Chirantan Banerjee, MD
Leukoaraiosis has been studied in several retrospective as well as prospective studies, and its importance cannot be denied. It has been associated not only with future ischemic (most commonly lacunar) strokes, but also intracerebral hemorrhage, as well as cognitive and gait outcomes. It is now well accepted as an important neuroimaging correlate of cerebral small vessel disease.
Several cross-sectional studies over the years found an association between white matter hyperintensities (WMHs)/lacunes and decreased cerebral blood flow (CBF), with several of them hypothesizing that decreased CBF leads to cerebral small vessel disease (CSVD). But the question remains, “Which came first, decreased CBF or CSVD?”
In Stroke, van der Veen et al. investigate the association between WMHs/lacunes and CBF longitudinally over four years of follow-up. Five hundred seventy-five out of 1309 patients with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or an abdominal aortic aneurysm referred to their center in Netherlands were enrolled. Two blinded investigators adjudicated WMHs and lacunes on MRI at baseline and during follow-up. Phase contrast MR flow measurements were used to measure CBF/100ml. The authors carried out bidirectional analyses prospectively, testing associations of baseline CBF with progression of periventricular and deep WMH volume/lacunes over time, as well as baseline periventricular and deep WMH volume/lacunes with decline in pCBF over time. The models were adjusted for important confounders, including age, sex, HTn, DM, hyperlidemia etc., as well as non-lacunar infarcts. Interestingly, there was no association between baseline CBF and progression of WMHs/lacunes. However, baseline periventricular and deep WMHs, but not lacunes were associated with decline in CBF over time. The authors reflect that more WMHs (as opposed to lacunes) may lead to widespread decreased brain activity and impaired nitric oxide generation, thus requiring less CBF over time. The lack of association between baseline CBF and progression of WMH brings more questions than answers, and makes us wonder what other factors play a role in their pathogenesis. Cerebral autoregulation architecture, genetics, and amyloid are plausible contributors.
The authors do help us clarify the chicken and egg situation somewhat in this case, but the results generate more hypotheses than they solve. Further longitudinal or randomized studies are needed to help us better characterize the relationship between leukoaraiosis and CBF.
