Genetics of Central Nervous System Arteriovenous Malformations (GENE-MAV)

Recruiting

• Conditions: Arteriovenous Malformations

• Registration Number: NCT04772963
• Lead Sponsor: Fondation Ophtalmologique Adolphe de Rothschild

Brief Summary

Cerebral and medullary arteriovenous malformations (AVMs) lead to arterial and venous networks to communicate pathologically, creating an arteriovenous shunt. The occurrence of intracranial haemorrhage is the most important prognostic factor of AVMs because it is associated with a significant morbidity and mortality. The genetic, molecular and cellular mechanisms that cause vascular malformations of the central nervous system are partially known and the influence of genetic damage on the prognosis of AVMs is poorly known.

Detailed Description

Cerebral and medullary arteriovenous malformations (AVMs) are morphologically abnormal vessels located on the surface or in the cerebral or medullary parenchyma. These vascular lesions cause the arterial and venous networks to communicate pathologically, creating an arteriovenous shunt.

The prevalence of cerebral Cerebral and medullary AVMs in general population is difficult to establish given the rarity of the condition. However, it is estimated at around 1 per 10,000 inhabitants (0.01%). About 15-20% of the cerebral vascular accidents are asymptomatic at the time of diagnosis. The occurrence of intracranial haemorrhage is the most important prognostic factor because it is associated with a significant morbidity and mortality. The management of an AVM is usually carried out in a multidisciplinary way, combining interventional neuroradiology, neurosurgery and vascular neurology.

The genetic, molecular and cellular mechanisms that cause vascular malformations of the central nervous system are partially known. Several recent research works highlight mutations in the RAS-MAPK or MAPK-ERK signalling pathway in AVMs. In cases of cerebral AVMs considered to be sporadic, a somatic KRAS/BRAF mutation has recently been demonstrated in tissue samples of operated AVMs.

Except in the case of Hereditary Haemorrhagic Telangiectasia (HHT or Rendu-Osler-Weber syndrome), the influence of genetic damage on the prognosis of AVM is poorly known. It is also interesting to note that genetic screening is not routinely performed in patients with cerebro-medullary AVMs and that therefore the prevalence of these clinical entities in patients with AVMs is not known.

Study Timeline

• Study First Submitted: 2021-02-23
• Study First Submitted QC: 2021-02-23
• Study First Posted: 2021-02-26
• Study Start: 2022-02-17
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-21
• Primary Completion: 2026-03
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Patient with a vascular malformation of the cerebral or medullary identified on diagnostic imaging (angio-CT, angio-MRI or diagnostic angiography) for which clinical monitoring alone or intervention (endovascular treatment, surgery or radiosurgery) is planned in the centres participating in the research.

Exclusion Criteria

• Pregnant, parturient or breastfeeding woman

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Genetic mutation	limit of 12 month	Presence of a pathogenic mutation in one of the genes tested in the panel or identification of a pathogenic mutation following sequencing of the exome and/or transcriptome of the patient and/or his/her parents.

Trial Locations

Locations (1)

HOPITAL FONDATION Adolphe de ROTHSCHILD; 🇫🇷 Paris, France