Cerebral Small vessel disease stroke and dementia
Conditions
Interventions
Blood-brain barrier permeability
Cerebral small vessel Disease
Microvascular dysfunction
vascular inflammation
Sponsors
Medisch Universitair Ziekenhuis Maastricht
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Symptomatic SVD defined as - a history compatible with clinical lacunar stroke syndrome in the last 5 years with a recent small subcortical infarct visible on MRI scan or CT scan compatible with the clinical syndrome. -or cognitive impairment defined as visiting a memory clinic and a clinical dementia rating score of * 0.5, and capacity to consent with confluent deep WMH on MRI (defined on the Fazekas scale as deep WMH score * 2). - or a diagnosis of CADASIL established by molecular genetic testing of the NOTCH3 gene (presence of an archetypical, cysteine-affecting mutation) or the presence of granular osmiophilic material in ultrastructural, electron microscopy analysis of skin biopsy. * Age 18 years or older * Ability to undergo MRI * Capacity to give written informed consent * Independent in activities of daily living (Modified Rankin score
Exclusion criteria
Exclusion criteria: * Inclusion criteria are not met * Unwillingness or inability to give written consent * Pregnant or breastfeeding women, women of childbearing age not taking contraception. * Contraindications to MRI: pacemaker, metallic foreign body (including aneurysm clip in the brain), claustrophobia, pregnancy, neurostimulator, pacemaker or other kinds of implanted devices or insulin pump. * Contraindications to gadolinium contrast agent used for MRI * Other major neurological or psychiatric conditions affecting the brain and interfering with the study design (e.g. multiple sclerosis) * In case of clinical lacunar stroke syndrome other causes of stroke such as *50% luminal stenosis in large arteries supplying the area of ischaemia, major-risk cardioembolic source of embolism, other specific causes of stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug misuse) * Other stroke risk factor requiring immediate intervention that would preclude involvement in the study * Renal impairment (eGFR
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * BBB integrity as assessed using DCE-MRI brain scan * CVR as determined by BOLD MRI brain scan response to hypercapnic challenge (CO2 breathing as vasodilative stimulus) * PVS score, count, and volume on structural MRI brain scan, assessed using validated methods | — |
Secondary
| Measure | Time frame |
|---|---|
| * BP parameters (peak systolic, systolic, mean, diastolic arterial pressures, pulse pressures, and variability) * Systemic measures of vascular stiffness (PWV) * CSF pulsatility as an index of rate of passage of pulse waves through the brain (stiffness), measured using MRI brain scan. * Structural MRI markers of SVD * WMH, PVS, lacunes, microbleeds, individually and by total SVD score. * Circulating immune cells identified by FACS analysis | — |
Countries
Germany, United Kingdom
Outcome results
None listed