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In vivo metabotropic glutamate receptor type 5 abnormalities localize the epileptogenic zone in mesial temporal lobe epilepsy
Author(s) -
Lam Jack,
DuBois Jonathan M.,
Rowley Jared,
GonzálezOtárula Karina A.,
Soucy JeanPaul,
Massarweh Gassan,
Hall Jeffery A.,
Guiot MarieChristine,
RosaNeto Pedro,
Kobayashi Eliane
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25404
Subject(s) - epilepsy , temporal lobe , hippocampus , medicine , positron emission tomography , pathology , nuclear medicine , neuroscience , psychology
Objective Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole‐brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [ 11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site. Methods Thirty‐one unilateral MTLE patients and 30 healthy controls underwent [ 11 C]ABP688 PET. We compared partial volume corrected [ 11 C]ABP688 nondisplaceable binding potentials (BP ND ) between groups using region‐of‐interest and whole‐brain voxelwise analyses. [ 18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [ 11 C]ABP688 BP ND and [ 18 F]FDG uptake to compare lateralization and localization differences. Results [ 11 C]ABP688 BP ND was focally reduced in the epileptogenic hippocampal head and amygdala ( p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex ( p = 0.006). [ 11 C]ABP688 BP ND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [ 18 F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow‐up, 13 were seizure‐free (Engel Ia) and showed significantly lower [ 11 C]ABP688 BP ND in the ipsilateral entorhinal cortex. Interpretation [ 11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [ 18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1–11 ANN NEUROL 2019;85:218–228.