A systematic review of deep brain stimulation for the treatment of drug-resistant epilepsy in childhood

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Drug-resistant epilepsy (DRE) presents a therapeutic challenge in children, necessitating the consideration of multiple treatment options. Although deep brain stimulation (DBS) has been studied in adults with DRE, little evidence is available to guide clinicians regarding the application of this potentially valuable tool in children. Here, the authors present the first systematic review aimed at understanding the safety and efficacy of DBS for DRE in pediatric populations, emphasizing patient selection, device placement and programming, and seizure outcomes.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations. Relevant articles were identified from 3 electronic databases (MEDLINE, Embase, and Cochrane CENTRAL) from their inception to November 17, 2017. Inclusion criteria of individual studies were 1) diagnosis of DRE; 2) treatment with DBS; 3) inclusion of at least 1 pediatric patient (age ≤ 18 years); and 4) patient-specific data. Exclusion criteria for the systematic review included 1) missing data for age, DBS target, or seizure freedom; 2) nonhuman subjects; and 3) editorials, abstracts, review articles, and dissertations.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>This review identified 21 studies and 40 unique pediatric patients (ages 4–18 years) who received DBS treatment for epilepsy. There were 18 patients with electrodes placed in the bilateral or unilateral centromedian nucleus of the thalamus (CM) electrodes, 8 patients with bilateral anterior thalamic nucleus (ATN) electrodes, 5 patients with bilateral and unilateral hippocampal electrodes, 3 patients with bilateral subthalamic nucleus (STN) and 1 patient with unilateral STN electrodes, 2 patients with bilateral posteromedial hypothalamus electrodes, 2 patients with unilateral mammillothalamic tract electrodes, and 1 patient with caudal zona incerta electrode placement. Overall, 5 of the 40 (12.5%) patients had an International League Against Epilepsy class I (i.e., seizure-free) outcome, and 34 of the 40 (85%) patients had seizure reduction with DBS stimulation.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>DBS is an alternative or adjuvant treatment for children with DRE. Prospective registries and future clinical trials are needed to identify the optimal DBS target, although favorable outcomes are reported with both CM and ATN in children.</jats:p></jats:sec>

A Review of Neurostimulation for Epilepsy in Pediatrics

“…Other targets have included the centromedian nucleus of the thalamus (CMT), the subthalmic nucleus (STN), the globus pallidus, the cerebellum, the hippocampus, the caudate nucleus and the seizure onset zone itself [59]. The CMT has been targeted for the treatment of generalized epilepsy [8,60,61,62,63,64,65]. A recent review by Li and Cook [59] summarized three small (largest sample size N = 9) randomized-controlled trials of stimulation of the hippocampus for mesial temporal lobe epilepsy, with all three showing a reduction in seizure frequency (15%–40%) versus placebo [66,67,68].…”

“…There have been no randomized controlled trials for the use of DBS in pediatric patients with epilepsy. A recent systematic review identified case reports totaling 40 patients ages 4–18 who were treated with DBS for a variety of indications [60]. Five (12%) became seizure-free.…”

Thalamocortical dysrhythmia in intraoperative recordings of focal epilepsy

“…Finally, these findings provide further support for the rapidly expanding field of neuromodulation for the treatment of focal epilepsy. In addition to Level I evidence for deep brain stimulation of the thalamus for treatment of epilepsy in adults (Fisher et al 2010), a recent systematic review of 40 children, many of them with focal pathology, also showed significant improvements with thalamic stimulation (Yan et al 2019). A focus on changes in impaired neural oscillations, both as biomarkers and targets of therapies, will be critical in the increasing application of neuromodulatory devices for epilepsy.…”

Sleep architecture and homeostasis in children with epilepsy: a neurodevelopmental perspective

“…62 Deep brain stimulation targeted at the centromedian or anterior thalamic nuclei is an emerging treatment modality in refractory childhood epilepsies. 63 However, the stimulation of these nuclei, which are closely associated with the ascending arousal system, may lead directly to electroclinical arousals in a voltage-dependent manner. 64…”