Andreas Charidimou1, Rolf H Jäger1, Andre Peeters1, Yves Vandermeeren1, Patrice Laloux1, Jean-Claude Baron1, David J Werring2. 1. From the Stroke Research Group, Department of Brain Repair and Rehabilitation, National Hospital for Neurology and Neurosurgery (A.C., D.J.W.), Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery (R.H.J.), and Department of Brain Repair and Rehabilitation (R.H.J.), UCL Institute of Neurology, London, United Kingdom; Department of Neurology, Cliniques Universitaires UCL Saint Luc, Brussels, Belgium (A.P.); Department of Neurology, CHU Dinant Godinne (Y.V., P.L.) and Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom (J.-C.B.); and UMR 894 INSERM-Université Paris 5, Sorbonne Paris Cité, Paris, France (J.-C.B.). 2. From the Stroke Research Group, Department of Brain Repair and Rehabilitation, National Hospital for Neurology and Neurosurgery (A.C., D.J.W.), Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery (R.H.J.), and Department of Brain Repair and Rehabilitation (R.H.J.), UCL Institute of Neurology, London, United Kingdom; Department of Neurology, Cliniques Universitaires UCL Saint Luc, Brussels, Belgium (A.P.); Department of Neurology, CHU Dinant Godinne (Y.V., P.L.) and Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom (J.-C.B.); and UMR 894 INSERM-Université Paris 5, Sorbonne Paris Cité, Paris, France (J.-C.B.). d.werring@ucl.ac.uk.
Abstract
BACKGROUND AND PURPOSE: We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid. METHODS: Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4-point visual rating scale and were classified as high (score>2) or low degree (score≤2) for prespecified analyses. Independent risk factors for high CSO-PVS degree were investigated in logistic regression. RESULTS: The final cohort consisted of 138 cerebral amyloid angiopathy patients (mean age, 71.8 years; 95% confidence interval, 70.2-73.4 years; 52.2% men). High CSO-PVS degree was present in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3 sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS 45.9% versus 13.5%; P<0.00005; for disseminated cSS 31.8% versus 0%; P<0.00005). In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78; 95% confidence interval, 1.64-13.87; P=0.004) was an independent predictors of high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS. CONCLUSIONS: High degree of CSO-PVS is highly prevalent in sporadic cerebral amyloid angiopathy and is related to cSS. Our findings suggest that severe leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired interstitial fluid drainage from cerebral white matter, although determining the causal direction of this relationship requires prospective studies.
BACKGROUND AND PURPOSE: We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid. METHODS: Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4-point visual rating scale and were classified as high (score>2) or low degree (score≤2) for prespecified analyses. Independent risk factors for high CSO-PVS degree were investigated in logistic regression. RESULTS: The final cohort consisted of 138 cerebral amyloid angiopathypatients (mean age, 71.8 years; 95% confidence interval, 70.2-73.4 years; 52.2% men). High CSO-PVS degree was present in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3 sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS 45.9% versus 13.5%; P<0.00005; for disseminated cSS 31.8% versus 0%; P<0.00005). In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78; 95% confidence interval, 1.64-13.87; P=0.004) was an independent predictors of high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS. CONCLUSIONS: High degree of CSO-PVS is highly prevalent in sporadic cerebral amyloid angiopathy and is related to cSS. Our findings suggest that severe leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired interstitial fluid drainage from cerebral white matter, although determining the causal direction of this relationship requires prospective studies.
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