Brain drain for brain gain: Potential applications of robotic-assisted lymphatic microsurgery in the management of neurological disorders

Authors: Watson JA, Knoedler S, von Reibnitz D, Zurfluh CE, Imholz C, Esposito G, Schreiner SJ, Gousopoulos E, Cai A, Kollarik S, Giovanoli P, Baumann C, Lindenblatt N.

Affiliation: University Hospital Zurich, Switzerland.

Journal: Plastic and Reconstructive Surgery – Global Open; October 2025.

PMID: 41050965

Key takeaways

• Brain parenchyma lacks a traditional lymphatic system. Instead, the glymphatic system clears brain waste via CSF-interstitial exchange (sleep/AQP4)

• Meningeal lymphatics (true/traditional lymphatics) drain this resultant CSF and to deep cervical nodes.

• Deep cervical lymphovenous anastomosis (LVA) is proposed to augment CNS lymphatic outflow; early Alzheimer’s reports show feasibility and cognitive gains.

• Multiple prospective trials in Alzheimer’s and Parkinson’s are underway; robust validation remains needed.

• Robotic systems (e.g., Symani, MUSA) may improve precision for deep-neck lymphatic reconstruction.

Background

Modern research describes a two-component CNS clearance network composed of the glymphatic system and meningeal lymphatic vessels. The brain generates substantial metabolic waste, including lactate, misfolded proteins, and byproducts of high neuronal activity, yet it lacks traditional lymphatic vessels within the parenchyma. To maintain homeostasis within the fixed intracranial space, it relies on a specialized mechanism in which cerebrospinal fluid (CSF) enters periarterial spaces, travels through astrocytic endfeet enriched with aquaporin 4 (AQP4), and mixes with interstitial fluid through convective CSF and interstitial exchange. The resulting fluid then clears along perivenous pathways before draining into dural lymphatic vessels and ultimately to the deep cervical lymph nodes.

Glymphatic activity increases during slow wave sleep, when reduced noradrenergic tone expands the interstitial space and facilitates AQP4 dependent flow. Arterial pulsatility, preserved astrocytic polarity, and intact meningeal lymphatics support efficient clearance. In contrast, aging, vascular comorbidity, trauma, and ischemia impair these pathways and reduce waste removal.

Dysfunction of this system is increasingly associated with accumulation of beta amyloid, tau, and alpha synuclein, impaired neuroimmune surveillance, and worsened edema. These mechanisms link glymphatic and meningeal lymphatic impairment to Alzheimer and Parkinson disease, traumatic brain injury, and hemorrhagic conditions. Collectively, these insights provide the biologic rationale for augmenting cervical lymphatic outflow as a strategy to enhance CNS waste clearance, including the use of deep cervical lymphovenous anastomosis (LVA).

Objective

Review neurolymphatic physiology, synthesize early evidence for enhancing CNS lymphatic efflux via deep cervical LVA, and discuss how robotics may enable safe, precise translation.

Methods

• Narrative review of glymphatic/meningeal lymphatic literature and disease associations.

• Appraisal of initial clinical reports using deep cervical LVA for cognitive dysfunction.

• Summary of registered clinical trials and practical/ethical considerations for future studies.

Results

• Physiology: AQP4-dependent glymphatic flow clears neurotoxic proteins; human imaging (eg, DTI-ALPS, MRI-visible perivascular spaces) and animal models link impaired glymphatic/meningeal lymphatic function to β-amyloid, tau, and α-synuclein aggregation, neuroinflammation, and edema.

• Clinical signal (AD case reports): Deep cervical LVA has been described in an elderly cognitive impairment case (Lu 2022) and a 2024 AD case using a supermicrosurgical cervical shunting technique (Li 2024), with reported postoperative cognitive improvement; controlled data are not yet available.

• Multiple prospective trials registered in Alzheimer’s and Parkinson’s; no published Parkinson’s LVA outcomes yet.

  • Alzheimer’s disease

    • NCT06448442

    • NCT06448975

    • ChiCTR2500095309

    • ChiCTR2400093030

    • ChiCTR2400089883

    • ChiCTR2400094603

    • ChiCTR2400084617

  • Parkinson’s disease

    • ChiCTR2400091857

• Robotics: First-in-human robotic central lymphatic reconstructions and larger series show patent anastomoses and symptom improvement, supporting feasibility for cervical LVA.

Conclusion

Enhancing CNS lymphatic efflux via deep cervical LVA is promising but investigational; rigorous mechanistic and clinical validation is required before routine adoption.

Strengths & limitations

• Strengths: Clear synthesis of emerging neurolymphatic science; practical roadmap for surgical approaches and robotic facilitation.

• Limitations: Evidence base is mainly case reports/early series; no randomized or controlled data; ethical considerations remain.

Clinical relevance

For reconstructive microsurgeons and neurology/neurosurgery teams, cervical LVA, potentially with robotic assistance, could become an adjunct to improve protein clearance and inflammation. Use only within trials or protocols.