Meningitis: MOGAD Case Series Highlights Underrecognition
Meningitis: A New Phenotype of MOGAD?
Table of Contents
Unveiling a Surprising Connection in Neurological Disease
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recognized autoimmune disorder affecting the central nervous system. While typically associated with optic neuritis and transverse myelitis, emerging research suggests a broader spectrum of clinical presentations, with meningitis now being identified as a potential, albeit less common, phenotype. A recent study published in JAMA Neurology highlights this intriguing association, prompting a re-evaluation of how we understand and diagnose MOGAD.
The Meningeal Manifestation of MOGAD
The study, authored by Flanagan and colleagues, delves into the characteristics of patients presenting with meningitis who were afterward diagnosed with MOGAD.This research sheds light on a cohort of individuals whose initial symptoms mimicked aseptic meningitis,a condition often attributed to infections or other inflammatory processes.
Key Findings from the Study:
Meningeal Inflammation: In one patient,brain and meningeal biopsies revealed a critically importent inflammatory infiltrate. This included CD4+ T cells, CD20+ B cells, and microglia within the meninges. Crucially, the biopsies also showed cortical subpial demyelination and remyelination, a hallmark of demyelinating diseases. The absence of MOG immunostaining in normal control meninges further supports the idea that this inflammatory process is linked to MOGAD.
Diagnostic Overlap: The study noted that a notable proportion of meningitis attacks were initially misattributed to MOGAD. specifically, three meningitis attacks were initially diagnosed as MOGAD, with two of these being relapse attacks. This underscores the diagnostic challenge and the importance of considering MOGAD in the differential diagnosis of meningitis.
Evolution to Demyelination: Within the group of patients presenting with meningitis, a significant number (17 out of 34) developed new clinical features or MRI lesions that indicated an evolution towards a core demyelinating event. This progression typically occurred within a median of 17 days from the initial presentation.
MOGAD Criteria Fulfillment: At the final follow-up, a substantial majority of patients (27 out of 34) met the established criteria for MOGAD. The remaining seven patients experienced a single, monophasic meningitis attack, with clear positive MOG IgG results in most cases.
The Role of MOG in Meningeal Inflammation
The researchers propose that while MOG might not be the primary target in the meningeal inflammation observed, its presence in the broader MOGAD spectrum is undeniable. The absence of MOG in normal meninges and transcriptomic data showing minimal MOG expression in human meninges suggest that MOG might not be the initial antigenic trigger for this specific presentation.
However, the possibility of a cortical MOG origin with secondary meningeal inflammation is considered, given the pathological findings of cortical demyelination. The limitations of MRI in detecting subtle cortical involvement further complicate the diagnostic picture.The authors also acknowledge that MOG may not be the sole initiating antigenic target in all cases.
The retrospective nature of the study presents certain limitations. The authors emphasize the need for caution when expanding the MOGAD spectrum, as low-titer MOG IgG can be found in other conditions. Still, the majority of patients in this study met MOGAD criteria with clear positive MOG igg results and no choice etiologies identified, lending significant weight to the observed association.
This research opens new avenues for understanding MOGAD and its diverse clinical manifestations. It highlights the importance of a thorough diagnostic approach, notably in cases of unexplained meningitis, where MOGAD should be considered. Further prospective studies are warranted to solidify this association and refine diagnostic strategies for this evolving understanding of MOGAD.
References:
- Aboseif A, Kim nn, Bou G, Nathoo N, Pique J, Kerbrat A, Audoin B, Demortiere B, Bourre B, Ciron J, Chen jj, Cacciaguerra L, Toley M, Quek Aml, gombley G, Marignier R, Hacohen y, flanagangan Ep. Mengitis as an attack phenottype of mylin olagodendrocyte glycoprotein antibody-associated disease. Jama neurol.2025 Jun 16. DOI: 10.1001/jamaneu