The general aim of this study is to investigate if the early markers seen in presymptomatic patients predict progression of the disease. Furthermore, we can study if the disease markers we found in the mutation carriers predict disease severity.
ID
Source
Brief title
Condition
- Neurological disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) 7T: The quantitative measure of phase shifts, visual score of cortical
microinfarcts and striped cortex 2) 3T: WMH and DPVS volume and measurement of
vascular reactivity, 3) CSF concentrations of Aß40 and Aß42, 4) Estimation of
clinical severity and disease progression of HCHWA-D by using neurological and
neuropsychological standardized tests.
Secondary outcome
na
Background summary
Sporadic cerebral amyloid angiopathy (sCAA) is a common cerebrovascular disease
of the elderly that is caused by deposition of vascular amyloid-*. The absence
of reliable, non-invasive diagnostic tests is a major problem in diagnosing CAA
and until now the diagnosis can only be made post mortem. A group of CAA
patients with a pure form of vascular amyloid in whom a genetic basis for the
disease has been identified are patients with hereditary cerebral hemorrhage
with amyloidosis-Dutch type (HCHWA-D). HCHWA-D is considered to be a good model
to study sCAA. In HCHWA-D patients, the presence of the disease can be
determined based on a genetic test. Consequently, HCHWA-D is an ideal model to
study early phases of CAA, since the presence of the disease can be assessed
reliably, irrespective of the presence of signs and symptoms.
In our previous study on HCHWA-D our goal was to find early markers for
sCAA based on HCHWA-D. Therefore, we used 7T and 3T MRI, cerebral spinal fluid
(CSF) and clinical characteristics, such as cognitive tests, neurological
measures and blood measurements. Using these methods we were able to
demonstrate several early markers of the disease. 7T MRI showed that cortical
microinfarcts and an increased cortical phase shift in the occipital lobe are
early markers of the disease. 3T MRI demonstrated that white matter
hyperintensity (WMH) and dilated perivascular spaces (DPVS) volume are already
significantly increased in the presymptomatic stage of the disease and the
blood oxygen levels-dependent (BOLD) signal after a visual checkerboard
stimulus was significantly decreased in the occipital lobe in presymptomatic
mutation carriers. CSF analysis of amyloid-*40 (A*40) and amyloid-*42 (A*42)
proteins demonstrated decreased levels in the presymptomatic stage of the
disease. But also our research in the symptomatic patients showed several new
markers and insights in the disease. Now, we are very interested if these
(early) markers are predictive for the clinical stages of the disease and if
the markers we found can predict severity of the disease.
Study objective
The general aim of this study is to investigate if the early markers seen in
presymptomatic patients predict progression of the disease. Furthermore, we can
study if the disease markers we found in the mutation carriers predict disease
severity.
Study design
Combined longitudinal and cross-sectional study.
Study burden and risks
This is a non-therapeutic group relatedness study. In order to achieve the aim
of the study HCHWA-D patients who participated in the previous study are
needed, because of the extensive presence of pure vascular amyloid and a
genetically proven diagnosis and the early markers we found in these patients.
To learn more about the pathophysiology and the development of CAA during the
presymptomatic phase of HCHWA-D we need both presymptomatic and symptomatic
HCHWA-D mutation carriers. The study day consists of two MRI scans, a
neuropsychological assessment and a neurological exam which all have no
consequences for the health of the participants. Lumbar puncture is optional.
Contra-indications will be carefully investigated per subject to minimize the
risks. Burden will be kept at a minimum by using short protocols.
Albinusdreef 2
Leiden 2300 RC
NL
Albinusdreef 2
Leiden 2300 RC
NL
Listed location countries
Age
Inclusion criteria
Participant in the previous study.;- HCHWA-D mutation carriers
* Ability and willingness to provide written informed consent (see appendix).
* Age *18 years old.;- Control subjects
* Age *18 years old.
Exclusion criteria
- Other definite cause of hemorrhage. Exclusion causes are excessive anticoagulation (INR >3.0), antecedent head trauma or ischemic stroke, CNS tumor, vascular malformation, vasculitis, and blood dyscrasia. - Contra-indication to MRI scanning: * Claustrophobia * Pacemakers and defibrillators * Nerve stimulators * Intracranial clips * Intraorbital or intraocular metallic fragments * Cochlear implants * Ferromagnetic implants * Hydrocephalus pump * Intra-utrine device * An iron wire behind the teeth * Permanent make-up * Tattoos above the shoulders - Specific contraindications to fMRI * History of ischemic stroke, transient ischemic attack, carotid/intracranial artery stenosis. * Seizure within prior year. * Noncorrectable visual impairment. - Severe physical restrictions (completely wheelchair dependent) - Contraindications for a lumbar puncture, including any tumour, compressio medullae, signs and symptoms of increased intracranial pressure, local infections of the skin, and a coagulopathy including use of anti-coagulant drugs or platelet-inhibitors.
Design
Recruitment
metc-ldd@lumc.nl
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 | NL59968.058.17 |