Clinical trial NCT06271785: Prognostic Value of High-resolution Electrical Source Imaging on the Success of Pediatric Focal Epilepsy Surgery
Official title: ISEPEE : Prognostic Value of High-resolution Electrical Source Imaging on the Success of Pediatric Focal Epilepsy Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Epilepsy in Children
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2024-02-22
Enrollment: 120
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study investigates the usefulness of high resolution electrical source imaging (HR-ESI) in the setting of presurgical evaluation of drug-resistant focal epilepsy in children.

This method is based on an estimation of the intra-cerebral source that produces a signal recorded by scalp electrodes by solving the inverse problem, taking into account attenuation factors resulting from particular conductivity properties of the cerebral, peri-cerebral and cranial tissues.

Electrical sources are then fused on structural magnetic resonance imaging (MRI).

Scalp EEG recorded using 64 to 256 electrodes refers to as high resolution EEG (HR-EEG), leading to HR-ESI.

Studies based on small population of children or on mixt population of children and adults showed that HR-ESI has accuracy values, i.e. percentage of true positives (electrical source localized in the brain area resected and success of surgery) and true negatives (electrical source localized outside the brain area resected and failure of surgery) among the total population, ranging from 50 to 80%.

Discrepancies between studies could be explained by the limited number of patients included or by the mixture of pediatric and adult data.

Another limitation of previously published studies is that the spatial pattern of dipole source distribution was not taken into account to determine prediction accuracy of ESI.

Studies using magnetoencephalography (MEG) to perform magnetic source imaging (MSI) suggest that the spatial pattern of dipole source distribution needs to be considered, a spatially-restricted dipole distribution being associated with better post-surgical outcome when resected.

To tackle these issues, the investigators aim to conduct the first large prospective multicentric study in children with focal epilepsy candidates to surgery to assess prediction accuracy of ESI based on the finding of tight clusters of dipoles.

This is original as this pattern (tight versus loose cluster of dipoles) has been studied by several researchers using MEG but not using HR-EEG.

The investigators make the hypothesis that HR-EEG will allow to identity good candidates for epilepsy surgery and thus to offer this underutilized treatment in more children with better post-surgical outcome.

Among the secondary objectives, the investigators will address methodological issues related to the resolution of the inverse problem (methods using distributed sources models versus methods based on equivalent dipole estimation), the potential added value to model high-frequency oscillations (HFO), and the investigators will assess the cost-utility of the HR-ESI procedure.

Detailed description: This study investigates the usefulness of high resolution electrical source imaging (HR-ESI) in the setting of presurgical evaluation of drug-resistant focal epilepsy in children.

This method is based on an estimation of the intra-cerebral source that produces a signal recorded by scalp electrodes by solving the inverse problem, taking into account attenuation factors resulting from particular conductivity properties of the cerebral, peri-cerebral and cranial tissues.

Electrical sources are then fused on structural magnetic resonance imaging (MRI).

Scalp EEG recorded using 64 to 256 electrodes refers to as high resolution EEG (HR-EEG), leading to HR-ESI.

Studies based on small population of children or on mixt population of children and adults showed that HR-ESI has accuracy values, i.e. percentage of true positives (electrical source localized in the brain area resected and success of surgery) and true negatives (electrical source localized outside the brain area resected and failure of surgery) among the total population, ranging from 50 to 80%.

Discrepancies between studies could be explained by the limited number of patients included or by the mixture of pediatric and adult data.

Another limitation of previously published studies is that the spatial pattern of dipole source distribution was not taken into account to determine prediction accuracy of ESI.

Studies using magnetoencephalography (MEG) to perform magnetic source imaging (MSI) suggest that the spatial pattern of dipole source distribution needs to be considered, a spatially-restricted dipole distribution being associated with better post-surgical outcome when resected.

To tackle these issues, the investigators aim to conduct the first large prospective multicentric study in children with focal epilepsy candidates to surgery to assess prediction accuracy of ESI based on the finding of tight clusters of dipoles.

This is original as this pattern (tight versus loose cluster of dipoles) has been studied by several researchers using MEG but not using HR-EEG.

The investigators make the hypothesis that HR-EEG will allow to identity good candidates for epilepsy surgery and thus to offer this underutilized treatment in more children with better post-surgical outcome.

Among the secondary objectives, the investigators will address methodological issues related to the resolution of the inverse problem (methods using distributed sources models versus methods based on equivalent dipole estimation), the potential added value to model high-frequency oscillations (HFO), and the investigators will assess the cost-utility of the HR-ESI procedure.

The study focuses on epileptic children who are candidates to a procedure of epilepsy surgery aiming to make them seizure-free. The principle of epilepsy surgery is to remove the brain area that generates patient's seizures, i.e. the seizure onset zone (SOZ). Candidates are patients with focal seizures that do not completely respond to the medical treatment and impact their quality of life. This represents 5-10% of epileptic children. Pre-surgical evaluation of these patients consists to perform in a first step non-invasive methods aimed to localize the SOZ: video-EEG in order to characterize usual seizures of the patient and to record and localize interictal epileptiform discharges (IED), MRI to search for a structural epileptogenic lesion, and positron emission tomography (PET) with fluorodeoxyglucose (FDG) to search for a brain area showing abnormal FDG uptake. After this so-called phase 1 work-up, the case is discussed in a multidisciplinary meeting, resulting in one of the 3 following decisions: (1) surgical resection when information from phase 1 is considered as sufficient, (2) continuation of the surgical process by performing a phase 2 evaluation, i.e. an invasive EEG recording using intracranial electrodes implanted by stereotaxy (SEEG), when information from phase 1 is considered as insufficient but made possible to pose a hypothesis regarding the localization of the SOZ, and (3) rejection for surgery. In children, epilepsy makes patient seizure-free in 60-80% of the cases. HR-ESI is a relatively new method that has been developed to localize non-invasively the SOZ with the hope to decrease the number of patients rejected for surgery or oriented to phase 2, and to increase the rate of success of epilepsy surgery.

Eligibility criteria: Inclusion Criteria:

1. Age≥2 and \<17 years;
2. Drug-resistant focal epilepsy (failure of at least 2 well-conducted drug trials);
3. Phase 1 pre-op evaluation with scalp video-EEG recording, MRI and PET-FDG suggesting that the patient could be a good candidate for epilepsy surgery;
4. Recent scalp EEG record (within 12 months) showing the presence of interictal spikes;
5. High-quality and recent (within 6 months) structural MRI with 3D-T1 sequences covering the whole brain and the scalp available.

Exclusion Criteria:

1. Behavioral deficits making recording of scalp EEG impossible without sedation;
2. Informed consent form not signed by the parents;
3. Patient not affiliated to a social security system

Primary outcomes:
measure: Prediction accuracy index
timeFrame: 24 months
Secondary outcomes:
measure: Localization of the epileptogenic zone (Baseline)
timeFrame: Baseline
measure: Localization of the epileptogenic zone (After Surgery)
timeFrame: 24 months (= V3)
measure: preoperative accuracy of epileptogenic source localization
timeFrame: 12 months (= V2)
measure: prognostic value of HFO
timeFrame: 24 months (= V3)
measure: Impact of method of sources reconstruction, conditions of EEG recordings and sampling rate
timeFrame: 3 months (= V1)
measure: health-economic modeling
timeFrame: 24 months (= V3)
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers university hospital, Pédiatric department
city: Lille
country: France
facility: Lille University Hospital, Clinical Neurophysiology Department
city: Lyon
country: France
facility: Civil Hospices of Lyon, Functional Neurology Department
city: Marseille
country: France
facility: Marseille Timone University Hospital, Epileptology and Cerebral Rhythmology Department
city: Nancy
country: France
facility: Nancy University Hospital, Neurology Department
city: Paris
country: France
facility: Paris Neck University Hospital, Pediatric department
city: Paris
country: France
facility: Paris Robert-Debré University Hospital, Department of Physiology, Pediatric functional explorations
city: Paris
country: France
facility: Rothschild Ophtalmologic Fondation, Pediatric neurosurgery Department
city: Rennes
country: France
facility: Rennes University Hospital, Pediatric department
Study officials:
References: