RESUMO
OBJECTIVE: Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the central nervous system. It affects young subjects and has a poor prognosis both on a functional and vital level. Therefore, it is imperative to reduce the frequency of relapses. The purpose of this study was to evaluate the clinical and neuroradiological effectiveness of rituximab (RTX) on active forms of NMO. METHODS: We conducted a 2-year open prospective multicenter study that included 32 patients treated with RTX at a dose of 375 mg/m2/week for 1 month. When the number of circulating CD19+ B cells reached 1%, a maintenance therapy was started, consisting of two infusions of 1 g of RTX, administered at a 15-day interval. The primary objective was to reduce the annual relapse rate (ARR), in comparison to that observed in the 2 years before treatment onset. RESULTS: Rituximab administration reduced the ARR from 1.34 to 0.56 (p = 0.0005). The average Expanded Disability Status Scale (EDSS) score significantly improved by 1.1 point, from 5.9 (2-9) to 4.8 (0-9) after 2 years (p = 0.03). Anti-aquaporin-4 antibodies' level predicted treatment failure (p = 0.03). Frequency of Gad+ lesions in spinal cord decreased from 23.3 to 14.2%. RTX treatment did not prevent the death of three patients (treatment failure in two patients and acute myeloid leukemia in a patient previously treated with mitoxantrone). CONCLUSION: Rituximab is clinically effective in active forms of NMO, although few patients are resistant to the treatment.
Assuntos
Fatores Imunológicos/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Rituximab/uso terapêutico , Resultado do Tratamento , Adolescente , Adulto , Anticorpos/sangue , Aquaporina 4/genética , Aquaporina 4/imunologia , Avaliação da Deficiência , Feminino , Gadolínio/farmacocinética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Fatores de Tempo , Adulto JovemAssuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/patologia , Alcoolismo/complicações , Núcleos Anteriores do Tálamo/patologia , Hemorragia Cerebral/patologia , Fórnice/patologia , Síndrome de Korsakoff/patologia , Transtornos do Sistema Nervoso Induzidos por Álcool/diagnóstico , Núcleos Anteriores do Tálamo/irrigação sanguínea , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Fórnice/irrigação sanguínea , Humanos , Síndrome de Korsakoff/diagnóstico , Síndrome de Korsakoff/etiologia , Masculino , Pessoa de Meia-Idade , Deficiência de Tiamina/etiologia , Deficiência de Tiamina/terapiaRESUMO
BACKGROUND: Despite similarities, neuromyelitis optica (NMO) can be distinguished from multiple sclerosis (MS) by clinical, radiological and serological findings. OBJECTIVE: This case-control study aimed to determine whether patients with NMO or with MS in an Afro-Caribbean population originating from French West Indies shared the same or different HLA class I and II pattern distribution. METHODS: The association with HLA class II (DRB1 and DQB1) alleles was tested in 42 NMO patients, 163 MS patients and 150 healthy controls. HLA-DRB1 and DQB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: By comparison with healthy controls, significantly increased frequency of HLA-DRB1 03 (26.2% vs. 13%, odds ratio 2.4, 95% confidence interval 1.31-4.28, p after correction, cp 0.045) was observed in patients with NMO. By contrast, in MS patients, HLA-DRB1 15 (24.8% vs. 13%, odds ratio 2.21, 95% CI 1.45-3.36, cp < 0.0015), but not DRB1 03 allele, was positively associated with the disease. Moreover, a modest protective effect of HLA-DRB1 11 in the MS group, independently of DRB1 15 association, was found (13.7% vs. 7% in controls, odds ratio 0.48, p 0.006), but did not survive Bonferroni correction. CONCLUSION: In conclusion, comparison of the HLA-DRB1 and DQB1 distribution in NMO and MS in this Afro-Caribbean population shows important differences in the HLA associations among NMO and MS.