Removal of lymph nodes in the neck may disrupt the drainage of cerebrospinal fluid from the brain and contribute to cognitive impairment. This is reported in a new study by scientists at Weill Cornell Medicine in the United States, published in the scientific journal Neuron.
The researchers found that patients with head and neck cancer who had undergone cervical lymphadenectomy — surgery to remove nearby lymph nodes to reduce the spread of cancer — had higher rates of cognitive impairment compared with the general population.
In preclinical studies, the scientists demonstrated how the procedure may disrupt the brain’s waste-clearance system, leading to fluid accumulation and a molecular process known as oxidative stress, which damages cellular proteins and triggers inflammation. “Your body produces lymphatic fluid to wash away waste from every organ, including the brain. If this system fails, the negative consequences can accumulate over time,” explained Dr. Laura Santambrogio, a professor of radiation oncology at Weill Cornell Medicine.
Neck lymphedema — swelling caused by impaired lymphatic drainage — is a common complication after lymphadenectomy. However, the consequences of impaired drainage of lymphatic fluid from the brain have not previously been studied in detail.
The researchers analyzed records from 1,035 patients who had undergone cervical lymphadenectomy without additional chemotherapy or radiation therapy. The rate of cognitive impairment was higher than estimates for corresponding age groups in the general population.
About 18% of patients younger than 65 experienced cognitive impairment within two years of the procedure. In the general population, the overall risk of developing mild or severe cognitive impairment in this age group is 4–6%.
Among patients older than 65, 25% of those who underwent surgery developed cognitive impairment, compared with 10–22% in the general population. Although the findings indicate an association between cervical lymphadenectomy and subsequent cognitive impairment, further research is needed to confirm a direct causal relationship.
The scientists also studied a second group of 59 patients who had undergone cervical lymphadenectomy without radiation or chemotherapy at the Technical University of Munich. These patients underwent brain MRI scans before and after surgery. The scans showed accelerated enlargement of a structure known as the temporal horns of the ventricles after surgery, indicating brain atrophy or shrinkage. This effect was more pronounced when lymph nodes were removed from both sides of the neck.
To identify the underlying biological mechanisms, the researchers conducted experiments in animal models. When fluid could no longer drain normally from the brain, brain cells showed signs of increased oxidative stress and elevated levels of proteins associated with inflammation.
The researchers also found that proteins such as synapsin, which are involved in signaling between neurons, became damaged and clumped together. These dense aggregates differed from beta-amyloid plaques and thin strands of tau protein characteristic of Alzheimer’s disease.
The scientists plan to conduct a prospective study that will follow patients over time after cervical lymph node removal.
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