Cerebrospinal Fluid Absorption Revisited: Do Extracranial Lymphatics Play a Role?

Abstract

It would seem heretical to suggest that extracranial lymphatic vessels play a major role in the volumetric clearance of cerebrospinal fluid (CSF) from the cranial vault. It is well established that there are no lymphatics within the brain parenchyma, and it has been assumed that the drainage of CSF into the venous system occurs predominantly through the arachnoid villi and granulations. Nonetheless, a physiological association between extracellular fluid in the brain and extracranial lymph has been appreciated for more than 100 years. More important, recent studies in adult experimental animals have demonstrated that on average, one-half of the total volume of CSF absorbed from the cranial compartment was removed by extracranial lymphatics. Our objective in writing this review is to outline the experimental data that support the hypothesis that extracranial lymphatic vessels play an important role in CSF transport in the adult. Additionally, we will develop the hypothesis that lymphatic vessels may provide the primary route through which CSF is cleared from the cranial subarachnoid space in the fetus. With this new conceptual framework, we will reassess hydrocephalus from a lymphatic perspective to determine if impaired CSF transport through extracranial lymphatics might contribute to the development of this disease.