MOGAD — Myelin Oligodendrocyte Glycoprotein Antibody Disease: A Distinct Disease, Not MS and Not NMOSD

MOGAD is an inflammatory demyelinating disorder caused by antibodies against myelin oligodendrocyte glycoprotein (MOG), a protein on the outer surface of the myelin sheath. It was established as a distinct disease entity in 2018, once a validated cell-based assay for MOG-IgG became available. It differs from MS in its antibody (MS has no defining antibody), its MRI pattern (fluffier, more cortical lesions; longer optic nerve lesions with perineural enhancement), its CSF (oligoclonal bands are usually absent in MOGAD but present in about 90% of MS patients), and — most importantly for treatment — in which therapies work. MS disease-modifying therapies such as natalizumab, fingolimod, and ocrelizumab are not established treatments for MOGAD.

Both are antibody-mediated demyelinating diseases that attack the optic nerves and spinal cord, but they are distinct. MOGAD is MOG-IgG positive and AQP4-IgG negative; NMOSD is AQP4-IgG positive. MOGAD pathology is complement-independent and T-cell mediated, while NMOSD is complement-dependent. MOGAD produces shorter spinal cord lesions and more cortical brain involvement; NMOSD produces longitudinally extensive transverse myelitis and area postrema attacks. MOGAD generally has a better prognosis per attack and responds better to steroids. And unlike NMOSD, where essentially all patients need long-term preventive immunotherapy, in MOGAD that decision depends on whether the course is monophasic or relapsing.

MOGAD is diagnosed by detecting anti-MOG IgG antibodies in the blood using a cell-based assay (live-cell CBA). The type of assay matters a great deal: ELISA is not reliable for MOG-IgG and produces false positives, which can lead to a patient being incorrectly labelled with MOGAD and treated accordingly. KIMS uses the cell-based assay. Testing is ideally performed before or early in high-dose steroid treatment, since antibody titres can fall with immunosuppression. AQP4-IgG is tested at the same time, because MOGAD patients are AQP4-IgG negative by definition.

Approximately 50–60% of MOGAD patients have a monophasic course — a single attack followed by recovery and no further episodes. The remaining 40–50% relapse. There is no way to know with certainty at the time of a first attack which group a patient falls into, which is why follow-up matters: persistently positive MOG-IgG on repeat testing after the acute episode is associated with a higher relapse risk, while seroconversion to negative suggests a monophasic course. At KIMS the decision to start long-term preventive treatment is made on this basis rather than started automatically after a first attack.

High-dose intravenous methylprednisolone is the first-line treatment for an acute attack, usually followed by an oral steroid taper — because relapses can occur when steroids are withdrawn too quickly. MOGAD responds better to steroids than NMOSD does, and most attacks recover well. For severe attacks that do not respond adequately to steroids — severe optic neuritis with poor visual recovery, or myelitis with significant weakness — plasma exchange is used. IVIG is also effective in acute MOGAD and is often preferred in children. All three are available at KIMS, with neuro-ICU support where the attack involves respiratory compromise or extensive cord oedema.

For patients with a relapsing course, maintenance IVIG has the strongest published evidence for relapse prevention and is a first-choice option, particularly in children. Rituximab is commonly used off-label, though the response in MOGAD is less consistent than in AQP4-IgG positive NMOSD and some patients relapse despite adequate B-cell depletion. Mycophenolate mofetil, azathioprine, and low-dose oral prednisolone are also used, alone or in combination. What should not be used are the MS-specific disease-modifying therapies — natalizumab, fingolimod, and ocrelizumab are not established for MOGAD.

Yes — MOGAD occurs at all ages, and in children it is an important cause of what would otherwise be labelled ADEM. In children the typical presentations are ADEM-like attacks with encephalopathy and optic neuritis; in adults, optic neuritis, transverse myelitis, and brainstem syndromes predominate. A proportion of children previously diagnosed with ADEM are MOG-IgG positive, and identifying them matters because it changes both the relapse risk assessment and the long-term treatment plan. IVIG is particularly useful in paediatric MOGAD, both acutely and as maintenance therapy.

Yes. MOGAD may account for a proportion of patients previously diagnosed as seronegative NMOSD, or as recurrent bilateral optic neuritis of unclear aetiology — particularly where testing predated the availability of a validated cell-based MOG-IgG assay in India. Any patient with recurrent optic neuritis or ADEM-like attacks who is AQP4-IgG negative should be tested for MOG-IgG. The answer changes the treatment plan, so it is worth establishing. Call 040-44885000 to arrange a neuroimmunology review at KIMS; please bring prior MRI films and antibody reports.