title: The clinical spectrum of Caspr2 antibody-associated disease.
abstract: OBJECTIVE
  To report a large cohort of patients with antibodies against contactin-associated protein-like 2 (Caspr2) and provide the clinical spectrum of this disorder.
  
  
  METHODS
  Serum and CSF samples were assessed at 2 neuroimmunology centers in Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were confirmed with 2 independent techniques, including brain immunohistochemistry and cell-based assay. Clinical information was obtained by the authors or provided by treating physicians after patients' informed consent.
  
  
  RESULTS
  Median age at symptom onset was 66 years. Of 38 patients, 34 were male. Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent syndromes included limbic encephalitis (42%) and Morvan syndrome (29%). Seventy-seven percent of the patients had ≥3 of the following symptoms: encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or weight loss. A tumor, mostly thymoma, occurred in 19% of the patients. Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients and 25% had clinical relapses.
  
  
  CONCLUSIONS
  Caspr2 antibodies associate with a treatable disorder that predominantly affects elderly men. The resulting syndrome may vary among patients but it usually includes a set of well-established symptoms. Recognition of this spectrum of symptoms and consideration of the protracted clinical course are important for early diagnosis of this disorder. Prompt immunotherapy and tumor therapy (if needed) often result in improvement.
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Agnes
authors.initials: A
authors.lastname: van Sonderen
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Ariño
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Petit-Pedrol
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Frank
authors.initials: F
authors.lastname: Leypoldt
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Peter
authors.initials: P
authors.lastname: Körtvélyessy
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Wandinger
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Eric
authors.initials: E
authors.lastname: Lancaster
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wirtz
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Marco W J
authors.initials: MW
authors.lastname: Schreurs
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Peter A E
authors.initials: PA
authors.lastname: Sillevis Smitt
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: From the Departments of Neurology (A.v.S., P.A.E.S.S., M.J.T.) and Immunology (M.W.J.S.), Erasmus University Medical Center, Rotterdam; Department of Neurology (A.v.S., P.W.W.), Haga Teaching Hospital, the Hague, the Netherlands; Department of Neurology (H.A., F.G.), Hospital Clinic, University of Barcelona; Neuroimmunology Program (H.A., M.P.-P., F.G.) and Department of Neurology, Hospital Clinic (J.D.), Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neuroimmunology (F.L.), Institute of Clinical Chemistry, Christian-Albrechts-University; Department of Neurology (F.L.), University Hospital Schleswig-Holstein, Kiel; Department of Neurology (P.K.), University Hospital Magdeburg; Neuroimmunology (K.-P.W), Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein Campus Lübeck; Department of Neurology (K.-P.W), University of Lübeck, Germany; Department of Neurology (E.L.), University of Pennsylvania (J.D.), Philadelphia; and Department of Neurology (J.D.), Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. m.titulaer@erasmusmc.nl.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Titulaer
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D004194:Disease / Q000523:psychology*; D005260:Female; D006801:Humans; D020363:Limbic Encephalitis / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D008875:Middle Aged; D020385:Myokymia / Q000150:complications / Q000175:diagnosis / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D013577:Syndrome
chemical_list: D001323:Autoantibodies; C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins