Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.

Research and progress on biomarkers of neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are a demyelinating disorder of the central nervous system based on the involvement of the optic nerve and/or spinal cord. The disease is characterized by high recurrence and disability. NMOSD is mainly diagnosed by AQP4-IgG and MOG-IgG. However, there are still some patients with negative or undetermined double-antibody, and AQP4-IgG and MOG-IgG cannot indicate the clinical disease activity. Therefore, it is urgent to explore interesting biomarkers in serum and cerebrospinal fluid to promote early clinical diagnosis and/or as a target for diagnosis and treatment. This article summarized the research progress in serum and cerebrospinal fluid biomarkers of astrocytes, neurons, myelin sheath, and other damage after the onset of NMOSD. Besides the value of microglial activation-related proteins in the diagnosis and treatment of NMOSD was prospected, so as to promote the research progress of NMOSD.

Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus: A predominantly population-based study.

BACKGROUND: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. OBJECTIVE: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE. METHODS: The study included a predominantly population-based cohort with clinical and serological investigations of 208 patients with SLE, followed prospectively since 1995. All patients received immunosuppressive treatment. NMOSD was evaluated retrospectively based on the 2015 International Panel for NMOSD Diagnosis (IPND) criteria. Polymorphisms in programmed cell death protein 1 (PDCD-1) PD-1.3 G/A were genotyped. AGP4-IgG and other autoantibodies, including myelin oligodendrocyte glycoprotein (MOG), was determined blinded to clinical diagnosis. RESULTS: Of 208 patients with SLE, 45(22%) had neuropsychiatric (NP) SLE, and CNS involvement predominated in 30 of 45 (67%) patients. Serum AQP4-IgG was detected in 2 of 30 (6.7%) neuropsychiatric SLE (NPSLE) patients both of whom had myelitis and antiphospholipid syndrome; one patient also had myasthenia gravis. None had MOG-IgG. PD-1.3A allele was not associated with SLE nor with NPSLE. CONCLUSION: AQP4-IgG autoimmune syndrome may rarely co-exist with SLE, and such patients have other NMOSD-typical syndromes such as myelitis.

A population-based prospective study of optic neuritis.

BACKGROUND: Optic neuritis (ON) is often associated with multiple sclerosis (MS). Early diagnosis is critical to optimal patient management. OBJECTIVE: To estimate the incidence of acute ON and the rates of conversion to MS and antibody-mediated ON. METHOD: Population-based prospective study was performed in patients with ON from three ophthalmological departments and 44 practicing ophthalmologists from 2014 to 2016. Ophthalmological and neurological examination, magnetic resonance imaging (MRI), determination of aquaporin-4(AQP4)-IgG and myelin-oligodendrocyte glycoprotein (MOG)-IgG were investigated blindly. RESULTS: In all, 63 patients were evaluated and 51 fulfilled the criteria for ON. All were Caucasian, with female:male ratio of 2.2:1 and a median age of 38 years (16-66); 44 (86%) had a single episode of ON (four bilateral), while 7/51 (14%) had recurrent ON. The overall age-specific incidence was 3.28 (2.44-4.31) per 100,000 person years, 2.02 for men and 4.57 for women. At follow-up, 20 patients met the diagnostic criteria for MS, MRI lesions disseminated in space and time in 17/20 patients. AQP4-IgG was detected in none, MOG-IgG was detected in two patients. CONCLUSION: The prospective incidence of ON was estimated. MRI enabled a diagnosis of MS in a subgroup of patients. Antibody-mediated ON with specificity for MOG was detected in 4% of cases.

Therapeutic plasma exchange for neuromyelitis optica attacks: Evidence and challenges from a real-world cohort from Brazil.

Therapeutic plasma exchange (TPE) can improve disability recovery after neuromyelitis optica spectrum disease (NMOSD) attacks, but its effectiveness and safety in Latin-American patients with access barriers and diverse ethnicity is underexplored. We carried out a retrospective cohort study with NMOSD patients that underwent TPE. 84 NMOSD attacks in 68 patients were evaluated. Despite a median 25-day delay from symptom onset to TPE, 65,5% of patients showed significant improvement. Adverse events occurred in 39% of patients, usually transitory and with no fatalities.

Vitamin D status and neuromyelitis optica spectrum disease: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: There's an increasing body of evidence on vitamin D deficiency and the risk of neuromyelitis optica spectrum disorder (NMOSD). The aim of this meta-analysis was to assess serum vitamin D levels in patients with NMOSD versus healthy controls. METHODS: We searched PubMed, EMBASE, Cochrane Library, Web of Science and CNKI for publications up to November 2022 and explored the relationship between NMOSD and serum vitamin D levels. The standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Begg's test, Egger's test, and Egger's funnel plot were adopted to evaluate publication bias. RESULTS: 6 studies (including 319 patients and 595 healthy controls) met the inclusion criteria and all compared vitamin D levels in patients with NMOSD versus healthy controls. Levels of serum vitamin D detected in NMOSD patients were significantly lower than those in healthy controls (SMD=-1.57, 95% CI=-2.27 ∼ -0.87, P<0.001, I2 = 94.6%). The results of the different sensitivity analysis remained statistically significant, which demonstrated the robustness of the meta-analysis. There was no significant publication bias in our meta-analysis (P>0.05). CONCLUSION: Patients with NMOSD showed significantly reduced vitamin D levels compared with healthy controls. Our findings highlighted the importance of measuring vitamin D levels in patients with NMOSD. Multi-center randomized controlled trials with large samples will further confirm whether the association is casual and modifiable.

Rituximab Therapy for Double Seronegative Neuromyelitis Optica Spectrum Disease.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system disease presenting as optic neuritis, myelitis, and brainstem syndromes. It may be aquaporin-4 seropositive, anti-myelin oligodendrocyte glycoprotein (MOG) antibody seropositive, or double seronegative. Double-seronegative NMOSD can pose a diagnostic and therapeutic challenge. Treatment typically aims to decrease the incidence of relapse, for which high-dose intravenous methylprednisolone is the first-line agent. Non-steroid treatments include azathioprine, mycophenolate mofetil, and rituximab. This case describes a 45-year-old female presenting with left arm numbness and weakness for three months. She had been previously diagnosed with optic neuritis in 2013 but was lost to follow-up. Progression of weakness warranted admission to the neurology department. Diagnostic work and imaging were suggestive of neuromyelitis optica. Tests for aquaporin-4, anti-MOG, immunoglobulin G, and immunoglobulin M in the cerebrospinal fluid were all negative. Initial treatment comprised methylprednisolone; however, due to the progression of symptoms, she was given two cycles of rituximab. Rituximab targets the CD20 antigen in B cells and is thought to reduce the risk of relapse and the severity of NMOSD. The patient's Barthel index score, expanded disability status scale score, and motor examination improved after two cycles of rituximab.

A Comparative Review of Typical and Atypical Optic Neuritis: Advancements in Treatments, Diagnostics, and Prognosis.

Optic neuritis (ON) is a debilitating condition that through various mechanisms, including inflammation or demyelination of the optic nerve, can result in partial or total permanent vision loss if left untreated. Accurate diagnosis and promptly initiated treatment are imperative related to the potential of permanent loss of vision if left untreated, which can lead to a significant reduction in the quality of life in affected patients. ON is subtyped as "typical" or "atypical" based on underlying causative etiology. The etiology of ON can be differentiated when appropriate diagnostic testing is performed. Using history taking, neuroimaging, and visual testing to localize the underlying pathology of ON in a time-sensitive manner is critical in mitigating these unsatisfactory outcomes. Herein, we examine the differences in presentation, pathophysiology, and treatments of typical ON causes, like multiple sclerosis (MS), and atypical causes such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) ON. The present investigation places focus on both neuroimaging and visual imaging in the differentiation of ON. Additionally, this review presents physicians with a better understanding of different presentations, treatments, and prognoses of ON.

The Characteristics of Cognitive Proficiency in Patients with Acute Neuromyelitis Optica Spectrum Disease and its Correlation with Serum Aquaporin-4 Antibody Titer.

Objective: To explore the characteristics and dynamic evolution of cognitive impairment in patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: Twenty-five patients with acute NMOSD and 30 age-matched healthy individuals were consecutively recruited in this study. The Montreal Cognitive Assessment (MoCA), Chinese Version of Rey Auditory Vocabulary Learning Test (CRAVLT), Verbal Fluency Test (VFT), Digital Span Test (DST), Paced Auditory Serial Addition Task 3/2s version (PASAT-3/2), Rey−Osterrieth Complex Figure Test (ROCF) and Stroop Color and Word Test (CWT) were used to evaluate cognitive function. The correlations between cognitive function and serum aquaporin-4 (AQP-4) antibody titer were analyzed. Results: Sixty-four percent of patients with acute NMOSD had cognitive dysfunction. MoCA (p < 0.001), CRAVLT-N7 (p = 0.004), CRAVLT-N8 (p = 0.011), ROCF-C (p = 0.005), ROCF-R (p < 0.001), PASAT-3 (p = 0.013), PASAT-2 (p = 0.001) and CWT-A (p = 0.017) were significantly worse in patients with acute NMOSD than those in control group. During follow-up visits, significant differences of serum AQP-4 antibody titers were still noted in NMOSD patients (p < 0.001), while no significant differences were found by MoCA. Conclusion: A high number of patients with acute NMOSD suffer from cognitive dysfunction. Serum AQP-4 antibody titers can decrease during disease remission, while obvious cognitive decline in these patients still exists.

Clinical Characteristics and Outcomes of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder With Brainstem Lesions as Heralding Prodrome.

Objective: The present study sought to differentiate multiple sclerosis and neuromyelitis optica spectrum disorder patients at their first attack by describing and distinguishing their clinical features, radiographic characteristics, and immunologic characteristics of serum and cerebrospinal fluid. Methods: We retrospectively studied 58 patients with multiple sclerosis (MS) and 52 patients with neuromyelitis optica spectrum disorder (NMOSD) by referencing brainstem lesions as the prodromal events. Their demographics and presentation at the time of the first attack was evaluated including their gender, age, clinical features of the first attack, the expanded disability status scale (EDSS), brainstem lesion(s) by head MRI, and immunological indices of serum and cerebrospinal fluid. Results: The NMOSD group had more female patients (4.8 vs. 1.9, p < 0.05), and was older than the MS group (37.81 ± 16.60 vs. 27.57 ± 11.17, p <0.001). NMOSD patients also had a significantly higher association with autoimmune diseases or positive autoimmune antibodies (p < 0.01). There was no significant difference in the EDSS scores between the two groups (p = 0.420). Central hiccups, vomiting, and pyramidal tract signs were more common in the NMOSD group than the MS group (p < 0.001, p < 0.001, p < 0.01), while eye movement abnormalities were more common with MS (p < 0.01). There were no significant differences in other clinical manifestations such as vertigo, diplopia, limb weakness, numbness, and eating difficulty. MS patients were more likely to have midbrain and pons imaging lesions (p < 0.001, p < 0.001), while NMOSD patients had more lesions in the medulla oblongata (p < 0.001). The lesions in the MS group were mostly located in the periphery, while those in the NMOSD group were centrally located (p < 0.001, p < 0.001). Patchy lesions were more common in MS patients (p < 0.001), while large lesions were more common in the NMOSD group (p < 0.001). Finally, serum AQP4 Ab was found only in the NMOSD group (p < 0.001). Conclusion: Patients with MS and NMOSD have differentiating clinical manifestations at the time of their first brainstem lesions which include central hiccups, vomiting, pyramidal tract signs, and abnormal eye movements. Additionally, distinct imaging manifestations such as lesion location(s) and morphology may also aid in the development of pathognomonic criteria leading to timely initial diagnosis of MS and NMOSD.

Aquaporin 4-positive neuromyelitis optica spectrum disorder with meningoencephalitis-like onset: A case report.

Neuromyelitis optica spectrum disease (NMOSD) is a debilitating autoimmune inflammatory demyelinating disease of the central nervous system. The relationship between harboring an infection and NMOSD is currently unclear and needs further investigation. This article reports meningoencephalitis-like manifestations, including fever, headache, neck resistance, seizures, and pleocytosis, accompanied by nausea and vomiting, in a patient with serum AQP4 antibody-positive area postrema syndrome (APS). In the presence of aseptic meningitis combined with clinical symptoms such as optic neuritis and myelitis, the possibility of NMOSD diagnosis can be considered. However, for patients with unknown causes, especially combined with aseptic meningitis, a probable differential diagnosis of NMOSD is considered.

COVID-19 Vaccination Attitudes With Neuromyelitis Optica Spectrum Disorders: Vaccine Hesitancy and Coping Style.

Background: Vaccination is an important method by which to stop the spread of coronavirus disease 2019 (COVID-19) in a population. Patients with neuromyelitis optica spectrum disorders (NMOSD) have unstable immune function and receive immunosuppressive therapy frequently, so they are hardly to make a decision to receive vaccination. Our study investigated the vaccine hesitancy and coping styles in patients with NMOSD to analyze the relationship between vaccine hesitancy and coping styles, and elucidate the factors influencing vaccine hesitancy. Methods: A convenient sampling method was used to recruit participants. The Adult Vaccine Hesitancy Scale and Medical Coping Modes Questionnaire were used to measure the vaccine hesitancy and coping style of the participants. Pearson correlation, multiple stepwise, linear regression, and one-way analysis of variance were used to analyze the data. Results: A total of 262 NMOSD patients were investigated. The score of vaccine hesitancy in NMOSD patients is lower (21.13 ± 4.355) than 25 points which indicated the patient is not considered to have vaccine hesitancy. The score for vaccine hesitancy was negatively correlated with the confrontation and avoidance coping styles (r = -0.481 and r = 0.423). That adoption of the coping styles of confrontation and avoidance as well as the residence of the patient were predictors of vaccine hesitation in NMOSD patients (R 2(adj) = 0.29, P < 0.001). In addition, the vaccine hesitancy scores of NMOSD patients residing in rural areas were significantly higher than those of patients living in urban areas (P < 0.01). Comparing with each level of education, the scores were not statistically significant in vaccine hesitancy and coping styles (P > 0.05). Conclusions: This study reveals that the NMOSD patients is not considered to have vaccine hesitancy, Patients who tend to adopt confrontation and avoidance coping styles have less vaccine hesitancy. Health authorities and medical specialist teams should strengthen effective vaccination information for patients with NMOSD, such as expert consensus or guidelines through various media to help them with decision-making. The significance of vaccination, the safety and side effects of COVID-19 vaccination and predicting of epidemiological trends of COVID-19 should be emphasized. More attention should be paid to NMOSD patients who living in rural areas.

Evaluation of Thiol Homeostasis in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

Objectives: The aim of this pilot study was to evaluate dynamic thiol-disulfide homeostasis as a novel oxidative stress parameter in multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) to better understand the role of thiol homeostasis in neuroimmunological diseases. Methods: A total of 85 participants were included in this study, consisting of 18 healthy controls, 52 patients diagnosed with MS, seven with NMOSD, and eight with MOGAD. We measured total thiol (-SH+-S-S-) and native thiol (-SH) levels in the serum of all the participants, and in a subset of patients (n = 11), these parameters were investigated in paired cerebrospinal fluid (CSF) and serum samples. Dynamic disulfide concentrations were calculated separately. Finally, we determined if there was any relationship between clinical features and dynamic thiol homeostasis. Results: There was a statistically significant difference between serum and CSF levels of biomarkers of thiol homeostasis. Serum total thiol (317.88 ± 66.04) and native thiol (211.61 ± 44.15) levels were significantly lower in relapsed patients compared to those in remission (368.84 ± 150.36 vs. 222.52 ± 70.59, respectively). Conclusions: Oxidative stress plays a crucial role in the physiopathology of neuroimmunological diseases. Thiol homeostasis may be useful for monitoring disease activity.

Comparative Study of Brain fMRI of Olfactory Stimulation in Neuromyelitis Optica Spectrum Disease and Multiple Sclerosis.

Objective: To observe the characteristics of brain fMRI during olfactory stimulation in patients with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS), compare the differences of brain functional activation areas between patients with NMOSD and MS, and explore the characteristics of olfactory-related brain networks of NMOSD and MS. Methods: Nineteen patients with NMOSD and 16 patients with MS who met the diagnostic criteria were recruited, and 19 healthy controls matched by sex and age were recruited. The olfactory function of all participants was assessed using the visual analog scale (VAS). Olfactory stimulation was alternately performed using a volatile body (lavender and rose solution) and the difference in brain activation was evaluated by task-taste fMRI scanning simultaneously. Results: Activation intensity was weaker in the NMOSD group than in the healthy controls, including the left rectus, right superior temporal gyrus, and left cuneus. The activation intensity was stronger for the NMOSD than the controls in the left insula and left middle frontal gyrus (P < 0.05). Activation intensity was weaker in the MS group than the healthy controls in the bilateral hippocampus, right parahippocampal gyrus, right insula, left rectus gyrus, and right precentral gyrus, and stronger in the left paracentral lobule among the MS than the controls (P < 0.05). Compared with the MS group, activation intensity in the NMOSD group was weaker in the right superior temporal gyrus and left paracentral lobule, while it was stronger among the NMOSD group in the bilateral insula, bilateral hippocampus, bilateral parahippocampal gyrus, left inferior orbital gyrus, left superior temporal gyrus, left putamen, and left middle frontal gyrus (P < 0.05). Conclusion: Olfactory-related brain networks are altered in both patients, and there are differences between their olfactory-related brain networks. It may provide a new reference index for the clinical differentiation and disease evaluation of NMOSD and MS. Moreover, further studies are needed.

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG).

Neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AE), myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are antibody-mediated neurological diseases. They have mostly female predominance, affecting many women during childbearing age. Interactions between the underlying disease (or necessary treatment) and pregnancy can occur in every of these illnesses. Herein, we present the characteristics of NMOSD, AE, MG and LEMS in general, and review published data regarding the influence of the different diseases on fertility, pregnancy, puerperium, treatment strategy during pregnancy and post-partum period, and menopause but also male factors. We summarise key elements that should be borne in mind when confronted with such cases.

Different alteration patterns of sub-macular choroidal thicknesses in aquaporin-4 immunoglobulin G antibodies sero-positive neuromyelitis optica spectrum diseases and isolated optic neuritis.

PURPOSE: The ocular choroid is a sensitive biomarker of vascular perfusion in optic neuritis (ON) patients due to its vascular structures. The purpose of this study was to evaluate alterations in sub-macular choroidal thicknesses (sub-MCT) in aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) sero-positive neuromyelitis optica spectrum disease (AQP4-IgG+/NMOSD) and isolated ON (ION) patients using optical coherence tomography (OCT). METHODS: A total of 208 ON patients (275 eyes) and healthy controls (HCs) who underwent sub-MCT and retinal microstructure detection with OCT were enrolled in this study. RESULTS: Among all the ON patients, 102 (49.0%) cases were identified as serum AQP4-IgG-positive, with 106 (51.0%) cases being negative, excluding multiple sclerosis as the ION cohort. The sub-MCT in the AQP4-IgG+/NMOSD patients decreased in 0-6 months after ON attacks. However, for the ION cohort, the sub-MCT decreased in 0-2 months and then stayed normal or slightly increased in 2-4 months after the first ON attack, finally sharply decreasing after 6 months. For unilateral AQP4-IgG+/NMOSD patients, eyes without ON also presented retinal layer thinning and sub-MCT slight reduction independent of ON attacks. CONCLUSIONS: The sub-MCT in AQP4-IgG+/NMOSD patients were reduced at all stages of ON, which distinguished the ION patients as decreasing only at chronic stage of ON. It implied that ocular vascular hypoperfusion plays a potential role in ON pathogenesis and the different patterns could be caused by the distinct pathogenesis of AQP4-IgG+/NMOSD and ION.

Epidemiology of neuromyelitis optica spectrum disorder in Denmark (1998-2008, 2007-2014).

Epidemiological studies of the uncommon disorder neuromyelitis optica spectrum disorder (NMOSD) may be difficult to interpret because of the evolving nature of diagnostic criteria, differences in the definition and accuracy of NMOSD diagnosis, the completeness of case ascertainment, and variability in assays for the disease-specific biomarker aquaporin-4 (AQP4)-IgG. A sub-group of patients with the clinical syndrome NMOSD lack detectable AQP4-IgG and in these cases an accurate diagnosis requires precise diagnostic algorithms and longitudinal follow-up. Consecutive sets of criteria for NMO/NMOSD have been introduced during the two last decades. Such criteria need validation in different populations. Detection of other autoantibodies, such as IgG specific for myelin oligodendrocyte glycoprotein or for glial fibrillary acidic protein in a sub-group of AQP4-IgG-negative NMOSD patients, has improved over the past decade and may lead to overlap of the clinical syndromes/phenotypes. This review begins by summarizing current knowledge on the widening clinical spectrum of NMOSD. Subsequently, we describe two epidemiological studies from Denmark carried out in two different decades (1998-2008 and 2007-2014) and comment on the differences in study design, patient ascertainment, and interpretation of results. These factors may explain some of the observed differences, reflecting the complexity and providing a clear example of this development.

Long-term tolerability, safety and efficacy of rituximab in neuromyelitis optica spectrum disorder: a prospective study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a B-cell-mediated disease with autoimmunity towards the astrocyte water channel aquaporin-4 (AQP-4) in the central nervous system. OBJECTIVE: To assess the long-term safety and efficacy in NMOSD patients receiving maintenance therapy with B-cell-depleting agent rituximab for more than 2 years. METHOD: NMOSD patients were included prospectively from 2014 to 2018 and received continuous cycles of rituximab infusions biannually. Incidence of adverse events (AE), serious AEs (SAE), and infusion-related AEs were evaluated through monthly phone calls and neurological examination every 4 months. RESULTS: A total of 44 NMOSD patients were included, of those 30 were treatment naive (68%). The mean age was 37.2 years with 79.5% females. With overall observation period of 31.6 ± 7.3 months (24-48 months), tolerability was assessed as satisfactory in most cases. We observed infusion reactions (mostly mild) in 31.8% of patients and 31.8% never experienced any AEs after a mean 5.1 cycles of rituximab therapy. Rituximab was also beneficial in terms of improvement in relapse rate (from 0.26 ± 0.54 to 0, P = 0.003) and Expanded Disability Status Scale (from 4.1 ± 1.8 to 3.1 ± 1.8, P < 0.001). Stratification according to AQP4-IgG serostatus showed no difference between groups. CONCLUSION: Rituximab treatment is well tolerated, safe, and efficacious with a minor risk of mild infusion reactions for NMOSD patients.

Clinical Characteristics, Treatment Outcomes and Predictive Factors in Optic Neuritis.

BACKGROUND: The causes, clinical presentations and treatment outcomes of optic neuritis are distinct among different populations. Early diagnosis based on clinical presentations plays an important role in treating optic neuritis patients. OBJECTIVE: The study aimed to determine clinical characteristics, treatment outcomes and predictive factors of treatment outcomes in optic neuritis patients with and without demyelinating disease. METHODS: A retrospective descriptive study of optic neuritis patients carried out between January 2009 and December 2016 was done. Univariate analysis and multivariate logistic regression analysis were used to evaluate the predictive factors of treatment outcomes. RESULTS: Among 150 patients with optic neuritis, 58 patients were diagnosed with Neuromyelitis Optica Spectrum Disease (NMOSD), 23 patients were diagnosed with Multiple Sclerosis (MS) and 69 patients were idiopathic. The age at presentation in the NMOSD group was significantly younger than the MS group and the idiopathic group. The female:male ratio was significantly lower in the idiopathic group than in the NMOSD group. The initial Best Corrected Visual Activity (BCVA) of 20/20-20/60 (p = 0.001) and the idiopathic group (p =0.030) was associated with good visual outcomes. Initial BCVA of < 20/200 (p = 0.009) and the NMOSD group (p < 0.001) was associated with poor visual outcomes. CONCLUSION: NMOSD is a more common cause of optic neuritis than MS in Thai population. Female patients with poor initial VA, poor response to steroids treatment, and presenting recurrent attacks are highly suspicious for NMOSD. Optic neuritis without associated demyelinating disease has a better visual outcome and lower recurrence rate.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Inflammatory demyelinating CNS syndromes include, besides their most common entity multiple sclerosis (MS), several different diseases of either monophasic or recurrent character-including neuromyelitis optica spectrum disorders (NMOSDs) and acute disseminated encephalomyelitis (ADEM). Early diagnostic differentiation is crucial for devising individual treatment strategies. However, due to overlapping clinical and paraclinical features diagnosis at the first demyelinating event is not always possible. A multiplicity of potential biological markers that could discriminate the different diseases was studied. As the use of autoantibodies in patient management of other autoimmune diseases, is well-established and evidence for the critical involvement of B cells/antibodies in disease pathogenesis in inflammatory demyelinating CNS syndromes increases, antibodies seem to be valuable diagnostic tools. Since the detection of antibodies against aquaporin-4 (AQP-4), the understanding of immunopathogenesis and diagnostic management of NMOSDs has dramatically changed. However, for most inflammatory demyelinating CNS syndromes, a potential antigen target is still not known. A further extensively studied possible target structure is myelin oligodendrocyte glycoprotein (MOG), found at the outermost surface of myelin sheaths and oligodendrocyte membranes. With detection methods using cell-based assays with full-length, conformationally correct MOG, antibodies have been described in early studies with a subgroup of patients with ADEM. Recently, a humoral immune reaction against MOG has been found not only in monophasic diseases, but also in recurrent non-MS diseases, particularly in pediatric patients. This review presents the findings regarding MOG antibodies as potential biological markers in discriminating between these different demyelinating CNS diseases, and discusses recent developments, clinical implementations, and data on immunopathogenesis of MOG antibody-associated disorders.