Johannes Reil (1759–1813) working in Halle and Berlin described the island (Insula Reilii) 1796 as hidden part of the folded cortex located under temporal- and fronto-parietal operculum. The insula is “burried” in the fissura Sylvii (first description by Sylvius, Frans de le Boe, anatomist in Amsterdam1641). The insula is differentiated in three anatomical regions: The regio insularis agranularis, the regio insularis propea granularis and the regio insularis granularis. Insight into the function mediated by the insula was given by invasive brain stimulations.
Invasive explorations using electro stimulations of cortical regions in the sylvian fissure [1,2,3,4] demonstrated that the insula is responsible for sensory cognitive and emotional functions, in addition the insula participates in autonomic functions. Painful sensations were elicited mostly from the posterior third of the insula. This is congruent with the findings of case two with ictal pain all over the patient’s body. During electric stimulation pain miss sensations only were triggered elicited by insular and secondary somatosensory cortex (SII) stimulations not by stimulating primary somatosensory cortex (SI) or other cortical regions [5]. Other functions concern empathic feeling, emotional reactions to pain, gustatory smell or hearing changes.
Invasive explorations with electrostimulations in cortical regions of the sylvian fissure [1] provoked sensations such as a feeling of sinking, nausea, pain in the navel area, rising epigastric sensations, pain ipsilateral abdominal contralateral in rib region. The insula has far reaching connections [2] with the neocortex, basal ganglia, thalamus, limbic structures and olfactory cortex. Because of rapid propagation of ictal activity of the insula to different connected lobes recorded ictal signs may be already the result of spread. Therefore difficulties do exist to distinguish whether the symptoms originate from the insular or its surrounding structures.
Semiology
For the differentiation of insular seizures with nonepileptic psychogenic seizures or other focal epilepsies the knowledge of the semiology of insular seizures is an important precondition.
Diagnostic leading ictal signs concern:
Awareness, laryngeal constriction, throat discomfort (suffocation, breathlessness as a result of tonic constriction of throat muscles), paresthesia, chest constriction, dyspnea, dysarthric speech, unpleasant abnormal sensoric sensations (case 1 and 2) like electric sensation, temperature increase or pain are characteristic. The signs may initially arise in the perioral region. From there they can spread bilaterally to extremities or other parts of the body. In addition motoric signs like hyperkinetic movements [6] (case 1 and 2), tonic contractions of eye, arc de cercle, face or extremity muscles, aphasia or dysarthria may occur. Further symptoms can be epigastric aura, gustatory sensations, hypersalivation, visceral motoric signs (vomiting, defecation urge), auditory hallucinations, sensory aphasia or autonomic such as bradycardia (left insula), tachycardia (right insula). The recognition of the ictal semiology can be hampered by the fact that seizures appear not infrequently during sleep [7,8,9,10,11,12,13,14].
Penfield and Jasper [1] pointed out that seizures originating in the insula may have a semiology similar to that of temporal lobe seizures.
Several ictal phenomena can be explained by the connectivity of different brain regions. Indirect connection parallel and lateral to the classic fasciculus arcuatus connects the Broca-region with the inferior parietal lobe. This perisylvian tract may explain ictal conduction aphasia [15] and focal-motoric phenomena in the face or extremities by connections to frontal lobe regions. Neuronal cerebral regions in the granular fields of the insula are large and bilaterally represented. This explains the existence of bilateral paresthesia (case 2). The second sensory area has a key position with regard to somatic informations to the limbic structures also for the tactile memory. In addition the insula has a “gate function” between somatosensoric region S1 and S2 as well as limbic structures in the temporal lobe e.g. amygdala. The temporal pole is interpreted as limbic integration cortex, which connects orbitofrontal and insular cortical functions. Laryngeal sensations and oral automatisms as well as gustatory perceptions are comprehensible by insular opercular representations for the function of ingestion. Diffusion tensor investigations (tractography) showed connections through the inferior parietal cortex.
Three spreading pathways in the epileptic system were differentiated:
-
1
Temporal-lateral fissure-insular lobe, mainly the insular operculum
-
2
Temporal-limbic system-insular lobe, inner structure of tempus and/or temporal pole.
-
3
Inner side-orbitofrontal-insular lobe, including the inner side of the insular lobe and the orbitofrontal cortex [16]. Insular-opercular sleep related seizures may occur with initial viscerosensitive or somatosensory symptoms and tonic-dystonic asymmetric posturing and/or hyperkinetic movements, including bimanual/bipedal activity as well as ballistic motor signs [17]. Opercular seizures may be manifested with initial laryngeal or other ictal signs typically seen in insular epilepsy, too [18].
Etiology
In case 1 an FCD is detected in MRI.
Causes mostly detected are low grade tumors (27%), focal cortical dysplasia (FCD)(21%), vascular malformation, cavernomas (19%), atrophy/ gliosis (17%) and normal tissue (8%) [19]. Genetic defects were described in operculo-insular epilepsy cases, including mutations in the CHRNB2 and CHRNA4 genes in patients with sleep-related hyperkinetic seizures [20].
In a family with reflex bathing epilepsy a temporo-insular epileptogenic network was reported with a Q555X mutation in synapsin 1 on chromosome Xp11-q21 [21].
Imaging
In case 1 an extended FCD right frontal in pars opercularis and insula is shown by structural MRI.
MR-Spectroscopy detects a decrease of NAA inside of the dysplasia, frontal right in comparison to the opposite side. In case 2 no abnormal finding in MRI was detected. From other cases we know that MRI is very helpful in discovering subtle lesions like FCD or small tumors. Occasionally MRI also detects a secondary hippocampal sclerosis [9]. During presurgical evaluation the MRI of the operculo-insular area turned out normal or showed uncertain findings in 72% [22].
In difficult cases voxel based morphometry [23], ictal SPECT or PET [20, 24] provide additional informations.
Electrophysiology
Surface EEG
Surface EEG often fails to detect the insular focal epileptic activity (case 1 no epileptiforme activity, case 2 later during the seizure temporal. Ictal discharges often are missed in surface EEG. Ictal flattening can be the only surface EEG change. In case of seizure onset in the anterior insula propagated epileptiform activity may be wrongly recorded as seizure onset in frontal or temporal areas or if true seizure onset is in posterior insula parts then in central regions.
SPECT, PET, MEG
In operculo-insular epilepsy ictal SPECT correctly identified the focus in 65% and provided misleading information in 18% [25]. MEG pointed to the insula in case 1 and insular-temporal region in case 2.
MEG source localization was superior in localizing insular focal epileptic activity compared to simultaneous surface EEG, PET and SPECT [23, 26, 27]. In the cases reported by Heers et al. [23] subtle lesions were missed in MRI. MEG and MAP permitted to proceed to presurgical evaluation using selective MEG guided invasive exploration with depth electrodes, thus epileptogenic lesions could be successfully resected.
Invasive recordings
In case 2 ictal onset only could be localized by SEEG. The scheme of electrode implantation is shown in Fig. 7. The electro-anatomic localization of ictal SEEG onset matches with the clinical localization hypothesis by ictal semiology interpretation.
If a clear location of a tumorous lesion is detected in the anterior part of the insula and ictal semiology is congruent with noninvasive diagnostics no further extensive invasive exploration may be necessary. However in other situations depth recordings in the insula and temporal- or frontal lobe are recommended e.g. using stereoelectroencephalography (SEEG).
SEEG can detect simultaneous insular-opercular seizure onset in patients with sleep related paroxysmal motor behaviours [17]. In MRI normal cases extensive individual sampling also of extrainsular regions to which the insula is closely connected should be performed [28].