Usefulness of the MFIS-K, FSS, and FACIT-F Fatigue Scales in Korean Patients With MS, NMOSD, and MOGAD.

BACKGROUND AND PURPOSE: Fatigue is common in demyelinating disorders of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aimed to validate the usefulness of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Fatigue Severity Scale (FSS) relative to the Korean version of the Modified Fatigue Impact Scale (MFIS-K) in Korean patients with MS, NMOSD, and MOGAD. METHODS: There were 294 patients with MS (n=120), NMOSD (n=103), or MOGAD (n=71) enrolled in a prospective demyelinating CNS registry. Fatigue was measured using the FACIT-F, MFIS-K, and FSS. Sleep quality, quality of life, depression, and pain were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 36-item Short-Form Survey (SF-36), and Beck Depression Inventory-II (BDI-II). RESULTS: The MFIS-K, FACIT-F, and FSS scores showed high internal consistencies and strong correlations with each other in the MS, NMOSD, and MOGAD groups. The scores on all three fatigue scales were correlated with PSQI, SF-36, and BDI-II results in the three groups. The areas under the receiver operating characteristic curves for the FSS and FACIT-F were 0.834 and 0.835, respectively, for MS, 0.877 and 0.833 for NMOSD, and 0.925 and 0.883 for MOGAD. CONCLUSIONS: These results suggest that the MFIS-K, FSS, and FACIT-F are useful and valuable assessment instruments for evaluating fatigue in Korean patients with MS, NMOSD, and MOGAD.

Longitudinal change of serum NfL as disease activity biomarker candidate in MOGAD: A descriptive cohort study.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) is an autoinflammatory disease of the central nervous system. MOGAD often follows a relapsing course that can lead to severe disability, but monophasic disease is possible as well. Currently, there is an unmet clinical need for disease activity biomarkers in MOGAD. Serum neurofilament light chain (sNfL) is a sensitive biomarker for neuroaxonal damage. However, data on longitudinal change of sNfL as disease activity biomarker for MOGAD are scarce. OBJECTIVE: To describe the longitudinal course of sNfL in adult patients with MOGAD in an active as well as a stable disease state in relation to clinical parameters and serum MOG-IgG titers. METHODS: We conducted a retrospective, exploratory, monocentric cohort study of adult patients with MOGAD. Cohort 1 consisted of five patients in whom NfL was tested as part of their routine clinical workup, all of which had active disease (maximum 6 months since last attack, median 3 months). Cohort 2 comprised 13 patients, which were tested for NfL in the context of a longitudinal study at predefined time intervals, mostly during remission (median 10 months since last attack). sNfL was measured using single molecule array (Simoa) technology at least at two time points (median 3) within a median observation time of 5 months in cohort 1, and at baseline and after a median duration of 12 months in cohort 2. MOG-IgG titers were measured by a fixed cell-based assay. RESULTS: Change in sNfL correlated positively with change in MOG-IgG titers (rho=0.59, p = 0.027). The variability of sNfL (difference between highest and lowest level) during the observation period was higher in patients who had an attack within six months before baseline (median 37 [interquartile range [IQR] 10-64] pg/ml vs. 2.3 [IQR 1-5] pg/ml, p = 0.006). sNfL increased in patients with an attack during the observation period. Patients with baseline sNfL measurement within two weeks after attack symptom onset displayed relatively low initial sNfL with an increase afterwards. CONCLUSIONS: Longitudinal sNfL change correlates with MOG-IgG titer change and may be a promising biomarker candidate for disease activity in MOGAD. Increasing sNfL levels might be utilized to adjudicate suspected attacks. In acute attacks, sNfL increase may occur with a delay after symptom onset.

Low T3 syndrome is associated with the severity of myelin oligodendrocyte glycoprotein antibody-associated disease exacerbation.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune inflammatory disease of the central nervous system, (CNS) different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). While numerous studies have delved into the involvement of thyroid antibodies (ATAbs) and thyroid function in NMOSD and MS. The objective of this study is to explore the clinical significance of thyroid dysfunction and ATAbs abnormalities in adult patients with MOGAD. Methods: 36 adult inpatients diagnosed with MOGAD and 47 sex- and age-matched healthy controls were enrolled. Patients were divided into two groups based on the presence or absence of low T3 syndrome. Demographics, clinical characteristics, and results of auxiliary examinations were compared across the subgroups. Moreover, an analysis was conducted to explore the correlations between thyroid hormone levels and Expanded Disability Status Scale (EDSS) scores. Results: Thyroid dysfunction was notably more frequent in MOGAD patients than healthy controls (p < 0.0001), particularly low T3 syndrome (p=0.03). Furthermore, subgroup analyses revealed that the low T3 syndrome group exhibited higher EDSS scores and a higher proportion of individuals with EDSS scores > 3, in comparison to the non-low T3 syndrome group (p = 0.014, p = 0.046). However, no significant differences were observed in demographic characteristics, annual relapse rates, clinical phenotypes, laboratory and MRI results, and EEG abnormalities between the two groups. Additional Spearman's analysis showed significantly negative correlations between the TT3 and FT3 levels with EDSS scores (r = -0.367, p = 0.028; r = -0.377, p = 0.024). Typical brain lesions and paralateral ventricle lesions were significantly rare in patients with positive ATAbs compared to those with negative ATAbs (p = 0.0001, p = 0.03), although the incidence of ATAbs abnormalities did not differ significantly between MOGAD patients and healthy controls. Conclusions: Overall, this study confirmed thyroid dysfunction, especially low T3 syndrome, is frequent in adult MOGAD patients. Patients with low T3 syndrome exhibited elevated EDSS scores and a significantly higher incidence of unfavorable condition. additionally, the correlation analysis model manifests that FT3 and TT3 levels were negatively correlated with EDSS scores. These evidences indicate that low T3 syndrome is associated with the severity of MOGAD exacerbation.

An Aberrant Case of Neuromyelitis Optica Spectrum Disorder With a Review of Literature.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, acquired demyelinating condition predominantly affecting middle-aged women and is characterized by spinal cord inflammation and optic neuritis. Anti-aquaporin 4 (AQP4) antibodies are typically seen in NMOSD. However, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) shares clinical and imaging similarities. In NMOSD, longitudinally extensive spinal cord lesions (LESCLs), optic neuritis predominantly affecting the posterior aspect of optic nerves, and optic radiations are seen on magnetic resonance imaging (MRI). The brain parenchymal lesions particularly involve the dorsal medulla (area postrema). The report presents a case of a 26-year-old female with recurrent episodes of weakness, pain, and sensory symptoms in both upper and lower limbs who was initially treated for multiple sclerosis. Upon experiencing new symptoms of blurred vision and ataxia, an MRI of the spine and brain was performed, which showed short-segment cervical cord involvement and a lesion in the conus medullaris, raising the suspicion of NMOSD. Subsequent antibody testing confirmed the presence of anti-AQP4 antibodies. While the involvement of the conus medullaris is classically associated with MOGAD, unusual findings in the present case highlight the importance of comprehensive imaging evaluation and raising awareness among clinicians and radiologists regarding the imaging spectrum of NMOSD, thus facilitating timely diagnosis and tailored treatment strategies.

A comparative study of hypothalamic involvement in patients with myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, and multiple sclerosis.

BACKGROUND AND PURPOSE: We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging. RESULTS: Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy. CONCLUSIONS: MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

Alterations of brain structural and functional connectivity networks topology and decoupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

OBJECTIVE: To investigate the alteration in structural and functional connectivity networks (SCN and FCN) as well as their coupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and determine if these properties could serve as potential biomarkers for the disease. MATERIALS AND METHODS: In total of 32 children with MOGAD and 30 age- and sex-matched healthy controls (HC) were employed to construct the SCN and FCN, respectively. The graph-theoretical analyses of the global properties, node properties of the 90 brain nodes, and the structural-functional connectivity (SC-FC) coupling of the two networks were performed. The graph-theoretical properties that exhibited significant differences were analyzed using partial correlation analysis in conjunction with the clinical scales, including the expanded disability status scale (EDSS), modified Rankin scale (mRS), and pediatric cerebral performance category (PCPC) of the MOGAD group. Subsequently, a machine learning model was developed to discriminate between MOGAD and the HC group, aiming to explore the potential of these properties as biomarkers. RESULTS: The SCN of the MOGAD group exhibited aberrant global properties, including an increased characteristic path length (Lp) and a decreased global efficiency (Eg), along with reduced nodal properties such as degree centrality (Dc), nodal efficiency (Ne), and local efficiency in multiple nodes. The FCN of the MOGAD group only exhibited decreased Dc, Ne, and betweenness centrality in two nodes of nodal properties. Besides, MOGAD showed a significant decrease in SC-FC coupling compared to the HC group. The analysis of partial correlation revealed significant correlations between several properties and the scales of EDSS and mRS in the MOGAD group. The machine learning method was used to extract six features and establish the model, achieving a classification accuracy of 82.3% for MOGAD. CONCLUSIONS: Pediatric MOGAD showed a more pronounced impairment in the SCN along with decoupling of SC-FC. Both partial correlation analysis and discriminant modeling suggest that alterations in brain network properties have the potential as biomarkers for assessing brain damage in MOGAD.

Brain lesion microstructure in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein disease.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) diagnosis are based on the presence of serological and magnetic resonance imaging (MRI) biomarkers. Diffusion tensor imaging (DTI), neurites orientation dispersion and density imaging (NODDI), and the Spherical Mean Technique (SMT) may be helpful to provide a microstructural characterization of the different types of white matter lesions and give an insight about their different pathological mechanisms. The aim of the study was to characterize microstructural differences between brain typical lesions (TLs) and nontypical lesions (nTLs). METHODS: A total of 17 NMOSD and MOGAD patients [9 Aquaporin4 (AQP4) + NMO, 2 seronegative-NMO, 6 MOGAD] underwent MRI scans on a 3 Tesla MAGNETON PRISMA. Diffusion parameters (fractional anisotropy; mean diffusivity [MD]; intracellular volume fraction [ICVF]; extra-neurite transverse diffusivity; and extra-neurite MD; neurite signal fraction) were obtained using DTI, NODDI, and SMT. Microstructural parameters within lesions were compared through a generalized linear model using age, sex, and total lesion volume as covariates. RESULTS: In NMOSD/MOGAD whole cohort (total lesions = 477), TLs showed increased MD and decreased ICVF compared to nTLs (p < .05), indicating higher inflammation and axonal loss. Similar results were found also in the AQP4 + NMO subgroup (decreased ICVF, p < .05). Furthermore, in NMOSD/MOGAD whole cohort and in AQP4 + NMO subgroup, TLs showed a trend toward higher EXRATRANS than nTLs, suggesting a more severe degree of demyelination within TLs. CONCLUSIONS: TLs and nTLs in NMOSD/MOGAD showed different diffusion MRI-derived microstructural features, with TLs showing a more severe degree of inflammation and fiber disruption with respect to nTLs.

Optic Nerve Imaging in Multiple Sclerosis and Related Disorders.

Optic neuritis is a common feature in multiple sclerosis and in 2 other autoimmune demyelinating disorders such as aquaporin-4 IgG antibody-associated neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease. Although serologic testing is critical for differentiating these different autoimmune-mediated disorders, MR imaging, which is the preferred imaging modality for assessing the optic nerve, can provide valuable information, suggesting a specific diagnosis and guiding the appropriate serologic testing.

Contributions of CSF interleukin-6 elevation to the pathogenesis of myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare neuroinflammatory disorder characterized by acute episodes of central nervous system (CNS) demyelination. Previous studies have reported elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) of MOGAD patients. OBJECTIVE: We examined if CSF IL-6 level increase is associated with clinical parameters in MOGAD. METHODS: IL-6 levels were measured using 44 CSF samples during the acute phase and 6 samples during recovery from 34 MOGAD patients, as well as 65 CSF samples from 45 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4Ab + NMOSD), 107 samples from 76 multiple sclerosis patients, and 45 samples from neurodegenerative disease patients. Associations between IL-6 levels and clinical parameters in MOGAD were also evaluated. RESULTS: CSF IL-6 levels were significantly comparably elevated during acute-phase in MOGAD and AQP4Ab + NMOSD, but declined following the acute phase. Among MOGAD patients, CSF IL-6 level was significantly correlated with CSF cell count, greater in patients with brain lesions than spinal cord lesions, and higher in CSF than serum, suggesting that excessive IL-6 is produced predominantly in CNS. Neurological recovery was tended to be poorer in MOGAD patients with higher CSF IL-6 level. CONCLUSION: CSF IL-6 may play important roles in the pathogenesis of MOGAD, especially in CNS inflammation.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Report.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a newly discovered autoimmune demyelinating disorder. The clinical manifestations of MOGAD are divergent but often characterized by inflammatory central nervous system (CNS) deficits such as optic neuritis, encephalitis, or transverse myelitis that predominantly affect the pediatric population. Despite the distinct features often associated with MOGAD, the disease exhibits a diverse range of clinical manifestations, making timely diagnosis and treatment challenging. In particular, distinguishing MOGAD from multiple sclerosis (MS) is important for adequate treatment and the prevention of relapsing disease. In this report, we present a rare case of MOGAD in a 57-year-old male who initially exhibited symptoms of bilateral optic nerve edema and flame hemorrhage. This led to an initial misdiagnosis of pseudotumor cerebri. Serological analysis at a tertiary care center ultimately led to the diagnosis of MOGAD after multiple visits to the ophthalmologist with worsening vision deficits.

Optic chiasm involvement in multiple sclerosis, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein-associated disease.

BACKGROUND: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated. AIMS: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON-) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers. METHODS: Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied. RESULTS: ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON- AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON- RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = -1.15, 95% confidence interval (CI) = -1.819 to -0.490, p = 0.001), worse visual acuity (RC = -0.026, 95% CI = -0.041 to -0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group. CONCLUSION: OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL.

Cognitive and psychopathological features of neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease: A narrative review.

Clinicians are becoming increasingly aware of the cognitive and psychopathological consequences of neurological diseases, which were once thought to manifest with motor and sensory impairments only. The cognitive profile of multiple sclerosis, in particular, is now well-characterised. Similar efforts are being made to better characterise the cognitive profile of other central nervous system inflammatory demyelinating autoimmune disorders. This review discusses the current understanding of the cognitive and psychological features of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Detailed analysis of the cognitive sequelae of the above conditions can not only assist with understanding disease pathogenesis but also can guide appropriate management of the symptoms and consequently, improve the quality of life and long-term outcomes for these patients. This narrative review will also identify research gaps and provide recommendations for future directions in the field.

Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.

Clinical Research into Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.

Aberrant white matter microstructure detected by automatic fiber quantification in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) is an idiopathic inflammatory demyelinating disorder in children, for which the precise damage patterns of the white matter (WM) fibers remain unclear. Herein, we utilized diffusion tensor imaging (DTI)-based automated fiber quantification (AFQ) to identify patterns of fiber damage and to investigate the clinical significance of MOGAD-affected fiber tracts. METHODS: A total of 28 children with MOGAD and 31 healthy controls were included in this study. The AFQ approach was employed to track WM fiber with 100 equidistant nodes defined along each tract for statistical analysis of DTI metrics in both the entire and nodal manner. The feature selection method was used to further screen significantly aberrant DTI metrics of the affected fiber tracts or segments for eight common machine learning (ML) to evaluate their potential in identifying MOGAD. These metrics were then correlated with clinical scales to assess their potential as imaging biomarkers. RESULTS: In the entire manner, significantly reduced fractional anisotropy (FA) was shown in the left anterior thalamic radiation, arcuate fasciculus, and the posterior and anterior forceps of corpus callosum in MOGAD (all p < 0.05). In the nodal manner, significant DTI metrics alterations were widely observed across 37 segments in 10 fiber tracts (all p < 0.05), mainly characterized by decreased FA and increased radial diffusivity (RD). Among them, 14 DTI metrics in seven fiber tracts were selected as important features to establish ML models, and satisfactory discrimination of MOGAD was obtained in all models (all AUC > 0.85), with the best performance in the logistic regression model (AUC = 0.952). For those features, the FA of left cingulum cingulate and the RD of right inferior frontal-occipital fasciculus were negatively and positively correlated with the expanded disability status scale (r = -0.54, p = 0.014; r = 0.43, p = 0.03), respectively. CONCLUSION: Pediatric MOGAD exhibits extensive WM fiber tract aberration detected by AFQ. Certain fiber tracts exhibit specific patterns of DTI metrics that hold promising potential as biomarkers.

MOG-IgG testing strategies in accordance with the 2023 MOGAD criteria: a clinical-laboratory assessment.

BACKGROUND: Live cell-based assay (LCBA) is the gold standard for MOG-IgG detection, and fixed CBA (FCBA) is a widely used commercial alternative. Recent criteria attributed a diagnostic value to MOG-IgG titration with both LCBA and FCBA, with low-titre samples requiring additional supporting features for MOGAD diagnosis. However, FCBA titration is not validated. We aimed to assess the impact of the criteria-based MOG-IgG testing in MOGAD diagnosis. METHODS: Thirty-eight serum samples of LCBA MOG-IgG1-positive MOGAD patients were titred on MOG-IgG LCBA and FCBA, and the presence of supporting features for MOGAD assessed. MOGAD criteria were evaluated in four testing scenarios: (a) FCBA without titration; (b) FCBA with titration; c) LCBA without titration; (d) LCBA with titration. RESULTS: FCBA without titration failed to reach MOGAD diagnosis in 11/38 patients (28.9%, negative results in 5, lack of supporting features in 6). Patients with unconfirmed diagnosis had optic neuritis (ON, n = 8), or transverse myelitis (TM, n = 3). FCBA with titration allowed MOGAD diagnosis in 4 additional patients. Correlation between LCBA and FCBA titres was moderate (Spearman's rho 0.6, p < 0.001). CONCLUSIONS: FCBA yields high rate of misdiagnosis mainly due a lower analytical sensitivity. FCBA titration provides a moderate diagnostic advantage in FCBA positive patients.

Clinical and imaging features of patients with late-onset myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: There is an age-dependent change in the clinical phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the clinical features of late-onset MOGAD have not been well described. METHODS: Clinical data of 110 MOGAD patients, including 21 late-onset patients with onset age greater than or equal to 50 years old were retrospectively analyzed. RESULTS: Compared to pediatric- and younger adult-onset ones, late-onset MOGAD patients experienced milder disease onset (p < 0.001), more monophasic course (p < 0.001), fewer relapses (p = 0.007), less cerebrospinal fluid leukocytosis (p = 0.021), less longitudinally extensive transverse myelitis (onset p = 0.026, whole course p = 0.028), fewer lesions in basal ganglia (whole course p = 0.012), thalamus (whole course p = 0.040) and cerebellum (whole course p = 0.028). However, they had more cerebral symptoms (p = 0.021 onset and whole course), more lesions in white matter (onset p = 0.005, whole course p < 0.001) and periventricular area (onset p = 0.026), along with longer and delayed therapeutic intervention (p < 0.001). The main differences in clinical characteristics between late-onset patients with and without these brain involvements might be comorbidities. CONCLUSIONS: Late-onset MOGAD are more likely to experience delayed diagnosis. Brain involvement may be modulated by comorbidities of the elderly, which alter the clinical manifestations of late-onset MOGAD.

A longitudinal analysis of brain volume changes in myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relapsing demyelinating condition. There are several cross-sectional studies showing evidence of brain atrophy in people with MOGAD (pwMOGAD), but longitudinal brain volumetric assessment is still an unmet need. Current recommendations do not include monitoring with MRI and assume distinct attacks. Evidence of ongoing axon loss will have diagnostic and therapeutic implications. In this study, we assessed brain volume changes in pwMOGAD over a mean follow-up period of 2 years and compared this to changes in people with multiple sclerosis (pwMS). METHODS: This is a retrospective single-center study over a 7-year period from 2014 to 2021. MRI brain scans at the time of diagnosis and follow-up in remission were collected from 14 Caucasian pwMOGAD, confirmed by serum myelin oligodendrocyte glycoprotein immunoglobulin G antibody presence, detected by live cell-based assays. Total brain volume (TBV), white matter (WM), gray matter (GM), and demyelinating lesion volumes were assessed automatically using the Statistical Parametric Mapping and FMRIB automated segmentation tools. MRI brain scans at diagnosis and follow-up on remission were collected from 32-matched pwMS for comparison. Statistical analysis was done using analysis of variance. RESULTS: There is evidence of TBV loss, affecting particularly GM, over an approximately 2-year follow-up period in pwMOGAD (p < .05), comparable to pwMS. WM and lesion volume change over the same period were not statistically significant (p > .1). CONCLUSION: We found evidence of loss of GM and TBV over time  in pwMOGAD, similar to pwMS, although the WM and lesion volumes were unchanged.