Diagnosis Of Neuromyelitis Optica Spectrum Disorder Research Articles

Safety and efficacy of inebilizumab for the treatment of neuromyelitis optica spectrum disorder: end-of-study results from the open-label period of the N-MOmentum trial

Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study

BackgroundThe risk–benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of...

Soluble biomarkers for Neuromyelitis Optica Spectrum Disorders: a mini review.

The Neuromyelitis Optica Spectrum Disorders (NMOSD) constitute a spectrum of rare autoimmune diseases of the central nervous system characterized by episodes of transverse myelitis, optic neuritis, and other demyelinating attacks. Previously thought to be a subtype of multiple sclerosis, NMOSD is now known to be a distinct disease with unique pathophysiology, clinical course, and treatment options. Although there have been significant recent advances in the diagnosis and treatment of NMOSD, the field still lacks clinically validated biomarkers that can be used to stratify disease severity, monitor disease activity, and inform treatment decisions. Here we review many emerging NMOSD biomarkers including markers of cellular damage, neutrophil-to-lymphocyte ratio, complement, and cytokines, with a focus on how each biomarker can potentially be used for initial diagnosis, relapse surveillance, disability prediction, and treatment monitoring.

Reduced serum IgG galactosylation is associated with increased inflammation during relapses of neuromyelitis optica spectrum disorders.

Post-translational modifications of antibodies, with a specific focus on galactosylation, have garnered increasing attention in the context of understanding the pathogenesis and therapeutic implications of autoimmune diseases. However, the comprehensive scope and the clinical significance of antibody galactosylation in the context of Neuromyelitis Optica Spectrum Disorder (NMOSD) remain enigmatic.The primary aim of this research was to discern disparities in serum IgG galactosylation levels between individuals in the acute stage of NMOSD relapse and their age- and sex-matched healthy counterparts. A total of fourteen untreated NMOSD patients experiencing an acute relapse phase, along with thirteen patients under medication, were enrolled, and an additional twelve healthy controls of the same age and gender were recruited for this investigation. Western blot and lectin enzyme techniques were used to determine the level of IgG galactosylation in the serum samples from these subjects. The expression of CD45+, CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD16+CD56+ in peripheral blood leukocytes was measured by flow cytometry. The enzyme-linked immunosorbent assay (ELISA) was also used to quantify the amounts of IgG. Magnetic particle luminescence assays are used to detect cytokines. Robust statistical analysis was executed to ascertain the potential associations between IgG galactosylation and the aforementioned immune indices. In the context of NMOSD relapses, serum IgG galactosylation exhibited a notable decrease in untreated patients (0.2482 ± 0.0261), while it remained comparatively stable in medicated patients when contrasted with healthy controls (0.3625 ± 0.0259) (p=0.0159). Furthermore, a noteworthy inverse correlation between serum IgG galactosylation levels and the Expanded Disability Status Scale (EDSS) score during NMOSD relapse was observed (r=-0.4142; p=0.0317). Notably, IgG galactosylation displayed an inverse correlation with NMOSD relapse among peripheral blood CD45+, CD3+, CD3+CD8+, CD19+ cells, as well as with IL-6 and IL-8. Nevertheless, it was not determined whether IgG galactosylation and CD3+CD4+ T cells or other cytokines are statistically significantly correlated. Our research identified reduced IgG galactosylation in the serum of NMOSD patients during relapses, significantly correlated with disease severity, thereby providing a novel target for the diagnosis and treatment of NMOSD in the realm of medical research.

Neuromyelitis Optica Spectrum Disorder (NMOSD) or Chronic-Relapsing Inflammatory Optic Neuropathy (CRION)?: A Challenge in Diagnosis and Treatment

Abstract
 Introduction : Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory, immune-mediated central nervous system disease targeting the AQP4-water channel membrane protein of the optic nerve and the spinal cord. This case report aims to present a case of seroconverting NMOSD which was initially diagnosed as chronic relapsing inflammatory optic neuropathy (CRION).
 Case Illustration : 15-year-old female with recurrent, steroid-dependent optic neuritis of the LE. During the first attack, brain MRI showed optic nerve inflammation with normal brain findings. Initial test for AQP4-IgG, MOG-Ab and ANA profile were negative. The diagnosis of CRION was made. Treatment with corticosteroid and immunosuppressant agent was maintained for one year. After treatment cessation, however, LE optic neuritis recurred with bilateral lower limb weakness. Spinal MRI showed signs of longitudinal extensive transverse myelitis. Re-testing for AQP4-IgG showed positive result. Diagnosis of NMOSD was made, and the patient was treated with high-dose intravenous corticosteroid followed by oral dose, and immunosuppressant. Final visual acuity of the LE was 1.0, with minimal residual visual field defect and good motor function.
 Discussion : During the initial attack, the patient did not meet the 2015 NMOSD international consensus diagnostic criteria. The AQP4-IgG was negative and no other corresponding signs and symptoms. The criteria was met one year after: optic neuritis, LETM and positive seroconversion of AQP4-IgG.
 Conclusion : Diagnosing NMOSD is at times challenging especially during initial attack. Retesting of the AQP4- IgG is at times necessary in seronegative patients, especially in children showing ADEM-like event with optic neuritis and LETM to achieve diagnosis and proper treatment strategy.

T1 hypointense brain lesions in NMOSD and its relevance with disability: a single institution cross-sectional study

BackgroundT1 hypointense lesions are considered a surrogate marker of tissue destruction. Although there is a shortage of evidence about T1 hypointense brain lesions, black holes, in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD), the clinical significance of these lesions is not well determined.ObjectivesThe impact of T1 hypointense brain lesions on the clinical status and the disability level of patients with NMOSD was sought in this study.MethodsA total of 83 patients with the final diagnosis of NMOSD were recruited.Aquaporin-4 measures were collected. The expanded disability status scale (EDSS) and MRI studies were also extracted.T1 hypointense and T2/FLAIR hyperintense lesions were investigated. The correlation of MRI findings, AQP-4, and EDSS was assessed.ResultsT1 hypointense brain lesions were detected in 22 patients. Mean ± SD EDSS was 3.7 ± 1.5 and significantly higher in patients with brain T1 hypointense lesions than those without them (p-value = 0.01). Noticeably, patients with more than four T1 hypointense lesions had EDSS scores ≥ 4. The presence of T2/FLAIR hyperintense brain lesions correlated with EDSS (3.6 ± 1.6 vs 2.3 ± 1.7; p-value = 0.01). EDSS was similar between those with and without positive AQP-4 (2.7 ± 1.6 vs. 3.2 ± 1.7; p-value = 0.17). Also, positive AQP-4 was not more prevalent in patients with T1 hypointense brain lesions than those without them (50.9 vs 45.4%; p-value = 0.8).ConclusionWe demonstrated that the presence of the brain T1-hypointense lesions corresponds to a higher disability level in NMOSD.

Neuromyelitis optica spectrum disorders relapses and seasonal influence in an equatorial country cohort.

Information about seasonal distribution of Neuromyelitis optica spectrum disorders (NMOSD) attacks, particularly in tropical countries, has rarely been described and the reported data are diverse. To evaluate influence of seasonal variation in NMOSD relapses in an equatorial country. Exploratory observational, retrospective ecological study in a cohort of patients with NMOSD followed from January 2008 to December 2019. Data of demographic, clinical information, characteristics of relapses and seasonal temporal variation were recorded. Also, the annual, monthly and intra-annual seasonal variation of relapses was quantified. A negative binomial regression was used to estimate the associations between the number of relapses and climatic and temporal variables. One hundred thirteen patients were included, most of them were female (89.38%), with a mean age at NMOSD diagnosis was 44.97 (±13.98) and the median of relapses per patient were 2 relapses (IQR 1-3). The patients presented 237 relapses, most of these in AQP4 seropositive patients (87.76%) and longitudinal extensive myelitis was the most frequent type of relapse (53.59%). According to the temporal variation, relapses were more common in the second rainy season (28.69%) during November and December. However, there weren't significant differences in the number of relapses between seasons and climatic variables in the multivariable model. The number of NMOSD relapses in this equatorial country cohort did not exhibit any significant associations with climatic variations, including changes in rainy or dry seasons.

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.

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. 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. 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. 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.

Heidenhain variant of Creutzfeldt-Jakob disease masquerading as neuromyelitis optica spectrum disorder: recognizing when apheresis is not the answer.

The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after.

Neuromyelitis optica spectrum disorder mimicking stroke: A case report and literature review

Hemiparesis is a frequently observed manifestation of stroke but exceptionally rare in the context of neuromyelitis optica spectrum disorder (NMOSD). In this case, a 68-year-old woman initially presented with acute right-sided weakness, leading to suspicion of ischemic stroke. However, her symptoms worsened despite treatment with aspirin and statins. Subsequent spinal MRI and aquaporin 4 antibody testing confirmed the diagnosis of NMOSD. The administration of methylprednisolone and immunoglobulin resulted in improved clinical outcomes. This case serves as an illustrative example of the diverse manifestations encountered in NMOSD and underscores the significance of considering this potential etiology in elderly patients to facilitate prompt diagnosis and therapeutic intervention.

Comprehensive Metabolic Fingerprints Characterize Neuromyelitis Optica Spectrum Disorder by Nanoparticle-Enhanced Laser Desorption/Ionization Mass Spectrometry.

Timely screening of neuromyelitis optica spectrum disorder (NMOSD) and differential diagnosis from myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are the keys to improving the quality of life of patients. Metabolic disturbance occurs with the development of NMOSD. Still, advanced tools are required to probe the metabolic phenotype of NMOSD. Here, we developed a fast nanoparticle-enhanced laser desorption/ionization mass spectrometry assay for multiplexing metabolic fingerprints (MFs) from trace plasma and cerebrospinal fluid (CSF) samples in 30 s. Machine learning of the plasma MFs achieved the timely screening of NMOSD from healthy donors with an area under receiver operator characteristic curve (AUROC) of 0.998, and it comprehensively revealed the dysregulated neurotransmitter and energy metabolisms. Combining comprehensive MFs from both plasma and CSF, we constructed an integrated panel for differential diagnosis of NMOSD versus MOGAD with an AUROC of 0.923. This approach demonstrated performance superior to that of human experts in classifying two diseases, especially in antibody assay-limited regions. Together, this approach provides an advanced nanomaterial-based tool for identifying vulnerable populations below the antibody threshold of aquaporin-4 positivity.

Diagnostic criteria and treatment of neuromyelitis optica spectrum disorders (NMOSD)

Neuromyelitis optic spectrum disorders (NMOSD) are rare, severely disabling diseases of the central nervous system. They are characterized by periodic, unpredictable exacerbations that lead to an accumulation of irreversible neurologic damage. Despite existing possibilities for diagnosing NMOSD, it can be difficult to make the correct diagnosis in clinical practice. Current treatment options for NMOSD include drugs that affect the pathogenesis of the disease, including complement C5 inhibitors, with which experience is still limited, but published data from clinical trials demonstrate high efficacy of these drugs with an acceptable safety profile. The article reviews the main current approaches to the diagnosis and treatment of NMOSD.

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

ObjectiveElectrolyte 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. MethodsThis cross-sectional study collected data from the nationwide administrative Diagnosis Procedure Combination (DPC) database and evaluated the overlap profiles. ResultsAmong 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. ConclusionsPatients 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.

Differentiation between multiple sclerosis and neuromyelitis optica spectrum disorder using a deep learning model

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the central nervous system (CNS) with similar characteristics. The differential diagnosis between MS and NMOSD is critical for initiating early effective therapy. In this study, we developed a deep learning model to differentiate between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using brain magnetic resonance imaging (MRI) data. The model was based on a modified ResNet18 convolution neural network trained with 5-channel images created by selecting five 2D slices of 3D FLAIR images. The accuracy of the model was 76.1%, with a sensitivity of 77.3% and a specificity of 74.8%. Positive and negative predictive values were 76.9% and 78.6%, respectively, with an area under the curve of 0.85. Application of Grad-CAM to the model revealed that white matter lesions were the major classifier. This compact model may aid in the differential diagnosis of MS and NMOSD in clinical practice.

The temporal relationship of paraneoplastic aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and breast cancer: a systematic review and meta-analysis.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy with evidence of neuroinflammation and demyelination that affects the central nervous system and is mediated by aquaporin-4 (AQP4) immunoglobulin (IgG). AQP4-IgG may also be present in paraneoplastic syndromes secondary to malignancy such as breast cancer. A systematic review and meta-analysis of the literature were completed using PubMed, Scopus, and ScienceDirect databases (CRD42022352109). A total of 12 publications, which included 19 cases, met the inclusion criteria and were assessed in both the qualitative and quantitative synthesis. The mean age was 51.26 years (SD: 13.12, SEM: 3.01), and 100% of the cases were reported in women. Speech abnormalities and symptoms of myelopathy were the most observed neurological manifestations. MRI often revealed longitudinally extensive transverse myelitis (LETM) involving the cervical spine. Three of 19 (15.9%) cases were diagnosed with NMOSD and breast cancer within the same month. Five of 19 (26.1%) cases had a diagnosis of breast cancer preceding that of NMOSD. Eight of 19 (42.1%) cases were diagnosed with breast cancer after NMOSD. The median time of breast cancer diagnosis was 1.0 months (range 216 months) after NMOSD. The diagnosis of breast cancer most often occurs after the onset of the paraneoplastic NMOSD symptoms. However, a wide time range for the diagnosis of breast cancer was observed both before and after the onset of neurological symptoms. Older women with a new diagnosis of NMOSD should be considered for frequent breast cancer screening.

Association of retinal microvascular abnormalities and neuromyelitis optica spectrum disorders with optical coherence tomography angiography.

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune central nervous system diseases characterized by the immune system's abnormal attack on glial cells and neurons. Optic neuritis (ON) is one of the indicators of NMOSD, often starting unilaterally and potentially affecting both eyes later in the disease progression, leading to visual impairment. Optical coherence tomography angiography (OCTA) has the potential to aid in the early diagnosis of NMOSD by examining ophthalmic imaging and may offer a window for disease prevention. In this study, we collected OCTA images from 22 NMOSD patients (44 images) and 25 healthy individuals (50 images) to investigate retinal microvascular changes in NMOSD. We employed effective retinal microvascular segmentation and foveal avascular zone (FAZ) segmentation techniques to extract key OCTA structures for biomarker analysis. A total of 12 microvascular features were extracted using specifically designed methods based on the segmentation results. The OCTA images of NMOSD patients were classified into two groups: optic neuritis (ON) and non-optic neuritis (non-ON). Each group was compared separately with a healthy control (HC) group. Statistical analysis revealed that the non-ON group displayed shape changes in the deep layer of the retina, specifically in the FAZ. However, there were no significant microvascular differences between the non-ON group and the HC group. In contrast, the ON group exhibited microvascular degeneration in both superficial and deep retinal layers. Sub-regional analysis revealed that pathological variations predominantly occurred on the side affected by ON, particularly within the internal ring near the FAZ. The findings of this study highlight the potential of OCTA in evaluating retinal microvascular changes associated with NMOSD. The shape alterations observed in the FAZ of the non-ON group suggest localized vascular abnormalities. In the ON group, microvascular degeneration in both superficial and deep retinal layers indicates more extensive vascular damage. Sub-regional analysis further emphasizes the impact of optic neuritis on pathological variations, particularly near the FAZ's internal ring. This study provides insights into the retinal microvascular changes associated with NMOSD using OCTA imaging. The identified biomarkers and observed alterations may contribute to the early diagnosis and monitoring of NMOSD, potentially offering a time window for intervention and prevention of disease progression.

Late and very late onset neuromyelitis optica spectrum disorders – a case series

Background and purpose: Neuromyelitis optica spectrum disorders are a group of autoimmune diseases leading to severe visual and motor impairment with a median disease onset at 39 years. Materials and methods: We present a case series of four AQP4-Ab positive neuromyelitis optica spectrum disorders patients, with a median age at onset of 67 years (ranging 54–72), in whom neuromyelitis optica spectrum disorder was not suspected at first, given unusual age and age-associated comorbidities. Results: Severe spinal cord involvement was the main finding in all patients. Two patients additionally manifested brainstem impairment in the form of area postrema syndrome and double vision. The therapeutic process included intravenous steroid pulses followed by long-term immunosuppression. Two of the patients died within a year of the diagnosis due to respiratory failure (one due to SARS-CoV-2 infection). One patient was started on satralizumab therapy with a significant motor improvement and good tolerance. One patient decided to suspend immunosuppressive treatment due to treatment-related gastrointestinal complaints. Conclusion: Based on the presented case series and the literature review, we assume that neuromyelitis optica spectrum disorders diagnosis should be considered regardless of age and comorbidity. New highly effective therapies with monoclonal antibodies are currently available. Early diagnosis and proper treatment may improve the outcome and prevent further visual and motor disability.

Establishment of a comprehensive diagnostic model for neuromyelitis optica spectrum disorders based on the analysis of laboratory indicators and clinical data.

To establish a comprehensive diagnostic model for neuromyelitis optica spectrum disorders (NMOSDs) based on laboratory indicators and clinical data. A retrospective method was used to query the medical records of patients with NMOSD from January 2019 to December 2021. At the same time, clinical data of other neurological diseases were also collected for comparison. Clinical data of the NMOSD group and non-NMOSD group were analyzed, and the diagnostic model was established based on these data. In addition, the model was evaluated and verified by the receiver operating curve. A total of 73 patients with NMOSD were included, and the ratio of males to females was 1:3.06. The indicators that showed differences between the NMOSD group and non NMOSD group included neutrophils (P = 0.0438), PT (P = 0.0028), APTT (P < 0.0001), CK (P = 0.002), IBIL (P = 0.0181), DBIL (P < 0.0001), TG (P = 0.0078), TC (P = 0.0117), LDL-C (P = 0.0054), ApoA1 (P = 0.0123), ApoB (P = 0.0217), TPO antibody (P = 0.012), T3 (P = 0.0446), B lymphocyte subsets (P = 0.0437), urine sg (P = 0.0123), urine pH (P = 0.0462), anti-SS-A antibody (P = 0.0036), RO-52 (P = 0.0138), CSF simplex virus antibody I-IGG (P = 0.0103), anti-AQP4 antibody (P < 0.0001), and anti-MOG antibody (P = 0.0036). Logistic regression analysis showed that changes in ocular symptoms, anti-SSA antibody, anti-TPO antibody, B lymphocyte subsets, anti-AQP4 antibody, anti-MOG antibody, TG, LDL, ApoB, and APTT had a significant impact on diagnosis. The AUC of the combined analysis was 0.959. The AUC of the new ROC for AQP4- and MOG- antibody negative NMOSD was 0.862. A diagnostic model was successfully established, which can play an important role in differential diagnosis of NMOSD.

Temporal Relationship of Breast Cancer and Paraneoplastic Neuromyelitis Optica Spectrum Disorder (NMOSD) (P13-5.001)

<h3>Objective:</h3> A systematic review and meta-analysis was conducted in order to characterize the temporal relationship between the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) and breast cancer. <h3>Background:</h3> Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory and demyelinating disorder affecting the optic nerve and spinal cord more frequently than other parts of the central nervous system (CNS). NMOSD was recognized as a unique condition with a chronic, relapsing course after the identification of IgG-class antibodies that bind to the water channel aquaporin-4 (AQP4-IgG) in serum from individuals with NMO. Typically this is an idiopathic autoimmune disorder, although there is increasing evidence behind the expression of AQP4 antibodies in the setting of an underlying tumor with NMOSD manifesting as a paraneoplastic syndrome. <h3>Design/Methods:</h3> This systematic review and meta-analysis was completed in accordance PRISMA guidelines. A literature search was conducted on PubMed/PubMed Central/MEDLINE, Scopus, and ScienceDirect databases. The review was registered with PROSPERO (Registration ID: CRD42022352109). <h3>Results:</h3> The search strategy yielded a total of 10 records, from which 16 cases were identified. Triple-negative breast cancer was the most prevalent form of breast cancer. Seven cases recorded the presence of longitudinally extensive transverse myelitis (LETM) involving the cervical and thoracic cord. Five cases identified lesions on magnetic resonance imaging (MRI) within the brainstem. And four cases described lesions within the cerebrum and/or cerebellum. Intravenous methylprednisolone (IVMP) was the most common agent used in the acute management of NMOSD. On average the diagnosis of NMOSD occurred 1.4 months before that of breast cancer. <h3>Conclusions:</h3> NMOSD is a rare autoimmune condition that can occur in a paraneoplastic manner. The diagnosis of NMOSD precedes that of breast cancer with a mean time of 1.4 months. Triple-negative breast cancer is the most commonly identified subtype. Common MRI findings include LETM of the cervical and thoracic cord as well as brainstem lesions. <b>Disclosure:</b> Dr. Sivakumar has nothing to disclose. Dr. Srichawla has nothing to disclose. Dr. Cheraghi has nothing to disclose.

Most Opticospinal Demyelination is NMOSD, not MS-A 17-year UK Longitudinal Cohort Study (P5-3.003)

<h3>Objective:</h3> To evaluate clinical outcomes in a cohort of patients with Opticospinal Demyelination (OSD). <h3>Background:</h3> Classification of central nervous system inflammation has progressed with the identification of aquaporin-4 (AQP4) antibodies in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibodies in MOG antibody disease (MOGAD) in addition to multiple sclerosis (MS). However, as defined in 2003, patients with opticospinal demyelination (optic neuritis (ON), short-segment transverse myelitis (TM), and brain imaging not supportive of MS) do not fulfil internationally approved criteria for MS, NMOSD, or MOGAD. <h3>Design/Methods:</h3> Between 2003–2005, 128 cases of OSD were reported via the British Neurological Surveillance Unit. In 2011, 2015 and 2022 patients and physicians were contacted for clinical, radiological, and serological (e.g., AQP4-IgG and MOG-IgG) data as part of a prospective longitudinal cohort study. <h3>Results:</h3> Of 128 cases, 67 (52%) patients fulfilled OSD diagnostic criteria. At 17 years 39/60 patients (65%) now met NMOSD diagnostic criteria, 14 (23%) had MS and 7 (12%) had OSD. The median time to diagnosis of NMOSD was 107 months (85–261) and to MS was 189 months (79–346). The median age of OSD patients at onset was 37 (25–48) years and 5/7 were male. A relapsing course was observed in 6/7 patients with a median annualised relapse rate of 0.22 (0.13–0.49). At last follow-up the median EDSS was 2.5 (range; 1–6.5) and only 2/7 patients had an EDSS&gt;3.5. <h3>Conclusions:</h3> OSD is diagnostically distinct from MS, NMOSD, and MOGAD. However, after 2 decades most OSD patients reached a diagnosis of NMOSD or MS, so OSD may lie on a spectrum with these conditions. Of the 12% of cases that retained OSD classification, all but 1 had a relapsing course but rates of significant disability were low. Future studies should focus on characterising diagnostic and prognostic biomarkers in this unique subtype of non-MS CNS inflammation. <b>Disclosure:</b> Dr. Forcadela has nothing to disclose. Dr. Rocchi has nothing to disclose. Dr. Panicker has nothing to disclose. Kerry Mutch has nothing to disclose. Dr. Huda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. Dr. Jacob has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ALEXION. Dr. Hamid has nothing to disclose.