Risk of depression and anxiety in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD). OBJECTIVES: MS/NMOSD cohorts were collected from Korean National Health Insurance Service, using the International Classification of Diseases-10th and information on Rare Intractable Disease program. Patients who were younger than 20 years, had a previous depression/anxiety, or died in the index year were excluded. METHODS: Hazard ratios (HRs) of depression/anxiety in pwMS and pwNMOSD from controls matched 1:5 for age, sex, hypertension, diabetes, and dyslipidemia were calculated using Cox regressions with a 1-year lag period and estimated over time. RESULTS: During a mean follow-up of 4.1 years, adjusted hazard ratios (aHR) for depression were 3.25 (95% confidence interval (CI) = 2.59-4.07) in MS and 2.17 (1.70-2.76) in NMOSD, and aHRs for anxiety were 1.83 (1.49-2.23) in MS and 1.56 (1.26-1.91) in NMOSD. The risks of anxiety/depression did not differ between MS and NMOSD and were highest in the second year after diagnosis of MS/NMOSD. The relative risk of depression was higher in younger pwMS/pwNMOSD, and the relative risk of anxiety was higher in pwMS who was male, had low income, or lived in a non-urban area. CONCLUSION: The risk of depression and anxiety was increased in pwMS/pwNMOSD.

Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea.

INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

Risk of fracture in neuromyelitis optica spectrum disorder and multiple sclerosis: a nationwide cohort study in South Korea.

PURPOSE: Interest in fractures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has considerably increased in the last decade. However, few studies have compared the incidence of fractures between patients with MS and NMOSD using a nationwide database. This study aimed to evaluate the differences in the risk of fracture between patients with NMOSD and MS compared to that in healthy controls using cohort data from a Korean nationwide database. METHODS: In this retrospective cohort study, data from the National Health Insurance Service (NHIS) database from January 2010 to December 2017 were analyzed. A total of 1,217/1,329 patients with MS/NMOSD free of fractures at the index date were included. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus, and dyslipidemia. The mean follow-up durations after the index date were 4.40/4.08 years for patients with MS/NMOSD and 4.73/4.28 for their matched controls. RESULTS: The adjusted hazard ratios (aHRs) with 95% confidence intervals of any, hip, and vertebral fractures were 1.81 (1.43-2.28), 3.36 (1.81-6.24), and 2.01 (1.42-2.99) times higher for patients with MS than for controls, respectively, and they were 1.85 (1.47-2.34), 3.82 (2.05-7.11), and 2.84 (1.92-4.21) times higher for patients with NMOSD than for controls, respectively. No significant differences were observed in the incidence of fractures between the MS and NMOSD groups. Patients with MS/NMOSD had a 1.8-fold higher risk of fracture than matched controls, and the risk of hip fracture was especially high (3- to 4-fold higher). CONCLUSIONS: Clinicians need to regularly assess patients with MS/NMOSD for the risk of fractures and take preventative measures to reduce it.

Fracture risk in Parkinson's disease according to its severity and duration.

Fracture risk was elevated in Parkinson's disease (PD) patients compared with controls in this nationwide study. Among PD patients, the risk of fracture increased linearly with PD severity, whereas no difference in fracture risk was observed according to PD duration. INTRODUCTION: Parkinson's disease (PD) is reported to be associated with a high risk of fractures. Several studies found an association between severity and duration of PD and falls or bone mineral density, but those factors have not been considered in most previous research. The aim of this study was to determine the fracture risk in PD patients according to their disease severity and duration. METHODS: This population-based, retrospective cohort study used data from the Korean National Health Insurance Service database. The study population included 10,333 patients with prevalent PD and 6,501,464 comparison cohort. Fracture risks according to the prevalence, severity, and duration of PD were evaluated using Cox proportional hazard methods. RESULTS: Fracture risk was elevated in PD patients at all sites compared with controls (adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.44-1.56 for any fracture). When comparing fracture sites, hip fractures showed the largest risk increase in PD patients (aHR 2.16, 95% CI 1.95-2.38). Among PD patients, the risk of any fracture increased linearly with PD severity and was highest in patients with severe disease (aHR 1.65, 95% CI 1.53-1.79 compared with controls). Meanwhile, no significant association was observed between PD duration and fracture risk. CONCLUSIONS: The prevalence of PD was related to an increased risk of fractures in this nationwide study, and PD severity was linearly associated with fracture risk. PD prevalence and severity should be considered when evaluating the risk factors of fracture in clinical practice.

Risk of stroke in multiple sclerosis and neuromyelitis optic spectrum disorder: a Nationwide cohort study in South Korea.

BACKGROUND: People with multiple sclerosis (MS) are more likely to develop stroke than those without. However, little is known about the association between neuromyelitis optica spectrum disorder (NMOSD) and the risk of stroke. We aimed to estimate the risk of stroke in patients with MS and NMOSD in South Korea. METHODS: Data from the Korean National Health Insurance between January 2010 and December 2017 were analysed. A total of 1541/1687 adult patients with MS/NMOSD, who were free of stroke were included. Matched controls were selected based on age, sex and the presence of hypertension, diabetes mellitus and dyslipidaemia. RESULTS: The risk of developing stroke was 2.78 times higher (adjusted HR (aHR), 95% CI 1.91 to 4.05) in patients with MS compared with controls matched by age, sex, hypertension, diabetes mellitus and dyslipidaemia. The risk of stroke in NMOSD was also higher than that in matched controls (aHR=1.69, 95% CI 1.10 to 2.61) and not statistically different from that of MS (p=0.216). The patients with MS had a higher risk for either of ischaemic or haemorrhagic stroke (HR=2.63 and 2.93, respectively), whereas those with NMOSD had a higher risk for ischaemic stroke (HR=1.60) with marginal statistical significance. CONCLUSIONS: The risk of stroke is increased in patients with MS and NMOSD and seemed comparable between the two conditions. This is the first study that estimates the risk of stroke in patients with MS and NMOSD within the same population.

Risk of Parkinson's disease in multiple sclerosis and neuromyelitis optica spectrum disorder: a nationwide cohort study in South Korea.

BACKGROUND: Neurodegeneration is associated with pathogenesis of both multiple sclerosis (MS) and neuromyelitis optica (NMOSD). Parkinson's disease (PD) is a representative neurodegenerative disease, however, whether MS or NMOSD is associated with risk of PD is not known. METHODS: MS and NMOSD cohorts were collected from the Korean National Health Insurance Service between 1 January 2010 and 31 December 2017, using International Classification of Diseases 10th revision diagnosis codes and information in the Rare Intractable Disease management programme. The PD incidence rate that occurred after a 1-year lag period was calculated and compared with that of a control cohort matched for age, sex, hypertension, diabetes and dyslipidaemia in a 1:5 ratio. RESULTS: The incidence rates of PD in patients with MS and NMOSD were 3.38 and 1.27 per 1000 person-years, respectively, and were higher than that of their matched control groups. The adjusted HR of PD was 7.73 (95% CI, 3.87 to 15.47) in patients with MS and 2.61 (95% CI, 1.13 to 6.02) in patients with NMOSD compared with matched controls. In both patients with MS and NMOSD, there were no significant differences in relative risk when stratified by sex, age, diabetes, hypertension and dyslipidaemia. CONCLUSION: The PD risk was higher in patients with MS and NMOSD compared with healthy controls and was particularly high in patients with MS. Further investigations should be performed to determine the pathophysiology and occurrence of PD in patients with MS and NMOSD.

Acute myocardial infarction risk in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: The link between neuromyelitis optica spectrum disorder (NMOSD) and cardiovascular disease is currently unclear. OBJECTIVE: To determine the acute myocardial infarction (MI) risk in patients with MS and NMOSD. METHODS: This study analyzed the Korean National Health Insurance Service database between January 2010 and December 2017. The included patients comprised 1503/1675 adults with MS/NMOSD who had not experienced ischemic heart disease or ischemic stroke at the index date. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus (DM), and dyslipidemia. RESULTS: The risks of developing MI were 2.61 (hazard ratio (HR), 95% confidence interval (CI) 1.73-3.95) and 1.95 (95% CI = 1.18-3.22) times higher in MS and NMOSD compared with the control populations. Patients with NMOSD had a similar MI risk compared with patients with MS, after adjusting for age, sex, income, hypertension, DM, and dyslipidemia (HR = 0.59, 95% CI = 0.34-1.02, p = 0.059). Among each patient group, the MI risk did not differ significantly with age (20-39, 40-64 or ⩾65 years), sex, or the presence of hypertension, DM, or dyslipidemia. CONCLUSION: The MI risk increased in MS and NMOSD and seemed to be comparable between NMOSD and MS.

Comparison of MOG and AQP4 antibody seroprevalence in Korean adults with inflammatory demyelinating CNS diseases.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

Physician- and self-assessed myasthenia gravis activities of daily living score.

INTRODUCTION: The Myasthenia Gravis-Activities of Daily Living (MG-ADL) profile scale is a simple-to-use instrument. We aimed to validate this scale in the Korean language and compare physician- and self-assessed MG-ADL scores (pMG-ADL-K and sMG-ADL-K). METHODS: pMG-ADL-K and sMG-ADL-K and MG Composite (MGC) scores were obtained from patients. The correlation between pMG-ADL-K and MGC and the relationship between the pMG-ADL-K and sMG-ADL-K were assessed using the Cronbach α and the Spearman coefficient. By intraclass correlation coefficient (ICC), the reliability of each sub-item of pMG-ADL-K and sMG-ADL-K was evaluated. RESULTS: We included data from 40 patients. The pMG-ADL-K score showed a strong correlation with the MGC score (rho = 0.80, P < 0.01). The Cronbach α was 0.98 between pMG-ADL-K and sMG-ADL-K, and sub-items showed good consistency (ICC 0.684-0.985, P < 0.001). DISCUSSION: The MG-ADL-K is a valid tool and the sMG-ADL-K shows excellent correlation with pMG-ADL-K. Both the pMG-ADL-K and sMG-ADL-K can be used to measure MG severity. Muscle Nerve 57: 419-422, 2018.

The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder.

B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs. The phenotype and frequency of B cell and T cell subsets in the peripheral blood were measured by flow cytometry. We defined Breg cells as IL-10-producing B (B10) cells, which are CD19+CD39+CD1d+IL-10+. The potential relations were evaluated between specific lymphocyte subsets and AQP4-ab intensity measured by the cell-based indirect immunofluorescence assay. The frequency of B10 cells was higher in patients with NMOSD regardless of the disease status than that in HCs (attack samples; p = 0.009 and remission samples; p < 0.001, respectively). In addition, the frequency of IL-17+ Treg cells among Treg cells was higher during remission than during an attack (uncorrected p = 0.032). Among the lymphocyte subsets, B10 cells alone showed a positive correlation with the intensity of AQP4-ab positivity (ρ [rho] = 0.402 and p = 0.031). It was suggested that the suppressive subsets including B10 and IL-17+ Treg cells might have important roles in controlling disease status in NMOSD. Further functional studies may help to elucidate the immunological role of B10 and IL-17+ Treg cells in NMOSD.

Clinical characteristics of late-onset neuromyelitis optica spectrum disorder: A multicenter retrospective study in Korea.

BACKGROUND: There are currently few studies regarding late-onset neuromyelitis optica spectrum disorder (LO-NMOSD). OBJECTIVE: We aimed to describe the characteristic features of patients with LO-NMOSD in Korea. METHODS: Anti-aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder (NMOSD) from nine tertiary hospitals were reviewed retrospectively. The patients were divided into two groups based on age of onset: LO-NMOSD (⩾50 years of age at onset) versus early-onset neuromyelitis optica spectrum disorder (EO-NMOSD) (<50 years of age at onset). Clinical, laboratory, and magnetic resonance imaging (MRI) parameters were investigated. RESULTS: Among a total of 147 patients (125 female; age of onset, 39.4 ± 15.2 years), 45 patients (30.6%) had an age of onset of more than 50 years. Compared to patients with EO-NMOSD, patients with LO-NMOSD had more frequent isolated spinal cord involvement at onset (64.4% vs 37.2%, p = 0.002), less frequent involvement of the optic nerve (40.0% vs 67.7%, p = 0.002), and less frequent brain MRI lesions (31.1% vs 50.0%, p = 0.034). Furthermore, there was a significant positive correlation between age of onset and Expanded Disability Status Scale (EDSS) score at last follow-up ( r = 0.246, p = 0.003). CONCLUSION: Age of onset could be an important predictor of lesion location and clinical course of patients with NMOSD.

Decreased hemoglobin levels, cerebral small-vessel disease, and cortical atrophy: among cognitively normal elderly women and men.

BACKGROUND: Decreased hemoglobin levels increase the risk of developing dementia among the elderly. However, the underlying mechanisms that link decreased hemoglobin levels to incident dementia still remain unclear, possibly due to the fact that few studies have reported on the relationship between low hemoglobin levels and neuroimaging markers. We, therefore, investigated the relationships between decreased hemoglobin levels, cerebral small-vessel disease (CSVD), and cortical atrophy in cognitively healthy women and men. METHODS: Cognitively normal women (n = 1,022) and men (n = 1,018) who underwent medical check-ups and magnetic resonance imaging (MRI) were enrolled at a health promotion center. We measured hemoglobin levels, white matter hyperintensities (WMH) scales, lacunes, and microbleeds. Cortical thickness was automatically measured using surface based methods. Multivariate regression analyses were performed after controlling for possible confounders. RESULTS: Decreased hemoglobin levels were not associated with the presence of WMH, lacunes, or microbleeds in women and men. Among women, decreased hemoglobin levels were associated with decreased cortical thickness in the frontal (Estimates, 95% confidence interval, -0.007, (-0.013, -0.001)), temporal (-0.010, (-0.018, -0.002)), parietal (-0.009, (-0.015, -0.003)), and occipital regions (-0.011, (-0.019, -0.003)). Among men, however, no associations were observed between hemoglobin levels and cortical thickness. CONCLUSION: Our findings suggested that decreased hemoglobin levels affected cortical atrophy, but not increased CSVD, among women, although the association is modest. Given the paucity of modifiable risk factors for age-related cognitive decline, our results have important public health implications.

Usefulness of the MFIS-K, FSS, and FACIT-F Fatigue Scales in Korean Patients With MS, NMOSD, and MOGAD.

BACKGROUND AND PURPOSE: Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. METHODS: There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). RESULTS: The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. CONCLUSIONS: These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.

Risk of depression in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea.

Depression is frequently reported in amyotrophic lateral sclerosis (ALS) due to the disastrous prognosis of progressive motor impairment, but the risk of depression in ALS is still unclear. Therefore, we investigated the risk of depression in ALS and analyzed the effect of ALS-related physical disability on the risk of developing depression using the Korean National Health Insurance Service (KNHIS) database. A total of 2241 ALS patients, as defined by the International Classification Diseases (ICD, G12.21) and Rare Intractable Disease codes (V123), and 1:10 sex- and age-matched controls were selected from the KNHIS. After applying exclusion criteria (non-participation in national health screening, history of depression, or having missing data), 595 ALS patients and 9896 non-ALS individuals were finally selected. Primary outcome is newly diagnosed depression during follow-up duration defined by ICD code (F32 or F33). A Cox regression model was used to examine the hazard ratios (HRs) after adjustment for potential confounders. During the follow-up period, 283 cases of depression in the ALS group and 1547 in the controls were recorded. The adjusted HR for depression in ALS was 9.1 (95% confidence interval [CI] 7.87-10.60). The risk of depression was slightly higher in the disabled ALS group (aHR 10.1, 95% CI 7.98-12.67) than in the non-disabled ALS group (aHR 8.78, 95% CI 7.42-10.39). The relative risk of depression was higher in younger patients than in older patients, and in obese patients than in non-obese patients. Our study showed that ALS patients have an increased risk of depression compared to non-ALS individuals.

The risk of type 2 diabetes mellitus in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study.

BACKGROUND AND OBJECTIVES: An association has been suggested between premorbid type 2 diabetes mellitus (T2DM) and the risk of multiple sclerosis (MS). However, little is known about the risk of developing T2DM in MS and neuromyelitis optica spectrum disorder (NMOSD). This study aimed to determine the T2DM risk in patients with MS and NMSOD. METHODS: The Korean National Health Insurance Service database was analyzed, and 1,801 and 1,721 adults with MS and NMOSD, respectively, who were free of T2DM between January 2010 and December 2017, were included. Matched controls were selected based on age, sex, and the presence of hypertension and dyslipidemia. RESULTS: The risk of developing T2DM was 1.54 times higher in NMOSD than in the controls (adjusted hazard ratio [aHR], 95 % confidence interval [CI] = 1.20-1.96). However, increased T2DM risk was not observed in MS (aHR = 1.13, 95 % CI = 0.91-1.42). The T2DM risk in patients with NMOSD was higher in those who received steroid treatment (aHR = 1.77, 95 % CI = 1.36-2.30) but not in those who did not (aHR = 0.59, 95 % CI = 0.24-1.43, p for interaction = 0.02). DISCUSSION: T2DM risk was increased in NMOSD but not in MS. Administering steroid treatment to patients with NMOSD may increase their T2DM risk.

Quality of life in patients with myelin oligodendrocyte glycoprotein antibody associated disease compared to patients with AQP4-IgG positive neuromyelitis optica spectrum disorders: A Korean multicenter study.

BACKGROUND: Little is known about the quality of life (QOL) of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We compared QOL and associated factors in patients with MOGAD and aquaporin4 IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: This multicenter questionnaire study compared the QOL of 41 patients with MOGAD and 78 with AQP4-IgG positive NMOSD. Patients who were positive for AQP4-IgG or MOG antibodies were included. WHO Quality of Life Scale Brief Version was used to assess QOL in physical, psychological, social, and environmental domains. QOL, sleep quality, pain, fatigue, and depression were compared between the two groups. The factors associated with QOL in each group and the entire cohort were analyzed. RESULTS: The proportion of patients with poor QOL was not significantly different between MOGAD (51.22 %) and AQP4-IgG positive NMOSD (58.97 %, p = 0.054). In the MOGAD group, the pain score (ß=-1.032, p = 0.001) and depression score (ß=-0.694, p = 0.007) were negatively associated with physical and psychological QOL, respectively. Sleep quality was negatively associated with physical (ß=-1.506, p = 0.034) and psychological (ß =-2.064, p = 0.033) QOL. When the entire cohort was analyzed, a positive MOG antibody was independently associated with worse psychological QOL (ß=-8.998, p = 0.013) compared to positive AQP4-Ab after adjustment for sleep quality, depression, fatigue, and pain. CONCLUSIONS: The overall QOL of the patients of MOGAD was comparable to that of AQP4-IgG positive NMOSD. Patients with MOGAD were experiencing sleep disorder, fatigue, and depression at similar degrees to those of patients with AQP4-IgG positive NMOSD. Further consideration of sleep quality and psychological QOL is required to improve QOL in patients with MOGAD.

Potential prognostic value of rheumatoid factor in anti-aquaporin 4-immunoglobin G-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies. METHODS: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD. RESULTS: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001). CONCLUSION: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR.

Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.

Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods: The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.