LGI1 Encephalitis and IgG4-Related Disease: Rare Conditions Collide

Abstract

Objectives: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis and IgG4-related disease (IgG4RD) have traditionally been regarded as 2 distinct disease entities.

Methods: We detail the presentation, investigations, and management of a patient who showed typical signs and symptoms of LGI1 encephalitis and also found to possess pancreatic changes and a serum profile in keeping with IgG4RD.

Results: Serum and CSF analyses at presentation showed a significant hyponatraemia (117 mmol/L), elevated IgG4 concentration (1.73 g/L), and the presence of LGI1 antibodies. MRI revealed symmetrical diffuse T2-weighted hyperintensity and mild swelling throughout both medial temporal lobes. CT of the chest, abdomen and pelvis revealed an edematous, bulky pancreas with loss of lobulation, typical for IgG4RD. A glucocorticoid weaning regimen was commenced, facilitated by 2 rituximab infusions, with the patient showing an effective treatment response. HLA testing confirmed the presence of HLA DRB1 and HLA DQB1 risk alleles.

Discussion: This case suggests that there may be shared mechanisms between LGI1 encephalitis and IgG4RD, supported by common risk HLA associations and treatment strategies/responses. To our knowledge, this represents the first instance that LGI1 encephalitis and IgG4RD have been reported in the same patient and emphasizes the continued development of our understanding of the wide range of IgG4-mediated conditions.

Figure 1. MRI Brain Imaging

Axial fluid-attenuated inversion recovery (FLAIR) MRI sequences (A, B) at presentation demonstrating T2-weighted hyperintensity in the ventral right putamen (A, arrow) and in both medial temporal lobes (B, arrows). Coronal T1-weighted image displays corresponding mildly increased T1-weighted signal in the ventral right putamen (C, with magnified bottom panel). Axial postcontrast T1-weighted image shows asymmetric abnormal enhancement of the right hippocampus (D, with magnified panel). Repeat FLAIR (E, F) and susceptibility-weighted sequences (G) 6 months after presentation and therapy shows regression of prior abnormal high T2-weighted signal (E, F) with new mild volume loss in the affected regions and new mineralization of the ventral right putamen (G, arrow). FDG-PET/CT performed 3 weeks into presentation (and after commencement of corticosteroids) fused with T2-weighted axial MRI (H) demonstrates corresponding asymmetric hypometabolism in the affected ventral right putamen (arrow).

Figure 2. CT of the Chest, Abdomen, and Pelvis Imaging

Axial contrast-enhanced CT portovenous phase imaging of the abdomen at presentation (A) with a magnified panel of the pancreas (B) demonstrates minimal peripancreatic fat stranding and diffuse enlargement of the pancreas with loss of the definition of the pancreatic clefts causing a “sausage-shape” morphology, typical of IgG4-related disease. Repeat CT (C) with a magnified panel (D) 5 months later demonstrates resolution of the fat stranding and reduced pancreatic swelling.