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.

Migraine in 746 patients with multiple sclerosis.

Migraine adds to the burden of patients suffering from multiple sclerosis (MS). The ID-migraine is a useful tool for screening migraine, and the Migraine Disability Assessment questionnaire can evaluate disease burden. The aim of the present study was to assess the presence and burden of migraine in patients with MS. METHODS Patients diagnosed with MS attending specialized MS units were invited to answer an online survey if they also experienced headache. RESULTS The study included 746 complete responses from patients with MS and headache. There were 625 women and 121 men, and 69% of all the patients were aged between 20 and 40 years. Migraine was identified in 404 patients (54.1%) and a moderate-to-high burden of disease was observed in 68.3% of the patients. CONCLUSION Migraine is a frequent and disabling type of primary headache reported by patients with MS.

Migraine in 746 patients with multiple sclerosis / Enxaqueca em 746 pacientes com esclerose múltipla

ABSTRACT Migraine adds to the burden of patients suffering from multiple sclerosis (MS). The ID-migraine is a useful tool for screening migraine, and the Migraine Disability Assessment questionnaire can evaluate disease burden. The aim of the present study was to assess the presence and burden of migraine in patients with MS. Methods: Patients diagnosed with MS attending specialized MS units were invited to answer an online survey if they also experienced headache. Results: The study included 746 complete responses from patients with MS and headache. There were 625 women and 121 men, and 69% of all the patients were aged between 20 and 40 years. Migraine was identified in 404 patients (54.1%) and a moderate-to-high burden of disease was observed in 68.3% of the patients. Conclusion: Migraine is a frequent and disabling type of primary headache reported by patients with MS.

RESUMO Enxaqueca piora o sofrimento do paciente que tem esclerose múltipla (EM). ID-migraine é uma ferramenta útil para seleção de pacientes com enxaqueca e Migraine Disability Assessment (MIDAS) é um questionário que avalia o impacto da doença. O objetivo do presente estudo foi avaliar a presença e impacto de enxaqueca em pacientes com EM. Métodos: Pacientes diagnosticados com EM e tratados em clínicas especializadas foram convidados a responder um questionário online se também apresentassem cefaleia. Resultados: O estudo incluiu 746 participantes com cefaleia e EM que preencheram completamente as respostas. Foram 625 mulheres e 121 homens, sendo 69% dos pacientes com idade entre 20 e 40 anos. Enxaqueca foi identificada em 404 pacientes (54,1%) e moderado a grave impacto da doença foi observado em 68,3% dos casos. Conclusão: Enxaqueca é uma cefaleia primária frequente e incapacitante relatada por pacientes com EM.

Polymorphisms in the CIITA -168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients.

It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). OBJECTIVE: We examined the impact of CIITA polymorphisms -168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. METHODS: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). RESULTS: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA -168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA -168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA -168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. CONCLUSION: These data suggest that CIITA -168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

Clinical Characteristics of Patients With Neuromyelitis Optica Spectrum Disorders With Early Onset.

Neuromyelitis optica spectrum disorder is a severe and disabling disease that manifests with severe relapses of optic neuritis, longitudinally extensive myelitis, and/or brainstem syndromes. The disease is complex and, although onset typically occurs in middle age, children and adolescents may be affected. The present study adds to the literature through detailed clinical data from 36 Brazilian patients with neuromyelitis optica spectrum disorder starting before age 21. This was a retrospective assessment of medical records from 14 specialized units in Brazil. The results showed that the course of neuromyelitis optica spectrum disorder was worse in patients with disease onset before the age of 12 years. Gender and ethnic background did not influence disability accumulation. Over a median period of 8 years, 14% of the patients who presented the initial symptoms of neuromyelitis optica spectrum disorder before the age of 21 years died. In conclusion, the present study adds to the reports from other authors examining the severity of early-onset neuromyelitis optica spectrum disorder.

Polymorphisms in the CIITA -168A/G (rs3087456) and CIITA +1614G/C (rs4774) may influence severity in multiple sclerosis patients / Os polimorfismos no gene CIITA - 168A/G (rs3087456) e CIITA +1614G/C (rs4774) podem influenciar a gravidade em pacientes com esclerose múltipla

ABSTRACT It is currently unknown how genetic factors may influence the clinical course of multiple sclerosis (MS). Objective: We examined the impact of CIITA polymorphisms −168A/G (rs3087456) and +1614G/C (rs4774) on the risk of disability progression, severity and on responses to first-line immunomodulator treatments. Methods: Genomic DNA was extracted from blood samples. We used ABI3730xl and GeneMapper v.4.0 software to identify genotype variations. All patients were followed up and clinically reassessed at three-month intervals. Disability progression was measured by the Expanded Disability Status Scale and disease severity by the Multiple Sclerosis Spasticity Scale (MSSS). Results: We included 37 men and 80 women. We found no evidence regarding the influence of the single nucleotide polymorphisms studied in the Expanded Disability Status Scale or therapeutic response of the evaluated drugs. We performed a logistic regression analysis with the MSSS and found that a less severe MS course was associated with wild type CIITA −168AA and CIITA +1614GG, as the chance of the patient progressing to MSSS2 and MSSS3 decreased in 61% and 75% with CIITA −168AA and 66% and 75% with CIITA +1614GG, respectively (p < 0.0001). Although less significant, the CIITA +1614 GC also pointed to a less severe MS course and the chance of the patient progressing to MSSS3 decreased 79% (p = 0.015). We also observed that the CIITA −168GG genotype was more frequent in MSSS2 and MSSS3 and had 40% lower odds ratio to becoming more severe MS. Conclusion: These data suggest that CIITA −168AA, CIITA +1614GG and CIITA +1614 GC polymorphisms may be associated with a better MS clinical course. This knowledge may be useful for a better understanding of MS and its therapeutic management.

RESUMO Atualmente não se sabe como os fatores genéticos podem influenciar o curso clínico da esclerose múltipla (EM). Objetivo: Examinamos o impacto dos polimorfismos CIITA −168A/G (rs3087456) e CIITA +1614G/C (rs4774) no risco de progressão da incapacidade, gravidade e resposta aos tratamentos imunomoduladores de primeira linha. Métodos: O DNA genômico foi extraído de amostras de sangue. Utilizamos o software ABI3730xl e GeneMapper v.4.0 (Applied Biosystems) para identificar variações genotípicas. Todos os pacientes foram acompanhados e reavaliados clinicamente em intervalos de três meses. A progressão da incapacidade foi medida pela EDSS e a gravidade da doença pelo MSSS. Resultados: Incluímos 37 homens e 80 mulheres. Não encontramos evidências sobre a influência dos SNPs estudados no EDSS e na resposta terapêutica aos fármacos avaliados. Realizamos uma análise de regressão logística com o MSSS e observamos uma evolução menos grave da EM associada aos tipos selvagens CIITA −168AA e CIITA +1614GG, pois a chance do paciente atingir MSSS2 e MSSS3 diminuiu em 61%/75%, e 66/75% respectivamente (p < 0,0001). Embora menos significativo, o CIITA +1614GC também foi relacionado com evolução menos grave da EM e a chance do paciente atingir o MSSS3 diminuiu 79% (p = 0,015). Nós também observamos que o genótipo CIITA −168GG foi mais frequente no MSSS2 e MSSS3 e teve uma razão de chance 40% menor para atingir forma mais grave da EM. Conclusão: Estes dados sugerem que os polimorfismos CIITA −168AA, CIITA +1614GG e CIITA +1614GC podem estar associados a um melhor curso clínico da EM. Este conhecimento pode ser útil para uma melhor compreensão da EM e o seu manejo terapêutico.

Default-mode network and deep gray-matter analysis in neuromyelitis optica patients.

OBJECTIVE: The aim of our study was to detect functional changes in default-mode network of neuromyelitis optica (NMO) patients using resting-state functional magnetic resonance images and the evaluation of subcortical gray-matter structures volumes. MATERIALS AND METHODS: NMO patients (n=28) and controls patients (n=19) were enrolled. We used the integrated registration and segmentation tool, part of FMRIB's Software Library (FSL) to segment subcortical structures including the thalamus, caudate nucleus, putamen, hippocampus and amygdalae. Resting-state functional magnetic resonance images were post-processed using the Multivariate Exploratory Linear Optimized Decomposition into Independent Components, also part of FSL. Average Z-values extracted from the default-mode network were compared between patients and controls using t-tests (P values <0.05 were considered statistically significant). RESULTS: There were areas of increased synchronization in the default-mode network of patients compared to controls, notably in the precuneus and right hippocampus (corrected P<0.01). The frontal area had decreased synchronization in patients compared to controls (corrected P<0.01). There were no observed differences between patients and controls in subcortical volumes or average Z-values values for default-mode network. CONCLUSION: The hyperactivity of certain default-mode network areas may reflect cortical compensation for subtle structural damage in NMO patients.

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.

Natalizumab adverse events are rare in patients with multiple sclerosis / Eventos adversos por natalizumabe são raros em pacientes com esclerose múltipla

To assess the prevalence and the profile of adverse events (AE) of natalizumab in patients with multiple sclerosis (MS). Data collection from neurologists attending to patients with MS at specialized units in Brazil. 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. 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. .

Avaliar a prevalência e o perfil dos eventos adversos (EA) por natalizumabe em pacientes com esclerose múltipla (EM). Coleta de dados fornecidos por neurologistas de unidades especializadas em EM no Brasil. No estudo, foram incluídos dados de 103 pacientes em tratamento em centros de infusão de 16 unidades de EM em 9 estados brasileiros. O número total de infusões foi 1.042. Setenta e nove pacientes (76,7%) não apresentaram nenhum EA. Vinte e quatro pacientes (23,3%) apresentaram apenas EA leves. Foram relatados três importantes EA, incluindo duas mortes. Embora não necessariamente ligadas à droga, estas EA devem ser levadas em consideração. O perfil de EA para natalizumabe mostrou que em 97% dos pacientes não houve EA ou houve apenas EA leves. No entanto, dadas as preocupações com segurança da droga, o uso deste medicamento deve continuar restrito às unidades de EM sob os cuidados de neurologistas especializados. .

The effects of long-term exposure to disease-modifying drugs during pregnancy in multiple sclerosis.

BACKGROUND AND OBJECTIVE: Women with multiple sclerosis (MS) who intend to get pregnant are often advised to discontinue disease modifying therapy (DMT) prior to conception. This recommendation is not based on medical evidence and may interfere with disease control by immunomodulatory drugs. The present study was designed to help discuss the effect of DMT for MS on pregnancy and on disease course. PATIENTS AND METHODS: Retrospective data from 152 pregnancies of 132 women with MS were collected by the physician in charge of the case. All data were entered into a specific file for qualitative and quantitative statistical analysis. RESULTS: From the total group of patients, 89 pregnancies occurred without any exposure to MS drugs, while 61 pregnancies occurred with at least eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and neonatal complications was similar in both groups, except for the newborn weight and height which was smaller for mothers receiving medications. Mothers' post-delivery relapse rate and EDSS scores in the follow-up period were significantly higher in the absence of treatment. CONCLUSION: It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised.

Clinical response to interferon beta and glatiramer acetate in multiple sclerosis patients: a Brazilian cohort.

INTRODUCTION: Many patients with multiple sclerosis (MS) are currently receiving treatment with interferon beta (IFNb) and glatiramer acetate (GA). Identifying nonresponders patients is important to define therapy strategies. Several criteria for treatment response to IFNb and GA have been proposed. OBJECTIVE: It was to investigate the response to treatment with IFNb-1a, IFNb-1b and GA among relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: We analyzed treatment response to IFNb and GA in ninety-one RRMS patients followed for at least one year. Clinical response was established by clinical criteria based on relapses, disability progression or both. RESULTS: We observed a proportion of nonresponders, ranging from 3.3 to 42.9%, depending on the stringency of the criteria used. CONCLUSIONS: Our sample of Brazilian patients with MS has similarities when compared to other studies and there was no statistically significant difference regarding age, gender, ethnicity or disease duration between responders and nonresponders.

Clinical response to interferon beta and glatiramer acetate in multiple sclerosis patients: a Brazilian cohort / Resposta terapêutica ao interferon beta e ao acetato de glatiramer em pacientes com esclerose múltipla: estudo de uma coorte brasileira

INTRODUCTION: Many patients with multiple sclerosis (MS) are currently receiving treatment with interferon beta (IFNb) and glatiramer acetate (GA). Identifying nonresponders patients is important to define therapy strategies. Several criteria for treatment response to IFNb and GA have been proposed. OBJECTIVE: It was to investigate the response to treatment with IFNb-1a, IFNb-1b and GA among relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: We analyzed treatment response to IFNb and GA in ninety-one RRMS patients followed for at least one year. Clinical response was established by clinical criteria based on relapses, disability progression or both. RESULTS: We observed a proportion of nonresponders, ranging from 3.3 to 42.9%, depending on the stringency of the criteria used. CONCLUSIONS: Our sample of Brazilian patients with MS has similarities when compared to other studies and there was no statistically significant difference regarding age, gender, ethnicity or disease duration between responders and nonresponders.

INTRODUÇÃO: Muitos pacientes com esclerose múltipla (EM) estão atualmente recebendo tratamento com interferon beta (IFNb) e acetato de glatiramer (AG). Identificar pacientes não respondedores é importante para definir estratégias terapêuticas. Foram propostos vários critérios para definir a resposta ao tratamento com IFNb e AG. OBJETIVO: Foi investigar a resposta ao tratamento com IFNb-1a, IFNb-1b e AG entre pacientes com esclerose múltipla remitente-recorrente (EMRR). MÉTODOS: Analisamos a resposta ao tratamento com IFNb e AG em 91 pacientes com EMRR acompanhados por um período de pelo menos um ano. A resposta clínica foi estabelecida por critérios baseados em surtos, progressão da incapacidade ou ambos. RESULTADOS: Observamos uma proporção de não respondedores que variou de 3,3 a 42,9%, dependendo do rigor do critério utilizado. CONCLUSÕES: Nossa amostra de pacientes brasileiros com EM tem semelhanças quando comparada a outros estudos e não apresentou diferença estatisticamente significativa entre respondedores e não respondedores com relação à idade, sexo, etnia ou duração da doença.

Brain MRI abnormalities in Brazilian patients with neuromyelitis optica.

Brain abnormalities in neuromyelitis optica (NMO) have been reported previously, but the pathophysiological mechanism and clinical relevance of these abnormalities are poorly understood. We assessed the prevalence and patterns of brain MRI abnormalities in a Brazilian cohort of patients with NMO. Conventional brain MRI and medical records from 24 Brazilian patients with NMO were retrospectively evaluated. Brain MRI were classified into four subgroups: normal, non-specific lesions, multiple sclerosis (MS)-like lesions, and typical lesions. Brain lesions were detected in 19 patients (79.2%). Fourteen patients (58.3%) had non-specific lesions, three (12.5%) had MS-like lesions, and two (8.3%) had typical lesions. Differences between these subgroups with respect to the Expanded Disability Status Scale (EDSS) scores (p=0.86) were not significant. This study demonstrates a high prevalence of brain abnormalities in Brazilian patients with NMO; however, we did not find a significant relationship between these abnormalities and EDSS scores.

Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study.

We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4%) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3% were male and follow-up range was 8.5 to 16 years. Two cases (13.3%) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3%) presented MRI with multiple large lesions. CSF was normal in 73.3%. The severe disability observed at EDSS onset improved in 86.66% patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.

Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study / Encefalomielite aguda disseminada: características clínicas e estudo de associação com os alelos HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602 e DPA1*0301

We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4 percent) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3 percent were male and follow-up range was 8.5 to 16 years. Two cases (13.3 percent) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3 percent) presented MRI with multiple large lesions. CSF was normal in 73.3 percent. The severe disability observed at EDSS onset improved in 86.66 percent patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.

Avaliamos as frequencia, características demográficas, clínicas e de associação genética dos alelos HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 e DPA1*0301 em pacientes com diagnóstico de encefalomielite aguda disseminada (ADEM) em população com doença desmielinizante do SNC. Quinze (8,4 por cento) pacientes de nossa série foram diagnosticados como ADEM. A média de idade foi 35,23 anos (variando entre 12 e 77), 53,3 por cento eram homens e o tempo de acompanhamento variou entre 8,5 e 16 anos. Dois casos (13,3 por cento) apresentaram infecção prévia, um apresentou processo desmielinizante para infeccioso e outro havia se submetido a vacinação para hepatite B quatro semanas antes. O EDSS variou entre 3,0 e 9,5. Oito pacientes (53,3 por cento) apresentaram grandes lesões na RM. O LCR foi normal em 73,3 por cento. A incapacidade grave quantificada pelo EDSS foi seguida de melhora importante em 86,6 por cento dos pacientes. A susceptibilidade genética na ADEM foi significativamente associada com os alelos HLA DQB1*0602, DRB1*1501 e DRB1*1503 (p<0,05) nos pacientes com quadro monofásico.

Multiple sclerosis outcome and morbi-mortality of a Brazilian cohort patients.

We studied the clinical and evolution characteristics of multiple sclerosis (MS) patients followed since the onset of HUCFF/UFRJ in 1978. The diagnosis of MS was based on Poser's et al. and MC Donald's et al. criteria. From 188 patients, 122 were included. Eighty-five were females. The mean age onset was 32.2 years-old (range 6.0 to 61.0+/-10.3), mainly Caucasians (82/67%). The relapsing-remitting course (MSRR) was more frequent (106/86.8%). Monosymptomatic onset was significantly more frequent in Caucasians than in Afro-Brazilians (p<0.05). Seventeen patients had benign form of MS and these patients presented association with MSRR when compared with severe form (p=0.01). The mortality rate was 2.12% (4 patients died). This study was similar to other Brazilian series with regard to sex and age, and lack of correlation between EDSS and number of relapses; it confirmed south-southeast African-descendants gradient distribution and association between first mono-symptomatic relapses and Caucasian; we found lower frequency of benign forms.

Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-gamma (INF-gamma) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (p<0.0001), PLP (p=0.0002) and MBP (p<0.0001), and solely IgA to MBP (p<0.0001). INF-gamma (p=0.61) levels were similar to healthy controls. Increased production of IL-4 (p=0.0084) indicates an important role for this cytokine in the activation of Th2 regulatory cells and of the IgA producers B lymphocyte indicating activation of humoral immunity.

Multiple sclerosis outcome and morbi-mortality of a Brazilian cohort patients / Caracteristicas clínico-evolutivas e morbi-mortalidade de uma coorte de pacientes brasileiros com esclerose múltipla

We studied the clinical and evolution characteristics of multiple sclerosis (MS) patients followed since the onset of HUCFF/UFRJ in 1978. The diagnosis of MS was based on Poser's et al. and MC Donald's et al. criteria. From 188 patients, 122 were included. Eighty-five were females. The mean age onset was 32.2 years-old (range 6.0 to 61.0±10.3), mainly Caucasians (82/67 percent). The relapsing-remitting course (MSRR) was more frequent (106/86.8 percent). Monosymptomatic onset was significantly more frequent in Caucasians than in Afro-Brazilians (p<0.05). Seventeen patients had benign form of MS and these patients presented association with MSRR when compared with severe form (p=0.01). The mortality rate was 2.12 percent (4 patients died). This study was similar to other Brazilian series with regard to sex and age, and lack of correlation between EDSS and number of relapses; it confirmed south-southeast African-descendants gradient distribution and association between first mono-symptomatic relapses and Caucasian; we found lower frequency of benign forms.

Estudamos as características clínico-evolutivas de pacientes com esclerose múltipla (EM) acompanhados no HUCFF-UFRJ desde 1978. Foram usados critérios de Poser et al. e MC Donald et al. para o diagnóstico de EM. De 188, 122 foram incluídos. Oitenta e cinco eram mulheres. A média de idade de início foi 32,2 anos (6,0-61,0±10,3), predominando caucasianos (n=82/67 por cento). A forma recorrente-remitente (EMRR) foi mais freqüente (n=106/86,8 por cento). Formas mono-sintomáticas no primeiro surto foram significativamente mais freqüentes em caucasianos do que em afro-brasileiros (p<0,05). Dezessete pacientes apresentavam a forma benigna (13,9 por cento) e 43 a grave (35,2 por cento). A forma benigna foi associada com a EMRR (p=0,01). A taxa de letalidade 2,12 por cento (4 óbitos). Nossos resultados são semelhantes aos de outras séries brasileiras no que se refere ao sexo e idade, e falta de correlação entre EDSS e número de surtos; confirmamos gradiente sul-sudeste de distribuição afro-descendente, associação significativa entre primeiro surto mono-sintomático e caucasianos e menor freqüência de formas benignas.

Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica / Marcadores imunológicos em pacientes com diagnóstico de neuromielite óptica

Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-γ (INF-γ) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (p<0.0001), PLP (p=0.0002) and MBP (p<0.0001), and solely IgA to MBP (p<0.0001). INF-γ (p=0.61) levels were similar to healthy controls. Increased production of IL-4 (p=0.0084) indicates an important role for this cytokine in the activation of Th2 regulatory cells and of the IgA producers B lymphocyte indicating activation of humoral immunity.

A neuromielite óptica (NMO) é doença inflamatória do sistema nervoso central, caracterizada por mielite aguda ou subaguda grave e neurite óptica unilateral ou bilateral. Este estudo objetiva analisar parâmetros imunológicos de pacientes com critérios de Wingerchuck et al. (1999) para NMO. O método de ELISA avaliou a produção de IgG e IgA para antígenos da proteína básica da mielina (MBP), o proteolipídeo (PLP) 95-116, a glicoproteina associada ao oligodendrócito (MOG) 92-106 e as citocinas interleucina-4 (IL-4) e interferon-gama (INF-γ). Foram incluνdos 28 pacientes com NMO pareados com controles saudáveis. Pacientes com NMO apresentaram níveis significativamente elevados de imunoglobulinas reativas dos isotipos IgG para MOG (p<0,0001), PLP (p=0,0002) e MBP (p<0,0001) e IgA somente para MBP (p<0,0001). Os níveis de INF-γ (p=0,61) foram semelhantes aos controles. A produção elevada de IL-4 (p=0,0084) indica papel importante na ativação de células regulatórias Th2 e linfócitos B produtores de IgA e da ativação da imunidade humoral.