Multitasking Compensatory Saccadic Training Program for Hemianopia Patients: A New Approach With 3-Dimensional Real-World Objects

Producción CientíficaPurpose: To examinewhether a noncomputerized multitasking compensatory saccadic training program (MCSTP) for patients with hemianopia, based on a reading regimen and eight exercises that recreate everyday visuomotor activities using threedimensional (3D) real-world objects, improves the visual ability/function, quality of life (QL), and functional independence (FI). Methods: The 3D-MCSTP included four in-office visits and two customized homebased daily training sessions over 12weeks. A quasiexperimental, pretest/posttest study designwas carried out with an intervention group (IG) (n = 20) and a no-training group (NTG) (n = 20) matched for age, hemianopia type, and brain injury duration. Results: The groups were comparable for the main baseline variables and all participants (n = 40) completed the study. The IGmainly showed significant improvements in visual-processing speed (57.34% ± 19.28%; P < 0.0001) and visual attention/retention ability (26.67% ± 19.21%; P < 0.0001), which also were significantly greater (P < 0.05) than in the NTG. Moreover, the IG showed large effect sizes (Cohen’s d) in 75% of the totalQL and FI dimensions analyzed; in contrast to the NTGthat showed negligiblemean effect sizes in 96% of these dimensions. Conclusions: The customized 3D-MCSTP was associated with a satisfactory response in the IG for improving complex visual processing, QL, and FI. Translational Relevance: Neurovisual rehabilitation of patientswith hemianopia seems more efficient when programs combine in-office visits and customized home-based training sessions based on real objects and simulating real-life conditions, than no treatment or previously reported computer-screen approaches, probably because of better stimulation of patients´ motivation and visual-processing speed brain mechanisms

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

Totes les malalties cerebrovasculars/ictus; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Trombosi venosa cerebralTodas las enfermedades cerebrovasculares/ictus; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Trombosis venosa cerebralAll cerebrovascular diseases/stroke; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cerebral venous thrombosisBackground Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. Aim To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. Methods Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). Results Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. Conclusions COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.The author(s) received no financial support for the research, authorship, and/or publication of this article

Principles of precision medicine in stroke

The era of precision medicine has arrived and conveys tremendous potential, particularly for stroke neurology. The diagnosis of stroke, its underlying aetiology, theranostic strategies, recurrence risk and path to recovery are populated by a series of highly individualised questions. Moreover, the phenotypic complexity of a clinical diagnosis of stroke makes a simple genetic risk assessment only partially informative on an individual basis. The guiding principles of precision medicine in stroke underscore the need to identify, value, organise and analyse the multitude of variables obtained from each individual to generate a precise approach to optimise cerebrovascular health. Existing data may be leveraged with novel technologies, informatics and practical clinical paradigms to apply these principles in stroke and realise the promise of precision medicine. Importantly, precision medicine in stroke will only be realised once efforts to collect, value and synthesise the wealth of data collected in clinical trials and routine care starts. Stroke theranostics, the ultimate vision of synchronising tailored therapeutic strategies based on specific diagnostic data, demand cerebrovascular expertise on big data approaches to clinically relevant paradigms. This review considers such challenges and delineates the principles on a roadmap for rational application of precision medicine to stroke and cerebrovascular health

Stimuli Characteristics and Psychophysical Requirements for Visual Training in Amblyopia: A Narrative Review

Active vision therapy using perceptual learning and/or dichoptic or binocular environments has shown its potential effectiveness in amblyopia, but some doubts remain about the type of stimuli and the mode and sequence of presentation that should be used. A search was performed in PubMed, obtaining 143 articles with information related to the stimuli used in amblyopia rehabilitation, as well as to the neural mechanisms implied in such therapeutic process. Visual deficits in amblyopia and their neural mechanisms associated are revised, including visual acuity loss, contrast sensitivity reduction and stereopsis impairment. Likewise, the most appropriate stimuli according to the literature that should be used for an efficient rehabilitation of the amblyopic eye are described in detail, including optotypes, Gabor’s patches, random-dot stimuli and Vernier’s stimuli. Finally, the properties of these stimuli that can be modified during the visual training are discussed, as well as the psychophysical method of their presentation and the type of environment used (perceptual learning, dichoptic stimulation or virtual reality). Vision therapy using all these revised concepts can be an effective option for treating amblyopia or accelerating the treatment period when combining with patching. It is essential to adapt the stimuli to the patient’s individual features in both monocular and binocular training.The authors C.J.H.-R., D.P.P., A.M.-M., D.d.F., L.L.-V., M.B.C.-M. have been funded by CDTI (Centro para el Desarrollo Tecnológico Industrial, Ministry of Economy and Competitiveness of Spain) and FEDER (Fondos Europeos de Desarrollo Regional) funds by means of the program PID (“Proyectos de Investigación y Desarrollo”) in the context of the Project NEIVATECH (“Neuroplasticity through virtual reality for amblyopia”, application number 111705). The author León Morales-Quezada is supported by funding from the Spaulding Research Catalyst award. The author David P Piñero has been also supported by the Ministry of Economy, Industry and Competitiveness of Spain within the program Ramón y Cajal, RYC-2016-20471

Visual processing speed in hemianopia patients secondary to acquired brain injury: a new assessment methodology

Producción CientíficaBackground: There is a clinical need to identify diagnostic parameters that objectively quantify and monitor the effective visual ability of patients with homonymous visual field defects (HVFDs). Visual processing speed (VPS) is an objective measure of visual ability. It is the reaction time (RT) needed to correctly search and/or reach for a visual stimulus. VPS depends on six main brain processing systems: auditory-cognitive, attentional, working memory, visuocognitive, visuomotor, and executive. We designed a new assessment methodology capable of activating these six systems and measuring RTs to determine the VPS of patients with HVFDs. Methods: New software was designed for assessing subject visual stimulus search and reach times (S-RT and R-RT respectively), measured in seconds. Thirty-two different everyday visual stimuli were divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities (10o, 20o, and 30o). Thus, for each HVFD and control subject, 96 S- and R-RT measures related to VPS were registered. Three additional variables were measured to gather objective data on the validity of the test: eye-hand coordination mistakes (ehcM), eye-hand coordination accuracy (ehcA), and degrees of head movement (dHM, measured by a head-tracker system). HVFD patients and healthy controls (30 each) matched by age and gender were included. Each subject was assessed in a single visit. VPS measurements for HFVD patients and control subjects were compared for the complete test, for each stimulus complexity group, and for each eccentricity. Results: VPS was significantly slower (p < 0.0001) in the HVFD group for the complete test, each stimulus complexity group, and each eccentricity. For the complete test, the VPS of the HVFD patients was 73.0% slower than controls. They also had 335.6% more ehcMs, 41.3% worse ehcA, and 189.0% more dHMs than the controls. Conclusions: Measurement of VPS by this new assessment methodology could be an effective tool for objectively quantifying the visual ability of HVFD patients. Future research should evaluate the effectiveness of this novel method for measuring the impact that any specific neurovisual rehabilitation program has for these patients

Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry

Background and purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and inhospital mortality among patients according to stroke etiology. Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20–6/16/20). Results:Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p Conclusions: Our findings suggest that cryptogenic stroke among COVID-19 patients carries a significant risk of early mortality

The neuronal ischemic tolerance is conditioned by the Tp53 Arg72Pro polymorphism

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of prosurvival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulatorMDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult bymodulatingmitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.This work was funded by The Instituto de Salud Carlos III grants CP14/00010 (M.D.-E.); PI15/00473 and RD12/0014/ 0007 (A.A.); CM14/00096 (ME.R.-A.); RD16/0019/0018 (C.R.); and Junta de Castilla y Leon grant BIO/SA35/15 (M.D.-E.), and the European Regional Development Fund (R.V.) was funded by the FPU program (Ministerio de Educación)

Insights onto the magnetic coupling at hexaferrite-based hard/soft bilayer systems

IBERTRIVA 2019 X Iberian Conference on Tribology – IBERTRIB, XI Iberian Vacuum Conference - RIVA, Seville, Spain,June 26-28Magnets are used in a variety of applications, such as generators, magnetic recording media, components in RF and microwave devices. However, many of these magnets contain s rare earths, critical elements whose extraction is environmentally harmful and that present price volatility risks. Their replacement by cheaper and more environmentally friendly materials is therefore sought. In our case, we have focused on magnetically hard strontium hexaferrite (SrFe 12O19, SFO) as the base for alternative permanent magnets (Figure 1a). The atomic arrangement of this ferrite results in a high magnetocrystalline anisotropy and a coercive field, however, its magnetization is moderate (1). It is well known that the coupling between a magnetically hard and soft material improved magnetization while avoiding a high cost in coercitivity loss (2). However, results have been disappointing so far as structural and geometrical limitations make it extremely challenging to fabricate. In this work, we aim at further understanding the magnetic coupling at hard -soft interfaces involving ferrites, for which we have deposited soft iron and cobalt metals on top of SrFe12O19 thin films with controlled easy-axis of magnetization. SFO thin films have been obtained by RF magnetron sputtering at 260W followed by a subsequent annealing in air of 850ºC. Their structure and composition was characterized by Raman spectroscospy (Figure 1b), Mössbauer spectroscopy, X-ray photoemission spectroscopy and low-energy electron microscopy (LEEM). We have grown the magnetically soft layer by molecular-beam epitaxy and we have analyzed the resulting bilayer system through photoemission electron microscopy, LEEM and vibrating-sample magnetometry. References [1] R.C. Pullar, Hexagonal ferrites: a review of the synthesis, properties and applications of hexaferrite ceramics, Progress in Materials Science 57 (2012), pp 1191¿1334. [2] Eric E. Fullerton, J. S. Jiang, M. Grimsditch, C. H. Sowers, and S. D. Bader, Exchange-spring behavior in epitaxial hard/soft magnetic bilayers, Phys. Rev. B 58 (1998) 1219

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA) : rationale and design

Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona- AS ymptomatic I ntracranial A therosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from its early stages and to identify new potential therapeutic targets for this condition

Proteins and pathways in atrial fibrillation and atrial cardiomyopathy underlying cryptogenic stroke

Atrial fibrillation (AF) is one of the most prevalent causes of cryptogenic stroke. Also, apart from AF itself, structural and remodelling changes in the atria might be an underlying cause of cryptogenic stroke. We aimed to discover circulating proteins and reveal pathways altered in AF and atrial cardiomyopathy, measured by left atrial volume index (LAVI) and peak atrial longitudinal strain (PALS), in patients with cryptogenic stroke. An aptamer array (including 1310 proteins) was measured in the blood of 20 cryptogenic stroke patients monitored during 28 days with a Holter device as a case-control study of the Crypto-AF cohort. Protein levels were compared between patients with (n = 10) and without AF (n = 10) after stroke, and the best candidates were tested in 111 patients from the same cohort (44 patients with AF and 67 without AF). In addition, in the first 20 patients, proteins were explored according to PALS and LAVI values. Forty-six proteins were differentially expressed in AF cases. Of those, four proteins were tested in a larger sample size. Only DPP7, presenting lower levels in AF patients, was further validated. Fifty-seven proteins correlated with LAVI, and 270 correlated with PALS. NT-proBNP was common in all the discovery analyses performed. Interestingly, many proteins and pathways were altered in patients with low PALS. Multiple proteins and pathways related to AF and atrial cardiomyopathy have been revealed. The role of DPP7 as a biomarker for stroke aetiology should be further explored. Moreover, the present study may be considered hypothesis-generatin