Abstract
Background: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is one of the most prevalent forms of autoimmune encephalitis in the pediatric population. However, its diagnosis remains challenging due to the broad spectrum of clinical manifestations (psychiatric symptoms and seizures most typically) and mainly normal neuroimaging findings. Recent literature has highlighted an association with inflammatory demyelinating disorders, further complicating the differential diagnosis.
Case Description: A 13-year-old girl presented with new-onset epileptic seizures, behavioral disturbances and MRI abnormalities suggestive of a demyelinating disease involving both the brain and spinal cord. Immunosuppressive treatment was initiated, consisting of high-dose corticosteroids and plasma exchange, followed by second-line treatment with rituximab. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibodies were detected in the cerebrospinal fluid (CSF), while all other tested antibodies, including MOG IgG (Myelin Oligodendrocyte Glycoprotein) and AQP4 IgG (Aquaporin-4), were negative in both CSF and serum. Eight months later, the patient experienced a clinical relapse, which responded favorably to repeated rituximab administration. Notably, no symptoms or signs compatible with demyelinating disease were observed throughout the disease course.
Conclusion: Overlapping syndromes involving anti-NMDARE, multiple sclerosis (MS), MOG antibody-associated disease (MOGAD) and AQP4-antibody-negative neuromyelitis optica spectrum disorder (NMOSD) are increasingly recognized in clinical practice. Although these overlap syndromes remain uncommon in the pediatric population, they represent an important diagnostic consideration due to their implications for treatment and prognosis. Spinal cord abnormalities, as observed in this case of an anti-NMDARE-MS overlap syndrome, are particularly rare and underscore the complexity of diagnosing and treating primary autoimmune encephalitis with coexisting demyelinating disorders.
Keywords
Anti-N-methyl-D-aspartate receptor encephalitis, Demyelinating diseases, Overlap syndromes, Spinal lesion