Brainstem Syndrome Research Articles

NMOSD and MOGAD: an evolving disease spectrum.

Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG)-a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future.

Unveiling GFAP Astrocytopathy: Insights from Case Studies and a Comprehensive Review of the Literature.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, which was first identified in 2016, is an immune-mediated inflammatory disorder of the nervous system characterized by antibodies targeting GFAP. The exact pathogenic mechanisms, as well as the role of anti-GFAP antibodies, remain unclear; however, it seems that neuroinflammation is mediated by specific CD8+ T-cells and that neoplasms or viral infections can act as the initial trigger. Although the clinical spectrum of the disease is broad and heterogenous, GFAP astrocytopathy most commonly presents as meningoencephalitis with or without myelitis. Other symptoms include headache, visual disturbances, extrapyramidal or brainstem syndromes, and psychiatric manifestations including psychosis. The disease has a characteristically favorable response to steroid treatment while relapses occur in approximately 20-30% of the patients. We present two cases of GFAP astrocytopathy admitted to our hospital: a 43-year-old male with persistent headache and a 59-year-old female with acute dysarthria and swallowing difficulties followed by cognitive and behavioral symptoms. Additionally, we conduct a comprehensive review of the literature to elucidate the role of anti-GFAP antibodies in disease pathogenesis and examine imaging characteristics, clinical manifestations, and treatment options for this recently described neuroimmunological condition. This review presents two unusual cases of GFAP-astrocytopathy and provides evidence for the pathogenesis, clinical presentation, imaging characteristics and treatment options of the disease.

L’anisocorie intermittente comme signe révélateur de la sclérose en plaques récurrente-rémittente

A 36-year-old male presented for an examination reporting intermittent anisocoria of one week duration. Over a period of one-month, ocular findings consisted of intermittent and variable anisocoria, diplopia, and torsional nystagmus. A diagnosis of relapsing-remitting multiple sclerosis (MS) was made using the McDonald criteria based on brainstem syndrome, optic neuropathy, transverse myelitis symptoms, multifocal areas of demyelination in the spinal cord on MRI, and the absence of MS mimickers in lab work. In this case report, eye care providers are alerted to the possibility of intermittent anisocoria as a presenting sign of relapsing-remitting multiple sclerosis.

Charcot-Marie-Tooth Type 2 Disease and Relapsing Remitting Multiple Sclerosis Coexistence

Multiple sclerosis (MS) and Charcot-Marie-Tooth disease (CMT) association has been reported, namely in CMTX and CMT1A. A 37-year-old woman with CMT type 2 (MFN2 mutation) developed subacute brainstem syndrome (left internuclear ophthalmoplegia, facial palsy and ataxia). Brain magnetic resonance imaging revealed infratentorial, periventricular and subcortical lesions, typical of MS (positive CSF oligoclonal bands, negative anti-aquaporin 4 and anti-MOG antibodies). Patient underwent natalizumab, reaching NEDA-3 – no evidence of disease activity - (3-years follow-up). Patients with MFN2 mutations may disclose optic atrophy and periventricular white matter T2 signal changes mimicking MS. Notwithstanding, this is, probably, the first report of proven concomitance between both conditions.

Autoimmune GFAP Astrocytopathy-Beyond the Known Horizon, India's First Multifaceted Institutional Experience.

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an immune-mediated inflammatory disease of the central nervous system, the clinical phenotype of which includes meningoencephalitis, myelitis, optic neuritis, seizures, movement disorders, autonomic dysfunction among others, affecting people across all ages. Due to its recent discovery, there is a paucity of literature on this topic and an absolute lack of Indian case series. Purpose: This study aims to shed light on the variable presentations of anti-GFAP astrocytopathy and review the existing literature on the topic. Methods: This was a retrospective study that included all patients who tested positive in the cerebrospinal fluid(CSF) and/or serum for GFAP immunoglobulin G between February 2023 and August 2023, after obtaining ethical clearance. Relevant clinical, demographic data was collected from the electronic medical records. A descriptive analysis of data was done and the current available literature was reviewed. Results: Our case series included four patients (F:M::3:1) with a median age of 28 years at symptom onset. Two of the cases had a relapsing-remitting disease pattern, while the other two had monophasic illnesses. The clinical spectrum we encountered included ataxia, tremors, myoclonus, seizures, recurrent myelitis, brain stem syndromes, autonomic dysfunction and psychiatric manifestations. All four patients responded remarkably to steroids and two patients are on rituximab therapy. Conclusion: Autoimmune GFAP astrocytopathy encompasses an expanding clinical spectrum and should be considered in the context of myelitis, optic neuritis, ataxia, papillitis, seizures, autonomic dysfunction and movement disorders occurring in isolation or more commonly in varying combinations. Our case series, the first in India, shows a favourable clinical profile and the primary hurdle encountered in all four cases was to establish a diagnosis, further stressing the need for a predictive diagnostic algorithm.

Cancer-associated neuromyelitis optica spectrum disorder: a case report with literature review.

Neuromyelitis optica spectrum disorders (NMOSD) is one of autoimmune inflammatory diseases and is characterized by area postrema syndrome, brainstem syndrome, optic neuritis, and/or myelitis. Typical myelitis is longitudinally extended transverse myelitis (LETM) which extends over three vertebral bodies. Several previous case reports have suggested association between cancer and NMOSD. A 50-year-old woman had breast cancer and underwent mastectomy and, 10 months later, she had developed acutely progressive dysbasia. Spine MRI showed LETM in 13 vertebrae length and blood test revealed positive anti-aquaporin 4 (anti-AQP4) antibody based on enzyme-linked immunosorbent assay with index of over 40. She was treated by intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin, followed by oral prednisolone. The condition had mostly recovered after the treatment. A small population of NMOSD has the aspect of paraneoplastic neurological syndrome. The age of onset in patients with cancer-associated NMOSD tends to be higher than that in individuals with NMOSD due to any causes of NMOSD.

Millard–Gubler Syndrome due to Parenchymal Neuro-Behcet’s Syndrome Lesion: A Rare Case Report

Behcet's disease; it is a vascular-inflammatory chronic recurrent disease that can affect many systems in the body. Millard–Gubler syndrome is one of the brainstem syndromes that occur due to lesions involving the ventral part of the caudal pons. We wanted to present a case of Millard–Gubler syndrome, which developed due to Behçet’s syndrome lesion in the pons ventral region in a patient who presented with limitation of outward gaze on the left, inability to close the left eye completely, inability to completely wrinkle the left side of the forehead, and loss of contralateral muscle strength.

Neuromyelitis optic spectrum disorder following COVID- 19 (ChAdOx1-S) vaccine

Neuromyelitis optic spectrum disorder is an autoimmune demyelinating astro- cytopathy of central nervous system. It has emerged as a distinct clinical entity following the discovery of pathogenic antibody named AQP4-IgG against aquaporin-4 water channels in astrocytes. The clinical spectrum includes optic neuritis, acute myelitis, acute brain stem syndrome, area postrema syndrome, acute diencephalic syndrome and symptomatic cerebral syndrome.This case describes a young male patient who presented with subacute onset painful visual impairment of left eye along with bilateral lower limb weakness and numbness in the background of recent vaccination for covid-19 infection. Examination revealed bilateral papillitis and bilateral flaccid paraparesis with a sensory level at T4 level. Investigations revealed a longitudinally extensive myelitis spanning the entire length of the spinal cord, bilateral optic neuritis, positive serum AQP4-IgG antibodies with negative infective screening and autoimmune profile. Central nervous system demyelination has been observed with all types of covid-19 vaccines.

Multiple Sclerosis: An Emergency Medicine-Focused Narrative Review

BackgroundMultiple sclerosis (MS) is a rare but serious condition associated with significant morbidity. ObjectiveThis review provides a focused assessment of MS for emergency clinicians, including the presentation, evaluation, and emergency department (ED) management based on current evidence. DiscussionMS is an autoimmune disorder targeting the central nervous system (CNS), characterized by clinical relapses and radiological lesions disseminated in time and location. Patients with MS most commonly present with long tract signs (e.g., myelopathy, asymmetric spastic paraplegia, urinary dysfunction, Lhermitte's sign), optic neuritis, or brainstem syndromes (bilateral internuclear ophthalmoplegia). Cortical syndromes or multifocal presentations are less common. Radiologically isolated syndrome and clinically isolated syndrome (CIS) may or may not progress to chronic forms of MS, including relapsing remitting MS, primary progressive MS, and secondary progressive MS. The foundation of outpatient management involves disease-modifying therapy, which is typically initiated with the first signs of disease onset. Management of CIS and acute flares of MS in the ED includes corticosteroid therapy, ideally after diagnostic testing with imaging and lumbar puncture for cerebrospinal fluid analysis. Emergency clinicians should evaluate whether patients with MS are presenting with new-onset debilitating neurological symptoms to avoid unnecessary testing and admissions, but failure to appropriately diagnose CIS or MS flare is associated with increased morbidity. ConclusionsAn understanding of MS can assist emergency clinicians in better diagnosing and managing this neurologically devastating disease.

Clinical and radiographic features of a cohort of adult and pediatric subjects in the Pacific Northwest with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a newly described clinical entity comprised of isolated or recurrent attacks of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), encephalitis, or seronegative NMOSD. Prior studies report that 30–80 % of children and adults with MOGAD go on to have relapses though there are no reliable predictors. The objectives of this study were to (1) describe the demographic, clinical, and radiographic patterns of MOGAD at our center and (2) identify possible predictors of relapsing disease. MethodsSingle-center retrospective cohort study of pediatric and adult subjects with MOGAD evaluated at least once at our center between January 1, 2017 and September 30, 2022. Eligible subjects had a history of positive MOG-IgG and consistent clinical syndrome comprised of an initial attack of optic neuritis (ON), transverse myelitis (TM), ADEM, cerebral cortical encephalitis, seronegative neuromyelitis optica (simultaneous ON and TM), isolated brainstem or cerebellar syndrome, or other (not fitting into another group). Relapsing subjects or those remaining monophasic at 12 months were included in the analyses of predictors of relapsing disease. Covariates included age, sex, race/ethnicity, and index event phenotype. Unadjusted and adjusted risk ratios were calculated for pediatric and adult subjects. ResultsWe describe the demographic, clinical, and radiographic characteristics of 58 subjects with MOGAD. Covariates from 48 subjects were analyzed for predictors of relapsing disease. In adults, Hispanics and non-White non-Hispanics were at increased risk of relapsing disease compared to non-Hispanic Whites [Adjusted RR 1.52 (95 % CI: 1.01, 2.30)]. There were no significant associations in the pediatric group. ConclusionThis study is the first to describe a cohort of MOGAD in the Pacific Northwest. Our findings highlight racial and ethnic differences in risk of relapsing MOGAD in adults. Further studies on racial and ethnic differences in MOGAD are needed to confirm these findings.

Epidemiologic and clinical characteristics of neuromyelitis optica spectrum disorder patients, A seven years follow-up study from Iran.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare neuroinflammatory disease characterized by recurrent relapses. The most common signs are myelitis and optic neuritis. It can also present by cerebral or brain stem syndromes. There are still many challenges in its diagnosis and treatment, and long-term follow-up studies are needed to see the disease course over time. We established an electronic registration system of NMOSD patients starting from October 2015 in Kashani hospital, Isfahan, Iran. Every suspected patient was documented and included in the follow-up system to survey their disease course. Anti-aquaporine 4 (AQP4) antibody checked for all by cell-based assay method. All information such as demographic and clinical data and laboratory and MRI findings were documented. Participants were followed up for any relapses, new paraclinical tests and drug changes. This study is based on the definite NMOSD cases (according to the 2015 criteria) characteristics and clinical course during 7 years of registration. The study included 173 NMOSD cases and 56 ones were seropositive for AQP4 Ab. Their mean age was 40.02±11.11 years (45.78 in the seropositive group). The mean age at disease onset was about 30.16 years. The mean time of follow-up by our registration system is 55.84±18.94 months (54.82 months in seropositive ones). The annual relapse rate is estimated as 0.47±0.36. Long extended transvers myelitis (LETM) was present in the baseline MRI of 77 patients (44.5%), while 32 of them did not show any related clinical symptoms. 124 patients revealed an abnormality in the first brain MRI. 27 individuals suffer hypothyroidism as the most common comorbid disease. The disease seems to be more prevalent in the west and southwest areas of Isfahan province. The mean age of onset is higher than Multiple Sclerosis (MS) patients, but there are notable pediatric cases too. It should also be noticed that cervical LETM can be asymptomatic at first. Brain MRI abnormalities are frequently observed. The disease is more prevalent in the geographical areas where showing high MS prevalence.

Claude’s Syndrome: A Case Report of Rare Midbrain Syndrome from Bangladesh

Claude's syndrome is a rare brainstem syndrome with ipsilateral third nerve palsy and contralateral ataxia. Here we present a case of a 60-year-old male with Claude's syndrome due to cerebral infarct. The patient had left-sided pupil sparing third nerve palsy with right-sided ataxia. MRI of the brain revealed infarct in the left half of the tegmentum of the midbrain. MRA of the brain was unremarkable. The patient improved gradually and was almost asymptomatic after one month. Though the syndrome was first described a century ago, it warrants particular attention from clinicians due to its rarity and atypical features. JAFMC Bangladesh. Vol 18, No 2 (December) 2022: 72-74

Overlap syndrome of anti-aquaporin 4 positive neuromyelitis optica spectrum disorder and primary Sjögren's syndrome: a systematic review of individual patient data.

Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4years and NMOSD onset was 43.2 ± 19.8years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome.

Recontextualizing Neuromyelitis Optica as a Systemic Condition: A Perspective

Neuromyelitis optica spectrum disorder (NMOSD), a demyelinating CNS disorder in which inflammatory cells infiltrate the spinal cord and optic nerve, has been identified as an AQP4-IgG-positive disease. Some of its most common clinical characteristics are optic neuritis, acute myelitis, area postrema syndrome, and brainstem syndrome. However, the relationship between aquaporin-4 (AQP4) and NMOSD appears to be involved in pathologies outside of the CNS due to the fact that autoimmune, muscular, and paraneoplastic syndromes are more common in patients with NMOSD. This perspective presents an analysis of the current literature on neuromyelitis optica in an effort to further understand and compile pathologies that arise outside of the CNS secondary to NMOSD. Recontextualizing neuromyelitis optica as a systemic condition will facilitate greater diagnostic ability and improved treatment approaches.

Pediatric Neuromyelitis Optica Spectrum Disorder

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating disease with a high relapse rate and risk of disability accrual. The condition is an astrocytopathy, with antibodies to the aquaporin-4 (AQP4) water channel being detected in AQP4-IgG seropositive disease. Presentation is uncommon in the pediatric age range, accounting for about 3%-5% of cases. NMOSD is more prevalent in populations of Black or East Asian ancestry. Core clinical syndromes include optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, acute diencephalic syndrome, and symptomatic cerebral syndrome. First-line treatment options in pediatrics include rituximab, azathioprine, and mycophenolate mofetil. Over half of children with AQP4-IgG seropositive NMOSD develop permanent disability, particularly in visual and motor domains. Novel therapeutic targets in the adult population have been developed and are changing the treatment landscape for this disorder.

Riboflavin and Histidine Metabolisms Are Two Key Pathways Related to the Clinically Isolated Syndrome (CIS): A WGCNA-based In silico Analysis

Background: As an inflammatory disorder, Multiple Sclerosis (MS) causes demyelination, as well as axonal and neuronal injury in the central nervous system (CNS). Several clinical signs may be the indicators of MS among which, Clinically Isolated Syndrome (CIS) is the first symptom caused by the inflammation and demyelination of CNS. CIS is characterized by symptoms such as optic neuritis, brain stem or cerebellar syndrome, spinal cord syndrome, or sometimes cerebral hemispheric dysfunction. Objective: So far, metabolic pathways involved in the development of CIS are not fully understood. Therefore, in this study, weighted gene co-expression network analysis (WGCNA) has been used to identify differentially expressed genes in CIS disease and the main pathways associated with it. Methods: We grouped differentially expressed genes along with the functionally related genes into large modules to obtain their direct and indirect relationships. Results: The results have identified two new pathways associated with CIS, including riboflavin and histidine metabolism-involved pathways. Conclusion: Riboflavin and histidine metabolism-involved pathways may be considered potential therapeutic goals for CIS management in the future.

The epidemiology and burden of neuromyelitis optica spectrum disorder, multiple sclerosis, and MOG antibody-associated disease in a province in Thailand: A population-based study.

Central nervous system inflammatory demyelinating diseases (CNSIDDs) have notable interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a mainland Southeast Asian country, is unknown. To determine the cumulative incidence, point prevalence, and disease burden of neuromyelitis optica spectrum disorder (NMOSD) and other CNSIDDs in Thailand using population-based data of Chumphon. Searching for CNSIDD patients at a public secondary care hospital in Chumphon, the only neurology center in the province, from January 2016 to December 2021 was implemented using relevant ICD-10-CM codes. All diagnoses were individually ascertained by a retrospective chart review. Cumulative incidence, point prevalence, attack rate, mortality rate, and disability-adjusted life years (DALYs) were calculated. Aquaporin 4-IgG-positive NMOSD was the most prevalent CNSIDD in the Thai population at 3.08 (1.76-5.38) per 100,000 persons. The prevalence of multiple sclerosis (MS) followed at 0.77 (0.26-2.26) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at 0.51(0.14-1.87) per 100,000 adults. In the pediatric population, the incidence of acute disseminated encephalomyelitis was 0.28 (0.08-1.02) per 100,000 persons/year. Among other idiopathic demyelinating diseases, idiopathic optic neuritis had the highest incidence at 0.58 (0.24-0.92) per 100,000 persons/year, followed by acute transverse myelitis at 0.44 (0.14-0.74). Idiopathic demyelinating brainstem syndrome was also observed at 0.04 (0.01-0.25) per 100,000 persons/year. Although most had a fair recovery, disability was worst among NMOSD patients with DALYs of 3.61 (3.00-4.36) years per 100,000 persons. Mortality rate was the highest in NMOSD as well. CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian populations. A nationwide CNSIDDs registry would better elaborate the epidemiology of these diseases.

Systemic lupus erythematosus with acute ischemic optic neuropathy complicated with neuromyelitis optica: a case report

BackgroundNeuromyelitis optica is a relapsing–remitting disease characterized by a recurrent attack of optic neuritis and transverse myelitis; sometimes associated with acute brainstem syndrome. Systemic lupus erythematosus is an autoimmune multisystem disorder in which ocular involvement such as acute ischemic optic neuropathy is a rare manifestation. However, neuromyelitis optica can be associated with systemic lupus erythematosus.Case presentationA 24-year-old Bangladeshi woman was admitted to the hospital with complaints of sudden, progressive, painless vision loss in both eyes, and progressive weakness in both lower limbs for 48 hours. She also gave a history of arthralgia, a photosensitive skin rash, intermittent fever, oral ulcerations, and alopecia for the last 2 months. On examination, the fundus was suggestive of bilateral acute ischemic neuropathy, and examinations of the lower limb revealed spastic paraparesis with sensory abnormality. Laboratory investigations revealed the presence of positive anti-aquaporin 4 antibody, strongly positive antinuclear antibody, and anti-ds DNA with the longitudinally extensive lesion on magnetic resonance imaging of the spinal cord. She was treated with methylprednisolone, hydroxychloroquine, and mycophenolate, and was discharged with improvement of her paraparesis. However, her vision did not improve substantially.ConclusionThe importance of this report is to shed some light on the occurrence of two devastating complications that is, bilateral acute ischemic optic neuropathy in systemic lupus erythematosus complicated by neuromyelitis optica, as well as evidence of rare presentations for systemic lupus erythematosus and treatment modalities of ischemic optic neuropathy with systemic lupus erythematosus.

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.

Exposure to TNF Inhibitors is Rare at MOGAD Diagnosis

Objective To assess the potential association between TNF-inhibitors and MOGAD Background The association of tumor necrosis factor-a (TNF)-inhibitors with MS has previously been suggested, whereas little is known about MOG-IgG-associated disease (MOGAD) in the context of these drugs. We recently encountered two patients who developed MOGAD while receiving TNF-inhibitors, prompting a search for similar cases in the literature and clinical practice. Design/Methods The two cases were seen at Mayo Clinic, Rochester (bilateral optic neuritis) and the University-Hospital of Sassari (brainstem syndrome). Three additional cases of MOGAD presenting during treatment with TNF-inhibitors were identified through Pubmed. We searched the medical records of 336 MOGAD patients seen at the Mayo Clinic, to assess if they had been treated with TNF-inhibitors. Results A total of 5 patients were identified. The median age at MOGAD presentation was 40 years (range, 36-49); 4/5 were male (80%). The median time from TNF-inhibitor initiation to MOGAD presentation was 6.5 years (range, 2-18). Of 4 patients who discontinued the TNF-inhibitor due to MOGAD onset, two subsequently had a MOGAD relapse. While in another patient, neurological symptoms subsided with corticosteroids despite TNF-inhibitor being maintained. The frequency of MOGAD presenting during TNF-inhibitors treatment at Mayo Clinic was 0.3% (1/336 cases). Conclusions We found that MOGAD is unlikely to present during treatment with TNF-inhibitors. The outcomes in these patients seemed not to be influenced by TNF-inhibitor treatment duration or discontinuation. These findings suggest the benefit of TNF-inhibitor withdrawal is not obvious, and the choice of discontinuing vs maintaining treatment with TNF-inhibitors should be weighted based on symptoms severity and activity status of the underlying systemic disorder. When withdrawal is considered, immunosuppression with agents potentially effective for both MOGAD and the immune-mediated disease originally managed by the TNF-inhibitor, could serve as dual purpose treatment.