simulated driving performance of 30 chronic stroke patients (>3 months), including 15 patients with ischemic stroke (IS) and 15 patients with subarachnoid hemorrhage (SAH), and 20 age-matched controls. A preliminary analysis was performed, subdividing IS patients into right (n = 8) and left (n = 6) hemispheric lesions and SAH patients into middle cerebral artery (MCA, n = 5) and anterior communicating artery (n = 6) territory. A secondary analysis was conducted to investigate the cognitive correlates of driving.ResultsNine patients (30%) exhibited impaired simulated driving performance, including four patients with IS (26.7%) and five patients with SAH (33.3%). Both patients with IS (2.3 vs. 0.3, U = 76, p 0.6, p

BackgroundPhysicians often do not initiate or intensify treatments when clearly warranted, a phenomenon known as therapeutic inertia (TI). Limited information is available on educational interventions to ameliorate knowledge-to-action gaps in TI.ObjectivesTo evaluate the feasibility and efficacy of an educational intervention compared to usual care among practicing neurologists caring for patients with multiple sclerosis (MS).MethodsWe conducted a pilot double-blind, parallel-group, randomized clinical trial. Inclusion criteria included neurologists who are actively involved in managing MS patients. Participants were exposed to 20 simulated case-scenarios (10 cases at baseline, and 10 cases post-randomization to usual care vs. educational intervention) of relapsing–remitting MS with moderate or high risk of disease progression. The educational intervention employed a traffic light system (TLS) to facilitate decisions, allowing participants to easily recognize high-risk scenarios requiring treatment escalation. We also measured differences between blocks to invoke decision fatigue. The control group responded as they would do in their usual clinical practice not exposed to the educational intervention. The primary feasibility outcome was the proportion of participants who completed the study and the proportion of participants who correctly identified a high-risk case-scenario with the “red traffic light.” Secondary outcomes included decision fatigue (defined as an increment of TI in the second block of case-scenarios compared to the first block) and the efficacy of the educational intervention measured as a reduction in TI for MS treatment.ResultsOf 30 neurologists invited to be part of the study, the participation rate was 83.3% (n = 25). Of the 25 participants, 14 were randomly assigned to the control group and 11 to the intervention group. TI was present in 72.0% of participants in at least one case scenario. For the primary feasibility outcome, the completion rate of the study was 100% (25/25 participants). Overall, 77.4% of participants correctly identified the “red traffic light” for clinical-scenarios with high risk of disease progression. Similarly, 86.4% of participants correctly identified the “yellow traffic light” for cases that would require a reassessment within 6–12 months. For the secondary fatigue outcome, within-group analysis showed a significant increased prevalence of TI in the second block of case-scenarios (decision fatigue) among participants randomized to the control group (TI pre-intervention 57.1% vs. TI post-intervention 71.4%; p = 0.015), but not in the active group (TI pre-intervention 54.6% vs. TI post-intervention 63.6%; p = 0.14). For the efficacy outcome, we found a non-significant reduction in TI for the targeted intervention compared to controls (22.6 vs. 33.9% post-intervention; OR 0.57; 95% CI 0.26–1.22).ConclusionAn educational intervention applying the TLS is feasible and shows some promising results in the identification of high-risk scenarios to reduce decision fatigue and TI. Larger studies are needed to determine the efficacy of the proposed educational intervention.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03134794.

Apnea test is a crucial requirement for determining the diagnosis of brain death (BD). There are few reports considering clinical complications during this procedure. We describe a major complication during performing the apnea test. We also analyse their practical and legal implications, and review the complications of this procedure in the literature. A 54 year-old man was admitted for impaired consciousness due to a massive intracerebral hemorrhage. Six hours later, he had no motor response, and all brainstem reflexes were negative. The patient fulfilled American Academy of Neurology (AAN) criteria for determining BD. During the apnea test, the patient developed pneumothorax, pneumoperitoneum, and finally cardiac arrest. Apnea test is a necessary requirement for the diagnosis of brain death. However, it is not innocuous and caution must be take in particular clinical situations. Complications during the apnea test could be more frequent than reported and may have practical and legal implications. Further prospective studies are necessary to evaluate the frequency and nature of complications during this practice.El test de apnea (AT) es un requerimiento esencial para el diagnóstico de muerte encefálica. Hay pocos estudios que consideren complicaciones clínicas relacionadas con este procedimiento. Describimos un paciente que desarrolló una complicación mayor mientras se efectuaba el test de apnea. Realizamos una revisión de las complicaciones relacionadas con este procedimiento en la literatura. CASO CLÍNICO: Un hombre de 54 años fue admitido por deterioro del sensorio debido a una hemorragia intracerebral. Seis horas posteriores, el paciente no tenía respuesta motora, y todos los reflejos del tronco cerebral estaban abolidos. El paciente cumplía con los criterios diagnósticos de Muerte Encefálica de acuerdo a lo establecido por la Academia Americana de Neurología. Durante el test de apnea, el paciente desarrolla súbitamente pneumotorax, pneumoperitoneo, y finalmente paro cardíaco. CONCLUSIÓN: El test de apnea es un requerimiento necesario para determinar el diagnóstico de muerte encefálica. No obstante, no es un procedimiento inocuo. Complicaciones durante este procedimiento pueden ser mas frecuentes que lo reportado en la literatura y tiene implicancias prácticas y legales.

Ischemic mechanisms in patients with brain and heart attacks have been studied for more than 150 years. Antiplatelets agents did show benefit in secondary prevention. Aspirin is the most common antiaggregant in clinical use today. However, the benefit produced by the "best" antiplatelet regimen in stroke prevention is lower than 40%. The adherence of circulating platelets to the subendothelium is mediated by glycoprotein (GP) residing on the cell's surface. GPIIb/IIIa is the most important platelet membrane receptor that mediates the process of platelet aggregation, and thrombus formation. Thus, new drugs that block the GPIIb/IIIa receptor have recently emerged. Clinical trials using these agents have shown effectiveness in acute coronary syndromes. However, the absence of studies in cerebrovascular disease and the potential hemorrhagic complications questioned their use in stroke prevention. We review the clinical trials using the new GPIIb/IIIa agents in myocardial ischemia, and consider the potential implications for cerebrovascular disease.Los mecanismos de isquemia en infarto de miocardio y enfermedad cerebrovascular (ECV) han sido estudiados por mas de 150 años. Drogas antiplaquetarias mostraron un beneficio en la prevención secundaria. La aspirina es el mas común de los antiagregantes usados en la practica clínica. No obstante, el beneficio producido, aun con el "mejor" tratamiento antiagregante, en la prevención de ECV es inferior al 40%. La adhesión plaquetaria es un proceso mediado por glicoproteinas (GP) de la membrana celular. GPIIb/IIIa es un receptor de membrana plaquetaria que interviene en el proceso de agregación plaquetaria y formación del trombo. Estudios clínicos con nuevos agentes que bloquean a este receptor mostraron ser efectivos en los síndromes coronarios agudos. No obstante, la falta de estudios en ECV y las potenciales complicaciones hemorrágicas, limitan su uso en la prevención de stroke. Revisamos los mecanismos de trombogenésis y los estudios clínicos con los nuevos agentes GPIIb/IIIa, considerando sus implicancias en ECV.