Progression of Relapsing-Remitting Multiple Sclerosis despite the new era of treatments / Progressão da Esclerose Múltipla Remitente-Recorrente apesar da nova era de medicamentos / Progresión de la esclerosis múltiple recurrente-remitente a pesar de la nueva era de las drogas

Objective. The present study aims to evaluate the conditions associated with the progression of Multiple Sclerosis (MS) and patients' dysfunctions. Methods. We perform aretrospective longitudinal analytical observational study in 46 patients with MS from a polyclinic in Rio de Janeiro, Brazil. We used the Expanded Disability Status Scale (EDSS) to rank the pa-tients according to their disability and establish a correlation with risk factors, treatment, and time of disease. Results. Of 46 patients, 69.6% were female, and 67.4% were white. Patients with fewer functional systems affected at the beginning of the disease had a longer time for disease progression, according to EDSS. Low-efficacy drugs led to a high rate of discon-tinuation of the treatment. Patients who used a continuous treatment took longer to reach higher EDSS values than those who discontinued treatment. Conclusion. Despite the control of MS with high-effective drugs, there is still some disability for the patient. The factors that influenced the progression of the disability were: multiple symptoms at the beginning of the disease, more than 30 years old at the beginning of the MS, delay in diagnosis and initiation of treatment, among others. (AU)

Objetivo. O presente estudo tem como objetivo avaliar as condições associadas à progressão de doença e disfunções dos pacientes com Esclerose Múltipla (EM). Métodos. Estudo observacional analítico longitudinal retrospectivo com 46 pacientes com EM de uma policlínica do Rio de Janeiro, Brasil. Foi utilizada a Escala de Incapacidade Funcional Expan-dida (EDSS) para classificar os pacientes de acordo com a incapacidade e estabelecer correlação com fatores de risco, tratamento e tempo de doença. Resultados. Dos 46 pacientes, 69,6% eram do sexo feminino e 67,4% eram brancos. Pacientes com menos sistemas funcionais afetados no início da EM levaram maior tempo para progressão da doença. Medicamentos de baixa eficácia foram associados a uma alta taxa de descontinuação do tratamento. Pacientes em trata-mento contínuo levaram maior tempo para atingir valores mais altos de EDSS comparado com pacientes que descon-tinuaram o tratamento. Conclusão. Apesar do controle da EM com medicamentos de alta eficácia, os pacientes ainda apresentam alguma incapacidade. Os fatores que influenciaram a progressão da incapacidade foram: múltiplos sintomas no início da doença, mais de 30 anos no início da EM, atraso no diagnóstico e início do tratamento, entre outros. (AU)

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.

Neurological symptoms and neuroimaging alterations related with COVID-19 vaccine: Cause or coincidence?

Although vaccination against Coronavirus disease-2019 (COVID-19) is still occurring, several adverse effects temporally related to these vaccines are already being reported, even if through isolated case reports. In the present study, we describe the lesions seen on magnetic resonance imaging (MRI) of three patients who developed neurological symptoms after receiving the ChAdOX1 nCoV-19 vaccine (Oxford/AstraZeneca). The first patient presented with an ischemic stroke in the posterior limb of the left internal capsule, two days after vaccination. The second patient presented with a left facial nerve palsy, seven days after vaccination. The third patient presented with myelitis, eight days after receiving the vaccine. All patients presented the symptoms after the first dose of the vaccine and did not have a history of previous COVID-19. The real incidence of these types of complications is not known yet, but it is important to consider the possibility of COVID-19 vaccine complications, in patients with a recent history of vaccination and recent development of neurological symptoms, even though this association is only casual. Longitudinal studies are necessary to further analyze the incidence of the adverse effects of each vaccine against SARS-CoV-2.

Clinical Features of COVID-19 on Patients With Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND OBJECTIVES: To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described. RESULTS: Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection. DISCUSSION: Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations.

Neurological implications of SARS-CoV-2 infection: review of literature / Implicações neurológicas da infecção por SARS-CoV-2: revisão da literatura

The infection caused by the new coronavirus had its first case described in December 2019, in Wuhan, China, and reached a pandemic status in March 2020. Since then, knowledge about the different aspects of this infection has evolved, as well as increased reports concerning related neurological manifestations. Thus, the neurologist assumes a fundamental role in the care of these patients, who may have a clinical phenotype that goes beyond respiratory aspects. In the present study, we highlight the data available in the literature so far regarding the main neurological implications related to COVID-19 infection, in addition to calling attention for some aspects related to patients with previous neurological diseases who contract this infection.

A infecção causada pelo novo Coronavírus teve seu primeiro caso descrito em dezembro de 2019, em Wuhan, China e alcançou o status de pandemia em março de 2020. Desde então, o conhecimento sobre os diferentes aspectos da referida infecção evolui assim como aumentam relatos de manifestações neurológicas relacionadas. Assim, o neurologista assume papel fundamental na assistência desses pacientes, que podem ter um fenótipo clínico que ultrapassa os aspectos respiratórios. No presente estudo, destacamos os dados disponíveis na literatura até o presente momento no tocante às principais implicações neurológicas relacionadas à infecção pelo COVID-19, além de destacar alguns aspectos relativos aos pacientes com doenças neurológicas prévias que contraem a referida infecção.

Late Onset of Neuromyelitis Optica Spectrum Disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. NMOSD starting after the age of 50 years is considered a "late onset" (LO-NMOSD) and seems to be particularly aggressive. The objective of this paper is to present a series of 37 Brazilian patients with LO-NMOSD. METHODS: Retrospective data collection from medical records of patients with LO-NMOSD seen at 14 Brazilian specialized units. RESULTS: The ratio of women to men in the sample was 4.3 to 1. The patients were followed up for a median period of 4 years. Sex, age at disease onset, and ethnic background were not associated with the number of relapses or disability outcomes. Extensive longitudinal myelitis affected 86% of patients, while optic neuritis affected 70%, and brainstem syndromes were present in only 16% of these patients. Six patients are currently using some type of support for walking or are wheelchair-bound. Three have died. Therapeutic options for NMOSD were particularly complicated for these elderly patients, since medications for controlling NMOSD are, in essence, immunosuppressive. Long-term use of corticosteroids can be an issue when the patients have high blood pressure, diabetes mellitus, or dyslipidemia (conditions often seen in elderly individuals). CONCLUSION: This series of LO-NMOSD cases highlights the importance of prompt diagnosis and treatment for these patients.

Seroconversion of JCV antibodies is strongly associated to natalizumab therapy.

Previous infection with John Cunningham virus (JCV) increases the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) undergoing treatment with natalizumab. Patients who test negative for JCV antibodies must be assessed every six months due to the risk of seroconversion. Data from the United States of America, Portugal, Holland, France, United Kingdom and Sweden have shown a strong correlation between the use of natalizumab and JCV seroconversion. The authors present now data on patients from Brazil, as there are no data from Latin American countries published on this subject yet. A group of 86 patients with MS with negative results for antibodies against JCV were included in this analyses with at least two JCV antibodies testing. Twenty-five patients (29% of the total group) did not use natalizumab at any time, while the remaining 71% used natalizumab for a median period of 800 days (equivalent to 28 monthly infusions). Seroconversion was observed in 19 patients (22.1%). There was no association of seroconversion with gender, age, previous pulses of corticosteroid or specific MS-modifying drugs. The use of natalizumab was strongly associated to seroconversion (p < 0.0001). The present results confirm the influence of natalizumab therapy on JCV antibodies in several countries and continents.

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis.

Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). OBJECTIVE: To identify the serologic profile of JCV in patients with MS. METHODS: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. RESULTS: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. CONCLUSION: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis / Perfil sorológico do vírus John Cunningham (JCV) em pacientes com esclerose múltipla

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

RESUMO As opções terapêuticas para esclerose múltipla (EM) modificaram-se ao longo dos últimos anos, trazendo uma nova categoria de drogas com melhor perfil de eficácia. No entanto, estas drogas vieram com um novo perfil de potenciais eventos adversos que exigem que o neurologista os reconheça bem e rapidamente. Uma das complicações mais temidas destes tratamentos para a EM é a leucoencefalopatia multifocal progressiva (LEMP), causada pela reativação do vírus John Cunningham (JCV). Objetivo: Identificar o perfil sorológico de JCV em pacientes com EM. Métodos: Dados sorológicos de JCV foram obtidos através do ensaio por enzimas imuno-adsorvidas (ELISA) fornecido pelo programa STRATIFY-JCV. Resultados: Um total de 1.501 testes sanguíneos foram obtidos de 1.102 pacientes com EM. O grupo teve 633 pacientes (57,1%) soropositivos para anticorpos anti-JCV e 469 pacientes negativos (42,9%). Vinte e três pacientes se tornaram posivitos após resultados iniciais negativos para anticorpos anti-JCV. A taxa de soroconversão foi 18,5% em 22 meses. Conclusão: O perfil sorológico do JCV e a soroconversão nos pacientes brasileiros foi semelhante àquela descrita em outros países.

Correlation of clinical findings and brain volume data in multiple sclerosis.

Brain volume measurements are becoming an important tool for assessing success in controlling multiple sclerosis (MS) activity. MSmetrix (icometrix) is an easy-to-use platform, specific for MS magnetic resonance imaging (MRI) of the brain. It provides data on total brain volume, grey matter volume and lesion load volume. The objective of the present study was to assess whether disability and the number of relapses during the previous year correlated with brain volume measurements from MSmetrix. Data on 185 icometrix reports from patients with MS were used to evaluate the potential correlation between brain volume measurements and clinical parameters. There was a significant correlation between higher disability and decreased brain volume (total and grey matter). Increased lesion load in the brain and higher number of relapses in the previous year were also independently correlated with decreased brain tissue volume and with increased disability. This is the first study with real-world data to show that icometrix is a relevant tool for the study of brain volume loss in MS.

African ancestry is a predictor factor to secondary progression in clinical course of multiple sclerosis.

Background. Studies on the clinical course of multiple sclerosis have indicated that certain initial clinical factors are predictive of disease progression. Regions with a low prevalence for disease, which have environmental and genetic factors that differ from areas of high prevalence, lack studies on the progressive course and disabling characteristics of the disease. Objective. To analyse the long-term evolution to the progressive phase of the relapsing-remitting multiple sclerosis and its prognosis factors in mixed population. Methods. We performed a survival study and logistic regression to examine the influence of demographic and initial clinical factors on disease progression. Among 553 relapsing-remitting patients assisted at a Brazilian reference centre for multiple sclerosis, we reviewed the medical records of 150 patients who had a disease for ten or more years. Results. African ancestry was a factor that conferred more risk for secondary progression followed by age at the onset of the disease and the number of relapses in the year after diagnosis. A greater understanding of the influence of ancestry on prognosis serves to stimulate genetics and pharmacogenomics research and may clarify the poorly understood neurodegenerative progression of MS.

Differences in the progression of primary progressive multiple sclerosis in Brazilians of African descent versus white Brazilian patients.

Recent studies have suggested faster clinical progression and greater disability in multiple sclerosis patients of African descent. This study analysed the effect of ethnicity on progression and disability. Sixty-five patients with primary progressive multiple sclerosis were selected and classified as being of African descent or white. Time from onset of the disease until reaching Expanded Disability Status Scale grades 3, 6, and 8 was assessed, as well as irreversible disability (Expanded Disability Status Scale grade maintained for >or=6 months). In the African descent group, the median time to reach Expanded Disability Status Scale 3 was 1 year shorter (1 year vs 2 years, p= 0.02), and to reach Expanded Disability Status Scale 6 was 2 years shorter (3 years vs 5 years, p= 0.01) than in the group of white patients. According to the Kaplan-Meier survival curves, patients of African descent reached every disability stage faster than white patients (p= 0.03, p = 0.04, and p = 0.03, respectively, for Expanded Disability Status Scale grades 3, 6, and 8). As in United States and European patients of African descent, the more severe and faster progression of multiple sclerosis seen in Brazilian primary progressive multiple sclerosis patients of African descent suggests a possibly greater effect of ethnicity rather than environment on the progression of multiple sclerosis.