Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies

JAMA Neurol. 2017 Jan 1;74(1):50-59. doi: 10.1001/jamaneurol.2016.4226.


Importance: Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood.

Objective: To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis.

Design, setting, and participants: A cross-sectional study was conducted at the Departments of Neurology at Charité-Universitätsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015.

Main outcomes and measures: Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy).

Results: Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P < .001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; P < .001) memory deficits. These deficits were accompanied by pronounced hippocampal atrophy, including subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as impaired hippocampal microstructural integrity. Higher disease severity correlated with larger verbal memory deficits (RAVLT delayed recall, r = -0.40; P = .049), decreased volumes of left hippocampus (r = -0.47; P = .02) and left CA2/3 (r = -0.41; P = .04) and CA4/DG (r = -0.43; P = .03) subfields, and impaired left hippocampal microstructural integrity (r = 0.47; P = .01). In turn, decreased volume of the left CA2/3 subfield (RAVLT delayed recall, r = 0.40; P = .047) and impaired left hippocampal microstructural integrity (RAVLT recognition, r = -0.41; P = .04) correlated with verbal memory deficits. Basal ganglia MRI signal abnormalities were observed in only 1 patient, but a longer duration of faciobrachial dystonic seizures correlated with a reduction of pallidum volume (r = -0.71; P = .03). In contrast, no abnormalities of cortical gray matter or white matter were found. The latency between disease onset and initiation of immunotherapy was significantly correlated with verbal (RAVLT recall after interference, r = -0.48; P = .02) and visuospatial (ROCF delayed recall, r = -0.46; P = .03) memory deficits.

Conclusions and relevance: Anti-LGI1 encephalitis is associated with cognitive deficits and disability as a result of structural damage to the hippocampal memory system. This damage might be prevented by early immunotherapy.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Autoantibodies / blood*
  • Basal Ganglia / diagnostic imaging
  • Cognition Disorders / etiology*
  • Cross-Sectional Studies
  • Disability Evaluation
  • Female
  • HEK293 Cells / metabolism
  • Hippocampus / diagnostic imaging*
  • Humans
  • Immunotherapy
  • Intracellular Signaling Peptides and Proteins
  • Limbic Encephalitis* / blood
  • Limbic Encephalitis* / complications
  • Limbic Encephalitis* / diagnostic imaging
  • Limbic Encephalitis* / therapy
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Proteins / immunology*
  • Retrospective Studies


  • Autoantibodies
  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Proteins