Seby John, MD

Aribisala BS, Wiseman S, Morris Z, Valdés-Hernández MC, Royle NA, Maniega SM, et al. Circulating Inflammatory Markers Are Associated With Magnetic Resonance Imaging-Visible Perivascular Spaces But Not Directly With White Matter Hyperintensities. Stroke. 2014

In the last 15 years, cerebral SVD has been recognized as a major problem.  It causes a fifth of all strokes, and contributes to 45% of all dementias. The cause remains unknown and management is largely empirical.  C Miller Fisher’s detailed clinicopathological post-mortem studies provided the first insights into the pathogenesis of the disease, but mechanisms of SVD are still unclear.

In an article in Stroke, Aribisala and colleagues explore the association between inflammation and imaging markers of SVD. White matter hyperintensities (WMH) and perivascular spaces (PVS) are known features of SVD. The authors measured plasma fibrinogen, C-reactive protein and interleukin-6 in members of the Lothian Birth Cohort (all born in 1936) having a mean age of 73. A brain MRI was performed and neuroradiologists rated the PVS and WMH. They found a strong association between increased numbers of visible PVS and increased amounts of WMH. Inflammatory markers were weakly but significantly associated with PVS, but not with WMH.

The association between inflammation and PVS has been observed in settings outside of SVD. For example, the diameter of spaces increases during periods of active inflammation in multiple sclerosis. These changes are likely mediated through effects on the small perforating arterioles. But similar to Fisher’s study of the lacune that was done long after the patient suffered from a stroke, this study on elderly subjects may miss observations perhaps at the origins of the SVD process. A study on younger individuals examining peripheral and central inflammatory markers could show a different profile, tell us whether PVS predates WMH or if immunomodulators modify SVD course.
More information on the role of inflammation, and more importantly interventions targeting this mechanism is needed. Till there is more clarity on mechanisms, we shouldn’t assume that SVD is all a consequence of ischemia.