title: Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.
abstract: OBJECTIVE
  Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI).
  
  
  METHODS
  Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance.
  
  
  RESULTS
  We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well.
  
  
  CONCLUSIONS
  The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter.
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.|Department of NeuroCognition/Imaging, Life & Brain Center, Bonn, Germany.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0002-0459-8885
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.|Department of NeuroCognition/Imaging, Life & Brain Center, Bonn, Germany.|Department of Pediatrics, Klinikum Braunschweig, Braunschweig, Germany.
authors.forename: Jan-Christoph
authors.initials: JC
authors.lastname: Schoene-Bake
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Juri-Alexander
authors.initials: JA
authors.lastname: Witt
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Helmstaedter
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.|Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Malter
authors.affiliation: Institute of Experimental Immunology, affiliated with Euroimmun AG Luebeck, Luebeck, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Stoecker
authors.affiliation: Institute of Experimental Immunology, affiliated with Euroimmun AG Luebeck, Luebeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.|Department of NeuroCognition/Imaging, Life & Brain Center, Bonn, Germany.|Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Weber
authors.affiliation: Department of Epileptology, University of Bonn, Bonn, Germany.|Department of NeuroCognition/Imaging, Life & Brain Center, Bonn, Germany.|Center for Economics and Neuroscience, University of Bonn, Bonn, Germany.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D020363:Limbic Encephalitis / Q000175:diagnosis* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D024642:Potassium Channels, Voltage-Gated; D005968:Glutamate Decarboxylase
keywords: Diffusion tensor imaging; Epilepsy; MRI; Tract-based spatial statistics