By Elodie Vaz | Published on February 12, 2026 | 3 min readEpilepsy
is a chronic neurological disorder characterized by excessive and
hypersynchronized electrical discharges of cerebral neurons, leading to
recurrent seizures. It affects approximately 650,000 people in France and
several million worldwide, and manifests through highly variable clinical
episodes ranging from brief alterations of consciousness to generalized
convulsions. In about one third of patients, seizures are not controlled by
antiseizure medications, defining drug-resistant epilepsy with a major impact
on quality of life and associated neurological risks. In treatment-resistant
focal forms, surgical resection of the epileptogenic focus remains the
therapeutic gold standard, but its indication is limited by the accessibility
of the area to be operated on and by the neurological risks inherent to
invasive procedures.
Published
in late December 2025 in Epilepsia, the study by Samalens et al.
evaluates a radically different approach to treating pharmacoresistant focal
epilepsy: Microbeam Radiation Therapy (MRT). This method is based on the use of
extremely narrow, spatially fractionated X-ray microbeams generated by a
synchrotron, in order to create highly localized micro-lesions at the epileptic
focus without resorting to open surgery. The main objective of the study is to
determine whether this spatial distribution of X-ray radiation can effectively
reduce seizures while minimizing damage to healthy brain tissue, potentially
paving the way for a non-invasive therapeutic alternative to surgery.
Two
irradiation strategies to target the epileptic focus
“X-ray
microbeams were initially shown to be effective in eliminating tumors, much
like Gamma Knife, the reference radiosurgery technique for epilepsy. Gamma
Knife first proved effective against cancers before finding an application in
targeting epileptic foci in the brain. This translational approach seemed
relevant to us, and our results support it,” explains Loan Samalens, PhD
student and first author of the study, in an Inserm press release.
To
test this hypothesis, the researchers used a well-established murine model of
mesial temporal lobe epilepsy (MTLE) induced by unilateral kainate injection
into the hippocampus of mice, producing hippocampal sclerosis confirmed by MRI
and spontaneous, drug-resistant focal seizures. After validation of the lesion,
the animals were exposed to X-ray microbeams under several experimental
configurations.
Reduced
seizures with a dose-dependent effect
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.
