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BACKGROUND AND PURPOSE: Although plasmapheresis is becoming standard practice as a rescue therapy for neuromyelitis optica (NMO), evidence for the therapeutic efficacy of plasmapheresis is limited, and the effect of plasmapheresis on anti-aquaporin-4 (AQP4) levels in patients with NMO has not been reported. Here, our objective was to evaluate the clinical efficacy of therapeutic plasmapheresis and its effect on anti-AQP4 antibody levels in patients with NMO spectrum disorder (NMOSD). METHODS: We retrospectively reviewed the medical records of 15 patients with NMOSD who had 18 acute attacks and received plasmapheresis because they did not respond to high-dose intravenous methylprednisolone (IVMP) therapy. Anti-AQP4 antibodies were measured before and after plasmapheresis. The primary outcomes were functional improvements immediately and 6 months after plasmapheresis, and the secondary outcome was the change in anti-AQP4 antibody serum levels following plasmapheresis. RESULTS: Plasmapheresis following IVMP therapy led to significant improvement in 50% of the 18 attacks in 15 patients immediately after the procedure was completed, and in 78% (14 attacks) after 6 months. Plasmapheresis was generally well tolerated in all patients. Anti-AQP4 antibody serum levels declined significantly following plasmapheresis, to a mean of 15% of the preplasmapheresis levels. Lower scores on the visual outcome scale recorded before an attack were associated with significant immediate improvement upon the completion of plasmapheresis (p=0.03). CONCLUSIONS: Plasmapheresis following IVMP therapy effectively removed anti-AQP4 antibodies and was accompanied by a substantial improvement in the neurological disability of patients with NMOSD. Lower levels of pre-existing neurological damage may be associated with an improved acute response to plasmapheresis.
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OBJECTIVES: Recent case reports and series have shown that patients with neuromyelitis optica (NMO) experience clinical deterioration under interferon beta (IFN-ß) treatment. The objective of the present study was to evaluate whether and to what extent IFN-ß exacerbates NMO spectrum disorders (NMOSD). METHODS: We retrospectively reviewed the medical records of 40 patients with NMOSD who had been treated with IFN-ß for more than 6 months and whose disease duration was more than 1 year at the initiation of IFN-ß treatment. We evaluated their annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) scores before and after IFN-ß treatment. RESULTS: In total, 95% of patients exhibited an ineffective or exacerbated response to IFN-ß treatment and the mean ARR significantly increased after IFN-ß treatment (p = 0.002). The increased ARR > 50% under IFN-ß treatment was observed in 20 patients (50%). The mean EDSS score significantly increased following IFN-ß treatment (p < 0.001). CONCLUSION: In patients with NMOSD, IFN-ß treatment is not only ineffective for preventing relapses but also may even increase relapses significantly. Thus, a more careful diagnostic approach to differentiate NMO from multiple sclerosis and attention to decision of treatment is warranted for patients at high risk of NMO.
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Factores Inmunológicos/efectos adversos , Interferón beta/efectos adversos , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/patología , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of repeated rituximab treatment based on the assessment of peripheral circulating memory B cells over 24 months in patients with relapsing neuromyelitis optica (NMO). DESIGN: Prospective open-label study. SETTING: Institutional referral center for multiple sclerosis. Patients Thirty patients with relapsing NMO or NMO spectrum disorder. Intervention Treatment protocol of rituximab consisted of an induction therapy (375 mg/m² once weekly for 4 weeks or 1000 mg infused twice, with a 2-week interval between the infusions) followed by maintenance therapy. The maintenance therapy was repeated treatment with rituximab (375 mg/m², once) whenever the frequency of reemerging CD27+ memory B cells was more than 0.05% in peripheral blood mononuclear cells by flow cytometric analysis. MAIN OUTCOME MEASURES: Annualized relapse rate, disability (Expanded Disability Status Scale score), anti-aquaporin 4 antibody level, and safety of rituximab treatment. RESULTS: Of 30 patients, 28 showed a marked reduction in relapse rate while taking rituximab over 24 months. The relapse rate was reduced significantly, by 88%, and 70% of patients became relapse-free over 24 months. Disability either improved or stabilized in 97% of patients. Anti-aquaporin 4 antibody levels declined significantly following treatment with rituximab, consistent with the clinical response and the effect on CD27+ memory B cells. Repeated treatment with rituximab was generally well tolerated, and no clinically relevant adverse event leading to discontinuation of treatment was observed. CONCLUSION: Repeated treatment with rituximab appeared to produce consistent and sustained efficacy over 24 months with good tolerability in patients with NMO.
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Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Subgrupos de Linfocitos B/metabolismo , Memoria Inmunológica/fisiología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/tratamiento farmacológico , Adulto , Subgrupos de Linfocitos B/efectos de los fármacos , Esquema de Medicación , Femenino , Humanos , Memoria Inmunológica/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/inmunología , Estudios Prospectivos , Rituximab , Prevención Secundaria , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Although neuromyelitis optica has been traditionally regarded as a disease without brain involvement, brain abnormalities are not uncommon in patients with neuromyelitis optica-related disorders. METHODS: We aimed to characterize the brain magnetic resonance imaging (MRI) abnormalities in neuromyelitis optica spectrum disorder patients who are seropositive for anti-aquaporin-4 autoantibody (AQP4 Ab). Of 236 consecutive patients with inflammatory demyelinating central nervous system diseases, we retrospectively analyzed MRI characteristics of 78 patients who were seropositive for AQP4 Ab. RESULTS: For an average observational period of 6.3 years, 62 patients (79%) had brain lesions on MRI. Twenty-four patients (31%) had brain MRI abnormalities at the onset of disease, and 35 (45%) had symptomatic brain involvement. Characteristic brain MRI abnormalities were classified into five categories: (1) lesions involving corticospinal tracts (e.g. posterior limb of internal capsule and cerebral peduncle (44%); (2) extensive hemispheric lesions likely due to vasogenic edema (29%); (3) periependymal lesions surrounding aqueduct and the third and fourth ventricles (22%); (4) periependymal lesions surrounding lateral ventricles (40%); and (5) medullary lesions, often contiguous with cervical lesions (31%). Fifty-four patients (69%) showed at least one kind of brain abnormality among the five characteristic MRI lesions. Ten patients showed gadolinium-enhancing lesions, which were characterized by multiple patchy enhancing patterns with blurred margins. CONCLUSIONS: In central nervous system AQP4 autoimmunity, brain MRI abnormalities were more common than is generally appreciated and were characterized by their unique localization and configuration.