title: Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report.
abstract: BACKGROUND
  Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described in 2005 in association with ovarian teratoma. The diagnostic workup of this common autoimmune encephalitis includes cerebrospinal fluid analysis, electroencephalography, magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). In addition to standard diagnostics, we performed metabolic investigations using proton magnet resonance spectroscopy ((1)H-MRS).
  
  
  METHODS
  We describe the case of a non-limbic anti-NMDAR encephalitis with a long course of disease (21 months). Laboratory diagnostics showed antibodies against NMDAR; an MRI revealed unspecific findings. (1)H-MRS indicated a hypoglutamatergic state in the left prefrontal cortex associated with a left hemispherical hypometabolism on FDG-PET. Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms. Clinical improvement developed in parallel with remarkable normalization of cerebral glucose metabolism on FDG-PET.
  
  
  CONCLUSIONS
  This case of long-lasting extra-limbic anti-NMDAR encephalitis is of high clinical relevance. First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms. Second, it provides valuable insights into the pathophysiology of such anti-NMDAR encephalitis; these insights prove that anti-NMDAR encephalitis is linked not only to hyperglutamatergic signals but also to hypoglutamatergic states. These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.
authors.affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. dominique.endres@uniklinik-freiburg.de.|Freiburg Brain Imaging, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. dominique.endres@uniklinik-freiburg.de.
authors.forename: Dominique
authors.initials: D
authors.lastname: Endres
authors.affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. evgeniy.perlov@uniklinik-freiburg.de.|Freiburg Brain Imaging, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. evgeniy.perlov@uniklinik-freiburg.de.
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Perlov
authors.affiliation: Department of Neurology, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. oliver.stich@uniklinik-freiburg.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stich
authors.affiliation: Department of Neurology, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. sebastian.rauer@uniklinik-freiburg.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rauer
authors.affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. simon.maier@uniklinik-freiburg.de.|Freiburg Brain Imaging, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. simon.maier@uniklinik-freiburg.de.
authors.forename: Simon
authors.initials: S
authors.lastname: Maier
authors.affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. z.waldkircher@park-klinikum.de.
authors.forename: Zora
authors.initials: Z
authors.lastname: Waldkircher
authors.affiliation: Department of Radiology, Medical Physics, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. thomas.lange@uniklinik-freiburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department of Neuroradiology, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. irina.mader@uniklinik-freiburg.de.
authors.forename: Irina
authors.initials: I
authors.lastname: Mader
authors.affiliation: Department of Nuclear Medicine, University Medical Center Freiburg, Hugstetter Str. 64, 79106, Freiburg, Germany. philipp.meyer@uniklinik-freiburg.de.
authors.forename: Philipp Tobias
authors.initials: PT
authors.lastname: Meyer
authors.affiliation: Section of Experimental Neuropsychiatry, Department for Psychiatry& Psychotherapy, University Medical Center Freiburg, Hauptstr. 5, 79104, Freiburg, Germany. tebartzvanelst@uniklinik-freiburg.de.|Freiburg Brain Imaging, University Medical Center Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. tebartzvanelst@uniklinik-freiburg.de.
authors.forename: Ludger Tebartz
authors.initials: LT
authors.lastname: van Elst
mesh_terms: D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D001323:Autoantibodies / Q000378:metabolism; D001379:Azathioprine / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000627:therapeutic use; D064847:Multimodal Imaging / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use; D049268:Positron-Emission Tomography / Q000379:methods; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D001379:Azathioprine; D008775:Methylprednisolone