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February 03, 2021Article

Lacunes, Microinfarcts and Vascular Dysfunction in Cerebral Amyloid Angiopathy

Elif Gokcal, View ORCID ProfileMitchell J. Horn, Susanne J. van Veluw, View ORCID ProfileAina Frau-Pascual, Alvin S. Das, View ORCID ProfileMarco Pasi, View ORCID ProfilePanagiotis Fotiadis, Andrew D. Warren, Kristin Schwab, Jonathan Rosand, Anand Viswanathan, Jonathan R. Polimeni, Steven M. Greenberg, M. Edip Gurol
First published February 3, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011631
Elif Gokcal
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: egokcal@mgh.harvard.edu
Mitchell J. Horn
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • ORCID record for Mitchell J. Horn
  • For correspondence: mjhorn@mgh.harvard.edu
Susanne J. van Veluw
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: svanveluw@mgh.harvard.edu
Aina Frau-Pascual
2Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA
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  • ORCID record for Aina Frau-Pascual
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Alvin S. Das
3Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
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  • For correspondence: asdas@mgh.harvard.edu
Marco Pasi
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
4Univ-Lille.Inserm U1171. CHU Lille (Department of Neurology, Stroke Unit), Lille, France.
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  • ORCID record for Marco Pasi
  • For correspondence: marco.pasi85@gmail.com
Panagiotis Fotiadis
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • ORCID record for Panagiotis Fotiadis
  • For correspondence: pfotiad@gmail.com
Andrew D. Warren
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: awarren6@mgh.harvard.edu
Kristin Schwab
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: kschwab@mgh.harvard.edu
Jonathan Rosand
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: jrosand@partners.org
Anand Viswanathan
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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  • For correspondence: aviswanathan1@partners.org
Jonathan R. Polimeni
2Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA
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  • For correspondence: jrpolimeni@mgh.harvard.edu
Steven M. Greenberg
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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M. Edip Gurol
From the 1J. Philip Kistler Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA
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Citation
Lacunes, Microinfarcts and Vascular Dysfunction in Cerebral Amyloid Angiopathy
Elif Gokcal, Mitchell J. Horn, Susanne J. van Veluw, Aina Frau-Pascual, Alvin S. Das, Marco Pasi, Panagiotis Fotiadis, Andrew D. Warren, Kristin Schwab, Jonathan Rosand, Anand Viswanathan, Jonathan R. Polimeni, Steven M. Greenberg, M. Edip Gurol
Neurology Feb 2021, 10.1212/WNL.0000000000011631; DOI: 10.1212/WNL.0000000000011631

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Abstract

Objective We aimed to analyze the relationship of lacunes with cortical cerebral microinfarcts (CMI), to assess their association with vascular dysfunction and to evaluate their effect on the risk of incident intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA).

Methods The count and topography of lacunes (deep/lobar), CMIs and white matter hyperintensity (WMH) volume were retrospectively analyzed in a prospectively enrolled CAA cohort that underwent high-resolution research MRIs. The relationship of lacunes with CMIs and other CAA-related markers including time-to-peak (TTP) of blood-oxygen-level-dependent signal-an established measure of vascular dysfunction-was evaluated in multivariate models. Adjusted Cox regression models were used to investigate the relationship between lacunes and incident ICH.

Results The cohort consisted of 122 nondemented probable CAA patients (mean age, 69.4 ± 7.6 years). Lacunes were present in 31 patients (25.4%), all but one were located in lobar regions. Cortical CMIs were more common in patients with lacunes compared to patients without lacunes (51.6% vs 20.9%, p = 0.002). TTP was not associated with either lacunes or CMIs (both p > 0.2) but longer TTP response independently correlated with higher WMH volume (p = 0.001). Lacunes were associated with increased ICH risk in univariate and multivariate Cox-regression models (p = 0.048 and p = 0.026, respectively).

Conclusions Our findings show a high prevalence of lobar lacunes, frequently co-existing with CMIs in CAA, suggesting that these 2 lesion types may be part of a common spectrum of CAA-related infarcts. Lacunes were not related to vascular dysfunction but predicted incident ICH, favoring severe focal vessel involvement rather than global ischemia as their mechanism.

  • Received April 29, 2020.
  • Accepted in final form December 18, 2020.
  • © 2021 American Academy of Neurology

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