Case Of Neuromyelitis Optica Spectrum Disorder Research Articles

Etiological and clinical characterization of longitudinally extensive spinal cord lesions: A 12-year tertiary center experience.

Longitudinally extensive spinal cord lesions (LESCL) are characterized by T2-hyperintense signals spanning at least three vertebral body segments, with neuromyelitis optica spectrum disorders (NMOSD) being a significant cause. This study aimed to characterize the clinical, radiological, serological, and cerebrospinal fluid (CSF) features of LESCL and to compare NMOSD and non-NMOSD cases. We conducted a retrospective cross-sectional study of adult patients diagnosed with LESCL at our center over a twelve-year period collecting data on demographics, clinical presentations, MRI findings, CSF analysis, and serological testing for AQP4-IgG and MOG-IgG antibodies. Etiologies were reviewed based on current diagnostic criteria, with comparisons made between NMOSD and non-NMOSD LESCL. We identified 41 LESCL cases, with NMOSD as the most common etiology (29.3 %) followed by ischemia (14.6 %) and multiple sclerosis (9.8 %). The median length of lesions was seven vertebral segments. Pleocytosis was present in 48.6 % of CSF analyses, with oligoclonal bands found in 10 cases. AQP4-IgG antibodies were positive in 11 of 12 NMOSD patients. NMOSD patients were more likely to be female (p = p.006), and exhibit severe symptoms, such as quadriparesis (p = 0.03) and a cervical sensory level (p = 0.04). MRI findings showed a preference for cervical lesions in NMOSD (p = 0.001) and thoracic lesions in non-NMOSD LESCL (p = 0.007). LESCL exhibit considerable clinical diversity, with NMOSD being the predominant etiology. Characteristics such as female sex and cervical MRI involvement may indicate a higher likelihood of NMOSD, while cases in males with thoracic segment involvement may suggest non-NMSOD etiologies such as ischemia.

When the Expected Scenario Did Not Occur: A Novel NDUFA12 Mutation Resembling Neuromyelitis Optica Spectrum Disorder.

Mitochondrial complex I transfers electrons from NADH (nicotinamide adenine dinucleotide) to ubiquinone, facilitating ATP synthesis via a proton gradient. Complex I defects are common among the mitochondrial diseases, especially in childhood. NDUFA12, located in complex I's transmembrane domain, is not directly involved in catalytic activity, but the NDUFA mutations are associated with Leigh syndrome and complex I defects. Complex I deficiency typically manifests as bilateral brainstem lesions and presents with dystonia, hypotonia, and optic nerve damage. This article discusses a patient with an NDUFA12 mutation resembling neuromyelitis optica spectrum disorder clinically and radiologically, highlighting the importance of considering NDUFA12 mutations in dystonia and optic neuritis diagnoses, particularly in neuromyelitis optica spectrum disorder cases that do not respond to standard treatments. Further research on NDUFA12 variants is needed for a better understanding of their phenotypic spectrum and to enhance diagnostic accuracy.

Navigating Complexity in Pediatric NMOSD: Unusual Symptoms and Adverse Reactions: A Case Report

Background and Clinical Significance: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune demyelinating disorder of the central nervous system, characterized by the presence of aquaporin-4 (AQP4) antibodies and a high relapse rate. We provide information about the diagnosis, unusual symptoms, and treatment of a paediatric patient with NMOSD. Case Presentation: A 14-year-old girl was hospitalized for weakness and paraesthesia of the lower limbs (LL). The patient underwent detailed investigations and was diagnosed with NMOSD and cryptogenic organizing pneumonia. Initial treatment with methylprednisolone and prednisone yielded a favourable response. Therapy with mycophenolate was initiated. However, the patient experienced two more relapses, prompting the use of rituximab therapy with a favourable outcome and a two-year relapse-free follow-up period. Conclusions: Patients with NMOSD may have multisystemic inflammation, including organs outside the central nervous system. Our case report highlights a case of NMOSD, pulmonary involvement, and unusual adverse reactions to rituximab.

Genetic Insights into Therapeutic Targets for Neuromyelitis Optica Spectrum Disorders: A Mendelian Randomization Study.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe central nervous system disease primarily characterized by optic neuritis and myelitis, which can result in vision loss and limb paralysis. Current treatment options are limited in their ability to prevent relapses and mitigate disease progression, underscoring the urgent need for new drug targets to develop more effective therapies. The objective of this study is to identify potential drug targets associated with a reduced risk of NMOSD attacks or relapses through Mendelian randomization (MR) analysis, thereby addressing the limitations of existing treatment methods and providing better clinical options for patients. To identify therapeutic targets for NMOSD, a MR analysis was conducted. The cis-expression quantitative trait loci (cis-eQTL, exposure) data were sourced from the eQTLGen consortium, which included a sample size of 31,684. NMOSD (outcome) summary data were obtained from two of the largest independent cohorts: one cohort consisted of 86 NMOSD cases and 460 controls derived from whole-genome sequencing data, while the other cohort included 129 NMOSD patients and 784 controls. We performed a two-sample MR analysis to evaluate the association between single nucleotide polymorphisms (SNPs) and copy number variations with NMOSD. The MR analysis utilized the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses were conducted to assess the presence of horizontal pleiotropy and heterogeneity. Colocalization analysis was employed to test whether NMOSD risk and gene expression are driven by common SNPs. Additionally, a phenome-wide association study (PheWAS) was performed to detect disease outcomes associated with NEU1. Supplementary analyses included single-nucleus RNA sequencing (snRNA-seq) data analysis, protein-protein interaction (PPI) networks, and drug feasibility assessments to prioritize potential therapeutic targets. Two drug targets, COL4A1 and NEU1, demonstrated significant MR results in two independent datasets. Notably, NEU1 showed substantial evidence of colocalization with NMOSD. Additionally, apart from the association between NEU1 and NMOSD, no other associations were observed between gene-proxied NEU1 inhibition and the increased risk of other NMOSD-related diseases. This study supports the potential of targeting NEU1 for drug inhibition to reduce the risk of NMOSD. Further preclinical research and drug development are warranted to validate the efficacy and safety of NEU1 as a therapeutic target and to explore its potential in NMOSD treatment.

Spectrum of Auto-antibodies in NMO and MOG Associated CNS Demyelination- The SANMAD Study

This observational study explored coexisting organ-specific and non-organ-specific autoantibodies in Neuromyelitis optica spectrum disorder(NMOSD) and Myelin oligodendrocyte glycoprotein-IgG-1(MOG-IgG1) associated central nervous system demyelination(MOGAD) in a South Asian cohort from March 2017-2023. Of the 250 cases, 148 were MOGAD(82pediatric) and 102 were NMOSD(15 pediatric). 17.6% tested positive for ≥1 antibody, with NMOSD showing a higher positivity rate (25.5%) than MOGAD(12.2%,p=0.011). Double antibody positivity occurred more in NMOSD (5.9%vs.MOGAD,1.4%,p=0.045). Three NMOSD cases had Sjogren syndrome with higher Anti-Ro-52 prevalence(12.7%vs.4.1%,p=0.014). NMOSD patients with ≥1 antibody positivity had more constitutional symptoms (45.5%vs.23.1%,p=0.045). Significant associations were found between NMOSD and female gender, having ≥1 antibody-positive status, and testing positive for Anti-Ro-52 and SS-A antibodies (p<0.05).

Rituximab maintenance treatment outcomes in patients with relapsing neuromyelitis optica spectrum disorder: a monocentric retrospective analysis.

Some patients with neuromyelitis optica spectrum disorder (NMOSD) experience relapse after rituximab (RTX) treatment. In this retrospective study, we analyzed the recurrence-related clinical features, laboratory investigation results, and dosing protocol of 30 female patients with relapsing NMOSD with immunoglobulin G autoantibodies against aquaporin-4 and relapses during repeated 0.5 g RTX infusions as maintenance treatment. The median follow-up period was 6.62years. Thirty-five episodes were observed, with myelitis being the most frequent. The median expanded disability status scale change score was 0.50. The recurrence rate decreased by 44.23%/year with RTX infusion. Approximately 85.71% of the patients showed relapse without RTX infusion within 10months. Overall, RTX may be effective for relapsing NMOSD cases.

The association between dietary inflammatory index and risk of neuromyelitis optica spectrum disorder: a case–control study

ABSTRACT Background and aim: Neuromyelitis optica spectrum disorder (NMOSD) is a severe and rare inflammatory disease affecting the central nervous system through optic neuritis and transverse myelitis. Present study aimed to investigate the association between dietary inflammatory index (DII) and risk of NMOSD. Methods: In this case–control study, 30 NMOSD cases and 90 aged matched healthy individuals were recruited. Habitual dietary intakes were assessed by a validated 168-item food frequency questionnaire to calculate the DII score. A multiple adjusted regression was used to determine the odd ratio (OR) of NMOSD across DII tertiles. The Residual method was applied to adjust the energy intake. Results: Participants in the top of DII tertile were more likely to have NMOSD in the crude model compared to those with the lowest one (OR: 4.18; 95%CI: 1.43-12.21). It was the case when multivariable confounders were considered in adjustment model I (OR: 3.98; 95%CI: 1.34-11.82) and II (OR: 4.43; 95%CI: 1.36-14.38), such that, individuals with a greater DII score had 3.98 and 4.43-time higher risk of NMOSD in model I and II, respectively. Conclusion: The Present study suggests that greater adherence to a pro-inflammatory diet may be associated with an increased risk of NMOSD.

Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder

Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Pediatric neuromyelitis optica spectrum disorder: Case report of postrema syndrome

Link of Video Abstract: https://youtu.be/w-yWNre4RNg Introduction: Neuromyelitis Optica Spectrum Disorders (NMOSD) is an inflammatory disease of the optic nerve and spinal cord characterized by severe immune mediated axonal damage and demyelination. Optic neuritis, transverse myelitis, or combination of both are common first clinical attack symptoms. Area postrema syndrome was infrequently described as an initial presentation of pediatric NMOSD. Case Presentation: We present the case of 10-year-old male presents with fever, nausea, vomiting, hiccups, and vertigo suggesting an Area Postrema Syndrome. Brain Magnetic Resonance Imaging (MRI) with contrast shows a pathological lesion without contrast enhancement on the periventricle of the 3rd ventricle extends to the bilateral optic tracts. Whole spine MRI showed no abnormalities. Aquaporin-4 was found seropositive on lumbar puncture examination. He was treated with intravenous methylprednisolone for 5 consecutive days followed by IVIG for 5 days and mycophenolate mofetil as maintenance therapy. Patient then showed a significant improvement in symptoms. Conclusion: Pediatric NMOSD with core criteria of area postrema syndrome as the first clinical attack is rare. Relapse may occur, requiring further follow-up and maintenance therapy. We should raise awareness on the possibility of postrema syndrome in pediatric NMOSD cases that are intractable with medication.

Association Between Serum Interleukin-32 Level and Disease Status in Cases with Neuromyelitis Optica Spectrum Disorders.

Various cytokines are involved in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD), but whether serum interleukin-32 (IL-32) level is related to disease activity in cases with NMOSD remains poorly understood. Thus, we investigated the underlying role of IL-32 in NMOSD cases. Our observation recruited 32 cases with acute NMOSD, 36 NMOSD cases in remission, and 60 healthy individuals in this study. Serum concentrations of IL-32 were detected using ELISA. The associations among IL-32 levels and clinical characteristics were assessed by Spearman correlation coefficient and logistic regression analysis. IL-32 concentrations were strongly increased in cases with acute NMOSD [(52.06 ± 16.56) pg/mL] and NMOSD in remission [(25.78 ± 8.31) pg/mL] compared with healthy controls [(10.83 ± 6.94) pg/mL] (all p <0.001). ROC analysis suggested that the AUC for IL-32 and the combined diagnosis of acute NMOSD was 0.811 (P = 0.026, 95% CI 0.673-0.949), with a sensitivity of 0.800 and a specificity of 0.806. The level of IL-32 was positively correlated with EDSS scores in patients with acute NMOSD (r = 0.620, p < 0.001). EDSS score was independently associated with increased serum levels of LI-32 (B = 1.529, p < 0.001). Higher level of IL-32 is related to disease severity in NMOSD. Therefore, serum IL-32 may be a novel biomarker for acute NMOSD.

Big Data Analysis of Inflammatory Conditions Associated With Optic Neuritis.

Previous studies in the United States established multiple sclerosis (MS) as the most common cause of optic neuritis (ON). ON can be associated with other systemic inflammatory conditions including sarcoidosis, neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and lupus; however, prospective studies to establish risk of ON associated with these diseases are lacking. Furthermore, appropriate workup for ON is still debated. A deidentified electronic medical record of a tertiary care academic center was searched for ON and rheumatologic/neuro-inflammatory diseases in the medical history, diagnoses, and laboratory results; followed by the intersection of ON with each condition. We calculated frequency of systemic conditions among patients with ON and prevalence of ON in those conditions. We also calculated relative risk (RR) of underlying systemic conditions among patients with ON compared with the study patient population. In 6.7 million charts, 5,344 cases of ON were identified. Among those, MS occurred most commonly (20.6%), followed by NMOSD (10.5%). Conversely, ON occurred in 98.4% of NMOSD cases, 53.3% of MOGAD, and 10.0% of MS. NMOSD (RR = 1,233), MOGAD (RR = 688), and MS (RR = 126) had the highest RR among the conditions we evaluated. The subset analysis showed similar findings. The high RR for ON among patients with NMOSD and MOGAD suggests that clinical suspicion for ON should be high among patients with these conditions presenting with vision changes. Conversely, MS and NMOSD should initially be high on the differential diagnosis for any patient presenting with optic neuritis.

Significant up-regulation of lncRNAs in neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an immune-related demyelinating defect. Long non-coding RNAs (lncRNAs) might influence the pathobiology and progression of NMOSD. The current study assessed expression level of NEAT1, PANDAR, MEG3 and TUG1 lncRNAs in the peripheral blood of NMOSD patients compared with healthy individuals. All mentioned lncRNAs were shown to be over-expressed in total NMOSD cases, male NMOSD cases and female NMOSD cases compared with the matching control subgroups. MEG3 had the most robust over-expression in patients subgroups compared with normal subjects. There was no noteworthy difference in the expression of any of lncRNAs between female and male patients. MEG3 had an ideal performance in the differentiation of NMOSD cases from healthy persons (Sensitivity and specificity values = 100%). Other lncRNAs could also efficiently separate NMOSD cases from control subjects (AUC values = 0.97, 0.89 and 0.88 for PANDAR, NEAT1 and TUG1, respectively). Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD.

Epidemiologic and clinical characteristics of neuromyelitis optica spectrum disorder patients, A seven years follow-up study from Iran.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare neuroinflammatory disease characterized by recurrent relapses. The most common signs are myelitis and optic neuritis. It can also present by cerebral or brain stem syndromes. There are still many challenges in its diagnosis and treatment, and long-term follow-up studies are needed to see the disease course over time. We established an electronic registration system of NMOSD patients starting from October 2015 in Kashani hospital, Isfahan, Iran. Every suspected patient was documented and included in the follow-up system to survey their disease course. Anti-aquaporine 4 (AQP4) antibody checked for all by cell-based assay method. All information such as demographic and clinical data and laboratory and MRI findings were documented. Participants were followed up for any relapses, new paraclinical tests and drug changes. This study is based on the definite NMOSD cases (according to the 2015 criteria) characteristics and clinical course during 7 years of registration. The study included 173 NMOSD cases and 56 ones were seropositive for AQP4 Ab. Their mean age was 40.02±11.11 years (45.78 in the seropositive group). The mean age at disease onset was about 30.16 years. The mean time of follow-up by our registration system is 55.84±18.94 months (54.82 months in seropositive ones). The annual relapse rate is estimated as 0.47±0.36. Long extended transvers myelitis (LETM) was present in the baseline MRI of 77 patients (44.5%), while 32 of them did not show any related clinical symptoms. 124 patients revealed an abnormality in the first brain MRI. 27 individuals suffer hypothyroidism as the most common comorbid disease. The disease seems to be more prevalent in the west and southwest areas of Isfahan province. The mean age of onset is higher than Multiple Sclerosis (MS) patients, but there are notable pediatric cases too. It should also be noticed that cervical LETM can be asymptomatic at first. Brain MRI abnormalities are frequently observed. The disease is more prevalent in the geographical areas where showing high MS prevalence.

The Coexisting Neuromyelitis Optica Spectrum Disorder and Systemic Lupus Erythematosus: A Therapeutic Challenge.

Neuromyelitis Optica (NMO), or Devic's disease, is an immune-mediated, usually relapsing, central nervous system (CNS) demyelination disorder associated with optic neuritis and transverse myelitis. It is characterised by the presence of longitudinally extensive transverse myelitis (LETM) and antibodies against water channel aquaporin-4 (AQP4-immunoglobulin G [IgG]). The term NMO spectrum disorder (NMOSD) includes patients with limited forms of NMO who are at risk of recurrence. Often patients with NMO or NMOSD have an associated systemic autoimmune disease, most commonly systemic lupus erythematosus (SLE) or Sjogren syndrome (SS) or a related profile of non-organ-specific autoantibodies. The intriguing aspect of coexisting NMOSD and SLE is whether they are independent diseases that can coexist with each other or the serological findings specific to both diseases in a patient is a non-specific finding of no prognostic or therapeutic concern. We have presented two cases of NMOSD coexisting with SLE and based upon the existing evidence in the literature we present that the two conditions are independent of each other, and, at times, it can throw a therapeutic challenge to any clinician.

The prevalence and clinical phenotype of dual seropositive neuromyelitis optica spectrum disorders at a national reference center in South Asia.

Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune syndrome that is frequently positive for Aquaporin 4 (AQP4) IgG or Myelin Oligodendrocyte Glycoproteins (MOG) IgG. However, dual positivity to both is rare. To assess the prevalence of dual-positive NMOSD and outline its clinical phenotype. This is a retrospective cross-sectional study conducted at a tertiary healthcare center in South Asia between August 2018 and November 2021. The serum and/or CSF samples of suspected cases of NMOSD were tested for both AQP4-IgG and MOG-IgG using an Indirect immunofluorescence test on transfected cells. During the study period, 1935 cases of NMOSD were tested for both antibodies- 65 patients (3.35%; 57 females and 8 males) tested positive for AQP4-IgG, 217 patients (11.21%; 122 females and 95 males) tested positive for MOG-IgG and 3 patients (0.15%; 2 females and 1 male) showed dual positivity. There was a strong female preponderance in all three groups (87.69%, 56.22%, and 66.66% respectively). This study identified 3 patients with dual positivity. The first patient (42 years, Male) presented with area postrema syndrome initially and subsequently relapsed by developing right-sided numbness of the temporal area and limbs during which he tested dual positive. The second patient (27 years, Female) presented with bilateral optic neuritis (left>right) initially and subsequently relapsed following an episode of a seizure with left-sided hemiplegia. The third patient (25 years, Female) initially presented with acute bilateral optic neuritis and later developed left-sided hemiplegia post-recovery at which point she tested dual positive. Management using methylprednisolone was ineffective for all three patients, however, plasmapheresis and/or periodic rituximab injections produced an excellent response. Our study reports that the prevalence of dual-positive NMOSD is 0.15% and its clinical phenotype is more similar to NMO rather than MOG- associated disease.

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare chronic neuroinflammatory autoimmune condition. Since the onset of the COVID-19 pandemic, there have been reports of NMOSD clinical manifestations following both SARS-CoV-2 infections and COVID-19 vaccinations. This study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations. A Boolean search of the medical literature was conducted between December 1, 2019 to September 1, 2022, utilizing Medline, Cochrane Library, Embase, Trip Database, Clinicaltrials.gov, Scopus, and Web of Science databases. Articles were collated and managed on Covidence® software. The authors independently appraised the articles for meeting study criteria and followed PRISMA guidelines. The literature search included all case reports and case series that met study criteria and involved NMOSD following either the SARS-CoV-2 infection or the COVID-19 vaccination. A total of 702 articles were imported for screening. After removing 352 duplicates and 313 articles based on exclusion criteria, 34 articles were analyzed. A total of 41 cases were selected, including 15 patients that developed new onset NMOSD following a SARS-CoV-2 infection, 21 patients that developed de novo NMOSD following COVID-19 vaccination, 3 patients with known NMOSD that experienced a relapse following vaccination, and 2 patients with presumed Multiple Sclerosis (MS) that was unmasked as NMOSD post-vaccination. There was a female preponderance of 76% among all NMOSD cases. The median time interval between the initial SARS-CoV-2 infection symptoms and NMOSD symptom onset was 14 days (range 3-120 days) and the median interval between COVID-19 vaccination and onset of NMO symptoms was 10 days (range 1 to 97 days). Transverse myelitis was the most common neurological manifestation in all patient groups (27/41). Management encompassed acute treatments such as high dose intravenous methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG) and maintenance immunotherapies. The majority of patients experienced a favorable outcome with complete or partial recovery, but 3 patients died. This systematic review suggests that there is an association between NMOSD and SARS-CoV-2 infections and COVID-19 vaccinations. This association requires further study using quantitative epidemiological assessments in a large population to better quantify the risk.

Familial neuromyelitis optica spectrum disorders: Case series and systematic review.

Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder. To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD. A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to "genetic" and "NMOSD" were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics. We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03. Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

Relevance of Bright Spotty Lesions (BSLs) in Neuromyelitis Optica Spectrum Disorders (NMOSD): A Case Series (P1-3.013)

<h3>Objective:</h3> To highlight the diagnostic value of bright spotty lesions (BSLs) as a neuroimaging marker for neuromyelitis optica spectrum disorder (NMOSD). <h3>Background:</h3> NMOSD is an autoimmune central nervous system disease with a complex clinical course. Although longitudinally extensive transverse myelitis (LETM) is a significant magnetic resonance imaging (MRI) finding, it is not unique to NMOSD and is seen in various causes of myelitis. BSLs, defined as hyperintense intramedullary lesions on axial T2-weighted images, are a recent neuroimaging discovery whose specificity and ability to differentiate NMOSD from other demyelinating disorders have not been entirely investigated. <h3>Design/Methods:</h3> A single-center retrospective study of patients recruited at the Department of Neurology, West Virginia University, was conducted between August 1st, 2013, and February 28th, 2022. Eleven confirmed cases of seropositive NMOSD were included from a total of 37 patients. Comparison studies were done with a control group (n=18) of alternative causes of myelitis, including multiple sclerosis, idiopathic transverse myelitis, and neurosarcoidosis. All patients underwent MRIs of the brain and cervico-dorsal spine using our Siemens MAGNETOM® Verio 3.0T and MAGNETOM® Aera 1.5T machines, and two neuroradiologists manually reviewed the scans. <h3>Results:</h3> We report 11 seropositive NMO cases, all seen in women from 25–75 years at the time of diagnosis (most were older than 65). Presentations were diverse, including paresthesia, extremity weakness, and visual changes. Five of the 11 NMOSD patients (45%) had BSLs on spinal MRI, compared to none in the control group; of these, four (80%) also demonstrated LETM. Treatment with immunotherapy and symptomatic management led to clinical improvement in all cases. <h3>Conclusions:</h3> Axial-BSLs are a newly defined spinal MRI finding with high specificity for NMOSD, which can be used in combination with LETM to enhance their diagnostic potential. The absence of BSLs in our control group establishes its prolific role in distinguishing NMOSD from other etiologies of myelitis. <b>Disclosure:</b> Miss Beard has nothing to disclose. Dr. P has nothing to disclose. Dr. Sharma has nothing to disclose. Mrs. Jaiswal has nothing to disclose. Dr. Sriwastava has nothing to disclose.

Neuromyelitis Optica Spectrum Disorder Mimicking Pontine Stroke - A Cautionary Tale: Case Report and Systematic Literature Review (P13-5.014)

<h3>Objective:</h3> To report an unusual clinical pattern of Neuromyelitis Optica Spectrum Disorder (NMOSD) presenting as a pontine stroke mimic <h3>Background:</h3> A 58-year-old Hispanic woman presented to an outside hospital with right-sided numbness, blurry vision, and gait instability. Findings on brain MR imaging were thought to reflect acute pontine stroke; the patient commenced dual antiplatelet therapy. Three weeks later, she presented to our hospital with right-sided hemiparesis. Stroke workup was unrevealing for specific pathophysiology. She was readmitted about two weeks later with a new-onset right cranial nerve VI palsy with ipsilateral facial droop and tinnitus. Brain MRI demonstrated foci of diffusion restriction on DWI in the periventricular white matter and brainstem region suggesting rhombencephalitis of inflammatory or autoimmune origin. Despite IVIG infusion, the patient’s condition deteriorated and she was intubated for airway protection. Serological assays were positive for AQP4 and negative for all other autoantibodies, including anti-Gq1b. She was treated with methylprednisolone pulse dosing and plasmapheresis, followed by rituximab, with significant neurological improvement. <h3>Design/Methods:</h3> In addition to the case report, a systematic literature review was performed to identify NMOSD cases initially diagnosed as stroke. Publications were selected and curated in accordance with PRISMA guidelines. <h3>Results:</h3> Six NMOSD patients were initially thought to represent acute stroke. However, the persistence, progression, or recurrence of symptoms with additional history, follow-up neuroimaging, and further serological immune assays facilitated the accurate diagnosis of NMOSD. Notably, the age of onset in all cases was significantly more advanced than patients normally presenting with NMOSD (median age 32–41). <h3>Conclusions:</h3> NMOSD diagnosis should be considered in individuals presenting with atypical stroke-like symptoms, particularly in those greater than or equal to 41 years of age. This is important as early recognition and treatment with immune therapies can improve functional outcome. <b>Disclosure:</b> Dr. Huang has nothing to disclose. Dr. Arora has nothing to disclose. An immediate family member of Dr. Diamond has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Consultant360. An immediate family member of Dr. Diamond has received publishing royalties from a publication relating to health care. Dr. McFarlane has nothing to disclose. Dr. Najjar has nothing to disclose.

Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids.

The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.