We report, in a cohort of 16 patients presenting with epilepsy arising from the insulo-opercular cortex solely, the outcome following SEEG-guided radiofrequency thermocoagulation (RFTC). Good outcomes (Engel class 1) are reported in 88% at 2 months and 67% at 18 months among the 9 of the 16 cases who had electrodes implanted following parasagittal trajectories. No one had an Engel class 1 outcome at 1 year in the group of 7 patients who had electrodes inserted solely orthogonally. No complications occurred. The benefit-risk ratio of the SEEG-guided RFTC procedure proved to be particularly favorable for patients presenting an epileptogenic focus located in the insula or in the medial aspect of the operculum, especially when using parasagittally, rather than orthogonally, implanted electrodes to coagulate. Therefore, this technique could be used, in selected cases, as the first-line therapeutic option procedure related to insular epilepsy, providing, in many cases, complete control over epileptic disease.

The accurate definition of the seizure onset zone (SOZ) is a central problem in drug-resistant epilepsies. Signal processing methods may be used to complement the interpretation of SEEG recordings by quantifying interictal events and SOZ. In this chapter, we will describe some of these methods and focus on insular epilepsies with some detailed case examples.

Insular epilepsy has caught increasing attention in the presurgical evaluation of drug-resistant focal epilepsies, and it is evident that intracranial EEG recordings can be considered the best method to investigate such a deep-seated area of the brain, especially in non-lesional patients. Intracranial EEG recordings allow us to better understand the organization of epileptic EEG discharges involving the insular cortex and the complexity of the relationships between the insula and the different connected regions of the brain, particularly the opercular region. This peculiarity thus explains the heterogeneous clinical presentation of seizures arising from insular or insulo-opercular structures. While most patients have an epileptogenic zone extending beyond the insula, some have very focal ictal insular discharges, allowing the possibility of a restricted surgical resection. Consequently, only an appropriate sampling of the insula and of extra-insular connected structures can permit a precise identification of the epileptogenic zone and planning for a tailored resection.

Invasive EEG investigation of the insular cortex has been performed with increasing frequency since the mid-nineties, in various forms of focal drug-resistant epilepsies. These include patients with a clear-cut intra-insular epileptogenic lesion, such as a focal cortical dysplasia, as well as patients whose non-invasive pre-surgical evaluation suggests perisylvian epilepsy, temporal plus epilepsy, sleep hypermotor epilepsy, MRI-negative frontal, and parietal lobe epilepsies. SEEG is currently the preferred method to investigate the insula, using orthogonal, oblique, or a combination of both trajectories, with no evidence of higher risk of intracranial bleeding than in other brain regions. Intra-insular ictal EEG patterns are often characterized by a prolonged focal discharge restricted to one of the five insular gyri, militating for a dense enough sampling of the insular cortex in suspected insular epilepsies. SEEG also offers the potential to perform thermolesion of insular epileptogenic zones which, together with MRI-guided laser ablation, represent a possibly safer alternative treatment to open-skull surgical resection of the insula.

The insula was described more than two centuries ago, in 1809, by the anatomist Johann Christian Reil. However, the functional anatomy of the insular cortex and the importance of the insula in psychiatric and neurologic pathological conditions remained obscure for a long period after the initial description of Reil. The location and the complex functional organization of the insula explain, for instance, the difficulty researchers and clinicians had in defining its contribution in temporal lobe epilepsy. This introductory chapter reviews the important steps that led to a better understanding of the role of the insula in human focal epilepsy.

Approximately 70% of patients with insular epilepsy require invasive investigation prior to resective or ablative surgery. Two broad techniques can be employed to invasively sample the insula and insular epileptogenic network. The first and most commonly used technique, stereo-electroencephalography (SEEG), involves the placement of intracerebral electrodes through drill-holes under stereotactic conditions (with or without robotic assistance) in the insula and relevant peri-insular network targets. The open technique involves the placement of depth electrodes within the insular cortex following the opening of the Sylvian fissure, in addition to peri-Sylvian grids over the cortical convexities or strips over the fronto-temporal-basal lobes/interhemispheric space. While there are no guidelines to decide which method to resort to, there are relative advantages, disadvantages, and scenarios where each may be beneficial. The vast majority of centers favor the SEEG technique, as it is minimally invasive, is associated with the lowest morbidity, and is particular adapted for investigating insular epileptic networks that usually involve widespread multi-lobar anatomical sites and deep structures (e.g., cingulate, mesial temporal structures, etc.). SEEG is also well-suited for bilateral cases and cases that involve reoperations, both of which are not infrequent in insular epilepsy. Finally, SEEG is an appealing option in patients in whom minimally invasive ablation (laser ablation or radiofrequency ablation) is being considered. In SEEG, insular electrodes can be placed through a trans-opercular orthogonal approach and/or through an oblique parasagittal approach (trans-frontally and/or trans-parietally). The open technique, on the other hand, is particularly suited for patients with superficial lesional epilepsy in whom the epileptogenic zone is clearly unilateral but requires invasive functional mapping, such as dominant hemisphere temporal lobe epilepsy with suspected insular involvement.

Insular lobe seizures (ILS) may present with several subjective and objective symptoms. Somatosensory and viscerosensory symptoms, notably paresthesia and laryngeal constriction, are symptoms frequently encountered with ILS. Other manifestations may become only evident after the ictal discharge spreads to extra-insular structures. Depending on propagation pathways, ILS exhibit two main clinical patterns: (1) a perisylvian /temporo-perisylvian pattern and (2) a frontal-like pattern. Other miscellaneous clinical presentations include epileptic spasms, ecstatic, gelastic, reflex, and autonomic seizures.