Not Just Blood: Brain Fluid Systems and Their Relevance to Cerebrovascular Diseases

Abstract

troke research has largely focused on blood supply to the brain, particularly via large arteries leading from the heart, the muscular intracranial large arteries, large cerebral veins and venous sinuses, and more recently perforating arterioles, capillaries, and venules. However, these blood vessels only serve part of the brain's fluid management, nutrient delivery, and waste clearance system. The other, and until recently largely neglected, aspect of brain fluid and waste management is the system that flushes the brain, draining interstitial and cerebrospinal fluid (CSF) and waste from the cranial cavity. Details of this non-blood-vessel brain circulation are incomplete, but there is now enough clinical relevance for it to be the focus of this Advances in Stroke: Diagnosis and Imaging, particularly as key elements are now visible on routine magnetic resonance imaging (MRI).

Inferior Frontal Sulcal Hyperintensities on Brain MRI Are Associated with Amyloid Positivity beyond Age—Results from the Multicentre Observational DELCODE Study

“…We divided our regression models into potential (1) factors contributing to IFSHs and (2) outcomes associated with IFSHs. (1) In a first step, we performed univariate ordinal regression analyses with the total IFSH score (categories) as dependent variable and age, sex, years of education, and the dichotomous variables arterial hypertension, A+, T+, and AD pathology (A+ and T+ combined) as independent variables separately. Secondly, a multivariable ordinal regression analysis, which included all independent variables (except for AD pathology), was conducted.…”

“…The cerebrospinal fluid (CSF) in the regions immediately superior to the cribriform plate, particularly those corresponding to the inferior frontal sulci, may display elevated signal intensities in T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging [1]. The occurrence and extent of these hyperintensities, referred to as inferior frontal sulcal hyperintensities (IFSHs), have been proposed to be indicative of impaired CSF clearance and glymphatic dysfunction [2].…”

“…This is because CSF is presumed to enter the meningeal lymphatics in close proximity to the cribriform plate. The stagnation of proteins, blood, and cell debris in this region could lead to such hyperintensities [1].…”

Diffusion tensor free water MRI predicts progression of FLAIR white matter hyperintensities after ischemic stroke

“…Pathology studies have also found more venous collagenosis associated with a higher WMH burden ( 7 ). More recently, a role for impaired glymphatic drainage has also been proposed for the pathogenesis of WMH lesions ( 37 ). Arteriolosclerosis is the most common pathologic correlate to WMH on imaging, ( 38 ) and arteriolar stiffening, or reduced compliance, impairs vasomotion and paravascular fluid clearance, thereby resulting in interstitial fluid accumulation ( 39 ).…”