Discontinuation of Immunosuppressive Therapy in Patients With Neuromyelitis Optica Spectrum Disorder With Aquaporin-4 Antibodies.

OBJECTIVE: To evaluate the outcomes of immunosuppressive therapy (IST) discontinuation in patients with neuromyelitis optica spectrum disorder (NMOSD) after a sustained remission period. METHODS: We retrospectively reviewed the medical records of 17 patients with antiaquaporin-4 antibody-positive NMOSD who discontinued IST after a relapse-free period of ≥3 years. RESULTS: IST was discontinued at a median age of 40 years (interquartile range [IQR], 32-51) after a median relapse-free period of 62 months (IQR, 52-73). Among the 17 enrolled patients, 14 (82%) relapsed at a median interval of 6 months (IQR, 4-34) after IST discontinuation, 3 (18%) of whom experienced severe attacks; notably, all 3 of these patients had a history of severe attack before IST. These 3 patients received steroids, followed by plasma exchange for acute treatment, but 2 exhibited poor recovery and significant disability worsening at 6 months after relapse. CONCLUSIONS: IST discontinuation may increase the risk of relapse in seropositive patients with NMOSD even after 5 years of remission. Given the potentially devastating consequence of a single attack of NMOSD, caution is advised with IST discontinuation, particularly in patients with severe attack before IST.

Value of Area Postrema Syndrome in Differentiating Adults With AQP4 vs. MOG Antibodies.

Objectives: To compare the frequency of area postrema syndrome (APS) in adults with anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods: APS is defined as acute or subacute, single or combined, episodic or constant nausea, vomiting, or hiccups, persisting for at least 48 h, which cannot be attributed to any other etiology. The presence of APS was investigated in 274 adults with AQP4 antibodies and 107 adults with MOG antibodies from 10 hospitals. Results: The study population comprised Korean adults (≥18 years). At the time of disease onset, 14.9% (41/274) adults with AQP4 antibodies had APS, while none of the participants with MOG antibodies developed APS (p < 0.001). During the course of the disease, 17.2% (47/274) adults with AQP4 antibodies had APS in contrast to 1.9% (2/107) adults with MOG antibodies with APS (p < 0.001). Conclusions: APS, one of the core clinical characteristics of individuals with AQP4 antibodies, is an extremely rare manifestation in Korean adults with MOG antibodies.

Validation of the Korean Version of the 12-Item Multiple Sclerosis Walking Scale and Application to Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND PURPOSE: Gait problems are a primary complaint in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported measure assessing the impact of MS on the walking ability. We aimed to adapt and validate the Korean version of the MSWS-12 for the Korean population with MS and NMOSD. METHODS: Thirty-four MS and 35 NMOSD patients were recruited. The MSWS-12 questionnaire was translated into the Korean language and evaluated for its validity and reliability in these patients. RESULTS: The MS and NMOSD patients had mean ages of 35.9 and 42.1 years, respectively, median disease durations of 5.6 and 7.2 years, median Expanded Disability Status Scale (EDSS) scores of 2.75 (range, 0-6.5) and 3.5 (range, 0-7.5), and median baseline MSWS-12 total scores of 25 [interquartile range (IQR), 2.60-53.65] and 25 (IQR, 7.29-50.00). The baseline MSWS-12 total score in the patients with MS showed strong correlations with scores for the EDSS, timed 25-foot walk (T25FW), Multiple Sclerosis Impact Scale-29 (MSIS-29) physical dimension, and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS), with Spearman's correlation coefficients (ρ) of 0.922, 0.756, 0.933, and -0.874, respectively. In patients with NMOSD, the baseline MSWS-12 total score showed strong correlations with scores for the EDSS, MSIS-29 physical dimension, and SF-36 PCS (ρ=0.769, 0.910, and -0.852, respectively), and moderate correlations with scores for the T25FW and Fatigue Severity Scale-9 (ρ=0.597 and 0.630, respectively). CONCLUSIONS: The Korean version of the MSWS-12 appears to be a valid and reliable scale that can be used for Korean patients with MS. The MSWS-12 can also be applied to patients with NMOSD.

Comparison of Neuropathic Pain in Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis.

BACKGROUND AND PURPOSE: To compare the characteristics of neuropathic pain in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: From 2016 to 2018, 500 patients with NMOSD and MS from 6 referral hospitals in Korea underwent pain investigation. After the patients with current pain were matched for sex ratio and disease duration as confounding factors, PainDETECT questionnaires were assessed in 99 NMOSD and 58 MS patients to investigate neuropathic pain. The short form of the Brief Pain Inventory from 74 patients with neuropathic pain component was also analysed. RESULTS: According to the PainDETECT questionnaire, mechanical allodynia (p=0.014) and thermal hyperalgesia (p=0.011) were more severe in NMOSD patients than in MS patients. Strong involvements (score >3) of the pain in domains of tingling/prickling sensation (p=0.024), mechanical allodynia (p=0.027), sudden pain attacks (p=0.018), and thermal hyperalgesia (p=0.002) were significantly more frequent in NMOSD compared to MS patients. Among the patients experiencing pain with a neuropathic component, total pain-related interference (p=0.045) scores were significantly higher in NMOSD patients than in MS patients. In daily life, pain interfered with normal work (p=0.045) and relationships with other people (p=0.039) more often in NMOSD patients than in MS patients. Although pain medication was prescribed more frequently in NMOSD patients, the percentage of patients experiencing medication-related pain relief was lower in those patients. CONCLUSIONS: The severity of neuropathic pain and the pain-related interference in daily life were greater in NMOSD patients than in MS patients. Individualized analgesic management should be considered based on a comprehensive understanding of neuropathic pain in these patients.

Erratum to: High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis.

This corrects the article on p. 454 in vol. 15, PMID: 31591832.

High Seroprevalence and Index of Anti-John-Cunningham Virus Antibodies in Korean Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: The anti-John-Cunningham virus (JCV)-antibody serostatus and index are used in the risk stratification of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab. However, little information on these parameters is available for Asian countries. The purpose of this study was to determine the rate of seropositivity, index, and longitudinal index evolution in Korean patients with MS. METHODS: The antibody seroprevalence was analyzed in 355 samples from 187 patients with clinically isolated syndrome or MS using a second-generation, two-step, enzyme-linked immunosorbent assay. A 4-year longitudinal evaluation was applied to 66 patients. RESULTS: The overall antibody seroprevalence was 80% (n=149). Among antibody-positive patients, the index had a median value of 3.27 (interquartile range, 1.52-4.18), with 77% (n=114) and 56% (n=83) of patients having indices >1.5 and >3.0, respectively. The serostatus of 59 (89%) of the 66 patients did not change during the longitudinal analysis, while 3 (6%) of the 53 patients who were initially seropositive reverted to seronegativity, and 2 (15%) of the 13 patients who were initially seronegative converted to seropositivity. All patients with a baseline index >0.9 maintained seropositivity, and 92% of patients with a baseline index >1.5 maintained this index over 4 years. No patients developed PML (median disease duration, 8 years). CONCLUSIONS: The seroprevalence and index of anti-JCV antibodies in Korean patients with MS may be higher than those in Western countries.

Therapeutic Outcome of Alemtuzumab in Korean Patients with Multiple Sclerosis: 2-Year Follow-Up.

BACKGROUND AND PURPOSE: Alemtuzumab has shown high efficacy in clinical trials that primarily involved Western multiple sclerosis (MS) patients. To evaluate the therapeutic outcome of alemtuzumab in Korean patients with MS. METHODS: This study enrolled 23 consecutive patients who were treated with alemtuzumab from 2015 to 2018. Efficacy was evaluated using the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), and radiological activity. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of the EDSS score, and no radiological activity. The safety profiles were also assessed. RESULTS: The mean age was 36 years and 16 of the patients were female. Seventeen and 12 of 23 patients were followed up for 1 year and 2 years, respectively. The ARR was markedly reduced from 1.52 during the 1-year period preceding alemtuzumab administration to 0.21 after initiating alemtuzumab (p<0.001). During the first and second years after initiating alemtuzumab, EDSS worsening was observed in 3 (18%) and 0 (0%) patients, respectively, and radiological activity was exhibited in 9 (53%) and 4 (33%). NEDA was observed in 6 (35%) patients during the first year and in 8 (67%) patients during the second year. Intriguingly, one patient experienced 2 severe clinical exacerbations, which occurred at 10 months after the first and 10 months after the second infusion of alemtuzumab. Nineteen of the 23 patients exhibited infusion-associated reactions and 3 patients exhibited herpes zoster infection. Thyroid dysfunction occurred in two patients at 18 and 20 months after initiating alemtuzumab. CONCLUSIONS: Consistent with observations in Western populations, alemtuzumab therapy in Korean MS patients led to marked reductions of disease activity without unexpected safety issues.

Neutralizing Antibodies Against Interferon-Beta in Korean Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-ß) can develop neutralizing antibodies (NAbs) against IFN-ß that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-ß in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-ß for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-ß-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-ß-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-ß-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-ß.