Thymoma-associated stiff-person spectrum disorder with multiple autoantibodies: a case report with longitudinal follow-up

Abstract Background: Thymoma-associated stiff-person spectrum disorder (SPSD) with anti-glycine receptor (GlyR) antibodies is exceedingly rare, and evidence guiding its management remains limited. Case presentation: A 49-year-old woman with a type B1 thymoma presented with one month of progressive dysphagia, bilateral ptosis, restricted eye movement, and lower-limb stiffness. Anti-GlyR1-IgG, anti-GAD65-IgG, and anti-GAD67-IgG were detected in both serum and cerebrospinal fluid, with additional muscle-type anti-acetylcholine receptor (AChR)-IgG positivity in serum, and electrophysiology demonstrated widespread neuromuscular junction involvement. Thymectomy followed by first-line immunotherapy (corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil) produced only partial improvement. An individualized low-dose rituximab regimen (500 mg every 6 months) was then initiated. Over 24 months and five infusions, anti-GlyR1-IgG and AChR-IgG became undetectable, whereas anti-GAD65/67-IgG persisted and rose modestly (GAD65 from 1:100 to 1:300) without clinical worsening. Independent ambulation was achieved on July 11, 2024, and the patient remained relapse-free during follow-up. Persistent hypogammaglobulinemia developed, without serious infections. Conclusions: This case highlights the diagnostic complexity of thymoma-associated stiff-person spectrum disorder with multiple autoantibodies. Clinical outcomes and treatment safety should guide the interpretation of serial antibody findings.