Periventricular [11C]flumazenil binding for predicting postoperative outcome in individual patients with temporal lobe epilepsy and hippocampal sclerosis

Abstract

A third of patients with intractable temporal lobe epilepsy and hippocampal sclerosis (HS) are not seizure free (NSF) after surgery. Increased periventricular [11C]flumazenil (FMZ) binding, reflecting heterotopic neuron concentration, has been described as one predictor of NSF outcome at the group level. We aimed to replicate this finding in an independent larger cohort and investigated whether NSF outcome can be predicted in individuals.Preoperative [11C]FMZ summed radioactivity images were available for 16 patients with HS and 41 controls. Images were analyzed using SPM8, explicitly including the white matter, and correction for global radioactivity via group-specific ANCOVA. Periventricular increases were assessed with a mask and different cutoffs for distinguishing NSF and seizure free (SF) patients.NSF patients had increased [11C]FMZ binding around the posterior horn of the ventricles ipsilaterally (z = 2.53) and contralaterally (z = 4.44) to the seizure focus compared with SF patients. Compared with controls, SF patients had fewer periventricular increases (two clusters, total volume 0.87 cm3, zmax = 3.8) than NSF patients (two ipsilateral and three contralateral clusters, 6.15 cm3, zmax = 4.8). In individuals and at optimized cutoffs, five (63%) of eight NSF patients and one (13%) of eight SF patients showed periventricular increases compared with controls (accuracy 75%). Only one (2%) of the 41 controls had increases at the same cutoff.The association between periventricular [11C]FMZ increases and NSF outcome after temporal lobe resection for HS has been confirmed in an independent cohort on simple summed activity images. [11C]FMZ-PET may be useful for individual preoperative counseling with clinically relevant accuracy.

Advanced [18F]FDG and [11C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis

“…Patient details have been described in a previous study on [ 11 C]FMZ PET alone ( Yankam Njiwa et al, 2013 ). Briefly, sixteen patients (twelve women) fulfilled the criteria.…”

“…FMZ (RO 15-1788) was radiolabelled with 11 C via methylation ( Maziere et al, 1984 ). Unlabelled FMZ (0.01 mg/kg) and [ 11 C]FMZ (2.775 MBq/kg) were injected simultaneously ( Delforge et al, 1995 ), and twelve frames of increasing length were acquired over 55 min (for details, see ( Yankam Njiwa et al, 2013 )). Summed [ 11 C]FMZ radioactivity images were obtained from the attenuation and scatter corrected dynamic 3D series over the last five frames (20–55 min post injection), as these have been shown to yield particularly reliable measures ( Bouvard et al, 2012 ).…”

“…[ 11 C]FMZ summed radioactivity images and static [ 18 F]FDG images were first analysed using statistical parametric mapping (SPM8; Wellcome Department of Imaging Neuroscience, UCL, London, UK; http://www.fil.ion.ucl.ac.uk/spm ) and specific periventricular masks ( Hammers et al, 2005 ; Yankam Njiwa et al, 2013 ). Voxel-wise PET signal intensities across the whole brain were then used for RF classification.…”

“…Previous studies have shown that increased preoperative periventricular white matter (WM) FMZ binding was associated with NSF outcome after temporal lobe resection for HS. This was shown at the group level using volume-of-distribution images ( Hammers et al, 2005 ) and, with a larger control group, at the individual level using summed images ( Yankam Njiwa et al, 2013 ). The tentative explanation for this association is that increased periventricular binding relates to heterotopic neurons, i.e.…”

Neuroimaging of epilepsy

“…In patients with normal MRI, about 40% had reduced 11 C-FMZ binding, a proportion similar to FDG-PET (Lamusuo et al, 2000). One group has found that increased periventricular FMZ binding may identify potentially epileptogenic heterotopias in patients with temporal-lobe foci and MTS, that may account in some cases for poor outcome after temporal lobectomy (Yankam-Njiwa et al, 2013). FMZ PET can also help elucidate the pathophysiology of epilepsy syndromes.…”