This study examined whether cervical lymph node removal (lymphadenectomy) impairs brain waste clearance and causes cognitive harm — first in a retrospective cohort of cancer patients who had neck dissection without chemo-radiation, then mechanistically in mouse and rat models of abrupt vs. gradual disruption of cervical/submandibular lymphatic drainage.
Up to 25% of patients who underwent neck lymphadenectomy developed mild-to-severe cognitive impairment, and neuroimaging showed accelerated temporal horn enlargement after bilateral surgery. In rodent models, acute lymphatic disruption caused CSF metabolic stress and inflammation, hippocampal redox stress, oxidative post-translational protein modifications, and microaggregation distinct from Alzheimer's-type amyloid; gradual drainage reduction did not produce these changes.
The clinical arm is retrospective and limited to cancer patients, making it difficult to exclude disease- or treatment-related confounders fully. Rodent models involve abrupt surgical ligation, which may not perfectly replicate the range of human lymphadenectomy procedures. The distinct nature of the protein microaggregates (non-amyloid) and their long-term clinical trajectory remain uncharacterized.
Surgeons performing neck dissections — especially bilateral cervical lymphadenectomy — should be aware that disrupting meningeal lymphatic outflow may raise the risk of cognitive impairment in up to 1 in 4 patients. Preoperative counseling and postoperative cognitive monitoring warrant consideration, and gradual or staged approaches to lymph node removal may mitigate brain clearance deficits.
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