Eoin P. Flanagan, MB, BCh
(Credit: Mayo Clinic)
In a research letter recently published in JAMA Neurology, researchers highlighted that meningitis could be a feature of myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Using data from a prior study that investigated the frequency and characteristics of meningitis in MOGAD, this potential feature was not included in the 2023 diagnostic criteria for the disease.1,2
The previous study featured 810 patients with MOGAD, 34 (4%) of which had meningitis, with symptoms or signs at presentation that included headache (94%), fever (62%), nausea/emesis (56%), encephalopathy (50%), photophobia (38%), seizure (35%), nuchal rigidity (24%), or papilledema (12%). Notably, researchers noted that elevated cerebrospinal fluid (CSF) opening pressure occurred in 11 out of 18 patients with MOGAD in the study and 7 of the patients experienced leptomeningeal changes on their initial MRI scan.
“A meningitis attack phenotype occurred in 4% of the MOGAD cohort,” senior author Eoin P. Flanagan, MB, BCh, professor of neurology and chief of the Division of Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic, and colleagues wrote in the published research letter.1 “Given that 50% of the cohort developed intra-attack encephalopathy, evolved into a typical core demyelinating event, or both, meningitis may at times represent an early manifestation of meningoencephalitis or parenchymal disease, with demyelinating lesions initially absent due to radiologic lag.”
“All cases met the definition of aseptic meningitis, misdiagnoses and antimicrobial use were frequent, and MOG IgG testing and immunotherapy administration were often delayed, suggesting that meningitis/meningoencephalitis is an underrecognized feature of MOGAD attacks. Future updates of MOGAD diagnostic criteria could add meningitis/meningoencephalitis as an attack type, allowing earlier testing, diagnosis, and treatment before onset of parenchymal disease,” Flanagan et al noted.
This international study identified patients with MOGAD across 11 centers who had at least 1 symptom or sign of aseptic meningitis per criterion, CSF white blood cell count greater than 5/μL; MOG IgG positivity, absence of infectious or alternative etiologies, and lack of parenchymal brain involvement on MRI. Researchers tested the serum and CSF samples from the precipitants by fixed or live MOG IgG cell-based assay or both. In addition, pathology (n = 1) was assessed through EnVision FLEX (Dako) immunohistochemistry as performed previously.3 Investigators also reported the collected clinical variables from electronic medical records using descriptive statistics.
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In the research letter, authors noted that serum MOG IgG titers were assessed in 34 patients (live, n = 28; fixed, n = 6) and categorized as clear positive (n = 20), low positive (n = 3), or unavailable (n = 11). Among patients without a prior diagnosis of MOGAD, the median time for MOG IgG testing was 43 days (IQR, 12–563). Additionally, CSF MOG IgG was positive in all 5 patients who underwent CSF testing.
All patients initially presented with suspected infectious meningitis, with 68% who received antimicrobials and 32% who received first-line immunotherapy in a median of 10 days (IQR, 6.5–11.5) from presentation. In 1 patient, brain and meningeal biopsy revealed meningeal infiltration by CD4+ T cells, CD20+ B cells, and microglia, along with cortical subpial demyelination and remyelination; MOG immunostaining was absent in normal control meninges.
Authors also noted that 3 of the meningitis attacks presented in the study were initially attributed to MOGAD, which included 2 relapse attacks. In the group of patients with meningitis, 17 of them developed new clinical features or MRI lesions representing an evolution to a core demyelinating event in a median of 17 days (IQR, 11-25). At last follow-up, 27 of 34 patients fulfilled MOGAD criteria, and the 7 remaining patients had a single monophasic meningitis attack (clear positive, n = 6; persistent positive without titers available, n = 1).
“Lack of MOG immunostaining in control meninges and transcriptomic data showing absent or extremely low MOG in human meninges make it unlikely to be the primary target. A cortical MOG origin with secondary meningeal inflammation is possible, given the cortical demyelination pathologically and insensitivity of MRI for cortical involvement, or MOG may not be the primary initiating antigenic target,” Flanagan et al noted in the letter.1 “This study is limited by its retrospective nature. Expanding the MOGAD spectrum requires caution because low-titer MOG IgG may occur with other diseases, but most patients fulfilled MOGAD criteria and had a clear positive MOG IgG result without alternative etiologies identified.”