Older Patients Face Higher Risk of Smell Loss After Brain Base Endoscopic Surgery

A new study has found that older patients face a significantly higher risk of olfactory function decline when tumors deep at the base of the brain are removed via endoscopic surgery. Patients under 50 showed no notable change in smell function before and after surgery, while those aged 50 and older experienced a significant decline even when the same surgical technique was used. Bundang Seoul National University Hospital announced Monday that a joint research team led by Professor Cho Sung-woo of the Department of Otorhinolaryngology and Professor Hwang Ki-hwan of the Department of Neurosurgery evaluated olfactory function before and after surgery in 43 patients who underwent endoscopic skull base surgery at the hospital between 2021 and 2023. The skull base refers to the bottom portion of the cranial bone that encases the brain. It is located deep inside the skull, with critical cerebral blood vessels and cranial nerves densely clustered nearby. When tumors develop in this area, safely accessing the lesion itself poses a major challenge. In the past, surgeons performed craniotomies, opening the skull and gently retracting or displacing the brain to remove tumors. This approach had limitations, as the space gained by moving the brain was restricted, resulting in a narrow surgical field. Reaching from the top of the head down to the tumor at the base inevitably required passing major cerebral blood vessels and nerves, carrying a high risk of damage to normal brain tissue. In recent years, endoscopic skull base surgery — inserting an endoscope through the nose to remove skull base tumors — has become widely adopted. The technique leverages the fact that the bottom of the brain and the top of the nasal cavity are adjacent, allowing surgeons to reach the brain through the nose. However, because various surgical instruments including the endoscope must be maneuvered within the narrow nasal passage, olfactory nerve damage can occur, leading to reduced sense of smell. Olfactory nerves lack protective sheaths such as inner and outer membranes, making them vulnerable to physical stimulation. Cells that protect olfactory nerves do exist, but they are known to decrease with age. In endoscopic skull base surgery, the degree of olfactory nerve stimulation varies depending on the approach used to create a pathway for surgical instruments, such as excising part of the nasal bone. Previous studies had a limitation in that they compared patients' olfactory function without standardizing the surgical technique. This meant that even when post-surgical olfactory decline varied among patients, it was impossible to determine whether the cause was age or the surgical method. The research team selected patients who underwent the same surgical technique, then measured objective olfactory ability using the Cross-Cultural Smell Identification Test (CC-SIT) and subjective olfactory ability using an Olfactory Questionnaire (OQ). The CC-SIT has subjects smell odors and select the correct answer from multiple choices. The OQ asks respondents to self-report how well they can perceive smells. The analysis showed that among 30 patients aged 50 and older, both CC-SIT and OQ scores six months after surgery were significantly lower than pre-surgical levels. In contrast, 13 patients under 50 showed no notable change in either score. To understand how age and cellular characteristics relate to post-surgical olfactory function, the team directly analyzed olfactory mucosal cells from actual surgical patients. After staining the cells with fluorescent substances and observing them under a microscope, they found that older patients had fewer odor-detecting cells and fewer cells that aid olfactory regeneration. This suggests that older patients, lacking sufficient regenerative cells, have greater difficulty recovering even when exposed to the same level of surgical stimulation as younger patients. The study also confirmed that higher expression levels of S100 — a protein produced by cells that protect olfactory nerves — correlated with better preservation of olfactory function after surgery. S100 effectively acts as a shield protecting olfactory nerves from surgical stimulation. The findings also raise the possibility that S100 could serve as a biomarker for gauging the risk of olfactory decline. "We have established that a patient's age is an independent factor affecting olfactory decline after endoscopic skull base surgery," Professor Cho said. "This will contribute to developing age-specific treatment strategies to maximally preserve olfactory function in surgical patients." The study was supported by Bundang Seoul National University Hospital and the National Research Foundation of Korea's Early Career Researcher Support Program. It was published online in Rhinology, an international journal in the field of rhinology.

Older Patients Face Higher Risk of Smell Loss After Brain Base Endoscopic Surgery

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