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Study of Pathophysiology of Status Epilepticus and Dysimmune Encephalitis

Not Applicable
Recruiting
Conditions
Status Epilepticus
Dysimmune Encephalopathy
Interventions
Other: Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)
Registration Number
NCT04421846
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
400
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 3 : Control patientsBlood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)-
Group 1 : Status epilepticusBlood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)-
Group 2 : Dysimmune encephalitisBlood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)-
Primary Outcome Measures
NameTimeMethod
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 epilepticus9 months

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)

Secondary Outcome Measures
NameTimeMethod
Identification of new dysimmune abnormalities9 months

Lymphocyte phenotyping, cytokines quantification

Identification of new genetic pathways associated to dysimmune encephalitis and status9 months

Genetic biomarkers

Identification of new metabolic pathway that may participate in the excitotoxicity observed in status epilepticus or dysimmune encephalitis9 months

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).

Identification of specific EEG patterns associated to dysimmune encephalitis and/or status epilepticus9 months

EEG signals will be reviewed and classifiyed according to a EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs)

Trial Locations

Locations (1)

Hôpital de la Pitié Salpêtrière

🇫🇷

Paris, France

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