Anti-NMDA-receptor encephalitis and MOGAD associated optic neuritis: a case series

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a well-recognized autoimmune condition that often presents with neuropsychiatric symptoms and seizures. Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) often manifests as optic neuritis and, less frequently, as acute demyelinating encephalomyelitis or transverse myelitis. The co-occurrence of anti-NMDAR encephalitis and MOGAD is becoming increasingly recognized, but clinical series remain limited.

We present three patients with anti-NMDAR encephalitis and MOGAD optic neuritis (ON): two men, aged 19 and 26, and one woman, aged 36. Clinical presentations, signs, investigations, and management of each case are discussed. The 26-year-old man presented with altered mental status and concurrent vision loss. The 36-year-old woman presented with altered mental status during the encephalitis episode and developed vision loss 4 months after encephalitis. The 19-year-old man with a prior history of altered mental status, diagnosed with NMDA encephalitis 9 years earlier, presented with headache and vision loss. Abnormal T2/FLAIR lesions in the brain and/or spinal cord during the encephalitis episode and unilateral or bilateral optic nerve enhancement during the optic neuritis episode were detected on brain and orbital magnetic resonance imaging (MRI) in all patients. All patients tested positive for cerebrospinal fluid (CSF) anti-NMDAR antibodies during the encephalitis episode and had positive serum MOG titers during the optic neuritis episode. Each patient presented with bilateral, asymmetrically reduced visual acuity and diminished color vision. One patient exhibited bilateral temporal optic nerve pallor, while two patients had bilateral optic nerve edema. The diagnostic work-up revealed positive serum MOG titers (1:100, 1:10,000, and 1:10,000 in the 36/F, 26/M, and 19/M, respectively). The 36-year-old woman was treated with intravenous (IV) steroids, plasma exchange (PLEX), and rituximab during the encephalitis episode. During the optic neuritis episode, she was treated with IV steroids, IV immunoglobulin (IVIG), and rituximab, followed by long-term rituximab maintenance therapy. The 19-year-old man was treated for encephalitis with IV steroids, IVIG, and rituximab. During his optic neuritis episode, he received IV steroids, IVIG, and tocilizumab, followed by long-term tocilizumab maintenance therapy. The 26-year-old man was treated with IV steroids, PLEX, and rituximab during the acute episode, followed by long-term IVIG maintenance therapy. After achieving 2 years of stability that prompted the discontinuation of IVIG, the patient experienced a MOG-IgG-positive relapse 5 months later. This relapse was marked by a seizure-like episode and the appearance of new lesions on MRI. The acute symptoms resolved after treatment with intravenous steroids and IVIG. Subsequently, the patient was initiated on an indefinite maintenance IVIG regimen. Visual acuity in all patients improved to their baseline levels following treatment.

This series highlights the emerging overlap between anti-NMDAR encephalitis and MOGAD optic neuritis. Optic neuritis may occur months to years after encephalitis, underscoring the need for careful monitoring of patients with anti-NMDAR encephalitis who develop new visual symptoms. Dual autoimmunity may represent a distinct phenotype with implications for long-term immunotherapy.