ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.

Glial autoantibody prevalence in Chinese optic neuritis with onset after age 45: clinical factors for diagnosis.

Purpose: As glial autoantibody testing is not yet available in some areas of the world, an alternative approach is to use clinical indicators to predict which subtypes of middle-aged and elderly-onset optic neuritis (ON) have manifested. Method: This study was a single-center hospital-based retrospective cohort study. Middle-aged and elderly-onset ON patients (age > 45 years) who had experienced the first episode of ON were included in this cohort. Single- and multi-parametric diagnostic factors for middle-aged and elderly-onset myelin oligodendrocyte glycoprotein immunoglobulin-associated ON (MOG-ON) and aquaporin-4 immunoglobulin-related ON (AQP4-ON) were calculated. Results: From January 2016 to January 2020, there were 81 patients with middle-aged and elderly-onset ON, including 32 (39.5%) AQP4-ON cases, 19 (23.5%) MOG-ON cases, and 30 (37.0%) Seronegative-ON cases. Bilateral involvement (47.4%, P = 0.025) was most common in the MOG-ON group. The presence of other concomitant autoimmune antibodies (65.6%, P = 0.014) and prior neurological history (37.5%, P = 0.001) were more common in the AQP4-ON group. The MOG-ON group had the best follow-up best-corrected visual acuity (BCVA) (89.5% ≤ 1.0 LogMAR, P = 0.001). The most sensitive diagnostic factors for middle-aged and elderly-onset MOG-ON were 'follow-up VA ≤ 0.1 logMAR' (sensitivity 0.89), 'bilateral involvement or follow-up VA ≤ 0.1 logMAR' (sensitivity 0.95), 'bilateral involvement or without neurological history' (sensitivity 1.00), and 'follow-up VA ≤ 0.1 logMAR or without neurological history' (sensitivity 1.00), and the most specific factor was 'bilateral involvement' (specificity 0.81). The most sensitive diagnostic factors for middle-aged and elderly-onset AQP4-ON were 'unilateral involvement' (sensitivity 0.88), 'unilateral involvement or neurological history' (sensitivity 0.91), and 'unilateral involvement or other autoimmune antibodies' (sensitivity 1.00), and the most specific factor was neurological history (specificity 0.98). Conclusion: Based on our cohort study of middle-aged and elderly-onset ON, MOG-ON is less prevalent than AQP4-ON and Seronegative-ON. Using multiple combined parameters improves the sensitivity and negative predictive value for diagnosing middle-aged and elderly-onset MOG-ON and AQP4-ON. These combined parameters can help physicians identify and treat middle-aged and elderly-onset ON early when glial autoantibody status is not available.

Upregulation of C-X-C motif chemokine 12 in the spinal cord alleviated the symptoms of experimental autoimmune encephalomyelitis in Lewis rats.

Background: C-X-C motif chemokine 12 (CXCL12) is a chemokine that performs many functions. Studies have shown that CXCL12 can aggravate inflammatory symptoms in the central nervous system (CNS). Evidence also indicates that CXCL12 can promote the repair of myelin sheaths in the CNS in experimental autoimmune encephalomyelitis (EAE). Here, we investigated the function of CXCL12 in CNS inflammation by upregulating CXCL12 in the spinal cord and subsequently inducing EAE. Materials and methods: CXCL12 upregulation in the spinal cords of Lewis rats was induced by the injection of adeno-associated virus 9 (AAV9)/eGFP-P2A-CXCL12 after intrathecal catheter implantation. Twenty-one days after AAV injection, EAE was induced and clinical score was collected; Immunofluorescence staining, WB and LFB-PAS staining were used to evaluate the effect of CXCL12 upregulation. In the in vitro study, oligodendrocyte precursor cells (OPCs) were harvested, cultured with CXCL12 and AMD3100, and subjected to immunofluorescence staining for functional assessment. Results: CXCL12 was upregulated in the lumbar enlargement of the spinal cord by AAV injection. In each stage of EAE, upregulation of CXCL12 significantly alleviated clinical scores by inhibiting leukocyte infiltration and promoting remyelination. In contrast, the addition of AMD3100, which is a CXCR4 antagonist, inhibited the effect of CXCL12. In vitro, 10 ng/ml CXCL12 promoted the differentiation of OPCs into oligodendrocytes. Conclusion: AAV-mediated upregulation of CXCL12 in the CNS can alleviate the clinical signs and symptoms of EAE and significantly decrease the infiltration of leukocytes in the peak stage of EAE. CXCL12 can promote the maturation and differentiation of OPCs into oligodendrocytes in vitro. These data indicate that CXCL12 effectively promotes remyelination in the spinal cord and decreases the signs and symptoms of EAE.

Update on glial antibody-mediated optic neuritis.

Optic neuritis (ON) refers to inflammatory demyelinating lesions of the optic nerve, which can cause acute or subacute vision loss and is a major cause of vision loss in young adults. Much of our understanding of typical ON is from the Optic Neuritis Treatment Trial. Glial autoantibodies to aquaporin-4 immunoglobulin (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin (MOG-IgG) are recently established biomarkers of ON that have revolutionized our understanding of atypical ON. The detection of glial antibodies is helpful in the diagnosis, treatment, and follow-up of patients with different types of ON. AQP4-IgG and MOG-IgG screening is strongly recommended for patients with atypical ON. Research on the pathogenesis of NMOSD and MOGAD will promote the development and marketing of targeted immunotherapies. The application of new and efficient drugs, such as the selective complement C5 inhibitor, IL-6 receptor inhibitor, B cell-depleting agents, and drugs against other monoclonal antibodies, provides additional medical evidence. This review provides information on the diagnosis and management of glial antibody-mediated ON.

MOG antibody prevalence in adult optic neuritis and clinical predictive factors for diagnosis: A Chinese cohort study.

OBJECTIVE: Because AQP4/MOG antibody testing is not available in some parts of the world and there are often delays in obtaining results, it is particularly important to use clinical factors to predict the subtypes of adult optic neuritis (ON). METHODS: This was a single-center retrospective cohort study. RESULTS: The final analysis included 249 adult patients presenting with the first ON attack during January 2016 to January 2020. These included 109 (43.8%) AQP4-ON cases, 49 (19.7%) MOG-ON cases, and 91 (36.5%) Seronegative-ON cases. The proportion of optic disk swelling (ODS) and bilateral involvement in MOG-ON group was significantly higher than in the other two subgroups (P = 0.029, 0.001). The MOG-ON group had the best follow-up BCVA (P = 0.003). To predict adult AQP4-ON, unilateral involvement (sensitivity 0.88, NPV 0.77) was the most sensitivity predictors, while neurological history (specificity 0.96, PPV 0.65) and concomitant other autoimmune antibodies (specificity 0.76, PPV 0.65) were the most specific predictors. Using the parallel test 'unilateral or other autoimmune antibodies' increased sensitivity to 0.95, with an optimal NPV of 0.88. To predict adult MOG-ON, the most sensitive clinical characteristics were ODS (sensitivity 0.79, NPV 0.88), and follow-up VA ≤0.1logMAR (sensitivity 0.78, NPV 0.92), whereas the most specific values were prior neurological history or bilateral involvement, with specificities of 0.92 and 0.82, respectively. The sensitivity increased to 0.94, 0.97, and 0.97 when using the parallel clinical factors of 'bilateral or ODS or relapse', 'bilateral or ODS or follow-up VA ≤0.1logMAR', and 'ODS or follow-up VA ≤0.1logMAR', and the corresponding NPV (0.94, 0.97 vs 0.98). CONCLUSION: The proportion of MOG-ON (19.7%) was less than that of AQP4-ON and Seronegative-ON. Moreover, MOG-ON had a better prognosis and was more likely to be associated with ODS or bilateral involvement. The use of parallel clinical parameters improved the sensitivity for the diagnosis of adult MOG-ON and AQP4-ON.

Efficacy of Plasma Exchange Treatment for Demyelinating Optic Neuritis Associated with Various Serum Antibodies: A Prospective Cohort Study.

INTRODUCTION: To evaluate the value of plasma exchange (PE) for patients with three subtypes of demyelinating optic neuritis (ON): aquaporin-4 (AQP4) antibody-positive ON (AQP4-ON), myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON (MOG-ON), and AQP4 and MOG double-antibody-seronegative ON (D-ON). METHODS: A single-center prospective study compared the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at most severe onset, 1 day before intravenous high-dose methylprednisolone (IVMP) treatment, 1 day before PE treatment, after five-cycles of PE therapy, and at 1-, 3-, and 6-month follow-up visits. The proportions of eyes in each visual outcome category were also compared. Logistic regression and a receiver operating characteristic curve were used to analyze predicted factors for VA improvement. RESULTS: A total of 124 ON attacks of 122 patients were included. No significant differences were found in BCVA (P = 0.659) before and after PE therapy for 22 D-ON attacks, but VA improved in two of six MOG-ON patients. In 95 AQP4-ON patients suffering 96 attacks, the mean logMAR BCVA markedly improved and was steadily maintained after five-cycles of PE treatments (adjusted P < 0.001), with VA exhibiting a significantly increasing trend (adjusted P = 0.001) after PE treatment. The combination of the number of previous ON episodes and the time window to PE treatment showed accuracy of 74.7% for predicting an improvement in BCVA score ≥ 2 levels. In addition, a combination of logMAR VA before PE and the time window to PE treatment resulted in 83.4% accuracy in predicting whether VA would regain 1.0 logMAR. CONCLUSION: PE therapy effectively improves visual outcomes for AQP4-ON patients, but offers limited value for D-ON patients. Early initiation greatly increases likelihood of achieving VA improvement.

Comparative analysis of immunosuppressive therapies for myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: a cohort study.

AIMS: The optimal immunosuppressive therapy (IST) in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) remains uncertain. This study aimed to observe the disease course of MOG-ON and evaluate the therapeutic efficacy and tolerability of conventional immunosuppressants through Chinese cohort analysis. METHODS: This bidirectional cohort study included 121 patients with MOG-ON between January 2015 and December 2018. The clinical features and annualised relapse rate (ARR) of patients with and without IST were analysed. RESULTS: The median age at onset was 17.5 years, and the sex ratio (F:M) was 1.24. Of 121 patients, 77 patients relapsed and 61 patients were younger than 18 years at disease onset. The overall median ARR of 63 patients in the non-IST group was 0.5, with 46.0% patients showing relapse at a median follow-up of 33.5 months. In the IST group, the ARR decreased from 1.75 pre-IST to 0.00 post-IST in 53 patients who received IST exceeding 6 months, with 20.8% patients showing relapse at a median follow-up of 23.8 months. The relapse rates of patients treated with rituximab (RTX) and mycophenolate mofetil (MMF) were not statistically different, but the rate of discontinuation was significantly lower in the RTX-treated group (18.2% vs 57.7%, p=0.0017). CONCLUSION: This study provides Class III evidence that both MMF and RTX may lower disease activity in patients with MOG-ON, and RTX showed better tolerability than MMF. However, observation after a single attack remains a good option because less than half of patients not on treatment suffered a relapse.

Clinical predictive factors for diagnosis of MOG-IgG and AQP4-IgG related paediatric optic neuritis: a Chinese cohort study.

BACKGROUND: Different glial-autoantibodies-related paediatric optic neuritis (ON) are associated with different clinical characteristics and prognosis that require different treatments. Because glial autoantibody detection is not available in some parts of the world and there is often a delay in obtaining results, clinical factors that can be used to predict the subtype of paediatric ON are needed. METHODS: This was a single-centre retrospective cohort study. Children who presented with their first ON attack and with complete clinical data were included in the analysis. Single and multiple parameters for predicting paediatric myelin oligodendrocyte glycoprotein immunoglobin-associated ON (MOG-ON) and aquaporin-4 immunoglobin-related ON (AQP4-ON) were calculated. RESULTS: 78 paediatric patients had their first ON attack from January 2016 to December 2019, of whom 69 were included in the final analysis, including 33 MOG-ON cases, 17 AQP4-ON cases and 19 Seronegative-ON cases. For predicting paediatric MOG-ON, the most sensitive predictors were 'male or optic disc swelling (ODS) or bilateral' (sensitivity 0.97 (95% CI 0.82 to 1.00)) and 'follow-up visual acuity (VA) ≤0.1 logMAR or ODS' (sensitivity 0.97 (95% CI 0.82 to 1.00)), and the most specific factor was 'Age ≤11 y and simultaneous CNS involvement' (specificity 0.97 (95% CI 0.84 to 1.00)). For predicting paediatric AQP4-ON, the most sensitive predictor was 'Female or without ODS' (sensitivity 1.00 (95% CI 0.77 to 1.00)), and the most specific factors were Neurological history (sensitivity 0.94 (95% CI 0.83 to 0.98)) and follow-up VA >1.0 logMAR (sensitivity 0.96 (95% CI 0.86 to 0.99)). CONCLUSION: According to our data from a Chinese paediatric cohort, using multiple parameters increases the sensitivity and specificity of diagnosing paediatric MOG-ON and AQP4-ON. These can assist clinicians in diagnosing and treating paediatric ON when glial autoantibody status is not available.

Vision Prognosis and Associated Factors of Optic Neuritis in Dependence of Glial Autoimmune Antibodies.

PURPOSE: To assess the visual prognosis of optic neuritis (ON) in dependence of the glial autoimmune antibody status and associated factors. DESIGN: Longitudinal observational cohort study. METHODS: Patients with ON and measurements of serum concentrations of glial autoantibodies were consecutively and longitudinally examined with a minimal follow-up of 3 months. Patients with multiple sclerosis and double seronegative results were excluded. RESULTS: The study included 529 patients (aquaporin-4 immunoglobulin [AQP4-IgG] seropositive, n = 291; myelin oligodendrocyte glycoprotein immunoglobulin [MOG-IgG] seropositive, n = 112; double-seronegative, n = 126) with 1022 ON episodes (AQP4-IgG seropositive, n = 550; MOG-IgG seropositive, n=254; double-seronegative, n = 218). Prevalence of severe vision loss (best-corrected visual acuity [BCVA] ≤20/200 at the end of follow-up) was higher (P < .001) in the AQP4-IgG group (236/550; 42.9%) than in the seronegative group (68/218; 31.2%) and in the MOG-IgG group (15/254; 5.9%). Prevalence of good vision recovery (BCVA≥20/40) was higher (P < .001) in the MOG-IgG group (229/254; 90.2%) than in the seronegative group (111/218; 50.9%) and in the AQP4-IgG group (236/550; 42.9%). In multivariable logistic analysis, higher prevalence of severe vision loss was associated with AQP4-IgG seropositivity (odds ratio [OR] 1.66; 95% CI 1.14, 2.43; P = .008), male sex (OR 1.97, 95% CI 1.33, 2.93; P < .001), age at ON onset >45 years (OR 1.93, 95% CI 1.35, 2.77; P < .001), nadir vision ≤20/200 (OR 14.11, 95% CI 6.54, 36.93; P < .001), and higher number of recurrences (OR 1.35, 95% CI 1.14, 1.61; P = .001). Higher prevalence of good vision outcome was associated with MOG-IgG seropositivity (OR 8.13, 95% CI 4.82, 14.2; P < .001), age at ON onset <18 years (OR 1.78, 95% CI 1.18, 2.71; P = .006), nadir visual acuity ≥20/40 (OR 4.03; 95% CI 1.45, 14.37; P = .015), and lower number of recurrences (OR 0.60; 95% CI 0.50, 0.72; P < .001). CONCLUSION: Severe vision loss (prevalence in the AQP4-IgG group, MOG-IgG group, and seronegative group: 42.9%, 5.9%, and 31.2%, respectively) was associated with AQP4-IgG seropositivity, male gender, older age at onset, worse nadir vision, and higher number of recurrences.

Leber's hereditary optic neuropathy companied with multiple-related diseases.

Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases. Materials and methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018. Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time. Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.

Serial analyses of clinical spectra and outcomes in Chinese women with pregnancy-induced optic neuritis.

Objective: This study aimed to investigate the clinical spectra and outcomes in pregnancy-related optic neuritis (ON). Methods: We analyzed the clinical subtype and prognosis of women with pregnancy-related ON in the neuro-ophthalmology department of the First Medical Center at the Chinese PLA General Hospital from January 2014 to December 2019. Results: A total of 54 patients, including 21 (38.9%) with idiopathic ON (ION), 27 (50.0%) with aquaporin-4 (AQP4)-ON, and 6 (11.6%) with myelin oligodendrocyte glycoprotein (MOG)-ON, who experienced 58 informative pregnancies and 67 episodes of pregnancy-related ON were assessed. Among the ON attacks, there were 11 (16.4%) during pregnancy and 56 (83.6%) within 1 year postpartum (PP1) or after abortion, including 33 (49.3%) in the first trimester. In total, 14 (25.9%) patients with ON onset before pregnancy had a higher relapse rate during PP1 than within 1 year before pregnancy (p = 0.021), and 24 (85.7%) eyes with ION and nine (100%) with MOG-ON had significantly better visual outcomes (p ≥ 0.5) than those with AQP4-ON (14, 35%) (p < 0.001 and p < 0.001, respectively). Two AQP4-ON patients had premature birth and low baby weight, respectively. There were no birth defects or stillbirths. Conclusion: The significantly increased relapse rate and numerous cases of ON after pregnancy suggest that delivery adversely affects the course of ON.

Differences in the involved sites among different types of demyelinating optic neuritis in traditional MRI examination: A systematic review and meta-analysis.

Background: Magnetic resonance imaging (MRI) plays a significant role in assessing optic neuropathy and providing more detailed information about the lesion of the visual pathway to help differentiate optic neuritis from other visual disorders. This study aims to systematically review the literature and verify if there is a real difference in lesion location among different demyelinating optic neuritis (DON) subtypes. Methods: A systematic search was conducted including 8 electronic databases and related resources from the establishment of the database to August 25th, 2020. We classified DON into 5 subtypes and divided the visual pathways into five segments mainly comparing the differences in the involved visual pathway sites of different subtypes. Results: Fifty-five studies were included in the analysis, and the abnormal rate was as high as 92% during the acute phase (within 4 weeks of symptom onset). With respect to lesion location, the orbital segment of the optic nerve was the most frequently involved (87%), whereas optic tract involvement was very rare. Involvement of the orbital segment was more common in myelin oligodendrocyte glycoprotein antibody-related optic neuritis (MOG-ON) (78%) and chronic relapsing inflammatory optic neuropathy (CRION) (81%), while the lesion was found to be located more posteriorly in neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON). With respect to lesion length, approximately 77% of MOG-ON patients had lesions involving more than half of the optic nerve length. Conclusions: MRI examination is recommended for DON patients in the acute phase. In MOG-ON, anterior involvement is more common and the involved length is mostly more than 1/2 of the optic nerve length, whereas posterior involvement, intracranial segment, optic chiasm, or optic tract, is more common in NMOSD-ON. Prospero registration number: CRD42020222430 (25-11-2020).

Orbital Magnetic Resonance Imaging May Contribute to the Diagnosis of Optic Nerve Lymphoma.

Background: Optic nerve lymphoma can present a diagnostic challenge because of its confusing clinical features and the difficulty of obtaining lesion tissue for biopsy. The objective of this study was to find some flags of lymphomatous infiltration of optic nerves. Methods: We report two cases of optic nerve lymphoma and conduct a literature review to determine whether a common diagnostic characteristic can be identified. Results: We examined 22 optic nerve lymphoma cases. Thirteen cases were systemic lymphoma infiltration of the optic nerve, five were primary central nervous system lymphoma (PCNSL), and four were primary isolated optic nerve lymphoma. Twenty patients manifested significant enlargement of the lesions in orbital/brain MRI. Seventeen contrast-enhanced MRIs showed abnormal enhancement of the optic nerve. All PCNSL and isolated optic nerve lymphoma patients in the series showed marked enhancement. Moderate and subtle enhancement was found in systemic lymphoma patients only. At the enhancement site, six isolated optic nerve lymphoma and PCNSL patients presented intrinsic enhancement, ten systemic patients showed both optic nerve and sheath enhancement, and one demonstrated sheath enhancement. Cerebrospinal fluid (CSF) tests showed elevated protein levels in six patients, and a neoplasm in one patient. We found abnormality of CSF immunity in both of our patients. Conclusion: Combined characteristics of orbital MRI and CSF tests may facilitate expeditious suspicion establishment of optic nerve lymphoma.

Clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein antibody-seropositive optic neuritis in varying age groups: A cohort study in China.

PURPOSE: To investigate the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein antibody-seropositive optic neuritis (MOG-ON) in patients with varying ages of onset in China. METHODS: Patients displaying symptoms of MOG-ON were recruited from the Neuro-ophthalmology Department in the Chinese People's Liberation Army General Hospital from January 2016 to May 2018. They were assigned to one of three subgroups based on age of onset: pediatric (<18 years), young (18-46 years), and middle-aged (>46 years) MOG-ON. RESULTS: 110 patients (188 eyes) were assessed, including 58 pediatric (52.7%), 34 young (30.9%), and 18 middle-aged (16.4%) patients. Of the pediatric patients, 93.9% had good recovery of visual acuity (≥0.5) compared with 79.7% of young patients and 66.7% of middle-aged patients (p < .001). The annual relapse rate was lower in the pediatric group than young and middle-aged groups (0.32 ±â€¯0.50 vs 0.73 ±â€¯0.87 vs 0.49 ±â€¯1.08, p = .036). Six children (10.3%) were diagnosed with acute disseminated encephalomyelitis, while seven young patients (20.6%) were diagnosed with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder upon follow-up. The average peripapillary RNFL and macular GCIPL thicknesses were not statistically different between subgroups (p = .996, p = .608). Overall, MRIs of the optic nerve showed perineural enhancement in 52.0% of patients and longitudinal extensive involvement in 87.7%. MRIs also revealed a greater proportion of pediatric patients with intracranial optic nerve involvement than in the other two subgroups (45.4% vs. 21.2% vs. 36.7%, p = .014). CONCLUSION: Pediatric ON was the most common MOG-ON subgroup. Pediatric patients had different clinical features, including better recovery of visual acuity, lower annual relapse rate, and more intracranial optic nerve involvement than young and middle-aged patients. Additionally, age of onset may be a potential predictor for determining visual prognosis with MOG-ON.

Cytokines and chemokines expression in serum of patients with neuromyelitis optica.

OBJECTIVE: To study the differences in immunopathogenesis based on chemokine profile in neuromyelitis optica patients positive for AQP4 antibodies or MOG antibodies. PATIENTS AND METHODS: We measured 52 cytokines/chemokines using ELISA in 59 serum samples, which were divided into three groups according to CBA results: HCs (n=16), AQP4+ (n=20) and MOG+ (n=23). The regression equation (R 2>0.98) of the standard curve was calculated according to the standard concentration and the corresponding A value. And then the corresponding sample concentration was calculated according to the A value of the sample. RESULTS: Eleven of 52 measured serum cytokine/chemokines (CCL22/MDC, CCL13/MCP-4, CCL21/6Ckine, CCL27/CTACK, CCL8/MCP-2, CXCL14/BRAK, Contactin-1, Kallilrein 6/Neurosin, Midkine, VCAM-1 and Fas) were significantly different between MOG+ group and controls. Ten of 52 measured serum cytokine/chemokines (CCL1/I-309, CCL22/MDC, CCL28, CCL17/TARC, CCL27/CTACK, CXCL2/GRO beta, Contactin-1, Midkine, Chemerin and Synuclein-alpha) were significantly different between AQP4+ group and controls. There was no difference between serum AQP4+ and MOG+ groups for CC chemokines. All measured chemokines CXC except CXCL6/GCP-2 showed no significant differences in serum AQP4+ group compared to MOG+ group. However, there was significant difference between serum AQP4+ and MOG+ groups for C5/C5a and Midkine. C5/C5a and Midkine were significantly higher in AQP4+ group compared to MOG+ group (P<0.05). CONCLUSION: Our findings suggest that the differences of mean concentration in CXCL6/GCP-2, Midkine and C5/C5a probably reveal different immunologic mechanism between AQP4+ NMO and MOG+ NMO. This cytokine/chemokine profiling provides new insight into NMO pathogenesis associated with MOG antibody seropositivity and provides guidance to monitor inflammation and response to treatment in a way.

Clinical characteristics and prognosis of myelin oligodendrocyte glycoprotein antibody-seropositive paediatric optic neuritis in China.

BACKGROUND/AIMS: To investigate clinical characteristics and prognosis of paediatric optic neuritis (PON) in patients seropositive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in China. METHODS: Children displaying initial onset of optic neuritis (ON) were recruited from the Neuro-ophthalmology Department in the Chinese People's Liberation Army General Hospital from January 2016 to August 2017. They were assigned into three groups based on antibody status: MOG-Ab-seropositive ON (MOG-ON), aquaporin-4 antibody-seropositive ON (AQP4-ON) and double seronegative ON (seronegative-ON). RESULTS: Totally 48 patients were assessed, including 25 MOG-ON (52.1%), 7 AQP4-ON (14.6%) and 16 seronegative-ON (33.3%). The MOG-ON and seronegative-ON cohorts had equal ratios of female/male, but the AQP4-ON cohort was predominantly females (100%). The patients with MOG-ON were significantly younger at onset compared with the AQP4-ON group. Of the MOG-ON eyes, 97.6% had good recovery of visual acuity (VA) (≥0.5) compared with33.3% of AQP4-ON eyes (p<0.001). However, there was no significant difference compared with the seronegative-ON eyes (82.6%, p=0.052). Two children in the MOG-ON group ended up being diagnosed with acute disseminated encephalomyelitis, while only one patient in the AQP4-ON group developed neuromyelitis optica during follow-up. Patients with MOG-ON had thicker peripapillary retinal nerve fibre layers overall and in the superior and inferior quadrants than in patients with AQP4-ON (p=0.005, p=0.002 and p=0.024, respectively). In addition, the macular ganglion cell-inner plexiform in MOG-ON eyes became significantly thicker than in AQP4-ON eyes (p=0.029). Orbital MRI revealed a larger proportion of patients with MOG-ON had intracranial optic nerve involvement than patients with seronegative-ON (51.2% vs 17.4%, p=0.009). CONCLUSION: MOG-ON was the most common PON subtype in China. MOG-ON had different clinical features including earlier age of onset, equal female/male ratio, better recovery of VA and thicker peripapillary retinal nerve fibre and macular ganglion cell-inner plexiform layers. MOG-Abs may be a potential biomarker for determining visual prognosis with PON.

Distinct clinical characteristics of paraneoplastic optic neuropathy.

OBJECTIVE: Paraneoplastic optic neuropathy (PON) is relatively uncommon, and the visual outcomes and prognosis of this disease have not been well documented. The aim of this study was to investigate the clinical features and prognosis of antibody-mediated PON. METHODS: Clinical data were retrospectively collected from hospitalised patients diagnosed with PON at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital from January 2015 to June 2017. RESULTS: A total of seven patients (four females and three males, 13 involved eyes) were included with a mean age of 56.28±11.32 years (36-70 years). Simultaneous or early sequential bilateral eye involvement (5/7, 71.4%) was common in the patients with PON. Severe vision loss (≤0.1) was seen in 76.9% (10/13) of the eyes. There were 13 eyes in the acute phase of the disease, and six eyes presented with optic disc oedema. All patients had definite evidence of paraneoplastic-associated antibodies (three with serum positive for antiamphilphysin, one for anti-PNMA2 (Ma2/Ta), one for anti-Yo, one for anti-Ma2 and one for anti-CV2). All of the serum samples were negative for myelin oligodendrocyte glycoprotein antibody and two patients companied with seropositive for the aquaporin-4 antibody. Five patients had history of primary malignancy, including thyroid cancer, type B thymoma, testicular seminoma, cervical cancer and lung carcinoma. Two patients had positive paraneoplastic syndrome antibodies (anti-Yo and antiamphiphysin), but the solid tumour had not been found through a PET scan. Visual acuity in 9/13 (69.2%) eyes was below 0.1, and all of the patients survived to the follow-up with no metastatic lesions. CONCLUSIONS: PON is relative rare, with a predominance of bilateral involvement and more with a poor visual prognosis. Paraneoplastic antibody testing can contribute to the diagnosis of PON, distinct from other types of optic neuropathies, which can help doctors to find the primary cancer earlier to guide further treatment.

Different Characteristics of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody-Seropositive Male Optic Neuritis in China.

PURPOSE: To describe different clinical characteristics and prognosis of optic neuritis (ON) in male patients with seropositive aquaporin-4 antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in China. METHOD: Males with ON were recruited from the Neuro-ophthalmology Department of the Chinese People's Liberation Army, General Hospital from January 2016 to February 2018. They were assigned to two groups based on antibodies status: MOG-Ab-seropositive ON (MOG-ON) and aquaporin-4 Ab-seropositive ON (AQP4-ON). RESULTS: Seventy-six male patients were assessed, including 44 MOG-ON (57.9%) and 32 AQP4-ON (42.1%). The MOG-ON patients were significantly younger at onset compared to the AQP4-ON group (p < 0.001). Frequencies of optic disc swelling, presence of abnormal autoimmune antibodies, and elevated levels of CSF IgG were significantly higher in the AQP4-ON group than the MOG-ON group (p=0.040, p=0.016, and p=0.10, respectively). At the final visit, 85.3% of MOG-ON eyes had increased visual acuity (≥0.5) compared to 35.1% of AQP4-ON eyes (p < 0.001). The ratio of this steroid-dependent condition is higher in MOG-ON patients than the AQP4-ON group (p < 0.001). The ratio of conversion to NMO is higher in the AQP4-ON group than the MOG-ON group, with more AQP4-ON patients developing NMO by the follow-up (p=0.012). MOG-ON patients had thicker average peripapillary retinal nerve fiber layers and macular ganglion cell-inner plexiform than AQP4-ON patients (p=0.008 and p=0.012, respectively). Orbital MRI revealed more AQP4-ON patients had chiasmal involvement than MOG-ON patients (p < 0.001). CONCLUSION: Male MOG-ON patients had different clinical features including earlier age of onset, higher optic disc swelling ratio, better visual acuity recovery, thicker peripapillary retinal nerve fiber and macular ganglion cell-inner plexiform layers, and less chiasmal involvement than male AQP4-ON patients. Serum antibody may be a potential biomarker for determining visual prognosis in male ON.

The prevalence and prognostic value of myelin oligodendrocyte glycoprotein antibody in adult optic neuritis.

BACKGROUND AND OBJECTIVE: Adult demyelinating optic neuritis (ON) with positive myelin-oligodendrocyte glycoprotein antibody (MOG-Ab) has distinct clinical features. This study aimed to investigate the point prevalence, relationship with steroid dependency and prognosis value of MOG-Ab in adult ON. METHODS: Clinical data analysis was undertaken in adults with ON admitted between December 2014 and January 2016. Patients were classified into three groups based on aquaporin-4 antibody (AQP4-Ab) and MOG-Ab status: AQP4-ON, MOG-ON and seronegative-ON. RESULTS: A total of 158 adults with ON (190 eyes) were assessed, including 31 MOG-ON (19.6%), 67 AQP4-ON (42.4%) and 60 seronegative-ON (38.0%) cases. The female-to-male ratio was significantly lower in MOG-ON (1.8:1) than that in AQP4-ON (8.6:1) groups (p = .005). The median age, percentage of bilateral ON and visual loss at the nadir at onset was similar among the three groups. Thirty-eight eyes (76%) in the MOG-ON group showed good visual recovery (>20/40) in the final visit, which is statistically better than that in the AQP4-ON and seronegative-ON groups (p < .001 and p = .006, resoectively). Fifteen adults with ON (9.5%) showed dependency on steroid, which was particularly prominent in the MOG-ON group (11/31, 35.5%) and rarely presented in the AQP4-ON (2, 3.0%) and seronegative-ON (2, 3.3%) groups. Results suggested less loss of pRNFL in MOG-ON than that in AQP4-ON group (p < .001), and a larger proportion of canalicular segment involved in MOG-ON adults (p = .007 and p < .001). CONCLUSION: MOG-ON had the smallest proportion of acute demyelinating ON in Chinese adults. One third of adults with MOG-ON predominantly showed a substantial dependency on steroids and relapse on steroid reduction or cessation, which rarely presented in AQP4-ON and seronegative-ON adults.