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

Abstract

White matter hyperintensities (WMH) are prevalent. Although arteriolar disease has been implicated in their pathogenesis, venous pathology warrants consideration. We investigated relationships of WMH with histologic venous, arteriolar and white matter abnormalities and correlated findings with premortem neuroimaging. Three regions of periventricular white matter were sampled from archived autopsy brains of 24 pathologically confirmed Alzheimer disease (AD) and 18 age-matched nonAD patients. Using trichrome staining, venous collagenosis (VC) of periventricular veins (<150 µm in diameter) was scored for severity of wall thickening and occlusion; percent stenosis by collagenosis of large caliber (>200 µm) veins (laVS) was measured. Correlations were made between WMH in premortem neuroimaging and vascular and white matter pathology. We found greater VC (U(114) = 2092.5, p = 0.005 and U(114) = 2121.5, p = 0.002 for small and medium caliber veins, respectively) and greater laVS (t(110) = 3.46, p = 0.001) in patients with higher WMH scores; WMH scores correlated with VC (rs(114) = 0.27, p = 0.004) and laVS (rs(110) = 0.38, p < 0.001). By multiple linear regression analysis, the strongest predictor of WMH score was laVS (β = 0.338, p < 0.0001). VC was frequent in patients with periventricular infarcts identified on imaging. We conclude that periventricular VC is associated with WMH in both AD and nonAD patients and the potential roles of VC in WMH pathogenesis merit further study.