Impairment of daily occupations in multiple sclerosis: analysis of neuroimaging, general and social cognition, and reserve.

BACKGROUND: Multiple Sclerosis (MS) can impact performance of daily occupations in both relapsing-remitting (RRMS) and secondary-progressive (SPMS) clinical courses. Work force participation decreases with advancing physical disability but the influence of non-motor factors, neuroimaging, and reserve have been scarcely investigated. We aimed to evaluate MRI, clinical, and cognitive (social and general) factors associated with impairment in different daily occupations and address whether cognitive and brain reserve have a positive impact on the ability to maintain these activities. METHODS: We prospectively enrolled persons with MS (PwMS) who underwent clinical examination (Expanded Disability Status Scale - EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT), general neuropsychological assessment (Brief Repeatable Battery of Neuropsychological Tests - BRBN, including the Symbol Digit Modalities Test - SDMT), social cognition evaluation (Reading the Mind in the Eyes Test), cognitive reserve questionnaire, and MRI (FreeSurfer). We also enrolled healthy subjects for comparison as a control group. Daily occupations (employment, money management, and driving abilities) were assessed in all individuals with questionnaires. RESULTS: We included 62 PwMS (32 RRMS and 30 SPMS; mean age 42.8 years; median educational time 12.75 years) and 67 controls (mean age 39.7; median educational time 12.0 years) which were similar regarding demographics, education, and socioeconomic status (p > 0.1). Most PwMS (67.7%) had work-restrictions. They also reported fewer money management and driving abilities than controls (p < 0.001). Work-restriction was associated with physical disability (p = 0.006), SDMT and BRBN performance (p = 0.035 and p = 0.031, respectively), and T2-lesion volume (p = 0.022), with large effect sizes (d > 0.75). After hierarchical linear regression, money management was associated with hand dexterity, general and social cognition, and cognitive reserve (p < 0.03). Variables associated with driving abilities included fatigue, verbal fluency, striatum volume, and brain reserve (p < 0.05). CONCLUSIONS: PwMS have more frequent work-restrictions and impairment in money management and driving abilities compared to controls. Cognitive function, physical disability, and MS-lesion burden are strongly associated with work-restriction. Social cognition can also influence financial capacity. Cognitive and brain reserve can help retain some of these daily occupations.

Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome.

Background: The expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis. Case presentation: Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells. Conclusions: Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.

The Role of MRI in Differentiating Demyelinating and Inflammatory (not Infectious) Myelopathies.

Demyelinating and inflammatory myelopathies represent a group of diseases with characteristic patterns in neuroimaging and several differential diagnoses. The main imaging patterns of demyelinating myelopathies (multiple sclerosis, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, and myelin oligodendrocyte glycoprotein antibody-related disorder) and inflammatory myelopathies (systemic lupus erythematosus-myelitis, sarcoidosis-myelitis, Sjögren-myelitis, and Behçet's-myelitis) will be discussed in this article, highlighting key points to the differential diagnosis.

Neuromyelitis optica spectrum disorders with a benign course. Analysis of 544 patients.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) most commonly cause severe disability which is related to disease attacks. However, some patients retain good neurological function for a long time after disease onset. OBJECTIVES: To determine the frequency, demographic and the clinical features of good outcome NMOSD, and analyze their predictive factors. METHODS: We selected patients who met the 2015 International Panel for NMOSD diagnostic criteria from seven MS Centers. Assessed data included age at disease onset, sex, race, number of attacks within the first and three years from onset, annualized relapsing rate (ARR), total number of attacks, aquaporin-IgG serum status, presence of cerebrospinal fluid (CSF)-specific oligoclonal bands (OCB) and the Expanded Disability Status Scale (EDSS) score at the last follow-up visit. NMOSD was classified as non-benign if patients developed sustained EDSS score >3.0 during the disease course, or benign if patients had EDSS score ≤3.0 after ≥15 years from disease onset. Patients with EDSS <3.0 and disease duration shorter than 15 years were not qualified for classification. We compared the demographic and clinical characteristics of benign and non-benign NMOSD. Logistic regression analysis identified predictive factors of outcome. RESULTS: There were 16 patients with benign NMOSD (3% of the entire cohort; 4.2% of those qualified for classification; and 4.1% of those who tested positive for aquaporin 4-IgG), and 362 (67.7%) with non-benign NMOSD, whereas 157 (29.3%) did not qualify for classification. All patients with benign NMOSD were female, 75% were Caucasian, 75% tested positive for AQP4-IgG, and 28.6% had CSF-specific OCB. Regression analysis showed that female sex, pediatric onset, and optic neuritis, area postrema syndrome, and brainstem symptoms at disease onset, as well as fewer relapses in the first year and three years from onset, and CSF-specific OCB were more commonly found in benign NMOSD, but the difference did not reach statistical significance. Conversely, non-Caucasian race (OR: 0.29, 95% CI: 0.07-0.99; p = 0.038), myelitis at disease presentation (OR: 0.07, 95% CI: 0.01-0.52; p <0.001), and high ARR (OR: 0.07, 95% CI: 0.01-0.67; p = 0.011) were negative risk factors for benign NMOSD. CONCLUSION: Benign NMOSD is very rare and occurs more frequently in Caucasians, patients with low ARR, and those who do not have myelitis at disease onset.

Prevalência da esclerose múltipla em pacientes tratados com medicamentos modificadores do curso da doença utilizando dados do Sistema Único de Saúde brasileiro / Prevalence of multiple sclerosis in patients treated with disease-modifying drugs using data from the Brazilian Unified Health System

Objetivo: Compreender o cenário da esclerose múltipla (EM) em relação aos aspectos epidemiológicos, diagnósticos, progressão, tratamento e comorbidades no sistema público brasileiro. Métodos: Trata-se de um estudo retrospectivo e observacional utilizando os sistemas de dados do Departamento de Informática do Sistema Único de Saúde (DataSUS). Os dados utilizados foram obtidos por meio da base de dados do Sistema Ambulatorial/Sistema de Procedimentos de Alta Complexidade (SIA/SUS). Nessa base, o vínculo de registros foi por meio do Cadastro Nacional de Saúde (CNS). Para a quantificação de dados epidemiológicos, foram coletados os dados do Código de Endereçamento Postal (CEP), sexo e data de nascimento, além das bases de geolocalização dos pacientes. Considerou-se como desfecho primário a descrição epidemiológica da população de pacientes em uso ou que usaram MMCD para o tratamento da EM. Como desfecho secundário, consideraram-se as características dos pacientes (gênero, idade, idade ao diagnóstico e comorbidades). Resultados: Foram incluídos na análise 45.011 pacientes. Identificou-se predominância de pacientes do gênero feminino (72,9%) e com idade entre 31 e 60 anos (61,23%) diagnosticados com CID G35 no primeiro registro. A taxa de incidência de pacientes com EM foi maior (2,7 pacientes/100 mil habitantes) na região Sudeste, seguida pela região Sul (2,2 pacientes/100 mil). A prevalência na região Sul teve a maior taxa (18 pacientes/100 mil), seguida pelo Sudeste (16,7 pacientes/100 mil). As betainterferonas e o acetato de glatirâmer foram os medicamentos mais utilizados no primeiro tratamento. O acetato de glatirâmer foi o mais utilizado para o segundo tratamento no período de 2011 até 2017. Em 2018, os MMCD mais utilizados como segundo tratamento foram fingolimode e natalizumabe. A partir de 2019, fingolimode, fumarato de dimetila e natalizumabe foram os medicamentos mais utilizados como segundo tratamento, permanecendo nessa ordem até 2021. Para o terceiro tratamento, o natalizumabe foi o medicamento mais utilizado até 2017. Após esse período, o fingolimode passou a ser mais usado. Desde 2019, com o acesso ao fumarato de dimetila, os medicamentos mais prescritos foram, em ordem decrescente, fingolimode, natalizumabe e fumarato de dimetila. Conclusão: Estabelecer uma análise epidemiológica dos pacientes que usam MMCD para o tratamento da EM no Brasil, além do padrão de tratamento, são dados essenciais para a promoção do tratamento da EM de forma adequada, bem como para a implementação de políticas públicas locais, regionais e nacionais.

Objective: To understand the multiple sclerosis (MS) setting in relation to epidemiological aspects, diagnoses, progression, treatment and comorbidities in the Brazilian public system. Methods: This is a retrospective, observational study using the Unified Health System's Informatics Department [Departamento de Informática do Sistema Único de Saúde] data systems (DataSUS). The data used were obtained by means of the outpatient system/high-complexity procedure system (SIA/SUS) database. In this database, the association of entries was via the National Health Registration [Cadastro Nacional de Saúde] (CNS). For epidemiological data quantification, Zip Code, sex and date of birth information was collected, as well as data from patient geolocation databases. The epidemiological description of the patient population using or having used DMTs for MS treatment was considered as the primary endpoint. Patient characteristics (gender, age, age at diagnosis and comorbidities) were considered as the secondary endpoint. Results: 45,011 patients were included in the analysis. A predominance of female patients (72.9%) aged between 31 and 60 years (61.23%) and diagnosed with ICD code G35 in the first entry was identified. The incidence rate of patients with MS was higher (2.7 patients/100 thousand inhabitants) in the Southeast region, followed by the South region (2.2 patients/100 thousand). Prevalence in the South region had the highest rate (18 patients/100 thousand), followed by the Southeast region (16.7 patients/100 thousand). Interferons beta and glatiramer acetate were the most used drugs in the first treatment. Glatiramer acetate was the most used drug for the second treatment within the period from 2011 to 2017. In 2018, the most common DMTs used as second treatment were fingolimod and natalizumab. From 2019, fingolimod, dimethyl fumarate and natalizumab were the most used drugs as second treatment, remaining in this order until 2021. For the third treatment, natalizumab was the most used drug until 2017. After this period, fingolimod became more widely used. Since 2019, with access to dimethyl fumarate, the most prescribed drugs were, in decreasing order, fingolimod, natalizumab and dimethyl fumarate. Conclusion: Establishing an epidemiological analysis of patients using DMTs for MS treatment in Brazil, in addition to standard of care, results in critical data for adequately promoting MS treatment, as well as for implementing local, regional and national public policies.

Are we ready to define cognitive worsening in MS? How different cutoffs detect future cognitive worsening after six years of follow-up.

BACKGROUND: Although cognitive evaluation has been incorporated in recent MS clinical trials, the definition of cognitive progression is not clear and recent data are questioning the 4-point cutoff using the SDMT at the individual level. We aimed to evaluate the behavior of cognitive performance over time using different cutoffs. METHODS: Cognitive performance over six years was analyzed in a cohort of 42 relapsing-remitting MS patients and 30 controls using verbal/visual memory and information processing speed tests. Fixed cutoffs were: 10% and 20% change (all tests) and a 4- and 8-point change (SDMT). The relative cutoff established by regression-based models was a 1SD change. RESULTS: The distributions of "worsening", "stability", and "improvement" showed low concordance rates across the cutoffs (p < 0.001 for most comparisons). Most patients classified with worsening initially using fixed cutoffs had subsequent improvement in all cognitive tests, yielding a low sensitivity to predict later cognitive worsening. Using the relative cutoff, the proportion of patients with subsequent improvement was noticeably smaller. CONCLUSIONS: Fixed cutoffs classify a high proportion of patients with cognitive improvement. Most patients categorized with worsening initially presented subsequent improvement. Instead, the relative cutoff generally had a better performance. These data raise concerns about how we are defining cognitive worsening so far, especially at the individual level.

Acute Hepatitis with Positive Autoantibodies: A Case of Natalizumab-Induced Early-Onset Liver Injury.

BACKGROUND Natalizumab is an anti-integrin monoclonal antibody used as an alternative treatment regimen for patients with autoimmune disorders, especially multiple sclerosis and Crohn's disease. Natalizumab-induced liver injury has been rarely reported and may follow the first dose (with increases in liver enzymes usually after 6 or more days), or after multiple doses. In general, it is non-severe acute hepatitis (with a hepatocellular pattern) and autoantibodies can be positive, mainly anti-nuclear and anti-smooth muscle antibodies. CASE REPORT We are reporting the case of a 60-year-old woman diagnosed with multiple sclerosis previously treated with interferon-beta, dimethyl fumarate, and fingolimod, who presented jaundice 1 day after the first infusion of natalizumab. She had an early-onset acute hepatitis with aminotransferases levels higher than 1000 IU/L and total bilirubin almost 41 mg/dL. Anti-nuclear and anti-smooth muscle antibodies were positive and the histopathological analysis of the liver showed intrahepatic cholestasis associated with moderate necroinflammatory activity (subacute cholestatic hepatitis) and mild diffuse perisinusoidal fibrosis, which could be compatible with the hypothesis of drug-induced liver injury. The scenario of an autoimmune-like hepatitis led the medical team to start oral prednisone and she progressively improved in clinical and laboratory features. Serum levels of liver enzymes and bilirubin were normal within 3 months and there was no further increase after discontinuation of corticosteroid therapy. CONCLUSIONS Physicians should be aware of the risk of early-onset acute hepatitis in patients starting natalizumab, especially women with multiple sclerosis. Treatment with corticosteroid for a few months may be beneficial.

Gut microbiome in neuropsychiatric disorders.

BACKGROUND: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. OBJECTIVE: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. METHODS: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. RESULTS: targeted taxa were described and grouped from major studies to each disease. CONCLUSIONS: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.

Cytotoxic B Cells in Relapsing-Remitting Multiple Sclerosis Patients.

Background: Emerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) pathogenesis. Objective: To investigate whether CD19+ B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8+ T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients. Methods: In this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses. Results: RRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8+GzmB+ T lymphocytes when compared to healthy volunteers. An increase in circulating CD19+GzmB+ B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-ß (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8+ T lymphocytes, the expression of GzmB was significantly higher in CD19+Runx3+-expressing B cells when compared to CD19+Runx3- counterparts in RRMS patients. Conclusions: CD19+ B cells may exhibit cytotoxic behavior resembling CD8+ T lymphocytes in MS patients during different treatments. In the future, monitoring "cytotoxic" subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions.

Gut microbiome in neuropsychiatric disorders / O microbioma intestinal nas doenças neuropsiquiátricas

ABSTRACT Background: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. Objective: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. Methods: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. Results: targeted taxa were described and grouped from major studies to each disease. Conclusions: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.

RESUMO Antecedentes: Os transtornos neuropsiquiátricos são uma importante causa de morte e invalidez no mundo. Os mecanismos subjacentes a esses transtornos incluem uma constelação de etiologias estruturais, infecciosas, imunológicas, metabólicas e genéticas. Avanços nas técnicas de sequenciamento do DNA têm demonstrado que a composição do microbioma entérico é dinâmica e desempenha um papel fundamental não apenas na homeostase do hospedeiro, mas também em várias doenças. O microbioma entérico atua como mediador na sinalização das vias metabólica, neuroimune e neuroendócrina. Objetivo: Apresentar os estudos mais recentes sobre a possível influência do microbioma intestinal nas diversas doenças neuropsiquiátricas e discutir tanto os resultados quanto a eficácia dos tratamentos que envolvem a manipulação do microbioma intestinal. Métodos: foram examinadas algumas das evidências pré-clínicas e clínicas e estratégias terapêuticas associadas à manipulação do microbioma intestinal. Resultados: os táxons-alvo foram descritos e agrupados a partir dos principais estudos para cada doença. Conclusões: Entender a fundo a complexidade das interações ecológicas no intestino e sua associação com a suscetibilidade a certas doenças agudas e crônicas pode levar ao desenvolvimento de novos biomarcadores diagnósticos com base em alvos moleculares. Além disso, o estudo do microbioma intestinal pode auxiliar na otimização de tratamentos não farmacológicos emergentes, tais como o transplante de microbiota fecal, o uso de probióticos e intervenções nutricionais personalizadas. Dessa forma, terapias alternativas poderiam ser usadas para reduzir o impacto dos transtornos neuropsiquiátricos na saúde pública. Esperamos que esse conhecimento seja útil para médicos que cuidam de pacientes com diversos transtornos neuropsiquiátricos.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system.

The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system / Recomendações do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia (DCNI/ABN) e do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e Doenças Neuroimunológicas (BCTRIMS) sobre vacinação em geral e contra a SARS-CoV-2 para pacientes com doenças desmielinizantes do sistema nervoso central

ABSTRACT The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

RESUMO O DC de Neuroimunologia da ABN e o BCTRIMS trazem, nesse documento, as recomendações sobre vacinação da população com doenças desmielinizantes do sistema nervoso central (SNC) contra infecções em geral e contra o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2), causador da COVID-19. Destaca-se a gravidade do atual momento frente ao avanço da COVID-19 em nosso País, o que torna mais evidente e importante a criação de guia de referência para orientação aos médicos, pacientes e autoridades de saúde pública quanto à vacinação, meio efetivo e seguro no controle de determinadas doenças infecciosa. O DCNI/ABN e o BCTRIMS recomendam que os pacientes com doenças desmielinizantes do SNC (ex., EM e NMOSD) sejam constantemente monitorados, quanto a atualização do seu calendário vacinal, especialmente, no início ou antes da mudança do tratamento com uma droga modificadora de doença (DMD). É importante também salientar que as vacinas são seguras e os médicos devem estimular o seu uso em todos os pacientes. Evidentemente, deve ser dada especial atenção às vacinas com vírus vivos atenuados. Por fim, é importante que os médicos verifiquem qual DMD o paciente está em uso e quando foi feita a sua última dose, pois cada fármaco pode interagir de forma diferente com a indução da resposta imune.

Evaluation of diagnosis and treatment practices of Brazilian neurologists among patients with multiple sclerosis.

BACKGROUND: Recent changes to the diagnostic criteria for multiple sclerosis (MS) and new medications have had a major impact on the way in which specialists manage the disease. OBJECTIVE: To investigate factors considered by Brazilian neurologists in managing MS, and to identify how these contribute to diagnosis and treatment. METHODS: Potential participants were selected by a steering committee (MS experts who developed this survey). Only MS specialists were included in the study (neurologists who had completed a neuroimmunology fellowship or who were treating more than 30 MS patients). Links to the online questionnaire were distributed between March 2019 and January 2020. This questionnaire was composed of sections with hypothetical MS scenarios. RESULTS: Neurologists from 13 Brazilian states responded to the survey (n = 94). In the clinically isolated syndrome (CIS) scenario, the respondents agreed to treat patients with a high risk of MS diagnosis, whereas in the radiologically isolated syndrome (RIS) half of the respondents opted not to treat, even among high-risk patients. In cases of low-activity relapsing-remitting MS (RRMS), the choice of treatment was distributed among interferon beta, glatiramer acetate and teriflunomide, which were changed to fingolimod and natalizumab, as RRMS severity increased. The topics in which disagreement was found included practices regarding use of disease-modifying therapy (DMT) for pregnant patients and the washout period required for some DMTs. CONCLUSIONS: This study enabled identification of areas of agreement and disagreement about MS treatment among Brazilian neurologists, which can be used to update future protocols and improve patient management.

Decreased Neurofilament L Chain Levels in Cerebrospinal Fluid and Tolerogenic Plasmacytoid Dendritic Cells in Natalizumab-Treated Multiple Sclerosis Patients - Brief Research Report.

BACKGROUND: Neurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients. OBJECTIVE: To evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment. METHODS: CSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2+) were accessed through flow cytometry analyses. RESULTS: CSF levels of NfL were significantly reduced during NTZ treatment, while the serum levels of sHLA-G were increased. Moreover, NTZ treatment enhanced tolerogenic (HLA-G+, CD274+, and HLA-DR+) molecules and migratory (CCR7+) functions of pDCs in the peripheral blood. CONCLUSION: These findings suggest that NTZ stimulates the production of molecules with immunoregulatory function such as HLA-G and CD274 programmed death-ligand 1 (PD-L1) which may contribute to the reduction of axonal damage represented by the decrease of NfL levels in patients with MS.