Nearly 650,000 people in France live with epilepsy, and close to half are under the age of 20. This brain disorder encompasses a range of symptoms, including difficulties with cognition, sleep, or language.
The most well-known and dramatic manifestation of the condition is an epileptic seizure, which results from sudden, excessive bursts of electrical activity in the brain’s cortex.
Limited Options for Drug Resistance
The majority of patients – 60 to 70 percent – are treated with medications that control their epilepsy. However, for the remaining 30 to 40 percent, the disease is resistant to drugs and seizures continue. In these cases, surgery targeting and removing the affected area of the brain is the only option.
However, this is only feasible for a small number of patients because it can only be considered “if the area responsible for the seizures (the epileptogenic zone) is focal, unique, and sufficiently distant from highly functional areas (involved in language, motor skills, etc.),” according to the University Hospital of Rouen (Seine-Maritime).
For others, “palliative approaches, more or less invasive, have been developed for about thirty years,” notes Inserm. Stereotactic radiosurgery (Gamma Knife), which uses a broad gamma ray beam to damage and deactivate the epileptic focus in the brain, is currently the most widely used non-invasive therapy for focal epilepsies. However, the beam is not very precise, and the therapy is only effective in 50 percent of cases with significant side effects.”
Researchers are exploring modern approaches to treat epilepsy that doesn’t respond to medication. A team from Inserm and the University of Grenoble Alpes (UGA) is investigating a novel radiosurgery technique called Microbeam Radiation Therapy (MRT). According to Inserm, the researchers utilize a synchrotron – a large electromagnetic instrument – to divide an X-ray beam into extremely fine microbeams (50 µm, or the thickness of a hair).
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Dividing X-ray Beams into Microbeams
That’s why a team from Inserm and the University of Grenoble Alpes (UGA) has been exploring a new radiosurgery approach for treating drug-resistant epilepsies for nearly a decade. It’s called Microbeam Radiation Therapy (MRT). Inserm explains that, “the researchers use a synchrotron, a large electromagnetic instrument, to divide an X-ray beam into extremely fine microbeams (50 µm – micrometers, or the thickness of a hair).”
These microbeams can deliver very high doses of X-rays precisely and locally, targeting only the areas responsible for seizures without affecting neighboring tissues. “X-ray microbeams initially proved effective in eliminating tumors, as Gamma Knife has. This therapy has shown efficacy against cancers before finding an application for targeting epileptic foci in the brain. We found this translation relevant, and our results prove it,” explains Loan Samalens, a doctoral student and first author of the study.
Significant and Lasting Antiepileptic Effect
MRT was tested on a mouse model with mesial temporal epilepsy, a form of epilepsy that is resistant to drug treatments. Irradiation of the affected area with X-ray microbeams had an antiepileptic effect for two months. The occurrence of seizures was significantly and durably reduced. These results were published on December 23, 2025, in the journal *Epilepsia*.
“We started by irradiating the affected brain areas with a single trajectory at increasing doses. The more we increased the dose, the more effective the treatment was, but the higher the mortality rate. But by dividing the same dose into several trajectories, allowing the delivered X-ray dose to be distributed, we obtained better results. The treatment is more effective with fewer toxic effects. The results obtained are even more robust and relevant than the current reference treatment, Gamma Knife. A therapeutic effect is obtained without inducing the major side effects usually observed with conventional radiation therapies,” continues Loan Salamens.
Before a clinical application can be considered, the irradiation parameters still demand to be optimized, their long-term effects clarified, and the mechanisms of these microlesions on epilepsy understood. Because synchrotrons are relatively unique machines, the mechanism must also be reproducible without one.
“The goal is to verify that the principle of spatial fractionation can be applied without a synchrotron, with machines realistic for medical practice and grounded in reality for patients,” explains Antoine Depaulis, Inserm emeritus research director.
