Frequency of sleep disorders in patients with neuromyelitis optic spectrum disorders compared to a representative sample of the population of the São Paulo city

Introdução: O espectro de doença neuromielite óptica (NMOSD) é um distúrbio autoimune e inflamatório do sistema nervoso central, caracterizado por desmielinização do nervo óptico e medula espinal, com um curso recorrente na maioria dos casos. Uma porcentagem significativa dos doentes apresenta lesões cerebrais em regiões importantes para a arquitetura do sono. Objetivos: Descrever as características do sono na NMOSD; compará-las com o grupo controle; avaliar a relação entre as características clínicas da doença e as alterações do sono; e pesquisar suas associações com as lesões desmielinizantes observadas na ressonância magnética. Métodos: Estudo de caso-controle, no qual foram entrevistados, de maneira prospectiva e consecutiva, 62 pacientes entre setembro de 2014 e dezembro de 2016. Os participantes responderam aos principais questionários para avaliação do sono, cronotipo, fadiga e depressão. Os escores dos questionários foram comparados aos do grupo controle, utilizando-se propensity score matching para reduzir o viés na estimativa das diferenças entre as duas populações. Resultados: Pacientes com NMOSD apresentaram má qualidade do sono em sua maioria (62,9%); alto risco de apneia obstrutiva do sono em 29,03%; ausência de depressão em 45,18%; síndrome das pernas inquietas foi encontrada em 14,52%; fadiga leve a moderada foi encontrada em 38,71%; e cronotipo matutino em 46,77%. A comparação entre os pacientes e o grupo controle evidenciou pior qualidade do sono nos pacientes com NMOSD, assim como maior tendência à depressão. Aumentono sistema funcional (SF) esfíncter do EDSS (Expanded Disability Status Scale) prediz piora na qualidade do sono (B = 2,40); aumento no SF visual não interfere no cronotipo; e o SF piramidal não influencia na escala de gravidade de SPI. Não encontramos relação entre as alterações do sono e as lesões desmielinizantes presentes na RM do encéfalo e medula dos pacientes. Conclusão: Pacientes com NMOSD apresentam pior qualidade do sono e mais depressão do que a população geral mesmo tratados e com acompanhamento médico regular. Tratar as alterações esfincterianas das sequelas da NMOSD melhoram a qualidade de sono. O cronotipo dos pacientes é semelhante ao da população geral com idade média maior, o que pode sugerir envelhecimento cerebral precoce por atividade inflamatória crônica.Introduction: The neuromyelitis optic spectrum disorder (NMOSD) is an autoimmune and inflammatory disease of the central nervous system, characterized by demyelination of the optic nerve and spinal cord, with a recurrent course in most cases. A significant percentage of patients have brain lesions in regions that are important for sleep architecture. Objectives: Describe the sleep characteristics in NMOSD; compare them with a control group; evaluate the relationship between the clinical characteristics of the disease and sleep disorders; and evaluate its associations with the demyelinating lesions seen on magnetic resonance image (MRI). Methods: Case- control study, in which, 62 patients were prospectively and consecutively interviewed between September 2014 and December 2016. Participants answered questionnaires for assessing sleep, chronotype, fatigue and depression. The scores of the questionnaires were compared to those of the control group, using propensity score matching to reduce the bias in estimating the differences between the two populations. Results: Most NMOSD patients had poor sleep quality (62.9%); high risk of obstructive sleep apnea syndrome by 29.03%; absence of depression in 45.18%; restless legs syndrome was found in 14.52%; mild to moderate fatigue was found in 38.71%; and morning chronotype by 46.77%. The comparison between patients and the control group showed worse sleep quality in patients with NMOSD, as well as a greater tendency to depression. Increased EDSS (Expanded Disability Status Scale) sphincter functional system (FS) predicts worsening sleep quality (B = 2.40); increase in visual FS does not interfere with the chronotype; and pyramidal FS does not influence the SPI severity scale. We found no relationship between sleep disorders and demyelinating lesions present in patients' brain and spinal cord MRI. Conclusion: Patients with NMOSD have worse sleep quality and more depression than the general population, even under treatement and regular medical follow-up. Treating sphincter disorders in NMOSD sequelae improves sleep quality. The chronotype of patients is similar to that of the general population with a higher average age, which may suggest early brain aging due to chronic inflammatory activity

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers Natalizumabe no tratamento da esclerose múltipla: a experiência de dois centros brasileiros

Multiple sclerosis (MS) is a demyelinating, inflammatory disease of the central nervous system (CNS), presumably with an autoimmune etiopathogenesis. The first line therapies developed for the relapsing-remitting form of MS (RRMS) include disease modifying treatments (DMTs) as interferons (IFNs) beta and glatiramer acetate (GA) and they are known to be partially effective, with 20 -50% of treated patients experiencing a relapse or disability progression in a short period of time 1 . Natalizumab is a humanized monoclonal antibody that blocks the α-4 integrin, VLA-4, an adhesion molecule present on leukocytes surface, inhibiting their migration into CNS 2 . In the pivotal study AFFIRM, natalizumab reduced annualized relapse rate (aRR) by 68% and the risk of sustained disability progression by 42% over 2 years 2 . Although patients studied in AFFIRM were mostly treatment naïve RRMS patients, natalizumab is only approved for use in patient that failed treatment with DMTs or have highly active disease. This more restricted use of natalizumab is consequence of safety concerns related to risk of progressive multifocal leukoencephalopathy (PML), a rare but potentially life-threatening ABSTRACT Objective: Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in São Paulo. Method: We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) ≤ 3.0 vs patients with EDSS > 3. Results: Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy. Conclusion: Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability. Keywords: natalizumab, multiple sclerosis, disability progression, relapse rate. RESUMO Objetivo: Analisar as características clínicas e demográficas, assim como a eficácia e segurança do tratamento com natalizumabe (usado em terceira linha), por no mínimo 12 meses, em pacientes brasileiros acompanhados em dois centros de tratamento de esclerose múltipla, na cidade de São Paulo. Método: Avaliamos o efeito do tratamento com natalizumabe na taxa anualizada de surto (aRR) e progressão de incapacidade (medida por Expanded Disability Status Scale (EDSS)) em 75 pacientes tratados por, no mínimo 12 meses. Realizamos uma análise de subgrupo em pacientes com EDSS ≤ 3,0 e com EDSS > 3, para avaliar o impacto no tratamento, considerando-se o grau de incapacidade neurológica. Resultados: O tratamento com natalizumabe, por pelo menos um ano, reduziu a aRR em 91%, assim como melhorou a incapacidade neurológica. Em pacientes com EDSS ≤ 3,0 observamos um impacto maior do tratamento na incapacidade neurológica, reduzindo sua progressão em 51%, durante o período do estudo. O tratamento com natalizumabe é seguro, porém um paciente desenvolveu leucoencefalopatia multifocal progressiva. Conclusão: O tratamento com natalizumabe, em terceira linha terapêutica é seguro e eficaz especialmente, em pacientes com incapacidade neurológica leve (EDSS ≤ 3.0). Palavras-chave: natalizumabe, esclerose múltipla, progressão da incapacidade, taxa de surto

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers

Objective Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in São Paulo.Method We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) ≤ 3.0 vs patients with EDSS > 3.Results Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy.Conclusion Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability