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Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: practical considerations
  1. Maciej Juryńczyk1,2,
  2. Anu Jacob3,
  3. Kazuo Fujihara4,
  4. Jacqueline Palace5
  1. 1 Department of Neurology, Royal Hampshire County Hospital, Winchester, UK
  2. 2 Department of Neurology, University Hospital Southampton, Southampton, UK
  3. 3 Department of Neurology, Walton Centre, Liverpool, UK
  4. 4 Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
  5. 5 Department of Clinical Neurology, John Radcliffe University Hospital, Oxford, UK
  1. Correspondence to Dr Jacqueline Palace, John Radcliffe University Hospital, Oxford OX3 9DU, UK; jacqueline.palace{at}


The field of central nervous system (CNS) inflammatory diseases has recently broadened to include a new condition associated with pathogenic serum antibodies against myelin oligodendrocyte glycoprotein (MOG). This is distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody neuromyelitis optica spectrum disorders (NMOSD). MOG antibody-associated disease phenotypes are varied and range from classical neuromyelitis optica to acute demyelinating encephalomyelitis and cortical encephalitis. The diagnosis depends on using a reliable, specific and sensitive assay of the antibody. Clinical and imaging features of MOG-associated syndromes overlap with AQP4 antibody NMOSD but can be usually distinguished from MS: in particular, the silent lesions typical of MS that progressively increase lesion volume are rare in MOG antibody disease. The disease can relapse but medium-term immunosuppression appears to be protective. Permanent disability, particularly severe ambulatory and visual disability, is less frequent than in AQP4 antibody NMOSD and usually results from the onset attack. However, sphincter and sexual dysfunction after a transverse myelitis is common. Here we review the practical aspects of diagnosing and managing a patient with MOG antibody-associated disease.


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Multiple sclerosis (MS) is a common and heterogeneous inflammatory central nervous system (CNS) disease. Antibodies to denatured myelin oligodendrocyte glycoprotein (MOG) have been variably reported in MS, and MOG-induced demyelination has been used as an animal model of MS.1–3 However, more recently, MOG antibody disease has been recognised as a distinct clinical disorder with a different treatment.

MOG and assays to detect antibodies

MOG is a glycoprotein expressed selectively on oligodendrocytes, which are glial cells of the CNS. Although MOG is a minor constituent of myelin, its expression at the surface of the myelin sheaths makes it accessible for antibodies and a candidate for CNS-targeted autoimmune responses. MOG antibodies can fix complement, indicating their pathogenic potential.4 5

An optimised assay is essential for diagnosis. Previous assays detecting antibodies to linear or denatured MOG, or IgM MOG antibodies, will identify non-pathogenic antibodies, although these may be biomarkers of tissue damage.6 An optimised cell-based assay using a full-length conformationally intact MOG construct (rather than the shortened extracellular portion7) and a secondary antibody binding to class 1 IgG gives high sensitivity and specificity (figure 1).8 Note that current and historic literature includes cohorts of patients who have been identified using non-specific MOG assays and with low cut-offs for assay positivity.

Figure 1

(A) The schematic outline of cell-based assay. Human embryonic kidney (HEK) cells expressing full-length human myelin oligodendrocyte glycoprotein are incubated with the patient’s serum and a secondary antihuman IgG1 antibody. (B,C) The assay is assessed visually under an immunofluorescent microscope. MOG, myelin oligodendrocyte glycoprotein.

Clinical presentation in MOG antibody disease

The clinical spectrum of MOG antibody disease encompasses a broadening range of phenotypes, including neuromyelitis optica spectrum disorder (NMOSD),5 9–11 acute demyelinating encephalomyelitis (ADEM)7 12 13 and more recently focal cortical disease.14 15 It presents in both children and adults16–18 and can be monophasic or relapsing.

Figure 2 shows the distribution of onset presentation from a recent large UK study.16 Isolated optic neuritis is the most common onset presentation (55%–64%), with simultaneous bilateral involvement in 34%–44%.16 18 19 Bilateral optic neuritis is rare in MS and less common (around 30% of optic neuritis attacks) in aquaporin-4 (AQP4) antibody NMOSD.10 The optic nerve involvement is typically anterior and presents with papillitis, in contrast to the posterior optic nerve and chiasm involvement in AQP4 antibody NMOSD, although in both conditions there is usually a long lesion in the optic nerve.20

Figure 2

Onset attack breakdown in MOG antibody patients from a large UK study including 252 patients.16 ADEM, acute demyelinating encephalomyelitis; LETM, longitudinally extensive transverse myelitis; MOG, myelin oligodendrocyte glycoprotein; ON, optic neuritis; TM, transverse myelitis.

Transverse myelitis typically presents as a longitudinally extensive transverse myelitis (LETM)—defined on MR scan as extending continuously over at least three vertebral segments involving at least three continuous segments—but short transverse myelitis does occur and may be more common in older people. The transverse myelitis in MOG antibody disease involves the conus more often than in the AQP4 antibody LETM, which may explain the disproportionate sphincter and erectile dysfunction.10 11

An ADEM-like presentation is more common in children; MOG antibodies are found in over half of these and in virtually all patients with multiphasic ADEM (a new clinical event meeting the criteria for ADEM, with new clinical and radiological CNS lesions).21 22

Cortical encephalitis (usually unilateral) is a more unusual but interesting presentation.14 15 It presents with epileptic seizures, sometimes with abnormal behaviour or focal symptoms. MR scan of the brain in the acute phase usually shows unilateral mildly oedematous cortical lesion(s) best seen on fluid-attenuated inversion recovery images (figure 3). The prognosis is typically good, with the seizures and MRI brain lesions resolving,14 although there are exceptions.15

Figure 3

Examples of MRI lesions in myelin oligodendrocyte glycoprotein antibody patients (as pointed by white arrows). (A) Brainstem and bilateral cerebellar peduncle lesions in a 37-year-old woman. (B) Left deep grey matter lesions in a 4-year-old boy with acute demyelinating encephalomyelitis. (C) Confluent left temporoparietal lesions involving the cortex and the white matter in a 13-year-old boy. (D) Longitudinally extensive transverse myelitis lesions involving the conus in a 9-year-old boy. From left to right: lesion on a sagittal T2-weighted image, ring-like gadolinium enhancement on a T1-weighted image and central cord involvement on an axial T2-weighted scan. Further examples of myelin oligodendrocyte glycoprotein-antibody associated lesions are found in ref 29 .

The onset phenotype in MOG antibody disease varies with age (ADEM is more common in younger patients) but with not ethnicity or sex.16

Disease course

MOG antibody disease can be either monophasic or relapsing. The bias towards a relapsing course in those with longer disease duration may have arisen because the diagnostic tests have only become available recently, so such patients are only diagnosed now if referred with relapses. Large studies that include patients followed from disease onset, regardless of the treatment regimen, suggest that up to half of patients relapse within the first 2–3 years. Most relapses occur in the early months after the onset attack.16 18 The risk of relapse is lower in patients treated with prednisolone for at least 3–6 months, compared with patients treated for shorter periods of time. However, some patients may relapse many years after the onset attack and we have seen intervals of up to 40 years. The disappearance of MOG antibodies (this occurs in 18%–25% of patients within 1 year) is typically associated with cessation of relapses.16 18 23

Interestingly, optic neuritis is the most common type of relapse (70%–80%) as well as the most common onset attack.16 17 24 Occasionally relapses do lead to permanent disability in people who have recovered fully from their onset attacks. Thus, a mild onset attack can be followed by disabling attacks.

Optic neuritis

Isolated optic neuritis is characterised by poor visual acuity at nadir of attack and appears more commonly associated with papillitis (optic nerve head inflammation) than retrobulbar optic neuritis.25 MR scan of the orbits might show an extensive optic nerve T2 hyperintense lesion with swelling and involvement of the intraorbital segment which, in contrast to AQP4 antibody NMOSD, is often anterior and spares the optic chiasm.20 26 Typically, there is contrast enhancement of the optic nerve lesion and the perioptic tissue.20 26 Despite poor vision in the acute phase, most cases of optic neuritis in MOG antibody disease tend to resolve well, with only 10%–20% of patients left with permanent visual deficits (visual acuity 6/36 or worse in one eye). Severe bilateral residual deficits are exceptional (around 1% of patients).16

Transverse myelitis

LETM in MOG antibody disease often affects the lower thoracic cord and conus rather than the cervical region.10 11 Residual bladder, bowel and sexual dysfunction are common, but only a minority of patients have a permanent disability (around 5% cannot walk 100 m unaided).16 A patient with disproportionate sphincter and erectile disability with good motor recovery following transverse myelitis should have MOG antibodies assayed.

A LETM lesion in MOG antibody disease seen on MR scan of the spinal cord tends to be central and associated with swelling in the acute phase (in contrast to MS and similar to AQP4 antibody NMOSD).19 Timing of the scan in relation to the attack may be important as LETM in AQP4 antibody NMOSD can fragment into multiple short lesions resembling MS.27

Patients with LETM most often relapse with optic neuritis (70% of subsequent relapses),16 and if that happens or if they have simultaneous LETM and optic neuritis (around 10% at onset) they satisfy the most recent NMOSD criteria.

ADEM and other brain/brainstem manifestations

ADEM is a typical onset presentation of MOG antibody disease in children (around 40% in the UK study), particularly in young children (70% in <8 years old), but might also occur in adults (9%).16 Around 60% of children with ADEM have MOG antibodies.21 Importantly, persistence of MOG antibodies in children with ADEM appears to predict further relapses, particularly of optic neuritis or ADEM, which leads to phenotypes such as multiphasic disseminated encephalomyelitis or ADEM with optic neuritis.28 MOG antibody ADEM does not differ significantly from MOG antibody-negative ADEM in terms of clinical presentation or demographics, although there may be a higher cerebrospinal fluid (CSF) cell count and more widespread change on the MR brain scan.21 Patients with MOG antibody ADEM typically have large, poorly demarcated, bilateral white matter lesions and do not have MS-like ovoid periventricular lesions.21 29 In some children aged less than 7 years, the lesions are confluent and largely symmetrical, and might resemble leukodystrophy.30 In the Oxford cohort, 40% of patients with MOG antibody ADEM had some residual cognitive problems, including poor concentration or learning difficulties, but this was not assessed systematically.16

Recent studies have reported a form of MOG antibody-associated encephalitis that differs from ADEM in having more selective cortical involvement on imaging and presenting with seizures.14 15

MOG antibody disease can also present with isolated brainstem attacks, which are associated with fluffy brainstem lesions on MRI, typically located in the pons, medulla or cerebellar peduncles, and often adjacent to the fourth ventricle.29 Brainstem involvement might also be part of a severe presentation involving LETM and optic neuritis.31 The brain lesions in MOG antibody disease are difficult to distinguish from AQP4 antibody NMOSD but are distinct from MS.29 Although dorsal medullary and area postrema attacks (with associated lesions) have been considered pathognomonic for AQP4 antibody NMOSD, these can occur in MOG antibody patients16 32 and may be the onset presentation; however, a ‘full house’ area postrema attack (with intractable nausea, vomiting and hiccups) is still more common in AQP4 antibody disease. Other brainstem presentations include ophthalmoparesis, dysarthria, dysphagia and ataxia.32

CSF findings

The CSF findings during an acute MOG antibody attack are variable.16–18 Around half of the patients have elevated white cell counts, and in 5%–10% the lymphocyte count is as high as 100–300 cells/µL.16 Similarly around half have an elevated CSF protein concentration, which can be above 1 g/L in 10%.16 Interestingly, around 10% of patients have an elevated protein with a normal white cell count.16 Oligoclonal bands restricted to the CSF occur in up to 15% of patients.16 18


Dual positivity for both AQP4 and MOG antibodies is extremely rare when using specific assays. Some patients with MOG antibodies fulfil the ‘AQP4-antibody negative NMOSD’ criteria (figure 4).33 Such patients are required to have at least two symptomatic and anatomically located attack sites (although these can be within single or sequential attacks), with at least one being an optic neuritis, an LETM or an area postrema syndrome, and each having typical MRI appearances. Patients presenting with an NMOSD phenotype should ideally be tested for both of the antibodies because of the clinical overlap; the order may depend on the patient’s age of onset; for example, AQP4 antibodies are more common in adults while MOG antibodies are more common in children.

Figure 4

A schematic diagram showing how different MOG Ab phenotypes fit into the current neuromyelitis optica spectrum disorders criteria.33 Ab, antibody; ADEM, acute demyelinating encephalomyelitis; AQP4, aquaporin-4; LETM, longitudinally extensive transverse myelitis; MOG, myelin oligodendrocyte glycoprotein; NMOSD, neuromyelitis optica spectrum disorder; ON, optic neuritis; TM, transverse myelitis.

Previous reports of MOG antibodies being found in people with MS partly relate to the non-specific assays used (ELISA and western blot); perhaps also the diagnosis of ‘atypical’ MS was incorrect. Childhood MS was previously said to differ from adult MS,34 probably because many had MOG antibody disease.35 Additionally relapsing ADEM was often diagnosed as MS.36 Table 1 outlines the features that distinguish MOG antibody and AQP4 antibody diseases from MS (AQP4 antibody-associated imaging characteristics from37

Table 1

Demographic, clinical, laboratory and radiological differential features between CNS inflammatory diseases (AQP4 antibody NMOSD characteristics from ref 37)

Occasionally patients have low serum concentrations of MOG antibody (and AQP4 antibody) and are reported as ‘low positive’. These do not carry the specificity associated with unambiguously positive result. Therefore, when found, it is important to factor the clinical and imaging distinguishing features into the diagnostic process and to consider repeat testing.

We recommend limiting MOG antibody testing to patients whose clinical features are consistent with MOG antibody disease and not to screen all patients with MS or optic neuritis, for example. Indiscriminate testing will likely elevate the false-positive rate. Syndromes suggesting MOG antibody disease (and which should prompt testing) include ADEM, multiphasic disseminated encephalomyelitis, simultaneous optic neuritis and transverse myelitis, simultaneous bilateral optic neuritis, optic neuritis with papillitis, recurrent optic neuritis, and LETM and brainstem/cerebral cortical encephalitis (figure 5). MS-typical brain lesions on MRI are very unusual in MOG antibody or AQP4 antibody disease, including Dawson’s fingers, inferior temporal lobe lesions and S-shaped/curved juxtacortical lesions.38 In a patient who has already recovered from their attack, features that warrant testing include longitudinally extensive atrophy on spinal cord imaging (suggesting previous LETM), permanent sphincter/erectile dysfunction or poor vision following optic neuritis.29

Figure 5

An algorithm with proposed recommendations on the diagnosis and management of myelin oligodendrocyte glycoprotein antibody patients. *There is limited evidence for the prednisolone regimen; we reduce the dose from 0.5 to 0.75 mg/kg/day (typically 40–60 mg in adults) to 10–15 mg/day by month 6. Ab, antibody; ADEM, acute demyelinating encephalomyelitis; IST, immunosuppressants; LETM, longitudinally extensive transverse myelitis; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; ON, optic neuritis; TM, transverse myelitis.

Other useful differentiating features include the lack of a progressive phenotype in MOG antibody disease (and AQP4 antibody disease), with the disability being relapse-related (as opposed to MS). Conventional MRI supports this, at follow-up typically showing resolution of previous brain lesions and absence of new lesions outside of relapse.29 Table 1 shows features that help to distinguish between MOG antibody disease, AQP4 antibody NMOSD and MS.


The treatment of MOG antibody disease is largely adopted from AQP4 antibody NMOSD39 and much remains unclear. Acute relapses are usually treated immediately and the typical regimen comprises a course of 3–7 days of high-dose (0.5–1 g) intravenous/oral methylprednisolone followed by oral prednisolone. Patients with severe attacks or who respond poorly to corticosteroids should be treated early with plasma exchange (or intravenous immunoglobulin) with the aim of improving recovery.40

The optimal duration of initial immunosuppression after the first attack is still unclear. The relapse risk is highest in the early months after disease onset,16 and follow-on prednisolone cover seems to reduce the relapse risk. We recommend tailing to a low dose of oral prednisolone (such as 10 mg daily) for 6 months after the initial attack. Disappearance of MOG antibody seems to indicate remission. So we retest at 6 months and, if negative, we wean the patient off the corticosteroids.

Several factors may influence the decision to continue immunosuppression beyond 6 months in patients after a single initial attack. Relapses seem to occur only in those with persistent MOG antibody, while not all patients with persistent antibodies relapse. However, it is reasonable to consider treating patients with persistent antibodies for up to 12 months (figure 5) if tolerated. While it is common and convenient to continue oral corticosteroids, if disabling side effects prevent its use beyond 6 months, an alternative is to switch to a steroid-sparing immunosuppressant agent (taking into consideration the lag time to be effective).

The decision to treat patients who are clinically relapsing is easier. In such cases, it is reasonable to add a corticosteroid-sparing agent such as azathioprine, methotrexate or mycophenolate mofetil (and then gradually to reduce or withdraw the corticosteroids) with the usual precautions and monitoring. Not all patients with persistent MOG antibodies relapse, and there is no evidence that a severe onset attack predicts either further relapse or greater severity of future relapses. However, severe residual disability from the onset attack and persistent MOG antibodies may lead some patients and physicians to select longer term immunosuppression from onset, although this may not give the best risk-to-benefit balance. There are varied reports of the relative efficacy of maintenance intravenous immunoglobulin and rituximab,41 42 and thus the optimal relapse prevention regimen in MOG antibody disease is unclear. The ideal duration of long-term immunosuppression is also uncertain. If future studies bear out the observations that conversion to seronegativity supports remission, serial annual testing may help with the timing of withdrawal. Additionally although there are only limited data, we would not recommend using MS disease-modifying therapies, which may worsen AQP4 antibody disease.19 41

MOG antibody disease is recognised as a new antibody-mediated inflammatory demyelinating disease of the CNS. It can present at any age, in both males and females, and evenly across all ethnicities. Its clinical presentation varies and might involve ADEM (more common in children), optic neuritis, transverse myelitis, NMOSD and brainstem syndromes in older children and adults. The disease course can be monophasic or relapsing, with most relapses occurring early on. Attacks generally recover, but some patients are left with residual disability: mostly sphincter, erectile or visual. Medium-term immunosuppression may reduce the risk of further relapses.

There are many unanswered questions, including the pathological hallmark, long-term and optimal treatment regimens. Assays still have limited availability and variable specificity; thus, we do not advise indiscriminate testing. As most disability comes from the onset attack before the diagnosis is made, intense treatment of disabling CNS inflammatory attacks in general could improve the prognosis. Predictive factors for future relapses years downstream (and in particular for disabling relapses) have not been identified, and therefore clinicians need to weigh up the risks of long-term immunosuppression versus limiting treatment to aggressive relapse intervention if and when they occur.

Key Points

  • Myelin oligodendrocyte glycoprotein antibody disease is distinct from multiple sclerosis.

  • Its clinical and imaging features overlap with aquaporin-4 (AQP4) antibody neuromyelitis optica spectrum disorder (NMOSD).

  • In addition to NMOSD, it can present as acute demyelinating encephalomyelitis or as focal cortical disease.

  • It can be monophasic or relapsing but there is no progressive phase.

  • It is less disabling than AQP4 antibody NMOSD, but the most common residual features are visual and sphincter dysfunction.

  • Early medium-term corticosteroid treatment might reduce the risk of early relapses.

  • Long-term immunosuppression should be considered if there are severe or frequent relapses.


We thank Dr Mark Woodhall, Dr Giordani Passos and Dr Patrick Waters for the preparation of the CBA assay figure, and Dr Romina Mariano and Dr Silvia Messina for providing up-to-date information from the Oxford MOG antibody database (all from Nuffield Department of Clinical Neurosciences, University of Oxford).



  • Contributors All contributors meet the criteria for authorship.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned. Externally peer reviewed by Neil Robertson, Cardiff, UK.

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