title: Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor Encephalitis.
abstract: BACKGROUND
  The majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis suffer from persistent memory impairment despite unremarkable routine clinical magnetic resonance imaging. With improved acute care in these patients, neurocognitive impairment represents the major contributor to long-term morbidity and has thus become a focus of attention.
  
  
  METHODS
  Forty patients with anti-NMDAR encephalitis after the acute disease stage and 25 healthy control subjects underwent multimodal structural imaging that combined volumetry of hippocampal subfields with analysis of hippocampal microstructural integrity. Verbal and visuospatial memory performance was assessed in all patients and correlation and mediation analyses were performed to examine associations between hippocampal structural integrity, memory performance, and disease severity.
  
  
  RESULTS
  Hippocampal volumes were significantly reduced in patients and hippocampal subfield analysis revealed bilateral atrophy of the input and output regions of the hippocampal circuit. Microstructural integrity was impaired in both hippocampi in patients. Importantly, hippocampal volumetric and microstructural integrity measures correlated with memory performance and disease severity and duration. Mediation analysis revealed that hippocampal microstructure mediated the effect of disease severity on memory performance.
  
  
  CONCLUSIONS
  Data from this largest cohort of anti-NMDAR encephalitis patients that underwent extensive multimodal magnetic resonance imaging demonstrate that structural hippocampal damage and associated memory deficits are important long-term sequelae of the encephalitis. Correlation with disease duration and severity highlights the need for rapid diagnosis and adequate immunotherapy to prevent persistent damage to the hippocampus. Advanced imaging protocols may allow a more detailed analysis of structural damage to assess disease progression in clinical routine examinations and for therapy evaluation in prospective trials.
authors: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin; Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin. Electronic address: carsten.finke@charite.de.
authors: Carsten
authors: C
authors: Finke
authors: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin.
authors: Ute A
authors: UA
authors: Kopp
authors: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin.
authors: Anna
authors: A
authors: Pajkert
authors: Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin; Neurocure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin.
authors: Janina R
authors: JR
authors: Behrens
authors: Neuroimmunology Unit, Clinical Chemistry and Neurology, University Hospital Schleswig-Holstein, Kiel.
authors: Frank
authors: F
authors: Leypoldt
authors: Neurocure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin; Institute of Neuroradiology, University Medicine Goettingen, Goettingen; Experimental and Clinical Research Center; Charité-Universitätsmedizin Berlin; Max Delbrueck Center for Molecular Medicine.
authors: Jens T
authors: JT
authors: Wuerfel
authors: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin.
authors: Christoph J
authors: CJ
authors: Ploner
authors: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin; German Center for Neurodegenerative Diseases.
authors: Harald
authors: H
authors: Prüss
authors: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin; Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Berlin; Neurocure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin; Experimental and Clinical Research Center; Charité-Universitätsmedizin Berlin; Max Delbrueck Center for Molecular Medicine; Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Friedemann
authors: F
authors: Paul
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000523:psychology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D065852:Spatial Memory; D055815:Young Adult
keywords: Autoimmune encephalitis; Hippocampus; MRI; Memory; NMDA; NMDA receptor