Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Research Articles

Clinical profile and challenges faced in the management of optic neuritis: the Indian scenario.

Optic neuritis (ON) is a relatively common ophthalmic disease that has recently received renewed attention owing to immunological breakthroughs. We studied the profile of patients with ON with special reference to antibody-mediated ON and the challenges faced in its management. Caserecords of patients with ON presenting to a tertiary eye-care center in South India were analyzed. Data on demographics, presenting visual acuity (VA), clinical features, seropositivity for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), details of magnetic resonance imaging (MRI) of orbits and brain, and treatment were collected. Among138cases with acute ON, male: female ratio was 1:2. Isolated ON was present in 41.3% of cases. Antibody testing of sera was performed in 68 patients only due to financial limitations. Among these, 48.5% were MOG-IgG-seropositive, 11.76% were AQP4-IgG-seropositive, and 30.88% samples were double seronegative. Other causes included multiple sclerosis (n = 4), lactational ON (n = 4), tuberculosis (n = 2), invasive perineuritis (n = 2), COVID-19 vaccination (n = 2), and COVID-19 (n = 1). The mean presenting best corrected visual acuity (BCVA) was 1.31 ± 1.16 logMAR (logarithm of the minimum angle of resolution). The mean BCVA at 3months was 0.167 ± 0.46 logMAR. Only initial VA ≤ 'Counting fingers' (CF) had a significant association with the visual outcome for final VA worse than CF. The steep cost of investigations and treatment posed challenges for many patients in the management of ON. MOG-IgG-associated ON is common in India. Unfortunately, financial constraints delay the diagnosis and timely management of ON, adversely affecting the outcome.

Neutrophil to lymphocyte ratio may be a useful marker in distinguishing MOGAD and MS and platelet to lymphocyte ratio associated with MOGAD activity.

Clinical overlap is observed between multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein immunoglobulin-G (MOG-IgG) associated disease (MOGAD) and the difficulty in distinguishing between the two diseases. Here, we measured and compared the readily available neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) to determine whether these three biomarkers can help to distinguish MOGAD and MS at disease onset. The impact of these three biomarkers on MOGAD and MS relapse also needs to be explored. In this retrospective analysis, we obtained clinical and paraclinical data from the first attacks of MOGAD (N=31) and MS (N=50). Electronic medical records were used to collect demographic data (gender, age at onset), clinical symptoms, EDSS at onset, and medical treatments. The primary outcome was relapse within one year of onset. Four hematological parameters were recorded, including neutrophil count, platelet count, lymphocyte count, and monocyte count. NLR, PLR, and MLR were calculated and compared between MOGAD, MS, and HC. Receiver operator curve (ROC) analysis was performed to assess the ability of NLR, PLR, and MLR to distinguish between MOGAD and MS, MOGAD and HC, respectively. A logistic regression analysis was performed to determine the impact of NLR/PLR/MLR on MOGAD/MS relapse within one year of onset. Compared to HC, NLR is significantly higher in MOGAD and MS (p<0.001, p=0.04, respectively). The PLR and MLR are elevated in MOGAD compared to HC (p<0.001, p<0.001, respectively), and MLR in MS are also statistically higher than in HC (p=0.023). It is worth noting that NLR and PLR were much higher in MOGAD compared to MS (p<0.001, p=0.001, respectively), but a significant difference regarding MLR has not been found between MOGAD and MS. Based on ROC curve analyses, we found that using NLR, PLR, and MLR to discriminate between MOGAD and MS yielded a ROC-plot area under the curve (AUC) value of 0.794, 0.727, and 0.681, respectively. Meanwhile, the AUC of NLR, PLR, and MLR to discriminate between MOGAD and HC were 0.926, 0.772, and 0.786. Furthermore, the logistics analysis revealed a significant positive association between PLR and MOGAD relapse. NLR helps differentiate MOGAD and MS in disease onset, and higher PLR was related to MOGAD relapse.

Serum Vitamin D Levels and Status in Thai Optic Neuritis Subjects: A Case-Control Study.

ObjectiveTo measure serum total vitamin D or 25-hydroxyvitamin D [25(OH)D] levels and status in immune-based optic neuritis (ON) including neuromyelitis optica spectrum disorder (NMOSD)-ON, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)-ON, autoimmune-ON, and idiopathic-ON and compare them with age- and sex-matched healthy controls. The secondary objective was to analyze the association between serum 25(OH)D levels and ON attack severity (nadir best-corrected visual acuity; nadir BCVA).Materials and MethodsThis was a single-center, case–control study. We enrolled 59 subjects (19 NMOSD-ON, 6 MOGAD-ON, 11 autoimmune-ON, 23 idiopathic-ON) diagnosed with acute immune-based ON (any ON attacks) over 11 years. Electronic medical records were reviewed and demographic data (age at sampling, sex, aquaporin-4 immunoglobulin (AQP4-IgG); myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG); other biomarkers of autoimmune disorders), ON attack severity (nadir BCVA), and serum 25(OH)D levels in the acute phase of ON were collected. Serum 25(OH)D levels of 236 age- and sex-matched healthy controls were assessed.ResultsMean serum 25(OH)D levels were significantly lower in each group of immune-based ON compared with healthy controls (p < 0.001 for each ON group). However, mean serum 25(OH)D levels were not significantly different between four ON groups (NMOSD-ON, 20.18±5.90 ng/mL; MOGAD-ON, 23.07±4.94 ng/mL; autoimmune-ON, 21.14±5.29 ng/mL; idiopathic-ON, 19.56 ±5.12 ng/mL; p = 0.525). All immune-based ON subjects had vitamin D insufficiency or vitamin D deficiency. The prevalences of vitamin D insufficiency and vitamin D deficiency were significantly higher than in healthy controls in each ON group (both p < 0.05 in each ON group). No associations were observed between serum 25(OH)D levels and ON attack severity (nadir BCVA).ConclusionsThai immune-based ON subjects had lower serum 25(OH)D levels and higher prevalence of vitamin D insufficiency and vitamin D deficiency compared with age- and sex-matched healthy controls. Serum 25(OH)D levels were not associated with ON attack severity (nadir BCVA). We highly recommend that serum 25(OH)D levels be screened in all subjects with acute immune-based ON.

Coexistence of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G and Neuronal or Glial Antibodies in the Central Nervous System: A Systematic Review.

Background: Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) has been considered a diagnostic marker for patients with demyelinating disease, termed “MOG-IgG associated disorder” (MOGAD). Recently, the coexistence of MOG-IgG and other neuronal or glial antibodies has attracted extensive attention from clinicians. In this article, we systematically review the characteristics of MOG-IgG-related antibody coexistence syndrome. Methods: Two authors independently searched PubMed for relevant studies published before October 2021. We also manually searched the references of each related article. The appropriateness of the included studies was assessed by reading the titles, abstracts, and full texts if necessary. Results: Thirty-five relevant publications that met our inclusion criteria were finally included, of which fourteen were retrospective studies and twenty-one were case reports. A total of 113 patients were reported to show the coexistence of MOG-IgG and neuronal or glial antibodies. Additionally, 68.14% of patients were double positive for MOG-IgG and N-Methyl-D-Aspartate Receptor-IgG (NMDAR-IgG), followed by 23.01% of patients who were double positive for MOG-IgG and aquaporin4-IgG (AQP4-IgG). Encephalitis was the predominant phenotype when MOG-IgG coexisted with NMDAR-IgG, probably accompanied by imaging features of demyelination. Patients with dual positivity for MOG-IgG and AQP4-IgG experienced more severe disease and more frequent relapses. The coexistence of MOG-IgG and antibodies other than NMDAR-IgG and AQP4-IgG was extremely rare, and the clinical presentations were diverse and atypical. Except for patients who were double positive for MOG-IgG and AQP4-IgG, most patients with multiple antibodies had a good prognosis. Conclusions: MOG-IgG may coexist with neuronal or glial antibodies. Expanded screening for neuronal or glial antibodies should be performed in patients with atypical clinical and radiological features.

P.033 Detection of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G (MOG-IgG) by live and fixed cell-based assays

Background: MOG-IgG is associated with non-MS demyelinating disease of the optic nerves, spinal cord and brain. Specificity has been issue so we validated the live and fixed MOG-IgG CBAs against the Oxford Autoimmune Neurology Diagnostic Laboratory (OANG) live CBA as a comparator with high specificity. Methods: At BC Neuroimmunology lab (BCNI), 54 MOG-IgG serum samples previously positive by live-CBA at OANG and BCNI were blindly tested by commercial fixed CBA. All 54 MOG IgG positives came from MOG-IgG positive patients. In addition, 256 samples from healthy people and other neurolgic disease were tested. Results: The live MOG-IgG CBA performed at BCNI was 100% concordant (54/54) with OANG live CBA. In contrast, only 49/54 samples were found seropositive by the commercial fixed CBA. The BCNI live-CBA identified 3/256 control samples as positive while 6/256 controls were positive on the fixed commercial CBA. On this cohort the live CBA is 100% sensitive, 98.8% specific and has PPV of 95%. The commercial fixed MOG test is 91% sensitive, 97.6% specific and has PPV of 87.5%. Conclusions: BCNI live MOG-IgG CBAs are in 100% agreement with MOG-IgG. Three positive results in non-MOGAD associated clinical phenotype require further investigation. These data confirm the superiority of the live MOG CBA.

AQP4-IgG-seronegative patient outcomes in the N-MOmentum trial of inebilizumab in neuromyelitis optica spectrum disorder

BackgroundThe N-MOmentum trial, a double-blind, randomized, placebo-controlled, phase 2/3 study of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD), enrolled participants who were aquaporin-4-immunoglobulin G (AQP4-IgG)-seropositive (AQP4+) or -seronegative (AQP4−). This article reports AQP4− participant outcomes. MethodsAQP4-IgG serostatus was determined for all screened participants by a central laboratory, using a validated, fluorescence-observation cell-binding assay. Medical histories and screening data for AQP4− participants were assessed independently by an eligibility committee of three clinical experts during screening. Diagnosis of NMOSD was confirmed by majority decision using the 2006 neuromyelitis optica criteria. Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) serology (using a clinically validated, flow cytometry assay) and annualized attack rates (AARs) were evaluated post hoc. Efficacy outcomes were assessed by comparing pre-study and on-study AARs in treated participants. ResultsOnly 18/50 AQP4− screened participants (36%) were initially considered eligible for randomization; 16 were randomized and received full treatment, 4 to placebo (1 MOG-IgG-seropositive [MOG+]) and 12 to inebilizumab (6 MOG+). The most common reason for failure to pass screening among prospective AQP4− participants was failure to fulfill the 2006 NMO MRI criteria. In inebilizumab-treated AQP4− participants, on-study AARs (95% confidence interval [CI]) calculated from treatment initiation (whether from randomization or when received at the start of the open-label period) to the end of study were lower than pre-study rates: for all AQP4− participants (n = 16), mean (95% CI) AAR was 0.048 (0.02–0.15) versus 1.70 (0.74–2.66), respectively. For the subset of AQP4−/MOG+ participants (n = 7), AAR was 0.043 (0.006–0.302) after treatment versus 1.93 (1.10–3.14) before the study. For the subset of AQP4−/MOG− participants (n = 9), post-treatment AAR was 0.051 (0.013–0.204) versus 1.60 (1.02–2.38). Three attacks occurred during the randomized controlled period in the AQP4− inebilizumab group and were of mild severity; no attacks occurred in the AQP4− placebo group. The low number of participants receiving placebo (n = 4) confounds direct comparison with the inebilizumab group. No attacks were seen in any AQP4− participant after the second infusion of inebilizumab. Inebilizumab was generally well tolerated by AQP4− participants and the adverse event profile observed was similar to that of AQP4+ participants. ConclusionThe high rate of rejection of AQP4− participants from enrollment into the study highlights the challenges of implementing the diagnostic criteria of AQP4− NMOSD. An apparent reduction of AAR in participants with AQP4− NMOSD who received inebilizumab warrants further investigation.

Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G in the CSF: Clinical Implication of Testing and Association With Disability.

Background and ObjectiveTo investigate the clinical relevance of CSF myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) testing in a large multicenter cohort.MethodsIn this multicenter cohort study, paired serum-CSF samples from 474 patients with suspected inflammatory demyelinating disease (IDD) from 11 referral hospitals were included. After serum screening, patients were grouped into seropositive myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD, 31), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD, 60), other IDDs (217), multiple sclerosis (MS, 45), and non-IDDs (121). We then screened CSF for MOG-IgG and compared the clinical and serologic characteristics of patients uniquely positive for MOG-IgG in the CSF to seropositive patients with MOGAD.ResultsNineteen patients with seropositive MOGAD (61.3%), 9 with other IDDs (CSF MOG + IDD, 4.1%), 4 with MS (8.9%), but none with AQP4-IgG + NMOSD nor with non-IDDs tested positive in the CSF for MOG-IgG. The clinical, pathologic, and prognostic features of patients uniquely positive for CSF MOG-IgG, with a non-MS phenotype, were comparable with those of seropositive MOGAD. Intrathecal MOG-IgG synthesis, observed from the onset of disease, was shown in 12 patients: 4 of 28 who were seropositive and 8 who were uniquely CSF positive, all of whom had involvement of either brain or spinal cord. Both CSF MOG-IgG titer and corrected CSF/serum MOG-IgG index, but not serum MOG-IgG titer, were associated with disability, CSF pleocytosis, and level of CSF proteins.DiscussionCSF MOG-IgG is found in IDD other than MS and also in MS. In IDD other than MS, the CSF MOG-IgG positivity can support the diagnosis of MOGAD. The synthesis of MOG-IgG in the CNS of patients with MOGAD can be detected from the onset of the disease and is associated with the severity of the disease.Classification of EvidenceThis study provides Class II evidence that the presence of CSF MOG-IgG can improve the diagnosis of MOGAD in the absence of an MS phenotype, and intrathecal synthesis of MOG-IgG was associated with increased disability.

Infection-Related Myelopathies

Recent years have seen growing attention to inflammatory and infectious disorders of the spinal cord, not only due to the discovery of autoantibody-mediated disorders of the spinal cord [e.g., aquaporin-4 immunoglobulin G (IgG) antibodies and myelin oligodendrocyte glycoprotein IgG antibodies], but also due to the emergence of clusters of infection-related myelopathy, now known as acute flaccid myelitis. We review the spectrum of infection-related myelopathies and outline a nosological classification system based on association with infection. We describe the epidemiology and definitions of myelopathies, with a discussion of clinical presentation and neuroimaging features, and then turn to specific discussion of myelopathies due to direct pathogen invasion and those considered to be post- or parainfectious.

Optic chiasm involvement in AQP-4 antibody–positive NMO and MOG antibody–associated disorder

Background: Optic neuritis (ON) is often the presenting symptom in inflammatory central nervous system demyelinating disorders. Objective: To compare the frequency and pattern of optic chiasm involvement in patients with aquaporin-4-immunoglobulin G (AQP4-IgG)-associated ON to patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated ON. Methods: Retrospective review of all patients evaluated at Mayo Clinic, Stanford University and Ramathibodi Hospital who were found to have: (1) ON, (2) either MOG-IgG or AQP4-IgG by cell-based assay, and (3) magnetic resonance imaging (MRI) at the time of ON. MRI was reviewed for contrast enhancement of the optic chiasm and the pattern of involvement. Results: One hundred and fifty-four patients (74 AQP4-IgG and 80 MOG-IgG) were included. Among patients with AQP4-IgG-ON, 20% had chiasmal involvement, compared with 16% of patients with MOG-IgG-ON (p = 0.66). In patients with chiasmal involvement, longitudinally extensive optic nerve enhancement (from orbit extending to chiasm) was identified in 54% of MOG-IgG-ON patients, compared with 7% of AQP4-IgG-ON patients (p = 0.01). Conclusion: Chiasmal involvement of MOG-IgG-ON and AQP4-IgG-ON occur at more similar frequencies than previously reported. Furthermore, MOG-IgG-ON chiasmal involvement is more likely to be part of a longitudinally extensive optic nerve lesion.

Visual field loss and structure–function relationships in optic neuritis associated with myelin oligodendrocyte glycoprotein antibody

Background: A paradoxical discrepancy between severe peripapillary retinal nerve fiber layer (pRNFL) atrophy and good visual outcome had been reported in patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated optic neuritis (ON). However, only visual acuity (VA) was assessed. Objectives: To study visual field (VF) outcomes of patients with MOG-IgG-associated ON and evaluate the correlation between functional eye outcome and retinal structural changes assessed by optical coherence tomography. Methods: The records of 32 patients with MOG-IgG-associated ON who underwent ophthalmological examination at least 12 months after ON onset were reviewed. Degree of VF disability was determined by mean deviation (MD). Results: At final assessment (median, 35 months), 4.2% of 48 affected eyes (AE) had VA ⩽ 0.1, 40% had abnormal MD, and among AE with final VA ⩾ 1.0, 31% had mild to moderate damage. Thinning of the inner retinal layers was significantly correlated with MD impairment. Analysis demonstrated a threshold of pRNFL thickness (50 µm), below which MD was significantly worse (mean, −2.27 dB vs −17.72 dB; p = 0.0003). ON relapse was significantly associated with poor visual outcome assessed by MD. Conclusion: Functional impairment measured with VF is not rare, and MD assessment better reflects actual structural damage.

Editors' note: A multicenter comparison of MOG-IgG cell-based assays

In “A multicenter comparison of MOG-IgG cell-based assays,” Waters et al. compared 3 myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) cell-based assays (CBAs) from 3 international centers and found that the specificity was highest for the 2 live CBAs as compared to the fixed CBA (99.6% and 100% vs 98.1%). Furthermore, they reported that the positive predictive values (PPVs) were highest for the 2 live CBAs as compared to the fixed CBA (95.5% and 100% vs 82.1%). Budhram questions the value of these PPV calculations, noting that PPV is dependent on knowledge of disease prevalence, which is not always accurate in a case-control study, and clinician ordering practices. He recommends that clinicians be aware of the importance of appropriate patient selection when ordering MOG-IgG, particularly when using a fixed CBA. In “A multicenter comparison of MOG-IgG cell-based assays,” Waters et al. compared 3 myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) cell-based assays (CBAs) from 3 international centers and found that the specificity was highest for the 2 live CBAs as compared to the fixed CBA (99.6% and 100% vs 98.1%). Furthermore, they reported that the positive predictive values (PPVs) were highest for the 2 live CBAs as compared to the fixed CBA (95.5% and 100% vs 82.1%). Budhram questions the value of these PPV calculations, noting that PPV is dependent on knowledge of disease prevalence, which is not always accurate in a case-control study, and clinician ordering practices. He recommends that clinicians be aware of the importance of appropriate patient selection when ordering MOG-IgG, particularly when using a fixed CBA.

Reader response: A multicenter comparison of MOG-IgG cell-based assays.

I read with interest the article by Waters et al.1 In this much-needed case-control study, the authors determined high specificity of cell-based assays (CBAs) for myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), although the live CBAs had even higher specificity (>99%) than the Euroimmun-fixed CBA (98%). The authors then calculated a positive predictive value (PPV) of only 82% for the fixed CBA compared with >95% for the live CBAs. This calculation is problematic, however, because PPV depends on disease prevalence in the tested population and this is often not accurately represented in a case-control study design.2 Instead of calculating PPV in this study, I would have emphasized appropriate patient selection to avoid false-positives if using a fixed CBA with high, but imperfect, specificity for MOG-IgG. The true PPV of the fixed CBA will depend on clinicians' test-ordering practices.3 The authors stated that “MOG-IgGs will likely be commonly ordered in the clinical evaluation of a suspected demyelinating event,” even in patients with clinical diagnoses of multiple sclerosis1; although this may be true, one should remember that the onus to avoid false-positive results falls not only on the diagnostic assay but also on the clinician who determines which patients undergo testing.

Clinical phenotype, radiological features, and treatment of myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) optic neuritis.

To review the clinical characteristics, radiological manifestations and treatment of myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) optic neuritis. Serum antibodies to MOG have recently been found to be a biomarker of MOG-IgG-associated disorder (MOGAD), a demyelinating disease distinct from both multiple sclerosis (MS) and aquaporin-4-IgG neuromyelitis optica spectrum disorder (AQP4-IgG-positive NMOSD). The phenotype of MOGAD is broad and includes optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis (ADEM). Optic neuritis is the most common presentation in adults, whereas ADEM is the most common presentation in children. Clinical characteristics suggestive of MOG-IgG optic neuritis include recurrent optic neuritis, prominent disc edema, and perineural enhancement of the optic nerve on magnetic resonance imaging. Although the nadir of vision loss is severe with MOG-IgG optic neuritis, the recovery is typically better than AQP4-IgG optic neuritis and therefore has a favorable overall prognosis. Patients with relapsing disease will often need chronic immunotherapy. Rituximab, azathioprine, mycophenolate mofetil, and monthly intravenous immune globulin are the most commonly utilized treatments. MOGAD is a unique entity that is separate from both MS and AQP4-IgG-positive NMOSD. Recognition of the clinical and radiologic features allow for the correct diagnosis. Future randomized trials will determine the optimal treatment for MOGAD.

Refining cell-based assay to detect MOG-IgG in patients with central nervous system inflammatory diseases

BackgroundGiven that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG associated diseases. Here, we aim to validate a new in-house live cell-based assay (CBA) for screening MOG-IgG in patients with central nervous system inflammatory diseases. MethodsWe generated a full length MOG transfected HEK293 stable cell line using pIRES2-eGFP vector. Sera from 355 patients with central nervous system inflammatory diseases and 25 healthy individuals were evaluated for MOG-IgG seropositivity using in-house cell-based immunofluorescence assay (CBA-IF). The specificity of IgG (H + L) and IgG1-Fc secondary antibodies as well as IgM binding were determined by cell-based flow cytometry (CBA-FACS). The optimal cut-offs for determining seropositivity in CBA-FACS were calculated and the concordance of CBA-IF score and CBA-FACS was studied. The results of our CBA-IF were compared with the Oxford CBA-IF. Results11.5% (41/355) of patients were seropositive for MOG-IgG and had clinical phenotypes that were within the known clinical spectrum of MOG-IgG associated diseases. No typical multiple sclerosis patients, aquaporin-4-IgG positive neuromyelitis optica spectrum disorder or healthy individuals were MOG-IgG seropositive. Using CBA-FACS, the anti-human IgG (H + L) was found to be comparable to IgG1-Fc antibody. No IgM binding was observed in all the samples tested. CBA-IF score and CBA-FACS yielded high correlation. The concordance of the NCC CBA-IF with the Oxford CBA-IF was 98%. ConclusionWe have developed MOG-IgG CBAs that have different characteristics and benefits but with high specificity and concordance. The complementary use of two methods and follow-up study with larger cohort will increase the clinical usefulness of MOG-IgG CBAs.

Myelin oligodendrocyte glycoprotein immunoglobulin G-associated encephalomyelitis

The article discusses the role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in demyelinating diseases of the central nervous system. Clinical phenotypes of demyelinating syndromes associated with MOG-IgG that are currently included into neuromyelitis optica spectrum disorders (NMOSD) are described. However, it has been shown that encephalomyelitis associated with MOG-IgG (MOG-EM) has certain clinical, radiological, immunological and histopathological features that make it possible to single out these syndromes into a separate nosological form. We provide International recommendations that establish indications for testing MOG-IgG using cell-based assay. We discuss epidemiological issues and classification challenges of the disease. Various approaches to treatment and prevention of relapses of MOG-EM are analyzed.

Clinical analysis of neuromyelitis optica spectrum disorders in childhood

Objective: To explore clinical features and the effect of treatment of neuromyelitis optica spectrum disorders (NMOSD) in childhood. Methods: Children who were hospitalized in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2018 and meeting diagnostic criteria of NMOSD proposed by the International Panel for NMOSD Diagnosis in 2015 were summarized and followed up. The basic information, symptoms of each attack, locations and patterns of new lesions, features of cerebrospinal fluid, serologic markers, treatments and outcomes in these patients were analyzed. Thirty-three children were included in the study, with 13 males and 20 females. The median age of onset was 6.83 (4.25, 8.75) years. Compared aquaporin-4 immunoglobulin G (AQP4-IgG) associated NMOSD with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated NMOSD. Mann-Whitney U test was used for continuous variables and Fisher test for categorical variables in comparison between AQP4-IgG and MOG-IgG associated NMOSD. Wilcoxon test was used for annualized relapse rate (ARR) before and after adding disease-modifying drugs. Results: Optic neuritis (39% (13/33) in initial attacks and 49% (62/127) in total attacks) and myelitis (36% (12/33) in initial attacks and 26% (33/127) in total attacks) were the top two symptoms in both the initial attacks and all 127 attacks during follow-up. There was 42% (37/89) of brain magnetic resonance imaging (MRI) scans in acute phase showing new lesions in supratentorial white matter, with 43% (16/37) showing acute disseminated encepha lomyelitis (ADEM)-like or leukodystrophy-like patterns. AQP4-IgG was detected in 30% (10/33) patients, and MOG-IgG was detected in 55% (11/20) patients, with no combined positive case. In 20 patients treated with rituximab, two were treated after the initial attack. In the other 18 patients, the median annualized relapse rate decreased from 1.86 (1.52, 2.60) before treatment to 0.28 (0, 1.13) during treatment (Z=-3.376, P=0.001). Compared with AQP4-IgG associated NMOSD (10 cases), fever of unknown origin (8/40 vs. 0/33, P=0.007) was more common, area postrema syndrome (0/40 vs. 4/33, P=0.038) was fewer, cell count of cerebrospinal fluid (49.0 (17.5, 115.0) ×10(6)/L vs. 5.5 (3.0, 15.8)×10(6)/L, Z=-3.526, P=0.000) was higher in MOG-IgG associated NMOSD (11 cases). Conclusions: In childhood-onset NMOSD, optic neuritis and myelitis were top two symptoms. Childhood-onset NMOSD has high proportion of positive MOG-IgG. Lesions in supratentorial white matter are common. Rituximab could significantly decrease ARR of NMOSD in childhood. However, more studies should be conducted to explore the optimal treatment strategy in different antibody associated NMOSD.

Neuromyelitis optica and neuromyelitis optica spectrum disorders

The review is devoted to up-to-date data on epidemiology, aspects of the pathogenesis of neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD). The authors consider a role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in the syndromes phenotypically similar to NMO and NMOSD. Special attention is drawn to the methods of MOG-IgG antibodies detection and indications for testing. The approaches and management for treatment and prevention of NMO relapses, risks of complications during pregnancy and immediately after delivery, as well as methods for their prevention and treatment, are described.

Autoimmune and Paraneoplastic Myelopathies.

Prompt recognition of an inflammatory myelopathy is critical, as a specific diagnosis and management plan allows for optimal patient outcomes. Many treatment options are now available for autoimmune and paraneoplastic myelopathies, but specific management strategies and expected prognosis vary widely depending on the underlying etiology. An understanding of the relevant clinical details, imaging findings, and other diagnostic information that can help achieve a specific myelopathy diagnosis and treatment plan is essential for all neurologists, given the variety of contexts in which myelopathies are encountered. We provide an outline of the diagnostic evaluation and treatment of various inflammatory myelopathies seen in autoimmune and paraneoplastic diseases, including multiple sclerosis, aquaporin-4 immunoglobulin G (IgG) seropositive neuromyelitis optica spectrum disorder, sarcoidosis, myelin oligodendrocyte glycoprotein IgG associated disease, and other rare inflammatory myelopathies; we also highlight common mimickers of inflammatory myelopathies.

Prevalence and characteristics of transverse myelitis and neuromyelitis optica spectrum disorders in the United Arab Emirates: A multicenter, retrospective study.

To determine the epidemiology and characteristics of transverse myelitis (TM) and neuromyelitis optica spectrum disorders (NMOSD) in Abu Dhabi, United Arab Emirates. Retrospective chart review at four large government-run hospitals in Abu Dhabi between 2010 and 2016. Data collected included year of onset, presentation, laboratory results including aquaporin-4 immunoglobulin G (IgG)/myelin oligodendrocyte glycoprotein IgG antibodies and the occurrence of any relapses. A total of 46 individuals were identified. Of these, 23 (50%) were Emirati citizens. Within the overall group including pediatrics, the crude prevalence rate for monophasic TM was 1.0 per 100 000, and for NMOSD was 0.34 per 100 000. Incidence rates within the overall group for TM and NMOSD were 0.18 per 100 000 and 0.05 per 100 000, respectively. For Emirati citizens aged ≥20 years, the prevalence rate for monophasic TM was 2.46 per 100 000 and 1.76 per 100 000 for NMOSD, and the incidence was 0.57 per 100 000 and 0.17 per 100 000, respectively. The incidence of monophasic TM and NMOSD within the Emirati pediatric population (aged ≤19 years) was 0.18 per 100 000 and 0.06 per 100 000, respectively. The mean age of onset for monophasic TM was 36 years, and for NMOSD was 43 years. Nine patients had a positive aquaporin-4 IgG or anti-myelin oligodendrocyte glycoprotein IgG antibody result. Of the 30 participants with available laboratory cerebrospinal fluid analysis, 36.6% had elevated white blood counts (>5.0 × 106/L), and 43% had elevated protein levels. A total of 19 participants had documentation of oligoclonal bands or IgG index, and just four (21%) had either oligoclonal bands or elevated IgG index. The present study describes the epidemiology and characteristics of TM and NMOSD among populations in Abu Dhabi. The adult prevalence rate for Emirati citizens was 2.46 per 100 000 for monophasic TM, and 1.76 per 100 000 for NMOSD. The overall incidence was 0.18 per 100 000 and 0.05 per 100 000, respectively.

Neuromyelitis optica spectrum disorders: Comparison according to the phenotype and serostatus.

Objective:To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO.Methods:This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays.Results:Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10–77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presented more often with longitudinally extensive transverse myelitis (LETM) (p < 0.001), and had lower relapse rates (p = 0.015), but similar disability outcomes. Nonwhite ethnicity and optic neuritis presentation doubled the risk for developing NMO compared with white race (p = 0.008) or LETM presentation (p = 0.008). Nonwhite race (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.4–13.6) and older age at onset were associated with worse outcome (for every 10-year increase, HR 1.7, 95% CI 1.3–2.2). Patients with NMO and MOG-IgG (n = 9) had lower female:male ratio (0.8:1) and better disability outcome than AQP4-IgG-seropositive or double-seronegative patients (p < 0.001).Conclusions:In patients with AQP4-IgG, the similar outcomes regardless of the clinical phenotype support the unified term NMOSD; nonwhite ethnicity and older age at onset are associated with worse outcome. Double-seronegative and AQP4-IgG-seropositive NMO have a similar clinical outcome. The better prognosis of patients with MOG-IgG and NMO suggests that phenotypic and serologic classification is useful.