Multiple Factors Involved in the Pathogenesis of White Matter Lesions

Abstract

White matter lesions (WMLs), also known as leukoaraiosis (LA) or white matter hyperintensities (WMHs), are characterized mainly by hyperintensities on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. With the aging of the population and the development of imaging technology, the morbidity and diagnostic rates of WMLs are increasing annually. WMLs are not a benign process. They clinically manifest as cognitive decline and the subsequent development of dementia. Although WMLs are important, their pathogenesis is still unclear. This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors. In particular, the attribution of WMLs to chronic ischemia secondary to venous collagenosis and cerebral blood flow autoregulation disruption seems reasonable. With the development of gene technology, the effect of genetic factors on the pathogenesis of WMLs is gaining gradual attention.

Figure 1

Neuroimaging features of white matter lesions: (a) periventricular white matter lesions on T2-weighted MRI. (b) Deep/subcortical white matter lesions on T2-weighted MRI. (c) Periventricular white matter lesions on MRI (FLAIR image). (d) Deep/subcortical white matter lesions on MRI (FLAIR image). FLAIR: fluid-attenuated inversion recovery.

Figure 2

Hypothesis about the pathogenesis of WMLs. JVR: jugular venous reflux; PWE: pulse wave encephalopathy; BBB: blood brain barrier; WMLs: white matter lesions.