LAUSR

Introduction Acute encephalitis is a debilitating neurological disorder that manifests a rapidly progressive encephalopathy caused by brain inflammation. One of the antibody revealed limbic encephalitis (LE) is the VGKC-LE, usually occurs around 60s, shows relatively good response to immunotherapy, but sometimes smolders over years. MRI in LE shows signal and volume changes of mesial temporal structures. Studies quantifying volume change in LE are scarce. This study aims to investigate the volumetric changes of the mesial temporal structures and whole brain in patients with smoldering limbic encephalitis associated with VGKC-LE. Methods We studied three VGKC-LE patients (age of onset: 50–65 years old) whom we have followed up from 2008 to 2017 (IRB# C0588-2). Volume of the hippocampi, amygdala, and whole brain was investigated sequentially along the follow-up period (86–103 months) by FreeSurfer software. Results In the subacute phase, the volume of bilateral hippocampi and amygdala normalized to the whole brain volume was above 2 S.D. of that of the age-matched control group. Although the absolute amygdalar volume decreased by 0.5–7.6%/year (control, 0.5–0.9%/year), the normalized amygdalar volume remained at around upper limit. Hippocampal volume decreased by 3.0–5.3%/year (control, 0.8%/year), and reached the lower limit (−2 S.D.) in two patients. In contrast, two patients showed gradual decrease of the whole brain volume, which rate (2.0 or 2.4 %/year) was higher than the control (0.5–0.7%/year). Conclusion The normalized amygdalar volume, although gradually decreasing in size over 5 years, remained at around normal upper limit, suggesting smoldering nature of inflammation. In addition to the hippocampal atrophy with more rapid rate than normal, unexpected whole brain atrophy developed despite repeated immunotherapy in two patients. Optimal treatment without delay based on the surrogate marker, i.e., volumetry, as well as cerebrospinal fluid, EEG, FDG-PET, psychometry findings is necessary. The volumetry is a more sensitive method than visual inspection to detect mild atrophy due to chronic epileptic or inflammatory pathogenesis.