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MOG antibody associated disorder (MOGAD)

Posted in Clinical Review Article on 21st Jun 2021

Kate LilleyKate Lilley, BCom/BA, MBBS, is an Advanced Trainee in Neurology at Gold Coast University Hospital. She completed her medical degree at the University of Queensland in 2012 and finished Basic Physician Training in Brisbane, 2018. She completed a Movement Disorders Fellowship at the Princess Alexandra Hospital prior to commencing Advanced Training.


Sudarshini Ramanathan, BSc (Med) MBBS (Hons) FRACP PhD, is a Clinician Scientist and Adult Neurologist with subspecialty expertise in neuroimmunology. She undertook an NHMRC Early Career Postdoctoral Fellowship at the John Radcliffe Hospital and University of Oxford in Oxford, UK. Her clinical and research focus is antibody-mediated demyelination and autoimmune encephalitis. She is a Senior Lecturer with the University of Sydney and Staff Specialist Neurologist at Concord Hospital in Sydney.

Russell DaleRussell C Dale. MBChB MRCP PhD, is Professor of Paediatric Neurology at Children’s Hospital at Westmead and University of Sydney. He has a clinical and fundamental science programme of research investigating the role of the immune system in brain disease in children. He has an NHMRC Investigator Grant and has published over 250 peer reviewed articles.


Fabienne BrilotFabienne Brilot, PhD, is a Neuroimmunologist Principal Research Fellow at the University of Sydney and the Children’s Hospital at Westmead. Her translational research programme focuses on immune-mediated brain disorders such demyelinating disorders and movement and psychiatric disorders. Her lab aims to discover biomarkers and explores the autoimmune response in patients to improve their diagnosis and treatment. She is principal investigator on several national grants and has published over 90 peer-reviewed articles.

Simon BroadleySimon BroadleyBSc, MBChB, PhD, FRACP, is Professor of Neurology at Griffith University and at Gold Coast University Hospital where he runs the CNS Inflammatory Diseases Clinic. He has over 20 years experience as a Clinician Scientist researching and managing people with multiple sclerosis and related disorders. He has over 140 published articles and has been a principal investigator on grants and clinical trials totalling A$9 million.

Correspondence to: Dr Kate Lilley, Department of Neurology, Gold Coast University Hospital, 1 Hospital Blvd, Southport, QLD 4125, Australia. Tel. +61 7 4433 1111 E.
Conflict of interest statement: None declared
Provenance and peer review: Submitted and externally reviewed
Date first submitted: 10/10/2020
Date resubmitted after peer review: 13/04/2021
Acceptance date: 14/04/2021
Published online: 21/06/2021
To cite: Lilley K, Ramanathan S, Dale RC, Brilot F, Broadley S. Adv Clin Neurosci Rehabil 2021;

Published under a Creative Commons license

Key take-home messages

  • MOGAD is a demyelinating pathology affecting adults and children, distinct from MS and NMOSD.
  • Clinical features are diverse and may mimic MS, AQP4 positive NMOSD or other autoimmune encephalitides.
  • Prompt diagnosis relies on clinical suspicion, MRI findings and access to a live cell-based assay.
  • Early immunosuppressive treatment and maintenance therapy reduces morbidity and prevents relapse and accumulated disability over time.


The existence of antibodies to myelin oligodendrocyte glycoprotein (MOG) in some patients with CNS demyelinating disease has been recognised for 30 years, but their clinical utility as biomarkers, and potential pathogenicity in humans has only become apparent in the past 15 years. The advent of more precise live cell-based assays for antibody detection in serum and cerebrospinal fluid (CSF) has greatly refined the clinical phenrotype of demyelinating diseases associated with MOG antibodies. Distinct patterns of MOG antibody associated disorder (MOGAD) include acute disseminated encephalomyelitis (ADEM) in children; and overlap with neuromyelitis optica spectrum disorders (including classical Devic’s presentations), optic neuritis, transverse myelitis, and focal encephalitis in both children and adults. A number of other rare presentations have also been described. Here we summarise what is currently known of the pathophysiology, clinical presentation and management of MOGAD.


Myelin Oligodendrocyte Glycoprotein (MOG) antibody associated disorder (MOGAD) is a unique demyelinating pathology affecting adult and paediatric populations. Its clinical presentation, investigation, management and prognostic considerations distinguish it from multiple sclerosis (MS) and AQP4 antibody associated neuromyelitis optica spectrum disorder (AQP4-NMOSD).1 Recognition of this distinction promotes targeted therapy and prospective research.


MOG is expressed on the outer sheath of myelin by mammalian CNS oligodendrocytes, prominently exposed to the extracellular space. While its biological role is poorly understood, its association with CNS disease is increasingly apparent.2 MOG antibody is encephalitogenic in vitro. It is likely to be peripherally produced, frequently of the IgG1 isotype, and demonstrates reactivity to an extracellular antigenic region around Proline42 in a large subset of patients.3 How it bypasses the blood-brain barrier remains unknown. MOGAD-like pathology has been induced by encephalitic viruses in transgenic mice expressing MOG antibody.2 Pathologically in the brain MOGAD, like MS, shows white matter demyelination characterised by perivenous inflammatory aggregates. In MS, lesions are predominantly leukocortical, have a CD8 T-cell infiltrate with chronic radial expansion, whilst in MOGAD plaques are intracortical, associated with a CD4 T-cell inflammatory infiltrate and show preserved AQP4 expression.4


The prevalence of MOGAD is not well established. A recent comparative survey has shown MOGAD is at least twice as common as AQP4-NMOSD.5 Existing cohort studies are small and frequently combine paediatric and adult samples. Age of onset ranges from 0–90 years. Unlike AQP4-NMOSD and MS, a female preponderance is not evident. There is insufficient data to establish ethnicity or latitude as risk factors. There are limited reports of association with other autoimmune diseases but fewer than seen with AQP4-NMOSD.2,6

Clinical Presentation

The MOGAD clinical phenotype is diverse and varies with age.2,7 A prodromal infection is reported in up to 47% in some studies.6

Optic neuritis (ON) is the most frequent presentation in adults and children over 9 years. The rate of simultaneous or sequential, bilateral ON is higher than seen in MS or AQP4-NMOSD.7 Papillitis is frequently identified in MOGAD, consistent with the anterior visual pathway involvement often seen in this condition.6,8 Symptom resolution is anticipated but up to 20% of patients may have permanent visual impairment. Relapse of ON is common.

Transverse myelitis (TM) may occur in isolation or with ON to mimic Devic’s disease. It is the second most frequent presentation in adults and older children.2 TM in MOGAD may mimic that seen in AQP4-NMOSD and MS. Both longitudinally extensive and short segment TM are observed. Early bowel, bladder and sexual dysfunction, reflecting central cord and conus involvement, increases suspicion for MOGAD.8,9 Residual paraparesis is less common than in AQP4-NMOSD.7

Acute disseminated encephalomyelitis (ADEM) is the most common initial presentation in children under 9 years.2 Indeed, MOG antibody accounts for the majority of ADEM and non-ADEM autoimmune encephalitis (AE) presentations in children8,10 and is associated with a higher risk of relapse than MOG antibody negative disease.2

Paediatric MOGAD encephalitis can result in poor long term outcome (mRS>2) with progression to leukodystrophy or cortical atrophy.10 ADEM in adults is rare but MOG antibody is increasingly identified in clinically diverse cases of focal and rhombo- encephalitis, with and without leptomeningeal enhancement.7,8 Seizures and refractory status epilepticus have been reported in both adults and children with cortical encephalitis or as an isolated phenomenon.10 Brain stem syndromes are recognised, but infrequent. The area postrema is less frequently affected than in AQP4-NMOSD.8 Patients with AE (including NMDAR and LGI1 AE) have been identified as having anti-MOG antibodies with and without current or prior clinical or MRI evidence of demyelination.11

Relapse rates in children and adults with MOGAD approach 30 and 40-84% respectively at 5 years, with the majority of second attacks occurring in the first 12 months.10,12,13 Delayed diagnosis and heterogeneous treatment may have inflated these figures. Prospective trials examining relapse following targeted immunosuppression from diagnosis in MOGAD will increase accuracy of rates. Risk of relapse is unrelated to clinical phenotype, may differ from initial presentation in both phenotype and severity, is associated with cumulative disability, and can be associated with rapid weaning and cessation of steroid treatment.2,6,12


Given important differences in management between these three demyelinating aetiologies, prompt diagnosis is paramount. All patients with monophasic or relapsing ON, TM or ADEM, without typical MS brain lesions, should be tested for both MOG and AQP4 antibodies before diagnosis and treatment of MS is considered. Screening patients with typical radiological features of MS for MOG antibodies is not recommended.15 Testing for MOG antibody should be reserved for circumstances of high pre-test probability.1,8 According to international expert consensus these include the above clinical syndromes with radiological evidence of demyelination and at least one associated feature described in Table 1.1

Table 1. Proposed diagnostic criteria for MOGAD

With reference to international consensus diagnostic guidelines1 and comprehensive review of imaging characteristics9

Live cell-based assays against full length human MOG antigen performed on serum is the gold standard for MOG antibody detection. Though titres fluctuate with disease activity and treatment, their role in monitoring or prognosis has not been established1,3,7 A negative titre at 6 or 12 months may represent remission.8 However, clinical relapses have been reported after a transient seronegative period.7,13 Fixed assays, though more readily available, are less sensitive3 and have a 10-15% false negative rate.14 ELISA detection of MOG-IgG is unreliable.14 MOG antibody titre in CSF is lower than serum due to predominant extrathecal production.1 CSF may show isolated, elevated protein, neutrophilic pleocytosis, non-specific leucocytosis and unmatched oligoclonal bands in up to 30% of patients.

Attempts to define MRI changes distinct to MOGAD continue. Salient examples are provided in Figure 1. Bilateral longitudinally extensive involvement of the optic nerves is more commonly seen in MOGAD and AQP4-NMOSD compared to MS. Involvement of the intra-orbital and anterior segment of the optic nerve with relative sparing of the chiasm and retrochiasmatic tracts distinguishes MOGAD from AQP4-NMOSD (which more often affects the posterior segment of the optic nerve, chiasm, and optic tracts) and MS (limited segment).9 Optic perineuritis with perineural and orbital fat contrast enhancement is present in ~30% of cases.9 At follow-up, enhancement resolves, T2 high signal may persist and atrophy may be evident.9

MOG antibodies Figure 1

Figure 1: Typical MRI appearances seen in MOG antibody related demyelination: (A) unilateral optic neuritis (arrow) on T2 coronal image showing hyperintense T2 signal change and swelling of the left optic nerve; (B) gadolinium enhancement on T1 coronal image (arrow) in the same case; (C) bilateral optic neuritis (arrows) on T2 coronal image showing hyperintense T2 signal change and swelling of the optic nerves; (D) unilateral optic neuritis showing gadolinium enhancement of a short section of the left optic nerve (arrow); (E) representative axial FLAIR image of the brain showing no lesions; (F) ADEM on axial FLAIR image of the brain showing large, ovoid, hyperintense periventricular lesions (arrows); (G) ADEM on coronal FLAIR image of the brain showing cortical hyperintensity (arrow); (H) periventricular, subcortical and juxtacortical T2 hyperintense lesions on FLAIR sequence may also be seen, together in this case with a symptomatic cortical/subcortical lesion (arrow) typical of focal encephalitis; (I) longitudinally extensive spinal cord lesion on T2 STIR sagittal image of the thoraco-lumbar spinal cord extending into the conus (arrows); (J-L) short segment, hyperintense T2 lesions of the mid-thoracic spinal cord (arrows) seen on sagittal (J) and axial images (K & L).

In TM, heterogeneous T2 high signal tends to involve both grey and white matter, >50% medullary cord and is associated with swelling or “pseudo-dilatation” of the ependymal canal.9 Signal is often brightest at the central part of the lesion. Enhancement can be variegated. Lesions therefore appear “cloud-like” on both T2 and contrast enhanced T1 sequences. Case reports document nodular or meningeal enhancement.9 At follow-up, enhancement resolves, T2 high signal may persist and atrophy may be evident but is less pronounced than in AQP4-NMOSD.

Brain lesions are only present in about a third of all cases and may be asymptomatic. Lesions may show ADEM-like confluence and a “fluffy” appearance even in adults (often without the encephalopathy seen in children presenting with ADEM) or have a more focal cortical appearance. Cloud-like infratentorial or brainstem lesions are rare but distinctive.9 The presence of Dawson’s fingers, lesions in the subcortical U fibres, adjacent to the lateral ventricles, or in the inferior temporal lobes are helpful in distinguishing MS from MOGAD.15


Early recognition and treatment with high dose corticosteroids are essential to minimise morbidity. Patients frequently respond rapidly to steroid therapy. Plasma exchange has also been reported as an effective acute therapy.2 Relapses tend to be observed when prednisolone dose falls below 10mg/day, when tapering takes place over less than 2 months, or within the first few months following cessation.2,6 Prolonged corticosteroid therapy with a slow taper (over 6-9 months) is increasingly accepted as first line treatment following first presentation.2,6,8 A prospective analysis of treatment in patients with MOGAD showed one third relapsed despite B cell depletion.16 Retrospective studies of rituximab, azathioprine, mycophenolate, IVIg and corticosteroids demonstrate reductions in relapse rate, better EDSS at follow-up, and that maintenance immunosuppression should be instituted in patients with a relapsing disease course.2,6,10,12 Treatment with cyclophosphamide, methotrexate and mitoxantrone was too infrequent to extrapolate therapeutic efficacy.12 In the absence of treatment protocols, switching maintenance therapy in the event of relapse may be beneficial6. MS specific therapies have been largely shown to be less efficacious in MOGAD.

There are no established means to identify the small proportion of adult patients with monophasic MOGAD. The risk versus benefit of ceasing therapy needs to be discussed on a case by case basis. Given relapse seems to be more common in adult ON,3,6 the authors are reluctant to discontinue maintenance therapy in patients who have sustained permanent visual impairment. Patients with preserved visual acuity may have retinal nerve fibre layer atrophy, and OCT may be a useful adjunctive clinical investigation to help guide therapeutic decisions.


The long-term implications of MOGAD remain poorly understood. Follow-up studies have been short (3-5 years) and heterogenous. Morbidity correlates with the severity of attacks. The impact on visual acuity, mobility and cognition over the longer term may be less severe than AQP4-NMOSD or MS groups when effective treatment is initiated promptly. However, residual disability remains significant for many.2,6,12 Paediatric MOGAD has less relapse and better long term recovery than adult disease, so combined cohort studies may underestimate the likelihood of relapse and morbidity in adults.7,10


MOGAD is a distinct demyelinating pathology affecting adults and children. Clinical features are diverse and may mimic MS, AQP4-NMOSD or other autoimmune encephalitides. Prompt diagnosis relies on clinical suspicion, MRI findings and access to live cell-based assays. This is essential as early immunosuppressive treatment reduces morbidity, and maintenance immunosuppression in the event of a relapsing course prevents accumulated disability over time. Prospective research should continue to define the clinical spectrum and work toward evidence-based diagnostic and management guidelines. Separate consideration of paediatric and adult cohorts is essential.


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