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Epilepsy
Research paper
NMDA receptor binding in focal epilepsies
  1. C J McGinnity1,2,3,
  2. M J Koepp4,5,
  3. A Hammers1,2,3,4,5,6,
  4. D A Riaño Barros1,2,
  5. R M Pressler7,
  6. S Luthra8,
  7. P A Jones8,
  8. W Trigg8,
  9. C Micallef9,
  10. M R Symms4,5,
  11. D J Brooks1,10,
  12. J S Duncan4,5
  1. 1Division of Neuroscience, Department of Medicine, Imperial College London, London, UK
  2. 2Medical Research Council Clinical Sciences Centre, London, UK
  3. 3Division of Imaging Sciences & Biomedical Engineering, Faculty of Life Sciences & Medicine, King's College London, London, UK
  4. 4Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK
  5. 5MRI Unit, Epilepsy Society, Chalfont St. Peter, UK
  6. 6The Neurodis Foundation, CERMEP Imagerie du Vivant, Lyon, France
  7. 7Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Trust, London, UK
  8. 8GE Healthcare plc, The Grove Centre, Amersham, UK
  9. 9National Hospital for Neurology and Neurosurgery, London, UK
  10. 10Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
  1. Correspondence to Professor J S Duncan, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, UK; j.duncan{at}ucl.ac.uk

Abstract

Objective To demonstrate altered N-methyl-d-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [18F]GE-179, a ligand that selectively binds to the open NMDA receptor ion channel, which is thought to be overactive in epilepsy.

Methods Eleven patients (median age 33 years, 6 males) with known frequent interictal epileptiform discharges had an [18F]GE-179 PET scan, in a cross-sectional study. MRI showed a focal lesion but discordant EEG changes in two, was non-localising with multifocal EEG abnormalities in two, and was normal in the remaining seven patients who all had multifocal EEG changes. Individual patient [18F]GE-179 volume-of-distribution (VT) images were compared between individual patients and a group of 10 healthy controls (47 years, 7 males) using Statistical Parametric Mapping.

Results Individual analyses revealed a single cluster of focal VT increase in four patients; one with a single and one with multifocal MRI lesions, and two with normal MRIs. Post hoc analysis revealed that, relative to controls, patients not taking antidepressants had globally increased [18F]GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [18F]GE-179 VT (−29%; p<0.002). There were no focal abnormalities common to the epilepsy group.

Conclusions In patients with focal epilepsies, we detected primarily global increases of [18F]GE-179 VT consistent with increased NMDA channel activation, but reduced availability in those taking antidepressant drugs, consistent with a possible mode of action of this class of drugs. [18F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy.

  • EPILEPSY
  • PET
  • NMDA
  • DEPRESSION

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/jnnp-2014-309897

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