Epilepsy: X-ray therapy for drug-resistant forms

Two main irradiation modalities were tested:

● Single-port irradiation with peak doses of 125 Gy, 250 Gy, or 500 Gy directed at the affected hippocampus,

● Multi-port irradiation (2 or 5 cumulative trajectories delivering 125 Gy at the target) to distribute the beam and reduce potential toxicity.

The epileptic phenotype was monitored by electroencephalography (EEG) over eight weeks following treatment, and histological analyses were performed to assess the tissue impact of the microbeams.




Lesions confined to targeted areas




The main results indicate that microbeam irradiation significantly reduces epileptic activity according to the following parameters:

● Dose-dependent reduction: Single-port irradiation at 125 Gy and 250 Gy led to a significant reduction in EEG-recorded epileptic events, demonstrating a clear antiepileptic effect correlated with the applied dose. However, at 500 Gy, despite seizure reduction, increased mortality was observed, suggesting acute toxicity at this level.

● Effects of multiple trajectories: Dose distribution across 2 or 5 trajectories improved antiepileptic efficacy while reducing collateral damage to surrounding tissues. The 5-port configuration offered the best compromise between seizure control and tissue tolerance.

● Targeted histological analysis: Tissue assessments showed that damage (neuronal loss, microgliosis, astrogliosis) was essentially confined to the microbeam paths, while adjacent areas remained largely free of necrosis or significant edema.

“MRT could represent an effective non-invasive therapeutic alternative for treatment-resistant epilepsy, but this technique still needs to be brought closer to clinical use. The synchrotron in Grenoble remains quite unique. We are therefore seeking to test mini-beams (375 µm) such as those that can be produced by less powerful X-ray irradiators already available in hospitals. The aim is to verify that the principle of spatial fractionation can be applied without a synchrotron, using machines that are realistic for medical practice and grounded in concrete benefits for patients,” explains Antoine Depaulis, Inserm emeritus research director, in the same press release.

While these preclinical results are promising, clinical translation of this technology to humans remains a major challenge. The limited availability of clinical synchrotrons, the need for further optimization of dose parameters, and a detailed understanding of the mechanisms underlying the antiepileptic effect are all obstacles that must be overcome before any therapeutic application. Future studies will also need to investigate the long-term effects of this treatment and adapt the technique to more accessible X-ray sources in hospital settings. Nevertheless, this approach opens a new potential non-invasive avenue for the management of pharmacoresistant epilepsies, which until now have been limited by conventional surgical options.


    Read next: LITT vs. Surgery: The Revolution in Temporal Epilepsy Treatments?




About the author – Elodie Vaz 
Health journalist, graduated from the CFPJ in 2023, Élodie explores the marks that illnesses leave on bodies and, more broadly, on human life. A state-registered nurse since 2010, she spent twelve years at patients’ bedsides before trading her stethoscope for a notebook. She now examines the connections between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.