Clinical trial NCT04802135: Creation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy
Official title: Creation of a Register of Patients With Neonatal-onset Epileptic Encephalopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Epileptic Encephalopathy
Keywords: EOEE
epilepsy
KCNQ2
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2021-03-17
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Retrospective observational study initially then prospective with inclusion of all patients with a KCNQ2-REE whose diagnosis was made in the EPIGENE network

Brief summary: Electrical activity emerges in the third trimester of pregnancy, plays an important role in the construction of cortical maps, and is impaired in patients with severe early epileptic encephalopathies (EOEE). EOEE are rare and severe epileptic syndromes characterized by epilepsy that begins within the first three months of life and is associated with rapid deterioration of motor, cognitive and behavioral skills.

There is a genetic basis for the EOEE. Together with other laboratories, the investigators have identified de novo pathogenic variants in the KCNQ2 gene encoding the Kv7.2 subunit of the Kv7 / M potassium channel, a channel known to control neuronal excitability in the brain and spinal cord. via the current M (IM). Pathogenic variants of the KCNQ2 gene represent the main cause of EOEE and the term KCNQ2-related epileptic encephalopathy (KCNQ2-REE) is now used to define this condition.

KCNQ2-REE patients have a remarkably homogeneous phenotype at the start, with epilepsy that begins in the first days after birth, seizures that result in tonic muscle spasms that last from 1 to 10 seconds, and an interictal EEG called "suppression-burst". "That is, paroxysmal bursts of activity interspersed with periods of electrical silence. In this group, more than 50% of the patients present a remission of the epilepsy and a quasi-normalization of the EEG which can occur a few weeks to several months after the onset of the seizures. Despite this positive evolution in terms of seizures, the developmental progression is abnormal and the phenotype is severe with an absence of language, autistic behavior and a subsequent development of motor disorders such as diplegia, spasticity, ataxia or dystonia.

The ambition of this project is to increase knowledge of epileptic encephalopathies linked to KCNQ2 at the clinical and molecular levels, to decipher the pathophysiological mechanisms and to propose therapeutic strategies.

This project aims to better describe the clinical, EEG, imaging, developmental and long-term follow-up characteristics of patients carrying the KCNQ2 mutation identified in the laboratory.


Eligibility criteria: Inclusion Criteria:

* Epilepsy beginning before 1 month of life, and requiring the initiation of anti-epileptic treatment
* Without occasional cause
* Without brain malformation explaining epilepsy
* No opposition from parents / guardians
* Possibility for parents to complete parent questionnaires

Exclusion Criteria:

* Neonatal attacks of occasional cause (glycemic disorder, infection, etc.)
* Acquired neonatal epilepsy (post-anoxic encephalopathy, stroke sequelae, etc.)
* Neonatal epilepsy related to a brain malformation

Primary outcomes:
measure: importance of the developmental disorder
timeFrame: Month 36
measure: definition of the active phase of epilepsy
timeFrame: Month 36
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: CHU Brest
city: Lille
country: France
facility: CHRU Lille
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Hospices Civils Lyon
city: Marseille
country: France
facility: Hôpital La Timone
city: Montpellier
country: France
facility: CHU Montpellier
city: Paris
country: France
facility: APHP Pitié Salpêtrière
city: Paris
country: France
facility: APHP Robert Debré
city: Paris
country: France
facility: Hôpital Necker
city: Rennes
country: France
facility: CHU Rennes
city: Strasbourg
country: France
facility: CHRU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: Assistance Publique - Hôpitaux de Marseille
name: Jean Olivier Arnaud
role: STUDY_DIRECTOR
References: