Case Report: Anti-LGI1 encephalitis during FcRn inhibition with efgartigimod for myasthenia gravis: implications for the limitations of IgG recycling blockade.

OBJECTIVES

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated autoimmune encephalitis is a treatable disorder characterized by subacute cognitive impairment. Efgartigimod is a neonatal Fc receptor (FcRn) antagonist that reduces circulating IgG levels. It is approved for the treatment of generalized myasthenia gravis (MG) and has recently been explored as a therapeutic option for antibody-mediated neurological diseases. We report a patient who developed anti-LGI1 antibody-associated encephalitis during ongoing efgartigimod therapy despite reduced serum IgG levels, raising considerations regarding the mechanisms of central nervous system autoimmunity under FcRn inhibition.

METHODS

A 72-year-old woman with thymoma-associated MG receiving efgartigimod was evaluated after presenting with rapidly progressive memory impairment. Clinical assessment included neurological examination, brain magnetic resonance imaging, cerebrospinal fluid analysis, and serological testing for neuronal and paraneoplastic antibodies.

RESULTS

Brain magnetic resonance imaging revealed bilateral medial temporal lobe hyperintensities. Cerebrospinal fluid analysis showed negative LGI1 antibodies and a normal IgG index (0.524), with no evidence suggestive of intrathecal IgG synthesis. Subsequent serological testing confirmed anti-LGI1 antibody positivity, and anti-titin antibodies were also detected. High-dose intravenous methylprednisolone therapy resulted in marked clinical improvement.

DISCUSSION: This case highlights a clinically relevant scenario in which autoimmune encephalitis can arise during FcRn inhibition therapy, suggesting that reduction of circulating IgG alone may be insufficient to prevent central nervous system autoimmunity. The absence of intrathecal IgG synthesis raises the possibility that pathogenic antibodies were predominantly derived from the peripheral compartment. These findings underscore the pharmacodynamic limitations of FcRn inhibition, particularly in the setting of thymoma-associated immune dysregulation.