Neuromodulation methods in the treatment of drug-resistant epilepsy: history, clinical efficacy and unresolved issues. A literature review

Abstract

Drug-resistant epilepsy affects approximately one-third of patients and is often not amenable to resective surgery due to the bilateral nature of the epileptogenic network, multifocality, or localization of the seizure onset zone within eloquent cortical areas. In such cases, neuromodulation techniques are preferable, as they enable targeted modulation of key nodes within epileptic networks without the need for brain tissue resection. The purpose of this review is to analyze the development, anatomical and physiological rationale, clinical efficacy, safety, and applications of neuromodulation methods in drug-resistant epilepsy. These include deep brain stimulation of thalamic nuclei (anterior nucleus of the thalamus [ANT-DBS] and centromedian nucleus [CM-DBS]), stimulation of mesial temporal structures, vagus nerve stimulation (VNS), and responsive neurostimulation (RNS). A comprehensive review of Russian and international literature indexed in PubMed/MEDLINE, eLIBRARY. RU, and CyberLeninka was conducted, supplemented by reference lists of relevant publications. A total of 50 sources were included (4 Russian and 46 international). In focal drug-resistant epilepsy, stimulation of the anterior nucleus of the thalamus appears to be the most well-founded and effective approach (as demonstrated in the SANTE trial). In contrast, for generalized and multifocal epilepsies, including Lennox-Gastaut syndrome, stimulation of the centromedian nucleus is commonly employed. In patients unsuitable for resective surgery, hippocampal and amygdala stimulation serves as a tissue-sparing option, particularly in mesial temporal lobe epilepsy. Vagus nerve stimulation, including closed-loop systems with ictal tachycardia detection, provides a significant reduction in seizure frequency with a favorable safety profile. Responsive neurostimulation offers the most personalized closed-loop approach, with progressive efficacy over time and additional diagnostic value. Therefore, neuromodulation expands therapeutic options for drug-resistant epilepsy. However, key unresolved issues remain, including prediction of therapeutic response, standardization of patient selection, optimization of stimulation parameters, and assessment of long-term cognitive and affective outcomes.