Clinical efficacy of plasmapheresis in patients with neuromyelitis optica spectrum disorder and effects on circulating anti-aquaporin-4 antibody levels.

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.

Does interferon beta treatment exacerbate neuromyelitis optica spectrum disorder?

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.

Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years.

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.

Characteristic brain magnetic resonance imaging abnormalities in central nervous system aquaporin-4 autoimmunity.

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.