Myelin oligodendrocyte glycoprotein (MOG) is a protein expressed on the surface of myelinating oligodendrocytes in the central nervous system (CNS) (1). MOG antibodies mediate cytotoxicity against MOG-expressing cells through multiple mechanisms (2), leading to an inflammatory demyelinating CNS disorder termed MOG antibody-associated disorders (MOGAD), characterized by the presence of MOG autoantibodies. MOGAD represents a distinct disease spectrum separate from multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MOGAD lesions can extensively involve the CNS, presenting with diverse clinical manifestations including optic neuritis, meningoencephalitis, brainstem encephalitis, and myelitis. These may occur as a single symptom or in various combinations of the above (3). Previous studies have extensively summarized the clinical and imaging characteristics of MOG antibody-associated diseases. In recent years, case reports of MOGAD and its cortical encephalitis clinical phenotype have garnered significant scholarly attention, with seizures potentially constituting a component of MOGAD’s clinical presentation. Patients with seizures in MOG antibody-associated diseases are increasingly being identified; however, studies on adult MOG antibody-associated diseases presenting with seizures as the initial symptom remain scarce, and their clinical manifestations and imaging features remain uncertain. The prevalence of MOGAD is approximately 1.3–2.5 per 100,000, with an annual incidence of about 3.4–4.8 per 100,000 (4). A domestic meta-analysis (5) reported a seizure incidence of 20.5% in MOGAD. Furthermore, patients with cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes exhibit a higher risk of seizures, with 37.3% experiencing epileptic episodes. Compared to patients with multiple sclerosis and AQP4-NMOSD, seizures are more common in MOGAD patients (5, 6). An increasing number of individuals recognize that epileptic seizures may occur concurrently with or precede demyelinating events, representing a unique clinical feature of MOGAD, mainly accompanied by epileptic seizures with or without brain disorders (7). The precise etiology of seizures in MOGAD patients remains unclear. This study retrospectively analyzed 7 cases of adult MOGAD patients presenting with seizures as the initial manifestation, investigated their clinical features to facilitate early diagnosis and treatment of the disease, and a systematic review of previous cases presenting with FLAMES was conducted.

MOGAD is a unique demyelinating disease of the central nervous system, characterized by the existence of pathogenic antibodies against MOG. This disorder exhibits specific clinical manifestations and unique characteristics, with clinical courses ranging from monophasic to relapsing and a wide spectrum of clinical phenotypes. It is noteworthy that disease presentations differ significantly depending on the age group of patients. Multiple studies have demonstrated that clinical phenotype distribution differs between adult and pediatric MOGAD, with the incidence being higher in the pediatric population than in adults (8). Hor and Fujihara (4) reported that regarding the age-specific incidence of MOGAD (with a mean age of onset of approximately 30 years), approximately 30% of cases occur in the pediatric age group; the prevalence of MOGAD is approximately 1.3–2.5 per 100,000 population, and the annual incidence is approximately 3.4–4.8 per 100,000 population. With increasing awareness of the disease and easier access to MOG antibody testing, the prevalence is expected to rise in the future.

Seizures represent a clinical manifestation of central nervous system inflammatory demyelinating diseases, usually emerging during the acute stage. Notably, seizures as the presenting symptom in adult MOGAD are extremely rare, whereas such seizures are comparatively infrequent in MS and NMOSD. Among pediatric MOGAD cases, the male-to-female ratio generally falls between 1:1 and 1:2, with a median seizure onset age of 6 years (range 2–14 years) and a seizure incidence of 10.5–18.6% (9). One study (10) indicated that seizures were the predominant symptom in 88.9% of 236 pediatric multifocal encephalopathy cases, mostly manifesting as focal seizures, while a minority of patients developed status epilepticus. These findings align with those reported by Budhram et al. (11). In a study of the Han population in northern China, acute seizures occurred in 21.3% of MOGAD patients, a rate significantly higher than the 0.4% observed in NMOSD patients (12). Retrospective data have shown that 20.5% of MOGAD patients experience seizures, with elevated seizure risk noted in those with cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (5). As MOGAD incidence increases, the pathogenic mechanisms of adult-onset MOGAD with seizures as the presenting symptom remain poorly elucidated. A study by Wang et al. (13) demonstrated the presence of fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in MOG antibody-associated cortical encephalitis with seizures (FLAMES). FLAIR imaging of FLAMES patients revealed cortical abnormalities most frequently located in the frontal lobe (58.8%), parietal lobe (70.6%), and temporal lobe (64.7%). Common seizure types included focal-to-generalized tonic–clonic seizures (28.6%) and tonic–clonic seizures of unknown origin (38.1%). Along with the growing recognition of MOGAD, case reports of cortical encephalitis with seizures as the main manifestation have gradually increased (14). As described by Budhram et al. (15), cortical encephalitis presenting with seizures manifests clinically as headache, fever and seizures, with typical imaging findings showing hyperintensities on fluid-attenuated inversion recovery (FLAIR) sequences in unilateral or bilateral cortical regions on brain magnetic resonance imaging (MRI), and white matter involvement is generally absent. The pathological features of FLAMES include mild inflammatory changes in the cortex and subcortex without obvious demyelination (16). Typically, cerebral cortical injury induced by seizures presents as hyperintensity on diffusion-weighted imaging (DWI); transient focal hyperintensity on DWI sequences accompanied by decreased apparent diffusion coefficient (ADC) is a characteristic finding of cytotoxic edema. In contrast, in patients with MOGAD-associated cortical encephalitis complicated by seizures, hyperintensity is observed on T2/FLAIR sequences of brain MRI, indicating interstitial edema (17). In the present study, all 7 patients had seizures as their presenting symptom, with 3 cases complicated by fever and 4 by headache. Abnormal brain MRI findings were noted in 3 patients, manifesting as cortical hyperintensities on T2/FLAIR sequences; lesions were punctate or patchy in morphology, with partial lesion swelling, involving the temporal lobe (n = 2), parietal lobe (n = 1), and occipital lobe (n = 1). Cortical FLAIR hyperintensities on brain MRI are helpful for identifying suspected MOGAD-related cortical encephalitis. Literature retrieval (11, 13, 16, 18, 19) showed that most MOG antibody-positive cortical encephalitis patients had seizures, among whom some patients presented with fever and/or headache; several patients were initially misdiagnosed with central nervous system infection, similar to two cases in our present study. Upon admission, these two cases were diagnosed as “viral meningoencephalitis” according to their medical history but failed to respond to symptomatic treatments like antiviral and anti-inflammatory regimens. Thus, we highlight to clinicians that many febrile patients with MOG antibody-associated disease may be underdiagnosed, as cellular-based autoantibody assays are ineffective for their immunological screening. Additionally, MOG antibody screening is likely to be omitted in patients lacking specific clinical features, such as Cases 4 and 7.

Seizures may present alone. Foiadelli et al. (20) documented that focal seizures can occur in patients with unremarkable brain MRI, which predicts the development of classic MOG antibody-associated demyelination in the following days or months. Notably, 4 patients in the present study had seizures as their presenting symptom, with 2 developing headache and fever within 24–48 h post-onset; no lesions were identified on brain MRI, a finding rarely described or summarized in prior literature. We therefore recognize both the uniqueness and rarity of this clinical phenotype, while noting that its correlation with disease severity and clinical outcomes remains undefined. Further multicenter data are required to validate its clinical significance and investigate the potential mechanisms of negative brain MRI—such as ultra-early undetectable lesions, predominant functional impairment, or subtle lesions undetectable by current imaging modalities. These questions all deserve further in-depth exploration. Additionally, we urge clinicians to recognize such neuroimmune-associated manifestations without positive imaging findings to minimize underdiagnosis. Clinicians should be vigilant that demyelinating events or encephalitis can develop following seizures, even after a prolonged interval post-seizure; according to Ramanathan and Yılmaz, these seizures initially manifest as unexplained episodes (21, 22). As is widely recognized, the immune system exerts a key role in epileptogenesis. Liu et al. (9) found that TPO antibody levels increase markedly during epileptic seizures; while these antibodies may be involved in the development and recurrence of immune-associated seizures, they lack specificity as biomarkers for MOGAD. As described by Ogawa et al. (23), seizures are extremely common, and MOG-IgG itself may have no obvious association with unilateral cortical encephalitis complicated by seizures; instead, autoimmune disease and MOG-IgG may coexist. Studies have confirmed that anti-MOG antibodies can overlap with other autoimmune antibodies, such as coexistence with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies (24). MOG antibody-associated cerebral cortical encephalitis patients presenting with seizures show favorable responses to corticosteroid therapy and excellent outcomes (18, 23). Conversely, long-term antiepileptic drug (AED) treatment does not significantly decrease the incidence of acute seizures or epilepsy in terms of preventing recurrent seizures or de novo epilepsy (12).

The present study has several limitations. Firstly, it was a retrospective study with a small sample size of merely 7 patients. Secondly, it remains unclear whether seizures are isolated episodes or secondary to cortical encephalitis in adult MOGAD cases presenting with seizures as the initial manifestation. Future prospective, large-scale, multicenter cohort studies are required to systematically characterize this subset of adult MOGAD patients.