Abstract
Objective
To characterize regional brain atrophy patterns, evaluate their association with regional leucine‐rich glioma‐inactivated‐1 (
LGI1
) gene expression, and identify clinical predictors of hippocampal atrophy in LGI1 autoimmune encephalitis (AE).
Methods
This study compared regional brain volumes in LGI1‐AE patients versus age‐ and sex‐matched healthy controls (HC) and Alzheimer's disease (AD) patients.
LGI1
gene expression was derived from the Allen Human Brain Atlas. Multivariable linear regression and generalized linear models were utilized.
Results
A total of 55 LGI1‐AE patients were included. Median age was 68 years (IQR 62.5–74.2 years) at volumetric analysis, after 19 months (IQR 11–45 months) from symptom onset. Compared with HC (
n
= 55) and AD patients (
n
= 55), LGI1‐AE patients had greater regional atrophy of the hippocampus, insula, caudate, and putamen (
p
p
LGI1
gene expression (Spearman
ρ
= 0.7,
p
= 0.005). Severe cognitive deficits at diagnosis (
β
= −0.56;
p
= 0.002) and longer disease duration (
β
= −0.01;
p
= 0.001) independently predicted total hippocampal volume (
R
2
= 0.31).
Interpretation
LGI1‐AE demonstrates a distinct pattern of limbic and striatal atrophy that differs from AD and aligns with regional
LGI1
expression, supporting a model of selective network vulnerability. Greater baseline cognitive impairment and longer disease duration independently associated with hippocampal atrophy, underscoring the potential importance of early diagnosis and treatment to limit structural brain injury. ANN NEUROL 2026