Multimodal Study of the Human Brain Epilepsy Tissue

Study Overview
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Brief Summary
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The TIPI2 study is a blood and tissue collection protocol to create an annotated biorepository to support research in drug-resistant epilepsy. The aim of the study will be to identify new pathophysiological pathways. For this purpose, the investigators will investigate with a multimodal approach blood and brain samples from patients undergoing a surgery for focal drug-resistant epilepsy. The adult patients will be enrolled either during the pre-surgical evaluation or right before the surgery.

Detailed Description
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This study aims to investigate blood and brain samples from patients with drug-resistant epilepsy in order to identify new pathophysiological biomarkers. The investigators will first conduct multimodal research, including: electrophysiological analyses immunohistochemistry and genetic studies biochemistry analyses Samples will be stored at -80°C for future research. Patients will undergo a follow-up evaluation within the 36 months following the surgery. New clinical data and biological samples will be collected then.

Official Title
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Multimodal Study of the Human Brain Epilepsy Tissue

Conditions
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Focal Drug-resistant Epilepsy

Intervention / Treatment
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* Other: Blood and tissue collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 yo or above patients with a focal drug-resistant epilepsy patients hospitalized for a pre-surgical evaluation or for an epilepsy surgery consent obtained from the patient, or legally authorized representative affiliated to a social security system Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: epileptic patients<br>All patients will be enrolled in the same arm. Patients can be enrolled during the pre-surgical evaluation (group 1) or in the days preceding the surgery (group 2). | Other: Blood and tissue collection<br>* Blood will be collected for group 1 during (i) the enrolment visit, (ii) in the 24 hours following a seizure, (iii)before the surgery and (iv) in the 36 months following the surgery. The left-over tissue, not useful for diagnostic purpose, will be kept for research. Blood will be collected for group 2 right before the surgery and in the 36 months following the surgery. The left-over tissue not useful for diagnostic purpose will be kept for research.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by immuno-histological methods | The investigator will identify inflammatory cells (astrocytes, microglia, lymphocytes and neutrophil polynuclear cells) in the post-operative brain tissue, and will calculate if there is an increase of a part of these cells in the area, defined as the seizure onset zone, as compared to the non-epileptic areas. | At the day of surgery; analyses are based on the post-operative tissues | 
| Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by electrophysiological methods | The investigator will record local field potentials and neuronal firing rate from post-operative tissues, and we will research an increase of the rate of interictal epileptiform discharges and of the frequency of the neuronal firing in the seizure-onset zone, as compared to those in non-epileptic areas. | At the day of surgery; analyses are based on the post-operative tissues | 
| Identification of new pathophysiological mechanisms leading to focal drug-resistant epilepsy : analysis by RNA sequencing methods | The investigator will measure the expression of mRNA in cells of different parts of the post-operative brain tissue, and we will research specific expression of mRNA in the Seizure onset zone, as compared to that in other non-epileptic areas. | At the day of surgery; analyses are based on the post-operative tissues | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of new pathophysiological mechanisms associated with the occurrence of a seizure : analysis of biomarkers by ELISA methods | The investigator will measure several proteins by Elisa, and we will define if there is a specific increase of some proteins in the sample after a seizure, as compared to the level of these proteins far from a seizure. | from inclusion day to 36 months after the surgery | 
| Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of biomarkers by ELISA methods | The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients. | from inclusion day to 36 months after the surgery | 
| Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of blood cell subtypes by flow cytometry | The investigator will measure the different blood cells by flow cytometry, and we will define if there is a specific increase of some cell populations in the sample from epileptic patients, as compared to the level of these cell populations in non-epileptic patients. | from inclusion day to 36 months after the surgery | 
| Identification of new pathophysiological mechanisms associated with an active epilepsy : analysis of inflammation biomarkers by digital ultra-sensitive quantitation of proteins methods | The investigator will measure several inflammatory proteins including cytokines, and we will define if there is a specific increase of some proteins in the sample from epileptic patients, as compared to the level of these proteins in non-epileptic patients. | from inclusion day to 36 months after the surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Focal drug-resistant epilepsy, Surgery, Biorepository, Biomarkers