title: Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis.
abstract: OBJECTIVE
  Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis.
  
  
  METHODS
  Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry.
  
  
  RESULTS
  Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls.
  
  
  CONCLUSIONS
  Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Finke
authors.forename: Ute A
authors.initials: UA
authors.lastname: Kopp
authors.forename: Michael
authors.initials: M
authors.lastname: Scheel
authors.forename: Luisa-Maria
authors.initials: LM
authors.lastname: Pech
authors.forename: Carina
authors.initials: C
authors.lastname: Soemmer
authors.forename: Jeremias
authors.initials: J
authors.lastname: Schlichting
authors.forename: Frank
authors.initials: F
authors.lastname: Leypoldt
authors.forename: Alexander U
authors.initials: AU
authors.lastname: Brandt
authors.forename: Jens
authors.initials: J
authors.lastname: Wuerfel
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Ploner
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
mesh_terms: D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D056784:Leukoencephalopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D055815:Young Adult