Clinical Features of Coexisting Anti-NMDAR and MOG Antibody-Associated Encephalitis: A Systematic Review and Meta-Analysis

Coexisting anti-NMDAR and MOG antibody (anti-NMDAR-IgG(+)/MOG-IgG(+))-associated encephalitis have garnered great attention. This study aimed to perform a secondary analysis to determine the clinical features of this disease. We searched several databases for related publications published prior to April 2021. A pooled analysis was conducted with the fixed-effects model using the Mante-Haenszel method (I-2 <= 50%), or the random-effects model computed by the DerSimonian-Laird method (I-2 > 50%). Stata software (version 15.0 SE) was used for the analyses. Nine observational studies and 16 case reports (58 cases with anti-NMDAR-IgG(+)/MOG-IgG(+), 21.0 [8.5, 29.0] years, male 58.6%) were included. The incidences (95%CI) of anti-NMDAR-IgG(+)/MOG-IgG(+) in the patients with serum MOG-IgG(+) and CSF anti-NMDAR-IgG(+) were 0.09 (0.02-0.19) and 0.07 (0.01-0.19), respectively. The median [IQR] of CSF anti-NMDAR antibody titer was 32 [10, 100], and the serum anti-MOG antibody titer was 100 [32, 320]. The prominent clinical symptoms were encephalitic manifestations, including seizures (56.9%) and abnormal behavior (51.7%), rather than demyelinating manifestations, such as speech disorder (34.5%) and optic neuritis (27.6%). Relapse occurred in 63.4% of anti-NMDAR-IgG(+)/MOG-IgG(+) patients, in whom 50.0% of cases relapsed with encephalitic manifestations, and 53.8% relapsed with demyelinating manifestations. The common MRI changes were in the cortex or subcortex (70.7%) and brainstem (31.0%). 31.3% of patients presented with unilateral cerebral cortical encephalitis with epilepsy and 12.5% displayed bilateral frontal cerebral cortex encephalitis. Anti-NMDAR-IgG(+)/MOG-IgG(+) patients showed more frequent mental behavior (OR, 95%CI, 68.38, 1.36-3,434.37), involuntary movement (57.86, 2.53-1,325.11), sleep disorders (195.00, 7.07-5,380.15), and leptomeninge lesions (7.32, 1.81-29.58), and less frequent optic neuritis (0.27, 0.09-0.83) compared to anti-NMDAR-IgG(-)/MOG-IgG(+) patients and presented more common relapse (5.63, 1.75-18.09), preceding infection (2.69, 1.03-7.02), subcortical lesions (116.60, 4.89-2,782.09), basal ganglia lesions (68.14, 2.99-1,554.27), brainstem lesions (24.09, 1.01-574.81), and spinal cord lesions (24.09, 1.01-574.81) compared to anti-NMDAR-IgG(+)/MOG-IgG(-). In conclusion, anti-NMDAR-IgG(+)/MOG-IgG(+) was rarely observed, but the incidence rate of relapse was very high. The overall symptoms seemed to be similar to those of NMDAR encephalitis.

Automated summary

Coexisting anti-NMDAR and MOG antibody-associated encephalitis, although rare, can present with clinical features resembling NMDAR encephalitis, with a high incidence of relapse. Patients with both antibodies showed more mental behavior and involuntary movement symptoms, but less optic neuritis, compared to those with only one type of antibody, and had a higher likelihood of relapse and specific lesions on MRI.