Brief research report: WGCNA-driven identification of histone modification genes as potential biomarkers in AQP4-Associated optic neuritis.

Introduction: Neuromyelitis Optica spectrum disorder (NMOSD) is an autoimmune disease characterized by anti-aquaporin-4 (AQP4) auto-antibodies. The discovery of antibodies AQP4 and myelin oligodendrocyte glycoprotein (MOG) has expanded our understanding of the pathogenesis of neuromyelitis optica. However, the molecular mechanisms underlying the disease, particularly AQP4-associated optic neuritis (AQP4-ON), remain to be fully elucidated. Methods: In this study, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the transcriptomic profiles of peripheral blood samples from patients with AQP4-ON and MOG-positive optic neuritis (MOG-ON), compared to healthy controls. Results: WGCNA revealed a brown module (ME brown) strongly associated with AQP4-ON, which correlated positively with post-onset visual acuity decline. A total of 132 critical genes were identified, mainly involved in histone modification and microtubule dynamics. Notably, genes HDAC4, HDAC7, KDM6A, and KDM5C demonstrated high AUC values in ROC analysis, indicating their potential as biomarkers for AQP4-ON. Conclusion: Our findings provide novel insights into the molecular signature of AQP4-ON and highlight the potential of systems biology approaches in identifying biomarkers for NMOSD. The identified histone modification genes warrant further investigation for their role in disease pathogenesis and as therapeutic targets.

Neuromyelitis Optica: A Peek Into the Brain Through the Eyes.

A rare demyelinating syndrome, known as neuromyelitis optica, is characterized by optic neuritis and transverse myelitis. A 27-year-old female presented to the eye department, with complaints of sudden progressive diminution of vision in both eyes (left eye more than right eye), acutely not being able to move both her eyes, double vision on lateral gazes with chronic dryness and irritation. Examination revealed restricted extraocular movements in all gazes. Magnetic resonance imaging of orbit showed retrobulbar optic neuritis. Blood tests revealed positive neuromyelitis optica myelin oligodendrocyte glycoprotein antibodies after which diagnosis of neuromyelitis optica was made.

Inter-tissue differences in oxidative stress susceptibility reveal a less stable endothelial barrier in the brain than in the retina.

Oxidative stress can impair the endothelial barrier and thereby enable autoantibody migration in Neuromyelitis optica spectrum disorder (NMOSD). Tissue-specific vulnerability to autoantibody-mediated damage could be explained by a differential, tissue-dependent endothelial susceptibility to oxidative stress. In this study, we aim to investigate the barrier integrity and complement profiles of brain and retinal endothelial cells under oxygen-induced oxidative stress to address the question of whether the pathomechanism of NMOSD preferentially affects the brain or the retina. Primary human brain microvascular endothelial cells (HBMEC) and primary human retinal endothelial cells (HREC) were cultivated at different cell densities (2.5*104 to 2*105 cells/cm2) for real-time cell analysis. Both cell types were exposed to 100, 500 and 2500 µM H2O2. Immunostaining (CD31, VE-cadherin, ZO-1) and Western blot, as well as complement protein secretion using multiplex ELISA were performed. HBMEC and HREC cell growth phases were cell type-specific. While HBMEC cell growth could be categorized into an initial peak, proliferation phase, plateau phase, and barrier breakdown phase, HREC showed no proliferation phase, but entered the plateau phase immediately after an initial peak. The plateau phase was 7 h shorter in HREC. Both cell types displayed a short-term, dose-dependent adaptive response to H2O2. Remarkably, at 100 µM H2O2, the transcellular resistance of HBMEC exceeded that of untreated cells. 500 µM H2O2 exerted a more disruptive effect on the HBMEC transcellular resistance than on HREC. Both cell types secreted complement factors H (FH) and I (FI), with FH secretion remaining stable after 2 h, but FI secretion decreasing at higher H2O2 concentrations. The observed differences in resistance to oxidative stress between primary brain and retinal endothelial cells may have implications for further studies of NMOSD and other autoimmune diseases affecting the eye and brain. These findings may open novel perspectives for the understanding and treatment of such diseases.

A Comprehensive Management of Devic's Disease: A Pediatric Case Study.

Devic's disease, also known as neuromyelitis optica (NMO), is an uncommon autoimmune condition that affects the optic nerves and spinal cord. It is characterized by recurrent optic neuritis and myelitis, which can cause paralysis and visual impairment. Because NMO mimics multiple sclerosis, diagnosing it is difficult and necessitates particular testing, such as magnetic resonance imaging (MRI) and aquaporin-4 antibody detection. Patients with NMOs are susceptible to severe, erratic episodes that can result in rapid impairment. As such, timely and efficient therapy with immunosuppressive medicines and continued supportive care are crucial. Improving mobility, strength, coordination, and quality of life while treating the functional deficiencies associated with NMOs requires the use of physiotherapy. This case study emphasizes how crucial it is to manage a young NMO patient using a multidisciplinary strategy in order to maximise results. This case report discusses a 16-year-old male presenting with a sudden onset of balance impairment, slurred speech, difficulty walking and breathing, and weakness in limbs, with the right side more affected. Over three months, he experienced increasing eyesight issues, fatigue, tremors during activities of daily living, difficulty swallowing, and night cramps. Diagnostic investigations including MRI, angiography, visual evoked potentials (VEP) study, and cerebrospinal fluid (CSF) analysis confirmed demyelinating changes consistent with NMO, also known as Devic's disease. The patient received management with steroidal medications, immunosuppressants, and plasma therapy, along with physiotherapy rehabilitation. The physiotherapy protocol aimed to address muscle weakness, coordination impairment, balance issues, fine motor deficits, fatigue, sensory impairment, and dependence on activities of daily living. Motor, sensory, and cranial nerve assessments were conducted, revealing impairments consistent with NMO. Outcome measures pre- and post-intervention showed improvements in functional independence, balance, and fatigue severity. The medical management included a combination of medications and investigations to manage NMO symptoms and monitor disease progression. The physiotherapeutic approach employed a multidisciplinary strategy focusing on education, exercise, and functional tasks to improve the patient's quality of life and independence.

Unravelling the Complexity of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disorder characterized by recurrent episodes of demyelination affecting the central nervous system. The following case report showcases a thorough analysis of a 21-year-old female patient presenting with MOGAD, outlining her clinical presentation, diagnostic workup, treatment protocol, and long-term management outcomes. Through a multidisciplinary approach, we aim to augment the understanding of this complex neurological entity and steer optimal therapeutic interventions.

Tumefactive Demyelinating Lesions: An Illustrative Pediatric Case With an Atypical Presentation and Literature Review.

Tumefactive demyelinating lesions remain a rare entity and a source of diagnostic difficulty. Here, we report the case of a teenage girl who presented with a one-month history of progressive quadriparesis and symptoms of intracranial hypertension. Brain MRI showed multiple large subcortical white matter lesions with both open- and closed-rim enhancement on gadolinium injection. The patient subsequently underwent a brain biopsy which showed an inflammatory infiltrate and no signs of malignancy. She was treated with pulse intravenous methylprednisolone at a dose of 500mg per day for five days and had rapid improvement. Her symptoms fully resolved after three months. This case highlights the need for better recognition and diagnosis of tumefactive demyelination, potentially avoiding unnecessary invasive diagnostic procedures such as brain biopsies.

Efgartigimod as rescue treatment in acute phase of neuromyelitis optica spectrum disorder: A Case Report.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD. Case presentation: We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period. Conclusion: As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.

Neuromyelitis Optica and Immune Thrombocytopenic Purpura Treated With Rituximab in a Patient With Combined Neurologic and Hematologic Disorder: A Case Report.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory demyelinating disease of the central nervous system affecting the optic nerves and spinal cord. Immune thrombocytopenia (ITP), on the other hand, is an autoimmune disorder characterized by a platelet count of <100 in the absence of any known condition that could be associated with thrombocytopenia. This case report focuses on a 56-year-old female presenting with the unique coexistence of NMOSD and ITP. A 56-year-old woman of Russian descent had a sudden onset of right eye blindness at the age of 24 and was diagnosed with multiple sclerosis. She developed petechial rashes on both lower extremities two weeks before consultation with no associated findings. Cranial MRI revealed multiple nodular and patchy areas of hyperintense signals on T2-weighted/fluid-attenuated inversion recovery without restricted diffusion. A thoracolumbar MRI revealed long segment foci of intramedullary cord non-enhancing abnormal hyperintense signal from T2 to T11. Cerebrospinal fluid aquaporin 4 IgG was negative. A complete blood count revealed platelets of 4 × 109/L, leading to the management of ITP. She was started on methylprednisolone 1 g/day for five days. Her platelet count improved eventually and rashes resolved. Rituximab treatment was initiated at a dose of 1 g on day 1 and day 15. On the 18th day of admission, the Expanded Disability Status Scale and functional score improved to 6.0 from 7.0 upon admission.

Double Seronegative Neuromyelitis Optica Spectrum Disorder with Longitudinally Extensive Transverse Myelitis and Optic Neuritis: A Challenging Case Report.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuroinflammatory disease of the central nervous system, typically manifesting in the optic nerves, spinal cord, and other regions of the central nervous system. We hereby report a case of a 16-year-old girl who presented with a six-month history of transverse myelitis with an acute episode of bilateral retrobulbar optic neuritis. MRI revealed patchy contrast enhancements over bilateral retrobulbar intraorbital optic nerves together with long-segment spinal cord hyperintensities (C2 to T2 level). Visual evoked potential testing during the acute presentation showed the absence of P100 bilaterally. However, both serum AQP4-IgG and MOG-IgG were reported to be negative. Despite remarkable improvement in bilateral optic nerve functions, she continued to have disabling bilateral lower limb spasticity, contractures, and loss of bilateral lower limb sensation after five cycles of plasma exchange. This case summarizes the challenges to diagnosing double seronegative NMOSD and its immediate therapeutic significance.

2.5D transfer deep learning model for segmentation of contrast-enhancing lesions on brain magnetic resonance imaging of multiple sclerosis and neuromyelitis optica spectrum disorder.

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are the two mimic autoimmune diseases of the central nervous system, which are rare in East Asia. Quantitative detection of contrast-enhancing lesions (CELs) on contrast-enhancing T1-weighted magnetic resonance (MR) images is of great significance for assessing the disease activity of MS and NMOSD. However, it is challenging to develop automatic segmentation algorithms due to the lack of data. In this work, we present an automatic segmentation model of CELs based on Fully Convolutional with Attention DenseNet (FCA-DenseNet) and transfer learning strategy to address the challenge of CEL quantification in small-scale datasets. Methods: A transfer learning approach was employed in this study, whereby pretraining was conducted using 77 MS subjects from the open access datasets (MICCAI 2016, MICCAI 2017, ISBI 2015) for white matter hyperintensity segmentation, followed by fine-tuning using 24 MS and NMOSD subjects from the local dataset for CEL segmentation. The proposed FCA-DenseNet combined the Fully Convolutional DenseNet and Convolutional Block Attention Module in order to improve the learning capability. A 2.5D data slicing strategy was used to process complex 3D MR images. U-Net, ResUNet, TransUNet, and Attention-UNet are used as comparison models to FCA-DenseNet. Dice similarity coefficient (DSC), positive predictive value (PPV), true positive rate (TPR), and volume difference (VD) are used as evaluation metrics to evaluate the performances of different models. Results: FCA-DenseNet outperforms all other models in terms of all evaluation metrics, with a DSC of 0.661±0.187, PPV of 0.719±0.201, TPR of 0.680±0.254, and VD of 0.388±0.334. Transfer learning strategy has achieved success in building segmentation models on a small-scale local dataset where traditional deep learning approaches fail to train effectively. Conclusions: The improved FCA-DenseNet, combined with transfer learning strategy and 2.5D data slicing strategy, has successfully addressed the challenges in constructing deep learning models on small-scale datasets, making it conducive to clinical quantification of brain CELs and diagnosis of MS and NMOSD.

Immunosuppressive therapy and COVID-19 infection in patients with NMOSD.

INTRODUCTION: To evaluate whether treated with immunosuppressants in neuromyelitis optica spectrum disorder (NMOSD) shows an effect on the severity and outcomes of COVID-19 Omicron variant. METHODS: This is a substudy of a single-center clinical trial involving human umbilical cord mesenchymal stem cells (hUC-MSCs) in NMOSD patients. NMOSD patients with hUC-MSCs treatment, NMOSD patients without hUC-MSCs treatment, and matched healthy controls (HC) were included. Demographic information, NMOSD-related clinical features, comorbidities, use of disease-modifying therapy, COVID-19 vaccination status, COVID-19 clinical features, COVID-19 clinical outcomes, and NMOSD-related disease activity were obtained through online questionnaires or phone calls. RESULTS: The majority of NMOSD patients received long-term treatment with mycophenolate mofetil (68.8%) or azathioprine (22.9%), and 50% received oral glucocorticoid. During the epidemic, 97.4% of NMOSD patients infected with COVID-19 had asymptomatic or mild forms, with only two patients (2.6%) requiring hospitalization. None of these patients required tracheal intubation or admission to the intensive care unit. Clinical symptoms were found to be more prevalent in HC groups. Additionally, the HC groups had higher fever-recorded temperatures. NMOSD patients who received hUC-MSCs treatment had shorter disease duration than patients who did not receive hUC-MSCs treatment. DISCUSSION: Immunosuppressant-treated patients with NMOSD have a similar risk of COVID-19 infection as the general population, but the disease duration is shorter and the clinical symptoms are less severe. Among our NMOSD patients who received hUC-MSCs treatment, COVID-19 outcomes were favorable, with no increased risk of severe COVID-19. Prospective studies on immunotherapies are needed to help determine best treatment practices.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Following Adenovirus Meningitis After First Delivery: Case Report and Literature Review.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a group of central nervous system (CNS) demyelinating diseases caused by autoantibodies against myelin oligosaccharide protein (MOG), a myelin sheath component protein, and present with a variety of symptoms, including optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, and corticobasal encephalitis. It is currently unknown at what point in life MOGAD can develop or how it can be triggered by autoimmune mechanisms. Here, we report a case of a mature woman who suffered from adenoviral meningitis one month after childbirth and developed MOGAD but was able to return to child rearing with high-dose methylprednisolone therapy. This case suggests that the risk of developing MOGAD early after childbirth may be increased. The case also suggested that adenoviral infection may be involved in the development of MOGAD.

An Observational Study of Multi-Faceted Demyelinating Disorders.

BACKGROUND AND OBJECTIVES: Idiopathic inflammatory demyelinating diseases of the central nervous system (IIDCDs) are wide-ranging disorders due to their similarities and differences. In order to address these conditions, studying their characteristics is essential. The endpoints of our study were to assess the incidence, presenting features, MRI findings, and predictors of disease progression of prevalent demyelinating disorders. MATERIAL AND METHODS: This prospective, observational study was conducted at Srirama Chandra Bhanja (SCB) Medical College and Hospital, India, from August 2018 to November 2021. Individuals of 18-65 years of age with common demyelinating disorders were assessed at baseline, six, 12, and 24 months. Univariate and multivariate analyses were performed for the assessment of predictors. We used R software (version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria) for data analysis. RESULTS: Two hundred twenty (79%) of 278 enrolled participants completed this study. The mean age of the study population was 52.3±11.4 years. One hundred thirty-eight (63%) of them were males. The most common IIDCD in our study was neuromyelitis optica spectrum disorder (NMOSD: 87, 39.5%), followed by multiple sclerosis (MS: 72, 32.7%), acute transverse myelitis (ATM: 35, 15.9%), and acute disseminated encephalomyelitis (ADEM: 26, 11.8%). The univariate analysis revealed that male gender, diabetes mellitus, and history of smoking or alcoholism were significant predictors of the disease progression. CONCLUSION: The IIDCDs were polysymptomatic at the initial presentation. Male diabetics are more prone to progressive disorders. However, multivariate analysis did not provide statistically significant results.

Potential Role of Antibodies against Aquaporin-1 in Patients with Central Nervous System Demyelination.

Aquaporins (AQPs; AQP0-AQP12) are water channels expressed in many and diverse cell types, participating in various functions of cells, tissues, and systems, including the central nervous system (CNS). AQP dysfunction and autoimmunity to AQPs are implicated in several diseases. The best-known example of autoimmunity against AQPs concerns the antibodies to AQP4 which are involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathy, causing also CNS demyelination. The present review focuses on the discovery and the potential role of antibodies against AQP1 in the CNS, and their potential involvement in the pathophysiology of NMOSD. We describe (a) the several techniques developed for the detection of the AQP1-antibodies, with emphasis on methods that specifically identify antibodies targeting the extracellular domain of AQP1, i.e., those of potential pathogenic role, and (b) the available evidence supporting the pathogenic relevance of AQP1-antibodies in the NMOSD phenotype.

An Atypical Presentation of Chronic Inflammatory Myelin Degeneration in Neuromyelitis Optica (NMO).

Neuromyelitis optica (NMO) is an autoimmune disorder characterized by aquaporin-4 (AQP4) IgG autoantibodies. These autoantibodies induce chronic neuroinflammatory damage to the spinal cord and optic nerve. NMO clinically manifests as relapsing and overlapping neurodegenerative episodes of optic neuritis (ON) and transverse myelitis (TM). Contrasting from other autoimmune neurodegenerative disorders, NMO has a poor prognostic profile often involving permanent neurological disability. We present a case of a 65-year-old male who presented with a progressive weakening in his left upper and lower extremities with reduced sensation and was found to have an acute flare of NMO. We explore the broad symptomatology involved in the disorder along with relevant crucial imaging findings pointing toward the diagnosis of NMO. Finally, we discuss treatment modalities in the context of our patient's clinical course and prognostic factors. Early intervention and suppression of relapse in this neuroinflammatory neurodegenerative disorder can help decrease the duration of acute flares and improve long-term outcomes for patients affected by NMO.

Diagnostic challenge in children with an acquired demyelinating syndrome: an illustrative case report.

The clinical-radiological and biological overlap of the spectrum of pediatric demyelinating disorders makes the diagnostic process of a child with an acquired demyelinating syndrome truly challenging. We present a 9-year-old girl with subacute symptoms of severe decrease in bilateral visual acuity and gait ataxia. An urgent MRI showed inflammatory-demyelinating lesions affecting the periaqueductal gray matter, the cerebellar hemispheres, the area postrema as well as both optic nerves and chiasm. Likewise, multisegmental involvement of the cervical and dorsal spinal cord was found, with short and peripheral lesions. Anti myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) were positive in cerebrospinal fluid (CSF) and weakly in serum. Oligoclonal bands (OB) were positive in CSF. Based on all this, the diagnosis of MOG antibody disease (MOGAD) with a neuromyelitis optica spectrum disorder (NMOSD)-like picture was made. Given the good clinical and radiological recovery after the acute phase treatment, and that anti MOG Abs became negative, it was decided to keep the patient without specific treatment. However, during follow-up, while the patient was asymptomatic, a control brain MRI showed the appearance of new lesions with morphology and topography suggestive of multiple sclerosis (MS). This, added to the presence of OB, made the diagnosis of pediatric-onset MS (POMS) likely. Immunosuppressive treatment was restarted with a good response since then. Unlike adult-onset MS, children with POMS may usually not have entirely typical clinical and radiological features at presentation. In many cases, the time factor and close clinical and radiological monitoring could be critical to make an accurate diagnosis.

Fahr's syndrome as a manifestation of autoimmune polyendocrine syndrome-1 and its unusual association with neuromyelitis optica spectrum disorder.

Fahr's syndrome, also known as bilateral striopallidodendate calcinosis, is a rare inherited neurodegenerative illness characterized by abnormal calcium deposition in several areas of the brain, resulting in a wide range of neuropsychological symptoms. Fahr's syndrome, secondary to autoimmune polyendocrine syndrome type 1, which includes adrenal insufficiency and mucocutaneous candidiasis in addition to hypoparathyroidism, is exceedingly rare. No case report has been documented to date to show the co-occurrence of Fahr's syndrome and neuromyelitis optica spectrum disorder. Here, we discuss the case of a 30-year-old man with a previous history of seizures and symptoms of ectodermal dystrophy presented with seizures, left-sided hemiparesis, dysarthria, and other characteristics indicative of severe hypocalcemia. The neuroimaging findings strongly suggested Fahr's syndrome, with radiographic evidence of Neuromyelitis optica spectrum disorder as longitudinal extensive transverse myelitis in the cervical spinal cord, high titers of serum aquaporin-4 antibodies, and demyelinating neuropathy on nerve conduction studies. This distinct neuropsychological presentation and neuroimaging findings led to the diagnosis of Fahr's syndrome as a result of hypoparathyroidism caused by autoimmune polyendocrine syndrome type 1 with cooccurrence of neuromyelitis optica spectrum disorder. The patient's clinical symptoms improved considerably after he was treated based on a provisional diagnosis. The clinical importance of our case is significant for both neuropsychiatrists and endocrinologists, as autoimmune polyendocrine syndrome should be considered as the etiology of Fahr's syndrome. This case report also aims to report this unusual association of Neuromyelitis optica spectrum disorder with Fahr's syndrome to give the future prospective to know whether this association is incidental or there is a missing link between these two different disorders.

Associations between neuromyelitis optica spectrum disorder, Sjögren's syndrome, and conditions with electrolyte disturbances.

OBJECTIVE: Electrolyte disorders are among the important conditions negatively affecting the disease course of neuromyelitis optica spectrum disorder (NMOSD). Possible mechanisms may include renal tubular acidosis (RTA) accompanying Sjögren's syndrome (SS), syndrome of inappropriate antidiuretic hormone secretion (SIADH), and central diabetes insipidus (DI). Currently, the overlap profiles between these conditions remain uncertain. METHODS: This cross-sectional study collected data from the nationwide administrative Diagnosis Procedure Combination (DPC) database and evaluated the overlap profiles. RESULTS: Among the 28,285,908 individuals from 1203 DPC-covered hospitals, 8477 had NMOSD, 174108 had SS, 4977 had RTA, 7640 had SIADH, and 24,789 had central DI. Of those with NMOSD, 986 (12%) had SS. The odds ratio (OR) for a diagnosis of NMOSD in those with SS compared with those without was 21 [95% confidence interval (CI), 20-23]. Overlap between NMOSD and SS was seen both in males (OR, 28 [95% CI, 23-33]) and females (OR, 16 [15-17]) and was more prominent in the younger population. Among patients with SS, the prevalence of RTA was lower in patients with NMOSD compared with those without NMOSD. Patients with NMOSD showed a higher prevalence of SIADH (OR, 11 [7.5-17]; p < 0.0001) and DI (OR, 3.7 [2.4-5.3]; p < 0.0001). Comorbid SS in NMOSD was associated with a higher prevalence of DI. CONCLUSIONS: Patients with NMOSD are likely to have SS, SIADH, and central DI. RTA in SS does not facilitate the overlap between NMOSD and SS. SS in NMOSD may predispose patients to DI.