Natalizumab extended interval dosing: what about wearing-off effect?

BACKGROUND: Up to two thirds of patients with multiple sclerosis (MS) under natalizumab report a resurgence of symptoms at the end of the natalizumab cycle (wearing-off (WO) effect). At the outbreak of COVID-19, in line with the international recommendations for MS management, our centre switched all clinically stable patients on natalizumab therapy for more than one year from standard interval dosing (SID) to extended interval dosing (EID) with every six weeks infusions. This study aimed to evaluate the impact of EID in WO in MS patients under natalizumab. METHODS: An observational retrospective study in patients with MS under natalizumab on EID was conducted. A questionnaire regarding current (on EID) and past (on SID) experience of WO effect was applied. RESULTS: Seventy-six patients were included. No significant differences were found in the annual relapse rate after the switch to EID (p = 0.083). However, there was a significant increase in the proportion of patients complaining of WO from 38.2% to 56.6% (p = 0.001). Moreover, patients with WO on SID, referred a significant increase in severity (p = 0.019) and duration of WO symptoms (p = 0.029), due to an anticipation of the symptoms relative to the day of natalizumab infusion (p = 0.019), when switching to EID. Symptoms improved with treatment maintenance in 23.3% of patients; instead, a reduction in interval dosing was needed in 54.8% with symptom improvement. CONCLUSION: WO affects a significant proportion of MS patients under natalizumab. Its prevalence, severity, and duration increase on EID, therefore despite clinical effectiveness maintenance of this posology should be individualized.

Recurrent Rhombencephalitis Associated With Anti-GAD65 Antibody.

A 66-year-old man developed diplopia, ataxia, and right-hand dexterity loss. Brain MRI revealed T2-hyperintensities in the right cerebellar peduncles, pons, medulla, and cerebellum (Figure 1, A-D).

[Use of Gadolinium in Follow-Up MRI of Multiple Sclerosis Patients: Current Recommendations]. / Utilização de Gadolínio nas Ressonâncias Magnéticas de Controlo em Doentes com Esclerose Múltipla: Recomendações Atuais.

Multiple sclerosis is the most frequent demyelinating disease of the central nervous system and is characterized by early onset and progressive disability. Magnetic resonance imaging, due to its high sensitivity and specificity in the detection of demyelinating lesions, is the most useful diagnostic test for this disease, with the administration of gadolinium-based contrast agents being an important contribution to imaging interpretation. Although contrast is essential for diagnostic purposes, its routine use in monitoring disease activity, response to treatment, and related complications is controversial. This article aims to collate current recommendations regarding the use of gadolinium in the imaging follow-up of multiple sclerosis and establish effective and safe guidelines for clinical practice. The literature review was conducted in PubMed, using the terms 'multiple sclerosis', 'magnetic resonance imaging' and 'gadolinium', or 'contrast media'. Articles published between January 2013 and January 2023 concerning the safety of gadolinium and the use of these contrast agents in follow-up scans of adult patients diagnosed with multiple sclerosis were selected. Although no biological or clinical consequences have been unequivocally attributed to the retention of gadolinium in the brain, which were mostly reported with linear agents, health authorities have been recommending the restriction of contrast to essential clinical circumstances. In multiple sclerosis, the detection of subclinical contrast-enhancing lesions with no corresponding new/ enlarging T2-WI lesions is rare and has a questionable impact on therapeutic decisions. On the other hand, gadolinium has a higher sensitivity in the differential diagnosis of relapses, in the detection of recent disease activity, before and after treatment initiation, and in patients with a large lesion burden or diffuse/confluent T2-WI lesions. Contrary to progressive multifocal leukoencephalopathy screening, monitoring of immune restitution inflammatory syndrome also benefits from the administration of gadolinium. It is feasible and safe to exclude gadolinium-based contrast agents from routine follow-up scans of multiple sclerosis, despite their additional contribution in specific clinical circumstances that should be acknowledged by the neurologist and neuroradiologist.

A esclerose múltipla é a doença desmielinizante do sistema nervoso central mais frequente, caracterizando-se pelo início precoce e incapacidade progressiva. A ressonância magnética, pela elevada sensibilidade e especificidade na deteção de lesões desmielinizantes, é o exame complementar mais útil nesta patologia, sendo a administração de meios de contraste com gadolínio um importante contributo na interpretação imagiológica. Embora o contraste seja imprescindível no âmbito do diagnóstico, a sua utilização por rotina na monitorização da atividade de doença, resposta ao tratamento e respetivas complicações é controversa. O objetivo deste artigo é reunir as recomendações atuais relativas à utilização do gadolínio no seguimento imagiológico da esclerose múltipla e definir um protocolo clínico efetivo e seguro. A revisão da literatura foi conduzida na PubMed, recorrendo aos termos 'esclerose múltipla', 'ressonância magnética' e 'gadolínio' ou 'meio de contraste'. Foram selecionados artigos publicados entre janeiro de 2013 e de 2023 relativos à segurança do gadolínio e à sua utilização na ressonância magnética de controlo dos doentes adultos com diagnóstico de esclerose múltipla. Apesar de nenhuma consequência biológica ou clínica ter sido inequivocamente atribuída à retenção cerebral do gadolínio, que foi reportada maioritariamente com agentes lineares, as autoridades de saúde têm vindo a recomendar a restrição do contraste a circunstâncias clínicas essenciais. Na esclerose múltipla, a deteção de lesões subclínicas com captação de gadolínio sem tradução em lesões novas/aumentadas nas sequências ponderadas em T2 ocorre raramente e com impacto na decisão terapêutica questionável. Por outro lado, o gadolínio assume uma sensibilidade superior no diagnóstico diferencial de surtos clínicos, na deteção de atividade inflamatória recente, antes e após o início de uma terapêutica e nos doentes com elevada carga lesional ou lesões difusas/confluentes nas sequências ponderadas em T2. Contrariamente ao rastreio da leucoencefalopatia multifocal progressiva, a monitorização da síndrome inflamatória de reconstituição imunológica beneficia também da inclusão do gadolínio. É exequível e segura a exclusão do gadolínio no seguimento imagiológico de rotina da esclerose múltipla, apesar do seu contributo adicional em circunstâncias clínicas específicas que devem ser do conhecimento articulado do neurologista e neurorradiologista.

Prevalence, Incidence, and Mortality of Multiple Sclerosis in Coimbra, Portugal.

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system in young adults, representing the leading cause of nontraumatic disability in this population. The rising prevalence of MS worldwide makes it critical to recognize the absolute number of patients with MS, demanding the execution of a sustainable healthcare policy. In Portugal, only six studies evaluating MS rates were published, disclosing a prevalence of 64 cases per 100,000 persons and an incidence of 3.1 cases per 100,000 persons/year, but the mortality rates have not been reported. Thus, this observational, cross-sectional study aimed to assess MS prevalence, incidence, and mortality in the city of Coimbra, a region in the center of Portugal. Patients who fulfilled McDonald's Diagnosis Criteria (2017) for MS were recruited. Inclusion criteria were defined according to prevalence, incidence, and mortality studies. The baseline demographic and clinical characterization of the prevalence study population was performed. The MS prevalence rate in Coimbra was 143.45 cases per 100,000 inhabitants. Between 2018 and 2021, the cumulative incidence was 8.52 new cases per 100,000 persons/year. The mortality rate between 2018 and 2021 was 2.84 deaths per 100,000 inhabitants. MS prevalence and incidence in Coimbra are higher than reported in previous similar studies and comparable to Europe's mean prevalence and incidence.

A Preliminary Investigation of Salmonella Populations in Indigenous Portuguese Layer Hen Breeds.

The sustainability of agroecological systems, biodiversity protection, animal welfare, and consumer demand for higher quality products from alternative and extensive farming methods have reinforced interest in local breeds that are well adapted to low-input environments. However, food safety needs to be safeguarded to reinforce consumer confidence. The aim of this study was to conduct a preliminary investigation on the occurrence of Salmonella spp. in eggshells, hen's cloaca, and litter materials from autochthonous Portuguese laying hens raised in a semi-extensive system for small-scale production. A total of 279 samples from 31 flocks belonging to 12 farms were obtained, with 63 samples from the "Preta Lusitânica" breed, and 72 samples each from the remaining autochthonous breeds, namely, "Branca", "Amarela", and "Pedrês Portuguesa". None (0%) of the samples analyzed were positive for Salmonella spp. To the best of our knowledge, these are the first results of Salmonella evaluation from hen's cloaca, eggshells, and litter materials in autochthonous Portuguese chickens, suggesting that a semi-extensive production system can contribute to better food security and a lower risk to public health and the environment.

A systematic review of microstructural abnormalities in multiple sclerosis detected with NODDI and DTI models of diffusion-weighted magnetic resonance imaging.

Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.

Clinical Reasoning: A 24-Year-Old Pregnant Woman With Headache and Behavioral Change Progressing to Coma.

The broad differential diagnosis associated with progressive subacute encephalopathy can be intimidating, especially in a young, pregnant woman. In this case, a 24-year-old woman at 21 weeks of gestation presented with persistent, drug-resistant fronto-parietal headache, with subsequent progressive development of psychomotor lentification and inappropriate behavior. Physical examination was normal, as were routine laboratory parameters and CT findings, and these symptoms were initially interpreted in the context of chronic depression. Later, the patient developed generalized dystonia and fever, with rapid clinical deterioration, depression of consciousness and, eventually, progression to coma. This case emphasizes the complexity and challenges involved in the diagnostic approach to a patient with progressive subacute encephalopathy framed by worsening CNS symptoms. It highlights the clinical considerations and complementary investigation of various etiologies, in a step-by-step approach, ultimately leading to the final diagnosis. Early recognition and appropriate treatment of these conditions can lead to more favorable outcomes, particularly in gestating patients, where prompt intervention is crucial, and where critical decisions may have to be made regarding pregnancy and the safety of treatment options.

Task-based functional MRI challenges in clinical neuroscience: Choice of the best head motion correction approach in multiple sclerosis.

Introduction: Functional MRI (fMRI) is commonly used for understanding brain organization and connectivity abnormalities in neurological conditions, and in particular in multiple sclerosis (MS). However, head motion degrades fMRI data quality and influences all image-derived metrics. Persistent controversies regarding the best correction strategy motivates a systematic comparison, including methods such as scrubbing and volume interpolation, to find optimal correction models, particularly in studies with clinical populations prone to characterize by high motion. Moreover, strategies for correction of motion effects gain more relevance in task-based designs, which are less explored compared to resting-state, have usually lower sample sizes, and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes. Methods: We acquired fMRI data from 17 early MS patients and 14 matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and quantitatively compared the most used and easy to implement methods for correction of motion effects. We compared task-activation metrics obtained from: (i) models containing 6 or 24 motion parameters (MPs) as nuisance regressors; (ii) models containing nuisance regressors for 6 or 24 MPs and motion outliers (scrubbing) detected with Framewise Displacement or Derivative or root mean square VARiance over voxelS; and (iii) models with 6 or 24 MPs and motion outliers corrected through volume interpolation. To our knowledge, volume interpolation has not been systematically compared with scrubbing, nor investigated in task fMRI clinical studies in MS. Results: No differences in motion were found between groups, suggesting that recently diagnosed MS patients may not present problematic motion. In general, models with 6 MPs perform better than models with 24 MPs, suggesting the 6 MPs as the best trade-off between correction of motion effects and preservation of valuable information. Parsimonious models with 6 MPs and volume interpolation were the best combination for correcting motion in both groups, surpassing the scrubbing methods. A joint analysis regardless of the group further highlighted the value of volume interpolation. Discussion: Volume interpolation of motion outliers is an easy to implement technique, which may be an alternative to other methods and may improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other neurological populations.

Comparative Analysis between Synthetic Vitamin E and Natural Antioxidant Sources from Tomato, Carrot and Coriander in Diets for Market-Sized Dicentrarchus labrax.

Synthetic vitamin E is commonly used in aquafeeds to prevent oxidative stress in fish and delay feed and flesh oxidation during storage, but consumers' preferences tend towards natural antioxidant sources. The potential of vegetable antioxidants-rich coproducts, dried tomato (TO), carrot (CA) and coriander (CO) was compared to that of synthetic vitamin E included in diets at either a regular (CTRL; 100 mg kg-1) or reinforced dose (VITE; 500 mg kg-1). Natural antioxidants were added at 2% to the CTRL. Mixes were then extruded and dried, generating five experimental diets that were fed to European sea bass juveniles (114 g) over 12 weeks. Vitamin E and carotenoid content of extruded diets showed signs of degradation. The experimental diets had very limited effects on fish growth or body composition, immunomodulatory response, muscle and liver antioxidant potential, organoleptic properties or consumer acceptance. Altogether, experimental findings suggest that neither a heightened inclusion dose of 500 mg kg-1 of vitamin E, nor a 2% inclusion of natural antioxidants provided additional antioxidant protection, compared to fish fed diets including the regular dose of 100 mg kg-1 of vitamin E.

Posttranslational modifications of proteins are key features in the identification of CSF biomarkers of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system (CNS) characterized by demyelination and concomitant axonal loss. The lack of a single specific test, and the similarity to other inflammatory diseases of the central nervous system, makes it difficult to have a clear diagnosis of multiple sclerosis. Therefore, laboratory tests that allows a clear and definite diagnosis, as well as to predict the different clinical courses of the disease are of utmost importance. Herein, we compared the cerebrospinal fluid (CSF) proteome of patients with multiple sclerosis (in the relapse-remitting phase of the disease) and other diseases of the CNS (inflammatory and non-inflammatory) aiming at identifying reliable biomarkers of multiple sclerosis. METHODS: CSF samples from the discovery group were resolved by 2D-gel electrophoresis followed by identification of the protein spots by mass spectrometry. The results were analyzed using univariate (Student's t test) and multivariate (Hierarchical Cluster Analysis, Principal Component Analysis, Linear Discriminant Analysis) statistical and numerical techniques, to identify a set of protein spots that were differentially expressed in CSF samples from patients with multiple sclerosis when compared with other two groups. Validation of the results was performed in samples from a different set of patients using quantitative (e.g., ELISA) and semi-quantitative (e.g., Western Blot) experimental approaches. RESULTS: Analysis of the 2D-gels showed 13 protein spots that were differentially expressed in the three groups of patients: Alpha-1-antichymotrypsin, Prostaglandin-H2-isomerase, Retinol binding protein 4, Transthyretin (TTR), Apolipoprotein E, Gelsolin, Angiotensinogen, Agrin, Serum albumin, Myosin-15, Apolipoprotein B-100 and EF-hand calcium-binding domain-containing protein. ELISA experiments allowed validating part of the results obtained in the proteomics analysis and showed that some of the alterations in the CSF proteome are also mirrored in serum samples from multiple sclerosis patients. CSF of multiple sclerosis patients was characterized by TTR oligomerization, thus highlighting the importance of analyzing posttranslational modifications of the proteome in the identification of novel biomarkers of the disease. CONCLUSIONS: The model built based on the results obtained upon analysis of the 2D-gels and in the validation phase attained an accuracy of about 80% in distinguishing multiple sclerosis patients and the other two groups.

Optimizing EEG Source Reconstruction with Concurrent fMRI-Derived Spatial Priors.

Reconstructing EEG sources involves a complex pipeline, with the inverse problem being the most challenging. Multiple inversion algorithms are being continuously developed, aiming to tackle the non-uniqueness of this problem, which has been shown to be partially circumvented by including prior information in the inverse models. Despite a few efforts, there are still current and persistent controversies regarding the inversion algorithm of choice and the optimal set of spatial priors to be included in the inversion models. The use of simultaneous EEG-fMRI data is one approach to tackle this problem. The spatial resolution of fMRI makes fMRI derived spatial priors very convenient for EEG reconstruction, however, only task activation maps and resting-state networks (RSNs) have been explored so far, overlooking the recent, but already accepted, notion that brain networks exhibit dynamic functional connectivity fluctuations. The lack of a systematic comparison between different source reconstruction algorithms, considering potentially more brain-informative priors such as fMRI, motivates the search for better reconstruction models. Using simultaneous EEG-fMRI data, here we compared four different inversion algorithms (minimum norm, MN; low resolution electromagnetic tomography, LORETA; empirical Bayes beamformer, EBB; and multiple sparse priors, MSP) under a Bayesian framework (as implemented in SPM), each with three different sets of priors consisting of: (1) those specific to the algorithm; (2) those specific to the algorithm plus fMRI task activation maps and RSNs; and (3) those specific to the algorithm plus fMRI task activation maps and RSNs and network modules of task-related dFC states estimated from the dFC fluctuations. The quality of the reconstructed EEG sources was quantified in terms of model-based metrics, namely the expectation of the posterior probability P(model|data) and variance explained of the inversion models, and the overlap/proportion of brain regions known to be involved in the visual perception tasks that the participants were submitted to, and RSN templates, with/within EEG source components. Model-based metrics suggested that model parsimony is preferred, with the combination MSP and priors specific to this algorithm exhibiting the best performance. However, optimal overlap/proportion values were found using EBB and priors specific to this algorithm and fMRI task activation maps and RSNs or MSP and considering all the priors (algorithm priors, fMRI task activation maps and RSNs and dFC state modules), respectively, indicating that fMRI spatial priors, including dFC state modules, might contain useful information to recover EEG source components reflecting neuronal activity of interest. Our main results show that providing fMRI spatial derived priors that reflect the dynamics of the brain might be useful to map neuronal activity more accurately from EEG-fMRI. Furthermore, this work paves the way towards a more informative selection of the optimal EEG source reconstruction approach, which may be critical in future studies.

Outcomes on Social and Classic Cognition in adults with Pediatric-onset Multiple Sclerosis.

BACKGROUND: Cognitive impairment affecting classic and social domains has been consistently reported in patients with Multiple Sclerosis (MS). However, little is known about the cognitive outcomes, particularly on social cognition, in adults with pediatric-onset multiple sclerosis (POMS). OBJECTIVES: To compare the performance in classic and social cognitive domains between adults with POMS and adult-onset MS (AOMS). METHODS: A group of 30 patients with POMS (age onset <18 years) was compared with age-matched (AOAMS, n=30) and disease duration-matched (AODMS, n= 30) patients who developed MS after the age of 18 years. Cognitive performance was assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and Theory of Mind (ToM) tests. RESULTS: Cognitive impairment was more prevalent in POMS patients (40% vs. 16.7%, p=0.045), independently of age or disease duration, affecting more severely information-processing speed and visual memory domains. No statistically significant differences were found in ToM performance between patients with POMS and AOMS. When analyzing ToM performance according to age of disease onset (≤15 years; 15-20 years; ≥20 years), patients with disease onset ≤15 years old had significantly lower scores on ToM tests when compared to the other groups. CONCLUSION: Patients with POMS were more prone to develop impairment on classic cognitive domains than on ToM ability, when compared with AOMS patients. The interference of POMS with critical neurodevelopmental periods, specific for each cognitive domain, may explain different outcomes at adulthood on social and classic cognition.

Authentic leadership, nurse satisfaction at work and hospital accreditation: study in a private hospital network.

OBJECTIVES: to identify the dominant dimensions of the authentic leadership of nurses in a private hospital network and to verify the association with job satisfaction and accreditation. METHODS: cross-sectional, analytical study carried out in 11 hospitals with 282 nurses, of which 94 were leaders and 188 were led. Participants answered the Authentic Leardership Questionnaire and the Job Satisfaction Survey. RESULTS: there was a significant difference between the assessment of leaders and followers in all dimensions of the Authentic Leardership Questionnaire. Regarding the association of authentic leadership and job satisfaction, a significant positive moderate correlation was found among the employees. In hospitals accredited by the Joint Commission International, leaders were perceived as more transparent by their subordinates. CONCLUSIONS: there was correlation between authentic leadership and job satisfaction and authentic leadership and the accreditation model among the subordinates.

Primary intramedullary spinal-cord lymphoma (PISCL): a rare entity with a challenging diagnosis.

Primary intramedullary spinal-cord lymphoma (PISCL) is a rare cause of myelopathy and constitutes only 1% of central nervous system lymphomas. Delay to diagnosis is common due to its rarity, its similarity to other causes of myelopathy and the difficulties in obtaining pathological diagnosis. We report a case of PISCL and discuss the challenges faced on diagnosis, namely the impact of corticosteroids on histological findings, the usefulness of MRI, positron-emission tomography/CT (PET/CT) and repeated lumbar punctures.

Protective effects of cognitive and brain reserve in multiple sclerosis: Differential roles on social cognition and 'classic cognition'.

BACKGROUND: According to cognitive reserve (CR) and brain reserve (BR) theories, lifetime intellectual enrichment and maximal brain volume protect against cognitive decline. OBJECTIVE: To examine the effects of CR and BR on social cognition in multiple sclerosis (MS), and compare it with 'classic cognition'. METHODS: We included 60 MS patients and 60 healthy controls matched on age, sex, and education. Education was used has a proxy of CR and intracranial volume (ICV) as a proxy of BR. Participants underwent Theory of Mind (ToM) testing (Eyes Test, Videos Test), comprehensive neuropsychological assessment and 3Tesla brain MRI. Cortical and subcortical grey matter (GM) volumes were calculated. RESULTS: We found positive effects of education and ICV on general cognitive status and ToM performance, respectively. Higher education moderated the impact of subcortical GM atrophy on 'classic' cognitive status (R2=0.219, p=<0.001). Conversely, greater ICV attenuated the impact of cortical GM atrophy on Eyes Test (R2=0.158, p=0.002) and Videos Test (R2=0.198, p=0.001). Stratification for disease duration showed that the protective effect of education/ICV occurred in early stages of disease (<10 years). CONCLUSION: CR and BR have differential protective roles in MS, with BR having a positive effect on social cognition and CR on 'classic' cognitive domains.

Clinical effectiveness of reduced fingolimod dose in relapsing remitting multiple sclerosis-a Portuguese cohort.

BACKGROUND: Fingolimod is an oral daily treatment for relapsing remitting multiple sclerosis (RRMS). A decrease in lymphocytes count is a common side effect, whereby clinicians occasionally propose a reduced dose rather than its discontinuation. However, current data on the effectiveness of these regimens are scarce and contradictory. Our objective was to investigate if the fingolimod effectiveness is maintained with reduction in dosing frequency. METHODS: Retrospective and observational study of RRMS patients taking fingolimod-nondaily (FTY-ND) for at least 6 months. Propensity score-based matching was performed to select patients taking daily dose (FTY-ED) with comparable baseline characteristics: age, sex, disease duration, annualized relapse rate (ARR), and expanded disability status scale (EDSS). Afterwards, clinical and laboratorial assessment was evaluated in both groups. RESULTS: Thirty-six patients were included in each group (FTY-ED vs. FTY-ND). Decrease in lymphocytes count was the main reason for switching to FTY-ND (88.9%). Previous treatment with natalizumab was inversely associated with risk of reducing dose (OR 0.253, 95%CI = 0.08-0.807, p = 0.016). There were no significant differences in clinical disease activity between patients FTY-ED vs. FTY-ND: mean ARR 0.4 vs. 0.3 (p = 0.247), median EDSS 2.0 vs. 2.0 (p = 0.687), and proportion of patients with EDSS increase 8.3% vs. 13.9% (p = 0.453). FTY-ND was overall well tolerated and was associated with an increase in the mean lymphocytes count (362 ± 103 cells/mm3 to 541 ± 183 cells/mm3, p < 0.001). CONCLUSION: These data suggest that the effectiveness of FTY is maintained despite the reduction of the dose, minimizing the most common adverse events. These findings warrant further confirmation, ideally with randomized clinical trials.

Tumefactive demyelinating lesions spectrum disorders and the potential role of contemporary disease modifying treatments: a case report.

Marburg disease is a fulminant variant of multiple sclerosis (MS), in which the diagnosis may be particularly difficult and with high rates of mortality. We describe the case of a women with a clinical picture, radiographic features, and neuropathological findings consistent with the classical descriptions of Marburg disease. Initially, our patient did not improved with the acute phase treatments but later showed a good response to natalizumab (NTZ) treatment. This report highlights not only the utility of brain biopsy in the accurate diagnosis of this challenging condition but also the potential role of NTZ as an effective therapeutic option.

Authentic leadership, nurse satisfaction at work and hospital accreditation: study in a private hospital network / Liderazgo auténtico, satisfacción del enfermero en el trabajo y acreditación hospitalaria: estudio en una red de hospitales privado / Liderança autêntica, satisfação do enfermeiro no trabalho e acreditação: estudo em uma rede hospitalar privada

ABSTRACT Objectives: to identify the dominant dimensions of the authentic leadership of nurses in a private hospital network and to verify the association with job satisfaction and accreditation. Methods: cross-sectional, analytical study carried out in 11 hospitals with 282 nurses, of which 94 were leaders and 188 were led. Participants answered the Authentic Leardership Questionnaire and the Job Satisfaction Survey. Results: there was a significant difference between the assessment of leaders and followers in all dimensions of the Authentic Leardership Questionnaire. Regarding the association of authentic leadership and job satisfaction, a significant positive moderate correlation was found among the employees. In hospitals accredited by the Joint Commission International, leaders were perceived as more transparent by their subordinates. Conclusions: there was correlation between authentic leadership and job satisfaction and authentic leadership and the accreditation model among the subordinates.

RESUMEN Objetivos: identificar las dimensiones dominantes del liderazgo auténtico de los enfermeros en una red de hospitales privados y su correlación con la satisfacción laboral y con el modelo de acreditación. Métodos: es un estudio transversal, analítico, realizado en 11 hospitales entre 282 enfermeros, de los cuales 94 eran líderes y 188 liderados, que respondieron a los cuestionarios Authentic Leardership Questionnaire y Job Satisfaction Survey. Resultados: se observó una diferencia significativa entre la evaluación de los líderes y de los liderados, en todas las dimensiones del Authentic Leardership Questionnaire. Respecto a la asociación del liderazgo auténtico con la satisfacción laboral, la correlación era significativamente positiva para los liderados, considerándose moderada. En los hospitales, con el modelo Joint Commission International, los liderados percibían a sus líderes con mayor transparencia. Conclusiones: se ha encontrado una correlación entre el liderazgo auténtico y la satisfacción laboral y el modelo de acreditación entre los liderados.

RESUMO Objetivos: identificar as dimensões dominantes da liderança autêntica dos enfermeiros em uma rede hospitalar privada e correlacionar com a satisfação no trabalho e com o modelo de acreditação. Métodos: estudo transversal, analítico, realizado em 11 hospitais, com 282 enfermeiros, sendo 94 líderes e 188 liderados, que responderam aos questionários Authentic Leardership Questionnaire, Questionário de Liderança Autêntica e o Job Satisfaction Survey, Pesquisa de Satisfação no trabalho. Resultados: houve diferença significante entre a avaliação dos líderes e liderados, em todas as dimensões do Authentic Leardership Questionnaire. Em relação à associação da liderança autêntica com a satisfação do trabalho, para os liderados foi encontrada uma correlação significativamente positiva, sendo considerada moderada. Nos hospitais, com o modelo Joint Commission International, os líderes foram percebidos por seus liderados com maior transparência. Conclusões: foi encontrado correlação entre a liderança autêntica com a satisfação no trabalho e o modelo de acreditação entre os liderados.

Prediction of disease progression and outcomes in multiple sclerosis with machine learning.

Multiple Sclerosis is a chronic inflammatory disease, affecting the Central Nervous System and leading to irreversible neurological damage, such as long term functional impairment and disability. It has no cure and the symptoms vary widely, depending on the affected regions, amount of damage, and the ability to activate compensatory mechanisms, which constitutes a challenge to evaluate and predict its course. Additionally, relapsing-remitting patients can evolve its course into a secondary progressive, characterized by a slow progression of disability independent of relapses. With clinical information from Multiple Sclerosis patients, we developed a machine learning exploration framework concerning this disease evolution, more specifically to obtain three predictions: one on conversion to secondary progressive course and two on disease severity with rapid accumulation of disability, concerning the 6th and 10th years of progression. For the first case, the best results were obtained within two years: AUC=[Formula: see text], sensitivity=[Formula: see text] and specificity=[Formula: see text]; and for the second, the best results were obtained for the 6th year of progression, also within two years: AUC=[Formula: see text], sensitivity=[Formula: see text], and specificity=[Formula: see text]. The Expanded Disability Status Scale value, the majority of functional systems, affected functions during relapses, and age at onset were described as the most predictive features. These results demonstrate the possibility of predicting Multiple Sclerosis progression by using machine learning, which may help to understand this disease's dynamics and thus, advise physicians on medication intake.