title: Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22 patients.
abstract: OBJECTIVE
  We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).
  
  
  METHODS
  This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic techniques have been reported previously.
  
  
  RESULTS
  Patients' median age was 62 years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5-266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009).
  
  
  CONCLUSIONS
  Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome.
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Agnes
authors.initials: A
authors.lastname: van Sonderen
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Frank
authors.initials: F
authors.lastname: Leypoldt
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: David
authors.initials: D
authors.lastname: Houghton
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Michael
authors.initials: M
authors.lastname: Geschwind
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gelfand
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Paredes
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sabater
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia.
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
authors.affiliation: From the Service of Neurology (R.H., L.S., A.S., F.G.), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain; the Institute of Neurology (R.H.), Medical University of Vienna, Austria; the Department of Neurology (A.v.S., M.J.T.), Erasmus Medical Center, Rotterdam; the Department of Neurology (A.v.S.), Haga Hospital, the Hague, the Netherlands; the Department of Neurology and Institute of Clinical Chemistry (F.L.), University Medical Center Schleswig-Holstein Campus Lübeck, Germany; the Department of Neurology (D.H.), Ochsner Health System, New Orleans, LA; the Memory and Aging Center (M.G., J.G.) and the Department of Neurology (M.P.), University of California, San Francisco; Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), IDIBAPS, Hospital Clínic, Barcelona, Spain; and the Department of Neurology (J.D.), University of Pennsylvania, Philadelphia. jdalmau@clinic.ub.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology; D015897:Comorbidity; D004660:Encephalitis / Q000453:epidemiology* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018091:Receptors, AMPA / Q000276:immunology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2