Brandon Miranda

ENGL 21003

Professor Zayas

November 22, 2025

MOGAD: Rare? The Achilles of the Central Nervous System

Introduction

MOGAD or Myelin oligodendrocyte glycoprotein antibody-associated disease has had more recent fret within the science community as it only recently has had a quantified focus on its own as an autoimmune disease. Scientists has longed since discovered the myelin sheaths that bound the nerve cells which control various essential functions, and have discovered the very closely related family of autoimmune diseases that MOGAD had subtly expressed itself in between, such as Multiple Sclerosis (MS), Aquaporin-4 (AQP4), or Neuromyelitis Optic Spectrum Disorder (NMOSD) that similarly behave in the central nervous system (CNS). Standardizations for diagnosis requirements and identification have been recently updated as of 2023, while this criteria has become a successful tool in MOGAD diagnosis based on its leading factors, there also comes a modest generalization that manifests as a baseline. Researchers should continue to evaluate this criteria in large cohorts across the globe, and remain vigilant on the existing pre-factors the criteria addresses as severe and rare cases may be cause for alterations.

Reviewing MOGAD

Myelin oligodendrocyte glycoprotein (MOG) , which resides within the CNS, is managed under the outermost layer of myelin sheaths of lamellae as well as expressed on the surface of those oligodendrocytes. This glycoprotein, whose function has yet to be actualized, assimilates itself onto the myelin sheaths which control the rapid signal transmission of signals between cells in the CNS, likely to keep integrity. These MOG cells however, can succumb to pathogenic immunoglobulin G (IgG) antibodies that target their extracellular domain (Misu 2025).  This classification is now deemed as myelin oligodendrocyte antibody-associated disease (MOGAD), diversifies itself from MS, NMOSD and AQP4 with unique immunopathogenesis: demyelination with an abundant infiltration of CD4⁺ T-cells. 

MOGAD also displays a unique pathology that legitimatizes the distinct qualities of the family of immunodiseases.

Pathogenesis of MOGAD

  MOGAD adversely attacks myelin made up of fatty lipids and proteins from inside-out their sleeves or commonly referred to as sheaths. Signs of demyelination stem from the presence of lesions, these more spotty and patchy kinds of lesions appear at a more sporadic rate in the acute stage. MOGAD has a rapid centrifugal expansion of lesions from the perivenous epicenter due to the T cell infiltration and activation of innate immune cells (Misu 2025). The lesions then resemble a smoldered look. Compared to progressive MS, which similarly ‘smolders’  there is limited oligodendrocyte damage with antibody-mediation from indirect cytotoxicity to myelin-producing cells. Further investigation laments isotopic autoantibodies of MOG, named IgG1, mediates complement-dependent cytotoxicity (CDC) which can produce MOG-IgG (Misu 2025). This cytotoxicity is antibody-dependent cellular phagocytosis (ADCP), which is centralized in MOG-expressing cells, containing variants: IgG2, IgG3, and IgG4. The variants can then lead to the development of the various symptoms MOGAD patients face.

Features of MOGAD

Patients who contract MOGAD can experience various external complications stemming from major domains. Within the domains of symptoms come along various other complications, patients across all domains of MOGAD both common and obscure, constitutionally agree on body ache and pain (Bennett et al. 2025). MOGAD progression shows in the debilitation of physical ability in all patients regardless of domain they fall in. All patients also report at least one visual symptom of pain or visual loss, or neurological with headaches and speech difficulties, and finally sensory-motor impairment with weakness or balance issues (Bennett et al. 2025). A culmination of these symptoms destroy quality of life, putting patients through various challenges on mundane tasks, these adversities sourcing from the domains of MOG-IgG.

Domains of MOGAD

The three major domains of MOGAD that most patients are diagnosed with upon discovery are: Transverse Myelitis (TM), Optic Neuritis (ON), and Acute Disseminated Encephamyelitis (ADEM). Each of these domains are unpredictable and do not follow a pattern based on location or exposure, however there is commonality among frequency of particular diagnosis of MOGAD. Among the domains come optic neuritis and myelitis being the most frequent of initial symptoms (Liu et al. 2025). Relating back to the external factors patients experience as they contract MOGAD, the visual symptoms and motor impairment begin to take effect. It is noted that ON seems to occur at 50% in both children and adults (Misu 2025). Optic anomalies like ON can be considered a frontier of MOGAD presence, it has a common prognosis across all patients with MOGAD. However it is important to understand every legitimate prognosis:

Domains of MOGAD in Context:

Transverse Myelitis- The incomplete recovery from paraplegia paired with dysfunctional bladder (Misu 2025). Severe attacks occur from the acute stage, causing transverse symptoms: weakened motor skills, numbness, sphincter symptoms, cane and wheelchair. Symptoms stem from longitudinally extended lesions over three segments in the vertebrae, however more conus lesions found in MRI yields MOGAD patients to have more than 60% residual autonomic dysfunction possible requiring long-term catheterization (Misu 2025).

Optic Neuritis- Visual abnormalities, with poor visual recovery with reoccurence, typically vision loss of around 20/200, papillary edema, or eyeball pain, these symptoms reflect the severity of acute ON. (Misu 2025). ON in MOGAD distinguishes itself with the swelling of the peripapillary retinal fiber layer, and is more prone to relapse in adults than in children (Misu 2025).

Encephalopathy (ADEM)-When first present in both children and young adults but more commonly pediatric-onset, MOG-associated encephalitis may appear as monophasic or multiphasic, that in turn causes cerebral symptoms in the form of decreased consciousness, and reports of seizures (Misu 2025). It is agreed upon that monophasic ADEM may be treated with first-line immunotherapy, dormant monophasic ADEM does evolve to MOG-IgG^– with persistent relapsing yielding abundant MOG-IgG antibodies (Misu 2025). Severe forms of MOG-IgG induced ADEM or cases of hemisphere cortical encephalitis result in  new-onset refractory status epilepticus (NORSE) which immunotherapy and anti-epileptic treatments fail to relieve.

Realities of the Patient Experience I

• Introduce dialogue between Santi and I (for those reading my draft he’s my best friend with this disease), begin by talking about life leading up to and after the immediate effects of MOGAD now present in his lifestyle.
• Reference CSF-OSB (cerebro-spinal fluid (CSB)-restricted oligoclonal bands (OCB)) that is the precedent when sourcing for the new standards and criteria made to categorize MOGAD.

• Mention while acute MOGAD can be more treatable, it gives scientists both a good baseline but also a plain one as well. MOGAD still remains a complex and relatively fresh, susceptible to outlying cases and extreme unaccounted forms.
• Divulge the uncertainty in effectiveness in patient diagnosis/treatment, how the criteria can be very misleading in terms of misdiagnosis as well as relapse occurrence.

Counterargument (The Complicity in Expertise)

• Currently, researchers are very pleased with the standardizations which do yield more impressive results compared to previous analysis. They feel confident about the comparative results and heavily validate the data.
• Acknowledging the importance of distinguishing between MS and MOGAD as they are the closest related of the diseases, that the criteria has brought significance to rationing between the pediatric and adult onset of MOGAD
• Refer to the immediate response of case studies acknowledging the 2023 criteria as a ‘breath of fresh air’ to the already backlogged amount of cases from patients present with MOG-IgG antibodies awaiting accurate diagnosis and treatment.
• Explain that while there are clear benefits to the new standards, there is still so much to identify and the relapsing nature and severity of MOGAD can clearly derail the current standards. Reference CSF-OSB (cerebro-spinal fluid (CSB)-restricted oligoclonal bands (OCB))  & mimicry of MS that MOGAD presents as the precedent when sourcing for the new standards and criteria made to categorize MOGAD.

Treatment of MOGAD and the Calamity of Relapses

Relapse Cycle of MOGAD

On the subject of moving forward for the battle against MOGAD, comes a harrowing new challenge for researchers and clinicians as relapsing cycles in patients have sprouted new research as severe cases and new exceptions to MOGAD beliefs arise as more investigation is made. It is acknowledged that in antibody-mediated diseases such like MOGAD or NMOSD, disability accumulation is conferred by relapses (Kang et al. 2025). Researchers attribute the onslaught of MOG-IgG production to be a factor in play for relapse, and admit that despite treatment, relapse is common particularly after steroid withdrawal (Misu 2025). Groups that test this ‘relapse theory’ find that while in some cases, more early and singular, can be treated with no relapse, often the later stage and complex symptoms bring relapse probability higher. Further patterns are revealed as all cases of relapse after IST discontinuation group studies all have had prior relapsing courses, dubbed ‘contagion’ (Kang et al. 2025). This affirms the upended attention to long-term, frequent IST clinicians should provide as they continue to research MOGAD and establish pliant contingencies.

Existing Treatments of MOGAD

There are four types of ‘mainstream’ immunotherapies and medications to combat the development of MOGAD: Intravenous Methylprednisolone (IVMP), Plasma Exchange (PLEX), Intravenous Immunoglobulin (IVIG), the immunosuppressant medication such as Azathioprine (AZA) and mycophenolate mofetil (MMF), and rituximab. These are the best of the treatments available with the current efforts to catch up and fight against MOGAD, each treatment process in their right can or cannot be effective across any range of patients with MOGAD and should each should be understood when facing the unpredictable disease itself:

In Context:

Intravenous Methylprednisolone- Liquid dosage administered at high amounts of 1000mg/day for 3-5 days, followed by gradual tapering with steroids orally over the duration of weeks to months (Misu 2025). Usually effective upon initial episodes of acute inflammation, inducing neurological recovery.

Plasma Exchange- Highly effective in rapidly reducing circulating autoantibodies to improve neurological outcomes in patients with insufficient corticosteroids (Misu 2025). Initiated 7-10 days after steroid failure in a span of 5-7 sessions, it is often used against severe ON, TM , and fulminant encephalitis, this is paired with continued use of modification therapy with rituximab, azathioprine, and mycophenolate mofetil that shows favorable remission results and EDSS improvement.

Intravenous Immunoglobulin- Often used in immunosuppressive therapy (IST), it has gained popularity as it has been very successful in several small studies (Bilodeau et al. 2025). It also has gained popularity amongst younger populations of MOGAD patients as several other studies have found that IVIG has led to faster functional recovery for pediatric onset cases (Misu 2025). Rising interest in IVIG continues to grow as it even results in the lowest Annual relapse rates (ARR) from discontinuation of a period of 6+ months along with 72% relapse-freedom (Bilodeau et al. 2025).

Azathioprine, Mycophenolate Mofetil, and Rituximab- The three most common immunosuppressives used in the treatment of MOGAD, confirmed by an international study producing data showing that AZA was used 30% of the time, mycophenolate 25% and rituximab 17.3% (Bilodeau et al. 2025). MMF and AZA are also primarily used for NMOSD and when utilized together and in early succession, can reduce frequency of relapse. This does not however guarantee that relapse does not occur, as once the suppressants are removed, relapse is likely to occur again (Misu 2025). 

Realities of the Patient Experience II

• Reintroduce dialogue between Santi and I- looking to tie into how every case, monophasic or not, have different effects towards each individual, (with respect to the already similar types of symptoms). 
• Introducing a rare case of a 59-year old man who contracted aseptic meningitis, treated to later relapse with severe cranial neuritis that the patient unfortunately succumbed to. Clarify the uncertainty with available research to accurately guide patients to stable relapse-freedom, while also acknowledging patient financial struggles.
• Connect first case to other cases of rare phenotypes of MOGAD that present exceptions to most accepted guidelines and criteria leading the fight against MOGAD, all pertaining to the more unique form of MOGAD (aseptic meningitis), finally to the case study regarding the 56-year old man who needed stem cell transplant to recover from motor impairment and dysfunction caused by extended spinal lesions after relapsing from ON.
• Reaffirming the difficulties of treatment discontinuation for multiphasic MOGAD and the uncertainty and unpredictability the disease presents, MOGAD presents a major lapse of ability that scientists have not yet solved. More outlying cases and complex MOGAD phenotypes may have to drive the research inward for an even more unified approach at tackling MOGAD cases.
• End section with Santi on his reflection with his rare form of MOGAD, and what he would do differently had he known sooner about this life change.

Conclusion

• Review MOGAD briefly once more to the reader, as will need to reinstate the principle of this essay.
• Relate to Santi and the cases explored throughout the sections, connecting this ‘elephant’ of relapsing rates and rare phenotypes that steer to an unclear and unexplored region of MOGAD research.
• Acknowledge once more that the standardizations existing currently are on par and very useful for the layman case of MOGAD, and while that remains efficient for a good portion of patients diagnosed, it does not cover the gray areas where there are still very many current and future patients that are the ‘exceptions’.
• Close paper urging for more research and vigilance into the current practices in MOGAD treatment, to not grow fully complicit with commonlike results and to revisit the current criteria for a more concise diagram of diagnosis.

Work Cited

Bennett, J.-L., et al.. (2025). Patient experience of myelin oligodendrocyte glycoprotein antibody-associated disease: Qualitative patient and clinician interviews informing the development of a conceptual model. Neurology and Therapy, 14(4), 1569–1587. https://doi.org/10.1007/s40120-025-00770-6 

Bilodeau, P.-A., et al. (2024) “Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease.” Multiple Sclerosis Journal, 30(3): 357-368, Epub 5 Feb. 2024  https://doi.org/10.1177/13524585241226830

Gu, M., et al. (2023). Characteristics of aseptic meningitis-like attack—an underestimated phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease. Multiple Sclerosis and Related Disorders, 78, 104939. https://doi.org/10.1016/j.msard.2023.104939

Hacohen, Y., & Marignier, R. (2025). Treatment discontinuation in Mogad: A reassuring step forward. Multiple Sclerosis Journal, 31(9), 1021–1022. https://doi.org/10.1177/13524585251336891

Kang, Y.-R., et al. (2025). Outcomes of immunosuppressive therapy discontinuation in patients with myelin oligodendrocyte glycoprotein antibody-associated disease. Multiple Sclerosis Journal, 31(9), 1102–1109. https://doi.org/10.1177/13524585251320046

Kim, K., et al.. (2023). Validation of the International Mogad Panel proposed criteria. Multiple Sclerosis Journal, 29(13), 1680–1683. https://doi.org/10.1177/13524585231198754

Liu, B., et al. (2025). Analysis of clinical features and literature review of myelin oligodendrocyte glycoprotein antibody-associated disease. Neurology Asia, 30 (1), 271-277. https://doi.org/10.54029/2025nfz

Luo, Y. L., et al. (2025). When mogad mimics MS: Diagnostic and therapeutic insights from a unique CNS demyelinating case. BMC Neurology, 25(1). https://doi.org/10.1186/s12883-025-04442-8

Misu, T. (2025). Myelin oligodendrocyte glycoprotein antibody-associated disease: pathophysiology, clinical patterns, and therapeutic challenges of intractable and severe forms. International Journal of Molecular Sciences, 26 (17), 8538-8538. https://doi.org/10.3390/ijms26178538

Ramdani, R., et al. (2025). Evaluation of the predictive value of CSF-restricted oligoclonal bands on residual disability and risk of relapse in adult patients with mogad: Mogadoc study. Multiple Sclerosis Journal, 31(3), 290–302. https://doi.org/10.1177/13524585241311435

Rechtman, A., et al. (2024). Assessing the applicability of the 2023 International Mogad Panel Criteria in real-world clinical settings. Journal of Neurology, 271(8), 5102–5108. https://doi.org/10.1007/s00415-024-12438-6

Sbragia, E.,et al. (2023). An aggressive form of Mogad treated with AHSCT: A case report. Multiple Sclerosis Journal, 30(4–5), 612–616. https://doi.org/10.1177/13524585231213792

Zhang, Y.-N., et al. (2025). Myelin oligodendrocyte glycoprotein antibody-associated disease presenting as aseptic meningitis and multiple cranial neuritis: A case report. BMC Neurology, 25(1). https://doi.org/10.1186/s12883-025-04287-1