Background:
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy) is a genetic disorder. It causes narrowing of the small blood vessels and can lead to strokes and dementia. Researchers want to monitor people with CADASIL over time.
Objective:
To learn more about how CADASIL affects a person s blood vessels over time.
Eligibility:
Adults ages 18 and older who have CADASIL, and healthy volunteers.
Design:
Participants will be screened with a medical record review.
Participants will have 4 study visits over 9 years. Visits will last 6 8 hours per day, for 2 4 days.
Participants will give blood and urine samples. They will have an electrocardiogram to record their heart s electrical activity. They will fill out a family tree. They will have tests that measure mental abilities like memory and attention. They may have a skin biopsy. They may have a lumbar puncture.
Participants will have an eye exam. Their pupils will be dilated. They will receive a dye via intravenous (IV) line. Pictures will be taken of their eyes.
Participants will have an imaging scan of their brain. They may receive a contrast agent via IV.
Participants blood flow and blood vessel flexibility will be measured. In one test, a probe will be pressed against the skin of the their wrist, neck, and groin. In another test, they will hold one arm still while a microscope makes videos of the blood flow through a fingernail. In another test, they will perform light exercise or other activities while wearing an elastic band around their head or probes placed on their arm or leg.
Healthy volunteers will complete some of the above tests.
Stated willingness to comply with all study procedures and availability for the duration of the study.
Male or female, aged 18 to 100 years (inclusive).
Established diagnosis of CADASIL or NOTCH3 mutations, as determined by genetic testing.
Healthy controls.
Pregnancy at time of consent.
Subjects who lack capacity to consent and don't have a legally authorized representative.
Subjects who decline to provide samples for blood and/or tissue studies.
Subjects who do not speak English.
We will follow up to 110 subjects in order to have 100 subjects with CADASIL (at least 80 new CADASIL subjects and up to 20 CADASIL subjects previously enrolled in our pilot study, if they would like to participate in this study as well) and up to 45 healthy controls with the goal of 40 healthy control subjects completing the study, withtotal accrual of 155 male and female, ages 18-100. Should anyone from the original patient cohort decide not to participate in this new study, additional patients will be recruited in order to meet our goal of having 100 CADASIL subjects enrolled in the study.
Case-control
Other
MRI
DeviceResearch pulse sequences.
This study will examine the pathogenesis of CADASIL through comprehensive clinical evaluations and molecular studies on biospecimens collected under this protocol from affected individuals.
To study the pathogenesis of CADASIL and obtain clinical evaluations and biospecimens from affected cohorts to identify underlying disease mechanism(s).
Clinical evaluations will be used to investigate variability of clinical phenotype during the study period.
To use Clinical evaluations to investigate variability of clinical phenotype during the study period. These studies will serve as baseline evaluations for future studies on the identification of underlying disease mechanism(s) and potential therapeutic approaches.
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