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J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1150-7. doi: 10.1136/jnnp-2014-309897. Epub 2015 May 19.

NMDA receptor binding in focal epilepsies.

Author information

1
Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Medical Research Council Clinical Sciences Centre, London, UK Division of Imaging Sciences & Biomedical Engineering, Faculty of Life Sciences & Medicine, King's College London, London, UK.
2
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK.
3
Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Medical Research Council Clinical Sciences Centre, London, UK Division of Imaging Sciences & Biomedical Engineering, Faculty of Life Sciences & Medicine, King's College London, London, UK Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK MRI Unit, Epilepsy Society, Chalfont St. Peter, UK The Neurodis Foundation, CERMEP Imagerie du Vivant, Lyon, France.
4
Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Medical Research Council Clinical Sciences Centre, London, UK.
5
Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Trust, London, UK.
6
GE Healthcare plc, The Grove Centre, Amersham, UK.
7
National Hospital for Neurology and Neurosurgery, London, UK.
8
Division of Neuroscience, Department of Medicine, Imperial College London, London, UK Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Abstract

OBJECTIVE:

To demonstrate altered N-methyl-d-aspartate (NMDA) receptor availability in patients with focal epilepsies using positron emission tomography (PET) and [(18)F]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 [(18)F]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 [(18)F]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 [(18)F]GE-179 VT (+28%; p<0.002), and the three patients taking an antidepressant drug had globally reduced [(18)F]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 [(18)F]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. [(18)F]GE-179 PET showed focal accentuations of NMDA binding in 4 out of 11 patients, with difficult to localise and treat focal epilepsy.

KEYWORDS:

DEPRESSION; EPILEPSY; NMDA; PET

Comment in

PMID:
25991402
PMCID:
PMC4602274
DOI:
10.1136/jnnp-2014-309897
[Indexed for MEDLINE]
Free PMC Article

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