Oligodendrocyte Glycoprotein Immunoglobulin Research Articles

The Varying Faces of MOGAD: A Case Series.

Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated disease (MOGAD) is an immune mediated demyelinating disorder initially described as a subtype of neuromyelitis optica spectrum disorder with antibodies against MOG. Recently, it has been described as a separate disease entity with unique clinical and radiological features. We herein report the clinical details of eight MOG-IgG-positive patients to highlight the peculiar and varied clinical and radiological features of this condition. Encephalitis was the most common presenting feature in our study, especially in pediatric cases. Tremors and parkinsonism were noted in four cases, of which one was a child. Monophasic course was noted in seven patients. Relapsing course was noted only in a single patient who was initiated on immunosuppressants. The clinical pictures highlight the importance of screening for anti-MOG in individuals with encephalitic and multiaxial symptoms in spite of having normal imaging. Acute demyelinating encephalomyelitis such as imaging features in the pediatric age group may also be a consideration for MOG testing.

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

Clinical, Demographic, and Radiological Characteristics of Patients Demonstrating Antibodies Against Myelin Oligodendrocyte Glycoprotein

Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Multicenter, retrospective, observational study. Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayıs University’s Faculty of Medicine were included in the study. Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG.

Two Cases of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Double-Positive Optic Neuritis Successfully Treated With Steroid Therapy.

Two Cases of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Double-Positive Optic Neuritis Successfully Treated With Steroid Therapy.

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.

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

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

Tumefactive demyelinating lesions: a retrospective cohort study in Thailand

Tumefactive demyelinating lesions (TDL), characterized by large (≥ 2 cm) demyelinating lesions mimicking tumors, are a rare manifestation of the central nervous system inflammatory demyelinating diseases (CNS-IDD). Distinguishing TDL from other brain lesions can be challenging, often necessitating biopsy or advanced diagnostics. The natural history of TDL varies among races. This study aimed to assess demographics, clinical and radiological features, laboratory findings, management, and outcomes of Thai patients with TDL. We retrospectively reviewed records of twenty-six patients with TDL from the Multiple Sclerosis and Related Disorders registry from two tertiary medical centers. Among 1102 CNS-IDD patients, 26 (2.4%) had TDL. The median age at TDLs onset was 34.5 years (range 17–75); 69.2% were female. Over 70% manifested TDL as their initial CNS-IDD presentation. Common presenting symptoms included motor deficits, sensory disturbances, and cognitive problems. About two-fifths exhibited multiple lesions, most frequently in the frontoparietal region (46.2%). Half of the patients showed an incomplete ring on post-contrast T1-weighted imaging, with peripheral diffusion-weighted imaging restriction in twenty-one patients. T2-hypointense rims were present in thirteen (56.5%) patients. Brain biopsy was performed in 12 cases (46.1%). Serum aquaporin-4 immunoglobulin was positive in 16.7% of tested (4/24) cases. Serum myelin oligodendrocyte glycoprotein immunoglobulin was negative in all thirteen patients tested. Twenty patients (76.9%) received intravenous corticosteroids for TDL attacks. After the median follow-up period of 48 months (range 6–300), 23.1% experienced CNS-IDD relapses. Median Expanded Disability Status Scale at TDL diagnosis was 4.3 (range 0.0–9.5), and improved to 3.0 (range 0.0–10.0) at the last follow-up. This study suggested that TDL were rare among Thai CNS-IDD patients, frequently presenting as a monophasic condition with a favorable outcome.

AUTOIMMUNE OPTIC NEUROPATHY (AON) PROFILE AT OPHTHALMOLOGY OUTPATIENT CLINIC OF A TERTIARY HOSPITAL IN SURABAYA, INDONESIA

Highlights Autoimmune optic neuropathy (AON) is one of the diseases that involve the central nervous system (CNS) and can result in disability if not treated quickly and appropriately. The autoimmune optic neuropathy (AON) patient’s profile, including disease etiology and therapy, is essential to minimize the incidence of AON. Abstract Background: Autoimmune optic neuropathy (AON) is a kind of optic neuritis that causes progressive and severe vision loss. The presence of an autoimmune disease usually characterizes the diagnosis of this disease. Several autoimmune processes that can cause AON are Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorder (NMOSD), Myelin Oligodendrocyte Glycoprotein Immunoglobulin (MOG-IgG), and other disorders, specifically systemic autoimmune disease, such as Systemic Lupus Erythematous (SLE), Sjogren’s Syndrome, and Sarcoidosis. Risk factors for AON involve young adults and women. Most of the patients received therapy according to the ONTT protocol and underwent outpatient treatment with oral methylprednisolone or prednisone. Objective: The study aimed to obtain the autoimmune optic neuropathy (AON) profile in patients at the Ophthalmology Outpatient Installation of Dr. Soetomo General Academic Hospital Surabaya, Indonesia, in the 2017-2022 Period. Material and Method: This retrospective descriptive study used medical records; 70 subjects were included. Result: Most subjects suffered from SLE (55.7%) as the cause of AON and received therapy according to the ONTT protocol, namely oral methylprednisolone or prednisone (67.1%) with outpatient therapy. Some patients were given other therapies (25.7%), such as mecobalamin and other B complex vitamins. Conclusion: AON is an uncommon condition. However, if not treated promptly and effectively, it can result in handicaps. This study may serve as a reference for future relevant research and as an attempt to prevent the disease.

Visual outcome measures in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) comprises various age-dependent clinical phenotypes and may be monophasic, multiphasic, or chronic. Optic neuritis (ON) is a common manifestation and frequently appears in combination with other MOGAD phenotypes, particularly in young children. Despite permanent structural damage to the retinal nerve fiber layer (RNFL), children often experience complete visual recovery. AimsTo analyze the progression and impact of MOGAD on the visual system of pediatric patients independently of the history of ON. MethodsThis retrospective study included children who met specific criteria: myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) seropositivity, acute presentation of MOGAD, and written general consent. Main outcome measures were global peripapillary retinal nerve fiber layer (pRNFL) thickness, and near and distance visual acuity, analyzed using descriptive statistics. ResultsWe identified 10 patients with median age of 7.7 years at first event: 7 patients manifested with acute disseminated encephalomyelitis (ADEM) (with ON 5/7, ADEM only 1/7, with transverse myelitis (TM) 1/7), 2 with isolated ON, and 1 patient with neuromyelitis optica spectrum disorder (NMOSD)-like phenotype with ON. Among ON patients, 5/8 were affected bilaterally, with 3 initially diagnosed with unilateral ON but experiencing subsequent involvement of the fellow eye. None of the patients without previous ON showed a deterioration of visual acuity and, if evaluated, a reduction of the pRNFL. ConclusionMost pediatric MOGAD-ON patients in our cohort presented with acute vison loss and optic disc edema. All patients achieved complete visual recovery, independent of number of relapses or initial visual loss. The pRNFL thickness decreased for several months and stabilized at reduced levels after 12 months in the absence of further relapses. MOGAD may not have subclinical/’silent’ effects on the visual system, as visual acuity and pRNFL were not affected in patients without ON.

Glymphatic System Dysfunction in Myelin Oligodendrocyte Glycoprotein Immunoglobulin G Antibody-Associated Disorders: Association with Clinical Disability.

Impaired glymphatic function has been suggested to be implicated in the pathophysiology of MS and aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder. This study aimed to investigate the interstitial fluid dynamics in the brain in patients with myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), another demyelinating disorder, using a noninvasive imaging technique called the diffusivity along the perivascular space (ALPS) index. A prospective study was conducted on 16 patients with MOGAD in remission and 22 age- and sex-matched healthy control subjects. MR imaging was performed using a 3T scanner, and the ALPS index was calculated using diffusion MR imaging data with a b-value of 1000 s/mm2. The ALPS index and gray matter volumes were compared between the 2 groups, and these parameters were correlated with the Expanded Disability Status Scale. The mean ALPS index of patients with MOGAD was significantly lower than that of healthy controls (Cohen d = 0.93, false discovery rate-corrected P = .02). The lower mean ALPS index was significantly associated with a worse Expanded Disability Status Scale score (Spearman ρ = -0.51; 95% CI, -0.85 to -0.02; P = .03). However, cortical volume and deep gray matter volume were not significantly different between the 2 groups, and they were not correlated with the Expanded Disability Status Scale. This study suggests that patients with MOGAD may have impaired glymphatic function, as measured by the ALPS index, which is associated with patient disability. Further study is warranted with a larger sample size.

A longitudinal analysis of brain volume changes in myelin oligodendrocyte glycoprotein antibody-associated disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a relapsing demyelinating condition. There are several cross-sectional studies showing evidence of brain atrophy in people with MOGAD (pwMOGAD), but longitudinal brain volumetric assessment is still an unmet need. Current recommendations do not include monitoring with MRI and assume distinct attacks. Evidence of ongoing axon loss will have diagnostic and therapeutic implications. In this study, we assessed brain volume changes in pwMOGAD over a mean follow-up period of 2years and compared this to changes in people with multiple sclerosis (pwMS). This is a retrospective single-center study over a 7-year period from 2014 to 2021. MRI brain scans at the time of diagnosis and follow-up in remission were collected from 14 Caucasian pwMOGAD, confirmed by serum myelin oligodendrocyte glycoprotein immunoglobulin G antibody presence, detected by live cell-based assays. Total brain volume (TBV), white matter (WM), gray matter (GM), and demyelinating lesion volumes were assessed automatically using the Statistical Parametric Mapping and FMRIB automated segmentation tools. MRI brain scans at diagnosis and follow-up on remission were collected from 32-matched pwMS for comparison. Statistical analysis was done using analysis of variance. There is evidence of TBV loss, affecting particularly GM, over an approximately 2-year follow-up period in pwMOGAD (p<.05), comparable to pwMS. WM and lesion volume change over the same period were not statistically significant (p>.1). We found evidence of loss of GM and TBV over time in pwMOGAD, similar to pwMS, although the WM and lesion volumes were unchanged.

Comparison of glial fibrillary acidic protein-immunoglobulin G-associated myelitis with myelin oligodendrocyte glycoprotein-immunoglobulin G-associated myelitis.

Glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG)-associated myelitis and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)-associated myelitis have rarely been compared. Therefore, this study aimed to explore the clinical, laboratory, and imaging features of them to identify the differences. Overall, 14 and 24 patients with GFAP-IgG-and MOG-IgG-associated myelitis, respectively, were retrospectively screened and included in the study. Among the 14 patients with GFAP-IgG-associated myelitis, the condition was more common in males (71.4%), with a median age of onset of 36.5 years, and more common in adults than in children (35.7%). In contrast, among the 24 patients with MOG-IgG-associated myelitis, the condition was equally divided between males and females, with a median age of onset of 9.5 years and more in children (66.7%) than in adults. The median age of onset of GFAP-IgG-associated myelitis was later than that of the MOG-IgG group. Isolated myelitis was rare in both groups. Elevated cerebrospinal fluid (CSF) protein levels were more prevalent in patients with GFAP-IgG-associated myelitis (64.3%) than in those with MOG-IgG-associated myelitis (16.7%) (p < 0.05), whereas patchy gadolinium enhancement of the cerebral lesion site was less common in patients with GFAP-IgG-associated myelitis than in those with MOG-IgG associated myelitis (p < 0.05). Six patients had a combination of other neurological autoantibodies, the specific mechanism of the overlapping antibodies remains unclear. Cerebrospinal fluid analysis and gadolinium enhanced MRI examination may help to distinguish the two kinds of myelitis.

Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

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.

Successful treatment with subcutaneous ofatumumab in an adolescent patient with refractory myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD)

Preventing relapse of myelin oligodendrocyte glycoprotein-immunoglobulin G-associated disease (MOGAD) with steroids and immunosuppressants is sometimes difficult. There is no standard treatment for refractory cases. We present the case of a 17-year-old female patient with longitudinally extensive myelitis, asymptomatic bilateral optic neuritis, and positive serum MOG-IgG. While taking steroids and several immunosuppressants during the following 14months, she suffered from two symptomatic relapses in the cerebrum and spinal cord, and multiple asymptomatic relapses in the cerebrum. The patient was negative for MOG-IgG at the second relapse of myelitis. Subcutaneous ofatumumab has suppressed relapse for 13 months. Ofatumumab can be considered a therapeutic option for refractory MOGAD.

Gut microbiota dysbiosis associated with different types of demyelinating optic neuritis in patients.

Demyelinating optic neuritis (DON) causes rapid vision loss in young and middle-aged people. The limited efficacy of treatment and the toxic side effects of drugs significantly affect the quality of life of patients with DON. Therefore, DON pathogenesis has always been a research hotspot in terms of prevention and treatment. Studies have suggested that gut microbiota imbalances may be involved in autoimmune disease development via the modulation of multiple inflammatory cytokines and anti-inflammatory metabolites. Therefore, this study aims to explore gut microbiota differences between healthy controls (HCs) and patients with DON. A total of 54 patients with DON and 41 HCs were recruited. Fecal and blood samples were collected before and after intravenous methylprednisolone pulse (IVMP) treatment. The Shannon index, gut microbiota structure, and differential bacteria were evaluated and compared. The Shannon diversity index was decreased in patients with DON (p < 0.001) but was higher after IVMP treatment (p < 0.05). In patients with DON, Blautia, Escherichia-Shigella, and Ruminococcus showed higher abundances, whereas Bacteroides, Faecalibacterium, Roseburia, Parabacteroides, Romboutsia, and Alistipes showed lower abundances compared to that in the HCs. After IVMP treatment, the Shannon index of the myelin oligodendrocyte glycoprotein-immunoglobulin G (+) (MOG-IgG (+)) and both aquaporin-4 (AQP4)-IgG (-) and MOG-IgG (-) groups increased (p < 0.05). Bacteroides was negatively correlated with interleukin (IL)-21, IL-17E, and tumor necrosis factor-α levels (p < 0.05, r=-0.54; p < 0.05, r= -0.50; p < 0.05, r =-0.55, respectively). Escherichia was positively correlated with macrophage inflammatory protein-3α (p < 0.05, r=0.51). Alistipes was negatively correlated with soluble CD40 ligand (p < 0.05, r=-0.52). The gut microbiota differed significantly between patients with DON and HCs; however, IVMP treatment may restore gut microbiota diversity and structure in patients with DON. Moreover, gut microbiota changes may play a role in DON pathogenesis.

Tumefactive Demyelination in MOG Ab-Associated Disease, Multiple Sclerosis, and AQP-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD. We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD (p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R 2 = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance. Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: an update.

Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.

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.

Update on glial antibody-mediated optic neuritis.

Optic neuritis (ON) refers to inflammatory demyelinating lesions of the optic nerve, which can cause acute or subacute vision loss and is a major cause of vision loss in young adults. Much of our understanding of typical ON is from the Optic Neuritis Treatment Trial. Glial autoantibodies to aquaporin-4 immunoglobulin (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin (MOG-IgG) are recently established biomarkers of ON that have revolutionized our understanding of atypical ON. The detection of glial antibodies is helpful in the diagnosis, treatment, and follow-up of patients with different types of ON. AQP4-IgG and MOG-IgG screening is strongly recommended for patients with atypical ON. Research on the pathogenesis of NMOSD and MOGAD will promote the development and marketing of targeted immunotherapies. The application of new and efficient drugs, such as the selective complement C5 inhibitor, IL-6 receptor inhibitor, B cell-depleting agents, and drugs against other monoclonal antibodies, provides additional medical evidence. This review provides information on the diagnosis and management of glial antibody-mediated ON.