Pearls & Oy-sters: Two Cases of Stereotactic EEG-Proven Insular Epilepsy With Nonlocalizing Scalp EEG and Interesting Semiologies

Discussion

The diagnostic process for insular epilepsy can be challenging because insular seizures can mimic seizures arising from elsewhere in the brain or even be mistaken for nonepileptic spells.^1,2 To summarize our cases, both patients had hypermotor seizures, which are usually frontal lobe in origin, but they also had sensory auras. In addition, our patients had nonlocalizing scalp EEGs demonstrating only subtle electrodecrement at ictal onset with stereotyped events, suggesting a deep seizure focus. Therefore, SEEG sampling was targeted to sample the sensory cortex and deep areas of the brain that could generate hypermotor seizures. Although both patients had nonlesional brain MRIs, their presurgical evaluations had some lateralizing features, such as the ictal SPECT and neuropsychological testing for case 1 and the ictal SPECT in case 2. Nevertheless, SEEG sampling was symmetric given the lack of strong lateralizing signs and to account for the possibility of false lateralization from fast spread of ictal activity to the contralateral insula.³ In case 1, 3 electrodes were placed in each insula for a total of 24 contacts (with 11 on the right), and in case 2, one electrode was placed in each insula for a total of 4 contacts (with 3 on the right).

Part of the difficulty in diagnosing insular epilepsy lies in the depth of the insula and the unusual semiologies it can produce. To review, the insula is an area of cortex located within the lateral sulcus and surrounded by the frontal, temporal, and parietal lobes. Human studies with in vivo tracers have demonstrated numerous connections between the insula and these surrounding structures, and functional neuroimaging has identified several regions of the insula that are involved in operations ranging from autonomic function to perception of visceral and somatic pain to auditory processing.⁴

From this, it follows that the semiology of insular epilepsy reflects not only the functions of the insula itself but also the connections between the insula and the surrounding brain structures as the seizure evolves and spreads.⁵ This results in considerable overlap between the semiology of insular epilepsy and that of temporal lobe, frontal lobe, or perisylvian epilepsy.^1,2 The dense connections between the bilateral insulae can even mimic bitemporal lobe epilepsy.³ The semiology of insular epilepsy can include characteristics such as auditory illusions, paresthesias or sensations of warmth, gastric rising, autonomic manifestations (tachycardia and hyperventilation), feelings of fear or anxiety, laryngeal constriction, and hyperkinetic movements.^6,-,8 This has been demonstrated both through observation and through cortical stimulation of the insula in SEEG patients.⁶ Nevertheless, insular seizures are diverse and can ultimately seem like seizures originating from many other areas of the brain.¹

Scalp EEG may be negative or nonlocalizing in cases of nonepileptic spells, seizures involving a small cortical area, or seizures involving deep cortical foci, as in our cases. Brain MRI can also be unremarkable in insular epilepsy. In a review of 25 patients who underwent operculoinsular cortectomy for epilepsy, 72% of them had MRIs that were normal or showed nonspecific findings,⁹ although focal insular abnormalities have also been reported.¹⁰ Other noninvasive modalities include MEG, ictal SPECT, interictal PET, and proton magnetic resonance spectroscopy. A study of 14 patients with known insular epilepsy demonstrated the superiority of MEG to ictal SPECT and interictal PET in localizing the seizure focus, whereas a study of proton magnetic resonance spectroscopy on 22 patients with epilepsy did not show a significant difference in spectroscopy findings between patients with insular seizures and those with extrainsular seizures.¹¹ Ultimately, details of the noninvasive workup and seizure semiology should be used to guide SEEG implantation during presurgical evaluation.⁷

The importance of correctly diagnosing insular epilepsy lies in the possibility of surgical treatment. For focal epilepsy, surgery is superior to prolonged medical therapy for seizure control and quality of life,¹² emphasizing the need to correctly identify the epileptogenic focus. On the contrary, postoperative complications and deficits are a risk of any epilepsy surgery that must be balanced with the goal of seizure control. Early experience with open insular resections showed high morbidity (20%–45%) and mortality,^13,14 but in a more recent series, insular lesionectomy was associated with an 8% rate of permanent morbidity and no mortalities.¹³ Transient postoperative deficits include changes in taste and smell, difficulties with speech or swallowing, hemiparesis, and alterations in sensory perception.^9,15 Permanent motor deficits are associated with resection of the caudal dorsal insula. Alternative treatments, such as responsive neurostimulation or stereotactic laser ablation, are recommended for treatment of seizures arising from this area.¹ It is fortunate that our patients did not have complications from their surgeries.

SEEG was crucial in localizing the epileptogenic zone in our patients because it can be difficult to diagnose insular epilepsy with noninvasive testing.⁷ In both patients, SEEG ictal evolution was only seen over the insula, mesial frontal cortex, and anterior cingulate gyrus. As a result, ictal activity was not clearly seen on scalp EEG, which instead showed generalized electrodecrement at event onset that was further obscured by movement artifact in both patients. These cases illustrate the importance of surgical evaluation in patients with refractory focal epilepsy. Resective surgery took place more than 30 years after epilepsy onset for both patients, including after many years of a diagnosis of nonepileptic spells in case 1. Surgery has subsequently improved quality of life, leading to seizure freedom in the first patient and significantly improved seizure burden in the second. These cases highlight the importance of recognizing the unusual semiology of insular epilepsy and the workup needed to identify it.