Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain

Neurology. 2021 Nov 22;10.1212/WNL.0000000000013077. doi: 10.1212/WNL.0000000000013077. Online ahead of print.


Perivascular spaces (PVS) are fluid filled compartments that are part of the cerebral blood vessel wall and represent the conduit for fluid transport in and out of the brain. PVS are considered pathologic when sufficiently enlarged to be visible on magnetic resonance imaging. Recent studies have demonstrated that enlarged PVS (ePVS) may have clinical consequences related to cognition. Emerging literature points to arterial stiffening and abnormal protein aggregation in vessel walls as two possible mechanisms that drive ePVS formation. In this review, we describe the clinical consequences, anatomy, fluid dynamics, physiology, risk factors, and in vivo quantification methods of ePVS. Given competing views of PVS physiology, we detail the two most prominent theoretical views and review ePVS associations with other common small vessel disease markers. As ePVS are a marker of small vessel disease and ePVS burden is higher in Alzheimer's disease, a comprehensive understanding about ePVS is essential in developing prevention and treatment strategies.

Keywords: Arterial stiffening; Cerebrospinal fluid; Intramural peri-arterial drainage; Perivascular spaces; β-amyloid.