Christopher Wilkins, MD
Koton S, Schneider ALC, Windham BG, Mosley TH, Gottesman RF, Coresh J. Microvascular Brain Disease Progression and Risk of Stroke: The ARIC Study. Stroke. 2020;51:3264–3270.
Evidence of cerebral microvascular disease can be seen on MRI in the form of diffuse subcortical white matter hyperintensities (WMH) and lacunar infarcts. Studies have shown that these signs of microvascular disease on MRI are associated with an increased risk of stroke, as well as poorer clinical outcomes following a stroke. However, there is less data on determining how much of an impact progression of WMHs and asymptomatic lacunar infarcts seen on MRI has on the incidence of stroke, which is what Koton et al. investigated in this study.
Participants for the study were chosen from the Atherosclerosis Risk in Communities (ARIC) study, which is a prospective cohort study that selected 15792 Black and White participants from 1987-1989 to determine the causes and the long-term consequences of atherosclerotic disease. A subset of the ARIC study participants was chosen to undergo one MRI of the brain between 1993-1995 and another between 2004-2006. This study included 907 participants who underwent both MRIs, had no clinical stroke prior to the second MRI and who were followed up through 12/31/17, or had died or were censored prior to that date. The amount of WMH on those MRIs was placed on a scale of 0-9 with 9 being the highest amount and lacunes were counted with each defined as a focal hyperintense lesion 3 to 20 mm in size. Progression of microvascular disease was measured by subtracting the WMH grade and number of lacunes on the first MRI from those on the second MRI. Time between first and second MRI ranged from 8.7 to 12.7 years.
At the time of the second brain MRI, 335 participants (37%) had WMH grade <2 and no lacune, 521 (57%) had WMH grade ≥2 or lacune, and 51 (6%) had WMH grade ≥2 and lacune. Comparing these results with the findings on the first MRI, it was found that 244 (38%) had no progression with no change in WMH grade or new lacune, 518 (57%) had mild progression with either ≥1 unit increase in WMH grade or new lacune, and 45 (5%) had moderate progression with both ≥1 unit increase in WMH grade and new lacune. There were 64 incident strokes occurring after the second brain MRI until 12/31/17. There were significant associations between incidence of stroke and presence of microvascular disease on second MRI after controlling for risk factors. Compared to participants with WMH grade <2 and no lacune, those with either WMH grade ≥2 or lacune had a hazard ratio of 2.16 (95% CI, 1.10-4.24) and those with both WMH grade ≥2 and lacune had a hazard ratio of 4.36 (95% CI, 1.73-11.00). There was a significant association between progression of combined WMH/lacune, but only in the moderate progression group with a hazard ratio of 3.03 (95% CI, 1.30-6.94), while the mild progression group was not statistically significant with a hazard ratio of 1.10 (95% CI, 0.62-1.94). When looking at progression of WMH or lacune individually, there was no statistically significant association except in the group of participants that had a 5 unit increase in WMH grade, which had a hazard ratio of 16.36 (95% CI, 1.93-138.53).
The results of this study are concordant with past studies showing that signs of more severe microvascular disease on MRI in the form of WMH and asymptomatic lacunar infarcts are associated with increased incidence of stroke. This study also shows, however, that the combined progression of WMH and asymptomatic lacunar infarct is associated with increased incidence of stroke. There are limitations to this study, such as the inclusion of only White and Black people, thus limiting the generalizability of the results. The small number of strokes in this cohort meant that evaluating for different types of stroke, namely ischemic vs. hemorrhagic and subtypes of ischemic stroke, would lead to underpowered results. This is crucial as some forms of stroke may be more or less associated with microvascular disease than others. Though effort was made to make sure the second MRI was consistent with the settings of the first MRI, there could be a discrepancy in slice location that can lead to error in measuring WMH and lacune progression.
This study highlights the impact that signs of microvascular disease on MRI have on stroke risk and how the progression of these microvascular changes on MRI should not be taken lightly. Though one could surmise that incidence of symptomatic small vessel strokes would be more associated with progression of WMH and asymptomatic lacunes on MRI than other subtypes of stroke, it would be helpful to have actual evidence looking at the different subtypes of stroke and determine which are associated with progression of these MRI findings. Imaging in future studies could also include GRE or SWI sequences to look for microbleeds, another sign of microvascular disease. Lastly it would be worthwhile to investigate if there’s a degree of medical management that could deter the progression of microvascular disease seen on MRI and whether deterrence of the progression actually leads to reduction in stroke incidence.
Among the three important etiologies of cerebral small vessel disease i.e. hypertension related, age related, and cerebral amyloid angiopathy related cerebral small vessel disease there are two other important emerged causes i.e. hyperhomocysteinuria, and the osteoporosis, which are quite common1,2,3. Besides these we may go for workup for vasculitis like Churgstrauss and Wegeners’mgranulomatosis etc. in an appropriate setting and in comorbid conditions.
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therapeutic challenges . Lancet Neurol 2010 Jul;9(7):689-701. DOI: 10.1016/S1474-4422(10)70104-6
2. Jeong-Min Kim, Kwang-Yeol Park, Hye Ryoun Kim et al. Association of Bone Mineral Density
to Cerebral Small Vessel Disease Burden. First published January 11, 2021, DOI:
3. Ki-Woong Nam, Hyung-Min Kwon, Han-Yeong Jeong, Jin-Ho Park, Hyuktae Kwon, Su-Min
Jeong . Serum homocysteine level is related to cerebral small vessel disease in a healthy population.
First published January 2, 2019, DOI: https://doi.org/10.1212/WNL.0000000000006816