1. To assess neuroimaging hallmarks of RVCL disease stages;2. To evaluate cerebrovascular reactivity as a biomarker of endothelial (dys)function in RVCL patients, in migraine patients and healthy controls;3. To identify shared pathophysiological…
ID
Source
Brief title
Condition
- Neurological disorders congenital
- Headaches
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. The prevalence and distribution of disease specific structural and
functional MRI abnormalities, including (i) brain (non-)lacunar infarcts, (ii)
white matter hyperintensities (deep and periventricular), (iii) widened
perivascular spaces, (iv) microbleeds, (v) cerebral *pseudotumor* mass lesions,
(vi) permeability of the blood brain barrier, (vii) white matter connectivity,
(viii) brain activity in rest.
2. Cerebrovascular reactivity after inducing hypercapnia as a measure of
endothelial function
Secondary outcome
not applicable
Background summary
Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL) is caused by mutations
in the TREX1 gene and manifests itself as a microangiopathy with a retinal
vasculopathy and in addition a wide range of cerebral and systemic conditions,
including migraine. Because of this association with migraine, RVCL is
considered a monogenic vascular model for migraine. The consecutive stages of
the disease, especially the early stages, remain to be identified. Previous
studies have suggested that dysfunction of endothelium is part of the
pathophysiologic pathway through which mutated TREX1 protein leads to the small
vessel disease manifestations of RVCL. Endothelial dysfunction is also
suggested to play a role in migraine.
We want to investigate if markers of RVCL are also involved in the more common
types of migraine. By unravelling how TREX1 mutations cause disease we hope to
obtain insights in the pathophysiology of migraine and other (neuro)vascular
disorders such as stroke and vascular dementia, and possibly to define new
treatment targets for these currently incurable diseases.
Study objective
1. To assess neuroimaging hallmarks of RVCL disease stages;
2. To evaluate cerebrovascular reactivity as a biomarker of endothelial
(dys)function in RVCL patients, in migraine patients and healthy controls;
3. To identify shared pathophysiological pathways of RVCL and migraine.
Study design
We will perform an observational cross-sectional study in RVCL patients.
Patients with migraine and age and sex matched control subjects will be
included as control groups.
Study burden and risks
MRI scans will be made after careful screening for contraindications for MRI
and obtaining written informed consent. MRI scans involve a negligible risk to
the participants* health. To further minimize the burden the total scan time is
limited to 60 minutes. Relatives of RVCL patients who wish to remain unaware of
their genetic status can participate on a research basis, and test results will
not be reported in the patients* hospital records or to treating physicians
that participate in the study.
The study is observational and aims to elucidate neuroimaging hallmarks of
disease stages, pathophysiological mechanisms and endothelial function in RVCL
an migraine. The LUMC can contribute significantly to the worldwide RVCL
research, as the Dutch RVCL population is the largest of the few populations
that have been identified so far. Identifying neuroimaging hallmarks for
recognizing (pre)clinical disease stages and possibly for predicting outcome or
future progression would be valuable for these patients. By including migraine
patients and healthy subjects as control groups, we hope to define whether
findings are specific to RVCL or whether there is an overlap between RVCL and
migraine. Overlapping results may help to elucidate (new) mechanisms in
migraine pathophysiology. Ultimately we hope that a better understanding of the
pathophysiology of RVCL as vascular migraine model will enable us to define new
treatment targets for these incurable diseases. Altogether we feel the
advantages of this study outweigh the minimal risks.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Patient group (RVCL and migraine):
- age >=18 years
- Diagnosed with :
i) RVCL with proven TREX1 mutation; AND/OR
ii) migraine with or without aura according to the criteria of the International Headache Society (IHS)
- ability and willingness to provide written informed consent;control subjects:
-age >=18 years
- Not genetically related to an RVCL patient OR genetic testing has ruled out TREX1 mutations
- no (history) of migraine attacks
- age and sex matched with the patients
- Ability and willingness to provide written informed consent
Exclusion criteria
All subjects:
- Subjects who do not want to be informed about unexpected findings that are considered serious, with prognostic or therapeutic consequences. This does not concern genetic test results.
- History of severe kidney dysfunction
- Previous allergic-like reaction to gadolinium-containing contrast agents
- Contraindications to MR Imaging (such as presence of metal objects in/on the body that cannot be removed);Migraine patients and control subjects:
- Presence of known (cerebro) vascular diseases such as overt manifestations of hypertensive/ atherosclerotic vascular disease, excessive anticoagulation (INR >3.0), CNS disorders, vasculitis, blood dyscrasia, diabetes mellitus, severe clinical relevant carotid artery stenosis. ;Specific exclusion criteria for participants in the cerebrovascular reactivity measurements:
- Severe asthma
- COPD
- Seizures within the previous year
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL47197.058.13 |