Study of Pathophysiology of Status Epilepticus and Dysimmune Encephalitis

Official title

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

Overview

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.

Interventions

• Other Blood sampling, cerebrospinal fluid , post-mortem cerebral tissues (NA for the Group 3)
  Collection of biological samples and clinical/paraclinical data
• Other Blood sampling, cerebrospinal fluid, stool sampling post-mortem cerebral tissues (NA for the Group 3)
  Collection of biological samples and clinical/paraclinical data

Primary outcome measures

• 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 [Time frame: 9 months and 24 months]

Secondary outcome measures (4)

• Identification of new dysimmune abnormalities [Time frame: 9 months and 24 months]
• Identification of specific EEG patterns associated to dysimmune encephalitis and/or status epilepticus [Time frame: 9 months and 24 months]
• Identification of new genetic pathways associated to dysimmune encephalitis and status [Time frame: 9 months and 24 months]
• Identification of new metabolic pathway that may participate in the excitotoxicity observed in status epilepticus or dysimmune encephalitis [Time frame: 9 months and 24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

France · 1 center

• Hôpital de la Pitié Salpêtrière — Paris

Identifiers

NCT: NCT04421846 · APHP200306 · 2020-A00053-36

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗