Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience / Espectro clínico de doença associada com anticorpos contra a glicoproteína de oligodendrócito de mielina no Brasil: uma experiencia de centro único

Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Resumo Antecedentes A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. Objetivo Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. Métodos Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. Resultados Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. Conclusão Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging? / NMOSD AQP4-IgG, MOGAD e NMOSD duplo soronegativo: é possível caracterizar o tipo de anticorpo pela ressonância magnética?

Abstract Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.

Resumo Antecedentes Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. Objetivo Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. Métodos Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. Resultados Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). Conclusão A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: an update / Neurite óptica associada com anticorpo contra a glicoproteína oligondendrócita da mielina: uma breve atualização

ABSTRACT 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.

RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.

Changes of corneal nerve fiber and the correlation analysis with visual acuity in demyelinating optical neuritis patients / 中华眼底病杂志

Objective:To investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity.Methods:A cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. Results:The CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm 2, (57.78±12.35) root/mm 2, (3.27±1.34) mm/mm 2, and (13.74±3.05) mm/mm 2, (70.95±13.14) root/mm 2, and (4.22±1.03) mm/mm 2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant ( t=4.089, 3.795, 2.773; P<0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm 2, (3.80±1.19) mm/mm 2, (47.97±8.86) fibers/mm 2, and (9.25±2.19) mm/mm 2, (2.72±1.19) mm/mm 2, (39.43±13.86) fibers/mm 2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant ( t=-4.002, -2.706, -2.306; P<0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm 2, respectively. The difference in corneal DC density between the two subgroups was statistically significant ( P<0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON ( r=-0.422, -0.456; P<0.05). Conclusions:There are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.

Anti-myelin oligodendrocyte glycoprotein-IgG associated disorders coexisting with brucellosis: a case report and literature review / 中华神经科杂志

Objective:To study the clinical characteristics and prognosis of Brucella and other pathogens infections complicated with anti-myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD). Methods:The clinical data of a patient with brucellosis complicated with MOGAD diagnosed in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in April 2022 were reported, and related case reports of infection coexisting with MOGAD were reviewed and summarized.Results:This case was a 44-year-old male, with recurrent fever and anorexia, followed by sudden weakness, numbness, pain in both lower limbs and dysuria, and then pain in the right neck. Magnetic resonance imaging showed lesions in the spine and spinal cord. Due to the positive myelin oligodendrocyte glycoprotein antibodies in cerebrospinal fluid and serum, and the growth of Brucella in blood culture, he was diagnosed as brucellosis complicated with MOGAD. After anti-brucellosis and glucocorticoid therapy, his symptoms improved. The literature on infection coexisting with MOGAD was reviewed and 22 cases were included. The infection sources included COVID-19, Borrelia burgdorferi, etc. No case of Brucella infection complicated with MOGAD had been reported. The main clinical manifestations of the 22 cases included myelitis (63.6%, 14/22), optic neuritis (40.9%, 9/22), acute disseminated encephalomyelitis (18.2%, 4/22), multiphasic disseminated encephalomyelitis (4.5%, 1/22) and meningoencephalitis (4.5%, 1/22). Magnetic resonance imaging was performed in 20 cases, showing spinal cord lesions in 12 cases (60.0%, 12/20), intracranial lesions in 10 cases (50.0%, 10/20) and optic nerve lesions in 6 cases (30.0%, 6/20). Cerebrospinal fluid examination was performed in 19 patients, of whom 13 (13/19) had increased cerebrospinal fluid cell count and 10 (10/18) had increased cerebrospinal fluid protein. Twenty-two patients received glucocorticoid therapy, of which 95.5% (21/22) responded well and 95.5% (21/22) had a good prognosis. Conclusions:Brucella and other pathogens infection may complicate with MOGAD, with similar clinical manifestations, and glucocorticoid therapy is effective.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents / Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Differential diagnosis of demyelinating diseases: what's new? / Diagnóstico diferencial das doenças desmielinizantes: o que há de novo?

ABSTRACT Background: Acquired demyelinating disorders lead to overlapping visual, pyramidal, sensory, autonomic, and cerebellar deficits and may lead to severe disability. Early diagnosis and start of treatment are fundamental towards preventing further attacks and halting disability. Objective: In this paper we provide an updated overview of the differential diagnoses of acquired demyelinating disorders. Methods: We performed a critical targeted review of the diagnoses of the most prevalent demyelinating disorders: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Results: We discuss the workup, diagnostic criteria and new biomarkers currently being used for the diagnosis of these disease entities taking into account the particularities of the Brazilian population and healthcare system. Conclusion: A comprehensive analysis of medical history, physical examination, biomedical and imaging data should be performed to obtain differential diagnosis. Diagnostic criteria should be mindfully employed considering ethnic and environmental particularities of each patient.

RESUMO Antecedentes: Doenças desmielinizantes adquiridas levam a déficits visuais, piramidais, sensitivos, autonômicos e cerebelares que se sobrepõem e podem conduzir a grave incapacidade. O diagnóstico e o início de tratamento precoces são fundamentais para a prevenção de surtos e ocorrência de incapacidade. Objetivo: Neste artigo, apresentamos uma visão geral atualizada sobre o diagnóstico diferencial de doenças desmielinizantes adquiridas. Métodos: Realizamos uma revisão crítica sobre o diagnóstico das doenças desmielinizantes mais prevalentes: esclerose múltipla (EM), doença do espectro neuromielite óptica (NMOSD) e doença associada ao anticorpo contra a glicoproteína da mielina do oligodendrócito (MOGAD). Resultados: Discutimos a investigação, os critérios diagnósticos e os novos biomarcadores atualmente empregados para o diagnóstico dessas doenças, levando em conta as particularidades da população e sistema de saúde brasileiros. Conclusão: Uma análise minuciosa do histórico médico, exame neurológico e exames biomédicos e de imagem deve ser realizada para se fazer um diagnóstico diferencial de doença desmielinizante. Critérios diagnósticos devem ser empregados cautelosamente considerando-se particularidades étnicas e ambientais de cada paciente.

COVID-19-associated optic neuritis – A case series and review of literature

Neuroophthalmic manifestations are very rare in corona virus disease?19 (COVID?19) infection. Only few reports have been published till date describing COVID?19?associated neuroophthalmic manifestations. We, hereby, present a series of three cases who developed optic neuritis during the recovery period from COVID?19 infection. Among the three patients, demyelinating lesions were identified in two cases, while another case was associated with serum antibodies against myelin oligodendrocyte glycoprotein. All three patients received intravenous methylprednisolone followed by oral steroids according to the Optic Neuritis Treatment Trail ptotocol. Vision recovery was noted in all three patients, which was maintained at 2 months of the last follow up visit

Clinical profile, imaging features and short term visual outcomes of Indian optic neuritis patients with and without seromarkers for myelin oligodendrocyte glycoprotein and neuromyelitis optica

Purpose: To analyze clinical profile, imaging features, and short?term visual outcomes of optic neuritis patients in Indian population with and without seromarkers for myelin oligodendrocyte glycoprotein (MOG)/neuromyelitis optica (NMO). Methods: Electronic medical records of 203 optic neuritis patients who presented between June 2018 and December 2019 to the Neuro?ophthalmology services of a tertiary care center in India were retrospectively analyzed. Results: Of 203 patients, 57 patients (28.08%) were positive for MOG?antibody and 20 patients (9.85%) were positive for NMO antibody. 114 patients (56.16%) were double?negative (negative for both antibodies) and 12 patients (5.91%) were diagnosed as multiple sclerosis (MS). None of the patients had both antibodies. Mean age of presentation was 31.29 ± 1.035 years. There was female preponderance in NMO?optic neuritis (NMO?ON) and MS?optic neuritis (MS?ON) groups (1:5). Mean vision on presentation was worse (logMAR 1.570 ± 0.863) in NMO?ON group. The mean visual acuity showed statistically significant recovery (logMAR 0.338 ± 0.639) in the final follow?up in MOG?optic neuritis (MOG?ON) group. Multivariate logistic regression analysis revealed poor visual outcome in patients presenting with retrobulbar neuritis, optic disc pallor, bilateral sequential optic nerve involvement, and with positive NMO antibody. Optic neuritis patients presenting with disc edema associated with pain and positive for MOG antibody were found to have a better visual outcome. Conclusion: In this Indian optic neuritis cohort, the prevalence of MOG?ON was higher than NMO?ON. MOG?ON had a better visual outcome than NMO?ON. The incidence of MS?ON was less compared to the western literature. A significant number of patients (114 patients, 56.16%) were double negative for both seromarkers and yet had presented with optic neuritis with no clinical or imaging features suggestive of MS/MOG associated disease (MOG AD)/NMO spectrum disorder (NMO SD).

Analysis of influencing factors related to the prognosis of visual acuity on myelin oligodendrocyte glycoprotein antibody positive optic neuritis after methylprednisolone pulse / 中华眼底病杂志

Objective:To analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy.Methods:A clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: <7 d group, 7-14 d and> 14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing.Results:Among the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship ( r=-0.48, 95% confidence interval -0.71--0.17, P=0.008). Comparing the logMAR BCVA between the intervention time >14 group with the <7 group and the 7-14 group, there were statistically significant difference ( P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. Conclusion:The timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.

Magnetic resonance imaging characteristics of brain lesions in myelin oligodendrocyte glycoprotein antibody associated demyelinating diseases and aquaporin-4 antibody positive neuromyelitis optica spectrum disorders / 中华神经科杂志

Objective:To investigate the distribution and morphological characteristics of brain magnetic resonance imaging (MRI) lesions in patients with myelin oligodendrocyte glycoprotein (MOG) antibody related demyelinating diseases and aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorders (NMOSD) and their clinical value in early diagnosis.Methods:A total of 35 patients with MOG antibody related demyelinating diseases [20 males and 15 females; aged 31 (25, 43) years] and 36 patients with AQP4 antibody positive NMOSD [3 males and 33 females; aged 42 (29, 54) years] were collected retrospectively from September 2018 to June 2021 in Chenzhou First People′s Hospital and the Affiliated Hospital of Qingdao University which were classified as MOG group and AQP4 positive group respectively. All patients underwent routine cranial MRI scanning before treatment and the location, shape and quantity of intracranial lesions were recorded. Wilcoxon rank sum test was used to compare the number of different types of lesions between the two groups. Logistic regression analysis was used to evaluate the significance of different lesions for the two diseases.Results:There were 7 types of lesions with significant differences in different parts and shapes. Stepwise Logistic regression showed that cortical and juxtacortical lesions ( OR=21.91, 95% CI 3.09-61.69, P<0.05) and infratentorial peripheral white matter lesions ( OR=10.48, 95% CI 2.00-18.89, P<0.05) were the most important risk factors in the MOG group. The incidence of cortical and juxtacortical lesions in the MOG group was 51.4% (18/35), which was higher than that in the AQP4 positive group (2.8%, 1/36; χ2=19.02, P<0.01). The incidence of infratentorial peripheral white matter lesions in the MOG group was 31.4% (11/35), which was higher than that in the AQP4 positive group (5.6%, 2/36; χ2=6.31, P<0.05). Receiver operating characteristic (ROC) curve showed that peripheral lesions [including 6 types of lesions such as supratentorial soft meningitis, cortical encephalitis, cortical and juxtacortical lesions, infratentorial soft meningitis, infratentorial soft meningeal demyelination and infratentorial peripheral lesions, area under curve (AUC)=0.93] were more important than cortical and juxtacortical lesions (AUC=0.75) and central lesions (supratentorial paraventricular white matter lesions, diencephalon, infratentorial paraventricular lesions,AUC=0.64), which had higher diagnostic efficiency. Conclusions:The incidence of intracranial lesions in MOG antibody related demyelinating disease was higher than that in AQP4 positive NMOSD, and the distribution and morphology of intracranial MRI lesions in the two diseases had their characteristic manifestations. Identifying the distribution patterns of peripheral lesions (distributed along pia mater) and central lesions (distributed along ependyma) had a certain reference significance for distinguishing the two groups of diseases.

Follow-up and recurrence markers analysis of anti-myelin oligodendrocyte glycoprotein IgG associated disorders in children / 中华神经科杂志

Objective:To summarize clinical features, outcome and prognosis of anti-myelin oligodendrocyte glycoprotein IgG associated disorders (MOGAD) in children, and to explore the markers of recurrent MOGAD.Methods:The clinical features, imaging, serum and cerebrospinal fluid immune markers, treatments and outcomes were analyzed and compared between children with monophasic and recurrent MOGAD, who were hospitalized in the Department of Neurology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics from January 2019 to February 2020.Results:A total of 22 children were included, of whom 8 patients (36.4%) had a recurrent course and 14 patients (63.6%) had a monophasic course. There was no statistically significant difference in sex, age of onset, clinical symptoms, modified Rankin Scale score, location of lesions and serum anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) titer, overall duration of total immunotherapy, positive antinuclear antibody and history of precursory infection between the two groups ( P>0.05). The serum MOG-IgG titer in the recurrent course group was more likely to remain unchanged or increased, and even increased after treatment, while there was no increase in the serum MOG-IgG titer in the monophasic course group, and the proportion of the patients with serum MOG-IgG titer decreased was higher in the monophasic course group (the monophasic course group: 6/8, the recurrent course group: 2/8), and there was statistically significant difference between the two groups ( P=0.030). The positive rate of MOG-IgG in cerebrospinal fluid in the recurrent course group was significantly higher than that in the monophasic course group at the first attack, the difference being statistically significant (the monophasic course group: 1/10, the recurrent course group: 4/6, P=0.036). The both groups were effecive to first-line immunotherapy, and the clinical symptoms and imaging were completely or partially recovered compared to the acute phase. Seven of 8 patients with recurrent MOGAD were treated with mycophenolate mofetil, and the recurrence rate decreased significantly [annual recurrence rate before treated with mycophenolate mofetil: 2.06 (1.36, 2.34) times/year, annual recurrence rate after treated with mycophenolate mofetil: 0 (0, 0) time/year, Z=-3.26, P=0.001]. The humoral immune status of children treated with mycophenolate mofetil was monitored regularly, and no obvious adverse reactions were found during the follow-up. Conclusions:At least one third of children with MOGAD were recurrent, and the serum MOG-IgG titer of children with recurrent MOGAD continued to be high, and even increased after treatment. Positive MOG-IgG in cerebrospinal fluid at the first attack was found to be a high risk factor for recurrence. The maintenance treatment of mycophenolate mofetil in patients with recurrent MOGAD can significantly reduce the annual recurrence rate and was well tolerated.

Advances in myelin oligodendrocyte glycoprotein antibody-associated disease / 国际儿科学杂志

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is one of inflammatory demyelinating disorders of the central nervous system.Due to the diverse and atypical clinical manifestations, positive rate of current detection methods is not high, and early diagnosis is difficult.This review aims to elucidate the research progress of the epidemiology, pathogenesis, clinical characteristics, diagnostic criteria, biological markers, treatment and prognosis of MOGAD, in order to improve the understanding of MOGAD for clinicians, so as to identify, treat and reduce the recurrence of MOGAD as early as possible.

Myelin-oligodendrocyte glycoprotein antibody-associated disease / 中华神经科杂志

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently-established autoimmune central nervous system demyelinating disease, characterized by the detection of serum anti-myelin-oligodendrocyte glycoprotein antibody of IgG1 type. Sharing similar clinical manifestations with multiple sclerosis and aquaporin-4 antibody positive neuromyelitis optica spectrum disorder, it has yet demonstrated a unique disease course, pathological and radiological features. Therefore, MOGAD should be regarded as a disease entity to carry out further investigation. This review intends to summarize its pathogenesis, diagnosis and treatment progresses, so as to provide guidance for clinical practice.

A case of limbic encephalitis with positive anti-leucine-rich glioma inactivated 1 protein antibody and anti-myelin oligodendrocyte glycoprotein antibody / 中华神经科杂志

A case of limbic encephalitis with positive anti-leucine-rich glioma inactivated 1 protein (LGI1) antibody and anti-myelin oligodendrocyte glycoprotein (MOG) antibody was reported. The patient was a middle-aged male with a history of retinal vein occlusion. The main symptoms were temporal lobe epilepsy, facial arm dystonia, autonomic nerve dysfunction. Magnetic resonance imaging showed long T 2 signal in the right hippocampus without enhancement and normal perfusion. Electroencephalogram showed paroxysmal slow wave and sharp slow wave in interictal period. Blood anti-MOG antibody, blood and cerebrospinal fluid anti-LGI1 antibody were double positive. The main diagnosis was limbic encephalitis. After treatment with hormone and gamma globulin, the symptoms were improved and double antibodies were turned negative. Anti-LGI1/MOG double positive cases are rare, and the clinical manifestations and imaging manifestations of double positive antibody cases are not completely consistent with those with each single antibody, with different characteristics. This report can help clinicians enhance awareness.

Analysis of clinical characteristics of patients with anti-myelin oligodendrocyte glycoprotein and anti-N-methyl-D-aspartate receptor antibody positive / 中华神经科杂志

Objective:To analyze the clinical characteristics of patients with double-positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody and anti-N-methyl-D-aspartate receptor (NMDAR) antibody, so as to raise awareness of such diseases and improve the prognosis.Methods:Eighteen patients (double positive group) with positive serum anti-MOG antibody and cerebrospinal fluid anti-NMDAR antibody in Huashan Hospital, Fudan University from March 2017 to March 2020 were retrospectively analyzed. Using the SPSS software for simple random sampling, anti-MOG group(20 cases) and anti-NMDAR group (20 cases) were randomly selected at the same time for comparison. The anti-MOG group referred to the patients only with positive serum anti-MOG antibody. While the anti-NMDAR group referred to the patients whose cerebrospinal fluid anti-NMDAR antibody was positive. The clinical characteristics, laboratory examination results, radiological characteristics and prognosis of the three groups were collected and analyzed.Results:There was no statistically significant difference in demographic data among the three groups ( P>0.05). The symptoms of patients in the double-positive group were divided into two categories by cluster analysis, which corresponded to the symptom groups obtained by cluster analysis of the anti-MOG group and the anti-NMDAR group, and the same result was verified by correspondence analysis. Compared with the anti-MOG group, the incidence of epilepsy (10/18 vs 3/20, P=0.016), psychosis and behavior change (8/18 vs 0/20, P=0.001), visual disturbances (8/18 vs 17/20, P=0.016), dysarthria/dysphagia (8/18 vs 1/20, P=0.007) was significantly different in the double-positive group ( P<0.017). Compared with the anti-NMDAR group, the incidence of ataxia (8/18 vs 19/20, P=0.001), psychosis and behavior change (12/18 vs 1/20, P<0.001) was significantly different in the double-positive group. There was no statistically significant difference in the combination rate of thyroid peroxidase antibody, thyroglobulin antibody and antinuclear antibody between two groups, and the cerebrospinal fluid pressure, white blood cell count, protein, glucose, chloride and positive rate of oligoclonal band were also not statistically different between two groups ( P>0.017; P<0.017 indicates statistically significant difference by Bonferroni corrected multiple comparisons). Compared with the anti-NMDAR group, whether the brain magnetic resonance imaging had lesions was different in double positive group (18/18 vs 8/20, P<0.001). The initial modified Rankin Scale (mRS) scores before treatment were different among the double positive group, anti-MOG group and anti-NMDAR group (3.72±0.96, 2.75±0.97, 3.95±0.76, respectively, F=10.004, P<0.001), but there was no statistically significant difference in the scores after six-month treatment (1.22±1.44, 0.40±0.75, 1.20±1.24, respectively, F=3.153, P=0.051), and the recurrence rate of the disease was different among the three groups (8/18, 14/20, 5/20, respectively, χ2=10.004, P=0.017). Conclusions:Anti-MOG antibodies and anti-NMDAR antibodies could exist at the same time, showing clinical phenotype overlap, which was a new syndrome called the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody-associated disease and NMDAR encephalitis, MNOS. The condition of MNOS patients was more severe than that of patients with MOG antibody-associated disease (MOGAD), but patients with MNOS, MOGAD, and anti-NMDAR encephalitis all responded well to immunosuppressive therapy. It was suggested that early second-line immunotherapy should be given to reduce the recurrence rate in patients with MNOS and MOGAD.

Comparison of clinical features and prognostic factors of 106 optic neuritis patients with anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody positive and anti-aquaporin 4 immunoglobulin G antibody positive / 中华神经科杂志

Objective:To compare the clinical features of patients with anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody (MOG-IgG) positive and anti-aquaporin 4 immunoglobulin G antibody (AQP4-IgG) positive optic neuritis or neuromyelitis optic spectrum disorders (NMOSD) along with optic neuritis, and to analyze prognostic factors.Methods:A total of 106 consecutive inpatients with optic neuritis as the main manifestation and with positive serum antibodies were collected in Department of Neurology, Beijing Tongren Hospital, Capital Medical University from July 2018 to August 2019. The patients were divided into MOG-IgG-positive optic neuritis (MOG-ON) group (35 cases) and AQP4-IgG-positive optic neuritis (AQP4-ON) group (71 cases) according to serum antibody type. The average follow-up period was 14.9 months (5-26 months). The clinical features and outcomes of patients with different serotypes of optic neuritis were compared, and the prognostic factors for different outcomes were analyzed.Results:Compared with AQP4-ON patients, MOG-ON patients were more common in males [37.1%(13/35) vs 15.5%(11/71), χ2=6.274], binocular involvement [48.6%(17/35) vs 19.7%(14/71), χ2=9.432], ocular pain [82.9%(29/35) vs 62.0%(44/71), χ2=4.770], papilledema [63.5%(33/52) vs 36.5%(31/85), χ2=9.442] and peripapillary hemorrhage [15.4%(8/52) vs 2.4%(2/85), χ2=6.286], and were rare in abnormality of other autoimmune indexes [11.4%(4/35) vs 52.1%(37/71), χ2=16.360] (all of them P<0.05). Similar to AQP4-ON, supratentorial and infratentorial tissues, the long segments of the cervical and thoracic cord and all parts of visual pathway were widely involved in MOG-ON, but the anterior segment of optic nerve in orbital was more frequently involved in MOG-ON than in AQP4-ON (χ2=17.506, P<0.001), while the optic nerve sheath was less involved in MOG-ON than in AQP4-ON (χ2=4.075, P=0.044). The proportion of corrected visual acuity ≥ 0.5 in MOG-ON patients (92.3%, 48/52) post three-month of disease onset was higher than that in AQP4-ON patients (50.0%, 34/68) (χ 2=24.374, P<0.001). Positive serum MOG-IgG was a favorable factor for vision acuity recovery in optic neuritis [ OR (95% CI): 11.537(2.090-63.690)], while older onset age [ OR (95% CI): 0.945 (0.908-0.983)], involvement with other nervous system [ OR(95% CI): 0.116 (0.031-0.439)], and involvement of optic nerve sheath [ OR(95% CI): 0.246 (0.066-0.916)] were adverse factors. The recurrence rate of MOG-ON (37.1%, 13/35) was lower than that of AQP4-ON (59.2%, 42/71; χ 2=4.550, P=0.033). The presence of other nervous system involvement was the promoting factor of optic neuritis recurrence [ OR (95% CI): 6.908 (2.312-20.634)]. Conclusions:Compared with AQP4-ON, MOG-ON patients are more common in men, presenting with binocular painful vision loss, optic disc edema and peri-disc hemorrhage, and involvement of the anterior orbital segment of the optic nerve, while involvement of the optic nerve sheath and other autoimmune index abnormalities are relatively rare. MOG-ON patients have better vision recovery and fewer recurrence after treatment than AQP4-ON. Older age of onset, participation of other nervous system, and immersion of optic nerve sheath, are adverse factors for recovery of optic neuritis, and involvement of other nervous system is also a promoting factor for recurrence of optic neuritis.

Progress on diagnosis and treatment of anti-myelin oligodendrocyte glycoprotein-IgG associated disorders in children / 中国小儿急救医学

Anti-myelin oligodendrocyte glycoprotein-IgG associated disorders(MOGAD) are the most common disorders among children with idiopathic central nervous system demyelination.MOGAD in children can be monophasic or multiphasic.Common clinical phenotypes include acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and optic neuromyelitis spectrum disorders, etc.Additionally, while rare phenotypes include encephalitis, overlapping syndrome, and cranial neuritis.For children with multiphasic MOGAD, the same phenotypes mentioned above can be repeated or combined with other phenotypes.At present, the cell-based assay is recommended to detect serum MOG-IgG level as the diagnostic basis, and the persistent presence of serum MOG-IgG level is a major risk factor for recurrence.There is a lack of high-quality clinical evidence for the treatment of disease modification in multiphasic MOGAD.Alternative drugs include azathioprine, mycophenolate mofetil, rituximab, and maintenance of intravenous immunoglobulin.The prognosis depends on the clinical phenotype, course of disease, and treatment.MOGAD is being recognized, and there are still many problems needed to be solved.

Induced experimental autoimmune encephalomyelitis shows the different phenotype of disease in C57BL / 6 mice with myelin oligodendrocyte glycoprotein35￣55 / 解剖学报

Objective To establish an experimental autoimmune encephalomyelitis (EAE) model in female C57BL / 6 mice aged 6-8 weeks and investigate its disease phenotype so as to build a better animal model of multiple sclerosis (MS) . Methods The EAE model was established in 50 female C57BL / 6 mice through intradermal injection of myelin oligodendrocyte glycoprotein 35-55 peptide. We assessed the disease progression daily according to a 15-point score for 90 days, and further observed the brain lesions in terms of pathology. Results There were three courses of disease in the EAE model: chronic course (3 mice), relapse and remission course (7 mice) and monophasic course (11 mice) . Interestingly, we identified some mice (28 mice) had changes in coat color, mental and motor activity, as well as inflammatory demyelinating lesions in the brain tissue although their neurological functions were scored as 0 point. Conclusion The EAE model in C57BL / 6 female mice shows disease phenotype similar to multiple sclerosis and can be used as a good animal model.