Antibody-associated Disease Research Articles

Renal Manifestations in CASPR2 Antibody-associated Diseases (P5-14.007)

Renal Manifestations in CASPR2 Antibody-associated Diseases (P5-14.007)

Trans-Synaptic Degeneration in the Visual Pathway in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON. Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell inner plexiform layer (GCIPL) were obtained using Heidelberg Spectralis. FreeSurfer7 was used to obtain the lateral geniculate nucleus (LGN), occipital volume fractions (to total estimated intracranial volume), and occipital cortical thickness. For the anterior visual pathway, the analysis was conducted using eyes, classified based on the history of ON (Eye-ON and Eye-NON) and compared with Eye-HC. The analysis of OCT and brain volumetric measures was conducted comparing MOGAD-ON, MOGAD-NON, and HC groups. The analysis of covariance with a Bonferroni-adjusted post hoc test was used to test differences between groups and linear regression analysis to evaluate OCT/MRI associations; age and sex were considered as covariates. 24 (70.5%) patients had a prior ON. Median pRNFL and GCIPL thickness (um) was significantly reduced in Eye-ON vs EyeNON and HC (pRNFL: 69.4 (17.3), 89.6 (13.7), 98.2 (11.7), p < 0.001; GCIPL: 55.8 (8.7), 67.39 (8.7), 72.6 (4.5), p < 0.001). pRNFL and GCIPL thickness had a negative correlation with the number of ON episodes (p = 0.025 and p = 0.031, respectively). LGN volume fraction was significantly lower in patients with MOGAD-ON than in HC (0.33 (0.05) vs 0.39 (0.04), p = 0.002). The occipital cortical thickness was lower in MOGAD-ON compared with MOGAD-NON and HC (p = 0.010). In patients with MOGAD-ON, pRNFL correlated with LGN volume (p = 0.006), occipital thickness (p = 0.002), and the medial occipital cortex (p = 0.002), but not the lateral occipital lobe. Compared with HC, MOGAD-ON exhibits reduced retinal thickness, primarily influenced by the presence and the number of prior ON episodes. Moreover, MOGAD-ON demonstrates significant atrophy in the retinal, subcortical, and cortical regions of the visual pathway, distinguishing them from MOGAD-NON and HC. These findings suggest that in patients with MOGAD neurodegeneration is tightly correlated with damage to the involved pathway.

Isolated Meningitis Is a Unique Clinical Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (P9-14.003)

Isolated Meningitis Is a Unique Clinical Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (P9-14.003)

Visual Evoked Potentials in MOG Antibody-associated Disease (P9-14.007)

Visual Evoked Potentials in MOG Antibody-associated Disease (P9-14.007)

Leber Hereditary Optic Neuropathy Plus Phenotype With Double Point Mutations (m.11778 G>A and m.14484T>C) and Concurrent Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD).

Leber Hereditary Optic Neuropathy Plus Phenotype With Double Point Mutations (m.11778 G>A and m.14484T>C) and Concurrent Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD).

The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies

BackgroundCertain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case.MethodsTo elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed.ResultsGFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80.ConclusionThe 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

A Case of Post Viral Acute Longitudinal Extensive Transverse Myelitis (LETM): MOGAD- A New Horizon

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children. It is a group of central nervous system demyelinating diseases caused by auto antibodies against myelin oligosaccharide protein, a myelin sheath component protein, and present with a variety of symptoms, including optic neuritis, longitudinal extensive transverse myelitis (LETM), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, and corticobasal encephalitis. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Here, we present a case of a young male with acute onset of spastic paraplegia with sphincters involvement and patchy loss of pinprick sensation with positive Anti-MOG Antibody shortly after viral febrile illness. Bangladesh Crit Care J March 2024; 12 (1): 62-67

Biomarkers for neuromyelitis optica: a visual analysis of emerging research trends.

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for biomarkers for neuromyelitis optica has been ongoing. Here, we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica. Research in this area is consistently increasing, with China and the United States leading the way on the number of studies conducted. The Mayo Clinic is a highly reputable institution in the United States, and was identified as the most authoritative institution in this field. Furthermore, Professor Wingerchuk from the Mayo Clinic was the most authoritative expert in this field. Keyword analysis revealed that the terms "neuromyelitis optica" (261 times), "multiple sclerosis" (220 times), "neuromyelitis optica spectrum disorder" (132 times), "aquaporin 4" (99 times), and "optical neuritis" (87 times) were the most frequently used keywords in literature related to this field. Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis. Furthermore, aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder. Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarker for myelin oligodendrocyte glycoprotein antibody-associated disease. Recent biomarkers for neuromyelitis optica include cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein, serum astrocyte damage biomarkers like FAM19A5, serum albumin, and gamma-aminobutyric acid. The latest prospective clinical trials are exploring the potential of these biomarkers. Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder. The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity, specificity, and safety for the accurate diagnosis of neuromyelitis optica.

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.

Advancing Expertise in the Understanding of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Masterclass Event Summary

A masterclass initiated, organised, and funded by UCB, sought to advance understanding and expertise of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD is a rare central nervous system (CNS) inflammatory disorder. It has only relatively recently been characterised as a separate entity to similar demyelinating conditions, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Differentiating MOGAD from MS and NMOSD can be challenging, but is essential to ensure a correct diagnosis in order to guide effective treatment and management. An increase in the availability of cell-based assays (CBA) for detection of autoantibodies directed against myelin oligodendrocyte glycoprotein (MOG) over the last decade has provided healthcare professionals with an important new diagnostic tool. However, the approach has limitations in terms of sensitivity and specificity, meaning results must be considered alongside clinical characteristics and neuroimaging. A proposed diagnostic pathway by the international MOGAD panel, published in March 2023, sets out the core clinical demyelinating events that could suggest MOGAD, when MOG-IgG testing may be appropriate, and when supporting clinical or MRI features are required to confirm a diagnosis. These consensus criteria are now being evaluated by centres around the world. This article will summarise the talks given by key opinion leaders from across Europe and the USA during the educational event. They discussed the pathology and presentation of MOGAD, how to integrate imaging into diagnostic pathways, and current management approaches. They also looked at possible future directions, in terms of novel treatment approaches.

MOGAD: A novel disease

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated inflammatory neurological disease and a new addition to the demyelinating disorders of the central nervous system(CNS).In MOGAD, specific antibodies (MOG IgG) targeting MOG protein lead to primary demyelination in the CNS, but notably spare astrocytes. The most frequent presentation in children is ADEM and in adult ON. We present a case of 20 year old female who visited our OPD with complaints of diminution of vision with muscular weakness and strain while walking with a history of two similar episodes in the past. The clinical characteristics, laboratory investigation and neuroimaging help in diagnosis. Although the prognosis is generally favorable but severe residual disability can also occur.This underscores the importance of identifying the causes of demyelination on time and prompt treatment of this rather novel disease by judicious use of steroids based on standard protocolresulting in the general well-being of the patient. The present case therefore highlights the need to create awareness of the Clinical-Lab-Imaging characteristics of MOGAD andalso suggests the importance of making a detailed multidisciplinary approach into the cause of optic neuritis for better prognosis.

Myelin oligodendrocyte glycoprotein antibody titers by fixed cell-based assay: positive predictive value and impact of sample collection timing.

In January 2023, our laboratory began performing serum myelin oligodendrocyte glycoprotein antibody (anti-MOG) titers by fixed cell-based assay (CBA). As a quality assurance (QA) assessment, we evaluated titer positive predictive value (PPV) as well as impact of sample collection timing on titers. Among patients who underwent antibody titers to distinguish between low-positive (<1:100) and clear-positive (≥1:100) anti-MOG, records were reviewed to classify results as true-positive (TP) or false-positive (FP) and facilitate PPV calculation. Timing of sample collection relative to administration of immunotherapy and symptom onset was determined for TP results. Overall PPV of anti-MOG was 70/85 (82%). The PPV of low-positive anti-MOG was significantly lower than clear-positive anti-MOG (72% vs. 95%, p = 0.009). The difference in PPV between low-positive and clear-positive anti-MOG was significant among adults tested, but not children. Among patients with TP anti-MOG, the proportion who received immunotherapy prior to sample collection was significantly higher and median time from symptom onset to sample collection was significantly longer for low-positive compared to clear-positive results. Overall PPV of anti-MOG testing by fixed CBA was reasonably high. The PPV of low-positive anti-MOG was significantly lower than clear-positive anti-MOG. This was driven by the significantly lower PPV of low-positive anti-MOG in adults, possibly reflecting the lower prevalence of MOG antibody-associated disease among adults tested. Timing of sample collection relative to administration of immunotherapy and symptom onset may substantially impact titers, indicating that testing should ideally be performed prior to immunotherapy and close to time of attack.

Cerebrospinal fluid eosinophils in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease

BackgroundEosinophils in cerebrospinal fluid (CSF) are an uncommon finding most often associated with parasitic infections, but have also been described in some neuroinflammatory disorders. Eosinophilic infiltration is not thought to be a typical feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aim to describe the rate of CSF eosinophil positivity in a cohort of pediatric MOGAD patients. MethodsSingle-center retrospective chart review of pediatric MOGAD patients. Clinical and laboratory data was collected from the electronic medical record and analyzed. ResultsOf 46 pediatric patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) identified, 38 patients fulfilling internationally proposed MOGAD diagnostic criteria were included for analysis. 6 patients with MOGAD were excluded as no CSF data was available, and 2 patients with positive MOG-IgG but diagnosis more consistent with MS were excluded. Median age was 7.3 years, and 19/38 (50 %) were female. Acute disseminated encephalomyelitis (ADEM) was the most common presenting phenotype (23/38, 61 %), and other phenotypes included optic neuritis (10/38, 26 %), transverse myelitis (3/38, 8 %), and neuromyelitis optica spectrum disorder (NMOSD) (2/38, 5 %). 12 of 36 (33 %) patients with all lumbar puncture (LP) data available had CSF eosinophils present, with eosinophil mean of 3 % and range from 1 % to 18 % of CSF while blood cells. ConclusionCSF eosinophils were present in one third of pediatric MOGAD patients, which is a higher rate than previously reported in either MOGAD or aquaporin-4 antibody positive NMOSD cohorts. Understanding the CSF composition of pediatric MOGAD patients helps to facilitate more prompt diagnosis and treatment and may shed light onto underlying pathologic mechanisms of disease with the goal to inform future therapeutic targets.

Less common phenotypes of myelin oligodendrocyte glycoprotein antibody-related diseases in children deserve more attention

BackgroundTo facilitate the identification of less common clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in children.MethodsWe retrospectively reviewed medical records of 236 patients with MOGAD. The following phenotypes were considered to be typical for MOGAD: ADEM, ON, TM, and NMOSD. Less common onset clinical phenotypes were screened out; their clinical and magnetic resonance imaging (MRI), diagnosis, treatment, and prognosis were summarized and analyzed.Results16 cases (6.8%) presented as cortical encephalitis, with convulsions, headache, and fever as the main symptoms. 15 cases were misdiagnosed in the early period. 13 cases (5.5%) showed the overlapping syndrome of MOGAD and anti-N-methyl-D aspartate receptor encephalitis (MNOS), with seizures (92.3%) being the most common clinical symptom. 11 cases (84.6%) showed relapses. The cerebral leukodystrophy-like phenotype was present in seven cases (3.0%), with a recurrence rate of 50%. Isolated seizures without any findings on MRI phenotype was present in three cases (1.3%), with the only clinical symptom being seizures of focal origin. Three cases (1.3%) of aseptic meningitis phenotype presented with prolonged fever.Conclusion40/236 (16.9%) of children with MOGAD had less common phenotypes. Less common clinical phenotypes of pediatric MOGAD are susceptible to misdiagnosis and deserve more attention.ImpactThis is the first comprehensive analysis and summary of all less commonl clinical phenotypes of MOGAD in children, while previous studies have only focused on a specific phenotype or case reports.We analyzed the characteristics of MOGAD in children and further revealed the reasons why these less common clinical phenotypes are prone to misdiagnosis and deserve more attention.Our research on treatment has shown that early detection of MOG antibodies and early treatment are of great significance for improving the prognosis of these patients.

Seizures in inflammatory demyelinating disorders of the central nervous system

BackgroundMultiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may be associated with acute symptomatic seizures and chronic epilepsy as well. The clinical features of the seizures and/or accompanying epilepsy seen in each disease group may vary. In this study, we aimed to contribute to the existing literature by describing the clinical features of seizures and epilepsy in our demyelinating patient population. MethodsWe retrospectively analyzed patients who were followed up in our tertiary referral center neurology demyelinating diseases outpatient clinic between 2019 and 2024. Patients who had at least one seizure before, simultaneously, or after the diagnosis of demyelinating disease were included in the study. ResultsAmong 1735 patients with MS, 40 had experienced at least one epileptic seizure (2.3 %). Thirty patients (1.7 %) had seizures that could not be explained by another factor than MS. When secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) were compared, the interval between MS-epilepsy diagnosis was longer and seizure recurrence was more in SPMS. However, the prognosis of epilepsy was good in both subtypes. There were 21 patients followed up with antibody-positive neuromyelitis optica spectrum disorder. No patient had a seizure during the follow-up. We identified 56 patients who fulfilled the criteria for MOGAD with high antibody titers. Seizures were observed in three of them (5.4 %). All of them had status epilepticus either at the onset or during the course of the disease. ConclusionEven rare, seizures constitute one of the important clinical features of the inflammatory demyelinating disorders of the central nervous system. The pathophysiologic mechanism underlying seizures in MS is still not clear. Seizures may occur through different mechanisms in patients where seizures are the initial symptom or a sign of relapse and those that occur spontaneously during the progressive course of the disease. Prevalence of status epilepticus was common in MOGAD patients. Given the rarity of the seizures in CNS demyelinating disorders, it is difficult the define clinical and pathophysiological characteristics of accompanying seizures and epilepsy. Future studies conducted on large patient groups will contribute to the existing literature.

Is there an immunological cross-reactivity of antibodies to the myelin oligodendrocyte glycoprotein and coronaviruses?

Recent reports indicated that myelin oligodendrocyte glycoprotein antibody-associated disease might be a rare complication after severe acute respiratory syndrome coronavirus 2 infection or vaccination. It is unclear whether this is an unspecific sequel of infection or vaccination or caused by possible immunological cross-reactivity of severe acute respiratory syndrome coronavirus 2 proteins and myelin oligodendrocyte glycoprotein. The aim of this study was therefore to elucidate whether there is an immunological cross-reactivity between severe acute respiratory syndrome coronavirus 2 spike or nucleocapsid proteins and myelin oligodendrocyte glycoprotein and to explore the relation of antibody responses against myelin oligodendrocyte glycoprotein and severe acute respiratory syndrome coronavirus 2 and other coronaviruses. We analysed serum samples from patients with severe acute respiratory syndrome coronavirus 2 infection and neurological symptoms with (myelin oligodendrocyte glycoprotein antibody-associated disease, n = 12) or without myelin oligodendrocyte glycoprotein-antibodies (n = 10); severe acute respiratory syndrome coronavirus 2 infection without neurological symptoms (n = 32); vaccinated patients with no history of severe acute respiratory syndrome coronavirus 2 infection and neurological symptoms with (myelin oligodendrocyte glycoprotein antibody-associated disease, n = 10) or without myelin oligodendrocyte glycoprotein-antibodies (n = 9); and severe acute respiratory syndrome coronavirus 2 negative/naïve unvaccinated patients with neurological symptoms with (myelin oligodendrocyte glycoprotein antibody-associated disease, n = 47) or without myelin oligodendrocyte glycoprotein-antibodies (n = 20). All samples were analysed for serum antibody responses to myelin oligodendrocyte glycoprotein, severe acute respiratory syndrome coronavirus 2, and other common coronaviruses (CoV-229E, CoV-HKU1, CoV-NL63 and CoV-OC43). Based on sample amount and antibody titres, 21 samples were selected for analysis of antibody cross-reactivity between myelin oligodendrocyte glycoprotein and severe acute respiratory syndrome coronavirus 2 spike and nucleocapsid proteins using affinity purification and pre-absorption. Whereas we found no association of immunoglobulin G and A myelin oligodendrocyte glycoprotein antibodies with coronavirus antibodies, infections with severe acute respiratory syndrome coronavirus 2 correlated with an increased immunoglobulin M myelin oligodendrocyte glycoprotein antibody response. Purified antibodies showed no cross-reactivity between severe acute respiratory syndrome coronavirus 2 spike protein and myelin oligodendrocyte glycoprotein. However, one sample of a patient with myelin oligodendrocyte glycoprotein antibody-associated disease following severe acute respiratory syndrome coronavirus 2 infection showed a clear immunoglobulin G antibody cross-reactivity to severe acute respiratory syndrome coronavirus 2 nucleocapsid protein and myelin oligodendrocyte glycoprotein. This patient was also seropositive for other coronaviruses and showed immunological cross-reactivity of severe acute respiratory syndrome coronavirus 2 and CoV-229E nucleocapsid proteins. Overall, our results indicate that an immunoglobulin G antibody cross-reactivity between myelin oligodendrocyte glycoprotein and severe acute respiratory syndrome coronavirus 2 proteins is rare. The presence of increased myelin oligodendrocyte glycoprotein-immunoglobulin M antibodies after severe acute respiratory syndrome coronavirus 2 infection may either be a consequence of a previous infection with other coronaviruses or arise as an unspecific sequel after viral infection. Furthermore, our data indicate that myelin oligodendrocyte glycoprotein-immunoglobulin A and particularly myelin oligodendrocyte glycoprotein-immunoglobulin M antibodies are a rather unspecific sequel of viral infections. Finally, our findings do not support a causative role of coronavirus infections for the presence of myelin oligodendrocyte glycoprotein-immunoglobulin G antibodies.

Isolated myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in adults: The importance of age of onset and prognosis-related radiological features

BackgroundMyelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) exhibits phenotypic diversity and it varies by age. However, less is known about whether the manifestations of isolated MOG antibody-associated optic neuritis (iMOG-ON) vary across different age groups. We aimed to investigate the clinical and prognostic features of iMOG-ON in young and middle-aged adult patients. MethodsPatients with iMOG-ON were enrolled in the Department of Neurology, Beijing Tongren Hospital, Capital Medical University between January 2018 and October 2021. Medical records were reviewed to obtain clinical data and orbital MRI images of adult patients with iMOG-ON. Multivariate linear regression analysis was performed to investigate the associations between final best-corrected visual acuity (BCVA) in logMAR and clinical characteristics. ResultsBased on the age of onset, 70 patients were divided into 2 groups: 38 young (< 46 years; female/male = 0.76:1) and 32 middle-aged (≥ 46 years; female/male = 5.56:1) adults. There were statistical differences in both the female-to-male ratio and frequencies of contrast enhancement of the optic nerve sheaths and surrounding orbital tissues between both groups (p = 0.001, p = 0.004, respectively). The average follow-up periods were 28.04 ± 11.22 months. The median final BCVA was 0 (0 - 0.50) logMAR and 0.5 (0.3 - 1.0) logMAR in the young and middle-aged patients, respectively (p = 0.000). The multivariate linear regression analysis indicated significant positive relationships between final BCVA and age of onset (p = 0.038, 95 % CI: 0.020 - 0.728), sex (p = 0.030, 95 % CI: -0.793 - -0.042), BCVA at nadir (p = 0.000, 95 % CI: 0.164 - 0.386), and numbers of segments of optic nerve lesions (p = 0.009, 95 % CI: 0.068 - 0.450) with a coefficient of determination (R2) of 0.359 after adjusting for prior attacks of ON, time intervals between sudden-onset vision loss and administration of intravenous methylprednisolone, and corticosteroid dosages. The worst final BCVA was observed in afflicted eyes with lesions extending across three segments of the optic nerve. ConclusionCompared to young adults with iMOG-ON, the middle-aged patients tended to have a female predominance, higher frequencies of perineural enhancement, and worse visual outcomes. In addition to age of onset, visual recovery may also be influenced by patient's sex, BCVA at nadir, and lengths of longitudinally expansive lesions of the optic nerve to a certain extent.

The diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in children

Over the last two decades, immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG), previously thought to be a biomarker of multiple sclerosis (MS), have been shown to cause a distinct disease called MOG antibody-associated disease (MOGAD). MOGAD accounts for approximately one-third of all demyelinating syndromes in children and is the second most common central nervous system (CNS) demyelinating disease after MS. The diagnosis is made by detecting anti-MOG IgG antibodies against the natural MOG antigen, in the presence of compatible clinical and neuroradiological features. However, due to controversies in the methodologies for detecting anti-MOG antibodies and their diagnostic cutoff values, as well as the expanding clinical spectrum, accurate diagnosis may be challenging, at least in a subset of patients. Clinical presentations of MOGAD vary by age; the highest rates are seen in acute disseminated encephalomyelitis in younger children and optic neuritis, myelitis, or brainstem symptoms in older children. Although it was previously thought to be a milder demyelinating disorder and to have a monophasic course in the majority of patients, recent studies have shown that relapses occur in about half of the patients and sequelae develop in a significant proportion of them, especially in those with persistently high antibody titers, leukodystrophy-like magnetic resonance imaging (MRI) lesions, and spinal cord involvement. However, due to the monophasic course in about half of the patients, long-term treatment is not recommended after the first clinical episode but is recommended for patients who experience relapse. Accurate and early diagnosis of MOGAD is essential for proper management and better outcome. This review covers the challenges in the diagnosis of MOGAD in children.

Clinical analysis of myelin oligodendrocyte glycoprotein antibody-associated disease in a diverse cohort of children: A single-center observational study

BackgroundPrognostic markers for relapse and neurological disability following the first clinical event in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remain lacking. We investigated the clinical profiles and early prognostic factors associated with relapsing disease or impaired functional outcome in a large single-center cohort of pediatric MOGAD. MethodsWe retrospectively analyzed the clinical and paraclinical data and treatment outcomes of children with MOGAD seen at Children's Health in Dallas, Texas from 2009 to 2022. Univariate analyses were used to evaluate factors from initial event associated with relapsing disease course and impaired functional outcome (modified Rankin scale [mRS] >1) at final follow-up. ResultsOur cohort comprised of 87 children of diverse race/ethnicity. Presentation with acute disseminated encephalomyelitis (ADEM) was more frequent in children aged ≤8 years and Caucasian background, whereas presentation with optic neuritis was more common in children aged >8 years and other race/ethnicity. 44.3 % (27/61) had relapsing disease course, of whom 48.0 % had multiple relapses. 30.3 % (23/76) had final mRS >1. Children with abnormal electroencephalogram had reduced relapse risk. Children with ADEM presentation, severe disease, low MOG-IgG titer, and central and systemic inflammation (represented by cerebrospinal fluid pleocytosis and serum leukocytosis, respectively) at onset had higher likelihood of final mRS >1. ConclusionAbnormal electroencephalogram at the first event was associated with reduced relapse risk while disease severity and peripheral inflammation significantly contributed to final neurological disability. Further studies are needed to validate these findings as early risk factors for disability and relapse and to identify optimal treatment strategies.

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

Background and ObjectivesMyelin 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. MethodsA 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. ResultsIn 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. ConclusionPediatric 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.