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Paediatric acquired demyelinating syndromes (pADS) attack white matter pathways in the brain during an important period of development. Affected children can experience poor functional outcomes, including deficits in specific cognitive domains. Understanding risk factors for poor outcome will guide clinical management of these children. One clinical phenotype which may differentially impact cognitive outcomes is the presence of autoantibodies to myelin oligodendrocyte glycoprotein (MOG). Preliminary research has suggested that cognitive difficulties exist in paediatric patients who test positive for MOG antibodies or MOGAD (Myelin Oligodendrocyte Glycoprotein Associated Disease) however, they experience a less severe profile compared to seronegative counterparts. The current study assesses children diagnosed with pADS who tested positive or negative for MOG-ab using standardised assessments of both intellectual functioning and academic ability. The results show that a subset of MOGAD patients experience clinically significant sequalae in intellectual functioning and academic ability. The neuropsychological profile also differed between children with and without MOG-ab positivity, with seronegative patients more likely to show a clinically relevant difficulties at the individual patient level. Whilst no differences existed at the group-level; the current study demonstrates the relative additional risk of intellectual/academic difficulty associated with MOG-ab seronegativity. This research further supports the growing perspective that MOG-positivity confers a more favourable neuropsychological outlook than is the case for their seronegative counterparts. This broadening consensus offers reassurance for clinicians, families, and patients.

UNASSIGNED: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data.
UNASSIGNED: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models.
UNASSIGNED: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25-1.73; aRR: 1.67; 95% CI: 1.19-2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack.
UNASSIGNED: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible.

Pro-inflammatory autoantigen-specific CD4+ T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced. Instead, exhaustion-associated co-inhibitory receptors were expressed together with FOXP3, the canonical regulatory T cell (Treg) transcription factor. Auto-Th cells responded in vitro to checkpoint inhibition and provided potent B cell help. Cells with the same exhaustion-like (ThEx) phenotype were identified in soluble liver antigen (SLA)-antibody-autoimmune hepatitis and BP180-antibody-positive bullous pemphigoid, AIDs of the liver and skin, respectively. While originally described in cancer and chronic infection, our data point to T cell exhaustion as a common mechanism of adaptation to chronic (self-)stimulation across AID types and link exhausted CD4+ T cells to humoral autoimmune responses, with implications for therapeutic targeting.

BACKGROUND: Seasonal variation in attacks of acute disseminated encephalomyelitis (ADEM1) is reported in some studies. Myelin oligodendrocyte glycoprotein (MOG) antibodies are found in up to 50 % of ADEM cases. Despite this, there has been no adequately powered study of seasonality in MOG antibody-associated disease (MOGAD). We sought to determine whether there was an effect of season on incidence of total attacks and onset attacks of MOGAD.
METHODS: We searched the large national Oxford-based NMO Service database to identify attacks of MOGAD occurring between 2010 and 2021. Month of each attack was extracted and Edwards\' test of seasonal variation was applied to determine whether there was a seasonal effect on total attacks and onset attacks.
RESULTS: Neither incidence of total attacks nor incidence of onset attacks varied significantly by month.
CONCLUSIONS: There is no evidence of seasonal fluctuations in the incidence of MOGAD attacks in the UK.

UNASSIGNED: Myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a relatively new disease entity in the field of demyelinating disorders. Its first diagnostic criteria have recently been published.
UNASSIGNED: We evaluated the positive predictive value (PPV) for MOG-IgG testing and report the clinical and radiologic features with respect to the recently published criteria.
UNASSIGNED: A retrospective study was conducted at three centers in Dallas, Texas. Patients with positive MOG-IgG testing on cell-based assays at any time were included. Positive cases were reviewed by at least two neuroimmunologists for fulfillment of the criteria.
UNASSIGNED: We included 235 patients. The PPV of seropositivity at any time was 78.3% overall, 52.6% for low titer, and 90.1% for high titer. Children had a higher PPV than adults (93.9% versus 67.2%). Positive predictive value was 6.3% in those without a core clinical demyelinating attack. Children more often have the typical imaging features of MOGAD in optic neuritis than adults.
UNASSIGNED: We report a PPV of 78.3% for MOG-IgG testing using the 2023 MOGAD diagnostic criteria. Children had higher PPV and frequency of supporting imaging features. Careful consideration is necessary when assigning patients with no core demyelinating event and low titers a MOGAD diagnosis.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is characterized by multiple phenotypic conditions such as acute disseminated encephalomyelitis, optic neuritis, and myelitis. MOGAD\'s spectrum is expanding, with potential symptoms of increased intracranial pressure that are similar to idiopathic intracranial hypertension (IIH). We report a boy with new-onset continuous headache and a brain MRI at onset suggesting idiopathic intracranial hypertension (IIH). The patient showed resistance to treatment with acetazolamide and, after one month, developed optic neuritis in the left eye. Laboratory tests documented positive MOG antibodies (anti-MOG) in the serum. The final diagnosis was MOGAD, with the initial symptoms resembling IIH.

UNASSIGNED: Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is a clinical entity distinct from multiple sclerosis and aquaporin-4 (AQP4+)-IgG-positive neuromyelitis optica spectrum disorder. There is a lack of evidence regarding the efficacy and safety of current treatments used for MOGAD.
UNASSIGNED: In this article, the authors review the currently available literature on the pharmacological management of MOGAD. This article is based on an extensive search for articles including meta-analyses, clinical trials, systematic reviews, observational studies, case series and case reports.
UNASSIGNED: Intravenous high-dose methylprednisolone is the most common therapy for acute attack with patients having a good treatment response. In cases with poor recovery, intravenous immunoglobulins (IVIG) or plasma-exchange proved to be effective. Maintenance therapies include mycophenolate mofetil, azathioprine, IVIG, oral corticosteroids, rituximab, and interleukin-6 receptor (IL6-R) antagonists. Rituximab is the most used drug while IL6-R antagonists emerged as an effective option for people not responding to current treatments. Larger prospective studies with longer follow-ups are needed to confirm whether the blockage of the IL6-R is an effective and safe option. Since there is no evidence of major safety issues related to the new available therapies, the authors believe that waiting for disease activity to consider a possible treatment change, is an unwise approach.

BACKGROUND: The clinical spectrum and diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has evolved in the setting of an optimized anti-MOG-IgG cell-based assay and expert consensus. The McDonald criteria for MS have been revised multiple times to improve the accuracy and specificity of diagnosis on a framework based on clinical presentation, MRI findings, and CSF results. While the uses of MS and MOGAD diagnostic criteria are helpful for typical cases, such utility for patients with overlapping clinical, laboratorial, and imaging features is unknown, posing diagnostic and management uncertainties.
OBJECTIVE: To report a multicenter cohort of patients with overlapping phenotypic features of MOGAD and MS and evaluate the application of new MOGAD diagnostic criteria.
METHODS: A collaborative retrospective cohort study was performed to identify patients with both positive serum anti-MOG-IgG and fulfillment of the MS revised 2017 McDonald criteria. Clinical and radiographic features of patients fulfilling inclusion criteria were reviewed longitudinally, including relapses, repeated MRI, and MOG-IgG testing in detail to allow the panel of expert opinion to assign to each case. The International MOGAD Panel proposed criteria were applied at onset and last follow-up to each case and compared to the expert author diagnosis assignment based on presentation, clinical and imaging features, and response to treatment.
RESULTS: Ten of 225 (4%) MOG-IgG seropositive cases met study inclusion criteria [seven of 10 were female; age at initial event: eight adults (mean age 26.8 years), two adolescents (mean age 14.5 years)]. AQP4-IgG was negative for all. Apart from serum titers of MOG-IgG, distinguishing clinical and radiographic features [i.e., clinical severity of the initial demyelinating event, radiographic features (optic nerve/spine/brain), and presence/absence of lesion normalization on serial scans] led to consensus of three separate classifications differing by degrees of shared features of MOGAD and MS. Patients were classified by expert panel into (1) Classic MOGAD even with MS-like, well-defined brain lesions, when severe events and most T2 lesions normalized (n = 5; MOG-IgG titers 1:100, 1:20, 1:160, 1:40, 1:200); (2) Classic RRMS included cases thought to have likely false positive or clinically irrelevant MOG-IgG, due to mild clinical events and no radiographic normalization of well-defined MS-like lesions (n = 3; MOG titers 1:20, 1:100, 1:40); (3) MOGAD and MS overlapping phenotype was defined by those with a combination of mild and severe clinical events, partial T2 lesion normalization, both well- and ill-defined lesions (n = 2; MOG titers 1:20, 1:100). The application of the International MOGAD Panel criteria categorized five patients (50%) in agreement with expert assignment. One additional patient was classified in agreement to assignment when MOGAD criteria were applied after serial MOG-IgG titers testing.
CONCLUSIONS: While the International MOGAD Panel diagnostic criteria have helped with accuracy for the diagnosis of this condition, in a group of patients seropositive for MOG-IgG with overlapping clinical and imaging features of RRMS criteria review may lead to increased accuracy. Serial serologies, repeated imaging, close attention to clinical course, and response to therapy are possible variables to consider for further refinement of MOGAD diagnostic criteria.

OBJECTIVE: We aimed to study the risks of relapse and long term disability in children with non-MS acquired demyelinating syndromes (ADS).
METHODS: In this prospective, multi-centre study, from the 14 UK pediatric neurology centres, children (<16 years) experiencing a first episode of ADS were recruited from 2010 to 2014. Case report forms were collected prospectively.
RESULTS: A total of 269 children were recruited and followed up for a median of 7.2 years. Median age at onset was 9y (IQR 9.5-14.5, 126 females). At last follow-up, 46 (18 %) had MS, 4 AQP4-Ab NMOSD and 206 (80 %) had other ADS, of which 27 (13 %) relapsed. Relapsing MOGAD was the diagnosis in 12/27, 6 were seronegative and 9 did not have antibodies tested. Frequency of relapse differed according to first presentation in non-MS ADS, being least likely in transverse myelitis (p = 0.025). In the non-MS group, MOG-Ab was predictive of relapse (HR = 8.42; p < 0.001) occurring 8 times as often decreasing over time. Long-term difficulties did not differ between children with monophasic vs relapsing diseases.
CONCLUSIONS: The risk of relapse in non-MS ADS depends on initial diagnosis, and MOG-Ab positivity. Long-term difficulties are observed regardless of relapses and are determined by presenting phenotype.