To determine whether reactive gliosis persists >3 years after SAH and whether this response relates to cognitive impairment after SAH.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
- Cognitive and attention disorders and disturbances
- Aneurysms and artery dissections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
All subjects will undergo neuropsychological testing on 5 cognitive domains,
and crude test scores will be transformed into z-scores based on scores of a
matched control group. . Outcomes will be dichotomized into cognitive impaired
or not-cognitive impaired. Furthermore, each subject will be asked to fill out
3 questionnaires to evaluate self-reported cognitive complaints. After this,
patients will proceed to undergo 3Tesla brain MRI and 60 minute dynamic
Positron Emission Tomography (PET) scanning using a [18F]DPA-714 ligand, where
a simplified reference tissue model (SRTM) will be used in quantitation with
cerebellar gray matter as pseudo-reference area. Using this method, tracer
binding potential (BPND) will be obtained as an estimator of distribution
volume ratio (DVR) and differences in BPND between subgroups. It will be
investigated if tracer binding potential is correlated with cognitive
impairment.
Differences in TSPO binding capacity between 3 groups:
- Patients with cognitive impairment at least 3 years after aSAH
- Patients without cognitive impairment at least 3 years after SAH
- Controls with unruptured intracranial aneurysms
Secondary outcome
- Domain and severity of cognitive impairment after SAH
- Results of questionnaires
- Demographic variables (as listed in paragraph 6.3. Study procedures)
- SAH characteristics (as listed in paragraph 6.3. Study procedures).
Background summary
Long-term cognitive impairment occurs in 30% of patients surviving aneurysmal
subarachnoid haemorrhage (SAH). Recent insights show that this impairment might
be due to loss of synapses or impaired synaptic function, caused by an
inflammatory response to injury known as reactive gliosis.
Study objective
To determine whether reactive gliosis persists >3 years after SAH and whether
this response relates to cognitive impairment after SAH.
Study design
Cross-sectional cohort study
Study burden and risks
No patient-specific benefits will be reached in this study. However, this study
has the group benefit of gaining insight in the (patho)physiology of these
cognitive impairment, while identifying potential treatment opportunities.
Risks associated with participation are very low to negligible: in radio ligand
injection there is a minor risk of infection. Furthermore, MRI scanning poses
minor known risks associated with the magnetic field, which we will address by
carefully screening subjects beforehand. [18F]DPA-714 PET-scanning has no
reported AEs or SAEs in prior research and radiation exposure has been shown to
be similar to other fluoride-labeled ligands, which is well under the threshold
as established by the European Association of Nuclear Medicine (EANM).
Heidelberglaan 100
Utrecht 3581CX
NL
Heidelberglaan 100
Utrecht 3581CX
NL
Listed location countries
Age
Inclusion criteria
Subjects (n = 14) with aSAH >3 years ago and cognitive impairment
- Admitted to the UMCU with aneurysmal SAH at least 3 years ago, defined as
o Blood on initial non-contrast CT or bilirubin in cerebrospinal fluid (CSF)
o A proven aneurysm, demonstrated by computed tomography angiography (CTA),
digital subtraction angiography (DSA) or magnetic resonance angiography (MRA)
- Genotyping of rs6971 must show that patient is a high affinity binder
- Functional independence (defined as modified rankin scale (mRS) or 0-2)
o mRS (Dutch) table can be found in Appendix 1
- Patient must have been at least 18 years of age at time of visit to the
outpatient clinic.
- Neuropsychological evaluation shows cognitive impairment.
Subjects (n = 14) with aSAH >3 years ago and no cognitive impairment
- Admitted to the UMCU with aneurysmal SAH at least 3 years ago, defined as
o Blood on initial non-contrast CT or bilirubin in CSF
o A proven aneurysm, demonstrated by CTA, DSA or MRA
- Genotyping of rs6971 must show that patient is a high affinity binder
- Functional independence (defined as mRS or 0-2)
o mRS (Dutch) table can be found in Appendix 1
- Patient must have been at least 18 years of age at time of visit to the
outpatient clinic.
- Neuropsychological evaluation shows no cognitive impairment.
Controls (n = 8) with unruptured aneurysms
- Admitted to the UMCU with an unruptured aneurysm, defined as
o A proven aneurysm, demonstrated by CTA, DSA or MRA
- Genotyping of rs6971 must show that patient is a high affinity binder
- Functional independence (defined as mRS of 0-2)
- Patient must have been at least 18 years of age at time of visit to the
outpatient clinic.
- Neuropsychological evaluation shows no cognitive impairment.
Exclusion criteria
- Contra-indication for PET-MRI scanning (such as severe lower back pain or
claustrophobia)
- Pregnancy
- Exposure to ionic radiation (clinical or experimental) in the past 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 | NL69428.041.19 |