Decreased serum tryptophan levels in patients with MOGAD:a cross-sectional survey.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of central nervous system (CNS). Tryptophan indole catabolites have been reported to associate with the inflammatory diseases of the CNS. However, the roles of tryptophan indole catabolites have been rarely elucidated in MOGAD. METHODS: This cross-sectional study enrolled forty MOGAD patients, twenty patients with other non-inflammatory neurological diseases (OND) and thirty-five healthy participants. Serum and cerebrospinal fluid (CSF) samples of MOGAD and OND subjects during clinical attacks, serum samples of healthy participants were obtained. The concentrations of tryptophan, indoleacetic acid (IAA), indoleacrylic acid (IA) and indole-3-carboxylic acid (I-3-CA) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The correlations between tryptophan indole catabolites and maintenance immunotherapy, disease duration, overall numbers of attacks, short-term outcome in MOGAD patients were investigated. RESULTS: Levels of serum tryptophan, IAA, IA and CSF tryptophan in MOGAD patients were significantly decreased, while levels of serum I-3-CA and CSF IA were markedly increased compared with OND patients and healthy controls. Levels of serum tryptophan, CSF tryptophan and IA were significantly decreased in MOGAD patients who had received maintenance immunotherapy within 6 months before the attack. In MOGAD patients, serum and CSF tryptophan conversely correlated with disease duration and overall numbers of attacks, and serum IA negatively correlated with disease duration. Furthermore, serum tryptophan in MOGAD patients negatively correlated with the modified Rankin Scale (mRS) scores at 3 months. CONCLUSION: This study manifested decreased serum tryptophan levels and serum tryptophan may be the potential marker to predict the short-term outcome in MOGAD patients.

The landscape of PBMCs in AQP4-IgG seropositive NMOSD and MOGAD, assessed by high dimensional mass cytometry.

OBJECTIVES: Data on peripheral blood mononuclear cells (PBMCs) characteristics of aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are lacking. In this study, we describe the whole PBMCs landscape of the above diseases using cytometry by time-of-flight mass spectrometry (CyTOF). METHODS: The immune cell populations were phenotyped and clustered using CyTOF isolated from 27 AQP4-IgG seropositive NMOSD, 11 MOGAD patients, and 15 healthy individuals. RNA sequencing was employed to identify critical genes. Fluorescence cytometry and qPCR analysis were applied to further validate the algorithm-based results that were obtained. RESULTS: We identified an increased population of CD11b+ mononuclear phagocytes (MNPs) in patients with high expression of CCR2, whose abundance may correlate with brain inflammatory infiltration. Using fluorescence cytometry, we confirmed the CCR2+ monocyte subsets in a second cohort of patients. Moreover, there was a wavering of B, CD4+ T, and NKT cells between AQP4-IgG seropositive NMOSD and MOGAD. CONCLUSIONS: Our findings describe the whole landscape of PBMCs in two similar demyelinated diseases and suggest that, besides MNPs, T, NK and B, cells were all involved in the pathogenesis. The identified cell population may be used as a predictor for monitoring disease development or treatment responses.

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE130-149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor-related protein 1 (LRP1) could block the restorative effects of APOE130-149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE-/- mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.

Profile and potential role of novel metabolite biomarkers, especially indoleacrylic acid, in pathogenesis of neuromyelitis optica spectrum disorders.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory and demyelinating disorder that can lead to serious disability and mortality. Humoral fluid biomarkers with specific, convenient, and efficient profiles that could characterize and monitor disease activity or severity are very useful. We aimed to develop a sensitive and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS)/MS-based analytical method for novel biomarkers finding in NMOSD patients and verified its function tentatively. Methods: Serum samples were collected from 47 NMOSD patients, 18 patients with other neurological disorders (ONDs), and 35 healthy controls (HC). Cerebrospinal fluid (CSF) samples were collected from 18 NMOSD and 17 OND patients. Three aromatic amino acids (phenylalanine, tyrosine, and tryptophan) and nine important metabolites that included phenylacetylglutamine (PAGln), indoleacrylic acid (IA), 3-indole acetic acid (IAA), 5-hydroxyindoleacetic acid (HIAA), hippuric acid (HA), I-3-carboxylic acid (I-3-CA), kynurenine (KYN), kynurenic acid (KYNA), and quinine (QUIN) were analyzed by using the liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method. The profile of IA was further analyzed, and its function was verified in an astrocyte injury model stimulated by NMO-IgG, which represents important events in NMOSD pathogenesis. Results: In the serum, tyrosine and some of the tryptophan metabolites IA and I-3-CA decreased, and HIAA increased significantly in NMOSD patients. The CSF levels of phenylalanine and tyrosine showed a significant increase exactly during the relapse stage, and IA in the CSF was also increased markedly during the relapse and remission phases. All conversion ratios had similar profiles with their level fluctuations. In addition, the serum IA levels negatively correlated with glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) levels in the serum of NMOSD patients were measured by using ultra-sensitive single-molecule arrays (Simoa). IA showed an anti-inflammatory effect in an in vitro astrocyte injury model. Conclusion: Our data suggest that essential aromatic amino acid tryptophan metabolites IA in the serum or CSF may serve as a novel promising biomarker to monitor and predict the activity and severity of NMOSD disease. Supplying or enhancing IA function can promote anti-inflammatory responses and may have therapeutic benefits.

Targeting chemoattractant chemokine (C-C motif) ligand 2 derived from astrocytes is a promising therapeutic approach in the treatment of neuromyelitis optica spectrum disorders.

Introduction: Aquaporin-4 immunoglobulin G (AQP4-IgG)-induced astrocytes injury is a key mechanism in the pathogenesis of neuromyelitis spectrum disorder (NMOSD), and although CCL2 is involved, its specific role has not been reported. We aimed to further investigate the role and potential mechanisms of CCL2 in AQP4-IgG-induced astrocyte injury. Methods: First, we evaluated CCL2 levels in paired samples of subject patients by automated microfluidic platform, Ella®. Second, we knock down astrocyte's CCL2 gene in vitro and in vivo to define the function of CCL2 in AQP4-IgG-induced astrocyte injury. Third, astrocyte injury and brain injury in live mice were assessed by immunofluorescence staining and 7.0T MRI, respectively. Western blotting and high-content screening were conducted to clarify the activation of inflammatory signaling pathways, and changes in CCL2 mRNA and cytokine/chemokines were measured by qPCR technique and flow cytometry, respectively. Results: There were greatly higher CSF-CCL2 levels in NMOSD patients than that in other non-inflammatory neurological diseases (OND) groups. Blocking astrocyte CCL2 gene expression can efficiently mitigate AQP4-IgG-induced damage in vitro and in vivo. Interestingly, prevention of CCL2 expression could decrease other inflammatory cytokines released, including IL-6 and IL-1ß. Our data suggest that CCL2 involves in the initiation and plays a pivotal role in AQP4-IgG-damaged astrocytes. Discussion: Our results indicate that CCL2 may serve as a promising candidate target for inflammatory disorder therapy, including NMOSD.

NMO-IgG Induce Interleukin-6 Release via Activation of the NF-κB Signaling Pathway in Astrocytes.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) that frequently affects the optic nerve and spinal cord. Interleukin-6 (IL-6) is considered a key cytokine in the pathogenesis of NMOSD, and the level of IL-6 is significantly increased in the sera and cerebrospinal fluid (CSF) of patients with NMOSD. We have reported that the production of IL-6 depends on the JAK/STAT3 signaling pathway. However, it is not clear whether the NF-κB-dependent inflammatory response stimulated by neuromyelitis optica IgG (NMO-IgG) could also drive the production of IL-6 in astrocytes. In this study, we used an in vitro model of primary rat astrocytes stimulated by NMO-IgG to study the role of the NF-κB signaling pathway in mediating the release of IL-6. First, we confirmed that the level of IL-6 was significantly higher in the sera of NMOSD patients than that of healthy people by humoral fluid analysis and that NMO-IgG can significantly induce the release of IL-6 from astrocytes by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Then, Western blotting and immunocytochemistry showed that NMO-IgG can activate the intracellular NF-κB signaling pathway. Finally, it was found that S3633, an inhibitor of the NF-κB signaling pathway, can effectively inhibit the increase in IL-6 levels. These results prove that the production of IL-6 is partly mediated by the NF-κB signaling pathway, providing a potential effective strategy for targeted treatment of NMOSD.

Soluble TREM2 is a potential biomarker for the severity of primary angiitis of the CNS.

Background: Primary angiitis of the central nervous system (PACNS) is a severe inflammatory disease, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) has been reported to be associated with inflammation of the CNS. However, the role of sTREM2 in PACNS remains unknown. Methods: We obtained serum and cerebrospinal fluid (CSF) samples from 18 patients diagnosed with PACNS, as well as 14 patients diagnosed with other neurological disorders with no evidence of inflammation. sTREM2 concentrations in the samples were detected by enzyme-linked immunosorbent assay. And routine CSF measurements of PACNS patients were analysed, including number of White Blood Cells (WBC), protein, Immunoglobulin G (IgG) index and CSF/serum quotients. Levels of inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-1ß, and complement C4, also were tested. The modified Rankin scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and activities of daily living (ADL) scores were obtained as indicators of disease severity. In PACNS patients, cerebral lesion volume was evaluated by magnetic resonance imaging. Results: sTREM2 levels in serum and CSF were significantly elevated in PACNS patients and significantly associated with the mRS, NIHSS and ADL scores as well as inflammatory cytokine levels. Additionally, positive correlations were observed between the cerebral lesion volume and the sTREM2 levels in both blood and CSF. Higher sTREM2 levels in either the blood or CSF seemed to predict a good prognosis in PACNS patients. Conclusion: Our results indicate an association between serum and CSF sTREM2 levels and the severity of neurological damage. Thus, sTREM2 represents a potential biomarker for monitoring disease and potentially predicting the prognosis of PACNS patients.

Thymic Involution and Altered Naive CD4 T Cell Homeostasis in Neuromyelitis Optica Spectrum Disorder.

Circulating T helper cells with a type 17-polarized phenotype (TH17) and expansion of aquaporin-4 (AQP4)-specific T cells are frequently observed in patients with neuromyelitis optica spectrum disorder (NMOSD). However, naive T cell populations, which give rise to T helper cells, and the primary site of T cell maturation, namely the thymus, have not been studied in these patients. Here, we report the alterations of naive CD4 T cell homeostasis and the changes in thymic characteristics in NMOSD patients. Flow cytometry was performed to investigate the naive CD4+ T cell subpopulations in 44 NMOSD patients and 21 healthy controls (HC). On immunological evaluation, NMOSD patients exhibited increased counts of CD31+thymic naive CD4+ T cells and CD31-cental naive CD4+ T cells along with significantly higher fraction and absolute counts of peripheral blood CD45RA+ CD62L+ naive CD4+ T cells. Chest computed tomography (CT) images of 60 NMOSD patients and 65 HCs were retrospectively reviewed to characterize the thymus in NMOSD. Thymus gland of NMOSD patients exhibited unique morphological characteristics with respect to size, shape, and density. NMOSD patients showed exacerbated age-dependent thymus involution than HC, which showed a significant association with disease duration. These findings broaden our understanding of the immunological mechanisms that drive severe disease in NMOSD.

Icariin ameliorates the cuprizone-induced acute brain demyelination and modulates the number of oligodendrocytes, microglia and astrocytes in the brain of C57BL/6J mice.

This study aimed at testing the hypothesis that treatment with icariin (ICA, a type of flavonoid) could mitigate the cuprizone (CPZ)-induced acute demyelination in the brain of mice and the potential mechanisms. Female C57BL/6J mice were fed continually with regular rodent chow or the chow supplemented with CPZ (0.2 % w/w) for six weeks to induce acute demyelination. The CPZ-fed mice were treated with vehicle or ICA at 12.5 or 25 mg/kg beginning at three weeks post CPZ feeding daily for three weeks. Their brain tissue sections were stained with oil red O, luxol-fast blue (LFB) and immunohistochemistry to characterize the levels of brain demyelination, myelin basic protein (MBP) and brain-derived neurotrophic factor (BDNF) and the numbers of oligodendrocytes (Ols), oligodendrocyte progenitor cells (OPCs), microglia and astrocytes in mice. Compared with the healthy controls, CPZ feeding caused the brain demyelination by increasing NG2+ OPCs, but decreased oil red O and LFB staining, MBP level and GST-pi+ Ols in the brain corpus callosum region of mice. Furthermore, CPZ feeding decreased the number of BDNF+ cells in the brain cortex and hippocampus regions, but increased microglia in the brain corpus callosum, cortex and caudate putamen, and astrocytes in the corpus callosum regions of mice. Treatment with ICA significantly mitigated or abrogated the toxic demyelination of CPZ by preserving MBP and BDNF proteins and modulating the numbers of Ols, OPCs, microglia and astrocytes in the brain of mice. ICA treatment significantly ameliorated the CPZ-mediated demyelination and modulated the number of Ols, microglia and astrocytes in the brain of mice.

Icariin ameliorates the progression of experimental autoimmune encephalomyelitis by down-regulating the major inflammatory signal pathways in a mouse relapse-remission model of multiple sclerosis.

This study aimed at investigating whether treatment with icariin (ICA) could modulate the progression of experimental autoimmune encephalomyelitis (EAE) and its potential mechanisms in SJL/J mice. Female SJL/J mice were immunized with PLP139-151 peptide to induce relapse-remitting EAE and the immunized mice were treated with vehicle alone (EAE) or ICA (12.5 or 25 mg/body weights) by gavage daily for 42 days. Compared with the control, the EAE mice developed relapse-remitting EAE and reduced body weights (15.76 ± 0.61 vs. 17.60 ± 0.98 g on day 13; 17.35 ± 0.44 vs. 18.46 ± 0.66 g on day 26), accompanied by severe inflammation with many microglia infiltrates and obvious demyelination in the spinal cord tissues. Conversely, ICA treatment significantly reduced the clinical scores (on day 13, 1.00 ± 0.16 and 1.10 ± 0.33 for ICA 12.5 and 25 mg/kg group, respectively vs. 1.62 ± 0.41 in the EAE group; on day 26, 0.50 ± 0.23 and 0.40 ± 0.24 for ICA 12.5 and 25 mg/kg group, respectively, vs. 1.56 ± 0.29 in the EAE group), mitigated the body weight reduction, spinal cord inflammation and demyelination in EAE mice (pathological scores of 2.33 ± 0.82 and 1.11 ± 0.57 for ICA 12.5 and 25 mg/kg, respectively; vs. 4.78 ± 1.13, P < 0.0001). Furthermore, ICA treatment significantly mitigated the EAE-increased iNOS, TNF-α, CD206 and TGF-ß1, but further reduced IL-10 mRNA transcripts in the brain mice. More importantly, ICA treatment significantly mitigated the inflammation-related NF-κB, AKT, ERK1/2, p38, c-Jun and MEK phosphorylation in the brain of EAE mice. ICA treatment ameliorates the progression of EAE by down-regulating the major inflammation-related signal pathways in mice.

Anti-NMDA receptor encephalitis concomitant with myelin oligodendrocyte glycoprotein antibody diseases: A retrospective observational study.

Anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) can coexist with myelin oligodendrocyte glycoprotein antibody (MOG-ab) disease.To characterize MOG-ab disease during NMDARe, we analyzed all the patients with MOG-ab disease and NMDARe from our hospital from December 2018 to December 2019 and data from a systematical review of previously published reports. Details of the patients identified were summarized and literature was reviewed.Four of thirty (14.2%) patients with anti-NMDARe had overlapping MOG-ab disease in our department. Analyze together with previously reported cases. Thirty-two NMDARe patients had overlapping MOG-ab disease. The onset age ranged from 3 to 48 years. Twenty-four patients (74%) developed abnormal behavior or cognitive dysfunction during the episodes of anti-NMDARe. None of these patients had tumors. 84% (27/32) patients received high doses of steroids as first-line immunotherapy and 28% (9/32) received mycophenolate mofetil (MMF) to prevent relapse. Twenty-six of twenty-seven (96%) had a good outcome.Steroids are the most common first-line immunotherapies in NMDARe overlapping MOG-ab disease. Most of the NMDARe patients overlapping MOG-ab disease have a good prognosis.

The antipsychotic-like effects of clozapine in C57BL/6 mice exposed to cuprizone: Decreased glial activation.

Cuprizone (CPZ), a copper chelator that has been shown to selectively damage white matter, can induce a novel animal model to mimic some symptoms of schizophrenia. This study aimed to examine the effect of clozapine (CLZ) on behavioural changes induced by CPZ exposure and try to explore the underlying mechanisms. Behavioural abnormalities associated with feeding mice a 0.4% (w/w) CPZ-containing diet were assessed by Y-maze, spontaneous locomotor activity, and climbing tests. CLZ treatment reversed the increase in total explored distance, exploring velocity, locomotor movements, climbing behaviours and glial activation induced by CPZ exposure. Our findings indicate that increased glial activation may be related to behavioural abnormalities in CPZ exposure mice and that anti-inflammatory properties may be involved in the CLZ mechanisms. CPZ short-term exposure with a higher dosage may offer a useful model to study some aspects of schizophrenia and evaluate the efficacy of antipsychotics.

CSF-S100B Is a Potential Candidate Biomarker for Neuromyelitis Optica Spectrum Disorders.

Astrocytic impairment is a pathologic feature of neuromyelitis optica spectrum disorder (NMOSD). S100B and glial fibrillary acidic protein (GFAP) are the two most commonly used astrocytic markers. The aim of this study was to evaluate whether CSF-S100B could serve as a marker of NMOSD. We enrolled 49 NMOSD patients [25 aquaporin-4 antibody (AQP4-Ab)-positive, 8 myelin-oligodendrocyte glycoprotein antibody (MOG-Ab)-positive, and 16 seronegative patients], 12 multiple sclerosis (MS) patients, and 15 other noninflammatory neurological diseases (OND) patients. The CSF levels of S100B and GFAP were measured by ELISA. Both CSF-S100B and GFAP levels significantly discriminated NMOSD from MS [area under curve (AUC) = 0.839 and 0.850, respectively] and OND (AUC = 0.839 and 0.850, respectively). The CSF-S100B levels differentiated AQP4-Ab-positive NMOSD from MOG-Ab-positive NMOSD with higher accuracy than the CSF-GFAP levels (AUC=0.865 and 0.772, respectively). The CSF-S100B levels also significantly discriminated MOG-Ab-positive patients from seronegative patients (AUC = 0.848). Both CSF-S100B and GFAP levels were correlated with the Expanded Disability Status Scale (EDSS) during remission. Only the CSF-S100B levels were correlated with the CSF WBC count and the EDSS during attack. The levels of CSF-S100B seemed to have a longer lasting time than the levels of CSF-GFAP, which may benefit patients who present late. As a result, CSF-S100B might be a potential candidate biomarker for NMOSD in discriminating, evaluating severity, and predicting disability.

Change of Th17 Lymphocytes and Treg/Th17 in Typical and Atypical Optic Neuritis.

BACKGROUND: Typical and atypical optic neuritis (ON) are two clinical types of autoimmune inflammatory diseases of the optic nerve that causes acute vision loss, and are difficult to distinguish in their early stages. The disturbance in the balance of Th17 and Treg lymphocytes is thought to play an essential role in these autoimmune inflammatory diseases. OBJECTIVES: To detect the clinical relevance of Th17 and Treg in peripheral blood and the ratio of Treg/Th17 in patients with typical and atypical ON. To determine whether analysis of Th17 and Treg lymphocytes will provides insights into the different disease phenotypes of typical and atypical ON. METHODS: We studied a consecutive series of patients aged 14-70 years who presented to our neurological department with typical ON (n = 30) or atypical ON (n = 33) within 4 weeks of their acute attacks. Routine clinical tests and ophthalmological examination were performed in all patients. Blood samples were collected from untreated patients and from gender- and age-matched healthy controls (n = 30). The proportion of peripheral blood Th17 cells and Treg cells was determined by flow cytometry. RESULTS: Patients with atypical ON had a higher proportion of Th17 cells than patients with typical ON (3.61 ± 1.56 vs 2.55 ± 1.74, P<0.01) or controls (1.45 ± 0.86, P<0.01). The proportion of Th17 cells in patients with typical ON was also markedly higher than in controls (P<0.01). The mean percentage of Treg cells in atypical ON (6.31 ± 2.11) and typical ON (6.80 ± 2.00) were significantly lower when compared to controls (8.29 ± 2.32, both P<0.01). No significant difference in Treg frequency was observed between typical ON and atypical ON (p>0.05). CONCLUSIONS: The frequency of Th17 cells is higher in atypical ON than typical ON, and patients with atypical ON have a greater imbalance of pro-inflammatory and regulatory cells than patients with typical ON when compared with controls. These changes are indicative of distinct pathological mechanisms and may provide useful information to distinguish typical and atypical ON.

Neurological outcome and predictive factors of idiopathic optic neuritis in China.

BACKGROUND: The neurological outcome and predictive factors of idiopathic optic neuritis (ION) in China are largely unknown. OBJECTIVE: The aim of this paper is to study the neurological outcome of Chinese ION and to investigate the early predictors for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). METHOD: Retrospective medical record review and supplementary follow-up of 107 ION patients was performed. Statistical analysis of the baseline characteristics as risk factors for ION patients converting into MS or NMOSD was performed. RESULTS: With an average disease course of 9.5years, 19 of the 107 (17.7%) ION patients developed either MS (9, 8.4%) or NMOSD (10, 9.3%). The estimated 5-year and 10-year combined accumulative risk rates were 14.1% and 26.0%, respectively. Significantly higher estimated accumulative conversion risk was found in female versus male (P=0.047), adult versus children (P=0.032), patients with brain MRI lesions versus patients without leasions (P=0.026), patients with CSF positive oligoclonal bands and/or elevated IgG index versus without (P=0.003) and patients with poor visual recovery versus patients with good recovery (P=0.007). Furthermore, brain white matter lesions and good visual recovery were statistically more common typically in MS converters compared with the NMOSD converters (P=0.01 and P=0.006, respectively). CONCLUSION: The combined conversion rate for ION to MS/NMO in Chinese population was lower than the reported rate for Western countries. In addition to some previously reported high risk factors, white matter lesions on the brain MRI at baseline and good visual recovery were found to be good predictors for Chinese ION converting into MS whereas poor visual recovery with a normal brain MRI suggested a higher likelihood of the ION converting into NMOSD.