title: Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic versus GAD65 autoantibody-associated limbic encephalitis.
abstract: To determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies.
  
  
  
  Eleven paraneoplastic-antibodies+ and eleven age- and gender-matched GAD-antibodies+ patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption.
  
  
  
  Immunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies+(55%) as compared to GAD-antibodies+(18%) patients (p<0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies+ and 73% of the GAD-antibodies+ group. After therapy, cognition improved significantly in the paraneoplastic-antibodies+, but not in the GAD-antibodies+ patients (p<0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies+as compared to paraneoplastic-antibodies+patients (p<0.05) over time.
  
  
  
  Our data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies+ subgroup of LE presenting autoantibodies against intracellular antigens.
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany. Electronic address: Niels.Hansen@ukb.uni-bonn.de.
authors.forename: N
authors.initials: N
authors.lastname: Hansen
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Widman
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany.
authors.forename: J-A
authors.initials: JA
authors.lastname: Witt
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany; Epilepsy Centre Hessen-Marburg, Department of Neurology, University of Marburg Medical Centre, Marburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Neuropathology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany.
authors.forename: A J
authors.initials: AJ
authors.lastname: Becker
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany.
authors.forename: C E
authors.initials: CE
authors.lastname: Elger
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Helmstaedter
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000097:blood / Q000276:immunology / Q000628:therapy*; D004827:Epilepsy / Q000097:blood / Q000276:immunology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000097:blood; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D020363:Limbic Encephalitis / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012640:Seizures / Q000097:blood / Q000276:immunology / Q000628:therapy*
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: Epilepsy; GAD65 autoantibodies; Immunotherapy; Limbic encephalitis; Paraneoplastic autoantibodies