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Research paper
Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease
  1. Frank Leypoldt1,
  2. Ralph Buchert2,
  3. Ingo Kleiter3,
  4. Jörg Marienhagen4,
  5. Mathias Gelderblom1,
  6. Tim Magnus1,
  7. Josep Dalmau5,
  8. Christian Gerloff1,
  9. Jan Lewerenz6
  1. 1Department of Neurology, University Medical Center Eppendorf, Hamburg, Germany
  2. 2Department of Nuclear Medicine, Charité, Berlin, Germany
  3. 3Department of Neurology, St Josef-Hospital, Ruhr University Bochum, Bochum, Germany
  4. 4Department of Nuclear Medicine, University Medical Center Regensburg, Regensburg, Germany
  5. 5Department of Neurology, IDIBAPS/Hospital Clinic, University of Barcelona, Barcelona, Spain
  6. 6Department of Neurology, University Hospital Ulm, Ulm, Germany
  1. Correspondence to Dr Frank Leypoldt, Department of Neurology, University Medical Center Eppendorf, Martinistr 52, Hamburg 20246, Germany; f.leypoldt{at} Dr Jan Lewerenz, Department of Neurology, Oberer Eselsberg 45, 89081 Ulm, Germany; jan.lewerenz{at}


Background Patients with encephalitis associated with antibodies against N-methyl-D-aspartate-receptor antibody (NMDAR-ab) encephalitis frequently show psychotic symptoms, amnesia, seizures and movement disorders. While brain MRI in NMDAR-ab encephalitis is often normal, abnormalities of cerebral glucose metabolism have been demonstrated by positron emission tomography (PET) with 18F-fluorodeoxyglucose(FDG) in a few usually isolated case reports. However, a common pattern of FDG-PET abnormalities has not been reported.

Methods The authors retrospectively identified six patients with NMDAR-ab encephalitis in two large German centres who underwent at least one whole-body FDG-PET for tumour screening between January 2007 and July 2010. They analysed the pattern of cerebral uptake derived from whole-body PET data for characteristic changes of glucose metabolism compared with controls, and the changes of this pattern during the course of the disease.

Results Groupwise analysis revealed that patients with NMDAR-ab encephalitis showed relative frontal and temporal glucose hypermetabolism associated with occipital hypometabolism. Cross-sectional analysis of the group demonstrated that the extent of these changes is positively associated with clinical disease severity. Longitudinal analysis of two cases showed normalisation of the pattern of cerebral glucose metabolism with recovery.

Conclusions A characteristic change in cerebral glucose metabolism during NMDAR-ab encephalitis is an increased frontotemporal-to-occipital gradient. This pattern correlates with disease severity. Similar changes have been observed in psychosis induced by NMDAR antagonists. Thus, this pattern might be a consequence of impaired NMDAR function.

  • encephalitis
  • NMDA
  • limbic encephalitis
  • brain glucose metabolism
  • immunology
  • paraneoplastic syndrome
  • neurooncology
  • neurogenetics
  • neuroimmunology
  • multiple sclerosis
  • neurochemistry
  • neurobiology

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  • FL and RB contributed equally to the manuscript.

  • Competing interests FL received honoraria from Abbot and Talecris and research support from the Werner-Otto-Stiftung. IK received speaker honoraria and travel reimbursements from Bayer Healthcare, Biogen Idec, Merck Serono and Novartis, and research funding from Bayer Healthcare and Deutsche Forschungsgesellschaft. JM received honoraria from PETNet, Erlangen, Germany and research support from the Bayerisches Wissenschaftsministerium and BMBF. MG received honoraria from Biogen Idec and research funding from the Landesexzellenzinitiative Hamburg. TM received honoraria from Talecris and research support from the Werner-Otto-Stiftung and Landesexzellenzinitiative Hamburg. JD received royalties from the editorial board of Up-To-Date; from Athena Diagnostics for a patent for the use of Ma2 as autoantibody test. He has received a research grant from Euroimmun, and his contribution to the current work was supported in part by grants from the National Institutes of Health and National Cancer Institute RO1CA89054, 1RC1NS068204-01, and a McKnight Neuroscience of Brain Disorders award. CG received research funding from the Deutsche Forschungs Gemeinschaft. JL received research support by the Thyssen Stiftung. RB discloses no conflicts of interest.

  • Patient consent Standardised patient consent forms were signed by all patients and controls.

  • Ethics approval This is a retrospective case series. Written permission was obtained from all patients and controls. Therefore, no Ethics Committee approval was obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.