Abstract
BACKGROUND: The central nervous system (CNS) was long believed to be devoid of lymphatic drainage. However, the discovery of the glymphatic system and meningeal lymphatics has revolutionized our understanding of cerebrospinal fluid homeostasis and neuroimmune interactions. The glymphatic system facilitates perivascular cerebrospinal fluid-interstitial fluid exchange and promotes neurotoxic waste clearance, whereas meningeal lymphatics serve as conduits between the CNS and peripheral lymphatic circulation. Dysfunction in these lymphatic efflux pathways has been implicated in the pathogenesis of neurological disorders such as Alzheimer disease, Parkinson disease, traumatic brain injury, and intracranial hemorrhage, where impaired waste removal contributes to protein aggregation, neuroinflammation, and hence, disease onset and progression. METHODS: Recent preliminary evidence suggests that surgical modulation of lymphatic drainage may offer novel therapeutic avenues for these disorders, with lymphatic microsurgery, particularly deep cervical lymphovenous anastomosis (LVA), proposed as an innovative procedure to enhance CNS lymphatic outflow. The first case reports in Alzheimer disease patients demonstrated not only the operative feasibility of LVA but also postoperative cognitive improvements. Despite these promising findings, systematic (pre)clinical studies remain scarce, calling for further research. RESULTS: This article examined the role of the brain lymphatic system in neurological disorders and discussed the potential of lymphatic microsurgery as a novel therapeutic intervention. We also highlight ongoing clinical trials and potential future innovations, including surgical robotic assistance, and report on 2 cases of deep neck LVA for central lymphatic disorders. CONCLUSIONS: By combining neurolymphatic research with surgical advances, LVAs have the potential to redefine therapeutic paradigms in CNS disorder management.