The goal of this clinical trial is to assess the feasibility, safety, and tolerance of MRI-guided High-Intensity Focused Ultrasound (HIFU) for the treatment of drug-resistant focal epilepsy in adult patients with MRI-visible brain lesions. The main question it aims to answer is whether HIFU can safely and effectively achieve the target ablative temperature (≥52 °C) within epileptogenic lesions, thereby enabling successful thermal ablation of the epileptogenic focus. This pilot, single-center study is single arm, prospective, non-comparative and uncontrolled. This will take place over a period of 24 months. After information (V1), inclusion (V2) and presurgical (V3) visits, a surgical visit will be performed during hospitalization in the neurosurgery department (V4) for HIFU therapy and 5 follow-up consultation visits (V5, V6, V7, V8, and V9 to J7, M1, M3, M6, and M12).
Epilepsy is a common, long-lasting neurological disorder with significant social ramifications. In France, it is estimated that over 500,000 individuals are affected by epilepsy, with 50,000 experiencing drug-resistant partial epilepsy. Approximately 10,000 patients with drug-resistant partial epilepsy may benefit from neurosurgical treatment to excise their epileptogenic focus. However, only 300 operations are performed annually in France. Epilepsy surgery not only has medical benefits (with 50-80% of operated patients being seizure-free), but also reduces the risk of excess mortality in this population. Furthermore, it is a cost-effective solution, as drug-resistant epileptic patients can cost up to $138,000 in treatment and monitoring throughout their lifetime. High-Intensity Focused Ultrasound (HIFU) is a noninvasive method that uses heat to destroy brain lesions, leading to coagulation and necrosis of the lesion under control. It has been successfully used to treat essential tremors, Parkinson's disease, and neuropathic pain, and may be used to treat epilepsy lesions that are inaccessible to conventional surgery, located in eloquent areas, or in patients with contraindications to general anesthesia. The goal of this study is to assess the feasibility, tolerance, and safety of HIFU use in lesions responsible for drug-resistant epilepsy, as this represents the first use of HIFU for this indication. Main objective : To assess the feasibility of employing HIFU-based thermoablation for the treatment of drug-resistant epilepsy caused by intracerebral lesions.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
\- HIFU-based thermoablation: non-invasive brain tissue ablation by a MRI-guided transcranial ultrasound (MRgFUS) system. • Installation of a stereotaxy frame: 4 cranial skin points under local anesthesia with Xylocaine, Perfalgan IV 2g in IVL, usual brushing protocol with iodized alcohol, and removal of stereotaxy frame • MRI with contrast agent administration acquisition and definition of the area to be treated and ultrasound parameters by neurosurgeons, neuroradiologists, and physicists. • Realization of thermoablation under real-time control using MRI and clinical control.
Surface EEG: assessment of residual seizures and interictal epileptiform activity.
Brain MRI in the Neuroradiology department to monitor lesion volume, possible reactive edema, and possible mass effect. The imaging protocol will include 3D T1, 3D T2, 3D FLAIR, SWI, Diffusion and 3D T1 after gadolinium injection sequences.
Target ablative temperature
Achievement of the target ablative temperature (at least one timepoint at 52 °C (15 °C above body temperature)) on calorimetric MRI sequences performed in real time during HIFU treatment (real-time quantitative measurements + CSV data extracted at the end of the procedure).
Time frame: During the procedure between 60 and 75 days after inclusion
Post-intervention complications of grade≥2
Clinical safety: Post-intervention complications at D30 of grade≥2 (complications requiring therapeutic intervention or after-effects or death) according to Mathon et al., Journal of Neurology, 2015.
Time frame: From day 0 to day 30 after the procedure.
Morphological MRI
Evaluation measured by morphological MRI corresponding to necrosis induced by MRI (axes, volume, ablation margins).
Time frame: From the day of the procedure up to 12 months after the procedure.
Thermometric MRI monitoring during HIFU thermoablation
Time frame: At D0 during the procedure
Cumulative thermal dose during HIFU thermoablation
Time frame: At D0 during the procedure
ILAE classification
Time frame: At 12 months after the procedure
Frequency of epileptic seizures
Number of epileptic seizures using the seizure diary starting
Time frame: From inclusion up to 12 months after the procedure
Intensity of epileptic seizures
Intensity of epileptic seizures using the seizure diary
Time frame: From inclusion up to 12 months after the procedure
Change in antiepileptic treatment
Number of antiepileptic drugs, modification in antiepileptic dose.
Time frame: From inclusion up to 12 months after the procedure
Antiepileptic effectiveness EEG
Surface EEG in comparison with pretreatment EEG (seizures, interictal abnormalities).
Time frame: From inclusion up to 12 months after the procedure
Neuropsychological evaluation
Change from pre-treatment assessment performed in the inclusion work-up of the neuropsychological assessment at M12
Time frame: At inclusion and at 12 months
Evaluation of quality of life
Mean change of global score of quality of life according to the quality of life in epilepsy inventory-31 (QOLIE-31) questionnaire from pre-treatment assessment during the inclusion work-up at M12.
Time frame: At inclusion and at 12 months
MRI-assessed radiological safety
Thermometric MRI monitoring on D0, induced edema on D7 and D30
Time frame: From the day of the procedure up to days 30 after the procedure
Adverse events related to HIFU treatment
Frequency, intensity, and severity of adverse effects collected during treatment and follow-up period
Time frame: From the D0 the day of procedure up to 12 months after the procedure
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