Nonhypertensive Cerebral Small-Vessel Disease

Abstract

Background and Purpose Cerebral small-vessel disease (SVD) is a common aging phenomenon that is exacerbated by hypertension and diabetes mellitus. It is regarded as an important cause of lacunar infarction and intracerebral hemorrhage. The present study was performed to highlight the existence and to some extent the frequency of pathologically verified SVD lacking in classic risk factors and to extend the scope of risk factor analysis. Methods The study group comprised 70 consecutively referred autopsy brains with microscopic evidence of SVD. In each case clinical records, autopsy reports, and central nervous system and systemic autopsy histology were reviewed. SVD was graded as mild, moderate, or severe in six standardized brain regions, and the results analyzed in relation to the presence or absence of classic SVD risk factors. Results SVD was manifest largely as concentric hyaline wall thickening; lipohyalinosis and fibrinoid necrosis were rarely observed. Thirty-one percent of cases failed to meet stringent clinicopathological criteria for significant prior hypertension. In 9% of cases, patients had been nonelderly, nondiabetic, and normotensive. Five of six cases lacking classic risk factors had systemic conditions known to enhance small-vessel permeability. Conclusions The nature of SVD appears to have been modified by effective treatment of hypertension. Classic risk factors are often absent. The hypothesis that a variety of conditions that enhance small-vessel permeability may contribute to the pathogenesis of SVD merits consideration.