The responsive neurostimulation (RNS) system, an adjunctive treatment for pharmacoresistant partial-onset seizures with 1 or 2 foci, has been available to patients aged 18 years or older since the device’s FDA approval in 2013. Herein, the authors describe their off-label application of this technology in 2 pediatric patients and the consequent therapeutic benefit without surgical complications or treatment side effects. A 14-year-old nonambulatory, nonverbal male with severe developmental delay was considered for RNS therapy for medically and surgically refractory epilepsy with bilateral seizure onsets in the setting of a normal radiological examination and a known neuropathological diagnosis of type I cortical dysplasia. The RNS system was implanted with strip electrodes placed on the left lateral frontal and right lateral temporal neocortex. At 19 months’ follow-up, cortical stimulation resulted in sustained reduction in both seizure frequency—3 seizures per day down from 15 to 30 per day—and seizure severity. The patient subsequently underwent a trial of corticothalamic stimulation with a right temporal cortical strip and a left thalamic depth electrode, which resulted in a further 50% reduction in seizure frequency. In a second case, a 9-year-old right-handed female with radiological evidence of a small watershed infarct on the left and medically refractory seizures was referred for presurgical evaluation. Invasive monitoring revealed an unresectable seizure focus in the eloquent cortex of the left posterior frontal and parietal lobes. The RNS device was implanted with cortical leads placed at the putative seizure focus. At 21 months after surgery, the patient had been seizure free for 4 months, following a 17-month period in which the seizure frequency had decreased from 12 per month to 2 per month, with associated functional and behavioral improvement. The authors’ results suggest that RNS may be a palliative option for children with intractable seizures whose condition warrants off-label use of the surgical device. The improved therapeutic effect noted with time and sustained RNS treatment points to a possible neuromodulatory effect.
Malgosia A. Kokoszka, Fedor Panov, Maite La Vega-Talbott, Patricia E. McGoldrick, Steven M. Wolf and Saadi Ghatan
Fedor Panov, Emily Levin, Coralie de Hemptinne, Nicole C. Swann, Salman Qasim, Svjetlana Miocinovic, Jill L. Ostrem and Philip A. Starr
Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via “broadband gamma” (50–200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool.
One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board–approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip.
One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG.
Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.
Fedor Panov, Sara Ganaha, Jennifer Haskell, Madeline Fields, Maite La Vega-Talbott, Steven Wolf, Patricia McGoldrick, Lara Marcuse and Saadi Ghatan
Approximately 75% of pediatric patients who suffer from epilepsy are successfully treated with antiepileptic drugs, while the disease is drug resistant in the remaining patients, who continue to have seizures. Patients with drug-resistant epilepsy (DRE) may have options to undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation. To date, treatment with responsive neurostimulation (RNS) has not been sufficiently studied in the pediatric population because the FDA has not approved the RNS device for patients younger than 18 years of age. Here, the authors sought to investigate the safety of RNS in pediatric patients.
The authors performed a retrospective single-center study of consecutive patients with DRE who had undergone RNS system implantation from September 2015 to December 2019. Patients were followed up postoperatively to evaluate seizure freedom and complications.
Of the 27 patients studied, 3 developed infections and were treated with antibiotics. Of these 3 patients, one required partial removal and salvaging of a functioning system, and one required complete removal of the RNS device. No other complications, such as intracranial hemorrhage, stroke, or device malfunction, were seen. The average follow-up period was 22 months. All patients showed improvement in seizure frequency.
The authors demonstrated the safety and efficacy of RNS in pediatric patients, with infections being the main complication.