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September 29, 2015; 85 (13) Article

Brain arterial remodeling contribution to nonembolic brain infarcts in patients with HIV

Jose Gutierrez, James Goldman, Andrew J. Dwork, Mitchell S.V. Elkind, Randolph S. Marshall, Susan Morgello
First published August 28, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001976
Jose Gutierrez
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
MD, MPH
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James Goldman
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
MD
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Andrew J. Dwork
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
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Mitchell S.V. Elkind
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
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Randolph S. Marshall
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
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Susan Morgello
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
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Citation
Brain arterial remodeling contribution to nonembolic brain infarcts in patients with HIV
Jose Gutierrez, James Goldman, Andrew J. Dwork, Mitchell S.V. Elkind, Randolph S. Marshall, Susan Morgello
Neurology Sep 2015, 85 (13) 1139-1145; DOI: 10.1212/WNL.0000000000001976

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Abstract

Background: Cerebrovascular disease is a cause of morbidity in HIV-infected populations. The relationship among HIV infection, brain arterial remodeling, and stroke is unclear.

Methods: Large brain arteries (n = 1,878 segments) from 284 brain donors with and without HIV were analyzed to obtain media and wall thickness and lumen-to-wall ratio, and to determine the presence of atherosclerosis and dolichoectasia (arterial remodeling extremes). Neuropathologic assessment was used to characterize brain infarcts. Multilevel models were used to assess for associations between arterial characteristics and HIV. Associations between arterial characteristics and brain infarcts were examined in HIV+ individuals only.

Results: Adjusting for vascular risk factors, HIV infection was associated with thicker arterial walls and smaller lumen-to-wall ratios. Cerebral atherosclerosis accounted for one-quarter of the brain infarcts in HIV+ cases, and was more common with aging, diabetes, a lower CD4 nadir, and a higher antemortem CD4 count. In contrast, a higher lumen-to-wall ratio was the only arterial predictor of unexplained infarcts in HIV+ cases. Dolichoectasia was more common in HIV+ cases with smoking and media thinning, and with protracted HIV infection and a detectable antemortem viral load.

Conclusions: HIV infection may predispose to inward remodeling compared to uninfected controls. However, among HIV+ cases with protracted immunosuppression, outward remodeling is the defining arterial phenotype. Half of all brain infarcts in this sample were attributed to the extremes of brain arterial remodeling: atherosclerosis and dolichoectasia. Understanding the mechanisms influencing arterial remodeling will be important in controlling cerebrovascular disease in the HIV-infected population.

GLOSSARY

cART=
combination antiretroviral therapy;
CI=
confidence interval;
CVD=
cardiovascular disease;
IEL=
internal elastic lamina;
LWR=
lumen-to-wall ratio;
MHBB=
Manhattan HIV Brain Bank;
OR=
odds ratio

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.

  • Supplemental data at Neurology.org

  • Editorial, page 1098

  • Received February 26, 2015.
  • Accepted in final form May 5, 2015.
  • © 2015 American Academy of Neurology
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