Enlarged perivascular spaces and florbetapir uptake in patients with intracerebral hemorrhage
Enlarged perivascular spaces in the centrum semiovale (CSO-EPVS) have been linked to cerebral amyloid angiopathy (CAA). To get insight into the underlying mechanisms of this association, we investigated the relationship between amyloid-β deposition assessed by 18F-florbetapir PET and CSO-EPVS in patients with acute intracerebral hemorrhage (ICH).
We prospectively enrolled 18 patients with lobar ICH (suggesting CAA) and 20 with deep ICH (suggesting hypertensive angiopathy), who underwent brain MRI and 18F-florbetapir PET. EPVS were assessed on MRI using a validated 4-point visual rating scale in the centrum semiovale and the basal ganglia (BG-EPVS). PET images were visually assessed, blind to clinical and MRI data. We evaluated the association between florbetapir PET positivity and high degree (score> 2) of CSO-EPVS and BG-EPVS.
High CSO-EPVS degree was more common in patients with lobar ICH than deep ICH (55.6% vs. 20.0%; p = 0.02). Eight (57.1%) patients with high CSO-EPVS degree had a positive florbetapir PET compared with 4 (16.7%) with low CSO-EPVS degree (p = 0.01). In contrast, prevalence of florbetapir PET positivity was similar between patients with high vs. low BG-EPVS. In multivariable analysis adjusted for age, hypertension, and MRI markers of CAA, florbetapir PET positivity (odds ratio (OR) 6.44, 95% confidence interval (CI) 1.32–38.93; p = 0.03) was independently associated with high CSO-EPVS degree.
Among patients with spontaneous ICH, high degree of CSO-EPVS but not BG-EPVS is associated with amyloid PET positivity. The findings provide further evidence that CSO-EPVS are markers of vascular amyloid burden that may be useful in diagnosing CAA.
KeywordsIntracerebral hemorrhage Cerebral amyloid angiopathy Perivascular spaces Amyloid PET Florbetapir
The authors thank the promoter of this study, CHU Toulouse.
This study was funded by Avid Radiopharmaceuticals, Toulouse Teaching Hospital (CHU) (local grant 2011 to N.R.) and the Institut des Sciences et du Cerveau de Toulouse. Avid Radiopharmaceuticals provided funding for the PET scanning and supplied the florbetapir precursor. This work has been in part supported by a grant from the French National Agency for Research called “Investissements d’Avenir” No. ANR-11-LABEX-0018-01. This work was supported by CHU Toulouse for regulatory and ethical approval and compliance. Nicolas Raposo was supported by a Fulbright Scholarship and received an Arthur Sachs Scholarship from the Harvard University Committee on General Scholarship and a Philippe Foundation research grant.
Compliance with ethical standards
Conflict of interest
Dr. Payoux reports personal fees from Lilly/Avid and from GE Heathcare. Dr. Albucher received consulting fees from Bayer and speaker honoraria from Boehringer Ingelheim, Bayer, and Pfizer. Dr. Calviere received consulting fees from Boehringer Ingelheim and travel grant from Boehringer Ingelheim and Pfizer. Dr. Chollet served as a consultant for Institut de Recherche Pierre Fabre and has received speaker honoraria from Bristol-Myers Squibb and Boston Scientific. Dr. Olivot received consulting fees from AstraZeneca, Servier, and Boston Scientific and speaker honoraria from Boehringer Ingelheim, Pfizer, and Bristol-Myers Squibb. Dr. Pariente is an associate editor of the Journal of Alzheimer’s Disease and has received speaker honoraria from Lilly, Roche, and Novartis. All other authors declare that they have no conflict of interest.
Role of the funder
The funders had no role in the design or conduct of the study; in the collection, management, analysis, or interpretation of the data; in the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Toulouse-Purpan Hospital Ethical Standards Committee on Human Experimentation; No. 1122302) and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from each participant (or a legally authorized representative) included in the study.