Multiple subpial transections with concomitant responsive neurostimulation of the insula: illustrative case

Abstract

BACKGROUND

Focal epilepsy arising from the eloquent cortex can be treated with palliative surgical interventions such as multiple subpial transection (MST) or responsive neurostimulation (RNS). These techniques can be performed to reduce the burden of disabling seizures while avoiding disability associated with resection of the eloquent brain.

OBSERVATIONS

A 17-year-old girl with a history of complex, refractory multifocal epilepsy and previous right anterior temporal lobectomy and left temporal neocortical RNS presented with refractory status epilepticus. Scalp electroencephalography showed seizures that began prior to RNS detection, suggesting a focus outside of the left anterior temporal lobe. MRI showed new edema throughout the left insula. MST and concurrent insular RNS lead placement were performed. The patient was discharged 2 weeks later, and at the 6-month follow-up, she had a 100-fold reduction in clinical seizures and RNS detections.

LESSONS

This technical report is the first description of 1) concurrent MST and RNS, and 2) placement of a paddle electrode for the RNS over the surface of the insula using a transsylvian approach.

Surgery in this case provided both immediate and sustained reduction in disabling seizures over several months.

https://thejns.org/doi/10.3171/CASE24445

Resection is the most effective treatment for drug-resistant focal epilepsy.¹ However, for focal epilepsy arising in the cortex where resection is likely to cause significant neurological deficits, multiple subpial transections (MSTs) were developed to interrupt seizure initiation and propagation, while maintaining most of the neurological function. MST can cause mild deficits, and its effectiveness can wane over time.² Over the past decade, responsive neurostimulation (RNS) has largely replaced this technique, given its increasing efficacy over time and low likelihood of causing neurological deficits.³ We report the surgical technique of a case in which the entire insular surface was treated via a transsylvian approach with MSTs and RNS delivered by a strip electrode laid across the insular surface.

Illustrative Case

Clinical Presentation

A 17-year-old girl with a history of complex, medically refractory, multifocal epilepsy previously treated with right anterior temporal lobectomy at age 7 and left-sided RNS for foci in the left superior temporal gyrus (STG) and the left hippocampus at age 12 presented with status epilepticus. Over the past 2 months, she had required hospitalization for status epilepticus on 2 other occasions, for 23 and 3 days, requiring intubation on one of these occasions. She had experienced complications, including pneumonia, urinary tract infection, arterial line injury, nonocclusive pulmonary thrombus, and delirium. On this third hospitalization, despite her multiple baseline antiseizure medications (clobazam, tiagabine, and perampanel vigabatrin) and trials of the ketogenic diet, steroid burst, propofol, midazolam, oral ketamine, clorazepate, and felbamate, as well as a trial of low-frequency RNS, she still had frequent seizures well above her baseline with an associated epileptic encephalopathy and again required intubation. At its highest, her seizure frequency was greater than 100 seizures per day.

Scalp electroencephalography (EEG) showed seizures that began prior to RNS detection, suggesting a focus outside of her anterior temporal lobe. MRI showed moderate edema throughout the left insula that had not been present on prior MR images (Fig. 1). This was the patient’s known dominant side, and she had had a complete right temporal lobectomy; an entire insulectomy would be expected to result in a significant language deficit with a possible motor deficit. Additionally, it was clear that she had a widespread epileptic network, so resection of even the entire insula would not be curative. The addition of an RNS lead to the insula was deemed important for future control of seizures from this eloquent area but was not expected to work immediately. Given her life-threatening super-refractory status epilepticus at the time, a strategy was developed at a multidisciplinary epilepsy conference to provide an immediate reduction in seizures by performing transsylvian MST throughout the insula and placing an RNS strip on the surface of the insula (Fig. 2). It was thought that this approach would confer less risk to her language function compared with resection, laser interstitial thermal therapy, or radiofrequency ablation.

FIG. 1.

Axial FLAIR MR image showing expansion and hyperintensity of the left insular gyri.

FIG. 2.

Illustrations demonstrating the configuration of the patient’s RNS pulse generator relative to the insular paddle electrode. MSTs of the insular gyri and an RNS strip laid across the insular surface are also shown.

Operative Technique

The patient was positioned supine with the head turned to the right. The incision for her prior craniotomy for RNS was reopened. The prior RNS lead in the STG was disconnected and removed, leaving the more active hippocampal lead in place. The dura was opened and retracted with sutures. With an operative microscope, the sylvian fissure was opened widely with sharp and blunt dissection with microscissors and Rhoton suction. Greenberg retractors were placed over the frontal and temporal opercula to provide broad exposure of the insular surface (Fig. 3).

FIG. 3.

Intraoperative photographs showing broad exposure of the insular gyri via a transsylvian approach (upper) and demonstrating the RNS paddle electrode laid across the insular surface (lower).

Starting at the anterior short gyrus and for each gyrus of the insula, low-amplitude bipolar electrocautery and then microscissors were used to make a punctate pial opening adjacent to the sulcus. A right-angle microhook was then used to make MSTs to a depth of approximately 2 mm in a direction perpendicular to the gyrus and at an interval of approximately 5 mm. This was repeated for each gyrus.

Following MST, a 4-contact paddle electrode was placed over the surface of the insula. The wide transsylvian dissection allowed the entire electrode paddle to rest on the surface of the insula without mass effect on the operculum or circular sulcus (Fig. 3). The electrode was connected to the RNS system. The lead of the electrode was secured to the dura with a 4-0 silk suture to prevent it from migrating. Postoperative CT showed good placement of the electrodes without mass effect, and the patient was returned to the ICU.

The insular lead was set to record for 1 week postoperatively. After having the MST, her seizure frequency decreased. The ICU team was able to wean her intravenous sedation, and she was extubated. After 1 week, the insular lead was turned on for treatment without side effects.

The patient was discharged home 2 weeks after surgery. At this time, she was having only 0–5 clinical seizures a day on average. She also noted that her seizures were shorter and she no longer had generalized tonic-clinic seizures without warning. She was able to return to school most days. She required ongoing titration and medication adjustments for seizure fluctuations but was able to attend her high school graduation and prom, 2 events her family reported that they did not expect would be possible. Her receptive and expressive language and motor strength and coordination were at her baseline. The patient’s immediate clinical improvement was followed by a continuous improvement over time in the number of RNS detections, which, in the 1st month postoperatively, numbered as high as 400 per recording epoch but subsequently decreased to 200 detections per recording epoch in the 2nd month postoperatively and single-digit detections per epoch by the 6th month postoperatively (Fig. 4).

FIG. 4.

Responsive neurostimulator activations over a 6-month period. There is an initial effect of MST followed by a rebound in electrographic activity and then a clear gradual improvement in seizure detections over time.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Status epilepticus is a neurological emergency. Mortality rates for patients with status epilepticus range from 8% to 50%, and neurosurgical intervention can have a major impact on mortality and morbidity.⁴ MST has been performed in the setting of status epilepticus and has been shown to grant greater than 75% seizure reduction in 70% of patients, but its efficacy might decrease over time.²,⁵,⁶ RNS has been performed in the setting of status epilepticus as well.⁷ It has been shown to achieve seizure reduction of 75% at 9 years, but its effect takes time and improves over time.³

Observations

The rationale for neurosurgical intervention in our case was repeated episodes of super-refractory status epilepticus, refractory to multiple concurrent antiseizure medications, infusions, dietary therapy, and RNS adjustments. The patient’s seizures were localized by imaging and EEG to the dominant insula: the seizures spread to the lateral left temporal neocortex but did not originate in the STG or hippocampus RNS electrodes, and there was an insular lesion on MRI. Insula resection was considered, but complete dominant insula resection was expected to be both highly morbid and not curative in our case. Insula resection, in general, remains an open question due to the potential high risk of eloquent opercular cortex and nearby white matter tracts.⁸ Rates of seizure freedom are high but so is morbidity.⁸ In 1 pediatric cohort of insular resection, temporary and permanent neurological deficits occurred in 24% and 10%, respectively, with the most common deficits being mono- or hemiparesis, facial weakness, and language deficits.⁹ The overall complication rate might be as high as 41%, possibly due to compromise in small perforating vessels from the middle cerebral artery (MCA) branches in and around the operculum and insula.¹⁰ Ablation and neuromodulation strategies have been proposed as an alternative to resection.¹¹ Our approach allows for direct visualization that these approaches do not, decreasing risk to the eloquent insula and opercular cortex.

The transsylvian approach described in our case allowed for clear visualization of the major MCA branches of the operculum and insula. The technique of MSTs is also designed to spare not just the blood supply of the insula, but because the insular cortex is only opened in intervals, and not across perforating arterioles, there is less risk to the motor function of the internal capsule and the language function of the arcuate fasciculus.

MST allowed for an immediate effect in breaking status epilepticus and reducing disabling seizures, as demonstrated in the clinical improvement in our case prior to turning on RNS. RNS, in turn, allows for a sustained treatment effect. As can be seen in the RNS data in Fig. 4, the RNS was treating insular seizures after MST, and RNS detections did increase despite clinical improvement in the 1st month (suggesting the efficacy of MST) before decreasing over the next 5 months (suggesting the efficacy of RNS).

Lessons

The transsylvian approach to the insula allows for direct visualization of the MCA branches and the entire insular surface for MST and placement of an RNS strip electrode. MST provided significant immediate seizure reduction, and this effect was sustained by the RNS paddle electrode over the insular surface. This report demonstrates the utility of an MST/RNS strategy that can be used for similar patients with severe, life-threatening, super-refractory, eloquent-onset focal status epilepticus.

Acknowledgments

The illustrations were created by Eo Trueblood.

Disclosures

Dr. DiGiovine reported personal fees from Neurelis Advisory Board outside the submitted work. Dr. Marsh reported grants (site PI for study) from Stoke Therapeutics, UCB pharma, Epygenix Pharma, and Takeda Pharma; personal fees from Acadia Pharmaceuticals and Neurogene Therapeutics; and grants from NIH outside the submitted work.

Author Contributions

Conception and design: Ziechmann, Galligan, Marsh, Kennedy. Acquisition of data: Ziechmann, Galligan, Marsh, Kennedy. Analysis and interpretation of data: Ziechmann, Kennedy. Drafting the article: Ziechmann, Kennedy. Critically revising the article: Ziechmann, Galligan, Marsh, Kennedy. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Ziechmann. Administrative/technical/material support: Galligan, Kennedy.

Supplemental Information

Previous Presentations

Portions of this work were presented as an oral presentation at the 34th Annual Pan Philadelphia Neurosurgery Conference, Philadelphia, PA, December 2, 2022.

Correspondence

Robert Ziechmann: Temple University Hospital, Philadelphia, PA. ziechmannr@chop.edu.