Innovative minimally invasive options to treat drug-resistant epilepsies

L Samalens; C Courivaud; J-F Adam; E L Barbier; R Serduc; A Depaulis

doi:10.1016/j.neurol.2023.05.006

Innovative minimally invasive options to treat drug-resistant epilepsies

Rev Neurol (Paris). 2023 Oct 3:S0035-3787(23)01038-X. doi: 10.1016/j.neurol.2023.05.006. Online ahead of print.

Authors

L Samalens¹, C Courivaud², J-F Adam³, E L Barbier², R Serduc⁴, A Depaulis⁵

Affiliations

¹ Université Grenoble-Alpes, Inserm, U1216, Grenoble Institut Neurosciences, 38000 Grenoble, France; Université Grenoble-Alpes, Inserm, UA7, STROBE, 38000 Grenoble, France.
² Université Grenoble-Alpes, Inserm, U1216, Grenoble Institut Neurosciences, 38000 Grenoble, France.
³ Université Grenoble-Alpes, Inserm, UA7, STROBE, 38000 Grenoble, France; Centre Hospitalier Universitaire Grenoble-Alpes, 38700 La Tronche, France.
⁴ Université Grenoble-Alpes, Inserm, UA7, STROBE, 38000 Grenoble, France.
⁵ Université Grenoble-Alpes, Inserm, U1216, Grenoble Institut Neurosciences, 38000 Grenoble, France. Electronic address: antoine.depaulis@univ-grenoble-alpes.fr.

PMID: 37798162
DOI: 10.1016/j.neurol.2023.05.006

Abstract

Despite the regular discovery of new molecules, one-third of epileptic patients are resistant to antiepileptic drugs. Only a few can benefit from resective surgery, the current gold standard. Although effective in 50-70% of cases, this therapy remains risky, costly, and can be associated with long-term cognitive or neurological side effects. In addition, patients are increasingly reluctant to have a craniotomy, emphasizing the need for new less invasive therapies for focal drug-resistant epilepsies. Here, we review different minimally invasive approaches already in use in the clinic or under preclinical development to treat drug-resistant epilepsies. Localized thermolesion of the epileptogenic zone has been developed in the clinic using high-frequency thermo-coagulations or magnetic resonance imaging-guided laser or ultrasounds. Although less invasive, they have not yet significantly improved the outcomes when compared with resective surgery. Radiosurgery techniques have been used in the clinic for the last 20years and have proven efficiency. However, their efficacy is not better than resective surgery, and various side effects have been reported as well as the potential risk of sudden unexpected death associated with epilepsy. Recently, a new strategy of radiosurgery has emerged using synchrotron-generated X-ray microbeams: microbeam radiation therapy (MRT). The low divergence and high-flux of the synchrotron beams and the unique tolerance to MRT by healthy brain tissues, allows a precise targeting of specific brain regions with minimal invasiveness and limited behavioral or functional consequences in animals. Antiepileptic effects over several months have been recorded in animal models, and histological and synaptic tracing analysis suggest a reduction of neuronal connectivity as a mechanism of action. The possibility of transferring this approach to epileptic patients is discussed in this review.

Keywords: Animal models; Drug-resistant; Focal epilepsy; Noninvasive therapy; Radiosurgery.

Publication types

Review