Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report

Abstract

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient’s symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.

Introduction

Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein that is exclusively situated on the surface of myelin within the central nervous system. Its primary function involves preserving oligodendrocyte surface stability and regulating the complement response. MOG antibody-associated disease (MOGAD) is a inflammatory demyelinating disease with diverse central nervous system-related symptoms and/or complications. Historically, common manifestations of MOGAD were believed to encompass optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), or an ADEM-like presentation. ¹ However, in recent years, there have been reports of atypical phenotypes within the spectrum of MOGAD disorders. These infrequent presentations include cortical encephalitis, brainstem and cerebellar deficits associated with demyelinating lesions, cranial nerve disease, and progressive white matter damage. ² Although uncommon, septic meningitis has emerged as a principal clinical feature within this spectrum. The present report describes a case of MOGAD that was characterized by an initial onset of isolated meningitis and had recurrent meningitis as its primary clinical feature. This uncommon condition can easily be mistaken for an infectious disease in its early stages, potentially leading to misdiagnosis.

The reporting of this study conforms to the CARE guidelines (for CAse REports). ³

Case presentation

A man in his early 30s presented at the hospital with a persistent severe headache and a low-grade fever that had persisted for 20 days, reaching a peak temperature of 37.9°C. Upon admission, he was initially diagnosed with an intracranial infection. The patient had no prior history of hypertension or diabetes and was in good health apart from these symptoms. There were no known genetic disorders within the patient’s family history.

The patient had a medical history of viral encephalitis on two occasions within the previous 11 years. In 2012, the patient presented with similar clinical manifestations to the current illness. Ancillary tests conducted during that period did not reveal any noteworthy abnormalities, and after receiving symptomatic treatment, the patient was discharged without any lasting neurological effects. The diagnosis at that time was of viral encephalitis. In 2017, the patient again visited our hospital because of encephalitis. Head magnetic resonance imaging (MRI) results showed no abnormalities. Throughout his hospitalization, three lumbar punctures were performed (Table 1). Despite this testing, the patient was again diagnosed with viral meningitis.

Table 1.

Lumbar puncture results.

	10 December 2017	15 December 2017	25 December 2017	9 January 2023
Leukocyte count	41 × 106/L	37 × 106/L	30 × 106/L	88 × 106/L
Single nucleated cell ratio	97.6%	94.6%	93.3%	79.6%
Polynuclear cell ratio	2.4%	5.4%	6.7%	20.4%
Total protein	285 mg/L	300 mg/L	231 mg/L	225 mg/L
Glucose	3.45 mmol/L	3.13 mmol/L	3.27 mmol/L	3.54 mmol/L
Chloride	125.9 mmol/L	125.1 mmol/L	125.5 mmol/L	125.8 mmol/L

Upon admission during the present visit, a physical examination revealed that the patient still experienced severe headache, low-grade fever (37.5°C), nausea, a slightly elevated heart rate, and positive signs of meningeal irritation; no abnormalities were detected in other physical or neurological examinations. No symptoms such as seizures or impaired consciousness were observed throughout the disease course. Based on his condition, the patient was provisionally diagnosed with meningitis. Routine blood tests and blood biochemical indices showed a leukocyte count of 11.75 × 10⁹/L. No abnormal results were detected in tests for eight preoperative items (hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, hepatitis B core antibody, human immunodeficiency virus antibody, Treponema pallidum-specific antibody, or hepatitis C virus antibody), hepatitis B penta, human immunodeficiency virus antibody, syphilis spirochete-specific antibody, hepatitis C virus antibody, or vitamin B12. The autoantibody spectrum, including anti-nuclear antibody profile, anti-cyclic citrullinated peptide antibody, anti-keratin antibody, anti-perinuclear factor, and an autoimmune liver disease-related antibody profile, all yielded negative results. Similarly, tests for complements and immunoglobulins (Ig), comprising complement C3, complement C4, IgA, IgG, and IgE, showed no abnormalities. Brain MRI scans conducted after admission displayed normal results (Figure 1), as did subsequent neck and chest MRI scans and a chest computed tomography. Further assessments, including a fundus examination, visual examination, and evoked potential tests, returned negative findings. Following admission, a lumbar puncture was promptly performed, revealing clear and colorless cerebrospinal fluid (CSF) with a pressure of 270 mmH₂O. The CSF analysis revealed a white blood cell count of 88 × 10⁶/L and CSF protein levels of 225 mg/L, whereas glucose and chloride levels remained within the normal range (Table 1). Furthermore, next-generation sequencing for CSF pathogens yielded no identifiable pathogens, and no exceptions were found in the oligoclonal bands. Subsequently, both CSF and serum samples were sent to Hebei Gene-Health Medical Laboratory Co., Ltd. (Shijiazhuang, China) for antibody testing using the Central Nervous Demyelinating Antibody Spectrum project panel, which includes aquaporin-4, myelin basic protein, glial fibrillary acidic protein, and MOG. Through cell-based assays, the matched CSF sample tested positive for MOG-IgG at a titer of 1:32, and the serum sample showed a positive MOG-IgG at a titer of 1:10 (positive cell-based assay retest on live cells, Figure 2). Consequently, a diagnosis of MOGAD was established, with isolated meningeal involvement identified as the primary clinical manifestation.

Figure 1.

Magnetic resonance imaging of the brain showing no typical imaging features of brain lesions. (a) T1, (b) T2, and (c) fluid-attenuated inversion recovery images.

Figure 2.

Cell-based assays showing positivity for MOG antibodies in both the blood and cerebrospinal fluid. (a) Serum and (b) cerebrospinal fluid.

After a comprehensive review of the patient’s medical history, clinical signs, symptoms, and ancillary tests, a consensus was reached and he was diagnosed with MOGAD. The patient was treated with 1000 mg intravenous methylprednisolone for 5 consecutive days; this resulted in a notable improvement in the patient’s condition, leading to discharge. Post-discharge instructions included the oral intake of prednisolone acetate starting at 60 mg/day, which was tapered by one tablet per week. Upon reaching a dose of 40 mg, the patient reduced intake by one tablet every 2 weeks until a dose of 15 mg was reached; this dose was then maintained for an extended period. After treatment, the patient’s headaches rapidly diminished and body temperature gradually normalized. Approximately 6 months post-treatment, the patient underwent a follow-up examination, which revealed no prior symptom recurrence and no residual neurological effects.

Discussion

As a relatively recent addition to the spectrum of autoimmune central nervous system disorders, the clinical range of diseases within MOGAD is currently under active exploration. Despite having clinical similarities with conditions such as multiple sclerosis and optic chiasmus spectrum disorders, MOGAD stands apart from these other conditions. Differential diagnosis relies on sex predisposition, prevalence rates, specific autoantibodies, histopathological characteristics, imaging observations, treatment responses, and overall outcomes.^2,4,5 MOGAD manifests differently across diverse demographic groups, with distinct primary clinical and imaging features. Its incidence tends to be higher among children than adults, and the phenotype of ADEM is more prevalent among younger populations. Common manifestations in this demographic include dyskinesia and ataxia. The typical MRI phenotype comprises cortical or subcortical high-signal lesions on fluid-attenuated inversion recovery (FLAIR) sequences, accompanied by heterogeneous enhancement following gadolinium administration.^6–8 Among adults, optic neuritis—characterized by sudden vision loss or impairment and eye pain exacerbated by eye movement—emerges more frequently. In MOGAD patients, optic nerve MRI often exhibits hyperintensity on T2-weighted images. Additionally, optical coherence tomography can identify post-optic neuritis symptoms, such as retinal changes or reduced thickness in the retinal nerve fiber layer surrounding the optic papilla.^9,10 The phenotype “FLAIR-hyperintense lesions in anti-MOG associated encephalitis with seizures” is associated with MOGAD; it commonly presents with seizures and cortical encephalitis damage, and is often observed through nuclear magnetic manifestations of cortical MRI FLAIR high-signal lesions.^8,11 Although MOGAD typically involves demyelination, negative MRI findings are not uncommon in these patients. However, as well as the typical or atypical MRI features observed in prior studies, normal imaging results may occur. In such cases, somatosensory evoked potentials can help to confirm the involvement of affected regions in the central nervous system.^12,13 Although atypical, fever symptoms manifest in approximately 9% to 60% of patients at disease onset, with variations depending on patient phenotypes. ¹⁴

The patient in the present report had previously experienced two episodes of meningitis and was admitted with symptoms including headache, nausea, low-grade fever, and positive signs of meningeal irritation. In contrast to typical MOGAD cases, our patient did not exhibit clinical or imaging indications of inflammatory demyelination during previous visits, leading to an initial misdiagnosis of viral meningitis. However, during the current visit, in which he presented with a similar clinical profile, the inclusion of antibody testing revealed positive serum MOG antibodies. As a result, the conclusive diagnosis was determined as MOGAD. Given the similarities between the patient’s three episodes and considering the high recurrence rate associated with MOGAD, ¹⁵ it is reasonable to infer that his initial two episodes were also instances of MOGAD. Thus, isolated recurrent meningitis was essentially the only clinical manifestation for this patient; the diagnostic importance of positive MOG antibodies is notably evident in this context. Of the current diagnostic methods, cell-based assays using human full-length MOG are therefore important for diagnostic accuracy. ²

In our patient, we investigated aseptic meningitis, which might represent a rare clinical phenotype of MOGAD. Several lines of reasoning support this conclusion. First, specific viral infections may target the meninges only, without affecting the brain parenchyma. This scenario may trigger an immune response, leading to isolated meningeal involvement. Second, throughout the disease course, no direct evidence of infection was detected in the patient. Furthermore, the rapid improvement of symptoms post-immunotherapy strongly suggests an immune-mediated response rather than an infectious etiology. However, our study also has some important limitations; for example, our study period for this patient needed to be longer. Although the disease manifestation was confined to the meninges in the reported case, more typical demyelination manifestations may emerge over a longer study period.

Based on our examination of the present case, we propose that aseptic meningitis may be a rare clinical phenotype of MOGAD. However, validation through further clinical studies is necessary to confirm this assertion.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605241233157 - Supplemental material for Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report

Supplemental material, sj-pdf-1-imr-10.1177_03000605241233157 for Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report by Xiaojie Wei, Chentong Zhao, Daqing Wang and Jingzhe Han in Journal of International Medical Research