Efgartigimod treatment for therapy-refractory autoimmune encephalitis with coexistent NMDAR and LGI1 antibodies: a case report and literature review

Abstract

The Fc receptor (FcRn) inhibitors can ameliorate autoimmune conditions such as myasthenia gravis through a rapid and specific clearance of serum IgG levels, and they also have potential for future use in a wider variety of antibody-mediated autoimmune diseases. Some patients with therapy-refractory autoimmune encephalitis (AE) continue to be unresponsive to initial and secondary treatment regimens. A 32-year-old male presented with predominant psychiatric symptoms and seizures, along with imaging evidence indicating multifocal cerebral cortical involvement. Neural antibody testing revealed dual positivity for N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) antibodies in both serum and cerebrospinal fluid (CSF). Human leukocyte antigen (HLA) genotyping revealed the presence of the DQB1*03:01 and DQB1*06:01 alleles in the patient. Treatment with efgartigimod, the FcRn inhibitor, led to significant clinical improvements accompanied by a significant decrease in both anti-NMDAR and anti-LGI1 antibody levels. Herein, we report a rare case of therapy-refractory anti-NMDAR AE coexisting with positive LGI1 antibodies. Efgartigimod demonstrates promising potential for treating antibody-mediated AE. Clinical trial number Not applicable.

Keywords: Anti-leucine-rich glioma-inactivated 1; Autoimmune encephalitis; Efgartigimod; N-methyl-D-aspartate receptor; Treatment.

Fig. 1

Brain magnetic resonance imaging. A and B Brain MRI shows T2/FLAIR and DWI signal hyperintensities involving multiple cortical areas of the right temporal, occipital and parietal lobes (arrow). C and D T2/FLAIR and contrast-enhanced MRI four months after symptom onset showed no specific abnormalities in the cerebral cortex

Fig. 2

Overview of patient’s disease history. Patient’s clinical course after initiation of immunotherapy. The graphic illustration depicts patient’s course of modified Rankin Scale, duration of mechanical ventilation, as well as the history of infections with administered antibiotic and antiviral therapies

Fig. 3

N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) antibodies in serum and CSF validated by cell-based assays. NMDAR-IgG levels in serum (A, 1:100) and CSF (B, 1:32) at disease onset, and in serum (E, 1:32) and CSF (F, 1:10) over two weeks after efgartigimod treatment initiation. LGI1-IgG levels in serum (C, 1:10) and CSF (D, 1:1) at disease onset, and in serum (G, 1:10) and CSF (H, negative) over two weeks after efgartigimod treatment initiation