Nature paper on CSF Drainage and its possible modulation

Babaji

Dear Listserv members,

Re:
Yoon, JH., Jin, H., Kim, H.J. et al. Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage. Nature 625, 768–777 (2024). https://doi.org/10.1038/s41586-023-06899-4

|Download|

Neurosurgeons and, scientists with an interest in CSF disorders and CSF dynamics would find the recently published paper by Yoon et al. from South Korea of immense interest! The exact pathways through which CSF drains into the blood circulation remains unsolved. This paper, based on experiments in mice, sheds light on the role of nasopharyngeal lymphatic plexus in the drainage of CSF. Moreover the study reports on modulation of CSF drainage through pharmacological manipulation of cervical lymphatics, suggesting of possible medical treatments for adult chronic hydrocephalus, Alzheimer's and other neurodegenerative diseases.

For most neurosurgeons, the working model of CSF absorption is CSF drainage through arachnoid villi into the sagittal venous sinus. This model is only part of the story but is helpful in most clinical circumstances. We have seen cases where this model does not account for patients alive with obstruction to CSF at the aqueduct or fourth ventricular outflow.

Yoon et al., in their paper published in Nature on the 10th of January 2024, cite several papers supporting CSF drainage into the deep cervical lymph nodes. They identify the nasopharyngeal lymphatic plexus as a significant hub in the drainage of CSF into the deep cervical nodes. They undertook their experiments in transgenic mice. They also utilized fluorescent markers for lymphatics and advanced imaging techniques.

What makes this paper further exciting and has implications for patients with hydrocephalus, particularly those with chronic hydrocephalus, is that the authors were able to modulate the rate of CSF drainage through the cervical lymphatics with phenylephrine and sodium nitroprusside, i.e. improved CSF drainage with low dose phenylephrine and sodium Nitroprusside (NO donor). However,

Deep cervical lymphatic vessels have smooth muscles cells in their wall. It is thought phenylephrine and sodium nitroprusside mediated their action through their effect on the muscle cells of the deep cervical lymphatic vessels. However, the nasopharyngeal lymphatic plexus does not have smooth muscles in its walls.  

The lymphatic vessels were sensitive to these medications, even in elderly rats with degenerative nasopharyngeal lymphatic plexus. The deduction is that chronic hydrocephalus and neurodegenerative diseases that are related to inadequate removal of CSF and metabolites, might be amenable to treatment by medications that improve CSF outflow through the deep cervical lymph nodes.

The investigators had performed surgery on the mice under general anaesthesia to remove muscles to expose nasopharyngeal and cervical lymphatics for imaging of the lymphatics. One of the study's limitations is whether these surgeries and anaesthesia had a confounding influence on the findings of the study.