Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologica...

Full description

Bibliographic Details
Main Authors: Arthur S. Walters, Paisit Paueksakon, Charles H. Adler, Michael Moussouttas, Leonard B. Weinstock, Karen Spruyt, Kanika Bagai
Format: Article
Language:English
Published: Wiley 2021-06-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.120.019627
_version_ 1811275145127395328
author Arthur S. Walters
Paisit Paueksakon
Charles H. Adler
Michael Moussouttas
Leonard B. Weinstock
Karen Spruyt
Kanika Bagai
author_facet Arthur S. Walters
Paisit Paueksakon
Charles H. Adler
Michael Moussouttas
Leonard B. Weinstock
Karen Spruyt
Kanika Bagai
author_sort Arthur S. Walters
collection DOAJ
description Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T‐cell marker); (3) CD19 (a B‐cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease (P=0.015) and gliosis (P=0.003). T cells were increased in RLS compared with controls (P=0.009) and tended to colocalize with microvascular disease (P=0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration. Conclusions Patients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T‐cell invasion may be a secondary phenomenon.
first_indexed 2024-04-12T23:32:50Z
format Article
id doaj.art-88f052d333d04674b849d90c9350a975
institution Directory Open Access Journal
issn 2047-9980
language English
last_indexed 2024-04-12T23:32:50Z
publishDate 2021-06-01
publisher Wiley
record_format Article
series Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
spelling doaj.art-88f052d333d04674b849d90c9350a9752022-12-22T03:12:14ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-06-01101110.1161/JAHA.120.019627Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With GliosisArthur S. Walters0Paisit Paueksakon1Charles H. Adler2Michael Moussouttas3Leonard B. Weinstock4Karen Spruyt5Kanika Bagai6Sleep Division Department of Neurology Vanderbilt University Medical Center Nashville TNDepartment of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville TNDepartment of Neurology Mayo Clinic College of Medicine Scottsdale AZCerebrovascular Division Department of Neurology Rutgers Medical School New Brunswick NJSpecialists in Gastroenterology and Washington University Saint Louis MOINSERM Neurocampus Lyon FranceSleep Division Department of Neurology Vanderbilt University Medical Center Nashville TNBackground Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T‐cell marker); (3) CD19 (a B‐cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease (P=0.015) and gliosis (P=0.003). T cells were increased in RLS compared with controls (P=0.009) and tended to colocalize with microvascular disease (P=0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration. Conclusions Patients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T‐cell invasion may be a secondary phenomenon.https://www.ahajournals.org/doi/10.1161/JAHA.120.019627cortexgliosismicrovascular diseaserestless legs syndromeT cells
spellingShingle Arthur S. Walters
Paisit Paueksakon
Charles H. Adler
Michael Moussouttas
Leonard B. Weinstock
Karen Spruyt
Kanika Bagai
Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cortex
gliosis
microvascular disease
restless legs syndrome
T cells
title Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis
title_full Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis
title_fullStr Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis
title_full_unstemmed Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis
title_short Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis
title_sort restless legs syndrome shows increased silent postmortem cerebral microvascular disease with gliosis
topic cortex
gliosis
microvascular disease
restless legs syndrome
T cells
url https://www.ahajournals.org/doi/10.1161/JAHA.120.019627
work_keys_str_mv AT arthurswalters restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis
AT paisitpaueksakon restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis
AT charleshadler restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis
AT michaelmoussouttas restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis
AT leonardbweinstock restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis
AT karenspruyt restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis
AT kanikabagai restlesslegssyndromeshowsincreasedsilentpostmortemcerebralmicrovasculardiseasewithgliosis