Neuromodulation in drug‐resistant epilepsy: A review of current knowledge

Abstract

Nearly 1% of the global population suffers from epilepsy. Drug‐resistant epilepsy (DRE) affects one‐third of epileptic patients who are unable to treat their condition with existing drugs. For the treatment of DRE, neuromodulation offers a lot of potential. The background, mechanism, indication, application, efficacy, and safety of each technique are briefly described in this narrative review, with an emphasis on three approved neuromodulation therapies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT‐DBS), and closed‐loop responsive neurostimulation (RNS). Neuromodulatory approaches involving direct or induced electrical currents have been developed to lessen seizure frequency and duration in patients with DRE since the notion of electrical stimulation as a therapy for neurologic diseases originated in the early nineteenth century. Although few people have attained total seizure independence for more than 12 months using these treatments, more than half have benefitted from a 50% drop in seizure frequency over time. Although promising outcomes in adults and children with DRE have been achieved, challenges such as heterogeneity among epilepsy types and etiologies, optimization of stimulation parameters, a lack of biomarkers to predict response to neuromodulation therapies, high‐level evidence to aid decision‐making, and direct comparisons between neuromodulatory approaches remain. To solve these existing gaps, authorize new kinds of neuromodulation, and develop personalized closed‐loop treatments, further research is needed. Finally, both invasive and non‐invasive neuromodulation seems to be safe. Implantation‐related adverse events for invasive stimulation primarily include infection and pain at the implant site. Intracranial hemorrhage is a frequent adverse event for DBS and RNS. Other stimulation‐specific side‐effects are mild with non‐invasive stimulation.

Personalized strategies of neurostimulation: from static biomarkers to dynamic closed-loop assessment of neural function

“…This is due to several reasons. First, seizure suppression neurostimulation methods are very diverse and rely on both invasive ( Velasco et al, 2022 ; Xue et al, 2022 ) and non-invasive ( Berényi et al, 2012 ) methodologies, the former representing a much better developed and wider frontier of investigation. Second, both modalities have closed loop solutions, including an FDA-approved system: Neuropace RNS ™ ; the importance of which will be further detailed in the next section.…”

A Comprehensive Review of Emerging Trends and Innovative Therapies in Epilepsy Management

“…The RNS system consists of a small neurostimulator device that is surgically implanted in the skull, along with one or two intracranial electrodes placed in or near the epileptogenic brain region responsible for seizure initiation [ 45 , 46 , 47 ]. The system operates on the fundamental principle of closed-loop neurostimulation, wherein it continuously monitors brain activity and delivers electrical stimulation in response to detected abnormal patterns [ 48 ]. The mechanism of action of RNS includes the following: (1) Monitoring brain activity: The implanted electrodes continuously record the electrical signals from the brain, detecting subtle changes that precede the onset of a seizure.…”

Neuromodulation in Children with Drug-Resistant Epilepsy

“…The RNS implantation is associated with surgery-related adverse effects like infection and pain at the site of implantation or intracranial hemorrhage with electrode implantation. 41…”

“…The RNS implantation is associated with surgery-related adverse effects like infection and pain at the site of implantation or intracranial hemorrhage with electrode implantation. 41 In selection of DBS targets for epilepsy, the anterior nucleus and the centromedian (CM) nucleus of the thalamus are most frequently utilized. 42 Hippocampal targets have been better investigated utilizing RNS (Neuropace trial), and other various investigations (including the ventral posteromedial nucleus and posterior hypothalamic region) for face pain and headaches have been studied with benefit noted when appreciated in aggregate, but additional controlled large studies are required.…”