Reliability of telemedicine evaluation for EDSS functional systems in multiple sclerosis.

Introduction: There was an increase in telemedicine during the COVID-19 pandemic to follow patients with multiple sclerosis (MS). However, there is scarce data if online evaluations can cover important information assessed during in-clinic appointments, especially the Expanded Disability Status Score (EDSS). This study aims to develop a remote evaluation tool for EDSS functional systems and compare the performance with face-to-face evaluations. Methods: This was a single-center study that included all MS patients followed up at outpatient clinics of Hospital São Lucas Pontifícia Universidade Católica do Rio Grande do Sul, between April and August 2022. Initially, patients were routinely in-clinic evaluated by one trained neurologist for EDSS. After, patients were evaluated remotely without any information about the in-clinic EDSS results. We used a standardized interview with an interactive video platform to evaluate EDSS functional systems by telemedicine. Results: Forty-nine participants completed the two steps. Intra-class coefficient was 0.97 (95% CI: 0.95-0.98), concordance for EDSS below 4.0 was 0.87 (95% CI: 0.77-0.93) and ≥4.0 was 0.97 (95% CI: 0.89-0.99). There was perfect agreement in the final EDSS in 71.4% of the online and in-clinic evaluations. In the multivariate analysis, the visual (beta = 0.453; p = 0.003) and pyramidal (beta = 0.403; p = 0.009) systems contributed significantly to the difference in the final EDSS. Conclusion: The telemedicine tool created in this study can detect changes in functional systems with reliable results compared to in-clinic EDSS assessment. Telemedicine evaluations may reduce the number of in-clinic visits and the disease burden for patients with MS.

Neurological syndromes and potential triggers associated with antibodies to neuronal surface antigens.

BACKGROUND: Autoantibodies against surface neuronal antigens have been associated with specific neurological presentations including autoimmune encephalitis (AE), with variable association with neoplasia and infections. METHODS: We described the phenotype and environmental associations of patients with neurological syndromes associated with antibodies against neuronal surface antigens who were referred to a tertiary center in the South of Brazil. All patients were tested for neuronal autoantibodies using cell-based assays. Clinical, radiological, and laboratory findings were retrospectively reviewed. RESULTS: We identified 16 patients, 15 had subacute, and one had a progressive disease course. Among patients with subacute onset, 11 (73 %) were N-Methyl-d-Aspartate receptor (NMDAr-IgG)+, 3 (20 %) were Leucine-rich Glioma-Inactivated-1 (LGI1-IgG)+, and 1 (6 %) was positive for Glycine receptor-IgG. The patient with a progressive disease course had antibodies against IgLON5. Most patients had disease onset in spring and summer suggesting environmental factors for the development of AE. Also, we observed a different pattern of brain lesions when NMDAr-IgG encephalitis followed herpes encephalitis and a previously unreported association with Rosai-Dorfman-Destombe disease. All patients with encephalopathy met criteria for possible AE and all proven NMDAr-IgG+ met criteria for NMDAr-IgG encephalitis. However, only one LGI1-IgG+ patient fulfilled clinical criteria for limbic encephalitis. All but one received high-dose intravenous methylprednisolone, 11 also had intravenous human immunoglobulin, and 4 plasma exchange. Furthermore, all patients received second-line immunotherapy. Importantly, most patients improved with immunotherapy, even when initiated later in the disease course. CONCLUSION: We identified seasonal variability associated with neuronal surface antibodies suggesting environmental triggers. Also, we described the coexistence of NMDAr-IgG encephalitis with histiocytosis. In our series, most patients received second-line immunotherapy. We observed neurologic improvement after treatment even in cases of delayed diagnosis. Increasing the recognition and availability of tests and treatments for these conditions is of paramount importance in low- and middle-income countries.

Latin American consensus recommendations on the risk of infections in people with multiple sclerosis treated with disease modifying drugs.

INTRODUCTION: The emergence of several therapeutic options in multiple sclerosis (MS), which significantly modify the immune system functioning, has led to the need for the consideration of additional factors, such as risk of infections, in the decision-making process. The aim of these consensus recommendations was to discuss and perform a practical guide to Latin American neurologists on the risk of infections at diagnosis, follow-up and prior to initiation of DMDs. METHODS: A panel of Latin American neurologists, experts in demyelinating diseases and dedicated to management and care of MS patients, gathered during 2021 and 2022 to make consensus recommendations on the risk of infections in PwMS treated with DMDs in Latin America. The RAND/UCLA methodology was developed to synthesize the scientific evidence and expert opinions on health care topics and was used for reaching a formal agreement. RESULTS: Recommendations were established based on relevant published evidence and expert opinion, focusing on: 1- baseline infection disease and vaccination status; 2- opportunistic infections; 3- progressive multifocal leukoencephalopathy; 4- genitourinary system infections; 5- respiratory tract infections; 6- digestive system infections, 7-others local infections and 8- COVID-19. CONCLUSION: The recommendations of this consensus seek to optimize the care, management and treatment of PwMS in Latin America. The standardized evidence-based care of pwMS infections will allow better outcomes.

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.

Therapeutic strategies in NMOSD and MOGAD patients: A multicenter cohort study in Latin America.

PURPOSE: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome. METHODS: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naïve (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up. RESULTS: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 0.60). CONCLUSION: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used.

Interleukin-31 and soluble CD40L: new candidate serum biomarkers that predict therapeutic response in multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease that affects the central nervous system (CNS), varying from relatively benign to severely disabling. Although the roles of several cytokines and chemokines in MS are well established, their roles in MS lesions and evolution remain a matter of debate. Soluble CD40L (sCD40L) is a ligand that induces lymphocyte proinflammatory activity by stimulating the activation and maturation of B cells, promoting isotype switching and affinity hypermutation. Circulating sCD40L levels reflect activation of the CD40-CD40L complex. The interaction between CD40 and CD40L is of fundamental importance, suggesting their role in MS pathogenesis. Interleukin-31 (IL-31) is a proinflammatory cytokine that plays a role in allergies, autoimmune diseases, and is a major factor in several chronic inflammatory diseases. IL-31 triggers the JAK-STAT pathway in several different cell types, to induce proliferation and tissue remodeling in fibroblasts, epithelial cells, and endothelial cells. Some studies have described a correlation between these two cytokines and decreased serum levels of sCD40L and IL-31 after MS treatment, accompanied by a lower inflammatory response. In this review, we emphasize the possible correlation and positive feedback between IL31 and sCD40L in the MS proinflammatory response. We also describe the justification for this hypothesis and whether it is possible to investigate these cytokines as biomarkers of MS.

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.

Encephalopathy Due to COVID-19 With Great Response to Glucocorticoids.

Minor neurological symptoms such as anosmia are relatively common manifestations of coronavirus disease 2019 (COVID-19). However, severe affection of the central nervous system (CNS) occurs in a minority of cases and its treatment and pathophysiology is not yet well understood. It has been described that encephalitis due to COVID-19 may be caused by the proinflammatory state due to the cytokine storm or direct invasion of the virus in the CNS. Here we present a case of a 66-year-old man with bipolar disorder and moderate respiratory COVID-19 symptoms who presented to the emergency department with a decreased level of consciousness. Brain computerized tomography (CT) showed no acute pathology. A thorough investigation of other possible causes of CNS affection was negative. The patient was treated with pulse therapy with methylprednisolone and presented a significant improvement of his neurological condition, being discharged with a complete neurological recovery five days after the start of the treatment. This case illustrates the importance of a high index of suspicion in diagnosing severe CNS impairment in mild respiratory COVID-19 cases. Also, this case corroborates with previous reports of glucocorticoid response in CNS impairment associated with COVID-19, although more robust studies are required to confirm this relation.

Multiple sclerosis care units in Latin America: Consensus recommendations about its objectives and functioning implementation.

OBJECTIVE: Currently, there are several reasons to promote worldwide the concept of multiple sclerosis care units (MSCU) for a better management of affected patients. Ideally, the MSCU should have some human and technical resources that distinguish and improve the care of affected patients; however, local, and regional aspects should be considered when recommending how these units should operate. The objective of these consensus recommendations was to review how MSCU should work in Latin America to improve long-term outcomes in MS patients. METHODS: A panel of neurology experts from Latin America dedicated to the diagnosis and care of MS patients gathered virtually during 2019 and 2020 to carry out a consensus recommendation about objectives and functioning implementation of MSCU in Latin America. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations focused on the objectives, human and technical resources, and the general functioning that MSCU should have in Latin America. CONCLUSIONS: The recommendations of these consensus guidelines attempt to optimize the health care and management of MS patients by setting how MSCU should work in our region.

Prevalence of multiple sclerosis in key cities of Brazil: a study in Passo Fundo, Southern Brazil.

BACKGROUND: To improve the comparability of multiple sclerosis (MS) prevalence across Brazilian regions, the Brazilian Committee for Treatment and Research in MS has implemented a standardized approach to assess the prevalence of the disease in five key cities, which were deemed representative of their regions in terms of socio-geographical features and where in-person revision of each case was feasible. OBJECTIVE: To report the point-prevalence of MS in Passo Fundo, one of the key cities in Southern Brazil. METHODS: We sought to identify all MS patients who were living in Passo Fundo on July 1st, 2015. The primary source for case ascertainment was records from the offices of neurologists and neurosurgeons practicing in the city. Multiple secondary sources were used to maximize identification of cases. All patients underwent in-person review of the diagnosis by a panel of neurologists with experience in MS. RESULTS: We identified 52 MS patients living in Passo Fundo on July 1st, 2015. The point-prevalence rate for MS was 26.4/100,000 population (95% confidence interval, 19.7 to 34.6/100,000). Among the MS cases, 42 (80.8%) were female, for a sex ratio of 4.2:1. Forty-six cases (88.5%) were categorized as relapsing-remitting MS, and the remaining 6 cases, as secondary progressive MS (11.5%). Other epidemiological and clinical features were comparable to national and international MS populations. CONCLUSIONS: The prevalence of MS in Passo Fundo is one of the highest reported in Brazil so far. Studies in other key Brazilian cities, using the same methodology, are currently being carried out.

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.

Prevalence of multiple sclerosis in key cities of Brazil: a study in Passo Fundo, Southern Brazil / Prevalência de esclerose múltipla em cidades-chave do Brasil: um estudo em Passo Fundo, no sul do Brasil

ABSTRACT Background: To improve the comparability of multiple sclerosis (MS) prevalence across Brazilian regions, the Brazilian Committee for Treatment and Research in MS has implemented a standardized approach to assess the prevalence of the disease in five key cities, which were deemed representative of their regions in terms of socio-geographical features and where in-person revision of each case was feasible. Objective: To report the point-prevalence of MS in Passo Fundo, one of the key cities in Southern Brazil. Methods: We sought to identify all MS patients who were living in Passo Fundo on July 1st, 2015. The primary source for case ascertainment was records from the offices of neurologists and neurosurgeons practicing in the city. Multiple secondary sources were used to maximize identification of cases. All patients underwent in-person review of the diagnosis by a panel of neurologists with experience in MS. Results: We identified 52 MS patients living in Passo Fundo on July 1st, 2015. The point-prevalence rate for MS was 26.4/100,000 population (95% confidence interval, 19.7 to 34.6/100,000). Among the MS cases, 42 (80.8%) were female, for a sex ratio of 4.2:1. Forty-six cases (88.5%) were categorized as relapsing-remitting MS, and the remaining 6 cases, as secondary progressive MS (11.5%). Other epidemiological and clinical features were comparable to national and international MS populations. Conclusions: The prevalence of MS in Passo Fundo is one of the highest reported in Brazil so far. Studies in other key Brazilian cities, using the same methodology, are currently being carried out.

RESUMO Introdução: Para melhor comparar a prevalência de esclerose múltipla (EM) nas diferentes regiões do Brasil, o Comitê Brasileiro para Tratamento e Pesquisa em Esclerose Múltipla implementou uma abordagem padronizada para avaliar a prevalência da doença em 5 cidades-chave, consideradas representativas de suas regiões em termos de características sociogeográficas e nas quais seria viável revisar cada caso pessoalmente. Objetivos: Descrever a prevalência pontual de EM em Passo Fundo, uma das cidades-chave, localizada no Sul do Brasil. Métodos: Buscamos identificar todos os pacientes com EM que viviam em Passo Fundo no dia 1( de julho de 2015. A fonte primária para identificação de casos foi os registros de consultórios de neurologistas e neurocirurgiões da cidade. Múltiplas fontes secundárias foram usadas para maximizar a identificação de casos. Todos os pacientes tiveram o diagnóstico revisado pessoalmente por um painel de neurologistas com experiência em EM. Resultados: Identificamos 52 pacientes com EM que viviam em Passo Fundo em 1( de julho de 2015. Assim, a prevalência pontual bruta de EM foi 26,4/100.000 habitantes (intervalo de confiança de 95%, 19,7 a 34,6/100.000). Entre os casos de EM, 42 (80,8%) eram mulheres, (razão de sexos: 4,2:1). Quarenta e seis casos (88,5%) foram categorizados como EM remitente-recorrente, e os 6 casos restantes como EM secundariamente progressiva (11,5%). As demais características epidemiológicas e clínicas foram comparáveis a populações de EM internacionais. Conclusões: A prevalência de EM em Passo Fundo é uma das maiores já relatadas no Brasil. Estudos em outras cidades-chave brasileiras, usando a mesma metodologia, estão em andamento.

Status of the neuromyelitis optica spectrum disorder in Latin America.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

Research priorities in multiple sclerosis in Latin America: A multi-stakeholder call to action to improve patients care: Research priorities in MS in LATAM.

As human and economic resources are limited, especially in Latin America (LATAM), it is important to identify research priorities to improve multiple sclerosis (MS) patients care in the region. The objective was to generate a multidisciplinary consensus on research priorities in MS for patients care in LATAM by involving healthcare professionals and MS patient associations. METHODS: consensus was reached through a four-step modified Delphi method designed to identify and rate research priorities in MS in LATAM. The process consisted of two qualitative assessments, a general ranking phase and a consensus meeting followed by a more detailed ranking phase RESULTS: a total of 62 participants (35 neurologists, 4 nurses, 12 kinesiologists, 7 neuropsychologists and 4 patient association members) developed the process. At the final ranking stage following the consensus meeting, each participant provided their final rankings, and the top priority research questions were outlined. 11 research priorities were identified focusing on healthcare access, costs of the disease, physical and cognitive evaluation and rehabilitation, quality of life, symptoms management, prognostic factors, the need of MS care units and patient's management in emergencies like COVID-19. CONCLUSION: this work establishes MS research priorities in LATAM from multiple perspectives. To pursue the actions suggested could launch the drive to obtain information that will help us to better understand the disease in our region and, especially, to better care for affected patients.

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM.

BACKGROUND: There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America. OBJECTIVE: The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19. METHODS: RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission. RESULTS: 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU. CONCLUSION: we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.

Prevalence of multiple sclerosis in key cities of Brazil. A study in Joinville, Southern Brazil.

BACKGROUND: The Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) has launched an initiative to determine the prevalence of multiple sclerosis (MS) in Brazil, based on key cities deemed representative of their regions in terms of demographic and environmental features. OBJECTIVE: To investigate the prevalence rate of MS in Joinville. METHODS: We reviewed the medical records of all patients who lived in Joinville and met the 2010 McDonald's diagnostic criteria revised for MS on the prevalence day (March 11, 2016). Potential MS patients included individuals treated by all practicing neurologists in the city and the ones found in patients' association and the database of the Municipal Department of Health. Advertisements about the survey were also broadcast on radio and television. Patients who were not living in Joinville on the prevalence day were excluded. All potential MS patients were invited to an in-person diagnostic review, carried out by a panel of experienced neurologists with special expertise in MS on March 11, 2016. RESULTS: The MS prevalence rate was 13.5 per 100,000 inhabitants (95% confidence interval [95%CI] 12.9-14.0/100,000). A total of 51 (66.2%) participants were females, and 26 (33.7%) were males (female to male ratio=1.9:1). Out of the 77 patients, 73 (94.8%) were Caucasians, and four (5.1%) were mixed-race. CONCLUSIONS: Despite its latitude location and European colonization, the prevalence rate was below expectation. The intense internal migration from regions with lower MS prevalence rates to Joinville may have played a role in attenuating the increased risk of MS associated with latitude gradient and European ancestry. Prevalence studies in other cities from Southern Brazil with no significant internal migration and taking part in this broad project may clarify this issue.