Abstract
Objective: To summarize the clinical characteristics, radiological features, treatments, and prognosis of patients with myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD) overlapped with NMDA receptor (NMDAR) encephalitis.
Methods: We retrospectively analyzed patients who exhibited dual positivity for MOG antibodies and NMDAR antibodies in serum/CSF from Jan 2018 to Jun 2023
Results: Ten patients with MOGAD and NMDAR encephalitis were enrolled. The median age of initial attacks was 23 (range: 10-43) years old. Common symptoms were cortical encephalopathies (8/10), focal neurological deficits (4/10), as well as other presentations including headache, fever, optic neuritis, and transverse myelitis. CSF pleocytosis was general (9/10, median 63.9 cells/μl). Lesions on brain MRI included brainstem (37.5%), cerebral cortex (33.3%), basal ganglia (25.0%), hippocampus (20.8%). The average follow-up duration was 25.4 months. 10/10 patients developed more than one relapse attacks, with MOG positivity before (10%), simultaneous (40%) or after anti-NMDAR encephalitis (50%). Most patients (7/10) had good response to first-line therapy, but experienced next relapse with an average interval of 6.7 (range: 2-14) months. We conducted initial analysis of lymphocyte subsets in these patients, which revealed CD3+ and CD4+ T cells increased after immunosuppressants medication (p < 0.01 and p < 0.05, respectively).
Conclusion: MOGAD overlapping with NMDAR encephalitis presents a distinct clinical phenotype which differs from either MOGAD or NMDAR encephalitis. Brainstem in combination with cortical lesions might be warning signs for this overlapping syndrome. Due to the high recurrent rates, we recommend early diagnosis and timely treatment with high-efficiency immunosuppressants at onset.
Introduction
Myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) [1]. Following the detection of a distinctive autoantibody against MOG in patients with specific clinical and imaging features, MOGAD was regarded as an isolated disease spectrum differentiating from aquaporin-4 seropositive neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis [2]. Optic neuritis (ON) and transverse myelitis (TM) are typical clinical presentations of MOGAD in adults, while acute disseminated encephalomyelitis (ADEM) is common in children [3]. Cerebral cortical encephalitis and brainstem or cerebellar demyelination is less common in MOGAD [4].
The anti-N-methyl-d-aspartate receptor (NMDAR) antibody mainly binds to the GluN1 subunit of the neuronal surface [5], which induces autoimmune encephalitis (AE). The defining features of NMDAR receptor encephalitis are abnormal mental behavior, epileptic seizures, altered consciousness, and central hypoventilation [6]. In a cohort study, patients with NMDAR encephalitis were tested for concurrent glial and neuronal surface antibody [7]. Of them, 4% exhibited co-existence with glia-antibodies, among which MOG-antibody was most frequently present. Another study showed that 3.3% of patients with anti-NMDAR encephalitis develop demyelinating disorders, either separately or simultaneously. Among these NMDAR antibody-positive patients, 12 (16.4%) tested positive for MOG antibody [8].
Apart from the phenomena of NMDAR encephalitis in combination with MOG-antibody positivity, an increasing number of cases have recently been reported in MOG antibody positive patients presenting with seizures or cortical and brainstem encephalitis [9, 10], indicating clinical entity distinct from typical MOGAD. These patients have episodes of encephalopathy and demyelination concomitantly or sequentially, in which dual positivity of anti-NMDAR and anti-MOG abs were detected [3, 11]. Other case reports and systematic reviews also revealed that prevalence of the overlapping syndrome may be underestimated [12]. Thus, it is considered important to identify serum MOG-positive patients overlapping with anti-NMDAR antibodies.
Data on the clinical and radiological features of MOGAD overlapping with NMDAR encephalitis are scarce, and the scope of published literature is mainly restricted to case reports [13-15]. Distinct clinical spectra were present in these patients, indicating that the overlapping syndrome is an independent disease entity that differs from patients with single antibody positivity. Hence, this study is aimed to provide a long-term retrospective analysis of MOGAD overlapping with NMDAR encephalitis in the last 5 years by summarizing clinical characteristics, imaging features, and evaluating treatments and prognosis.