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January 07, 2014; 82 (1) Article

White matter perivascular spaces

An MRI marker in pathology-proven cerebral amyloid angiopathy?

Andreas Charidimou, Zane Jaunmuktane, Jean-Claude Baron, Matthew Burnell, Pascale Varlet, Andre Peeters, John Xuereb, Rolf Jäger, Sebastian Brandner, David J. Werring
First published November 27, 2013, DOI: https://doi.org/10.1212/01.wnl.0000438225.02729.04
Andreas Charidimou
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Zane Jaunmuktane
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Jean-Claude Baron
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Matthew Burnell
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Pascale Varlet
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Andre Peeters
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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John Xuereb
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Rolf Jäger
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Sebastian Brandner
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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David J. Werring
From the Stroke Research Group (A.C., D.J.W.), Division of Neuropathology and Department of Neurodegenerative Disease (Z.J., S.B.), and Lysholm Department of Neuroradiology (R.J.), UCL Institute of Neurology, London, UK; The National Hospital for Neurology and Neurosurgery (A.C., R.J., D.J.W.), London, UK; Department of Clinical Neurosciences (J.-C.B.) and Department of Pathology (J.X.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK; Department of Neuropathology (J.-C.B., P.V.), Hospital Sainte-Anne, Paris, France; University Paris Descartes (J.-C.B., P.V.), Paris, France; Biomedical Research Centre (M.B.), UCL, UK; and Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc, Brussels, Belgium.
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Full PDF
Citation
White matter perivascular spaces
An MRI marker in pathology-proven cerebral amyloid angiopathy?
Andreas Charidimou, Zane Jaunmuktane, Jean-Claude Baron, Matthew Burnell, Pascale Varlet, Andre Peeters, John Xuereb, Rolf Jäger, Sebastian Brandner, David J. Werring
Neurology Jan 2014, 82 (1) 57-62; DOI: 10.1212/01.wnl.0000438225.02729.04

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Abstract

Objective: We investigated whether severe, MRI-visible perivascular spaces (PVS) in the cerebral hemisphere white matter (centrum semiovale) are more common in patients with pathology-proven cerebral amyloid angiopathy (CAA) than in those with pathology-proven non–CAA-related intracerebral hemorrhage (ICH).

Methods: Using a validated 4-point scale on axial T2-weighted MRI, we compared PVS in patients with pathology-proven CAA to PVS in those with spontaneous ICH but no histopathologic evidence of CAA. In a preliminary analysis restricted to patients with T2*-weighted gradient-recalled echo MRI, we also investigated whether including severe centrum semiovale PVS increases the sensitivity of existing diagnostic criteria for probable CAA.

Results: Fourteen patients with CAA and 10 patients with non–CAA-related ICH were included. Eight of the patients with CAA were admitted for symptomatic, spontaneous lobar ICH, 1 because of ischemic stroke, 1 with transient focal neurologic episodes, and 4 due to cognitive decline. Severe (>20) centrum semiovale PVS were more frequent in patients with CAA compared to controls (12/14 [85.7%; 95% confidence interval (CI): 57.2%–98.2%] vs 0/10 [1-sided 95% CI: 0%–30.8%], p < 0.0005); this was robust to adjustment for age. The original Boston criteria for probable CAA showed a sensitivity of 76.9% (95% CI: 46.2%–95%), which increased to 92.3% (95% CI: 64%–99.8%), without loss of specificity, after including severe centrum semiovale PVS.

Conclusions: Severe centrum semiovale PVS on MRI may be a promising new neuroimaging marker for the in vivo diagnosis of CAA. However, our findings are preliminary and require confirmation and external validation in larger cohorts of pathology-proven CAA.

GLOSSARY

AD=
Alzheimer disease;
CAA=
cerebral amyloid angiopathy;
CI=
confidence interval;
GRE=
gradient-recalled echo;
ICH=
intracerebral hemorrhage;
PVS=
perivascular spaces

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received April 26, 2013.
  • Accepted in final form September 23, 2013.
  • © 2013 American Academy of Neurology
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Letters: Rapid online correspondence

  • Cerebral Amyloid Angiopathy and Alzheimer's Disease
    • Gordon J Gilbert, Neurologist, Dept. of Biophysics and Molecular Physiolology, USF School of Medicine, Tampa, FLdrgg22@tampabay.rr.com
    • Gordon J. Gilbert, M.D., St. Petersburg, FL, USA
    Submitted January 16, 2014
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