13.1 Introduction

The insula of Reil was thought to be implicated in seizures in the 1950s. ¹ , ² The insular cortex remains somewhat inaccessible as it is buried in the sylvian fissure. This cortex is clearly of importance in epileptogenesis and is usually considered a “paralimbic” structure. ³ , ⁴ , ⁵ , ⁶ , ⁷ Deep to the insular cortex lie the extreme capsule, the claustrum, the external capsule, the putamen, and the pallidum (▶Fig. 13.1). In reports regarding “insular lesions,” it is common that these lesions involve these basal ganglia areas as well as the more superficial insular cortex. ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ Seizures are the most common clinical presentation of “insular” lesions, but epilepsy (chronic recurrent possibly intractable seizures) is most commonly related to low-grade gliomas. ¹⁴ , ¹⁵ Part of the reason for this could be presumed to be related to the paralimbic nature of the insular cortex. In addition, the proximity of the piriform cortex and the deep endopiriform area may also play a role in epileptogenesis. The deep endopiriform nucleus was first discovered to be a highly epileptogenic area in rats and termed “area tempestas” (AT) by Karen Gale and co-workers. ¹⁶ , ¹⁷ , ¹⁸ The existence of “AT” was subsequently supported in monkeys, ¹⁹ and there are some suggestions of its existence in man. ²⁰ The presumed location in man adjacent to, or within, the insular lobe may be an additional reason for insular involvement in epileptogenesis.

In nonlesional limbic-type seizures, there is indirect ² , ²¹ and more recently direct evidence of insular involvement as a component of the epileptogenic network. ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ Classic awake intraoperative stimulation studies of the insula resulted in sensory and autonomic phenomenology typical of complex partial seizure semiology. ¹ In particular, an abdominal rising sensation is thought to be associated with involvement of the amygdala and anterior insula. ²⁸ , ²⁹ The stimulation of the anteroventral insular cortex has been shown to increase gastrointestinal motility along with other autonomic changes, including changes in heart rate. ²⁵ , ³⁰ There has been a wealth of more recent data on insular involvement in spontaneous seizures in patients. ²³ , ²⁴ , ²⁵ , ²⁷ , ³¹ This has been derived from invasive electroencephalography (EEG) recordings during investigation for epilepsy surgery. Most of these studies of stereoelectroencephalography (SEEG) have been carried out according to the technique described by Talairach in the 1950s, in which a stereotactic angiogram is used for frame-based placement of depth electrodes via an orthogonal approach. ³² More recently, oblique targeting offers more contacts in the insula per electrode. ²⁶ , ²⁷ , ²⁸ The angiogram is particularly valuable in the context of insular studies, since electrodes need to safely navigate between cortical veins and the branches of the middle cerebral artery (MCA) in order to safely reach insular cortex; a CT angiography should provide an equivalent level of safety and facilitate oblique trajectory planning. ²⁷ The resulting studies and publications have given us additional insight into insular function by way of stimulation studies of the insular contacts of the electrodes. ²² , ³¹ , ³³ , ³⁴ , ³⁵ , ³⁶ Recording spontaneous seizures using the same technology has highlighted insular participation not only in seizure propagation but occasionally as a locus of primary seizure onset or of early network participation. ²⁶ , ³⁷ , ³⁸ , ³⁹

13.2 Insular Seizure Semiology

▶Table 13.1 tries to establish some criteria for clinically suspecting participation or origin of seizures in insular cortex. Unfortunately, there is considerable overlap in insular seizure semiology with not only typical temporal lobe clinical features ²³ but also with some features thought to be classically implicating the frontal lobe. ⁴⁰ , ⁴¹ , ⁴² , ⁴³ This may in part be due to the fact that there is a histological similarity between the anteroventral insula, the posterior orbitofrontal cortex, the piriform–cortical amygdalar complex, and the temporopolar cortex. It may also be due to rapid seizure propagation between these areas. Traditionally, nausea, vomiting (ictus emeticus), and autonomic features have been thought to be indicative of insular but also amygdalar involvement. ⁴⁴ Typical temporal lobe semiology such as a rising abdominal and thoracic sensation is in fact quite “amygdalo-insular.” ⁴⁵ Throat constriction or abdominal discomfort at seizure onset may be somewhat more suggestive of insular origin. ²⁴ , ⁴⁶ , ⁴⁷ , ⁴⁸ Nocturnal hypermotor seizures, previously thought to be typically of frontal lobe origin, can have an insular origin on SEEG. ⁴¹ , ⁴² , ⁴⁹ The search for clinically suggestive features of insular seizures is important while evaluating the necessity for invasive EEG studies with insular coverage.

13.3 Insular Anatomy and Function

The insular cortex in man is completely hidden within the sylvian fissure, and covered by fronto-orbital, parietal, and temporal opercular cortices. First described by Johann Christian Reil in 1809, this cortical “island” is triangular in shape and is surrounded by a “circular sulcus” that can also be divided into anterior, superior, and inferior components bordering the orbitofrontal, frontoparietal, and temporal opercula, respectively. An oblique central insular sulcus (which parallels and is most often an extension of the central sulcus proper) separates the insula into an anterior component consisting of three to four short anterior gyri, and the posterior insula, consisting of two long gyri. There are also usually two short transverse gyri at the orbitofrontal junction. Based on its connections and cytoarchitectonic characteristics, the insular cortex has been classified as a paralimbic structure by Mesulam and Mufson. ³ , ⁴ , ⁵ , ⁶ , ⁵⁰ There is immediate proximity between the piriform olfactory cortex (POC) and the limen of the insula which constitutes the anteroinferior corner of the insula). Both areas feature a three-layer allocortex. The cytoarchitectonic features of the cortex progress to six-layer neocortex with increasing distance from the POC, with a transitional cortex seen where the granule cell layer is not yet defined (dysgranular cortex). Within the insula, this change in histology occurs in a radial fashion as the distance from the limen increases. As a consequence, the anteroventral aspect of the insula, in closest proximity to the limen insula (LI), is histologically and functionally its most limbic portion. This is indeed the area of the insula with demonstrated autonomic connections and where awake stimulation mapping by Penfield has elicited abdominal sensations, increases in gastrointestinal motility and other autonomic responses. ¹ Changes in heart rate have also been elicited from this area, with suggestions that there may be a right–left insula difference in cardiac response. ³⁰ , ⁵¹ It is noteworthy that insular activity has been implicated as having a possible role in cardiac arrhythmia and death in stroke, and as a possible mechanism for sudden unexpected death in epilepsy (SUDEP). ⁵² , ⁵³ , ⁵⁴ , ⁵⁵ , ⁵⁶ , ⁵⁷ , ⁵⁸ , ⁵⁹ Regarding the latter, it has been postulated that epileptic activity involving the anteroventral insula may lead to cardiac arrest and SUDEP. It is of surgical importance to be aware of these autonomic effects, since cardiac and blood pressure changes can occur during surgery in these areas. Within the context of hemispherectomy variants, these autonomic effects have been implicated as a possible source of instability during surgery of which anesthesiology should be aware. ⁶⁰

Human awake mapping with SEEG has demonstrated gustatory responses in the more dorsal anterior insula. ⁴⁶ In the posterior insular cortex, sensory responses were evoked including pain responses. ³¹ , ³⁴ , ⁶¹ , ⁶² , ⁶³ This is concordant with many functional imaging (PET and fMRI) studies that show insular cortex activation in response to noxious stimuli. ⁶¹ , ⁶² , ⁶⁴ , ⁶⁵ , ⁶⁶ Conversely, dysarthria but no true dysphasia was elicited by SEEG stimulation. ⁴⁶ There is considerable literature in functional imaging and stimulation mapping that suggests some speech localization in the insular cortex in the dominant hemisphere. ³⁵ , ⁶⁷ , ⁶⁸ That any primary speech function may be localized in insular cortex is more difficult to establish, since surgical resection in the dominant hemisphere affects opercular cortex, where there is definite speech localization. Additionally, open stimulation studies probably activate white mater deep to insular cortex that may lead to disconnective types of speech disturbance or motor speech interference. ⁶⁹ , ⁷⁰ , ⁷¹ , ⁷² , ⁷³

The insula is also involved in higher level functions and integrative and behavioral functions. The insula has a role, in addiction, in particular to cigarette smoking. ⁷⁴ , ⁷⁵ Insular damage has been reported to affect interpersonal trust ⁷⁶ and resections for epilepsy have recently suggested increased irritability and anxiety when compared to patients following temporal lobe resections. ⁷⁷ The complex integrative nature of insular functions is a reflection of its extensive connections with surrounding cortical and subcortical areas (▶Fig. 13.2).

13.4 Vascular Anatomy and the Insular Lobe

As previously mentioned, access to the insula is restricted by its deep location and by its close relationship with the MCA. The insular cortex is vascularized exclusively by the MCA and the underlying basal ganglia and internal capsule are supplied to a major degree by the M1 segment of the MCA via the lateral lenticulostriate arteries (LSA; ▶Fig. 13.1). ⁷⁸ , ⁷⁹ , ⁸⁰ , ⁸¹ , ⁸² These usually do not extend as far laterally as the actual insular cortex, which is supplied by perforating arteries arising from the overlying M2 segments of the MCA with occasional branches of the distal M1 to the area of the limen before dividing into M2 segments in this location. There are also occasional branches from the opercular M3 segments coursing back to the insular cortex. It is particularly noteworthy that an M2 branch is consistently found in the central sulcus which subsequently supplies the central sulcus proper, thus the pre- and postcentral gyri. It is therefore particularly important to avoid compromising this artery.

A number of detailed anatomical studies have reviewed the vascular anatomy and supply of the insula. From a surgical perspective, it should be noted that a motor deficit from insular surgery that does not directly lesion the internal capsule is most likely to be the result of a vascular injury at one of four levels:

1. 
   

   The lateral LSAs arise from the M1 segment and enter the basal ganglia via the anterior perforated substance. Since these arteries also supply the internal capsule, vascular compromise can lead to hemiparesis from a vascular capsular insult.

   
   
2. 
   

   Perforating branches from the M2 supply the insular cortex. Anatomical studies estimate that 85 to 90% of these perforating arteries are short, supplying insular cortex and underlying extreme capsule only. Up to 10% of perforators extend further reaching the claustrum and extreme capsule. The functionally worrisome long perforators comprise only 3 to 5% of perforators but can go on to supply part of the internal capsule and corona radiata, especially posteriorly. ⁷⁸

   
   
3. 
   

   The artery of the central sulcus courses through the central sulcus of the insula. Injury can lead to vascular compromise of primary motor-sensory cortex.

   
   
4. 
   

   M2 and M3 branch manipulations can lead to ischemia or infarction, although often not with a permanent deficit.

13.5 Risks of Surgical Approaches to the Insula

Based on the previously described anatomical and physiological features, a risk assessment of surgery of the insula can be attempted. In the context of surgery for epilepsy, this must be weighed against the chances of controlling seizures with the planned surgery in order to establish a likely risk/benefit ratio. Since there are still many unknown aspects regarding insular function, an absolute risk assessment is not possible. With regard to results of insular surgery to control seizures, recent reports demonstrated good seizure control (75–85% Engel classes I + II) after low-grade glioma surgery presenting with poorly controlled seizures. ¹³ , ¹⁴ , ¹⁵ , ⁸³ Also, invasive EEG recorded insular ictal onset has been shown to be related to good results following resection (70–80% Engel classes I + II). ²⁶ , ²⁷ , ⁴⁷ , ⁴⁸ , ⁸⁴

In the risk assessment of surgical approaches to the insula, it is useful to differentiate between lesional surgery and nonlesional surgery. Lesions that are considered “insular” in the literature most often refer to those not only involving insular cortex but also deeper underlying structures including the basal ganglia. The risks of surgical approaches to these areas is different from an approach to the more superficial insular cortex alone, in that there is additional risk of a motor deficit by direct injury to the internal capsule or by vascular injury to the same by compromise of the lateral LSAs. This compounds the motor risks of superficial insular approaches where the long perforating arteries from the M2 branches or artery of the central sulcus are at risk.

Assessment of risk to speech function is not as straightforward as that for motor function. Clearly, in the dominant hemisphere, there is a speech risk in the approach itself, since frontal, parietal, and temporal opercular cortices are the classical locus for primary speech function. Therefore, any resection, retraction, manipulation, or vascular compromise to opercular cortex in the dominant hemisphere carries a risk to speech function. Stimulation mapping for speech function can help lower the risk to speech by helping to define opercular areas lacking obvious language function. Avoidance of resection or retraction of more eloquent opercular cortex should decrease risk to speech. ⁹ , ¹⁰ As previously mentioned, evidence of primary speech localization to the insular cortex itself is less prevalent, ³⁵ although a number of authors who have experienced with insular surgery recommend stimulation mapping of the insula itself ⁷² , ⁸⁵ , ⁸⁶ ; others do not. ⁹ , ⁸⁷ Some interference with speech function may be related to a disconnective effect at the level of the external capsule and not to actual cortical insular lesion. ⁷⁰ , ⁸⁵ This author prefers to consider awake speech mapping on a selective, case-by-case basis.

Risk to higher cognitive function is the most difficult of all to discuss regarding insular surgery, since the insula is the seat of multimodal integration. Anteroventrally, there is evidence of autonomic processing in close conjunction with the amygdalar complex (behavior, motivation, and learning). Dorsally and posteriorly, sensory (including pain), motor, and vestibule-auditory connections exist. Functional imaging also shows an insular role in the context of more complex auditory processing, pitch perception, and singing. ⁸⁸ , ⁸⁹ , ⁹⁰ , ⁹¹ In the context of a dominant hemisphere insular infarct, loss of verbal memory has been described, but these lesions are unlikely to have involved insular cortex in isolation. ⁶⁷ , ⁹² , ⁹³ , ⁹⁴ Overall, higher cognitive effects of insular surgery cannot be predicted at present.