Angiopathy; Cerebral, Cadasil
Conditions
Brief summary
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an cerebral microangiopathy secondary to mutations in the NOTCH3 gene located on chromosome 19. This disease is the most frequent of the hereditary vascular leukoencephalopathies. CADASIL begins between the ages of 20 and 40 with the appearance of hyper-signs of brain white matter visible on T2 sequences in magnetic resonance imaging (MRI). Before the age of 30, patients are most often asymptomatic. The disease is then responsible for different neurological manifestations: 1. Migraine attacks with aura occur on average in one in three patients, most often at the beginning of the course of the disease, sometimes even before the appearance of MRI abnormalities; 2. Transient ischemic strokes or strokes associated with small cerebral infarcts occur most frequently after the age of 50-60 years in more than two out of three patients; 3. Mood disorders are reported by one in three patients in the same age group; 4. Cognitive disorders that affect executive functions, especially after the age of 60, until the stage of severe dementia associated with walking disorders are observed during the course of the disease. To date, there is no treatment whose efficacy has been proven in CADASIL. Various studies have shown that the accumulation of the most destructive brain tissue lesions at the subcortical level was closely correlated in CADASIL with the clinical severity of patients (motor and cognitive disability). It is now possible to measure microstructural changes in brain tissue in diffusion imaging during the course of the disease, even before significant clinical changes are detected.
Interventions
DIAGNOSTIC_TESTCerebral Magnetic resonance imaging (MRI)
Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Inclusion Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Month 1 Cerebral Magnetic resonance imaging (MRI) 3 Tesla at Year 1
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Patients * Age from 18 to 80 years * Confirmed diagnosis (detection of a pathogenic mutation of the NOTCH3 gene) * Detailed clinical and MRI assessment of the disease (follow-up at the CERVCO) including Rankin score \<4 * Any contraindication to MRI or EEG examination (claustrophobia, presence of material with magnetic properties) * Social security insurance * Written consent. Controls * Age from 18 to 80 years * No history of neurological or psychiatric diseases * No history of migraine with aura * No history of vascular disease (peripheral arteries, heart, brain) * No known or treated diabetes * No known or treated hypercholesterolemia * Social security insurance * Written consent
Exclusion criteria
Patients * Patients with a contraindication to MRI or EEG examination (claustrophobia, material with magnetic properties: pacemaker, ferromagnetic material ...) * For MRI examination of neurovascular coupling: Patients with a treatment that may interfere with neurovascular coupling (in particular any treatment with non-steroidal anti-inflammatory drugs, psychotropic drugs, antihypertensive agents or statins) * Patients without a social security insurance * Patients under the age of 18 or over 80 at the time of the first visit * Patients unable to give their informed consent * Person referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the Public Health Code, defined by: * Pregnant, parturient or nursing woman * Person deprived of liberty by judicial or administrative decision * Person hospitalized without consent and not subject to a legal protection measure, and person admitted to a health or social institution for purposes other than research * Minor * Adult under legal protection measure (guardianship, guardianship or court order), an adult unable to express their consent and not subject to a protective measure * Person submitted to an exclusion period for another research (washout period) Controls * Subject with a contraindication to MRI or EEG examination (claustrophobia, material with magnetic properties: pacemaker, ferromagnetic material ...) * For MRI examination of neurovascular coupling: Subject with a treatment that may interfere with neurovascular coupling (in particular any treatment with non-steroidal anti-inflammatory drugs, psychotropic drugs, antihypertensive agents or statins) * Subject without a social security insurance * Subject under the age of 18 or over 80 years at the time of the first visit * Patients unable to give their informed consent * Person referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the Public Health Code, defined by: * Pregnant, parturient or nursing woman * Person deprived of liberty by judicial or administrative decision * Person hospitalized without consent and not subject to a legal protection measure, and person admitted to a health or social institution for purposes other than research * Minor * Adult under legal protection measure (guardianship, guardianship or court order), an adult unable to express their consent and not subject to a protective measure * Person submitted to an exclusion period for another research study (washout period)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intra-axonal | 1 year | Intra-axonal volume fraction |
| Extra-axonal | 1 year | Extra-axonal volume fraction |
| Intra-myelinic edema | 1 year | Volume fraction of intra-myelinic edema |
| Microvascular compartment fraction measured using diffusion MRI (IVIM) | 1 year | Measures of the Flowing blood volume fraction (corresponding to slow intra-voxel incoherent motion (IVIM) of water molecules in the cerebral microvasculature at voxel level) |
| variation | 1 year | Overall variation of cerebral blood flow over 20 and 40 seconds stimulations (area under a curve) |
| blood flow | 1 year | Maximum cerebral blood flow measured over 20 and 40 seconds stimulations |
| Slope | 1 year | Slope of the regression curve when cerebral blood flow is measured 15 and 35 seconds after the onset of the stimulation |
| Dynamics of the cerebral blood | 1 year | Dynamics of the cerebral blood flow curve between 15 and 35 seconds (model with dual component responses; fast (before 20 seconds) and slow (after 20 seconds)) |
Countries
France
Contacts
Primary ContactHugues CHABRIAT, MD, PhD
Backup ContactNathalie GASTELLIER, PhD
Outcome results
None listed