Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct autoimmune demyelinating disorder of the central nervous system (CNS), in which pathogenic IgG antibodies against the extracellular domain of myelin oligodendrocyte glycoprotein (MOG) on oligodendrocytes play a central role. MOGAD is neither classical multiple sclerosis (MS) nor aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD); it has its own pathophysiology, clinical phenotypes, MRI characteristics, and treatment profile.

Pathogenesis and Immunological Mechanisms

The pathogenesis of MOGAD is driven by an autoimmune antibody response against MOG, a protein located on the outer surface of myelin and the membrane of oligodendrocytes. It is a multicomponent process that includes several key mechanisms:

• Complement-dependent cytotoxicity (CDC): binding of MOG-IgG to its antigen on the oligodendrocyte surface activates the complement cascade with formation of the membrane attack complex and subsequent myelin damage.
• Antibody-dependent cellular cytotoxicity (ADCC): Fc fragments of MOG-IgG interact with Fc receptors on NK cells and macrophages, leading to targeted cell injury.
• T-cell–mediated inflammation: CD4+ T cells recognizing MOG epitopes sustain chronic inflammation, secrete proinflammatory cytokines, and recruit additional effector cells.
• Oligodendrocyte damage and demyelination with variable degrees of axonal injury and tissue necrosis.

Experimental studies have shown that antibodies to MOG are directly pathogenic in experimental autoimmune encephalomyelitis (EAE) models and generate a specific pattern of demyelinating lesions, distinct from typical MS patterns and from AQP4-mediated astrocytopathy in NMOSD.

Clinical Spectrum of MOGAD

MOGAD is characterized by a broad but fairly typical range of clinical phenotypes. Four main clinical forms are recognized.

Optic neuritis (ON)

• The most common manifestation in adults.
• Often bilateral, either simultaneous or sequential.
• Severe retro-orbital pain with eye movements, reduced visual acuity, impaired color vision.
• Compared with MS-associated ON, MOGAD more often involves long segments of the optic nerve, including retrobulbar portions and perineural sheaths.

Transverse myelitis

• May present as longitudinally extensive transverse myelitis (LETM) or as shorter lesions.
• Clinical features include weakness in the legs and/or arms, sensory disturbances, and bladder or bowel dysfunction.
• Outcomes of myelitis in MOGAD are generally more favorable than in AQP4-NMOSD.

Acute disseminated encephalomyelitis (ADEM)

• The predominant phenotype in children.
• Fever, encephalopathy, seizures, and multifocal neurological deficits.
• MRI shows multiple, bilateral, poorly demarcated white matter lesions, often with involvement of grey matter structures.

Cortical encephalitis / cortical encephalopathy

• Seizures, headache, and focal cortical symptoms.
• MRI reveals cortical and subcortical lesions, sometimes described as the FLAMES phenotype (FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures).

From the standpoint of disease course, MOGAD can be classified as:

• monophasic — a single clinical attack followed by long-term remission;
• relapsing — a series of attacks of ON, myelitis, ADEM-like episodes, or their combinations.

Relapse risk is higher in patients with persistent MOG-IgG seropositivity; however, seroconversion to a negative status also occurs.

Diagnosis of MOGAD and International Criteria

The diagnosis of MOGAD is based on the combination of clinical features, MRI findings, and serological confirmation of anti-MOG antibodies.

MOG-IgG Antibodies

The gold standard is an optimized cell-based assay (CBA) using full-length human MOG expressed on the surface of live cells. Testing is performed mainly in serum, and in selected cases in CSF.

• Highly specific CBAs help distinguish true positives from false positives that may occur with less specific techniques.
• Interpretation must take into account clinical context, MRI findings, and antibody titer.

International MOGAD Panel Consensus Criteria

The International MOGAD Panel has proposed diagnostic criteria that include:

• one or more “core clinical demyelinating events” (ON, myelitis, ADEM, cortical encephalitis, and others);
• compatible MRI findings (characteristic lesions of the optic nerves, spinal cord, and brain);
• seropositivity for MOG-IgG on a validated CBA;
• mandatory exclusion of MS and AQP4-positive NMOSD.

MRI Characteristics

Typical MRI features of MOGAD include:

• In ON — long segments of optic nerve involvement with perineural enhancement, sometimes with chiasmal involvement.
• In myelitis — longitudinally extensive or shorter cord lesions, often with marked swelling.
• In ADEM — multifocal, bilateral, poorly demarcated white matter lesions, frequently involving thalami, basal ganglia, and cortex.

Differential Diagnosis

The key differential diagnoses are:

• multiple sclerosis (typical periventricular and juxtacortical lesions, spinal cord involvement, CSF oligoclonal bands, classical MS clinical course);
• AQP4-positive NMOSD;
• other autoimmune, infectious, and paraneoplastic CNS disorders.

Accurate differentiation is critical because standard disease-modifying therapies for MS are ineffective in MOGAD and may worsen disease activity.

Treatment of Acute Attacks in MOGAD

Treatment of acute MOGAD attacks largely parallels approaches used in other autoimmune demyelinating diseases, but there are important nuances.

High-Dose Intravenous Corticosteroid Pulse Therapy

First-line therapy consists of:

• methylprednisolone 1 g/day IV for 3–5 days in adults;
• 20–30 mg/kg/day (up to 1 g/day) in children.

Most patients show a rapid clinical response. Visual recovery after ON in MOGAD is often better than in AQP4-NMOSD.

Plasma Exchange (PLEX)

PLEX is indicated in:

• severe attacks with marked neurological deficits;
• insufficient response to corticosteroids.

Typically, a course of 5–7 exchanges is performed on alternate days. PLEX is effective for both ON and myelitis.

Intravenous Immunoglobulin (IVIG)

IVIG at a total dose of 2 g/kg over 3–5 days is used:

• in steroid-refractory attacks;
• when PLEX is not feasible;
• frequently in children and in ADEM-like presentations.

Early and aggressive treatment (corticosteroids ± PLEX/IVIG) is associated with better functional outcomes and a lower risk of subsequent relapses.

Maintenance (Relapse-Prevention) Therapy in MOGAD

The goal of maintenance therapy is to reduce relapse frequency, prevent accumulation of disability, and improve long-term prognosis. Indications for initiating maintenance treatment include:

• relapsing disease course;
• severe initial attack with high risk of further relapses;
• significant residual neurological deficit after the first event;
• persistently high MOG-IgG titers.

Intravenous Immunoglobulin (IVIG) — the Most Effective Maintenance Therapy

Contemporary data indicate that maintenance IVIG is associated with the lowest annualized relapse rate (ARR) and the highest relapse-free probability in both adults and children with MOGAD.

• In large multicenter MOGAD cohorts:
  • IVIG: ARR ≈ 0.13; approximately 72% of patients relapse-free at ≥6 months;
  • rituximab: ARR ≈ 0.51; around 33% relapse-free;
  • mycophenolate mofetil (MMF): ARR ≈ 0.32; about 49% relapse-free.
• In pediatric cohorts, MMF can be particularly effective (ARR ≈ 0.15), but IVIG remains one of the most efficacious and safest options.

The safety profile of IVIG is favorable: serious adverse events are rare; more common side effects include headache, mild infusion reactions, and transient fatigue.

Mycophenolate Mofetil (MMF)

MMF is a steroid-sparing immunosuppressant used in both adults and children:

• in pediatric cohorts, ARR on MMF can reach ≈0.15, comparable to IVIG;
• in adults, MMF provides moderate reduction in relapse frequency and good tolerability;
• oral administration makes MMF attractive when long-term IVIG or repeated infusions are limited.

Rituximab and Other B-Cell–Depleting Therapies

Rituximab, widely used in NMOSD and other autoimmune disorders, is also employed in MOGAD:

• it significantly reduces relapse risk;
• however, breakthrough relapses may occur even with complete B-cell depletion;
• late-onset neutropenia has been described and requires regular blood monitoring;
• meta-analyses suggest that ARR on rituximab (≈0.5) is higher than with IVIG.

Rituximab remains an important option, especially when long-term IVIG is not feasible or in patients with coexisting autoimmune conditions, but it is not considered the “gold standard” for relapse prevention.

Azathioprine and Long-Term Corticosteroids

Azathioprine and long-term low-dose oral corticosteroid therapy are used less frequently as steroid-sparing options:

• they provide moderate efficacy;
• require regular laboratory monitoring of blood counts and liver function;
• chronic corticosteroid use is limited by systemic side effects (osteoporosis, metabolic complications, hypertension, etc.).

MS Disease-Modifying Therapies Are Inappropriate for MOGAD

MS-specific disease-modifying therapies (DMTs), such as interferon-β, fingolimod, and others, are:

• ineffective in MOGAD;
• in some reports, associated with increased relapse risk.

Therefore, classic MS DMTs are not recommended for MOGAD and may be potentially harmful.

Impact of Early Initiation of Maintenance Therapy

The MOGADOR2 study demonstrated that early initiation of maintenance therapy after the first clinical event of MOGAD significantly reduces relapse risk and improves long-term outcomes.

• Patients who started preventive treatment soon after disease onset had substantially higher relapse-free survival compared with those whose therapy was delayed.
• Delayed or absent maintenance therapy is associated with more frequent attacks and a higher risk of accumulating disability.

Emerging and Experimental Approaches: CAR-T and Cell-Based Therapies

Current Status of CAR-T Therapy in MOGAD

Chimeric antigen receptor T-cell (CAR-T) therapy is currently neither an established, approved, nor recommended treatment for MOGAD. As of late 2025:

• no clinical trials have demonstrated efficacy of CAR-T therapy specifically in patients with MOGAD;
• no consensus guidelines support the use of CAR-T in routine clinical practice for MOGAD;
• CAR-T is regarded as an experimental technology for highly refractory autoimmune CNS diseases.

Preclinical Data

In EAE models, several CAR-T–based strategies are under investigation:

• MOG-specific CAR-Treg cells designed to suppress autoimmune inflammation and promote remyelination;
• peptide–MHC class II CAR-T cells targeting MOG-reactive CD4+ T cells.

Both approaches have demonstrated reduction in disease activity and improved recovery in experimental models, but there are no clinical trials in humans with MOGAD yet.

Clinical Trials in Related Diseases

• Early-phase CAR-T trials are ongoing in AQP4-positive NMOSD and other antibody-mediated CNS disorders.
• Some basket trial designs plan to include patients with MOGAD, but no published results are available to date.

Overall Conclusion

At present:

• CAR-T therapy for MOGAD remains purely experimental;
• its future role will depend on the outcomes of clinical trials;
• the current treatment standard in MOGAD is based on IVIG, MMF, rituximab, and other established immunotherapies.

Prognosis

Overall, the prognosis in MOGAD is more favorable than in AQP4-positive NMOSD:

• visual recovery after ON is often complete or near-complete;
• the risk of severe irreversible myelopathy is lower;
• a substantial proportion of patients has a monophasic disease course;
• even in relapsing disease, timely maintenance therapy can markedly reduce the risk of accumulating disability.

Nonetheless, MOGAD remains a serious condition requiring early diagnosis, careful differential work-up, and appropriate immunotherapy.

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Patient FAQ: Simple Answers About MOGAD

What is MOGAD in simple terms?

MOGAD is an autoimmune disease in which the immune system mistakenly attacks the myelin sheath of nerves in the brain and spinal cord because of antibodies against the MOG protein. It is not multiple sclerosis and not “classic” neuromyelitis optica, but a separate disease.

What symptoms can MOGAD cause?

Most commonly:

• optic neuritis — visual loss and pain with eye movements;
• myelitis — weakness in the legs or arms, numbness, bladder and bowel dysfunction;
• in children — ADEM: fever, profound weakness, sometimes altered consciousness;
• seizures and headaches when the cerebral cortex is involved.

How is MOGAD different from multiple sclerosis?

MOGAD differs from MS in its underlying mechanisms, typical symptoms, MRI patterns, laboratory findings, and response to treatment. Importantly, MS disease-modifying therapies do not work in MOGAD and can worsen the disease, so a different therapeutic approach is required.

How is the diagnosis of MOGAD made?

The diagnosis is based on:

• a blood test for MOG-IgG (using a special cell-based assay);
• MRI of the brain, optic nerves, and/or spinal cord;
• a detailed neurological examination and assessment of symptoms.

It is also crucial to exclude other conditions, particularly MS and AQP4-positive neuromyelitis optica.

How serious is this disease?

MOGAD can cause severe symptoms, especially at first presentation. However, in many cases, there is complete or near-complete recovery after treatment. Some patients experience only a single attack (monophasic disease). In relapsing MOGAD, appropriately chosen therapy substantially reduces the risk of further attacks and disability.

Can vision recover after optic neuritis in MOGAD?

Yes, often it can. Unlike some other conditions (such as AQP4-NMOSD), visual recovery in MOGAD is usually better, especially when treatment is started promptly.

How are acute attacks of MOGAD treated?

Acute attacks are treated with:

• intravenous high-dose corticosteroids (pulse therapy);
• plasma exchange in severe or steroid-refractory cases;
• intravenous immunoglobulin (IVIG) in selected patients.

This approach helps to rapidly control inflammation and reduce the risk of permanent neurological deficits.

Is long-term treatment needed after the first attack?

Sometimes yes. If there is a risk of further attacks, the neurologist may recommend maintenance therapy to prevent relapses. Options include IVIG, mycophenolate mofetil (MMF), rituximab, and less commonly azathioprine or low-dose oral steroids. The regimen is individualized.

Is it true that IVIG is the best option for relapse prevention?

Current studies suggest that maintenance IVIG most often provides the lowest relapse rates and good tolerability, so in many cases it is considered a preferred option.

Do MS drugs help in MOGAD?

No. Medications used for MS (such as interferons, fingolimod, and other MS DMTs) do not help in MOGAD and may worsen the disease course. Correct diagnosis and tailored therapy are therefore essential.

What is the long-term outlook?

In many cases, the long-term outlook is good: visual function and other neurological functions can recover quite well; the risk of severe disability is lower than in some other demyelinating diseases. With appropriate treatment, MOGAD can often be controlled and patients can lead a full life.

Is CAR-T therapy used for MOGAD?

At present, no. CAR-T therapy is an experimental technology being studied in laboratory models and early clinical trials for other autoimmune diseases. For patients with MOGAD, standard immunotherapies remain the mainstay of treatment.

Can patients work, exercise, and plan a pregnancy?

In many cases, yes. After disease stabilization and under the supervision of a neurologist, people with MOGAD can often work, engage in physical activity, and plan a family, with individualized recommendations regarding treatment and follow-up.

References (with clickable DOIs)

1. Misu T. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Pathophysiology, Clinical Patterns, and Therapeutic Challenges of Intractable and Severe Forms. Int J Mol Sci. 2025;26(17):8538. doi:10.3390/ijms26178538

2. Andersen J, Brilot F. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): Insights Into Pathogenesis and Biomarkers of Prognosis. Semin Immunol. 2025;78:101944. doi:10.1016/j.smim.2025.101944

3. Mader S, Ho S, Wong HK, et al. Dissection of Complement and Fc-Receptor-Mediated Pathomechanisms of Autoantibodies to Myelin Oligodendrocyte Glycoprotein. Proc Natl Acad Sci U S A. 2023;120(13):e2300648120. doi:10.1073/pnas.2300648120

4. Ambrosius W, Michalak S, Kozubski W, Kalinowska A. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Current Insights Into the Disease Pathophysiology, Diagnosis and Management. Int J Mol Sci. 2020;22(1):E100. doi:10.3390/ijms22010100

5. Sechi E, Gastaldi M, Cortese R, et al. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): Practical Recommendations for Diagnosis and Management. J Neuroimmunol. 2025;410:578781. doi:10.1016/j.jneuroim.2025.578781

6. Marignier R, Hacohen Y, Cobo-Calvo A, et al. Myelin-Oligodendrocyte Glycoprotein Antibody-Associated Disease. Lancet Neurol. 2021;20(9):762–772. doi:10.1016/S1474-4422(21)00218-0

7. Banwell B, Bennett JL, Marignier R, et al. Diagnosis of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: International MOGAD Panel Proposed Criteria. Lancet Neurol. 2023;22(3):268–282. doi:10.1016/S1474-4422(22)00431-8

8. Sechi E, Cacciaguerra L, Chen JJ, et al. Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management. Front Neurol. 2022;13:885218. doi:10.3389/fneur.2022.885218

9. Li Y, Liu X, Wang J, Pan C, Tang Z. Clinical Features and Imaging Findings of Myelin Oligodendrocyte Glycoprotein-IgG-Associated Disorder (MOGAD). Front Aging Neurosci. 2022;14:850743. doi:10.3389/fnagi.2022.850743

10. Kwon YN, Kim B, Kim JS, et al. Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease. JAMA Neurol. 2024;81(10):1073–1084. doi:10.1001/jamaneurol.2024.2811

11. Bilodeau PA, Vishnevetsky A, Molazadeh N, et al. Effectiveness of Immunotherapies in Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease. Mult Scler. 2024;30(3):357–368. doi:10.1177/13524585241226830

12. Wang X, Kong L, Zhao Z, et al. Effectiveness and Tolerability of Different Therapies in Preventive Treatment of MOG-IgG-Associated Disorder: A Network Meta-Analysis. Front Immunol. 2022;13:953993. doi:10.3389/fimmu.2022.953993

13. Chen JJ, Flanagan EP, Bhatti MT, et al. Steroid-Sparing Maintenance Immunotherapy for MOG-IgG-Associated Disorder. Neurology. 2020;95(2):e111–e120. doi:10.1212/WNL.0000000000009758

14. Chen JJ, Huda S, Hacohen Y, et al. Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease. JAMA Neurol. 2022;79(5):518–525. doi:10.1001/jamaneurol.2022.0489

15. Fadda G, Armangue T, Hacohen Y, Chitnis T, Banwell B. Paediatric Multiple Sclerosis and Antibody-Associated Demyelination: Clinical, Imaging, and Biological Considerations for Diagnosis and Care. Lancet Neurol. 2021;20(2):136–149. doi:10.1016/S1474-4422(20)30432-4

16. Lu Q, Luo J, Hao H, et al. Efficacy and Safety of Long-Term Immunotherapy in Adult Patients With MOG Antibody Disease: A Systematic Analysis. J Neurol. 2021;268(12):4537–4548. doi:10.1007/s00415-020-10236-4

17. Nepal G, Kharel S, Coghlan MA, Rayamajhi P, Ojha R. Safety and Efficacy of Rituximab for Relapse Prevention in Myelin Oligodendrocyte Glycoprotein Immunoglobulin G (MOG-IgG)-Associated Disorders (MOGAD): A Systematic Review and Meta-Analysis. J Neuroimmunol. 2022;364:577812. doi:10.1016/j.jneuroim.2022.577812

18. Deschamps R, Guillaume J, Ciron J, et al. Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study. Neurology. 2024;103(3):e209624. doi:10.1212/WNL.0000000000209624

19. Ismail FS, Gallus M, Meuth SG, et al. Current and Future Roles of Chimeric Antigen Receptor T-Cell Therapy in Neurology: A Review. JAMA Neurol. 2025;82(1):93–103. doi:10.1001/jamaneurol.2024.3818

20. Zhang Y, Li D. Translational Insights From EAE Models: Decoding MOGAD Pathogenesis and Therapeutic Innovation. Front Immunol. 2025;16:1530977. doi:10.3389/fimmu.2025.1530977

21. Konitsioti AM, Prüss H, Laurent S, et al. Chimeric Antigen Receptor T-Cell Therapy for Autoimmune Diseases of the Central Nervous System: A Systematic Literature Review. J Neurol. 2024;271(10):6526–6542. doi:10.1007/s00415-024-12642-4

22. Brittain G, Roldan E, Alexander T, et al. The Role of Chimeric Antigen Receptor T-Cell Therapy in Immune-Mediated Neurological Diseases. Ann Neurol. 2024;96(3):441–452. doi:10.1002/ana.27029