Better spatial localization of the epileptogenic zone to overcome drug-resistant epilepsy

Mesiotemporal epilepsy is a form of epilepsy that is often drug-resistant. Doctors then have no choice but to offer patients surgery to remove the area of the brain responsible for the seizures, known as the “epileptogenic zone” (EZ). However, such surgery is only effective in 50-70% of cases, not least because of the difficulty of precisely locating the area of the brain to be removed.

During the preparation of her PhD, under the supervision of Florence Fauvelle, an INSERM researcher in the “Functional Neuroimaging and Cerebral Perfusion” team at GIN, Alicia Plaindoux worked on the development of a more efficient method for characterizing the epileptogenic zone.

"Locating the epileptogenic focus may require the implantation of intracranial electrodes and the recording of the brain's electrical activity while the patient is hospitalized for several days. This is an invasive and burdensome method for the patient, which unfortunately may not be sufficiently effective, notably due to the lack of spatial resolution of the electrodes", explains Florence Fauvelle.  "Using metabolomics*, we had already shown that the neurotransmitter GABA was strongly increased in the epileptogenic zone in epileptic mice, while Glx (glutamate + glutamine) was decreased.  We therefore used the GABA/Glx ratio as a biomarker specific to the epileptogenic zone".

The team, in collaboration with Vasile stupar, engineer at the IRMaGe MRI platform, developed an original magnetic resonance spectroscopic imaging (MRSI) method called MEGA-LASER CSI, coupled with dedicated data analysis, to map GABA and Glx in the brains of epileptic mice.

Neuroscientists have shown that the GABA/Glx ratio is much higher in the epileptogenic zone than in the rest of the brain or in healthy animals.

Their method therefore makes it possible to locate more precisely and non-invasively the area responsible for epileptic seizures. In the longer term, it could even be included in pre-surgical assessments as a method of spatially localizing the epileptic zone.

“This research work has produced many interesting and very robust results” confides Florence Fauvelle. "We hope that this method will soon be used on other animal models of epilepsy or other pathologies where GABA is deregulated. Ultimately, we hope to improve surgery for patients with focal epilepsy."
 

Reference : 

Mapping GABA+/Glx in experimental temporal lobe epilepsy using edited-MRSI at 9.4T
Alicia Plaindoux, Yann Le Fur, Clothilde Courivaud, Camille Beets, Loan Samalens, Julien Valette, Benjamin Lemasson, Emmanuel L. Barbier, Vasile Stupar, Florence Fauvelle
NeuroImage, Volume 315, 15 July 2025, 121274

* Metabolomics is a very recent science that studies all the primary metabolites (sugars, amino acids, fatty acids, etc.) present in a cell, organ or organism.