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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.

ZusammenfassungWährend zwei Drittel der PatientInnen mit Epilepsie durch Medikamente anfallsfrei werden, ist die Erkrankung bei 30 % pharmakoresistent. Bei pharmakoresistenter fokaler Epilepsie bietet die Epilepsiechirurgie eine etwa 65 %ige Chance auf Anfallsfreiheit. Vorab muss der Anfallsfokus exakt eingegrenzt werden, wofür bildgebende Methoden unverzichtbar sind. In den letzten Jahren hat sich in der Prächirurgie der Anteil von PatientInnen mit unauffälliger konventioneller Magnetresonanztomographie (MRT) erhöht. Allerdings konnte die Sensitivität der MRT durch spezielle Aufnahmesequenzen und Techniken der Postprozessierung gesteigert werden. Die Quellenlokalisation des Signals von Elektro- und Magnetenzephalographie (EEG und MEG) verortet den Ursprung iktaler und interiktaler epileptischer Aktivität im Gehirn. Nuklearmedizinische Untersuchungen wie die interiktale Positronen-Emissions-Tomographie (PET) und die iktale Einzelphotonen-Emissionscomputertomographie (SPECT) detektieren chronische oder akute anfallsbezogene Veränderungen des Hirnmetabolismus und können auch bei nichtlokalisierendem MRT auf den epileptogenen Fokus hinweisen. Alle Befunde zusammengenommen werden zur Planung eventueller invasiver EEG-Ableitungen und letztlich der chirurgischen Operation eingesetzt. Konkordante Befunde sind mit besseren chirurgischen Ergebnissen assoziiert und zeigen auch im Langzeitverlauf signifikant höhere Anfallsfreiheitsraten.

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.

While two thirds of patients with epilepsy become seizure-free with antiseizure medications, 30% remain drug-resistant. In drug-resistant focal epilepsy, epilepsy surgery offers an approximately 65% chance of becoming seizure-free; however, for a successful outcome of surgery a seizure focus must be precisely located, for which imaging techniques are essential. In recent years, the proportion of patients with apparently inconspicuous findings in magnetic resonance imaging (MRI) in the presurgical evaluation has increased. The sensitivity of MRI can be increased using special MRI sequences and MRI postprocessing techniques. Ictal and interictal source localization based on electroencephalography (EEG) and magnetencephalography (MEG) aim at determining the onset of interictal discharges and seizures. Nuclear medicine imaging techniques such as interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) can detect chronic or acute seizure-related changes in brain metabolism and can indicate an epileptogenic focus even if MRI is inconspicuous. The results of these techniques are used to plan invasive EEG recordings and subsequently surgery. Concordant findings are associated with better surgical outcomes and show significantly higher rates of seizure freedom in the long-term seizure outcome.Während zwei Drittel der PatientInnen mit Epilepsie durch Medikamente anfallsfrei werden, ist die Erkrankung bei 30 % pharmakoresistent. Bei pharmakoresistenter fokaler Epilepsie bietet die Epilepsiechirurgie eine etwa 65 %ige Chance auf Anfallsfreiheit. Vorab muss der Anfallsfokus exakt eingegrenzt werden, wofür bildgebende Methoden unverzichtbar sind. In den letzten Jahren hat sich in der Prächirurgie der Anteil von PatientInnen mit unauffälliger konventioneller Magnetresonanztomographie (MRT) erhöht. Allerdings konnte die Sensitivität der MRT durch spezielle Aufnahmesequenzen und Techniken der Postprozessierung gesteigert werden. Die Quellenlokalisation des Signals von Elektro- und Magnetenzephalographie (EEG und MEG) verortet den Ursprung iktaler und interiktaler epileptischer Aktivität im Gehirn. Nuklearmedizinische Untersuchungen wie die interiktale Positronen-Emissions-Tomographie (PET) und die iktale Einzelphotonen-Emissionscomputertomographie (SPECT) detektieren chronische oder akute anfallsbezogene Veränderungen des Hirnmetabolismus und können auch bei nichtlokalisierendem MRT auf den epileptogenen Fokus hinweisen. Alle Befunde zusammengenommen werden zur Planung eventueller invasiver EEG-Ableitungen und letztlich der chirurgischen Operation eingesetzt. Konkordante Befunde sind mit besseren chirurgischen Ergebnissen assoziiert und zeigen auch im Langzeitverlauf signifikant höhere Anfallsfreiheitsraten.

To determine long-term seizure outcome, use of antiseizure medication (ASM) and seizure recurrence risk after its withdrawal in patients with autoimmune encephalitis (AE) due to neuronal surface and GAD antibodies.In patients from a specialized AE outpatient clinic, we assessed seizure manifestation, ASM and immunotherapy at onset of AE as well as seizure occurrence, development of autoimmune-associated epilepsy (AAE) and use of ASM in the long-term. Data were collected from patients via telephone interviews and medical records.Out of 94 AE patients, 75 were analyzed; 47 patients had NMDAR, 17 LGI1, 7 GAD, 3 CASPR2 and 1 mGluR5 antibodies. Fifty-three of the 75 patients (71 %) experienced seizures, all of which for the first time occurred at AE onset. After a median follow-up of 6 years (range, 1-15), 47 of the 53 AE patients had 1-year terminal seizure remission, median duration of terminal seizure freedom was 5 years. Rate of 1-year terminal seizure remission was significantly higher in patients with neuronal surface antibodies (NMDAR 97 %, LGI1 93 %, CASPR2 100 %) compared to patients with GAD antibodies (20 %, p < 0.001). In seizure-free patients, ASM was withdrawn after 13 months (median) without any relapse seizures.Seizures are common in most forms of AE manifesting at disease onset in all cases. However, the development of AAE is rare and typically occurs in patients with GAD antibodies. Thus, in most AE cases with neuronal surface antibodies, ASM can be withdrawn after the acute phase of AE with low risk of seizure relapse.

Nuklearmedizinische Untersuchungen wie PET und SPECT werden v. a. bei nichtlasionellen Epilepsien in der prachirurgischen Epilepsiediagnostik eingesetzt. Auch bei unauffalliger MRT ist ein Hypometabolismus in der FDG-PET indikativ fur den epileptogenen Fokus, zudem kann sie bei Patienten mit limbischer Enzephalitis einen meist temporalen Hypermetabolismus darstellen. Iktales SPECT hat eine besonders hohe lokalisatorische Wertigkeit, wenn die Anfalle komplex-fokal sind und langer als 15 s dauern. Allerdings ist der Aufwand fur diese Diagnostik mit mehreren Tagen Video-EEG-Monitoring hoch. Sie wird daher bei nichtlasionellen oder diskordanten Fallen angewendet. Die iktale SPECT sollte mittels „post-processing“ vom interiktalen SPECT subtrahiert und auf das MRT koregistriert werden (z. B. SISCOM).

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)-[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-KAt 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).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.