Neuropsychiatric systemic lupus erythematosus with probable overlapping anti-neurexin-3α antibody-associated encephalitis: a case report

Neuropsychiatric systemic lupus erythematosus (NPSLE) is difficult to diagnose and treat because of its variable clinical manifestations and the lack of specific biomarkers. Anti-neurexin-3α antibody-associated autoimmune encephalitis is rare, and its overlap with NPSLE remains difficult to interpret because antineuronal antibody positivity may also occur within the broader spectrum of NPSLE-related immune dysfunction. We describe a 61-year-old woman with a previous diagnosis of systemic lupus erythematosus who developed acute choreiform involuntary movements of all four limbs, cognitive impairment, and sleep disturbance over one week. Anti-neurexin-3α antibodies were detected in paired serum and cerebrospinal fluid samples. She was treated with high-dose corticosteroids, intravenous immunoglobulin, and cyclophosphamide, and subsequently received telitacicept as SLE-directed maintenance therapy. At the 11-month follow-up, anti-neurexin-3α antibody titers had declined from 1:100 to 1:1 in CSF and from 1:1000 to 1:10 in serum. Involuntary movements and sleep disturbance had completely resolved, and cognitive function showed substantial improvement. This case highlights the diagnostic complexity of anti-neurexin-3α antibody positivity in patients with NPSLE. Although antibody positivity alone is insufficient to establish a distinct autoimmune encephalitis, the paired serum/CSF antibody positivity, tissue-based assay findings, atypical sleep–wake disturbance, and parallel improvement of clinical symptoms and antibody titers support the possibility of overlapping anti-neurexin-3α antibody-associated encephalitic features. Broad neuronal autoantibody screening may provide useful diagnostic information in selected patients with atypical NPSLE presentations, but results should be interpreted in conjunction with clinical features, CSF findings, neuroimaging, exclusion of alternative causes, and treatment response.