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18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in presurgical assessment in patients with drug-resistant focal epilepsy (DRE) if magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) do not localize the seizure onset zone or are discordant.In this multicenter, retrospective observational cohort study, we included consecutive patients with DRE who had undergone FDG-PET as part of their presurgical workup. We assessed the utility of FDG-PET, which was defined as contributing to the decision-making process to refer for resection or intracranial EEG (iEEG) or to conclude surgery was not feasible.We included 951 patients in this study; 479 had temporal lobe epilepsy (TLE), 219 extratemporal epilepsy (ETLE), and 253 epilepsy of uncertain lobar origin. FDG-PET showed a distinct hypometabolism in 62% and was concordant with ictal EEG in 74% in TLE and in 56% in ETLE (p .001). FDG-PET was useful in presurgical decision-making in 396 patients (47%) and most beneficial in TLE compared to ETLE (58% vs. 44%, p = .001). Overall, FDG-PET contributed to recommending resection in 78 cases (20%) and iEEG in 187 cases (47%); in 131 patients (33%), FDG-PET resulted in a conclusion that resection was not feasible. In TLE, seizure-freedom 1 year after surgery did not differ significantly (p = .48) between patients with negative MRI and EEG-PET concordance (n = 30, 65%) and those with positive MRI and concordant EEG (n = 46, 68%). In ETLE, half of patients with negative MRI and EEG-PET concordance and three quarters with positive MRI and concordant EEG were seizure-free postsurgery (n = 5 vs. n = 6, p = .28).This is the largest reported cohort of patients with DRE who received presurgical FDG-PET, showing that FDG-PET is a useful diagnostic tool. MRI-negative and MRI-positive cases with concordant FDG-PET results (with either EEG or MRI) had a comparable outcome after surgery. These findings confirm the significance of FDG-PET in presurgical epilepsy diagnostics.

Objective Overexpression of the drug transporter P‐glycoprotein (P‐gp) is thought to be involved in drug‐resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P‐gp substrate radiotracer (R)‐[11C]verapamil (VPM) together with the third‐generation P‐gp inhibitor tariquidar (TQD) to evaluate P‐gp function in individuals with drug‐resistant epileptogenic developmental lesions. Methods Twelve healthy controls (7 male, median age 45, range 35‐55 years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62 years) underwent VPM‐PET scans before and 60 minutes after a 30‐minute infusion of 2 and 3 mg/kg TQD. The influx rate constant, VPM‐K1, was estimated from the first 10 minutes of dynamic data using a single‐tissue compartment model with a VPM plasma input function. Statistical parametric mapping (SPM) analysis was used to compare individual patients with the healthy controls. Results At baseline, SPM voxel‐based analysis revealed significantly lower uptake of VPM corresponding to the area of the epileptogenic developmental lesion compared to 12 healthy controls (P < .048). This was accentuated following P‐gp inhibition with TQD. After TQD, the uptake of VPM was significantly lower in the area of the epileptogenic developmental lesion compared to controls (P < .002). Significance This study provides further evidence of P‐gp overactivity in patients with drug‐resistant epilepsy, irrespective of the type of lesion. Identifying P‐gp overactivity as an underlying contributor to drug‐resistance in individual patients will enable novel treatment strategies aimed at overcoming or reversing P‐gp overactivity.