Myelin oligodendrocyte glycoprotein associated disease (MOG-AD) is an inflammatory disorder of the central nervous system characterized by immune-mediated demyelination. We present a case of a patient with subacute to chronic progressive bilateral motor weakness associated with encephalopathy, which led to the diagnosis of MOG-AD. This case highlights the importance of recognizing the diverse clinical manifestations and the need for a multidisciplinary approach in the diagnosis and management of MOG-AD. In this review, we discuss the pathophysiology, diagnostic criteria, imaging findings, treatment strategies, and prognosis of MOG-AD based on the available literature.
Myelin-Oligodendrocyte Glycoprotein

Child ; Humans ; Myelin-Oligodendrocyte Glycoprotein

OBJECTIVE: To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens. METHODS: A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group ( RESULTS: For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% CONCLUSIONS More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.
Autoantibodies ; Child ; Humans ; Myelin-Oligodendrocyte Glycoprotein ; Optic Neuritis ; Recurrence ; Retrospective Studies

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. The aim of this study was to identify more genes associated with MS. METHODS: Based on the publicly available data of the single-nucleotide polymorphism-based genome-wide association study (GWAS) from the database of Genotypes and Phenotypes, we conducted a powerful gene-based GWAS in an initial sample with 931 family trios, and a replication study sample with 978 cases and 883 controls. For interesting genes, gene expression in MS-related cells between MS cases and controls was examined by using publicly available datasets. RESULTS: A total of 58 genes was identified, including 20 "novel" genes significantly associated with MS (p<1.40x10(-4)). In the replication study, 44 of the 58 identified genes had been genotyped and 35 replicated the association. In the gene-expression study, 21 of the 58 identified genes exhibited differential expressions in MS-related cells. Thus, 15 novel genes were supported by replicated association and/or differential expression. In particular, four of the novel genes, those encoding myelin oligodendrocyte glycoprotein (MOG), coiled-coil alpha-helical rod protein 1 (CCHCR1), human leukocyte antigen complex group 22 (HCG22), and major histocompatibility complex, class II, DM alpha (HLA-DMA), were supported by the evidence of both. CONCLUSIONS: The results of this study emphasize the high power of gene-based GWAS in detecting the susceptibility genes of MS. The novel genes identified herein may provide new insights into the molecular genetic mechanisms underlying MS.
Central Nervous System ; Dataset ; Gene Expression ; Genome-Wide Association Study* ; Genotype ; Humans ; Leukocytes ; Major Histocompatibility Complex ; Molecular Biology ; Multiple Sclerosis* ; Myelin-Oligodendrocyte Glycoprotein ; Phenotype

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and has long been used as an animal model for human multiple sclerosis. Development of EAE requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. Galectin-3 (Gal-3) is a member of the beta-galactoside-binding lectin family and plays an important role in inflammatory responses through its functions on cell activation, cell migration or inhibition of apoptosis. We investigated the functional role of Gal-3 in EAE mice following immunization with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. During the peak stage of EAE, the localization of Gal-3 in inflammatory cells markedly increased in subarachnoid membranes and perivascular regions of CNS. In contrast, Gal-3 was weakly detected in cerebrum and spinal of the recovery stage of EAE. Consistent with this finding, western blot analysis revealed that Gal-3 expression was significantly increased at the peak stage while it was slightly decreased at the recovery stage in the CNS. In addition, the population of CD11b+ macrophage expressing Gal-3 in spleen of EAE mice was markedly increased compared with control mice. In fact, most of activated macrophages isolated from spleen of EAE mice expressed Gal-3. Taken together, our results demonstrate that the over-expression of Gal-3 in activated macrophages may play a key role in promoting inflammatory cells in the CNS during EAE.
Animals ; Apoptosis ; Blotting, Western ; Cell Movement ; Central Nervous System ; Cerebrum ; Encephalomyelitis, Autoimmune, Experimental ; Galectin 3 ; Humans ; Immunization ; Macrophages ; Membranes ; Mice ; Models, Animal ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Spleen

BACKGROUNDWhether antibody to myelin oligodendrocyte glycoprotein (MOG) can be a diagnostic marker for multiple sclerosis (MS) is still controversial. Recent studies suggested that serum specific anti-MOG epitope antibody might be an MS specific marker. However, these studies did not include neuromyelitis optica (NMO) which might be proven to also have anti-MOG antibody. Hence, the present study was undertaken to investigate the clinical value of serum antibodies to 25 MOG epitopes in conventional MS (CMS) and NMO.

METHODSSerum anti-MOG epitope IgG was detected in 61 CMS patients, 54 NMO patients, and 77 healthy controls, using enzyme-linked immunosorbent assay (ELISA).

RESULTSAnti-MOG(27-38) IgG levels in both CMS and NMO patients were significantly higher than that in healthy controls (optical density (OD): 0.64 ± 0.38, 0.48 ± 0.23 vs. 0.19 ± 0.09; P = 0.000). CMS and NMO patients in relapse stage had significantly higher anti-MOG(27-38) IgG level than patients in remission stage (OD: 0.55 ± 0.14 vs. 0.24 ± 0.09, P = 0.027).

CONCLUSIONAlthough serum anti-MOG epitope IgG could not differentiate MS from NMO, it may be a useful marker for monitoring disease activity.

Adult ; Antibodies ; blood ; immunology ; Epitopes ; immunology ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis ; blood ; immunology ; Myelin-Oligodendrocyte Glycoprotein ; immunology ; Neuromyelitis Optica ; blood ; immunology

OBJECTIVE: To explore the model of chronic experimental autoimmune encephalomyelitis (EAE)for the further study of multiple sclerosis. METHODS: A total of 72 female SPF C57BL/6J mice (inbred strain, aged 8 approximately 10 weeks), were randomly divided into an EAE group, a blank group and an adjuvant group, and each group was divided into 3 subgroups: an onset group, a peak group and a chronic phase group. The EAE group was immunized with mMOG35-55. RESULTS: At the end of the study, and 83.3% of the mice in EAE group suffered the onset, and 8.3% of the mice died. The highest clinical score reached grade 5, namely paralysis of the whole body and then death. In the EAE group, after being immunized first, the mice were all anosis during the first 13 days. They got ill on the third week, and in about 20 approximately 24 days the clinical symptom reached the peak, and in 28 approximately 32 days the chronic phase arrived,when parts of the clinical symptoms got relieved. On the contrary, both the adjuvant group and the blank group were healthy all the time. Characteristic appearance was detected in the EAE group. CONCLUSION Antigen emulsion, mixture of artificially synthesized mMOG35-55 and complete Freundos adjuvant can successfully induce chronic EAE in the mice. The model of EAE duplicated in our study has the characteristics of high incidence, low death rate and stability, which can be used to carry out further research on multiple sclerosis.
Animals ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental ; chemically induced ; Female ; Freund's Adjuvant ; Glycoproteins ; Mice ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein ; Peptide Fragments ; Random Allocation

Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.
Animals ; Autoimmune Diseases ; Biomarkers ; Blotting, Western ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Humans ; Immunization ; Immunohistochemistry ; Inflammation ; Mice* ; Multiple Sclerosis ; Myelin Sheath ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Recurrence ; Spinal Cord ; Tacrolimus*

OBJECTIVE: To explore the therapeutic effect of Fasudil-modified splenic mononuclear cells (MNCs) in experimental autoimmune encephalomyelitis (EAE) and the possible mechanisms.
 METHODS: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to establish active immunity EAE model. Splenic MNCs were isolated on the 9th day after immunization and treated with or without Fasudil for 72 h in vitro. These cells were collected for analysis of the variance of T cell subtypes, the level of cytokines and the activity of Rho kinase (ROCK). MNCs (5×107 cells) were resuspended in 500 µL of phosphate buffer solution (PBS) and transferred into EAE model (intraperitoneal injection), which was divided into a PBS-MNCs group and a Fasudil-MNCs group. Changes of body weight and clinical symptom scores were observed.
 RESULTS: Splenic encephalitogenic MNCs from EAE mice on the 9th day after immunization could establish passive transfer EAE model. But Fasudil-treated MNCs did not trigger EAE development. Compared with the PBS-MNCs group, the loss of body weight was less in the Fasudil-MNCs group. The in vitro experiment indicated that Fasudil could suppress the activity of ROCK on MNCs (P<0.01), decrease the percentage of CD4+ T cells with the expression of interferon-γ (IFN-γ) and interleukin-17 (IL-17) (IFN-γ: P<0.01; IL-17: P<0.05), while increase the secretion of CD4+ T cells with the expression of transforming growth factor-β (TGF-β) and IL-10 (all P<0.001) . Furthermore, Fasudil could inhibit the release of IL-17 (P<0.001) and enhance the level of IL-10 (P<0.05).
 CONCLUSION Fasudil-modified cell therapy affects the occurrence and development of EAE by inhibiting the inflammatory reaction of helper T cell 1 (Th1) and Th17 while enhancing the immunoregulative effect of Th2.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; Female ; Interferon-gamma ; Interleukin-10 ; Interleukin-17 ; Mice ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; T-Lymphocytes ; Transforming Growth Factor beta ; rho-Associated Kinases

BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.
Animals ; Blotting, Western ; Central Nervous System ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental ; Mice ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Neuroprotective Agents ; Nitric Oxide Synthase Type II ; Spinal Cord ; Treatment Outcome ; Up-Regulation