A Review of Neurostimulation for Epilepsy in Pediatrics

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Abstract

Neurostimulation for epilepsy refers to the application of electricity to affect the central nervous system, with the goal of reducing seizure frequency and severity. We review the available evidence for the use of neurostimulation to treat pediatric epilepsy, including vagus nerve stimulation (VNS), responsive neurostimulation (RNS), deep brain stimulation (DBS), chronic subthreshold cortical stimulation (CSCS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We consider possible mechanisms of action and safety concerns, and we propose a methodology for selecting between available options. In general, we find neurostimulation is safe and effective, although any high quality evidence applying neurostimulation to pediatrics is lacking. Further research is needed to understand neuromodulatory systems, and to identify biomarkers of response in order to establish optimal stimulation paradigms.

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Most cited references 102

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Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

D Labiner, Mubashir M. B. Uthman, Clara I. Osorio … (1998)

The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

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Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

Giulio Ruffini, Michael Fox, Oscar Ripolles … (2014)

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). Copyright © 2013 Elsevier Inc. All rights reserved.

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Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response.

Dario Englot, F. Chang, Kurtis Auguste (2011)

Vagus nerve stimulation (VNS) was approved by the US FDA in 1997 as an adjunctive treatment for medically refractory epilepsy. It is considered for use in patients who are poor candidates for resection or those in whom resection has failed. However, disagreement regarding the utility of VNS in epilepsy continues because of the variability in benefit reported across clinical studies. Moreover, although VNS was approved only for adults and adolescents with partial epilepsy, its efficacy in children and in patients with generalized epilepsy remains unclear. The authors performed the first meta-analysis of VNS efficacy in epilepsy, identifying 74 clinical studies with 3321 patients suffering from intractable epilepsy. These studies included 3 blinded, randomized controlled trials (Class I evidence); 2 nonblinded, randomized controlled trials (Class II evidence); 10 prospective studies (Class III evidence); and numerous retrospective studies. After VNS, seizure frequency was reduced by an average of 45%, with a 36% reduction in seizures at 3-12 months after surgery and a 51% reduction after > 1 year of therapy. At the last follow-up, seizures were reduced by 50% or more in approximately 50% of the patients, and VNS predicted a ≥ 50% reduction in seizures with a main effects OR of 1.83 (95% CI 1.80-1.86). Patients with generalized epilepsy and children benefited significantly from VNS despite their exclusion from initial approval of the device. Furthermore, posttraumatic epilepsy and tuberous sclerosis were positive predictors of a favorable outcome. In conclusion, VNS is an effective and relatively safe adjunctive therapy in patients with medically refractory epilepsy not amenable to resection. However, it is important to recognize that complete seizure freedom is rarely achieved using VNS and that a quarter of patients do not receive any benefit from therapy.

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Author and article information

Journal

Journal ID (nlm-ta): Brain Sci

Journal ID (iso-abbrev): Brain Sci

Journal ID (publisher-id): brainsci

Title: Brain Sciences

Publisher: MDPI

ISSN (Electronic): 2076-3425

Publication date (Electronic): 18 October 2019

Publication date Collection: October 2019

Volume: 9

Issue: 10

Electronic Location Identifier: 283

Affiliations

[1 ]Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; starnes.donnie@ 123456mayo.edu (K.S.); wongkisiel.lily@ 123456mayo.edu (L.W.-K.)

[2 ]Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA; miller.kai@ 123456mayo.edu

Author notes

[* ]Correspondence: Lundstrom.brian@ 123456mayo.edu

Article

Publisher ID: brainsci-09-00283

DOI: 10.3390/brainsci9100283

PMC ID: 6826633

PubMed ID: 31635298

SO-VID: 717dfb61-c2c7-4f42-a16b-1f03caae3967

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

A Review of Neurostimulation for Epilepsy in Pediatrics

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Karger: Neurology and Neuroscience

Most cited references 102

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response.

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