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One of the brain disorders causing great damage to those who suffer from it is dyscalculia. Dyscalculia often causes math anxiety. This circumstance is characterized by feelings of tension and fear that interfere with performance in tasks related to Mathematics. Mathematics anxiety is not always caused by a learning difficulty but in cases where this difficulty exists, if it is not diagnosed and treated properly, it is not possible to eliminate the anxiety. By using the BAEP technique, it is possible to determine the existence of a certain type of learning disorder, which allows attention to be focused on remedying the specific cause that produces the anxiety. Due to the existence of multiple factors that cause anxiety, the neuronal system that is activated is a network of interconnected networks whose controllability we need to study. In this work, we also study the controllability of multiagent neural networks by simulating possible brain networks. Peer Reviewed Objectius de Desenvolupament Sostenible::4 - Educació de Qualitat Objectius de Desenvolupament Sostenible::3 - Salut i Benestar

Background: To describe the prevalence, clinical characteristics, impact of systemic steroids exposure and outcomes of delayed cerebral vasculopathy (DCV) in a cohort of adult patients with pneumococcal meningitis (PM). Methods: Observational retrospective multicenter study including all episodes of PM from January 2002 to December 2015. DCV was defined as proven/probable/possible based upon clinical criteria and pathological-radiological findings. DCV-patients and non-DCV-patients were compared by univariate analysis. Results: 162 PM episodes were included. Seventeen (10.5%) DCV-patients were identified (15 possible, 2 probable). At admission, DCV-patients had a longer duration of symptoms (>2 days in 58% vs. 25.5% (p 0.04)), more coma (52.9% vs. 21.4% (p 0.03)), lower median CSF WBC-count (243 cells/uL vs. 2673 cells/uL (p 0.001)) and a higher proportion of positive CSF Gram stain (94.1% vs. 71% (p 0.07)). Median length of stay was 49 vs. 15 days (p 0.001), ICU admission was 85.7% vs. 49.5% (p 0.01) and unfavorable outcome was found in 70.6% vs. 23.8% (p 0.001). DCV appeared 1-8 days after having completed adjunctive dexamethasone treatment (median 2,5, IQR = 1.5-5). Conclusions: One tenth of the PM developed DCV. DCV-patients had a longer duration of illness, were more severely ill, had a higher bacterial load at admission and had a more complicated course. Less than one third of cases recovered without disabilities. The role of corticosteroids in DCV remains to be established. (c) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Resumen Objetivo Conocer el grado de seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria e identificar factores asociados. Diseño Transversal multicéntrico. Emplazamiento Centros de salud de atención primaria de un área metropolitana (944.280 habitantes). Participantes Pacientes mayores de 18 años con diagnóstico de enfermedad cerebrovascular antes de 6 meses del estudio. Mediciones principales Extracción de historia clínica informatizada de variables demográficas, factores de riesgo y comorbilidad cardiovascular, fármacos, valores de presión arterial (PA), colesterol LDL y visitas por medicina y enfermería posteriores al episodio. Se consideró buen control: PA

BACKGROUND. TANGO2-related metabolic encephalopathy and malignant arrhythmias is a newly acknowledged autosomal recessive genetic disease caused by pathogenic variants in the TANGO2 gene. Clinical characteristics include recurrent acute metabolic crises related to rhabdomyolysis, prolongation of QT interval in the electrocardiogram and less frequently, a characteristic electrocardiographic pattern of Brugada Syndrome. These alterations lead to torsade de pointes (most common arrhythmia seen in this disorder) followed by ventricular tachycardia, ventricular fibrillation, and even in some cases, sudden cardiac death. Arrhythmias are the most usual cause of death in this patients and ventricular dysfunction is also described. Due to the extreme rarity of the disease, there are no standardized treatment protocols or guidelines. It is known that patients during non-acute periods tend to be without any cardiac arrythmia, but here is when it comes the importance of the rhythm monitoring by the remote cardiac monitor system with an implantable loop recorder. With this tool, apart from the education of familiars about the syndrome and genetic counselling, we try to detect earlier the arrythmias to treat our patients as soon as possible and thus prevent episodes of malignant arrhythmias and even sudden cardiac death. HYPOTHESY AND OBJECTIVES. In this cross-sectional study, we suggested that patients with TANGO2-related metabolic encephalopathy and arrhythmias diagnosed and/or managed in Hospital Sant Joan de Déu present a normal electrocardiogram during non-acute periods, measured by the remote cardiac monitor system. METHODS AND MATERIALS. It was designed a cross-sectional study with a total sample of 11 anonymized patients with TANGO2 - related metabolic encephalopathy and arrhythmias. The objective was to analyse demographical data, clinical characteristics, genetic background, and describe the electrocardiographic characteristics data during non- acute periods recorded by implantable loop recorder from June 2019 to now. RESULTS AND DISCUSSION. In this first-year follow-up post-implantation of implantable loop recorder we found a total of seven rhythm alterations during non-acute periods presented in three of the patients with implanted monitor. All these patients come up with bradycardias, two with sinoatrial block, one with auriculoventricular block of 1st grade and another one with paroxysmal supraventricular tachycardia. Consequently, it was implanted a heart pacemaker device in a patient with auriculoventricular block 1st grade symptomatic and bradycardia episodes, whether in the other two only periodical controls were requested as there are minor rhythm alterations. CONCLUSIONS. Our results conclude that not all patients with TANGO2-related metabolic encephalopathy and arrhythmia during non-acute periods included in our study, specifically three of them, do not present any rhythm alteration regardless of its severity and consequences. Other conclusions reached are that long QT isthe most frequent arrhythmia through metabolic crises and ventricular arrhythmias are the most fatal ones

Atrophy quantification is fundamental for understanding brain development and diagnosing and monitoring brain diseases. FSL-SIENA is a well-known fully automated method that has been widely used in brain magnetic resonance imaging studies. However, intensity variations arising during image acquisition may compromise evaluation, analysis and even diagnosis. In this work, we studied whether intensity standardisation could improve longitudinal atrophy quantification using FSL-SIENA. We evaluated the effect of six intensity standardisation methods—z-score, fuzzy c-means, Gaussian mixture model, kernel density estimation, histogram matching and WhiteStripe—on atrophy detected by FSL-SIENA. First, we evaluated scan–rescan repeatability using scans taken during the same session from OASIS (n=122). Except for WhiteStripe, intensity standardisation did not compromise the scan–rescan repeatability of FSL-SIENA. Second, we compared the mean annual atrophy for Alzheimer’s and control subjects from OASIS (n=122) and ADNI (n=147) yielded by FSL-SIENA with and without intensity standardisation, after adjusting for covariates. Our findings were threefold: First, the use of histogram matching was counterproductive, primarily as its assumption of equal tissue proportions does not necessarily hold in longitudinal studies. Second, standardising with z-score and WhiteStripe before registration affected the registration performance, thus leading to erroneous estimates. Third, z-score was the only method that consistently led to increased effect sizes compared to when omitted (no standardisation: 0.39 and 0.43 for OASIS and ADNI, z-score: 0.45 for both datasets). Overall, we found that incorporating z-score right after registration led to reduced inter-subject inter-scan intensity variability and benefited FSL-SIENA. Our work evinces the relevance of appropriate intensity standardisation in longitudinal cerebral atrophy assessments using FSL-SIENA.

Epileptic seizures are known to follow specific changes in brain dynamics. While some algorithms can nowadays robustly detect these changes, a clear understanding of the mechanism by which these alterations occur and generate seizures is still lacking. Here, we provide crossvalidated evidence that such changes are initiated by an alteration of physiological network state dynamics. Specifically, our analysis of long intracranial electroencephalography (iEEG) recordings from a group of 10 patients identifies a critical phase of a few hours in which time-dependent network states become less variable ("degenerate"), and this phase is followed by a global functional connectivity reduction before seizure onset. This critical phase is characterized by an abnormal occurrence of highly correlated network instances and is shown to be particularly associated with the activity of the resected regions in patients with validated postsurgical outcome. Our approach characterizes preseizure network dynamics as a cascade of 2 sequential events providing new insights into seizure prediction and control., Author summary Understanding and predicting the generation of seizures in epileptic patients is fundamental to improving the quality of life of the more than 1% of the world population who suffer from this illness. Although seizure prediction has made important advances over the last decade, there is a lack of understanding of the common principles explaining the transitions that brain activity undergoes before a seizure. In this study, we characterized this transition from a novel perspective grounded on the mathematical analysis of continuous recordings inside the brains of epileptic patients over several days using depth electrodes. We show that the critical period preceding a seizure unfolds in a two-stage process. It begins with a phase of several hours when the highly correlated activity in the preceding days is altered, and it proceeds with a second, shorter phase of decrease in global connectivity before the seizure onset. Furthermore, our analysis reveals that these global alterations are more locally manifested in areas that are selected for surgical treatment. Our study suggests that preseizure activity might follow global stereotyped dynamics that could be targeted and modulated to prevent epileptic seizures.

We investigated whether pre-treatment with statins is associated with surrogate markers of amyloid and hypertensive angiopathies in patients who need to start long-term oral anticoagulation therapy. A prospective multicenter study of patients naive for oral anticoagulants, who had an acute cardioembolic stroke. MRI was performed at admission to evaluate microbleeds, leukoaraiosis and superficial siderosis. We collected data on the specific statin compound, the dose and the statin intensity. We performed bivariate analyses and a logistic regression to investigate variables associated with microbleeds. We studied 470 patients (age 77.5 +/- 6.4 years, 43.7% were men), and 193 (41.1%) of them received prior treatment with a statin. Microbleeds were detected in 140 (29.8%), leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The presence of microbleeds, leukoaraiosis or superficial siderosis was not related to pretreatment with statins. Microbleeds were more frequent in patients with prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06-90.9) and in those pre-treated antiplatelets (OR 1.66, 95% CI 1.09-2.53). Prior treatment with statins was not associated with markers of bleeding-prone cerebral angiopathies in patients with cardioembolic stroke. Therefore, previous statin treatment should not influence the decision to initiate or withhold oral anticoagulation if these neuroimaging markers are detected., This study was funded by the Spanish Ministery of Health - Instituto Carlos III, Redes Tematicas de Investigacion Cooperativa (INVICTUS PLUS RD16/0019/0010) and Fondo de Investigaciones Sanitarias FI12/00296. The study also received funding from FEDER (Fondo Europeo de Desarrollo Regional). The study was done with the aid of the Stroke Project, Cerebrovascular Diseases Group of the Spanish Neurological Society.

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naïve participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with stroke, cognitive impairment, and cardiovascular death. Some predisposing factors - as aging, diabetes, hypertension - induce and maintain electrophysiological and ultrastructural remodeling that usually includes fibrosis. Interatrial conduction disturbances play a crucial role in the initiation of atrial fibrosis and in its associated complications. The diagnosis of interatrial blocks (IABs) is easy to perform using the surface ECG. IAB is classified as partial when the P wave duration is ≥120ms, and advanced if the P wave also presents a biphasic pattern in II, III and aVF. IAB is very frequent in the elderly and, particularly in the case of the advanced type, is associated with AF, AF recurrences, stroke, and dementia. The anticoagulation in elderly patients at high risk of AF without documented arrhythmias is an open issue but recent data suggest that it might have a role, particularly in elderly patients with structural heart disease, high CHA2DS2VASc (Congestive heart failure/left ventricular dysfunction, Hypertension, Age≥75 [doubled], Diabetes, Stroke [doubled] - Vascular disease, Age 65-74, and Sex category [female]), and advanced IAB. In this debate, we discuss the association of surface ECG IAB, a marker of atrial fibrosis, with AF and stroke. We also present the rationale that justifies further studies regarding anticoagulation in some of these patients. Sin financiación 1.812 JCR (2017) Q3, 80/128 Cardiac and Cardiovascular Systems UEM

During the postnatal development of cerebellum, lack of excitatory innervation from the mossy fibers results in cerebellar granule cell (CGC) apoptosis during the migration of the cells toward the internal granule cell layer. Accordingly, CGCs die by apoptosis when cultured in physiological KCl concentrations (5 mm; K5), and they survive in the presence of depolarizing conditions such as high KCl concentration (25 mm; K25) or N-methyl-d-aspartate (NMDA). We have recently shown that NMDA is able to exert a long lasting neuroprotective effect when added to immature (2 days in vitro) CGC cultures by inhibition of caspase-3 activity. Here we show that NMDA- and K25-mediated neuroprotection is associated with an increase in the levels of Bcl-2, an inhibition of K5-mediated increase in Bax, and the inhibition of the release of apoptogenic factors from mitochondria such as Smac/DIABLO and cytochrome c. Moreover, we have shown that similar effects are observed when c-Jun N-terminal kinases (JNKs) are inhibited and that treatment of CGC cultures with NMDA blocks K5-mediated JNK activation. These results allow us to postulate that the inhibition of JNK-mediated release of apoptogenic factors from mitochondria is involved in the NMDA protection from K5-mediated apoptosis of CGCs. info:eu-repo/semantics/publishedVersion

Curs 2012-2013, La teràpia aquàtica o hidroteràpia és una de les tècniques de fisioteràpia poc valorades pels beneficis que aporten. En aquest estudi analitzem com aquest tractament en el medi aquàtic pot beneficiar als pacients afectats de un accident vascular cerebral (AVC). Els participants d’aquest estudi son pacients els quals han patit un AVC en els últims dos anys. Aquest estudi serà dut a terme ha l’Hospital Sant Joan de Déu de Palma de Mallorca. La investigació consisteix en una combinació entre el mètode qualitatiu i el mètode quantitatiu, cada mètode aporta diferents visions de l’estudi amb la finalitat d’obtenir resultats més complets, arribant als objectius marcats. Per una banda, l’aspecte bio-psico-social serà avaluat utilitzant el mètode qualitatiu, realitzant entrevistes semi-estructures abans i després del tractament amb la finalitat d’obtenir la sensació que percep el pacient en cada moment. Per l’altre banda, l’espasticitat la valorarem mitjançant l’escala de Ashworth amb el mètode quantitatiu abans i després del tractament. Tenint en compte que poden sorgir varis limitacions com el temps de durada de l’estudi, la planificació o limitacions entre els participants, és un estudi interessant per valorar els canvis en la qualitat de vida d’aquestes persones., The hydrotherapy or aquatic therapy is group of physiotherapy techniques that provide physical benefits which are undervalued. In this research study we discuss how this treatment in the aquatic environment can benefit patients with stroke (CVA). Participants in this study are patients who have suffered a stroke in the last two years. This study is will perform in “Hospital Sant Joan de Déu” from Palma, Mallorca. The investigation consist of a combination of qualitative and quantitative method, each method provided different views of the study in order to obtain better results and reach goals. On the one hand, bio-psycho-social aspects will evaluate by using the qualitative method. This method consists of semi-structured interviews before and after treatment in order to get the feeling that the patient perceives at any time. On the other hand, spasticity is will assess by the Ashworth scale quantitative method before and after treatment. Several limitations can appear for example the duration of the study, limitations of the planning and differences among participants , Although all this limitations it will be an interesting study to assess the changes in the life quality.

Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system. The laboratory of MD is supported by Departament d’Universitats, Recerca i Societat de la Informació (DURSI) (Grups consolidats 09 2009SGR1313). This work was supported by FCT-08-0782, SAF2007-60827, SAF2010-16427, SAF2007-31093-E, Fondo de Investigación Sanitaria (FIS) (PI 082038), Marató TV3, Jerome Lejeune, Reina Sofia and Areces Foundations and EU (LSHG-CT-2006-037627; CureFXS ERare-EU/FIS PS09102673). The CIBER of Enfermedades Raras is an initiative of the ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background The 90-kDa ribosomal S6 kinase (Rsk) family is involved in cell survival. Rsk activation is regulated by sequential phosphorylations controlled by extracellular signal-regulated kinase (ERK) 1/2 and 3-phosphoinositide-dependent protein kinase 1 (PDK1). Altered ERK1/2 and PDK1 phosphorylation have been described in Huntington's disease (HD), characterized by the expression of mutant huntingtin (mhtt) and striatal degeneration. However, the role of Rsk in this neurodegenerative disease remains unknown. Here, we analyzed the protein levels, activity and role of Rsk in in vivo and in vitro HD models. Results We observed increased protein levels of Rsk1 and Rsk2 in the striatum of HdhQ111/Q111 and R6/1 mice, STHdhQ111/Q111 cells and striatal cells transfected with full-length mhtt. Analysis of the phosphorylation of Rsk in Hdh mice and STHdh cells showed reduced levels of phospho Ser-380 (dependent on ERK1/2), whereas phosphorylation at Ser-221 (dependent on PDK1) was increased. Moreover, we found that elevated Rsk activity in STHdhQ111/Q111 cells was mainly due to PDK1 activity, as assessed by transfection with Rsk mutant constructs. The increase of Rsk in STHdhQ111/Q111 cells occurred in the cytosol and in the nucleus, which results in enhanced phosphorylation of both cytosolic and nuclear Rsk targets. Finally, pharmacological inhibition of Rsk, knock-down and overexpression experiments indicated that Rsk activity exerts a protective effect against mhtt-induced cell death in STHdhQ7/Q7 cells transfected with mhtt. Conclusion The increase of Rsk levels and activity would act as a compensatory mechanism with capacity to prevent mhtt-mediated cell death. We propose Rsk as a good target for neuroprotective therapies in HD.

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action.