Unruptured Cerebral Aneurysm: Prediction of Evolution

Study Overview
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Brief Summary
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The protocol has many assets. A prospective nationwide recruitment allows for the inclusion of a large cohort of patients with UIA. It will combine accurate clinical phenotyping and comprehensive imaging with CAWE screening. Besides, it will enable to exploit metadata and to explore new pathophysiological pathways of interest by crossing clinical, genetic, biological, and imaging information.

Detailed Description
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Management of small (<7mm) unruptured intracranial aneurysms (UIA) remains controversial. Previous retrospective studies have suggested that post gadolinium arterial wall enhancement (AWE) of unruptured intracranial aneurysms on MR imaging may reflect aneurysm wall instability, and hence may highlight a higher risk of UIA growth over time. This multicentric prospective cohort aims at exploring vessel wall imaging findings of UIAs with consecutive follow-up to substantiate these assumptions.The objective is to develop diagnostic and predictive tools for the risk of IA evolution. The aim is to demonstrate in clinical practice the predictive value of (AWE) for UIA growth. The growth will be determined by any modification of the UIA measurement. Both UIA growth and the UIA wall enhancement will be assessed in consensus by two expert neuroradiologists.The French prospective UCAN project is a non-interventional international wide and multicentric prospective cohort. UIA of bifurcation between 3 and 7 mm for whom a clinical and imaging follow-up without occlusion treatment was scheduled by local multidisciplinary staff will be included. Extensive clinical, biological and imaging data will be recorded during a 3 years follow-up (visits at 1 and 3 years after inclusion).

Official Title
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Unruptured Cerebral Aneurysm: Prediction of Evolution

Conditions
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Unruptured Intracranial Aneurysm

Intervention / Treatment
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* Other: Unruptured intracranial aneurysms


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Subject carrying unruptured, asymptomatic and untreated typical IA of bifurcation, measured on conventional imaging (MRI, CTA or DSA) between 3 and 7 mm of larger diameter. Ability to be followed-up during 3 years decided in consensus multidisciplinary gathering. Age > 18 years old. Exclusion Criteria : A failure to obtain informed consent Contraindications for undergoing an MRI scan include : (heart pacemaker, a metallic foreign body (metal sliver) in their eye, or aneurysm clip in their brain, severe claustrophobia) Contraindications for a gadolinium contrast medium injection (:eGFR below 30 mL/min/1.73 m2, Previous or pre-existing nephrogenic systemic fibrosis, Previous anaphylactic/anaphylactoid reaction to gadolinium containing contrast agent, Acutely deteriorating renal function, Pregnancy and breast-feeding) A mycotic, fusiform-shaped, or dissecting IA, an IA in relation with an arteriovenous malformation A family history of polycystic kidney disease, Ehlers-Danlos syndrome, Marfan's syndrom, fibromuscular dysplasia, or Moya Moya disease Intra-cavernous UIA because the sinus cavernous that is fulfilled with venous blood precluded a reliable assessment of aneurysmal wall enhancement (AWE)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Unruptured intracranial aneurysms|UIA of bifurcation between 3 and 7 mm for whom a clinical and imaging follow-up without occlusion treatment was scheduled by local multidisciplinary staff will be included. Extensive clinical, biological and imaging data will be recorded during a 3 years follow-up (visits at 1 and 3 years after inclusion).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The aim is to evaluate in clinical practice the predictive value of UIA wall enhancement for UIA growth. It will allow to set up a secure, efficient and personalized follow-up. | In order to evaluate the informative value of AWE for UIA growth, investigators will consider as primary endpoint the growth of the UIA after the complete follow-up at 3 years. | 5 years | 
| Predictive value of UIA wall enhancement for UIA growth | This event could occur at any time during the follow-up if an UIA becomes symptomatic but will be systematically assessed by MRI. UIA growth will be assessed blindly and independently by two expert neuroradiologists, routinely involved in UIA management and disagreement will be solved by consensus with involvement of a third expert. UIA wall enhancement status will be defined independently by two different expert neuroradiologists, with > 5yrs experience in intracranial vessel wall imaging. Disagreement will be solved by consensus with involvement of a third expert. | at 1 year | 
| Predictive value of UIA wall enhancement for UIA growth | This event could occur at any time during the follow-up if an UIA becomes symptomatic but will be systematically assessed by MRI. UIA growth will be assessed blindly and independently by two expert neuroradiologists, routinely involved in UIA management and disagreement will be solved by consensus with involvement of a third expert. UIA wall enhancement status will be defined independently by two different expert neuroradiologists, with > 5yrs experience in intracranial vessel wall imaging. Disagreement will be solved by consensus with involvement of a third expert. | at 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life related to the growth of UIA. | Evaluation of the quality of life (QOL) of untreated patients with UIA during the follow-up. | 5 years | 
| AWE variation patterns related to the growth of UIA. | Detection of other AWE variation patterns related to growth during the follow-up in order to improve the follow-up of UIA patients | 5 years | 
| Clinical, genetics or biological factors related to the growth of UIA. | Clinical, genetic (blood serum level of circulating ANGPTL6) and biological (plasma factors as circulating ANGPTL6 levels, metalloproteinase…) features recorded. | 5 years | 
| Incidence of growth of UIA. | Incidence of growth, stratified by clinical, genetics or biological features. | 5 years | 
| Incidence of IA rupture | Incidence of IA rupture, stratified by clinical, genetics or biological features. | 5 years | 
| quality of life patients related to the growth of UIA. | Completion of standardized EQ5D questionnaire to measure quality of life patients | 5 years | 
| Construction of an automatized tool of AWE pattern | Construction and evaluation of an automatized tool of AWE patterns, as compared to the visual analysis of experts, in the form of a decision-making tool. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unruptured Cerebral Aneurysm, Aneurysm Prediction Growth, Unruptured Intracranial aneurysm