Neuromyelitis Optica Spectrum Disorder Research Articles

Identification of neurotransmitter imbalances in the cingulate cortex of NMOSD patients using magnetic resonance spectroscopy.

Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT).

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

Differentiating multiple sclerosis and neuromyelitis optica spectrum disorders through pontine trigeminal nerve lesions: A comparative MRI study

PurposeMultiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two major demyelinating diseases affecting the central nervous system (CNS). The objective of this study is to evaluate the prevalence of pontine trigeminal nerve lesions in patients diagnosed with MS and NMOSD using MRI. MethodsThis retrospective study included patients diagnosed with MS or NMOSD between July 2018 and July 2023. MS patients were clinically diagnosed using the 2017 McDonald criteria, while NMOSD patients were those who met the 2015 International Panel for NMO Diagnosis (IPND) criteria and were positive for Aquaporin-4 Antibody (AQP4-Ab). ResultsThe study included a total of 90 patients, with 45 diagnosed with MS and another 45 with NMOSD. Pontine trigeminal nerve lesions were observed in both MS and NMOSD, but were more prevalent in MS patients (20 % vs. 2 %, p = 0.008). Root entry zone (REZ) lesions were found in 4 of 45 MS patients, accounting for 9 % (95 % CI: 3 %–17 %), and were absent in the NMOSD group; however, there was no significant difference between the two groups (p = 0.12). Of the MS patients with pontine trigeminal nerve lesions, 6 out of 9 (63 %; 95 % CI, 36 %–98 %) exhibited bilateral lesions, which was significantly more prevalent compared to the NMOSD group (13 % vs. 0 %, p = 0.03). ConclusionsThe presence of pontine trigeminal nerve lesions, particularly when bilateral, are significantly more prevalent in MS patients than in those with NMOSD, suggesting their utility as a distinctive marker and potential diagnostic indicator specifically for MS.

GV-971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities.

Growing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV-971 in NMOSD. GV-971 is a drug used for treating mild-to-moderate Alzheimer's disease, which targets the gut-brain axis and reduces neuroinflammation. To evaluate GV-971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO-IgG into aged mice (11 months old) or using NMO-IgG along with complement injection and microbubble-enhanced low-frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV-971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis. Our findings indicated that GV-971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders. GV-971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders.

The levels of circulating cytokines and risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease affecting the central nervous system (CNS). NMOSD pathogenesis involves systemic inflammation. However, a causal relationship between circulating cytokine levels and NMOSD remains unclear. Mendelian randomization (MR) approaches were used to investigate the potential association between genetically determined circulating 19 inflammatory cytokines and 12 chemokines levels and the risk of developing NMOSD. After Bonferroni correction, the risk of aquaporin 4-antibody (AQP4-ab)-positive NMOSD was suggested to be causally associated with the circulating levels of three cytokines, including interleukin (IL)-4 [odds ratio (OR): 11.01, 95% confidence interval (CI): 1.16-104.56, P = 0.037], IL-24 (OR: 161.37; 95% CI: 2.46-10569.21, P = 0.017), and C-C motif chemokine 19 (CCL19) (OR: 6.87, 95% CI: 1.78-26.93, P = 0.006). These findings suggest that a genetic predisposition to higher levels of IL-4, IL-24, and CCL19 may exert a causal effect on the risk of AQP4-ab-positive NMOSD. Further studies are warranted to clarify how these cytokines affect the development of AQP4-ab-positive NMOSD.

Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study

Background: Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning. Methods: This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC. Results: Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = −0.60 and R = −0.64, respectively), inversely moderate in patients with MOGAD (R = −0.34 and R = −0.40, respectively), and weak in patients with NMOSD (R = −0.03 and R = −0.17, respectively). Conclusions: Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.

Pregnancy characteristics in Egyptian female patients with NMOSD.

Neuromyelitis optica spectrum disorder (NMOSD) primarily affects women of childbearing age. Studying the potential relationship between NMOSD and pregnancy characteristics and outcomes. This is a retrospective cohort study that was conducted on 66 married female patients diagnosed with NMOSD. All patients underwent a thorough review of their demographic and clinical history through their medical records and personal interviews. Additionally, a complete neurological examination was performed, along with the expanded disability status scale (EDSS) and a pregnancy registry questionnaire. After comparing married patients before and after disease onset, there was a significant increase in the number of abortions and the percentage of cesarean sections, as well as a decrease in the percentage of breastfeeding after disease onset. The p values were .02, <.001, and <.001, respectively, with odds ratios of 2.03, 5.13, and 6.17. Additionally, there was a rise in the occurrence of postpartum relapses, which accounted for 66% of all relapses after the disease onset. Most of these relapses (88.7%) occurred within the first 3 months postpartum. Presence of NMOSD increased the percentage of miscarriage, delivery by cesarean section, and decreased the chance of breastfeeding. In addition, pregnancy increases NMOSD relapse and subsequent disability.

Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder.

Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10. Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19+ IgD-, CD27-) and plasmablasts (PBs; CD19+, CD27hi, CD38hi). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab. DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200+ PBs produced more IL-10 than CD200- PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200+ PBs than patients during the acute attacks. Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200+ PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.

Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion.

AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear. Our study aims to clarify biological pathways distinguishing these diseases beyond autoantibodies and investigate variable BCD effects through proteomic comparisons. In a retrospective study, 1,463 serum proteins were measured in 53 AQP4-NMOSD, 25 MOGAD, 18 SN-NMOSD, and 49 healthy individuals. To identify disease subtype-associated signatures, we examined serum proteins in patients without anti-CD20 B-cell depletion (NoBCD). We then assessed the effect of BCD treatment within each subtype by comparing proteins between BCD-treated and NoBCD-treated patients. In NoBCD-treated patients, serum profiles distinguished the 3 diseases. AQP4-NMOSD showed elevated type I interferon-induced chemokines (CXCL9 and CXCL10) and TFH chemokine (CXCL13). MOGAD exhibited increased cytotoxic T-cell proteases (granzyme B and granzyme H), while SN-NMOSD displayed elevated Wnt inhibitory factor 1, a marker for nerve injury. Across all subtypes, BCD-treated patients showed reduction of B-cell-associated proteins. In AQP4-NMOSD, BCD led to a decrease in several inflammatory pathways, including IL-17 signaling, cytokine storm, and macrophage activation. By contrast, BCD elevated these pathways in patients with MOGAD. BCD had no effect on these pathways in SN-NMOSD. Proteomic profiles show unique biological pathways that distinguish AQP4-NMOSD, MOGAD, or SN-NMOSD. Furthermore, BCD uniquely affects inflammatory pathways in each disease type, providing an explanation for the disparate therapeutic response in AQP4-NMOSD and MOGAD.

Monoclonal Antibody Treatment for Relapse Prevention in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system that can lead to devastating neurological disabilities such as blindness and impaired mobility. Given that NMOSD can cause severe neurological deteriorations even with a single episode, exploring effective relapse prevention strategies in NMOSD is imperative. Recently, various biological monoclonal antibody therapies targeting diverse mechanisms have shown efficacy in preventing relapses in NMOSD, as evidenced by clinical trials. These monoclonal antibody therapies include complement inhibition (eculizumab and ravulizumab), B-cell depletion (rituximab and inebilizumab), and interleukin-6 receptor blockade (tocilizumab and satralizumab) mechanisms. Some of these therapies are now reimbursable, and this review summarizes their mechanisms, administration methods, reimbursement status in Korea, efficacy, and safety profiles in clinical practice.

Monoclonal Antibody Treatment for Relapse Prevention in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system that can lead to devastating neurological disabilities such as blindness and impaired mobility. Given that NMOSD can cause severe neurological deteriorations even with a single episode, exploring effective relapse prevention strategies in NMOSD is imperative. Recently, various biological monoclonal antibody therapies targeting diverse mechanisms have shown efficacy in preventing relapses in NMOSD, as evidenced by clinical trials. These monoclonal antibody therapies include complement inhibition (eculizumab and ravulizumab), B-cell depletion (rituximab and inebilizumab), and interleukin-6 receptor blockade (tocilizumab and satralizumab) mechanisms. Some of these therapies are now reimbursable, and this review summarizes their mechanisms, administration methods, reimbursement status in Korea, efficacy, and safety profiles in clinical practice.

Imaging Biomarkers for Differential Diagnosis of Central Nervous System Inflammatory Diseases

Inflammatory diseases of the central nervous system (CNS) include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis. In addition, various rheumatoid autoimmune diseases, autoimmune encephalitis, and medications such as immune checkpoint inhibitors can cause inflammation in the CNS. Radiological findings are very useful for us in differentiating inflammatory diseases of the CNS. On MRI, the shape, location, length/size, and gadolinium enhancement pattern of the lesions as well as the recovery and atrophy of the lesions following the acute phase, serve as important biomarkers for differentiating the diseases. In this review, we will highlight the typical characteristics MRI of optic neuritis, brain lesions, and myelitis in MS, NMOSD, and MOGAD, and outline the features of other inflammatory diseases of CNS.

Imaging Biomarkers for Differential Diagnosis of Central Nervous System Inflammatory Diseases

Inflammatory diseases of the central nervous system (CNS) include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis. In addition, various rheumatoid autoimmune diseases, autoimmune encephalitis, and medications such as immune checkpoint inhibitors can cause inflammation in the CNS. Radiological findings are very useful for us in differentiating inflammatory diseases of the CNS. On MRI, the shape, location, length/size, and gadolinium enhancement pattern of the lesions as well as the recovery and atrophy of the lesions following the acute phase, serve as important biomarkers for differentiating the diseases. In this review, we will highlight the typical characteristics MRI of optic neuritis, brain lesions, and myelitis in MS, NMOSD, and MOGAD, and outline the features of other inflammatory diseases of CNS.

Emotional Incontinence in a Patient with Neuromyelitis Optica Spectrum Disorder

The pathologic laughing is involuntary and associated with brain damage seen in a variety of disorders, which occurs as a result of lesions in various locations and is often seen associated with prefrontal or brainstem lesions. Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis and myelitis, and also develops brain lesions involving the bilateral diencephalic regions adjacent to the third ventricles, the brainstem and cerebellum surrounding the fourth ventricles, and the periventricular white matter adjacent to the lateral ventricles. Emotional incontinence refers to episodic laughing or crying, and occurs as a result of brain damage in various locations and is often seen associated with prefrontal or brainstem lesions. Emotional incontinence has been well described in multiple sclerosis, however the emotional incontinence in NMO has not been systemically documented. My report a characteristic patient with NMO showing the pathologic laughing as an initial manifestation, and the plasmapheresis therapy showed remarkable improvement in severity and occurrence of the pathologic laughing.

Emotional Incontinence in a Patient with Neuromyelitis Optica Spectrum Disorder

The pathologic laughing is involuntary and associated with brain damage seen in a variety of disorders, which occurs as a result of lesions in various locations and is often seen associated with prefrontal or brainstem lesions. Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis and myelitis, and also develops brain lesions involving the bilateral diencephalic regions adjacent to the third ventricles, the brainstem and cerebellum surrounding the fourth ventricles, and the periventricular white matter adjacent to the lateral ventricles. Emotional incontinence refers to episodic laughing or crying, and occurs as a result of brain damage in various locations and is often seen associated with prefrontal or brainstem lesions. Emotional incontinence has been well described in multiple sclerosis, however the emotional incontinence in NMO has not been systemically documented. My report a characteristic patient with NMO showing the pathologic laughing as an initial manifestation, and the plasmapheresis therapy showed remarkable improvement in severity and occurrence of the pathologic laughing.

A case report of seronegative neuromyelitis optica spectrum disorder treated with corticosteroids and intravenous immunoglobulin

Neuromyelitis optical spectrum disorders (NMOSD) are inflammatory and demyelinating autoimmune diseases ofthe central nervous system. We present the case of a male patient with seronegative NMOSD, who presented with area postrema syndrome; During hospitalization, he presented progressive neurological deterioration. In T2 flair of the brain MRI, hyperintense intramedullary lesions were evidenced, in the area postrema, in the brainstem and bilateral periventricular regions; the AQP4 dosage in serum and CSF were negative. The patient received treatment with Human Immunoglobulin for five days, which had a partial response to treatment.

Digital symbol-digit modalities test with modified flexible protocols in patients with CNS demyelinating diseases

Cognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants’ feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics.

Mechanisms of gastrointestinal toxicity in neuromyelitis optica spectrum disorder patients treated with mycophenolate mofetil: insights from a mouse model and human study.

Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Development and validation of a claims-based algorithm to identify patients with Neuromyelitis Optica Spectrum disorder

IntroductionNo validated algorithm exists to identify patients with neuromyelitis optica spectrum disorder (NMOSD) in healthcare claims data. We developed and tested the performance of a healthcare claims–based algorithm to identify patients with NMOSD. MethodsUsing medical record data of 101 adults with NMOSD, multiple sclerosis (MS), or myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), we tested the sensitivity and specificity of claims-based algorithms developed through interviews with neurologists. We tested the best-performing algorithm's face validity using 2016–2019 data from IBM MarketScan Commercial and Medicare Supplemental databases. Demographics and clinical characteristics were reported. ResultsAlgorithm inclusion criteria were age ≥ 18 years and (≥1 NMO diagnosis [or ≥ 1 transverse myelitis (TM) and ≥ 1 optic neuritis (ON) diagnosis] and ≥ 1 NMOSD drug) or (≥2 NMO diagnoses ≥90 days apart). Exclusion criteria were MS diagnosis or use of MS-specific drug after last NMO diagnosis or NMOSD drug; sarcoidosis diagnosis after last NMO diagnosis; or use of ≥1 immune checkpoint inhibitor. In medical record billing data of 50 patients with NMOSD, 30 with MS, and 21 with MOGAD, the algorithm had 82.0% sensitivity and 70.6% specificity. When applied to healthcare claims data, demographic and clinical features of the identified cohort were similar to known demographics of NMOSD. ConclusionsThis clinically derived algorithm performed well in medical records. When tested in healthcare claims, demographics and clinical characteristics were consistent with previous clinical findings. This algorithm will enable a more accurate estimation of NMOSD disease burden using insurance claims datasets.

Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.