Collagenosis of the Deep Medullary Veins: An Underrecognized Pathologic Correlate of White Matter Hyperintensities and Periventricular Infarction?

Area of Science:

• Neurology
• Pathology
• Neuroimaging

Background:

• White matter hyperintensities (WMH) are common, particularly in aging brains.
• While arteriolar disease is a known factor, the role of venous pathology in WMH pathogenesis is less understood.
• Alzheimer disease (AD) patients exhibit significant WMH burden.

Purpose of the Study:

• To investigate the association between white matter hyperintensities (WMH) and histological findings of venous and arteriolar pathology.
• To correlate premortem neuroimaging findings of WMH with postmortem neuropathological assessments.
• To explore the role of venous collagenosis (VC) and large vein stenosis (laVS) in WMH development.

Main Methods:

• Autopsy brains from 24 Alzheimer disease (AD) and 18 non-AD patients were analyzed.
• Trichrome staining was used to assess venous collagenosis (VC) severity and large vein stenosis (laVS) in periventricular white matter.
• Histopathological findings were correlated with premortem WMH scores from neuroimaging.

Main Results:

• Higher WMH scores were significantly associated with increased venous collagenosis (VC) and large vein stenosis (laVS).
• WMH scores showed positive correlations with both VC and laVS.
• Multiple linear regression identified laVS as the strongest predictor of WMH score (β = 0.338, p < 0.0001).
• Periventricular venous collagenosis was frequently observed in patients with periventricular infarcts.

Conclusions:

• Periventricular venous collagenosis (VC) is significantly associated with white matter hyperintensities (WMH) in both AD and non-AD individuals.
• These findings highlight the potential contribution of venous pathology, specifically VC, to the development of WMH.
• Further research into the pathogenetic mechanisms of VC in WMH is warranted.