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

BACKGROUND: Children 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 PRESENTATION: Two 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. CONCLUSIONS: Although 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.

Evaluation of brain and spinal cord lesion distribution criteria at disease onset in distinguishing NMOSD from MS and MOG antibody-associated disorder.

OBJECTIVE: To validate the recently proposed imaging criteria in distinguishing aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD) at disease onset in a Chinese population. METHODS: We enrolled 241 patients in this retrospective study, including 143 AQP4-ab-seropositive NMOSD, 73 MS, and 25 MOG-AD. Cacciaguerra's criteria were described as fulfillment of at least 2/5 conditions including the absence of the combined juxtacortical/cortical lesions, the presence of longitudinal extensive transverse myelitis (LETM) lesions, the presence of periependymal-lateral ventricles lesions, the absence of Dawson's fingers lesions, and the absence of periventricular lesions. RESULTS: Fulfillment of at least 3/5 conditions was able to differentiate NMOSD from MS with a good diagnostic performance (accuracy = 0.92, sensitivity = 0.91, specificity = 0.93), yet failed to differentiate NMOSD from MOG-AD. LETM lesions showed the highest accuracy (0.78), sensitivity (0.70), and specificity (0.97) for NMSOD. CONCLUSION: Our research suggested the utility of Cacciaguerra's criteria in a Chinese population at disease onset. A better diagnostic performance in NMOSD could be attained with at least 3/5 conditions fulfilled. Yet their utility in distinguishing NMOSD from MOG-AD was limited.

Myelin oligodendrocyte glycoprotein antibody-associated disease in a patient with symptoms of aseptic meningitis who achieved spontaneous remission: A case report and review of the literature.

BACKGROUND: A few case reports have described patients with myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelinating syndrome who presented with symptoms of aseptic meningitis. All such patients required immunotherapy. We report a patient with MOG-Ab-associated disorder (MOGAD) who presented with symptoms of aseptic meningitis and improved without treatment. CASE: A 13-year-old girl presented with fever, headache, decreased appetite, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and magnetic resonance imaging (MRI) showed leptomeningeal enhancement. The patient was diagnosed with aseptic meningitis at admission. However, there were no signs of recovery 4 days after admission (i.e., 8 days after disease onset). Therefore, we performed extensive investigations to identify the cause of the underlying infection and inflammation. On day 14 after admission, the serum MOG-Ab test performed at admission came back positive (1:128) and she was diagnosed with MOGAD. She was discharged on day 18 after admission, because her symptoms, CSF pleocytosis, and MRI findings had improved. About 6 weeks after discharge, MRI revealed hyperintensity without gadolinium enhancement. However, her serum MOG-Ab test was negative. We did follow-ups for 11 months but found no new neurological symptoms. DISCUSSION AND CONCLUSION: To the best of our knowledge, this is the first ever report of a pediatric patient with MOGAD experiencing spontaneous remission with no demyelinating symptoms during an extended follow-up period.

Identifying specific myelopathy etiologies in the evaluation of suspected myelitis: A retrospective analysis.

BACKGROUND: Myelopathies require prompt etiologic diagnosis. We aimed to identify a specific myelopathy diagnosis in cases of suspected myelitis to highlight clinicoradiologic differences. METHODS: In this retrospective, single-centre cohort of subjects with suspected myelitis referred to London Multiple Sclerosis (MS) Clinic between 2006 and 2021, we identified those with MS and reviewed the remaining charts for etiologic diagnosis based on clinical, serologic, and imaging details. RESULTS: Of 333 included subjects, 318/333 (95.5%) received an etiologic diagnosis. Most (274/333, 82%) had MS or clinically isolated syndrome. Spinal cord infarction (n = 10) was the commonest non-inflammatory myelitis mimic characterized by hyperacute decline (n = 10/10, 100%), antecedent claudication (n = 2/10, 20%), axial owl/snake eye (n = 7/9, 77%) and sagittal pencillike (n = 8/9, 89%) MRI patterns, vertebral artery occlusion/stenosis (n = 4/10, 40%), and concurrent acute cerebral infarct (n = 3/9, 33%). Longitudinal lesions were frequent in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (n = 7/7, 100%) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) (n = 6/7, 86%), accompanied by bright spotty (n = 5/7, 71%) and central-grey-restricted (n = 4/7, 57%) T2-lesions on axial sequences, respectively. Leptomeningeal (n = 4/4, 100%), dorsal subpial (n = 4/4, 100%) enhancement, and positive body PET/CT (n = 4/4, 100%) aided the diagnosis of sarcoidosis. Spondylotic myelopathies had chronic sensorimotor presentations (n = 4/6, 67%) with relative bladder sparing (n = 5/6, 83%), localizable to sites of disc herniation (n = 6/6, 100%). Metabolic myelopathies showed dorsal column or inverted 'V' sign (n = 2/3, 67%) MRI T2-abnormality with B12 deficiency. CONCLUSIONS: Although no single feature reliably confirms or refutes a specific myelopathy diagnosis, this study highlights patterns that narrow the differential diagnosis of myelitis and facilitate early recognition of mimics.

Effectiveness and tolerability of different therapies in preventive treatment of MOG-IgG-associated disorder: A network meta-analysis.

Background: Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear. Aim: To identify the efficacy and tolerability of different treatments for MOG-AD. Methods: Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI). Results: Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=-0.85, 95% CrI: -1.7 to -0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies. Conclusions: Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.

Etiologies of Acute Optic Neuritis in Thailand: An Observational Study of 171 Patients.

PURPOSE: To analyze the demographic patterns, clinical characteristics and etiologies of acute optic neuritis (ON). METHODS: This retrospective observational study included patients with acute ON who presented to a university hospital in Bangkok, Thailand, between January 2010 and March 2020. The demographic details, clinical characteristics and etiologies of acute ON were evaluated. RESULTS: A total of 171 patients were included in the study (78.4% [n=134] female; mean age 45 years [standard deviation 15.4 years]; 32.2% [n=55] bilateral involvement). The most common type of acute ON was idiopathic (51.5%), followed by neuromyelitis optica spectrum disorder (NMOSD, 30.9%), other autoimmune disorders (9.9%), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD, 5.3%), multiple sclerosis (MS, 1.8%), and postinfection (0.6%). In the other autoimmune disorders group, 2 patients developed systemic lupus erythematosus (1.2%), 2 Sjogren's syndrome (1.2%), 1 RA (0.6%), 1 anti-NMDAR (0.6%), 3 anti-Jo1 (1.8%), 2 c-ANCA (1.2%), 1 anti-centromere (0.6%), and 5 nonspecific autoimmune disorders (2.9%). In the idiopathic group, 38.6% developed single isolated ON, 1.8% relapsing isolated ON and 11.1% chronic relapsing inflammatory optic neuropathy. CONCLUSION: The most common form of acute ON in this study, similar to other Asian countries, was idiopathic. Idiopathic-ON shared some phenotypes with NMOSD and MOGAD. We also reported patients with anti-NMDAR, anti-Jo1, c-ANCA and anti-centromere disorders. Improvements in antibody detection have widened the range of possible etiologies of acute ON. The study highlighted the important role of antibodies in creating effective treatments in the future.

Clinical and imaging features and prognoses of myelin oligodendrocyte glycoprotein antibody associated disorders / 中华神经医学杂志

Objective:To explore the clinical and imaging features and prognoses of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD).Methods:Thirty-nine MOGAD patients, admitted to our hospital from January 2018 to April 2021, were chosen in our study. The clinical and imaging data and follow-up results of these patients at acute attack period (first-onset or relapse) were collected and their features were analyzed.Results:In these 39 patients with MOGAD, 20 patients (51.3%) had non-reversing course, and 19 patients (48.7%) had relapsing course. The clinical and imaging data of 55 episodes of these 39 patients were collected. In these 55 episodes, optic neuritis was noted in 27 episodes (49.1%), encephalitis was noted in 10 episodes (18.2%), brainstem encephalitis was noted in 8 episodes (14.5%), meningoencephalitis in 2 episodes (14.5%), myelitis in 3 episodes (5.5%), encephalomyelitis in 1 episode (1.8%), optic neuromyelitis in 1 episode(1.8%), optic neuritis+meningoencephalitis in 2 episodes (3.6%), and optic neuritis+encephalitis in 1 episode (1.8%). The positive rate of antinuclear antibody (ANA) was 11.1% (4/36); the cerebrospinal fluid results of 28 samples were collected from 22 patients, and CSF pleocytosis occurred in 67.9% of the samples with value of 54.89±67.70×10 6/L. Twenty-seven brain MRIs of 19 patients at the acute episode were collected; one completely normal MRI was recorded; among the remaining 26 MRIs, 6 were with one single lesion, 5 were with 2 lesions, and 15 were with 3 or more lesions; in terms of distribution, lesions involving brainstem and its adjacent structures were found in 9 MRIs, lesions involving diencephalon and deep gray matter were found in 7 MRIs, supratentorial white matter lesions were found in 13 MRIs, and cortical lesions were found in 13 MRIs. Meningeal enhancement were found in 4 contrast-enhanced brain MRIs (4/20). Long or short segmental myelitis in the spinal MRIs was noted in spinal lesions, involving cervical spinal cord, thoracic spinal cord and conus, and the "H" sign could be seen in the cross section. All patients received steroids therapy at the acute phase and the doses of steroids were tapered down gradually. Thirty-eight patients (97.4%) had good prognosis after 3 months of treatment. Conclusions:MOGAD is a disease entity widely involving the white matter, gray matter and meninges of the central nervous system with various clinical manifestations such as optic neuritis, encephalitis, brainstem encephalitis, meningoencephalitis and myelitis or a combination of the above. Immunotherapy is effective in most patients, but the recurrence rate is high, and some patients require long-term immunotherapy.