Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies

Item Type:	Article
Title:	Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies
Creators Name:	Finke, C. and Prüss, H. and Heine, J. and Reuter, S. and Kopp, U.A. and Wegner, F. and Then Bergh, F. and Koch, S. and Jansen, O. and Münte, T. and Deuschl, G. and Ruprecht, K. and Stöcker, W. and Wandinger, K.P. and Paul, F. and Bartsch, T.
Abstract:	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 Charite-Universitaetsmedizin 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.
Keywords:	Autoantibodies, Basal Ganglia, Cognition Disorders, Cross-Sectional Studies, Disability Evaluation, HEK293 Cells, Hippocampus, Immunotherapy, Limbic Encephalitis, Longitudinal Studies, Magnetic Resonance Imaging, Neuropsychological Tests, Proteins, Retrospective Studies
Source:	JAMA Neurology
ISSN:	2168-6149
Publisher:	American Medical Association
Volume:	74
Number:	1
Page Range:	50-59
Date:	January 2017
Official Publication:	https://doi.org/10.1001/jamaneurol.2016.4226
PubMed:	View item in PubMed

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