Is central benzodiazepine receptor imaging useful for the identification of epileptogenic foci in localization-related epilepsies?

Abstract

In the presurgical evaluation of patients with partial epilepsies, the most extensively studied functional neuro-imaging modality to define the origin of seizure onset is fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Generally, this technique reveals a widespread zone of interictal glucose hypometabolism in the region of the epileptogenic focus. However, the technique may miss the epileptogenic region and FDG PET abnormalities may extend beyond the seizure onset zone. Consequently, for the precise identification of epileptogenic regions more specific imaging probes than FDG are warranted. This review considers the clinical utility of iomazenil (IMZ) SPET and flumazenil (FMZ) PET for the precise localization of epileptogenic foci in partial epilepsy syndromes.

Neuroimaging in animal models of epilepsy

“…Application of this model to KASE rats during the chronic epilepsy phase (6 weeks after SE) revealed a decrease in the GABA A /cBZ receptor density in the hippocampus in vivo (Vivash et al, 2014). This is consistent with previous post-mortem studies in epilepsy models (Vivash et al, 2011) and several clinical studies in focal epilepsy (Goethals et al, 2003). In a clinical follow-up study, decreased binding of 18 F-FMZ in the epileptogenic zone of patients with TLE or extra-temporal epilepsy appeared to be more confined than that observed with FDG-PET (Vivash et al, 2013).…”

Sudden Onset Panic: Epileptic Aura or Panic Disorder?

“…49 It has not yet been proven that either of the available benzodiazepine ligands is more accurate for delineation of the seizure focus than the functional imaging techniques already in clinical use (as detailed above). 48,[50][51][52] There are promising indications. When hippocampal sclerosis was present, the area of abnormality was often larger on FDG-PET than on FMZ-PET, which more closely matched the epileptogenic zone as determined by intracranial EEG.…”

“…46,47 Ligands for the central benzodiazepine-GA-BA A receptor suitable for both PET (C 11 flumazenil, FMZ) and SPECT (I 123 iomazenil, IMZ) studies are available, although neither is yet approved for clinical use in the United States. 48 Temporal Lobe Epilepsy Reduced benzodiazepine receptor binding has been demonstrated (by autoradiography) in surgically resected specimens from temporal lobe epilepsy patients. 49 It has not yet been proven that either of the available benzodiazepine ligands is more accurate for delineation of the seizure focus than the functional imaging techniques already in clinical use (as detailed above).…”

Selective Antagonism of GABAA Receptor Subtypes: An In Vivo Approach to Exploring the Therapeutic and Side Effects of Benzodiazepine–Type Drugs

“…4243 With respect to the latter, use of [HC]flumazenil or [125I]iomazenil has been proposed as a potential diagnostic tool for identifying focal seizure points not detectable by conventional imaging methods. 42 Both flumazenil and iomazenil are non-selective BZ antagonists; therefore, a radiotracer derived from PCCT or a similar GABA A ai-preferring antagonist may have considerable potential as both an experimental and clinical diagnostic tool. Currently, no subtypeselective radiotracer is available, and a HC-labelled form of zolpidem proved unsuitable for development due to pharmacokinetic issues.…”