Cerebral small vessel diseases (cSVD) are diseases of brain tissue involving vessels (arterioles or capillaries) with a diameter of less than 400 microns. Within this group, CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is the most common familial form. CADASIL is due to mutations in the NOTCH3 gene located on chromosome 19. It is considered a unique model for the study of cSVD. CADASIL begins between the ages of 20 and 40, with the appearance of cerebral white matter hyper-signals visible on MRI. Before the age of 30, patients are usually asymptomatic. To date, there are no available treatments. To test new therapeutic approaches, we need biomarkers that are robust and sensitive enough to assess the effects of these treatments at an early stage of cSVD and over a relatively short period of time.
An ideal monitoring biomarker should be repeatedly and safely usable, easily accessible, accurate, reproducible and sensitive to disease progression or pharmacological intervention.
Alterations in neurovascular coupling (NVC) have been recognized as one of the earliest functional alterations occurring during cSVD. Cerebral functional magnetic resonance imaging (fMRI) is a brain imaging technique that measures the activity of brain areas in vivo by detecting local changes in blood flow. An important advantage of blood oxygen level-dependent functional MRI is that it enables the NVC to be probed in vivo, safely and repeatedly in humans.
Our central hypothesis is that functional MRI can provide such a biomarker for monitoring CNV disease progression in vivo using a dedicated fMRI protocol that can be used on a clinical MRI scanner, is reproducible and varies according to the severity of brain MRI lesions and/or clinical manifestations in CADASIL. A functional imaging study coupled with electroencephalogram has already revealed changes in the hemodynamic response to visual or motor stimuli in patients at the early stage of the disease. This study is exploring new imaging protocols to focus on the purest vascular response.
Age between 18 and 80 at the time of inclusion
Diagnosis confirmed by detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL.
Beneficiaries of a health insurance.
Written consent.
Contraindication to MRI examination
Disability: Rankin score ≥ 4
Moderate to severe dementia according to DSM 5 criteria or MMSE score ≤ 19
Pregnant, parturient or breast-feeding woman
Patients with a known mutation in the NOTCH3 gene
Case-control
Prospective
Functional MRI at 3T
RadiationAt inclusion
Functional MRI at 3T
RadiationAt inclusion and at 2 years for CADASIL patients without severe disability (mRS\<4)
Functional MRI at 3T
RadiationAt inclusion and at 2 years for CADASIL patients without severe disability (mRS\<4)
Variation in BOLD response
Variation in BOLD response on functional MRI during short-duration visual stimuli (area under the curve) and parameters derived from this response curve at the calcarine scissure For all patients and controls
Variation in BOLD response
Variation in BOLD response on functional MRI during short-duration visual stimuli (area under the curve) and parameters derived from this response curve at the calcarine scissure For CADASIL patients
Correlations between parameters derived from the response curve and age
Correlations between parameters derived from the response curve and gender
Correlations between parameters derived from the response curve and cardiovascular risk factors
Correlations between parameters derived from the response curve and modified Rankin score
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