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.

Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis.

The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

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.

Dengue fever in patients with multiple sclerosis taking fingolimod or natalizumab.

Dengue fever is the most prevalent mosquito-borne viral illness in humans. There may be different clinical manifestations of the disease, from mild symptoms to hemorrhagic forms of dengue fever and even neurological complications of this viral infection. Blood cells are usually affected, and thrombocytopenia is the hallmark of the disease. This paper presents 15 cases of dengue fever in patients with multiple sclerosis (MS) taking fingolimod or natalizumab. There were no complications of dengue fever or worse outcomes of MS in these patients, and only four of them needed short-term treatment withdrawal due to lymphopenia.

Safety of switching from natalizumab straight into fingolimod in a group of JCV-positive patients with multiple sclerosis.

OBJECTIVE: To assess safety of the switch between natalizumab and fingolimod without a washout period. METHODS: Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. RESULTS: After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. CONCLUSION: Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.

Alternatives for reducing relapse rate when switching from natalizumab to fingolimod in multiple sclerosis.

Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

How do we manage and treat a patient with multiple sclerosis at risk of tuberculosis?

Tuberculosis continues to be a serious health problem worldwide. The disease continues to be underdiagnosed and not properly treated. In conditions that affect the immune system, such as multiple sclerosis (MS), latent tuberculosis may thrive and reactivate during the use of immunomodulatory and immunosuppressive drugs. Among the best treatment options for patients with latent or active tuberculosis who have MS are IFN-ß, glatiramer acetate and mitoxantrone. Drugs leading to a reduced number and/or function of lymphocytes should be avoided or used with caution. Tuberculosis must always be investigated in patients with MS and treated with rigor.

The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis.

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Antiparasitic antibodies occur with similar frequency in patients with clinically established multiple sclerosis with or without oligoclonal bands in the cerebrospinal fluid.

UNLABELLED: The "hygiene hypothesis" postulates an inverse relationship between the prevalence of parasitic infections and the frequency of multiple sclerosis (MS). OBJECTIVE: It was to study whether antibodies against parasites could be demonstrated more frequently in blood serum from MS patients with oligoclonal bands (OCB) than from MS patients without OCB. METHODS: We studied serum samples from 164 patients who had previously been analyzed to investigate OCB. Parasitic antibodies were studied through unidimensional electrophoresis of proteins on polyacrylamide gel against Taenia antigens, searching for antiparasitic specific low molecular weight antibodies and also for antiparasitic nonspecific high molecular weight antibodies. RESULTS: Two of the 103 patients with no evidence of OCB had antibodies of low molecular weight and 59 of them had antibodies of high molecular weight. Of the 61 patients with evidence of OCB, one showed antibodies of low molecular weight and 16 showed antibodies of high molecular weight. CONCLUSION: Antiparasitic antibodies are detected with similar frequency in MS patients with OCB and in MS patients without OCB.

High levels of alexithymia in patients with multiple sclerosis / Altos índices de alexitimia foram observados em pacientes com esclerose múltipla

ABSTRACT: Alexithymia is a personality trait characterized by difficulties identifying and describing feelings. Some researchers describe high levels of alexithymia among patients with multiple sclerosis (MS) but literature data on this subject are scarce. Objective: The objective of the present study was to characterize findings of alexithymia in patients with MS. Methods: This cross-sectional case-control study included 180 patients with MS and a matched control group. Data for patients with MS included disease duration, number of demyelinating relapses and degree of neurological disability, as assessed by the Expanded Disability Scale Score (EDSS). In addition, the Hospital Anxiety and Depression (HAD) scale and the Toronto Alexithymia Scale (TAS) were used. Results: There were 126 women and 54 men in each group, with median age of 37 years and median education of 16 years. Patients with MS had higher degrees of depression (p<0.01), anxiety (p=0.01) and alexithymia (p<0.01) than did control subjects. For individuals with MS, depressive traits (p<0.01), anxious traits (p=0.03), higher age (p=0.02), lower education level (p=0.02), higher degree of disability (p<0.01) and not being actively employed (p=0.03) were associated with higher rates of alexithymia. Conclusion: Alexithymia was a relevant finding in patients with MS.

RESUMO: Alexitimia é um traço de personalidade caracterizado pelas dificuldades na identificação e descrição dos sentimentos. Alguns pesquisadores descrevem altos índices de alexitimia em pacientes com esclerose múltipla (EM), porém os dados na literatura são escassos. Objetivo: O objetivo do presente estudo foi caracterizar achados de alexitimia em pacientes com EM. Métodos: Este estudo transversal incluiu 180 pacientes com EM e um grupo controle pareado. Dados de pacientes com EM incluíram a duração da doença, número de surtos clínicos de desmielinização e grau de incapacidade neurológica avaliados pela Escala Expandida do Grau de Incapacidade (EDSS). Foram também utilizadas a escala Hospitalar de Ansiedade e Depressão (HAD) e a escala de Alexitimia de Toronto (TAS) foram utilizadas. Resultados: Cada grupo era constituído por 126 mulheres e 54 homens, com mediana de idade de 37 anos e mediana de escolaridade de 16 anos. Pacientes com EM apresentaram maior grau de depressão (p<0.01), ansiedade (p=0.01) e alexitimia (p<0.01) que os controles. Para pessoas com EM, traços depressivos (p<0.01), ansiosos (p=0.03), maior idade (p=0.02), menor nível educacional (p=0.02), maior grau de incapacidade (p<0.01) e o fato de não estar ativamente trabalhando (p=0.03) levaram a maiores níveis de alexitimia. Conclusão: Alexitimia foi um importante achado em pacientes com EM.

Natalizumab adverse events are rare in patients with multiple sclerosis.

OBJECTIVE: To assess the prevalence and the profile of adverse events (AE) of natalizumab in patients with multiple sclerosis (MS). METHODS: Data collection from neurologists attending to patients with MS at specialized units in Brazil. RESULTS: Data from 103 patients attending the infusion centers of 16 MS units in 9 Brazilian states were included in the study. The total number of infusions was 1,042. Seventy-nine patients (76.7%) did not present any AE. Twenty-four patients (23.3%) presented only mild AE. There were three major AE, including two deaths. These three occurrences, although not necessarily being drug-related, must be taken into consideration. CONCLUSION: The profile of AEs for natalizumab shows that 97% of patients have none or only mild AE. However, still due to safety worries, the use of this medication should be restricted to MS units under the care of specialized neurologists.

Nearly one-half of Brazilian patients with multiple sclerosis using natalizumab are DNA-JC virus positive.

OBJECTIVE: Natalizumab is a new and efficient treatment for multiple sclerosis (MS). The risk of developing progressive multifocal leukoencephalopathy (PML) during the use of this drug has created the need for better comprehension of JC virus (JCV) infection. The objective of the present study was to assess the prevalence of JCV-DNA in Brazilian patients using natalizumab. METHOD: Qualitative detection of the JCV in the serum was performed with real-time polymerase chain reaction (PCR). RESULTS: In a group of 168 patients with MS who were undergoing treatment with natalizumab, JCV-DNA was detectable in 86 (51.2%) patients. DISCUSSION: Data on JCV-DNA in Brazil add to the worldwide assessment of the prevalence of the JCV in MS patients requiring treatment with natalizumab.

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.

Multiple sclerosis starting before the age of 18 years: the Brazilian experience.

Multiple sclerosis (MS) starting in childhood and adolescence poses a challenge for diagnosis and management of the disease. The aim of the present study was to assess the characteristics of early onset MS in Brazilian patients. Methods Retrospective data collection from specialized MS units. Results From 20 MS units in 11 Brazilian states, 117 cases of MS starting before the age of 18 years were collected. These patients had an average of 10 years of disease duration, still typically with low disability and one relapse every 2.5 years. The mean age for disease onset was 13.7 years. Conclusion The present study introduces a large series of Brazilian cases of pediatric MS. Although some patients presented a very severe form of MS, on the whole the group of patients with MS starting in childhood or adolescence presented a relatively mild form of this disease in Brazil.

Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis / Consenso Brasileiro para o Tratamento da Esclerose Múltipla: Academia Brasileira de Neurologia e Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla

ABSTRACT The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

RESUMO O crescent arsenal terapêutico na esclerose múltipla (EM) tem permitido tratamentos mais efetivos e personalizados, mas a escolha e o manejo das terapias modificadoras da doença (TMDs) tem se tornado cada vez mais complexos. Neste contexto, especialistas do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia reuniram-se para estabelecer este Consenso Brasileiro para o Tratamento da EM, baseados no entendimento de que neurologistas devem ter a possibilidade de prescrever TMDs para EM de acordo com o que é melhor para cada paciente, com base em evidências e práticas atualizadas. Por meio deste documento, propomos recomendações práticas para o tratamento da EM, com foco principal na escolha e no manejo das TMDs, e revisamos os argumentos que embasam as estratégias de tratamento na EM.

Neurological complications following bariatric surgery.

OBJECTIVE: It was to report on Brazilian cases of neurological complications from bariatric surgery. The literature on the subject is scarce. METHOD: Cases attended by neurologists in eight different Brazilian cities were collected and described in the present study. RESULTS: Twenty-six cases were collected in this study. Axonal polyneuropathy was the most frequent neurological complication, but cases of central demyelination, Wernicke syndrome, optical neuritis, radiculits, meralgia paresthetica and compressive neuropathies were also identified. Twenty-one patients (80%) had partial or no recovery from the neurological signs and symptoms. CONCLUSION: Bariatric surgery, a procedure that is continuously increasing in popularity, is not free of potential neurological complications that should be clearly presented to the individual undergoing this type of surgery. Although a clear cause-effect relation cannot be established for the present cases, the cumulative literature on the subject makes it important to warn the patient of the potential risks of this procedure.

Safety of switching from natalizumab straight into fingolimod in a group of JCV-positive patients with multiple sclerosis / Segurança na mudança direta de natalizumabe para fingolimode em um grupo de pacientes com esclerose múltipla e positivos para JCV

ABSTRACT Objective To assess safety of the switch between natalizumab and fingolimod without a washout period. Methods Prospective data on 25 JCV positive patients who underwent this medication switch were collected and analyzed. Results After a median period of nine months from the medication switch, there were no safety issues to report. The patients had good disease control and no adverse events were reported. Conclusion Washout may not be necessary in daily practice when switching from natalizumab to fingolimod. Expertise on multiple sclerosis management, however, is essential for drug switching.

RESUMO Objetivo Avaliar a segurança na mudança entre natalizumabe e fingolimode sem período de washout. Métodos Dados prospectivos de 25 pacientes positivos para vírus JC que tiveram sua medicação modificada foram coletados e analisados. Resultados Após uma mediana de nove meses da troca de medicação, não havia aspectos de segurança a relatar. Os pacientes estavam com bom controle da doença e não foram relatados eventos adversos. Conclusão Washout pode não ser necessário na prática diária para a mudança entre natalizumabe e fingolimode. No entanto, expertise no manejo de esclerose múltipla é essencial para esta troca entre medicações.

Study of oligoclonal bands restricted to the cerebrospinal fluid in multiple sclerosis patients in the city of São Paulo.

The frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) varies widely in different populations. The objective of this study was to determine the frequency of these OCB in a group of MS patients in the city of São Paulo. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. Oligoclonal bands were found in 49 (54.4%) out of 90 patients with clinically definite MS; in (31.2%) of the 16 patients with clinically isolated syndrome; in 7 (17.9%) of 39 patients with inflammatory disorders of the central nervous system (IDCNS), and in none of the individuals with no neurological condition (control group). The specificity of the method was 100% when compared to the control group and 82.1% when compared to the IDCNS group. These results suggest that the frequency of CSF OCB is much lower in Brazilian MS patients from São Paulo city than that reported in MS series from Caucasian populations.

The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis / A experiência da vida real com complicações cardiovasculares na primeira dose de fingolimode

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Fingolimode é um tratamento novo e eficaz para esclerose múltipla (EM). A administração desta droga requer atenção especial para a primeira dose, uma vez que eventos adversos cardiovasculares podem ser observados nas seis horas iniciais da ingestão de fingolimode. O presente estudo consistiu de uma revisão de dados cardiovasculares de 180 pacientes com EM ao receberem a primeira dose de fingolimode. A taxa de bradicardia nestes pacientes foi maior do que aquele observada em estudos clínicos que tem critérios de inclusão muito rigorosos para seleção de pacientes. Menos de 10% dos casos necessitou de atenção especial, mas não houve casos fatais. Todos os pacientes exceto por um continuaram o tratamento após esta dose inicial. Este é o primeiro relato de dados de administração de fingolimode na vida real de pacientes brasileiros com EM, e um dos poucos trabalhos com estas características no mundo.

Antiparasitic antibodies occur with similar frequency in patients with clinically established multiple sclerosis with or without oligoclonal bands in the cerebrospinal fluid / Anticorpos antiparasitarios ocorrem com frequencia semelhante em pacientes com esclerose multipla quando ha e quando nao ha bandas oligoclonais no liquido cefalorraquidiano

The "hygiene hypothesis" postulates an inverse relationship between the prevalence of parasitic infections and the frequency of multiple sclerosis (MS). Objective: It was to study whether antibodies against parasites could be demonstrated more frequently in blood serum from MS patients with oligoclonal bands (OCB) than from MS patients without OCB. Methods: We studied serum samples from 164 patients who had previously been analyzed to investigate OCB. Parasitic antibodies were studied through unidimensional electrophoresis of proteins on polyacrylamide gel against Taenia antigens, searching for antiparasitic specific low molecular weight antibodies and also for antiparasitic nonspecific high molecular weight antibodies. Results: Two of the 103 patients with no evidence of OCB had antibodies of low molecular weight and 59 of them had antibodies of high molecular weight. Of the 61 patients with evidence of OCB, one showed antibodies of low molecular weight and 16 showed antibodies of high molecular weight. Conclusion: Antiparasitic antibodies are detected with similar frequency in MS patients with OCB and in MS patients without OCB.

A "hipótese da higiene" postula haver relação inversamente proporcional entre a prevalência de infecções por parasitas e a frequência da esclerose múltipla (EM). Objetivo: Foi verificar se em pacientes com EM aparecem anticorpos antiparasitários mais frequentemente no grupo com bandas oligoclonais (BOC) do que no grupo sem BOC. Métodos: Foram estudadas amostras de sangue de 164 pacientes previamente analisadas para investigar BOC. Foi feita eletroforese unidimensional de proteínas em gel de poliacrilamida contra antígenos de Taenia para pesquisa de anticorpos específicos de baixo peso molecular e também de anticorpos inespecíficos de alto peso molecular. Resultados: Dois dos 103 pacientes em que não havia BOC apresentaram anticorpos de baixo peso molecular, e 59 apresentaram anticorpos de alto peso molecular. Dos 61 pacientes em que não havia BOC, um apresentou anticorpos de baixo peso molecular e 16, anticorpos de alto peso molecular. Conclusão: Anticorpos antiparasitários foram detectados com frequência semelhante em doentes com EM independentemente da presença ou não de BOC.