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Peer-reviewedCC BY-NCStroke (Hoboken, N.J.)

Impact of White Matter Hyperintensities on Reperfusion Injury and Clinical Outcome After Successful Recanalization

  1. 1Department of Neurosurgery, Yamaguchi University School of Medicine, Japan (T.N., F.O., S.F., N.M., A.K., H.I.).
  2. 2Innovation Center for Translational Research, National Center for Geriatrics and Gerontology, Japan (R.K.).

Abstract

Background

Reperfusion injury (RI) is a major contributor to poor outcomes after successful recanalization in anterior circulation-large vessel occlusion. White matter hyperintensities (WMH) reflect chronic microvascular injury and are often associated with blood-brain barrier dysfunction or cerebral autoregulation impairment and may increase vulnerability to RI. We examined the association between WMH severity, RI, and clinical outcomes after successful recanalization.Methods

We retrospectively analyzed 236 patients with anterior circulation-large vessel occlusion who achieved modified Thrombolysis in Cerebral Infarction ≥2b. WMH severity was assessed using the Fazekas scale and dichotomized into absent-to-mild (score 0-3) and severe (score 4-6). RI was defined as parenchymal hematoma or malignant cerebral edema. Risk ratio (RR) was calculated, and causal mediation analysis was performed to assess the indirect effect of WMH on poor 90-day functional outcome (modified Rankin Scale of 3-6).Results

Severe WMH burden was present in 60 (25.4%) cases, RI occurred in 40 (16.9%) cases, and 128 (54.2%) cases had poor outcomes. Severe WMH was associated with an increased risk of RI (RR, 3.52 [95% CI, 1.97-6.29]; P<0.001). RI was independently associated with poor outcome (RR, 1.28 [95% CI, 1.01-1.62]; P=0.042), whereas WMH alone was not. In mediation analysis, severe WMH burden was not associated with poor outcome in terms of the total effect (RR, 1.02 [95% CI, 0.78-1.31]; P=0.744), but there was a significant indirect effect of severe WMH on poor outcome through RI (RR, 1.13 [95% CI, 1.04-1.30]; P=0.004).Conclusions

Severe WMH burden increases the risk of RI, which in turn adversely affects functional outcomes despite successful recanalization. WMH assessment may aid in identifying patients at higher risk of RI and support clinical risk stratification in anterior circulation-large vessel occlusion.

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BibTeX
@article{nishimoto2026impact,
  title = {{Impact of White Matter Hyperintensities on Reperfusion Injury and Clinical Outcome After Successful Recanalization}},
  author = {Takuma Nishimoto and Fumiaki Oka and Reo Kawano and Shunsuke Fujitsuku and Naomasa Mori and Akiko Kawano and Hideyuki Ishihara},
  journal = {Stroke (Hoboken, N.J.)},
  year = {2026},
  month = oct,
  doi = {10.1161/svin.126.002417},
  url = {https://europepmc.org/article/PMC/PMC13727217},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Impact of White Matter Hyperintensities on Reperfusion Injury and Clinical Outcome After Successful Recanalization
AU  - Takuma Nishimoto
AU  - Fumiaki Oka
AU  - Reo Kawano
AU  - Shunsuke Fujitsuku
AU  - Naomasa Mori
AU  - Akiko Kawano
AU  - Hideyuki Ishihara
PY  - 2026
DA  - 2026/10/02
JO  - Stroke (Hoboken, N.J.)
DO  - 10.1161/svin.126.002417
UR  - https://europepmc.org/article/PMC/PMC13727217
AB  - Background  Reperfusion injury (RI) is a major contributor to poor outcomes after successful recanalization in anterior circulation-large vessel occlusion. White matter hyperintensities (WMH) reflect chronic microvascular injury and are often associated with blood-brain barrier dysfunction or cerebral autoregulation impairment and may increase vulnerability to RI. We examined the association between WMH severity, RI, and clinical outcomes after successful recanalization.Methods  We retrospectively analyzed 236 patients with anterior circulation-large vessel occlusion who achieved modified Thrombolysis in Cerebral Infarction ≥2b. WMH severity was assessed using the Fazekas scale and dichotomized into absent-to-mild (score 0-3) and severe (score 4-6). RI was defined as parenchymal hematoma or malignant cerebral edema. Risk ratio (RR) was calculated, and causal mediation analysis was performed to assess the indirect effect of WMH on poor 90-day functional outcome (modified Rankin Scale of 3-6).Results  Severe WMH burden was present in 60 (25.4%) cases, RI occurred in 40 (16.9%) cases, and 128 (54.2%) cases had poor outcomes. Severe WMH was associated with an increased risk of RI (RR, 3.52 [95% CI, 1.97-6.29]; P<0.001). RI was independently associated with poor outcome (RR, 1.28 [95% CI, 1.01-1.62]; P=0.042), whereas WMH alone was not. In mediation analysis, severe WMH burden was not associated with poor outcome in terms of the total effect (RR, 1.02 [95% CI, 0.78-1.31]; P=0.744), but there was a significant indirect effect of severe WMH on poor outcome through RI (RR, 1.13 [95% CI, 1.04-1.30]; P=0.004).Conclusions  Severe WMH burden increases the risk of RI, which in turn adversely affects functional outcomes despite successful recanalization. WMH assessment may aid in identifying patients at higher risk of RI and support clinical risk stratification in anterior circulation-large vessel occlusion.
SN  - 2694-5746
ER  -