White matter disease (leukoaraiosis) was long considered a normal occurrence in the aging process. Recent studies, however, have associated leukoaraiosis with dementia and disability, though how and why it develops is still unknown.

The authors of a recent paper, funded by an ASNR Scholar Award and published in Annals of Neurology, have posited one possible etiology: tiny, subclinical strokes. To investigate the relationship between acute infarct and white matter disease, the authors performed a prospective observational study, recruiting 5 subjects over a 12-month period; all subjects were older than 55 years, had had both a brain MRI within 6 months and an MR angiogram of the neck, and lastly, had moderate-to-severe leukoaraiosis (Fazekas scale ≥ grade 2).

At weekly intervals for 16 weeks, the authors took MRI scans of the subjects’ brains. The presence of acute infarct was established using diffusion tensor imaging (DTI), and patients were assessed every fourth week for changes in linguistic capacity or physical symptoms. No new neurological symptoms were noted in any of the subjects throughout the course of the study.

In all, 9 acute infarcts in 3 patients were detected in the cerebral white matter during the 16 weeks, and these clinically silent lesions progressed such that they began to take on the appearance of pre-existing areas of leukoaraiosis. The video below, from the University of Toronto, shows a week-by-week time-lapse of the acute infarcts arising de novo in the white matter, and then changing to appear as leukoaraiotic lesions on MRI:

The authors caution that the small sample size and short duration of the study contribute to uncertainty, but nonetheless suggest that their research provides reason to believe that very small, silent acute infarcts are a cause of white matter disease.

References

Conklin J, Silver FL, Mikulis DJ, et al. Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks. Ann Neurol, published online October 30, 2014, 10.1002/ana.244285