Myelin Oligodendrocyte Glycoprotein Antibody-associated Disorders Research Articles

382 Severe manifestation of myelin oligodendrocyte glycoprotein antibody-associated disorder

382 Severe manifestation of myelin oligodendrocyte glycoprotein antibody-associated disorder

Novel Automated Chemiluminescent Immunoassay for the Detection of Autoantibodies Against Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders

Background/Objectives: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-related neurological disease that primarily affects the optic nerve and spinal cord. According to current international consensus guidelines for NMOSD, confirming the presence of aquaporin-4 immunoglobulin G antibody (AQP4-IgG) is one of the most important diagnostic criteria because AQP4-IgG is a significant diagnostic biomarker of NMOSD. Several assays are currently available for detecting AQP4-IgG, including cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs). However, each assay has certain disadvantages, including insufficient sensitivity and specificity, the need for sophisticated techniques, and semi-quantitative results. Methods: We developed a fully automated chemiluminescent enzyme immunoassay (CLEIA) to detect AQP4-IgG (AQP4-CLEIA). This assay utilizes the recombinant antigen purified from the newly generated AQP4-M23 stably expressing Chinese hamster ovary cell line and an anti-AQP4 monoclonal antibody as a calibrator. Results: In analytical performance studies, the assay demonstrates good precision and linearity over the entire measurement range. Moreover, this assay showed no high-dose hook effect and interference from endogenous substances. In clinical validation studies, patients with AQP4-IgG positive NMOSD, multiple sclerosis, or myelin oligodendrocyte glycoprotein antibody-associated disorder and healthy individuals were tested. A cutoff value of 10.0 U/mL was determined by receiver operating characteristic curves based on the results of a microscopic live CBA. The sensitivity and specificity for AQP4-IgG-positive NMOSD were 97.0% and 100.0%, respectively, at the cutoff value. Conclusions: The results suggest that AQP4-CLEIA is a convenient automated method for measuring AQP4-IgG titers in hospitals and clinical laboratories, offering an effective alternative to the gold-standard CBA.

Cerebrospinal fluid neurofilament light chain levels in children with acquired demyelinating syndrome.

To study the cerebrospinal fluid (CSF) neurofilament light chain (NfL) in pediatric acquired demyelinating syndrome (ADS) and its association with factors of laboratory and imaging results. We analyzed clinical data from children with ADS collected from May 2020 to January 2021 at the Department of Neurology of Guangzhou Women and Children's Medical Center. Enzyme-linked immunosorbent assays were used to detect the CSF NfL of patients. Thirty pediatric ADS patients (17 male, 13 female) were included in the study. The most frequent diagnosis was uncategorized ADS (36.7%, 11/30), followed by acute disseminating encephalomyelitis (ADEM) (23.3%, 7/30), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) (20.0%, 6/30), NMO (6.7%, 2/30), multiple sclerosis (MS) (6.7%, 2/30), and neuromyelitis optic spectrum disorders (NMOSD) (6.7%, 2/30). The median CSF NfL for the first time was 7,425.28 pg/ml (interquartile range, 1,273.51, >10,000 pg/ml). CSF NfL increase over normal value (<290.00 pg/ml for people younger than 30 years old) was seen in 98.7% of patients. Patients were divided into uncategorized ADS, ADEM, MOGAD, and MS/NMO/NMOSD groups, with no significant difference in CSF NfL between each group. The CSF NfL positively correlated with the immunoglobulin (Ig) G (ρ = 0.473) and IgE (ρ = 0.366). However, the CSF NfL did not correlate with CSF white blood count and CSF protein. Furthermore, there was no significant difference between patients with oligoclonal bands positive and without. The CSF NfL negatively correlated with interferon γ (ρ = -0.501), CD45 + CD3+ T (ρ = -0.466), CD45 + CD3 + CD4+ T (ρ = -0.466), and CD45 + CD3 + CD8+ T cells (ρ = -0.521). However, it did not correlate with CD45 + CD19+ B cells. CSF NfL in patients with cerebral white matter lesions in MRI was higher than in patients without. Moreover, the CSF NfL positively correlated with the number of brain MRI locations (ρ = 0.362). Nine patients underwent multiple detections of CSF NfL, and their CSF NfL for the last detection was not significantly different from the first. The CSF NfL increases significantly in pediatric ADS, and it can be a biomarker of neuro-axonal injury and a good indication of the extent of lesions.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) Presenting as Optic Neuritis: A Case Series

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) Presenting as Optic Neuritis: A Case Series

Clinico-radiologic Spectrum and Outcome of Pediatric Acquired Demyelinating Disorders of Central Nervous System: A Retrospective Indian Tertiary Care Hospital Cohort.

Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied. Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS (n = 27), ADEM (n = 16), NMOSD (n = 13), MS (n = 1), and MOGAD (n = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p = 0.004), spinal cord (p = 0.01), and cerebellar lesions (p = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% (n = 64) had good recovery, 8.6% (n = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed. The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.

Blood parameters in pediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Background and objectivesPatients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) clinically present e.g. with acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis (TM) or aquaporin-4-IgG (AQP4-IgG) negative neuromyelitis optica spectrum disorders (NMOSD)-like phenotypes. We aimed to analyze and compare blood parameters in children with MOGAD, AQP4-IgG-positive NMOSD (hence NMOSD), multiple sclerosis (MS) and healthy controls (HC). MethodsWe evaluated differences in complete blood counts (CBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and C-reactive protein (CRP) between these four groups and within the groups between clinical attack, acute treatment and remission. ResultsOur cohort consisted of 174 children and adolescents with a total of 550 timepoints: 66 patients had MOGAD (202 timepoints), 11 NMOSD (76 timepoints), 58 MS (219 timepoints) and 39 were HC (53 timepoints). At clinical attack, leukocyte counts were elevated in MOGAD compared to remission (p < 0.001) and compared to all other groups (p < 0.001). NLR was high in MOGAD and NMOSD, and PLR was high in NMOSD, however, after correction for multiple testing these findings did not remain significant. While glucocorticoids caused an increase of leukocyte counts and NLR in NMOSD and MS, these values remained stable during acute treatment in MOGAD. In remission, NLR normalized in MOGAD, while it stayed high in NMOSD. PLR increased in NMOSD and was significantly higher compared to all other groups. DiscussionSome blood parameters, mainly leukocyte and differential counts, might help clinicians to evaluate disease activity, differentiate relapses from pseudo-relapses and even distinguish between different disease entities.

Sensorineural Hearing Loss in Seropositive Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder

Sensorineural Hearing Loss in Seropositive Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder

Regional spinal cord volumes and pain profiles in AQP4-IgG + NMOSD and MOGAD.

Aquaporin-4-antibody-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) are relapsing neuroinflammatory diseases, frequently leading to chronic pain. In both diseases, the spinal cord (SC) is often affected by myelitis attacks. We hypothesized that regional SC volumes differ between AQP4-IgG + NMOSD and MOGAD and that pain intensity is associated with lower SC volumes. To evaluate changes in the SC white matter (WM), gray matter (GM), and pain intensity in patients with recent relapses (myelitis or optic neuritis), we further profiled phenotypes in a case series with longitudinal imaging and clinical data. Cross-sectional data from 36 participants were analyzed in this retrospective study, including 20 AQP4-IgG + NMOSD and 16 MOGAD patients. Pain assessment was performed in all patients by the Brief Pain Inventory and painDETECT questionnaires. Segmentation of SC WM, GM, cervical cord volumes (combined volume of WM + GM) was performed at the C2/C3 cervical level. WM% and GM% were calculated using the cervical cord volume as a whole per patient. The presence of pain, pain severity, and clinical disability was evaluated and tested for associations with SC segmentations. Additionally, longitudinal data were deeply profiled in a case series of four patients with attacks between two MRI visits within one year. In AQP4-IgG + NMOSD, cervical cord volume was associated with mean pain severity within 24 h (β = -0.62, p = 0.009) and with daily life pain interference (β = -0.56, p = 0.010). Cross-sectional analysis showed no statistically significant SC volume differences between AQP4-IgG + NMOSD and MOGAD. However, in AQP4-IgG + NMOSD, SC WM% tended to be lower with increasing time from the last attack (β = -0.41, p = 0.096). This tendency was not observed in MOGAD. Our case series including two AQP4-IgG + NMOSD patients revealed SC GM% increased by roughly 2% with either a myelitis or optic neuritis attack between visits. Meanwhile, GM% decreased by 1-2% in two MOGAD patients with a myelitis attack between MRI visits. In AQP4-IgG + NMOSD, lower cervical cord volume was associated with increased pain. Furthermore, cord GM changes were detected between MRI visits in patients with disease-related attacks in both groups. Regional SC MRI measures are pertinent for monitoring disease-related cord pathology in AQP4-IgG + NMOSD and MOGAD.

Myelin oligodendrocyte glycoprotein antibody‐associated disorders: An overview

AbstractIn recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.

Diagnostic Value of Multiparameter MRI-Based Radiomics in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders.

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) have a higher prevalence among children. For children undergoing the initial manifestation of MOGAD, prompt diagnosis has paramount importance. This study assessed the performance of multiparameter MRI-based radiomics in distinguishing patients with and without MOGAD with idiopathic inflammatory demyelinating diseases. We enrolled a cohort of 121 patients diagnosed with idiopathic inflammatory demyelinating diseases, including 68 children with MOGAD and 53 children without MOGAD. Radiomics models (T1WI, T2WI, FLAIR, and compound model) using features extracted from demyelinating lesions within the brain parenchyma were developed in the training set. The performance of these models underwent validation within the internal testing set. Additionally, we gathered clinical factors and MRI features of brain parenchymal lesions at their initial presentation. Subsequently, these variables were used in the construction of a clinical prediction model through multivariate logistic regression analysis. The areas under the curve for the radiomics models (T1WI, T2WI, FLAIR, and the compound model) in the training set were 0.781 (95% CI, 0.689-0.864), 0.959 (95% CI, 0.924-0.987), 0.939 (95% CI, 0.898-0.979), and 0.989 (95% CI, 0.976-0.999), respectively. The areas under the curve for the radiomics models (T1WI, T2WI, FLAIR, and the compound model) in the testing set were 0.500 (95% CI, 0.304-0.652), 0.833 (95% CI, 0.697-0.944), 0.804 (95% CI, 0.664-0.918), and 0.905 (95% CI, 0.803-0.979), respectively. The areas under the curve of the clinical prediction model in the training set and testing set were 0.700 and 0.289, respectively. Multiparameter MRI-based radiomics helps distinguish MOGAD from non-MOGAD in patients with idiopathic inflammatory demyelinating diseases.

Clinical features of MOGAD with brainstem involvement in the initial attack versus NMOSD and MS.

To assess the characteristics of Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) with brainstem involvement in the first event (BSIFE) and make comparisons with aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS). From 2017 to 2022, this study identified MOG-IgG-positive patients with brainstem or both brainstem and cerebellum lesions in the first episode. As a comparison group, AQP4-IgG-NMOSD (n=30) and MS (n=30) patients with BSIFE were enroled. Thirty-five patients (35/146, 24.0%) were the BSIFE of MOGAD. Isolated brainstem episodes occurred in 9 of the 35 (25.7%) MOGAD patients, which was similar to MS (7/30, 23.3%) but was lower than AQP4-IgG-NMOSD (17/30, 56.7%, P=0.011). Pons (21/35, 60.0%), medulla oblongata (20/35, 57.1%) and middle cerebellar peduncle (MCP, 19/35, 54.3%) were the most frequently affected areas. Intractable nausea (n=7), vomiting (n=8) and hiccups (n=2) happened in MOGAD patients, but EDSS of MOGAD was lower than AQP4-IgG-NMOSD (P=0.001) at the last follow-up. MOGAD patients with or without BSIFE did not significantly differ in terms of the ARR (P=0.102), mRS (P=0.823), or EDSS (P=0.598) at the most recent follow-up. Specific oligoclonal bands appeared in MOGAD (13/33, 39.4%) and AQP4-IgG-NMOSD (7/24, 29.2%) in addition to MS (20/30, 66.7%). Fourteen MOGAD patients (40.0%) experienced relapse in this study. When the brainstem was involved in the first attack, there was an increased likelihood of a second attack occurring at the same location (OR=12.22, 95%CI 2.79 to 53.59, P=0.001). If the first and second events were both in the brainstem, the third event was likely to occur at the same location (OR=66.00, 95%CI 3.47 to 1254.57, P=0.005). Four patients experienced relapses after the MOG-IgG turned negative. BSIFE occurred in 24.0% of MOGAD. Pons, medulla oblongata and MCP were the most frequently involved regions. Intractable nausea, vomiting and hiccups occurred in MOGAD and AQP4-IgG-NMOSD, but not MS. The prognosis of MOGAD was better than AQP4-IgG-NMOSD. In contrast to MS, BSIFE may not indicate a worse prognosis for MOGAD. When patients with BSIFE, MOGAD tent to reoccur in the brainstem. Four of the 14 recurring MOGAD patients relapsed after the MOG-IgG test turned negative.

Comparison of live and fixed cell-based assay performance: implications for the diagnosis of MOGAD in a low-middle income country.

Though considered optimal, live cell-based assay (LCBA) is often unavailable for the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) in resource-poor regions. This study was undertaken to determine the agreement between LCBA and the widely available fixed cell-based assay (FCBA), for recommending testing guidelines within our region. All consecutive patients in our registry with a MOGAD phenotype were tested. The results from a commercially available FCBA (Euroimmun, Germany) were compared with a validated "in-house" LCBA. Clinical and MRI data were available for correlation. Among the 257 patient samples tested, 118 (45.9%) were positive by FCBA titre ≥1: 10 and or LCBA titres ≥1: 160 titre and 139 samples were negative. There was robust agreement between the two assays (agreement 98.8%, Cohen's kappa 0.98 [95% CI- 0.95-1.00], Spearman correlation 0.97 (p < 0.0001). Among five discordant samples, four had clinical and or MRI data which supported an alternate diagnosis. There was a modest correlation between assay titres, particularly for samples with titres ≥ 1:100 in FCBA (Spearman's Rho 0.26, p 0.005). Thirty samples were positive by FCBA at < 1:100 titre and included 1:80 (20),1:40(7) and 1:10 (3) titres. Among them, 80% had clear positive titres when tested by LCBA. The FCBA tested with serum dilutions of 1:10 was highly predictive of MOGAD in our study and compared well with our "in-house" LCBA. The current recommendations for testing at higher dilutions need to be re-examined in light of our findings. The results of our study should ideally be replicated in a larger dataset but at the same time provide some guidance for the accurate diagnosis of MOGAD in resource-poor settings.

Two rare cases of myelin oligodendrocyte glycoprotein antibody-associated disorder in children with leukodystrophy-like imaging findings

BackgroundChildren with acquired demyelinating syndromes (ADS) whose sera are positive for myelin oligodendrocyte glycoprotein (MOG) immunoglobulin (IgG) can be diagnosed with MOG-IgG associated disorder (MOGAD). Cases with leukodystrophy-like imaging findings with recurrent MOGAD have rarely been reported.Case presentationTwo children with MOGAD, whose onset age was 6 months and 3 years, respectively, were admitted to the hospital due to fever and altered consciousness. In both children, MOG-IgG was detected in the serum using live cell-based assay. Brain magnetic resonance imaging (MRI) revealed leukodystrophy-like lesions with diffuse bilateral white matter. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis with normal or slightly increased protein levels and no oligoclonal bands. Metabolic and inflammatory blood/CSF markers were all negative. Full exon gene testing revealed normal results, and nuclear and mitochondrial DNA were normal. Despite regular immunotherapy and reduction of lesions based on brain MRI results, the patients repeatedly relapsed and had residual neurological dysfunction at 3–4 years of follow-up.ConclusionsAlthough MOGAD is a monophasic and benign condition, certain MOGAD patients can experience multiple relapses and residual neurologic deficits. The spectrum of clinical manifestations in MOGAD is wider in children than in previously reported cases, including cases with leukodystrophy-like imaging findings. Such imaging findings along with MOG-IgG may occur recurrently and result in severe neurological prognosis. Patients with extensive and confluent white matter lesions should undergo early testing of MOG-IgG to ensure early therapy. In refractory cases, MOGAD treatment may need to be escalated beyond the current therapy, which means second-line immunotherapy should be performed as early as possible and hormone levels should not be rapidly reduced. Early diagnosis and appropriate treatment may improve the prognosis of children with MOGAD.

Clinical feature and disease outcome in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder: a Chinese study

BackgroundTo identify factors associated with relapse risk and disability in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD).MethodBetween 2016 and 2021, 186 patients with MOGAD were included in the study. Factors associated...

Helicobacter pylori infection may influence prevalence and disease course in myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) similar to MS but not AQP4-IgG associated NMOSD.

Helicobacter pylori (Hp) persists after colonizing the gut in childhood, and potentially regulates host immune system through this process. Earlier studies have shown that Hp infection in childhood, may protect against MS in later life. Such an association was not seen with AQP4-IgG positive NMOSD, while the association with MOGAD is unclear. To evaluate frequency of Hp IgG among patients with MOGAD, MS, NMOSD and matched controls and its effect on disease course. To ascertain whether childhood socio economic factors were linked to prevalence of Hp infection. In all, 99 patients diagnosed to have MOGAD, 99 AQP4 IgG+ NMOSD, 254MS and 243 matched controls were included. Patient demographics, diagnosis, age at disease onset, duration and the last recorded expanded disability status scale (EDSS) were obtained from our records. Socioeconomic and educational status was queried using a previously validated questionnaire. Serum HpIgG was detected using ELISA kits (Vircell, Spain). Frequency of Hp IgG was significantly lower among MOGAD (28.3% vs 44%, p-0.007) and MS (21.2% vs 44%, p-0.0001) but not AQP4-IgG+ NMOSD patients (42.4% vs 44%, p-0.78) when compared to controls. Frequency of Hp IgG in MOGAD & MS patients combined (MOGAD-MS) was significantly lower than those with NMOSD (23.2% vs 42.4%, p- 0.0001). Seropositive patients with MOGAD- MS were older (p-0.001. OR -1.04, 95% CI- 1.01- 1.06) and had longer disease duration (p- 0.04, OR- 1.04, 95% CI- 1.002- 1.08) at time of testing. Educational status was lower among parents/caregivers of this study cohort (p- 0.001, OR -2.34, 95% CI- 1.48-3.69) who were Hp IgG+. In developing countries Hp infection may be a significant environmental factor related to autoimmune demyelinating CNS disease. Our preliminary data suggests that Hp may exert a differential influence -a largely protective role for MS-MOGAD but not NMOSD and may influence disease onset and course. This differential response maybe related to immuno-pathological similarities between MOGAD and MS in contrast to NMOSD. Our study further underscores the role of Hp as a surrogate marker for poor gut hygiene in childhood and its association with later onset of autoimmune diseases.

Clinical features of the first attack with leukodystrophy-like phenotype in children with myelin oligodendrocyte glycoproteinantibody-associated disorders.

Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) is identified autoimmune disorder with a predominance in paediatric patients, and the disease spectrum has expanded with clinical and radiological patterns. The aim of the study was to describe the clinical characteristics of the first attack with leukodystrophy-like phenotype with MOGAD in children. Patients hospitalized at the Children's Hospital of Chongqing Medical University from June 2017 to October 2021 with positive MOG antibodies and phenotype of leukodystrophy-like (symmetric white matter lesions) were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Four cases from 143 MOGAD patients were recruited, with two females and two males. The age of onset is all under 6 years old. At the last follow-up, four cases exhibited a monophasic course, including ADEM in three patients and encephalitis in one patient. The mean EDSS score at onset was 4.62 ± 2.93, and the modified Rankin score (mRS) was 3.00 ± 1.82. First-attack symptoms include fever, headache, vomiting, seizure, loss of consciousness, emotional and behavioural disorder, and ataxia. The brain MRI showed prominent extensive and essentially symmetric distribution lesions in the white matter. All patients showed clinical and partial radiological improvement after intravenous immunoglobulin and/or glucocorticoid treatment. The first attack with MOGAD onset of leukodystrophy-like phenotype was more frequently seen in younger children than other phenotype patients. The patients may show impressive neurologic disorders, but most patients who receive immunotherapy have a good prognosis.

Decipher potential biomarkers of diagnosis and disease activity for NMOSD with AQP4 using LC-MS/MS and Simoa

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) is an autoimmune demyelinating disease, leading recurrently relapses and severe disability. There is a need for new biomarkers to meet clinical needs in diagnosis and monitoring. MethodsThrough liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS) analysis, brain lesions from NMO animal models were analyzed to identify potential biomarkers. Then, we assessed the levels of serum glial fibrillary acidic protein (sGFAP), neurofilament light chain (sNfL), Tau protein (sTau) and Ubiquitin C-terminal hydrolase L1 (sUCHL1) using an ultrasensitive single molecule array (Simoa) of AQP4-IgG + NMOSD patients, myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) patients, multiple sclerosis (MS) patients and healthy controls (HCs). Additionally, we further explored the early diagnosis value of these proteins. ResultsThere were 72 differentially expressed proteins between the NMO and control groups. NfL abundance was elevated when GFAP, UCHL1, and Tau abundance was decreased in the NMO group. Then, we observed that the sGFAP and sUCHL1 levels in patients with NMOSD in the early stage were significantly increased compared to those in control participants. Combined ROCs of the sGFAP, sNfL, and sUCHL1 levels to better predict NMOSD with relapse stages was optimal. Notably, univariate and multivariate analyses demonstrated that the sGFAP and sNfL levels were higher in patients with brain lesions, while the sUCHL1 levels were higher in those with spinal cord lesions during recent relapse. ConclusionsThese findings suggested that sGFAP, sNfL, and sUCHL1 displayed good diagnostic performance in AQP4-IgG + NMOSD and could be novel candidates for early discrimination.

Efficacy and safety of rituximab in myelin oligodendrocyte glycoprotein antibody-associated disorders compared with neuromyelitis optica spectrum disorder: a systematic review and meta-analysis

BackgroundRituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders...

ATP line splitting in association with reduced intracellular magnesium and pH: a brain 31 P MR spectroscopic imaging (MRSI) study of pediatric patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGADs).

Over the past four decades, ATP, the obligatory energy molecule for keeping all cells alive and functioning, has been thought to contribute only one set of signals in brain 31 P MR spectra. Here we report for the first time the observation of two separate β-ATP peaks in brain spectra acquired from patients with myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGADs) using 3D MRSI at 7 T. In voxel spectra with β-ATP line splitting, these two peaks are separated by 0.46 ± 0.18 ppm (n = 6). Spectral lineshape analysis indicates that the upper field β-ATP peak is smaller in relative intensity (24 ± 11% versus 76 ± 11%), and narrower in linewidth (56.8 ± 10.3 versus 41.2 ± 10.3 Hz) than the downfield one. Data analysis also reveals a similar line splitting for the intracellular inorganic phosphate (Pi ) signal, which is characterized by two components with a smaller separation (0.16 ± 0.09 ppm) and an intensity ratio (26 ± 7%:74 ± 7%) comparable to that of β-ATP. While the major components of Pi and β-ATP correspond to a neutral intracellular pH (6.99 ± 0.01) and a free Mg2+ level (0.18 ± 0.02 mM, by Iotti's conversion formula) as found in healthy subjects, their minor counterparts relate to a slightly acidic pH (6.86 ± 0.07) and a 50% lower [Mg2+ ] (0.09 ± 0.02 mM), respectively. Data correlation between β-ATP and Pi signals appears to suggest an association between an increased [H+ ] and a reduced [Mg2+ ] in MOGAD patients.

Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.

Background and ObjectiveThe spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody–associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG‐IgG titers in children with MOGAD in correlation with clinical presentation and disease course.MethodsIn this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG–positive.ResultsOne hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG–negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG–negative.DiscussionIn this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG–negative, are shown to have a significantly reduced relapse risk.