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.

The “central vein sign” in inflammatory demyelination: The role of fibrillar collagen type I

“…Collagenosis of the deep medullary veins has been recently associated with periventricular T 2 hyperintensity in small vessel disease, 20 but the potential relationship of those changes to inflammation is unknown. Collagenosis of the deep medullary veins has been recently associated with periventricular T 2 hyperintensity in small vessel disease, 20 but the potential relationship of those changes to inflammation is unknown.…”

Ontario Neurodegenerative Disease Research Initiative (ONDRI): Structural MRI methods & outcome measures

“…Historically controversial Sachdev and Wen, 2005), this concept is based on several theories and research findings which suggest that WMH in close proximity to the ventricles (hence the term 'peri-ventricular') have a different pathological etiology (Gouw et al, 2011;Simpson et al, 2007) and are differentially correlated with cognitive/behavior deficits in comparison to the more distal dWMH (despite the confusing fact that pWMH are technically found in deeper white matter than dWMH). Additionally, recent imaging-pathology correlations suggest that pWMH may be indicative of venous collagenosis, a type of small vessel disease related to the deep medullary veins and venules (as opposed to the arterial side of the cerebral vasculature) (Black et al, 2009;Keith et al, 2017;Moody et al, 1995). It is also interesting to note that there is no standard consensus in the literature on how to define pWMH vs. dWMH, with some pa-pers using a proportional distance to the dura mater (Decarli et al, 2005a), some using an arbitrary cut-off (typically 13mm from the ventricles) (Sachdev et al, 2008), and others using a 3D connectivity algorithm (Ramirez et al, 2011;van den Heuvel et al, 2006) -the method that is currently supported by ONDRI (see Fig.…”

Increased Diameters of the Internal Cerebral Veins and the Basal Veins of Rosenthal Are Associated with White Matter Hyperintensity Volume

“…11 Periventricular venous collagenosis and large-caliber venous stenosis may be 1 mechanism through which WMHs and AD are associated, and venous collagenosis may increase overall resistance in the veins, leading to reduced blood flow to the deep white matter. 12 Venous outflow obstruction may also lead to decreased clearance of metabolic by-products and toxic misfolded proteins as seen in AD, resulting in ischemic stress. 12 Cerebral veins have typically been distinguished from the arterial and capillary systems by postmortem analysis with complex immunostaining.…”