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.

Stroke and transient ischemic attacks related to antiplatelet or warfarin interruption.

OBJECTIVE: Patients on anticoagulant or antiplatelet therapy are often required to discontinue these medications before and during surgical or invasive procedures. In some cases, the patient stops the treatment without medical supervision. These situations may increase stroke risk. To identify the ischemic stroke and transient ischemic attack (TIA) prevalence related to length of time of discontinuation of antiplatelet or vitamin K antagonist therapy, in a group of inpatients from a specialized neurological hospital in Brazil. METHODS: Cross-sectional, retrospective and descriptive study of stroke inpatients for three years. Medical reports were reviewed to find study participants, stroke characteristics, risk factors, reasons and time of drug interruption. RESULTS: In three years, there were 360 stroke and TIA inpatients, of whom 27 (7.5%) had a history of antiplatelet or vitamin K antagonist interruption correlated with the time of the event (81% ischemic stroke, 19% TIA). The median time between antiplatelet interruption and an ischemic event was five days, and 62% of events occurred within seven days after drug suspension. For vitamin K antagonists, the average time to the ischemic event was 10.4 days (SD = 5.7), and in 67% of patients, the time between drug discontinuation and the event was 7-14 days. The most frequent reason for drug suspension was patient negligence (37%), followed by planned surgery or invasive examination (26%) and side effects, including hemorrhage (18.5%). CONCLUSION: Antiplatelet or vitamin K antagonist suspension has a temporal relationship with the occurrence of stroke and TIA. Since these events are preventable, it is crucial that healthcare professionals convince their patients that drug withdrawal can cause serious consequences.

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.

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.

Patients' satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis.

OBJECTIVE: The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients' satisfaction with the treatment must be taken into consideration. METHODS: Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. RESULTS: One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. CONCLUSION: Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

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.

Avaliação neuropsicológica em adultos com Esclerose Múltipla: Revisão sistemática / Neuropsychological assessment in adults with multiple sclerosis: Systematic review

A Esclerose múltipla (EM) é considerada uma doença crônica que acomete mais frequentemente jovens adultos. Estima-se que 2,3 milhões de pessoas no mundo são afetadas pela doença. Pessoas com EM costumam apresentar alterações cognitivas e na sua qualidade de vida. A presente pesquisa visa a identificar e discutir os instrumentos de avaliação neuropsicológica utilizados atualmente com pessoas com diagnóstico de EM. Para tanto, foi realizada uma revisão sistemática da literatura. Este estudo mostrou a importância da investigação das funções cognitivas empessoas com diagnóstico de EM. As baterias breves mais utilizadas evidenciadas na revisão sistemática são Brief International Cognitive Assessment of Multiple Sclerosis (BICAMS), Multiple Sclerosis Functional Composite Measure (MSFC) e Brief Repeatable Battery of Neuropsychological Test (BNB-N). Os testes mais utilizados na avaliação neuropsicológica de paciente com EM são PASAT e SDMT, que enfocam a avaliação da velocidade de processamento e memória operacional. (AU)

Multiple sclerosis (MS) is considered a chronic disease that more often affects young adults. It isestimated that 2.3 million people live with MS worldwide. People with MS usually have changes in their cognition and quality of life. The present research aimed to identify and discuss the instruments of neuropsychological assessment currently used with people diagnosed with MS. A systematic review of literature was carried out. This study showed the importance of investigating cognitive functions in people diagnosed with MS. The most frequently used brief batteries found were Brief International Cognitive Assessment of Multiple Sclerosis (BICAMS), Multiple Sclerosis Functional Composite Measure (MSFC) and Brief Repeatable Battery of Neuropsychological Test (BNB-N). The most frequently used tests as part of the neuropsychological assessment of MS patients were PASAT and SDMT, which focus on assessing information processing speed and working memory.(AU)

Stroke and transient ischemic attacks related to antiplatelet or warfarin interruption / Acidente vascular cerebral e ataques isquêmicos transitórios relacionados à interrupção de antiplaquetários ou varfarina

ABSTRACT Patients on anticoagulant or antiplatelet therapy are often required to discontinue these medications before and during surgical or invasive procedures. In some cases, the patient stops the treatment without medical supervision. These situations may increase stroke risk. Objective To identify the ischemic stroke and transient ischemic attack (TIA) prevalence related to length of time of discontinuation of antiplatelet or vitamin K antagonist therapy, in a group of inpatients from a specialized neurological hospital in Brazil. Methods Cross-sectional, retrospective and descriptive study of stroke inpatients for three years. Medical reports were reviewed to find study participants, stroke characteristics, risk factors, reasons and time of drug interruption. Results In three years, there were 360 stroke and TIA inpatients, of whom 27 (7.5%) had a history of antiplatelet or vitamin K antagonist interruption correlated with the time of the event (81% ischemic stroke, 19% TIA). The median time between antiplatelet interruption and an ischemic event was five days, and 62% of events occurred within seven days after drug suspension. For vitamin K antagonists, the average time to the ischemic event was 10.4 days (SD = 5.7), and in 67% of patients, the time between drug discontinuation and the event was 7-14 days. The most frequent reason for drug suspension was patient negligence (37%), followed by planned surgery or invasive examination (26%) and side effects, including hemorrhage (18.5%). Conclusion Antiplatelet or vitamin K antagonist suspension has a temporal relationship with the occurrence of stroke and TIA. Since these events are preventable, it is crucial that healthcare professionals convince their patients that drug withdrawal can cause serious consequences.

RESUMO Pacientes em terapia anticoagulante ou antiagregante plaquetária frequentemente são solicitados a descontinuar essas medicações antes e durante procedimentos cirúrgicos ou invasivos. Se o paciente interromper tratamento sem supervisão médica, poderá aumentar de risco de acidente vascular cerebral (AVC). Objetivo Identificar prevalência de AVC isquêmico e ataque isquêmico transitório (AIT) associados à descontinuação de terapia antiplaquetária ou coumarínicos em pacientes internados em hospital especializado em atendimento neurológico no Brasil. Métodos Estudo transversal, retrospectivo de três anos, descritivo dos pacientes hospitalizados por AVC. A revisão de relatórios médicos determinou características do AVC, fatores de risco, motivos e tempo de interrupção medicamentosa. Resultados Em três anos, foram internados 360 pacientes por AVC ou AIT; destes, 27 interromperam temporariamente terapia antiplaquetária ou coumarínicos relacionando ao evento (81% acidente vascular cerebral isquêmico, 19% AIT). A prevalência foi de 7,5%. O tempo médio entre interrupção antiplaquetária e evento foi cinco dias, com 62% deles ocorrendo até sete dias após suspensão medicamentosa. Para coumarínicos, o tempo médio foi 10,4 dias (d.p.= 5,7), em 67% dos casos o tempo entre a descontinuação medicamentosa e o evento foi 7-14 dias. O motivo mais frequente para suspensão do medicamento foi negligência do paciente (37%), seguido por cirurgia planejada ou exame invasivo (26%) e efeitos colaterais, incluindo hemorragia (18,5%). Conclusão Suspensão de terapia de antiplaquetários ou coumarínicos tem relação temporal com ocorrência de AVC e de AIT. Esses eventos são passíveis de serem evitados, sendo imprescindível que profissionais de saúde convençam seus pacientes das consequências graves da retirada do medicamento.

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.

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.

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.

Patients' satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis / Satisfação e pontos de vista dos pacientes com esclerose múltipla em tratamento com drogas modificadoras da doença

ABSTRACT Objective The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

RESUMO Objetivo O tratamento da esclerose múltipla (EM) com drogas-modificadoras-da-doença (DMDs) está evoluindo e novas drogas estão sendo comercializadas. Eficácia e segurança são aspectos cruciais nas medicações, porém a satisfação do paciente com o tratamento deve ser levada em consideração. Métodos Entrevista individual com pacientes com EM investigando a satisfação e ponto de vista desta população em relação ao tratamento com DMDs. Resultados Cento e vinte e oito pacientes atendidos em unidades especializadas de EM de cinco cidades diferentes foram entrevistados. Mais de 80% dos pacientes estava bastante satisfeito com as medicações utilizadas, considerando aspectos de conveniência de uso e benefício das drogas. O único aspecto que pontuou menos foi tolerabilidade. Conclusão Parâmetros para melhor tratamento de EM devem incluir eficácia, segurança e satisfação dos pacientes com a DMD prescrita.

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.

Citofotometria do ADN de células do colo do útero infectadas e näo infectadas pelo papiloma vírus humano / Cytophotometric of the cervix cells DNA infected and non infected by the papiloma human virus

Este estudo tem como objetivo determinar características citofotométricas dos núcleos das células do colo uterino infectadas ou näo pelo HPV, considerando o número de cópias virais. Incluiu-se 69 pacientes entre 16 e 48 anos, que realizavam avaliaçäo ginecológica de rotina, citologia oncótica e colcoscopia. As suspeitas de lesäo por HPV à colcoscopia, foram consideradas grupo de estudo e submetidas à biópsia (n=40); as que näo apresentaram lesäo foram consideradas grupo controle (CT, n=29). Confirmou-se a infecçäo ou näo de HPV pela captura híbrida, quantificando ainda em baixa cópias virais (BC ,100) e altas cópias(AC.100). Realizou-se citofotometria pela coloraçäo de FEULGEN e uso do sistema SAMBA 4000. Os resultados demonstram: área nuclear menor em AC que CT e BC (p<0,05), com alta sensibilidade na diferenciaçäo de CT x AC e BC x AC; densidade óptica integrada maior em BC que CT e AC (p<0,05); BC e AC apresentaram maior índice de pequenos agrupamentos de cromatina e de contraste que CT; BC e AC apresentaram menor índice de grandes agrupamentos de cromatina e de energia que CT; a taxa de ploidia foi semelante entre os tres; BC apresentou mais núcleos nas fases S, G2 e M que CT. Concluiu-se que a citofotometria do ADN do núcleo das células do colo uterino foi capaz de diferenciar entre CT, BC e AC, em diferentes níveis de sensitividade e especificidade, segundo os diversos parâmetros analisados, dos núcleos infectados pelo HPV em comparaçäo aos näo infectados