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Abstract
Insular-onset seizures are rare and easily misdiagnosed. In this article, we aim to highlight the often distinctive semiology of seizures involving the insula with reference to three cases. We suggest three points to aid the recognition of seizures involving the insula: (1) Seizures originating in the insula frequently present with a sensation of laryngeal constriction, dyspnoea or unpleasant somatosensory symptoms; (2) Seizures involving the anterior insula may have a silent onset, but tend to propagate rapidly to motor areas causing motor or hypermotor symptoms; (3) Seizures involving the posterior insula cause somatosensory symptoms, which are normally contralateral to the seizure onset.
- Clinical Neurology
- Electrical Stimulation
- Epilepsy
- Sleep Apnoea
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Introduction
Just as ‘no man is an island’, the insular cortex, despite its misleading sobriquet, does not exist in isolation. Sitting deeply within the Sylvian fissure, the insular cortex and its connections play an important role in both normal brain function and seizure generation. Insular-onset seizures are rare but important to recognise. In this article, we aim to highlight the often distinctive semiology of seizures that arise in the insula, with reference to three cases.
Case 1
A 26-year-old man presented with a 2-year history of episodes of waking up in the night with a feeling of laryngeal constriction, shortness of breath and an intense feeling of fear. One year after these began, he had a witnessed generalised tonic–clonic seizure. Examination was normal. An MR scan of brain showed an area of polymicrogyria in the region of the right posterior opercula and insula (figure 1). Following treatment with lamotrigine, he remained seizure free.
MR scan of brain (coronal T2) showing polymicrogyria (white arrow) in the right posterior opercula and insula.
Case 2
A 65-year-old man gave a 6-month history of episodes of transient loss of consciousness preceded by a sensation of difficulty catching his breath. Witnesses described his face being pulled to the left side, followed rapidly by jerking of his whole body and a period of drowsiness with slow recovery afterwards. He had suffered a right middle cerebral artery infarction 8 months before the first of these episodes. On examination, he had a mild left hemiparesis with facial involvement. An ECG was normal. An electroencephalogram (EEG) showed intermittent bitemporal slowing, consistent with underlying cerebral vascular disease. An MR scan of brain showed a mature infarct in the right frontal lobe extending into the insular region (figure 2). He was treated with levetiracetam and was seizure free at 8 months follow-up.
MR scan of brain (A: axial fluid-attenuated inversion recovery and B: coronal T2) showing a mature infarction in the right frontal lobe, extending into the insular region.
Case 3
A 54-year-old woman presented with recurrent episodes of right-sided numbness. These were brief (lasting less than 30 s), unpleasant, stereotyped and were occurring daily. There were no associated movements, jerks or loss of awareness. Friends and colleagues had noticed some personality changes with difficulty sustaining attention and increased impulsivity. An MR scan of brain showed a large glioma in the left temporal lobe, extending into the left insula. She underwent resective surgery. Repeat imaging showed residual tumour in the dorsal-posterior left insula (figure 3). She continued to have daily episodes of brief hemisensory symptoms that proved refractory to antiepileptic medication.
MR scan of brain (axial fluid-attenuated inversion recovery) showing the residual insular component of a previously resected low-grade glioma.
Discussion
The insula, or island of Reil, was first described by Johann Christian Reili in 1809.1 2 It is located in the base of the Sylvian fissure, lying hidden beneath the frontal, parietal and temporal opercula, and is divided by the central sulcus into the anterior and posterior insula.3 The anterior insula comprises three or four short gyri and the posterior insula comprises one long gyrus.4 (figure 4) Its blood supply comes mainly from the middle cerebral artery.5
Anatomical illustrations showing the insula on the right side, exposed by removing the operculum (A) and a coronal section through the left insula (B).
The insula has extensive connections with limbic system regions, including the amygdala, entorhinal cortex, cingulate gyrus, hippocampus, as well as the basal ganglia, thalamus, temporal, frontal and parietal lobes.6 7 These extensive connections may explain why the insular cortex, although accounting for <2% of total cortical surface area, has been implicated in such a diverse range of functions, including pain processing, speech production and the processing of social emotions.8 A meta-analysis of functional neuroimaging studies identified four functionally distinct regions of the human insula, albeit with some overlap:9
socioemotional tasks activated the anteroventral insula
sensorimotor tasks activated the mid-posterior insula
olfactogustatory stimuli activated the central insula
cognitive tasks activated the anterodorsal insula.
Electrophysiological studies have shown that stimulating specific areas of the insula can generate somatosensory symptoms including pain, viscerosensory symptoms, somatomotor symptoms and visceroautonomic symptoms, as well as affecting speech processing.10–12 Isnard et al. combined clinical features, stereo-EEG and direct stimulation to identify a sequence of symptoms that suggested an insular-onset seizure. Crucially, the sequence began with a sensation of laryngeal constriction with thoracic oppression or dyspnoea, and was associated with unpleasant sensory symptoms (electricity or warmth) either restricted to the oral area or in a large somatic territory. In some, this was eventually followed by dysarthria and focal motor manifestations. There was full retention of consciousness throughout.11 Stimulation of specific insular subregions allowed some of these symptoms to be further localised. The authors explored most of the insular surface, except the most anterior area. Electrical stimulation of the posterior three-quarters of the explored area resulted in somatosensory symptoms, most of which were contralateral. These were either non-painful or painful or felt as a sensation of warmth.11 Other studies have confirmed that stimulating the dorsoposterior insula results in painful sensory symptoms.11 13 14 Stimulating the anterior three quarters of the explored area resulted in viscerosensory symptoms, including a feeling of laryngeal constriction and breathing discomfort.11 Stimulation of the lower posterior insula resulted in auditory responses, such as whistling. Other responses such as dysarthria appeared to be evoked by a more scattered distribution of stimulation in the explored area.11 Stephani et al.13 found that stimulating the anterior insula gave no symptoms. Additionally, Mazzola et al.15 found that stimulating the posterior insula generated vestibular symptoms. Involvement of the central autonomic network, including the insular cortex, may be a mechanism for ictal asystole.16 Stimulating the rostral-posterior insula in rats can cause tachycardia and stimulating the caudal-posterior insula causes bradycardia.17
In contrast to the anatomical precision of intracranial stimulation studies, localising insular-onset seizures from seizure descriptions can present a significant clinical challenge, especially if the MR scan is normal. The combination of high interconnectivity and rapid ictal propagation mean that the first clinical seizure symptoms do not always correspond to the ictal-onset zone. Rapid seizure propagation means that seizures originating in the insula may mimic seizures of both temporal and extratemporal onset. Conversely, seizure activity can also spread from surrounding temporal or frontal areas to the insular cortex, resulting in misleading seizure auras. Furthermore, mesiotemporal seizures may propagate to the ipsilateral or contralateral insula. The deep location of the insula makes it difficult to detect changes on scalp EEG, further increasing the uncertainty over seizure onset.18 Consequently, insular seizures may be mistaken for frontal, temporal or parietal lobe seizures; this may contribute to the failure rates of epilepsy surgery.19 Despite these pitfalls, it is important to be aware of and to recognise the clinical features of seizures involving the insula when interpreting patients’ seizure descriptions. In particular, the presence of a sensation of laryngeal constriction at seizure onset should alert the neurologist to the possibility of the seizure originating in the insular cortex rather than the medial temporal lobe, and sensory symptoms at onset may suggest a seizure originating in the posterior insula.
It is also important to consider insular seizures in a differential diagnosis of obstructive sleep apnoea. We have seen two patients initially referred with episodes of apparent apnoea or choking at night—and suspected as having obstructive sleep apnoea—who were in fact experiencing nocturnal seizures involving the insula. The stereotyped nature of the symptoms was a clue to the correct diagnosis, while the lack of snoring, obesity and the absence of significant excessive daytime sleepiness went against obstructive sleep apnoea.
Although we recognise that we have not proven the localisation of seizure onset with ictal recording in the three cases presented here, there is clear evidence of insular involvement on imaging. Furthermore, the seizure semiology usefully illustrates the recognised patterns of seizures involving the insula, which may be unfamiliar to clinicians (figure 5).
A broad diagrammatic representation of the semiology of seizures involving the insula, based on results from electrocortical stimulation. (A) Seizures involving the anterior insula may have a silent onset, but tend to propagate rapidly to motor areas causing motor or hypermotor symptoms. (B) Seizures involving the posterior insula may result in somatosensory responses, normally contralateral to the seizure onset. They may also result in vestibular sensations, auditory responses and possibly arrhythmias. Dorsal stimulation may result in pain, and ventral stimulation may result in a warmth sensation. (C) Widespread stimulation of the central two-thirds of the insula results in sensations of laryngeal constriction and breathing discomfort.
Seizures originating in the insula often begin with a sensation of laryngeal constriction, dyspnoea or unpleasant somatosensory symptoms.
Seizures involving the anterior insula may have a silent onset, but tend to propagate rapidly to motor areas causing motor or hypermotor symptoms.
Seizures involving the posterior insula cause somatosensory symptoms, normally contralateral to the seizure onset.
Seizures involving the insula are important among the differential diagnosis of obstructive sleep apnoea.
References
Footnotes
Contributors RW-T is the lead author and main contributor. RP has equally contributed to the manuscript and has read and approved it. Both authors agree to be accountable for all aspects of the work.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed. This paper was reviewed by Mark Manford, Cambridge, UK, and the second referee was Tim Wehner, London, UK.
↵ iJohann Christian Reil was a German physician, physiologist, anatomist and psychiatrist, who drew attention to the insula. He was the first to describe the arcuate fasciculus and the locus coeruleus and is also credited as having coined the term psychiatry. He died from typhus, caught treating the wounded during the Battle of Leipzig in the Napoleonic Wars.
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