Study of Pathophysiology of Status Epilepticus and Dysimmune Encephalitis

Study Overview
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Brief Summary
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COLETTE is an interventional study for which blood, cerebrospinal fluid and post-mortem tissues are collected in patients with status epilepticus or epilepsy associated to dysimmune encephalitis as well as in control patients, to better understand the pathophysiology of these severe epileptic disorders.

Detailed Description
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Epilepsy is one of the most common neurological condition which concerns around 50 million people worldwide. Epilepsy is characterized by a lasting predisposition to generate seizures. Epilepsy can present as heterogenous set of clinical symptoms and is related to extremely varied etiologies. Some epilepsies are triggered by antineuronal autoantibodies and/or complicated by a status epilepticus. These conditions may induce brain atrophy, and severe neurological sequels. The severity of these epilepsies requires significant efforts to (i) identify new therapeutic strategies able to control the evolution of dysimmune encephalitis and refractory status epilepticus, (ii) to identify their etiologies and (iii) to propose neuroprotective strategies. Therefore, the investigators will organize a collection of biological samples (blood, cerebrospinal fluid, post-mortem brain tissues) and paraclinical data (electroencephalogram, evoked potential, CT, MRI) in patients with severe epilepsies, whether or not associated with autoantibodies, and/or evolving into status epilepticus. This study should bring new insights allowing to better understand mechanisms that trigger the emergence of an epileptic brain (epileptogenesis) through : (i) the identification and characterization of new pathophysiological pathways involving autoimmunity directed against the cerebral cortex and associated with severe epilepsy (ii) the identification and characterization of pathophysiological pathways participating in the excitotoxicity observed in status epilepticus.

Official Title
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COLETTE : Study of the Pathophysiology of Status Epilepticus and Dysimmune Encephalitis and Identification of Valuable Biomarkers

Conditions
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Status Epilepticus, Dysimmune Encephalopathy

Intervention / Treatment
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* Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1: Patients aged 2 years or above, with status epilepticus. Affiliation to a French social security system excluding Aide Médicale Etat (AME). Patients or relatives have been informed and given free informed and written consent to participate Patients under legal protection (guardianship, curatorship) or not Group 2: Patients aged 2 years or above, with clinical signs of epilepsy associated to dysimmune encephalitis. Affiliation to a French social security system excluding Aide Médicale Etat (AME). Patients or relatives have been informed and given free informed and written consent to participate Patients under legal protection (guardianship, curatorship) or not Group 3: Patients aged 18 years or above, without status epilepticus and/or dysimmune encephalitis. Affiliation to a French social security system excluding Aide Médicale Etat (AME). Patients or relatives have been informed and given free informed and written consent to participate Patients under legal protection (guardianship, curatorship) or not Exclusion Criteria: Group 1: Women with known or clinically detected pregnancy. Patient deprived of liberty Patients with known neurodegenerative disease. Group 2: Women with known or clinically detected pregnancy. Patient deprived of liberty Patients have been already treated by corticoids or IgIV. Group 3: Women with known or clinically detected pregnancy. Patient deprived of liberty. Patients with status epilepticus. Patients with known neurodegenerative disease, brain tumor, severe head trauma, meningitis, subarachnoid hemorrhages, stroke.

Ages Eligible for Study
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Minimum Age: 2 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group 1 : Status epilepticus<br> | Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)<br>* Collection of biological samples and clinical/paraclinical data<br>|
| Other: Group 2 : Dysimmune encephalitis<br> | Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)<br>* Collection of biological samples and clinical/paraclinical data<br>|
| Other: Group 3 : Control patients<br> | Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)<br>* Collection of biological samples and clinical/paraclinical data<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of (i) antibodies in the plasma and in the cerebrospinal fluid of patients with dysimmune encephalitis and (ii) biomarkers for neuronal death in the plasma and in the cerebrospinal fluid of patients with status epilepticus | Looking for antibodies with cell-based binding assay or monospecific recombinant assay. Identification of biomarkers for neuronal death with electrochemiluminometric sandwich immunoassays (Kryptor and ModularE170, Roche Diagnostic) | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of new dysimmune abnormalities | Lymphocyte phenotyping, cytokines quantification | 9 months | 
| Identification of specific EEG patterns associated to dysimmune encephalitis and/or status epilepticus | EEG signals will be reviewed and classifiyed according to a EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs) | 9 months | 
| Identification of new genetic pathways associated to dysimmune encephalitis and status | Genetic biomarkers | 9 months | 
| Identification of new metabolic pathway that may participate in the excitotoxicity observed in status epilepticus or dysimmune encephalitis | Looking for diagnostic and prognosis biomarkers. Characterization of the brain cholesterol homeostasis with UPLC-MS/MS method and enzymatic assays. Evaluation of new biomarkers (proteins, lipids, genes). | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Status Epilepticus, Autoimmunity