MOGAD: An overview

Although MS is the most common inflammatory CNS disease, there are also other independent clinical pictures, such as MOG-associated diseases.

Myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) vs. MS

Multiple sclerosis was first described by the famous French neurologist Jean Martin Charcot in 1868 and is the most common inflammatory CNS disease. Over the past ten years or so, researchers have gradually discovered the key features behind "atypical" cases of MS.  Some of these autoimmune diseases, which also destroy the myelin layer, have been given different names in order to better distinguish them from MS. These include myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD).

The pathophysiology of MOGAD

Myelin oligodendrocyte glycoprotein (MOG) is a component of the myelin sheath that surrounds nerve fibres in the CNS. It is assumed that MOG plays a role as an adhesion molecule and thus provides structural integrity to the myelin sheath. It is formed late on the oligodendrocyte. In MOG-associated diseases, antibodies against MOG are secreted, which leads to inflammation and demyelination of the fibres.

Until a few years ago, antibodies against MOG were mainly found in children with demyelinating CNS diseases. However, they also occur in adults with optic neuritis (ON), NMOSD, myelitis, MS, acute disseminated encephalomyelitis (ADEM) and atypical demyelinating syndromes.1 Patients with antibodies against MOG appear to differ in clinical presentation, course and outcome from seronegative patients with the same disease.

The median age at first manifestation of a MOG-AB disease is between 30 and 35 years of age, with the first localisation in most cases being optic neuritis, which occurs more frequently on both sides.

Clinical features and diagnosis

MOGAD presents clinically in a variety of ways, which makes diagnosis difficult. Common symptoms include visual disturbances, motor weakness, loss of sensation and, in ADEM, encephalopathic symptoms. The diagnosis is based on the clinical presentation, MRI findings, the detection of MOG antibodies in serum, and the exclusion of other diseases.

MRI imaging is usually performed as part of the diagnostic work-up. Almost half of positive MOG-AB cases show cerebral or spinal lesions or abnormalities of the optic nerve.2 A cerebrospinal fluid (CSF) examination reveals CSF pleocytosis in some cases, while oligoclonal bands (OCB) occur less frequently than in MS.

Therapeutic approaches

The treatment of acute MOGAD episodes usually involves high doses of corticosteroids. If there is an inadequate response, plasmapheresis or intravenous immunoglobulins (IVIG) can be used.

There is a lack of sufficient studies on the effects of long-term immunomodulatory or immunosuppressive therapy; initial results show efficacy of azathioprine, mycophenolate mofetil and rituximab.3 The decision in favour of long-term therapy should be made on an individual basis, based on clinical activity and risk profile.

Prognosis and quality of life

The prognosis of MOGAD can vary. Some patients experience a full recovery after an episode, while others experience recurrent attacks and progressive disability. Maintaining quality of life requires individually tailored therapy and supportive measures, including physiotherapy, occupational therapy and psychological support.

Conclusions for medical practice: consider MOGAD in the differential diagnosis of MS 

MOGAD represents a separate category of demyelinating diseases of the CNS that differ from other demyelinating diseases in terms of clinical presentation, imaging, immunopathology and therapeutic response. In patients with optic neuritis and spinal symptoms, MOGAD should definitely be considered alongside MS and the monoclonal antibodies should be determined. Early diagnosis and customised therapeutic management are crucial to improve the outcome of patients.

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  1. Sepúlveda M, Armangue T, Martinez-Hernandez E, Arrambide G, Sola-Valls N, Sabater L, Téllez N, Midaglia L, Ariño H, Peschl P, Reindl M, Rovira A, Montalban X, Blanco Y, Dalmau J, Graus F, Saiz A. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J Neurol. 2016 Jul;263(7):1349-60. doi: 10.1007/s00415-016-8147-7. Epub 2016 May 4. PMID: 27147513; PMCID: PMC5831396.
  2. Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, Ciron J, Collongues N, Brassat D, Cotton F, Papeix C, Durand-Dubief F, Laplaud D, Deschamps R, Cohen M, Biotti D, Ayrignac X, Tilikete C, Thouvenot E, Brochet B, Dulau C, Moreau T, Tourbah A, Lebranchu P, Michel L, Lebrun-Frenay C, Montcuquet A, Mathey G, Debouverie M, Pelletier J, Labauge P, Derache N, Coustans M, Rollot F, De Seze J, Vukusic S, Marignier R; OFSEP and NOMADMUS Study Group. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology. 2018 May 22;90(21):e1858-e1869. doi: 10.1212/WNL.0000000000005560. Epub 2018 Apr 25. PMID: 29695592.
  3. Cobo-Calvo A, Sepúlveda M, Rollot F, Armangué T, Ruiz A, Maillart E, Papeix C, Audoin B, Zephir H, Biotti D, Ciron J, Durand-Dubief F, Collongues N, Ayrignac X, Labauge P, Thouvenot E, Bourre B, Montcuquet A, Cohen M, Deschamps R, Solà-Valls N, Llufriu S, De Seze J, Blanco Y, Vukusic S, Saiz A, Marignier R. Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease. J Neuroinflammation. 2019 Jul 2;16(1):134. doi: 10.1186/s12974-019-1525-1. PMID: 31266527; PMCID: PMC6607517.