Development of New Biomarkers With Magnetic Resonance Imaging for Longitudinal Studies in CADASIL Angiopathy

Développement de Nouveaux Biomarqueurs en Imagerie Par résonance magnétique Pour Les études Longitudinales Dans l'Angiopathie CADASIL

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.

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)