title: Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome.
abstract: OBJECTIVE
  We investigated a series of patients with LGI1 antibody (Ab)-related cognitive deterioration to determine the clinical presentation, long-term outcome, and LGI1 Ab evolution.
  
  
  METHODS
  We retrospectively analyzed the clinical information of 76 patients with LGI1 Ab-related cognitive deterioration. Presenting syndromes were classified as limbic encephalitis (LE), non-LE, or encephalopathy (normal MRI and no CSF pleocytosis). Frequency of relapses and clinical outcome were assessed in 48 patients with prolonged follow-up (median 39 months, range 18-200).
  
  
  RESULTS
  Sixty-three patients (83%) developed LE, 3 (4%) non-LE, and 10 (13%) encephalopathy. All patients received steroids, IV immunoglobulins (Ig), or both. At 2 years, 17 (35%; 95% CI 21%-49%) fully recovered, 17 (35%) became functionally independent but not at baseline or were unable to return to work, 11 (23%) required assistance because of moderate or severe cognitive deficits, and 3 (6%) died. Predictors of bad outcome included no response to initial immunotherapy (odds ratio 23.0, 95% CI 2.4-215.6, p = 0.006) and clinical relapses (odds ratio 10.2, 95% CI 1.0-100.1, p = 0.047) that occurred in 13 patients (27%). In all patients, the LGI1 Abs were IgG4 and usually detectable in both serum and CSF (only CSF, 8%). Abs remained positive in serum of 4 of 16 patients with long-term follow-up; 3 of these 4 patients fully recovered and none showed class switch to IgG1.
  
  
  CONCLUSIONS
  Up to 13% of patients with LGI1 Abs develop cognitive impairment without criteria of encephalitis. After immunotherapy, only 35% of patients return to their baseline cognitive function. Serum LGI1 Abs may remain detectable after full clinical recovery.
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Ariño
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Thais
authors.initials: T
authors.lastname: Armangué
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Petit-Pedrol
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sabater
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martinez-Hernandez
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hara
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Eric
authors.initials: E
authors.lastname: Lancaster
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: From the Neuroimmunology Program (H.A., T.A., M.P.-P., L.S., E.M.-H., M.H., A.S., J.D., F.G.), August Pi Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clínic, University of Barcelona, Spain; Department of Neurology (E.L., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (ICREA) (J.D.), Barcelona, Spain. fgraus@clinic.ub.es.
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D001927:Brain Diseases / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins; D020363:Limbic Encephalitis / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011506:Proteins / Q000276:immunology*; D013256:Steroids / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins; D013256:Steroids