Genetic and Electrophysiologic Study in Focal Drug-resistant Epilepsies

NCT02890641 | Recruiting

• 1 other identifier: GDR_2015_15
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

Brain somatic mutations are increasingly recognized as a major cause of focal epilepsies. These include mTOR pathway mutations underlying cortical malformations such as focal cortical dysplasia and hemimegalencephaly, and SLC35A2 mutations in MOGHE, and activating variants in the SHH pathway in hypothalamic hamartomas. This study aims to identify brain somatic mutations using paired blood-brain samples and trace DNA from stereo-EEG electrodes, and to perform functional validation of candidate variants in children with drug-resistant focal epilepsy.

Conditions

Drug-resistant Focal Epilepsies in Pediatric Population

Keywords

Focal Cortical Dysplasia; Cortical Malformation; Hemimegalencephaly; Tuberous sclerosis; Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE); Hypothalamic hamartomas; Refractory Focal Epilepsy; Rasmussen Encephalitis; Epilepsy Surgery; Struge-Weber Syndrome

Outcome Measures

Primary Outcomes (1)

• qualitative genetic analysis

  Detection of brain somatic mutations and functional studies

  baseline

Study Arms (1)

Children undergoing epilepsy surgery at the Rothschild Foundation, Paris.

Sequencing of paired blood-brain DNA samples, SEEG electrodes

Genetic: Sampling of blood, frozen resected tissues, and cerebrospinal fluid (CSF)

Interventions

Sampling of blood, frozen resected tissues, and cerebrospinal fluid (CSF) GENETIC

Sampling of blood, frozen resected tissue, saliva, and cerebrospinal fluid (CSF); sequencing of paired blood-brain DNA samples, SEEG electrodes

Children undergoing epilepsy surgery at the Rothschild Foundation, Paris.

Eligibility Criteria

• Age: 3 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children with focal drug-resistant epilepsy undergoing epilepsy surgery and their parents

You may qualify if:

• Children with focal drug-resistant epilepsy including Focal Cortical Dysplasia, Hemimegalencephaly, Tuberous Sclerosis, Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), Hypothalamic Hamartomas, Sturge-Weber syndrome, Rasmussen encephalitis, gliomas
• Their parents who have signed informed consent 1) for their child's participation (for parents) and 2) for themselves
• Social security coverage or foreign regime recognized in France

You may not qualify if:

• refusal to participate in the study
• contraindication to anaesthesia, to MRI or to surgery
• no medical insurance coverage

Sponsors & Collaborators

• Fondation Ophtalmologique Adolphe de Rothschild: lead

Study Sites (1)

Fondation Ophtalmologique Adolphe de Rothschld

Paris, 75019, France

RECRUITING

Related Publications (9)

• Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmuller G, Chipaux M, Baulac S. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol. 2019 Dec;138(6):885-900. doi: 10.1007/s00401-019-02061-5. Epub 2019 Aug 23.

  PMID: 31444548 RESULT

• Bonduelle T, Hartlieb T, Baldassari S, Sim NS, Kim SH, Kang HC, Kobow K, Coras R, Chipaux M, Dorfmuller G, Adle-Biassette H, Aronica E, Lee JH, Blumcke I, Baulac S. Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). Acta Neuropathol Commun. 2021 Jan 6;9(1):3. doi: 10.1186/s40478-020-01085-3.

  PMID: 33407896 RESULT

• Lee WS, Baldassari S, Chipaux M, Adle-Biassette H, Stephenson SEM, Maixner W, Harvey AS, Lockhart PJ, Baulac S, Leventer RJ. Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia. Ann Clin Transl Neurol. 2021 Feb;8(2):485-490. doi: 10.1002/acn3.51286. Epub 2021 Jan 12.

  PMID: 33434304 RESULT

• Kim S, Baldassari S, Sim NS, Chipaux M, Dorfmuller G, Kim DS, Chang WS, Taly V, Lee JH, Baulac S. Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients. Ann Neurol. 2021 Jun;89(6):1248-1252. doi: 10.1002/ana.26080. Epub 2021 Apr 20.

  PMID: 33834539 RESULT

• Barba C, Blumcke I, Winawer MR, Hartlieb T, Kang HC, Grisotto L, Chipaux M, Bien CG, Hermanovska B, Porter BE, Lidov HGW, Cetica V, Woermann FG, Lopez-Rivera JA, Canoll PD, Mader I, D'Incerti L, Baldassari S, Yang E, Gaballa A, Vogel H, Straka B, Macconi L, Polster T, Grant GA, Krskova L, Shin HJ, Ko A, Crino PB, Krsek P, Lee JH, Lal D, Baulac S, Poduri A, Guerrini R; SLC35A2 Study Group. Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the SLC35A2 Gene. Neurology. 2023 Jan 31;100(5):e528-e542. doi: 10.1212/WNL.0000000000201471. Epub 2022 Oct 28.

  PMID: 36307217 RESULT

• Checri R, Chipaux M, Ferrand-Sorbets S, Raffo E, Bulteau C, Rosenberg SD, Doladilhe M, Dorfmuller G, Adle-Biassette H, Baldassari S, Baulac S. Detection of brain somatic mutations in focal cortical dysplasia during epilepsy presurgical workup. Brain Commun. 2023 Jun 1;5(3):fcad174. doi: 10.1093/braincomms/fcad174. eCollection 2023.

  PMID: 37324239 RESULT

• Ribierre T, Bacq A, Donneger F, Doladilhe M, Maletic M, Roussel D, Le Roux I, Chassoux F, Devaux B, Adle-Biassette H, Ferrand-Sorbets S, Dorfmuller G, Chipaux M, Baldassari S, Poncer JC, Baulac S. Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy. Nat Neurosci. 2024 Jun;27(6):1125-1136. doi: 10.1038/s41593-024-01634-2. Epub 2024 May 6.

  PMID: 38710875 RESULT

• Sanders MWCB, Koeleman BPC, Brilstra EH, Jansen FE, Baldassari S, Chipaux M, Sim NS, Ko A, Kang HC, Blumcke I, Lal D, Baulac S, Lee JH, Aronica E, Braun KPJ. Somatic variant analysis of resected brain tissue in epilepsy surgery patients. Epilepsia. 2024 Dec;65(12):e209-e215. doi: 10.1111/epi.18148. Epub 2024 Oct 26.

  PMID: 39460693 RESULT

• Baldassari S, Klingler E, Teijeiro LG, Doladilhe M, Raoux C, Roig-Puiggros S, Bizzotto S, Couturier J, Gilbert A, Sami L, Ribierre T, Aronica E, Adle-Biassette H, Chipaux M, Jabaudon D, Baulac S. Single-cell genotyping and transcriptomic profiling of mosaic focal cortical dysplasia. Nat Neurosci. 2025 May;28(5):964-972. doi: 10.1038/s41593-025-01936-z. Epub 2025 Apr 30.

  PMID: 40307383 RESULT

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Cortical tissue removed during neurosurgical intervention for epilepsy, SEEG Electrodes, Blood, saliva and cerebrospinal fluid (CSF)

MeSH Terms

Conditions

Focal Cortical Dysplasia; Hemimegalencephaly; Tuberous Sclerosis; Hypothalamic hamartomas; Epilepsies, Partial; Encephalitis

Condition Hierarchy (Ancestors)

Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Megalencephaly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Epilepsy; Brain Diseases; Central Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Mathilde CHIPAUX, MD, PhD

  Fondation A de Rothschild

  PRINCIPAL INVESTIGATOR

• Stéphanie BAULAC, PhD

  Institut du Cerveau

  STUDY CHAIR

Central Study Contacts

Amelie YAVCHITZ, MD

CONTACT

+33 1 48 03 64 54; ayavchitz@for.paris

Mathilde CHIPAUX, MD, PhD

CONTACT

+33 1 48 03 69 43; mchipaux@for.paris

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2016
• First Posted: September 7, 2016
• Study Start: December 17, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

FR (1)