title: Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies.
abstract: OBJECTIVE
  Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.
  
  
  OBJECTIVE
  To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs.
  
  
  METHODS
  Retrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study.
  
  
  METHODS
  Analysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals.
  
  
  RESULTS
  Eight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor.
  
  
  CONCLUSIONS
  Patients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.
authors.affiliation: Service of Neurology, Hospital Clinic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Ariño
authors.affiliation: Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain3Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.affiliation: Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain4Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nuria
authors.initials: N
authors.lastname: Gresa-Arribas
authors.affiliation: Service of Neurology, Hospital Clinic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martínez-Hernández
authors.affiliation: Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Thaís
authors.initials: T
authors.lastname: Armangue
authors.affiliation: Sanford Children's Health Research Center, Sioux Falls, South Dakota.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kruer
authors.affiliation: Service of Neurology, Hospital La Paz, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Arpa
authors.affiliation: Service of Neurology, Hospital Severo Ochoa, Leganés, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Domingo
authors.affiliation: Service of Neurology, General Hospital Izola, Izola, Slovenia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Rojc
authors.affiliation: Service of Neurology, University Hospital Politècnic La Fe, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bataller
authors.affiliation: Service of Neurology, Hospital Clinic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain10Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain11Department of Neurology, University of Pennsylvania, Philadelphia.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: Service of Neurology, Hospital Clinic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D020361:Paraneoplastic Syndromes, Nervous System / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D012189:Retrospective Studies; D012737:Sex Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase