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ABSTRACT: BACKGROUND: Multiple sclerosis (MS) in Asia is thought to have different clinical characteristics from MS in Western countries; however, previous studies in Asia were performed without properly differentiating neuromyelitis optica (NMO) from MS. OBJECTIVES: To evaluate the clinical characteristics of MS in Korea after careful exclusion of potential explanations other than MS, particularly NMO spectrum disorder (NMOSD). METHODS: This study is a retrospective review of consecutive MS patients attending five referral hospitals in Korea. All patients' MS diagnoses were re-evaluated. RESULTS: Of the 105 patients, 70 were female and 35 were male. The mean age of onset was 30.4 years and the mean disease duration was 5.4 years. On initial magnetic resonance imaging (MRI), 58% and 64% fulfilled the criteria for dissemination in space for the 2005 and 2010 McDonald criteria, respectively. Spinal cord lesions were observed in 78% of patients, primarily present as multiple small lesions with a mean length of 0.9 vertebral segments. The median time from disease onset to an Expanded Disability Status Scale 6 was 20 years. CONCLUSIONS: After careful exclusion of NMOSD, we found that the clinical pattern of MS in Korea does not fundamentally differ from that seen in Western countries.
Multiple Sclerosis 02/2013; · 4.26 Impact Factor
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ABSTRACT: 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).
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.
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).
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.
Journal of Clinical Neurology 01/2013; 9(1):36-42. · 1.69 Impact Factor
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ABSTRACT: Advances in the understanding of central nervous system aquarporin-4 autoimmunity have promoted the recognition of diverse clinical presentations beyond the traditional view of neuromyelitis optica. We describe a patient who developed hemiparesis caused by an extensive cerebral lesion as an initial manifestation of central nervous system aquarporin-4 autoimmunity. Although the patient had no history of optic neuritis or myelitis, not only was serum anti-aquarporin-4 antibody positive, but an imaging, treatment response and histopathological features also revealed characteristic findings suggestive of central nervous system aquarporin-4 autoimmunity. The present case highlights the importance of a comprehensive evaluation for anti-aquarporin-4 antibody even in patients presenting with isolated cerebral lesions.
Multiple Sclerosis 07/2012; 18(9):1340-3. · 4.26 Impact Factor
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Journal of the neurological sciences 05/2012; 319(1-2):171; author reply 172. · 2.32 Impact Factor
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ABSTRACT: Recent case reports and series have shown that patients with neuromyelitis optica (NMO) experience clinical deterioration under interferon beta (IFN-β) treatment. The objective of the present study was to evaluate whether and to what extent IFN-β exacerbates NMO spectrum disorders (NMOSD).
We retrospectively reviewed the medical records of 40 patients with NMOSD who had been treated with IFN-β for more than 6 months and whose disease duration was more than 1 year at the initiation of IFN-β treatment. We evaluated their annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) scores before and after IFN-β treatment.
In total, 95% of patients exhibited an ineffective or exacerbated response to IFN-β treatment and the mean ARR significantly increased after IFN-β treatment (p = 0.002). The increased ARR > 50% under IFN-β treatment was observed in 20 patients (50%). The mean EDSS score significantly increased following IFN-β treatment (p < 0.001).
In patients with NMOSD, IFN-β 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.
Multiple Sclerosis 02/2012; 18(10):1480-3. · 4.26 Impact Factor
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ABSTRACT: Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.
Multiple sclerosis international. 01/2012; 2012:735486.
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ABSTRACT: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO).
To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4-Ab in 787 samples collected from 51 patients with definite or high-risk NMO.
AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations.
We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.
Multiple Sclerosis 09/2011; 18(5):578-86. · 4.26 Impact Factor
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ABSTRACT: Neuromyelitis optica (NMO) is an idiopathic inflammatory disorder of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. In Asia, NMO has long been considered a subtype of multiple sclerosis (MS). However, recent clinical, pathological, immunological, and imaging studies have suggested that NMO is distinct from MS. This reconsideration of NMO was initially prompted by the discovery of a specific antibody for NMO (NMO-IgG) in 2004. NMO-IgG is an autoantibody that targets aquaporin-4 (AQP4), the most abundant water channel in the CNS; hence, it was named anti-AQP4 antibody. Since it demonstrated reasonable sensitivity and high specificity, anti-AQP4 antibody was incorporated into new diagnostic criteria for NMO.The spectrum of NMO is now known to be wider than was previously recognized and includes a proportion of patients with recurrent, isolated, longitudinally extensive myelitis or optic neuritis, and longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease or with brain lesions typical of NMO. In this context, a new concept of "NMO spectrum disorders" was recently introduced. Furthermore, seropositivity for NMO-IgG predicts future relapses and is recognized as a prognostic marker for NMO spectrum disorders. Humoral immune mechanisms, including the activation of B-cells and the complement pathway, are considered to play important roles in NMO pathogenesis. This notion is supported by recent studies showing the potential pathogenic role of NMO-IgG as an initiator of NMO lesions. However, a demonstration of the involvement of NMO-IgG by the development of active immunization and passive transfer in animal models is still needed. This review focuses on the new concepts of NMO based on its pathophysiology and clinical characteristics. Potential management strategies for NMO in light of its pathomechanism are also discussed.
Journal of Clinical Neurology 09/2011; 7(3):115-27. · 1.69 Impact Factor
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ABSTRACT: 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).
Prospective open-label study.
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.
Annualized relapse rate, disability (Expanded Disability Status Scale score), anti-aquaporin 4 antibody level, and safety of rituximab treatment.
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.
Repeated treatment with rituximab appeared to produce consistent and sustained efficacy over 24 months with good tolerability in patients with NMO.
Archives of neurology 07/2011; 68(11):1412-20. · 6.31 Impact Factor
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ABSTRACT: Although brain abnormalities are being recognized more frequently in patients with neuromyelitis optica spectrum disorder (NMOSD), most brain lesions in previous reports have accompanied pre-existing NMOSD. Here, we describe clinical and imaging characteristics of patients with NMOSD who presented with brain symptoms as their first manifestation of the condition.
Anti-aquaporin-4 antibody was measured using cell-based assays and/or enzyme-linked immunosorbent assay in the sera of 257 patients with inflammatory diseases of the central nervous system who attended the multiple sclerosis clinic of the National Cancer Center, Korea, between May 2005 and December 2009. Eighty-three were seropositive, and 15 of these who presented with brain symptoms were included in this study. We retrospectively reviewed these individuals' clinical and radiological findings.
Patients with NMOSD were followed for a mean of 90 months. Median age at onset was 24 years (6-54 years) and there was a female preponderance (94%). The initial manifestation was classified into two groups according to clinical characteristics: encephalopathy mimicking acute disseminated encephalomyelitis or posterior reversible encephalopathy syndrome and characteristic brainstem symptoms such as intractable hiccup and vomiting. The majority of brain symptoms and lesions resolved. Intriguingly, eight patients (53%) experienced brain relapses that followed a similar pattern during the course of their disease.
It is important to recognize that NMO or NMOSD can initially present with brain symptoms.
Multiple Sclerosis 05/2011; 17(9):1107-12. · 4.26 Impact Factor
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ABSTRACT: To evaluate the efficacy and safety of mitoxantrone hydrochloride and determine how it exhibits a differential inhibitory effect on subsets of B cells in patients with highly relapsing neuromyelitis optica (NMO).
Retrospective case series with prospective follow-up.
Three referral medical centers in the Republic of Korea.
Twenty patients with highly relapsing NMO or neuromyelitis optica spectrum disorder who had at least 2 relapses during the year preceding the start of mitoxantrone treatment, despite other immunotherapies.
Infusions of mitoxantrone up to a maximum cumulative dose of 120 mg/m(2).
Annualized relapse rate, disability according to the Expanded Disability Status Scale score, and fraction of CD27(+)CD19(+) memory B cells.
During mitoxantrone treatment, the median annualized relapse rate was reduced by 75%, and 50% of patients became relapse free. Disability improved or stabilized in all patients. No patients had serious adverse effects during the mean follow-up period of 41 months after completing therapy. Flow cytometric analysis of cell surface markers revealed that mitoxantrone treatment preferentially affected CD27(+)CD19(+) memory B cells.
Treatment with mitoxantrone in patients with highly relapsing NMO significantly reduces relapse rates, resulting in subsequent functional stabilization or improvement.
Archives of neurology 12/2010; 68(4):473-9. · 6.31 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Multiple Sclerosis 10/2010; 16(10):1229-36. · 4.26 Impact Factor
