title: Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany2Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany3Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Finke
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany4German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Heine
authors.affiliation: Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ute A
authors.initials: UA
authors.lastname: Kopp
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
authors.affiliation: Department of Neurology, University of Leipzig, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Then Bergh
authors.affiliation: Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany8Medical Student, Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Koch
authors.affiliation: Institute of Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Olav
authors.initials: O
authors.lastname: Jansen
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münte
authors.affiliation: Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany11Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Institute for Experimental Immunology, Euroimmun AG, Lübeck, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Lübeck, Germany13Institute of Clinical Chemistry, Neuroimmunology Unit, University Hospital Schleswig-Holstein, Lübeck, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Wandinger
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany3Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany11Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany14Neurocure Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany15Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Neurology, Memory Disorders and Plasticity Group, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bartsch
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001479:Basal Ganglia / Q000000981:diagnostic imaging; D003072:Cognition Disorders / Q000209:etiology*; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D005260:Female; D057809:HEK293 Cells / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging*; D006801:Humans; D007167:Immunotherapy; D047908:Intracellular Signaling Peptides and Proteins; D020363:Limbic Encephalitis / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000628:therapy; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011506:Proteins / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins