Unmasking Anti-CASPR2 Syndrome in a Patient Treated for Myasthenia Gravis in the Era of New Treatments

Abstract

Introduction: Myasthenia gravis (MG) is an autoimmune disorder characterised by autoantibodies against the acetylcholine receptor (AChR-Ab). Morvan syndrome (MoS) is a rarer autoimmune disease with neuromyotonia, dysautonomia and encephalopathy, associated with antibodies targeting contactin-associated protein-like 2 (CASPR2) and may coexist with MG, particularly in patients with thymoma.

Case report: A 57-year-old man with AChR-Ab MG was treated with pyridostigmine and prednisone for one year and then presented with a severe exacerbation. The symptoms were not controlled despite intravenous immunoglobulins and plasmapheresis. Chest CT revealed a thymoma. Zilucoplan (a C5 complement inhibitor) was started, with rapid improvement. Efgartigimod (a neonatal Fc receptor (FcRn) antagonist) was added to stabilise residual symptoms prior to thymectomy. Three weeks after the third and final efgartigimod cycle, the patient had no symptoms of MG but began to develop profuse sweating, then generalised hypertonia, fasciculations, myoclonus and dysautonomia, consistent with MoS, which were confirmed by the presence of anti-CASPR2 antibodies. Symptoms improved markedly after resumption of efgartigimod.

Conclusion: This case provides the first evidence of the efficacy of efgartigimod in the treatment of MoS and suggests that FcRn inhibition may be beneficial in IgG4-mediated disorders beyond MG. It also highlights the importance of considering coexisting autoimmune conditions in thymoma, particularly when new symptoms occur under selective immune modulation. Finally, it emphasises the need to understand immunopathological mechanisms when choosing immunomodulatory treatment.

Keywords: anti‐CASPR2 autoantibody; autoimmunity; complement C5; myasthenia gravis; neonatal Fc receptor.