Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke

Abstract White matter hyperintensities of presumed vascular origin (WMH) are associated with various clinical sequelae. In stroke patients, the total WMH burden is linked to recurrent cerebrovascular events and worse clinical outcomes. As WMH also affect the integrity of large-scale structural brain...

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Main Authors: Samuel C. Olszówka, Benedikt M. Frey, Jan F. Feldheim, Lukas Frontzkowski, Paweł P. Wróbel, Winifried Backhaus, Focko L. Higgen, Hanna Braaß, Silke Wolf, Chi-un Choe, Marlene Bönstrup, Bastian Cheng, Götz Thomalla, Philipp J. Koch, Fanny Quandt, Christian Gerloff, Robert Schulz
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Neurological Research and Practice
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Online Access:https://doi.org/10.1186/s42466-025-00416-w
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author Samuel C. Olszówka
Benedikt M. Frey
Jan F. Feldheim
Lukas Frontzkowski
Paweł P. Wróbel
Winifried Backhaus
Focko L. Higgen
Hanna Braaß
Silke Wolf
Chi-un Choe
Marlene Bönstrup
Bastian Cheng
Götz Thomalla
Philipp J. Koch
Fanny Quandt
Christian Gerloff
Robert Schulz
author_facet Samuel C. Olszówka
Benedikt M. Frey
Jan F. Feldheim
Lukas Frontzkowski
Paweł P. Wróbel
Winifried Backhaus
Focko L. Higgen
Hanna Braaß
Silke Wolf
Chi-un Choe
Marlene Bönstrup
Bastian Cheng
Götz Thomalla
Philipp J. Koch
Fanny Quandt
Christian Gerloff
Robert Schulz
author_sort Samuel C. Olszówka
collection DOAJ
description Abstract White matter hyperintensities of presumed vascular origin (WMH) are associated with various clinical sequelae. In stroke patients, the total WMH burden is linked to recurrent cerebrovascular events and worse clinical outcomes. As WMH also affect the integrity of large-scale structural brain networks, we hypothesize that the extent of WMH-related network damage carries relevant information to explain outcome variability in addition to global WMH volume. Clinical and structural brain imaging data of 33 severely affected acute stroke patients were analyzed from two independent cohorts. Imaging data were acquired within the first two weeks after stroke. WMH-related localized and global network damage was derived. WMH network effects were differentially assessed for total, periventricular (pWMH), and deep WMH (dWMH). Using ordinal logistic regression analyses, network damage was associated with functional outcome at follow-up after three to six months. WMH were linked to a significant disconnection of multiple cortical and subcortical brain regions. Global and localized pWMH-related network damage affecting distinct brain regions of both hemispheres were independently associated with a worse outcome after adjustment for baseline symptom burden, age, brain infarct volume, and total WMH volume. Total and dWMH-related network disturbances did not show similar associations. This study indicates that pWMH-related network damage affecting specific brain regions is linked to functional outcome in acute stroke patients. It underscores the potential significance of pre-existing WMH-related network damage as a crucial factor in comprehending outcome variability after severe stroke.
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spelling doaj-art-4b82fcc64e6f4ec2836814040ba553392025-08-24T12:02:25ZengBMCNeurological Research and Practice2524-34892025-08-017111210.1186/s42466-025-00416-wLocalized network damage related to white matter hyperintensities is linked to worse outcome after severe strokeSamuel C. Olszówka0Benedikt M. Frey1Jan F. Feldheim2Lukas Frontzkowski3Paweł P. Wróbel4Winifried Backhaus5Focko L. Higgen6Hanna Braaß7Silke Wolf8Chi-un Choe9Marlene Bönstrup10Bastian Cheng11Götz Thomalla12Philipp J. Koch13Fanny Quandt14Christian Gerloff15Robert Schulz16Department of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, Charite University Medical Center BerlinDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfDepartment of Neurology, University Medical Center Hamburg-EppendorfAbstract White matter hyperintensities of presumed vascular origin (WMH) are associated with various clinical sequelae. In stroke patients, the total WMH burden is linked to recurrent cerebrovascular events and worse clinical outcomes. As WMH also affect the integrity of large-scale structural brain networks, we hypothesize that the extent of WMH-related network damage carries relevant information to explain outcome variability in addition to global WMH volume. Clinical and structural brain imaging data of 33 severely affected acute stroke patients were analyzed from two independent cohorts. Imaging data were acquired within the first two weeks after stroke. WMH-related localized and global network damage was derived. WMH network effects were differentially assessed for total, periventricular (pWMH), and deep WMH (dWMH). Using ordinal logistic regression analyses, network damage was associated with functional outcome at follow-up after three to six months. WMH were linked to a significant disconnection of multiple cortical and subcortical brain regions. Global and localized pWMH-related network damage affecting distinct brain regions of both hemispheres were independently associated with a worse outcome after adjustment for baseline symptom burden, age, brain infarct volume, and total WMH volume. Total and dWMH-related network disturbances did not show similar associations. This study indicates that pWMH-related network damage affecting specific brain regions is linked to functional outcome in acute stroke patients. It underscores the potential significance of pre-existing WMH-related network damage as a crucial factor in comprehending outcome variability after severe stroke.https://doi.org/10.1186/s42466-025-00416-wCerebral small vessel diseaseWMHBrain reserveFunctional outcomeRehabilitation
spellingShingle Samuel C. Olszówka
Benedikt M. Frey
Jan F. Feldheim
Lukas Frontzkowski
Paweł P. Wróbel
Winifried Backhaus
Focko L. Higgen
Hanna Braaß
Silke Wolf
Chi-un Choe
Marlene Bönstrup
Bastian Cheng
Götz Thomalla
Philipp J. Koch
Fanny Quandt
Christian Gerloff
Robert Schulz
Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
Neurological Research and Practice
Cerebral small vessel disease
WMH
Brain reserve
Functional outcome
Rehabilitation
title Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
title_full Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
title_fullStr Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
title_full_unstemmed Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
title_short Localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
title_sort localized network damage related to white matter hyperintensities is linked to worse outcome after severe stroke
topic Cerebral small vessel disease
WMH
Brain reserve
Functional outcome
Rehabilitation
url https://doi.org/10.1186/s42466-025-00416-w
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