Clinical trial NCT04772963: Genetics of Central Nervous System Arteriovenous Malformations (GENE-MAV)
Official title: Genetics of Central Nervous System Arteriovenous Malformations (AVM): Genotype-phenotype Correlation and Prognostic Impact on Patients with AVM
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Arteriovenous Malformations
Lead sponsor: Fondation Ophtalmologique Adolphe de Rothschild
Sponsor class: NETWORK
First posted: 2021-02-26
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The recruited population will be index cases with cerebrovascular cerebral vascular malformations treated in the participating centres

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.

Eligibility criteria: 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

Primary outcomes:
measure: Genetic mutation
timeFrame: limit of 12 month
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: HOPITAL FONDATION Adolphe de ROTHSCHILD
Study officials:
affiliation: Fondation Ophtalmologique Adolphe de Rothschild
name: Stanislas Smajda, MD
role: PRINCIPAL_INVESTIGATOR
References: