Neuromyelitis Optica Spectrum Disorder.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated inflammatory central nervous system (CNS) disease that has been gradually recognized in recent years and is currently considered as a distinct disease entity distinguished from multiple sclerosis and neuromyelitis optica spectrum disorder. Lately, the new diagnostic criteria for MOGAD proposed by the International MOGAD Panel were published.1 The new criteria cover six core clinical phenotypes (optic neuritis, myelitis, acute disseminated encephalomyelitis, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, and cerebral cortical encephalitis often with seizures), emphasize the positive serum MOG-immunoglobulin G (IgG) test (determined using cell-based assay) and exclusion of alternative causes, and include supporting clinical/neuroimaging features to offset possible deficiencies in antibody detection, aiming to provide precise diagnosis of MOGAD and avoid overdiagnosis. MOGAD, with diverse clinico-radiological manifestations, is deemed to be the “great mimic”. While the new diagnostic criteria may be relatively strict in clinical practice, we are concerned that some patients suffering from MOGAD may be omitted according to the current standards. For instance, some patients, who clearly tested positive for serum MOG-IgG, presented with fever, headache, and leptomeningeal enhancement on brain magnetic resonance imaging (MRI). In this clinical setting, MOG antibody-associated aseptic meningitis is the most reasonable diagnosis.2, 3 However, these patients are unlikely to be diagnosed with MOGAD according to the new criteria, given that meningitis does not fit into any of the six defined phenotype classifications. In another scenario, a few patients with seizures (a relatively common presentation in MOGAD4) may have normal brain MRI (especially at the disease onset),5 and may not sufficiently fulfil the new criteria, which can affect the early diagnosis of MOGAD, thus delaying immunotherapy. In addition, short segment myelitis (SSM, < 3 contiguous vertebral segments in length) is not uncommon in MOGAD. Ciron et al. evaluated 73 patients with MOGAD and found 28 (38.4%) had short lesions and 45 (61.6%) had long lesions at the first episode of myelitis.6 Moreover, the occurrence of conus medullaris involvement varied in different populations, which seems to be more uncommon in patients presenting in China (2/59 [3.4%]7), than those in Europe (22/73 [30.1%]6) and North America (21/51 [41.2%]8). Similarly, in our center with recent 5-year data, conus medullaris injury was observed in 2/17 [11.8%] cases with myelitis as the onset manifestation. SSM, with eccentric lesions and without conus medullaris involvement, can occur with low positive serum MOG-IgG. These patients would also fail to meet with the current criteria, but their clinical findings may still be relevant to MOG-IgG. Furthermore, MOG-IgG associated myelitis with negative initial spinal cord MRI occurred in 7/73 patients with MOGAD.9 For the patients with MRI-negative myelitis, if detected with low positive serum MOG-IgG, also challenge the diagnosis of MOGAD according to the new criteria, which may lead to the therapeutic dilemma. Moving forward, detailed studies of MOGAD are likely to identify additional clinico-radiological phenotypes, and the frequency of existing phenotypes will also change, and the diagnostic criteria need to be revised and updated with the times. Although there is still room for improvement, the publication of the 2023 criteria is a key step towards unifying and standardizing the diagnosis of MOGAD, pushing its research into a new era. We expect that the next version of MOGAD criteria will include the uncommon clinical phenotypes, which would allow clinicians to be more vigilant in identifying patients with MOGAD that are presenting with atypical manifestations. Furthermore, we suggest it would be beneficial to define levels of diagnostic certainty (such as possible/probable/definite MOGAD), similar to the diagnostic criteria for autoimmune encephalitis and paraneoplastic neurological syndromes. We believe that these approaches may be more advantageous in clinical diagnosis and management strategies, compensating for lower sensitivity from the current strict diagnostic criteria in the pursuit of higher specificity, so as to decrease underdiagnosis. Given that MOGAD is a treatable disease, but therapeutic regimens are still different from those for other inflammatory CNS diseases, early identification can facilitate timely and optimal treatment, thus improving the prognosis. Not applicable. The authors declare no conflict of interest. Not applicable. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning. This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC. Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD ( P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group ( P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant ( P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = -0.60 and R = -0.64, respectively), inversely moderate in patients with MOGAD (R = -0.34 and R = -0.40, respectively), and weak in patients with NMOSD (R = -0.03 and R = -0.17, respectively). Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.

Prognosis biomarkers in MOGAD: What can we learn from observational studies?

Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

Optic neuritis (ON) can present as the first demyelinating attack in both multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), which may require different treatment depending on the final diagnosis. We present 2 young Hispanic women who presented with ON during pregnancy, one of whom was diagnosed with MS and the other with MOGAD. We describe key clinical features to help differentiate between MS and MOGAD including ON features, brain and spinal MRI, CSF profiles, and serum MOG and aquaporin-4 (AQP-4) antibodies, which all can help guide clinicians to an ultimate diagnosis. Pregnancy is usually considered an immunotolerant state because complex immunologic shifts arising to support tolerance of the developing fetus seem to decrease the risk of relapses. However, relapses may still occur during pregnancy, and relapse rates increase immediately postpartum. Our cases raise the possibility that young Hispanic patients may face increased risk of demyelinating disease activity even during the relatively immunotolerant state of pregnancy. A high index of suspicion for demyelinating disease should be maintained to accelerate diagnosis and prevent disability.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: Presentation and outcomes of adults at a single center

ABSTRACTBackgroundComorbidities occur in aquaporin‐4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4‐NMOSD), myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), and double seronegative NMOSD (DN‐NMOSD), potentially contributing to a less favorable disease course.ObjectivesTo characterize comorbidities in AQP4‐NMOSD, MOGAD, and DN‐NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4‐NMOSD.MethodsFour hundred and forty‐two participants from the CROCTINO cohort were evaluated for comorbidities.ResultsIn AQP4‐NMOSD patients (n = 360), 43.5% (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) single and 25% (n = 5) multiple. In DN‐NMOSD (n = 33), 36.4% (n = 12) had comorbidities equally split. AQP4‐NMOSD patients had more multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4%, n = 65) than MOGAD (20%, n = 4, p = 0.09) and DN‐NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4‐NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN‐NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN‐NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4‐NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs. 0.49 ± 0.98, p < 0.001). OCT revealed reduced inner nuclear layer thickness in AQP4‐NMOSD with comorbidities compared to non‐comorbidity (B = −1.52, p = 0.047), more pronounced with CVC/RF (B = −2.96, p = 0.009).ConclusionComorbidities are frequent in AQP4‐NMOSD and MOGAD and are associated with ON frequency and disability. These findings highlight the need for proactive comorbidity management to improve patient care.

Pseudotumoural optic neuritis in myelin oligodendrocyte glycoprotein antibody-associated disease in children: Pseudotumoural optic neuritis in MOG antibody-associated disease.

ObjectivesTo examine volumetric magnetic resonance imaging (vMRI) in myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), compared to multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and healthy controls (HC).MethodsStandardized vMRI in MOGAD were compared to age, sex, and disease duration matched MS (5:1), and non‐matched NMOSD and HC, in mixed linear models with time and group interactions. Disability assessments included; patient determined disease steps (PDDS), manual dexterity (MDT), walking speed (WST), processing speed (PST), and contrast sensitivity tests (CST). Correlations between vMRI and disability in MOGAD were examined.ResultsA total of 293 patients were included; 32 MOGAD, 160 MS, 49 NMOSD, and 52 HC. MOGAD had a faster rate of volume loss in all brain regions compared to HC (p < 0.05). At baseline, MOGAD had preserved thalamic (0.000507, p = 0.005), caudate (0.000287, p = 0.004), and putamen (0.000341, p = 0.007) fractions than MS. Longitudinally, MOGAD had increased lateral ventricle fraction (LVF) (−0.000645, p = 0.032), but less hippocampal (0.000031, p = 0.044) and upper cervical cord area (UCCA) loss (1.482887, p = 0.005), compared to NMOSD. MOGAD had increased LVF (0.00529, p < 0.001), but less UCCA loss (0.538656, p = 0.042) longitudinally compared to MS. Among MOGAD, UCCA was associated with PDDS (−0.72, p = 0.004) and CST (0.60, p = 0.014). Whole brain fraction (WBF) was associated with PDDS (−0.66, p = 0.01) and PST (0.52, p = 0.019). LVF was associated with PDDS (0.78, p < 0.001).InterpretationMOGAD showed longitudinal brain volume loss compared to HC. Deep gray matter was relatively preserved compared to MS, while MS and NMOSD had greater UCCA loss, indicating regional differences in atrophy. Despite less overall atrophy, volume loss in MOGAD was associated with disability. ANN NEUROL 2025;98:1044–1056

Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) associated with COVID-19: A case series and review

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease

Background: The clinical course of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is variable. However, robust markers of poor outcome and/or relapse risk are still missing. Objective: To evaluate the frequency of cerebrospinal fluid-restricted oligoclonal bands (CSF-OCB) in a national cohort of adult MOGAD patients and to assess their prognostic value for the risk of relapse and severity. Methods: We included MOGAD adult patients fulfilling the MOGAD 2023 criteria who underwent CSF analysis at maximum 3 months from onset. Results: Data from 190 patients were collected. We found the presence of CSF-OCB in 32 patients (16.8%). Positive and negative CSF-OCB patients were similar for median age at onset, sex, clinical presentation, severity at onset, and residual disability. Relapses were more frequent in the CSF-OCB+ group (p = 0.049), particularly within the first year of follow-up (p = 0.007). Although CSF-OCB+ was more frequently associated with imaging features suggestive of multiple sclerosis (MS) (p = 0.014), 78% of these patients fulfilled the 2023 supportive features and 65% experienced lesion vanishing at follow-up magnetic resonance imaging (MRI). Conclusion: We found a higher risk of relapse in MOGAD with CSF-OCB particularly during the first year. Close attention is recommended regarding the risk of misdiagnosis with MS.

Aims/Background Pediatric acquired demyelinating disorders (ADS) include various monophasic and recurrent inflammatory conditions of the central nervous system (CNS). Optic neuritis (ON) is a demyelinating disease primarily affecting the optic nerve axons due to autoimmune inflammation. To investigate the clinical characteristics, ophthalmic manifestations, laboratory test results, and prognostic indicators of Chinese children and adolescents with ADS. Methods The clinical data of 57 patients with ADS treated in the Beijing Children's Hospital from March 2021 to December 2023, were retrospectively collected and analyzed. The primary outcomes include best-corrected visual acuity (BCVA) at onset, peripapillary retinal nerve fiber layers (RNFL) thickness, serum myelin oligodendrocyte glycoprotein (MOG) antibody level, aquaporin-4 (AQP4) antibody level, and final BCVA after hormone therapy. Results The analyses included 57 children and adolescents in the study, including 38 optic neuritis (ON), 12 neuromyelitis optica spectrum disorder (NMOSD), 5 acute disseminated encephalomyelitis (ADEM), and 2 multiple sclerosis (MS) patients. The median age of patients facing the initial attack of ON was 9 years (3-15 years), with 23 children and adolescents (40.4%) aged eight years or younger, and 37 patients (64.9%) were bilaterally affected. Half of the children and adolescents (15/30) were MOG-Ab seropositive, and 19.4% (6/31) were AQP4-Ab seropositive. Children and adolescents with NMOSD were more likely to have severe visual impairment at acute onset (p < 0.05), with 84.2% of them having low vision acuity (BCVA worse than 0.1), as compared with 64.9% in the ON group. The RNFL thickness of affected eye was thinner than unaffected eyes (median 72.0 μm vs. median 102.0 μm, p < 0.05). Patients with NMOSD exhibited lower RNFL thickness across all measured sectors compared to those with ON. Significant differences were noted in the average RNFL and in each specific region of the retina, including the temporal RNFL, nasal RNFL, nasal superior RNFL, nasal inferior RNFL, temporal superior RNFL, and temporal inferior RNFL (all p < 0.05). After the treatment with intravenous methylprednisolone, both patients with ON (52 eyes; 86.7%) or NMOSD (20 eyes; 90.9%) group had functional visual recovery (BCVA better or equal 0.4). Conclusion This study shows that Chinese children and adolescents with ADS present distinctive clinical features, including earlier onset and more bilateral involvement. Furthermore, NMOSD patients experience more severe visual acuity impairment and thinner peripapillary RNFL. All children and adolescents of ON or NMOSD respond well to methylprednisolone treatment.