Comment

978 www. thelancet. com/neurology Vol 14 October 2015 white matter tracts and large-calibre draining veins that emptied into sinus-associated cisternal compartments. 7, 9, 10 For example, tracers injected into the cortex and striatum drained in part along the medial internal cerebral veins, and ultimately along the internal jugular circulation. The drainage of interstitial solutes along the perivenous spaces of the glymphatic pathway seem to provide these solutes access to the sinus-associated lymphatics either directly, as these large veins merge to form the dural sinuses, or indirectly via the cisternal CSF compartments. It might be therefore appropriate to regard these two components (the perivascular pathways within the CNS parenchyma and the extra-axial meningeal lymphatic vessels) as serial elements of a functional system. One element supports the clearance of solutes from the brain to the CSF, whereas the other propels that solute-laden CSF on to the systemic vascular system.

The interaction between the perivascular glymphatic pathway and the sinus-associated lymphatic vessels might also play a part in immune surveillance of the CNS by peripheral immune cells. Louveau and colleagues5 reported that T lymphocytes were strongly associated with lymphatic vessels in the brain. Ligation of the collecting vessels draining to the deep cervical lymph nodes resulted in the distension of the dural lymphatic vessels and the accumulation of T lymphocytes, suggesting that these vessels provide a pathway for the movement of immune cells out of the cranium. The clearance of interstitial solutes, presumably along perivascular pathways, to peripheral lymph nodes outside the brain parenchyma suggests that this pathway might play a part in antigen presentation and immune surveillance of the CNS, even while maintaining the relative immune privilege of the brain parenchyma.