Presurgical localisation of drug-resistant focal epilepsy
For seizures that medication cannot control, a brain PET scan taken between seizures can spot the small area of brain that is misfiring, by showing it using less sugar than the tissue around it, helping surgeons plan an operation to remove it.
Overview
Around a third of people with epilepsy do not achieve seizure control with antiseizure medication and are candidates for evaluation toward resective surgery, which requires precisely identifying the epileptogenic zone - the area of brain that must be removed or disconnected to stop seizures. Interictal FDG PET (performed between seizures, ideally at least 24-48 hours after the last one) is one of the core presurgical tests alongside video-EEG monitoring and structural MRI, because the epileptogenic zone and the neural networks that sustain it typically show reduced glucose metabolism (hypometabolism) interictally, an effect that is usually more pronounced and spatially extensive than any corresponding reduction in blood flow.
The joint 2024 SNMMI/EANM guideline for brain FDG PET imaging (version 2.0) and the EANM practice guideline for appropriate PET and SPECT use in epilepsy specify continuous EEG monitoring starting before FDG injection and continuing for at least 20 minutes afterwards, precisely to confirm the scan captures a genuinely interictal state rather than a post-ictal one, which would show a different and misleading metabolic pattern. Performance is markedly better in temporal lobe epilepsy, where meta-analyses report roughly 79-95% sensitivity and specificity for lateralising the epileptogenic side, than in extratemporal epilepsy, where the epileptogenic zone is correctly identified in only about 38-67% of cases; PET's higher spatial resolution gives it an edge over interictal perfusion SPECT (84% versus 66% sensitivity in one meta-analysis for temporal lobe epilepsy).
Coregistration of PET with MRI, either on a combined PET/MRI system or by image fusion, is emphasised because it lets clinicians directly match a metabolic abnormality with any structural lesion (or reveal one that was missed on MRI alone), and because more limited extent of hypometabolism on PET carries prognostic value both for postsurgical seizure freedom and for postoperative cognitive outcome. Ictal SPECT, using an agent injected as close as possible to seizure onset (ideally within 20 seconds, via a pre-placed line and automatic injector during video-EEG monitoring), is a complementary technique used particularly when PET and MRI are discordant or non-lateralising, showing increased rather than decreased blood flow at the seizure focus during the seizure itself.
State of the art
- The SNMMI Procedure Standard/EANM Practice Guideline for Brain FDG PET Imaging, version 2.0 (2024), and the EANM practice guidelines for appropriate use of PET and SPECT in epilepsy (2024) are the current joint references for patient preparation, EEG timing, acquisition and interpretation.
- Reported sensitivity for lateralising temporal lobe epilepsy with interictal FDG PET is around 79-95% in pooled analyses, clearly outperforming interictal perfusion SPECT (about 66-84%), while extratemporal epilepsy localisation succeeds in only about 38-67% of cases.
- PET-MRI coregistration and quantitative asymmetry-index analysis are now standard adjuncts to visual reading, and the extent of hypometabolism carries prognostic value for both seizure and cognitive outcome after surgery.
Epilepsy affects an estimated 50-65 million people worldwide, and roughly 30-40% of those with epilepsy do not achieve seizure freedom with medication and are potential candidates for surgical work-up, of whom presurgical PET and video-EEG evaluation are core components in comprehensive epilepsy centres.
Interictal FDG PET, with continuous EEG monitoring from before injection to at least 20 minutes after, coregistered with MRI to localise the epileptogenic zone alongside video-EEG telemetry.
Ictal SPECT, with tracer injected as close as possible to seizure onset during video-EEG monitoring, to show focal hyperperfusion at seizure onset.
Subtypes & biomarkers
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Open problems and what is being done
Extratemporal epilepsy remains substantially harder to localise than temporal lobe epilepsy with any single imaging modality, and often needs invasive stereo-EEG in addition to PET and MRI.
Bilateral or diffusely symmetric hypometabolism can be missed on visual reading alone, a recognised pitfall the guideline specifically flags.
Timing relative to the last seizure is critical but not always practically achievable in busy epilepsy monitoring units, and inadvertent post-ictal imaging can produce misleading hypometabolic or hypermetabolic patterns.
Trials
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