Clinical Analysis of MOG Antibody-Associated Disease Overlapping with Anti-NMDAR Encephalitis

Background

In recent years, with the in-depth study of autoimmune encephalitis (AE) and demyelinating diseases of the central nervous system (CNS), scientists have identified some rare cases of overlapping syndromes. Among them, the overlap between MOG Antibody-Associated Disease (MOGAD) and Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis has attracted widespread attention. MOGAD is an inflammatory demyelinating disease of the CNS caused by antibodies against myelin oligodendrocyte glycoprotein (MOG), while anti-NMDAR encephalitis is an autoimmune encephalitis triggered by anti-NMDAR antibodies. Although these two diseases differ in clinical manifestations and pathological mechanisms, an increasing number of case reports have shown that some patients exhibit symptoms of both diseases simultaneously or sequentially, suggesting a potential connection between them.

However, systematic research on the clinical features, imaging findings, treatment strategies, and prognosis of the overlapping syndrome of MOGAD and anti-NMDAR encephalitis remains limited. Most related studies are confined to case reports, lacking large-sample, long-term follow-up data. Therefore, this study aims to retrospectively analyze patients diagnosed with the overlapping syndrome of MOGAD and anti-NMDAR encephalitis between 2018 and 2023, summarizing their clinical characteristics, imaging findings, treatment strategies, and prognosis, to provide clinicians with more comprehensive diagnostic and therapeutic references.

Source of the Paper

This paper was co-authored by researchers from the Department of Neurology at the Second Xiangya Hospital of Central South University, China, including Tianjiao Duan, Song Ouyang, Zhaolan Hu, Qiuming Zeng, and Weifan Yin. The study was funded by multiple projects, including the National Natural Science Foundation of China and the Natural Science Foundation of Hunan Province. The paper was published in 2025 in the European Journal of Neuroscience, with the DOI 10.1111/ejn.16654.

Research Process and Results

1. Patient Inclusion and Diagnostic Criteria

The study retrospectively analyzed 10 patients diagnosed with the overlapping syndrome of MOGAD and anti-NMDAR encephalitis at the Second Xiangya Hospital of Central South University between January 2018 and June 2023. Inclusion criteria included the detection of both MOG antibodies and anti-NMDAR antibodies in serum and/or cerebrospinal fluid (CSF), with a follow-up period of at least 3 months. Exclusion criteria included patients diagnosed with other antibody-positive AE or AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD).

2. Antibody Testing and Imaging Examination

Serum and CSF samples from all patients were tested for MOG antibodies and anti-NMDAR antibodies. MOG antibody testing was performed using a live cell-based assay (CBA), while anti-NMDAR antibody testing was conducted using a fixed CBA. Additionally, all patients underwent brain magnetic resonance imaging (MRI), and some patients also underwent optic nerve and spinal cord MRI.

3. Clinical Features and Laboratory Tests

Among the 10 patients, 6 were adults, and 4 were adolescents, with a median age of onset of 23 years (range: 10-43 years). The most common symptoms included encephalopathy (⁸⁄₁₀), headache (⁷⁄₁₀), fever (⁶⁄₁₀), optic neuritis (ON) (⁶⁄₁₀), and focal neurological deficits (⁴⁄₁₀). CSF analysis revealed pleocytosis in 9 patients (median: 63.9 cells/μl), and elevated protein levels in 4 patients (median: 426.1 mg/L).

4. Imaging Findings

Brain MRI showed abnormal signals in all patients, with the most commonly affected areas being the brainstem (37.5%), cerebral cortex (33.3%), basal ganglia (25.0%), and hippocampus (20.8%). Some patients also exhibited abnormal signals in the optic nerve and spinal cord.

5. Treatment Strategies and Prognosis

All patients received immunotherapy, including intravenous methylprednisolone (IVMP) and intravenous immunoglobulins (IVIG). Seven patients responded well to first-line treatment, but all patients experienced at least one relapse, with a median relapse interval of 6.7 months. Long-term immunosuppressive therapy (e.g., azathioprine, mycophenolate mofetil, and rituximab) was used to prevent relapses.

6. Lymphocyte Subset Analysis

Six patients underwent peripheral blood lymphocyte subset analysis during the acute phase and remission period. The results showed a significant increase in the proportion of CD3+ and CD4+ T cells after treatment (p < 0.01 and p < 0.05, respectively), while the proportion of CD8+ T cells and the CD4+/CD8+ ratio showed no significant changes.

Conclusions and Significance

This study is the first to systematically summarize the clinical features, imaging findings, treatment strategies, and prognosis of the overlapping syndrome of MOGAD and anti-NMDAR encephalitis. The findings suggest that this overlapping syndrome has a distinct clinical phenotype, differing from either MOGAD or anti-NMDAR encephalitis alone. Brainstem and cortical lesions may serve as warning signs for this overlapping syndrome. Due to the high relapse rate, early diagnosis and timely treatment with effective immunosuppressants are recommended.

Research Highlights

1. Distinct Clinical Phenotype: The overlapping syndrome of MOGAD and anti-NMDAR encephalitis exhibits clinical manifestations different from those of MOGAD or anti-NMDAR encephalitis alone, suggesting it may represent an independent disease entity.
2. High Relapse Rate: All patients experienced at least one relapse, indicating a high risk of recurrence and the need for long-term immunosuppressive therapy.
3. Lymphocyte Subset Analysis: This is the first report on changes in lymphocyte subsets in patients with the overlapping syndrome of MOGAD and anti-NMDAR encephalitis, providing new insights into its immune mechanisms.

Other Valuable Information

The limitations of this study include a small sample size, potential bias due to its retrospective design, and incomplete lymphocyte subset data. Future research should expand the sample size and conduct prospective studies to validate the findings of this study.

This study provides important clinical references for the diagnosis and treatment of the overlapping syndrome of MOGAD and anti-NMDAR encephalitis, offering significant scientific and practical value.