A 35-year-old man with a 10-year history of drug-resistant focal seizures (failed trials of levetiracetam, valproate, and lamotrigine) presents for surgical evaluation. Structural MRI shows no focal lesion. Which investigation is most appropriate as the next step to localize the seizure focus and guide surgical planning?

## Localization of Seizure Focus in Drug-Resistant Focal Epilepsy **Key Point:** Intracranial electrode recording (stereo-EEG or subdural grid) is the gold standard for precise localization of the seizure focus in drug-resistant focal epilepsy when non-invasive studies are inconclusive. ### Why Intracranial Recording is the Answer 1. **Gold standard for localization**: Stereo-EEG (depth electrodes) or subdural grids provide direct ictal and interictal recordings with millimeter-level spatial resolution, definitively identifying the seizure onset zone. 2. **Guides surgical planning**: Precise localization allows neurosurgeons to plan the extent and location of resection while minimizing damage to eloquent cortex. 3. **Prognostic value**: Intracranial recording confirms that the seizure focus is surgically accessible and resectable, predicting post-operative seizure freedom. 4. **Indicated when**: Structural MRI is normal or non-concordant with non-invasive EEG/imaging findings (MRI-negative drug-resistant epilepsy). ### Algorithm for Surgical Evaluation ```mermaid flowchart TD A[Drug-resistant focal seizure]:::outcome --> B[Structural MRI]:::action B --> C{MRI lesion visible?}:::decision C -->|Yes, concordant| D[Subdural grid or stereo-EEG]:::action C -->|No lesion| E[Non-invasive localization]:::action E --> F[PET, SPECT, MEG]:::action F --> G{Concordant focus?}:::decision G -->|Yes| H[Subdural grid or stereo-EEG]:::action G -->|No| I[Intracranial recording essential]:::urgent H --> J[Surgical resection]:::action I --> J ``` ### Comparison of Localization Investigations | Investigation | Modality | Sensitivity | Specificity | Role in Drug-Resistant Epilepsy | | --- | --- | --- | --- | --- | | **Stereo-EEG** | Intracranial depth electrodes | Highest | Highest | Gold standard for MRI-negative cases | | **Subdural grid** | Intracranial surface electrodes | High | High | Preferred when lesion is superficial | | **PET brain** | Metabolic imaging | 60–80% | Moderate | Localizes hypometabolic focus; non-invasive | | **SPECT** | Perfusion imaging | 50–70% | Moderate | Ictal SPECT shows hyperperfusion; less reliable than PET | | **MEG** | Magnetoencephalography | Moderate | Moderate | Useful in generalized epilepsy; limited in focal epilepsy | **High-Yield:** In MRI-negative drug-resistant focal epilepsy, the sequence is: (1) non-invasive studies (PET/SPECT/MEG) to narrow the focus, then (2) intracranial recording (stereo-EEG or subdural grid) to confirm the seizure onset zone and guide resection. **Clinical Pearl:** Stereo-EEG is preferred over subdural grids in MRI-negative cases because it can sample deep structures (hippocampus, insula) where the seizure focus may originate, whereas subdural grids only sample cortical surface.