Autonomic Nerve System Activity And Its Correlation With Prognosis In Patients With Hypothalamic Injury After Sellar Region Tumor Surgery

Background: Sellar region tumors are common diseases in neurosurgery.Tumors such as pituitary adenomas,craniopharyngiomas,meningiomas,and germ cell tumors often involve the hypothalamic region when they extend suprasellar.The hypothalamus is the highest center of the autonomic nervous system.Still,the status of autonomic nervous activity in patients with hypothalamic injury after sellar region tumor resection has received little attention,and the diagnosis and treatment of autonomic nervous dysfunction are often neglected.Heart rate variability(HRV)is the most commonly used autonomic nerve function evaluation index;it refers to the change in the cycle length of a heartbeat in normal sinus rhythm and describes the oscillation between successive heartbeats(RR interval).HRV has the advantages of being non-invasive,sensitive,quantitative,and intuitive and has been widely used to evaluate autonomic nerve activity and predict the prognosis in various disease states.Vanillylmandelic acid(VMA)is the primary metabolite of catecholamines.The content of VMA in urine changes with sympathetic nerve activity,and it is considered a biological marker that reflects sympathetic nerve activity.There are few studies on autonomic nerve dysfunction in patients with hypothalamic injury.Most of them evaluate autonomic nerve function in the postoperative follow-up period,and there are contradictions between the research results.There is still a lack of research on assessing autonomic nerve function in the early postoperative period.We tried to explore the state of autonomic nervous function in patients with hypothalamic injury in the early postoperative period by detecting HRV and 24 h urine VMA content.Objective: Detect the heart rate variability(HRV)and 24-hour urinary vanillylmandelic acid(VMA)levels in the perioperative period of patients with sellar region tumor involving the hypothalamus;evaluate the degree of hypothalamic injury based on postoperative brain MRI images;so that to explore the changes of autonomic nerve function in patients with hypothalamic injury after surgery for sellar region tumor.Meanwhile,to clarify the correlation between autonomic nervous activity and prognosis of patients with hypothalamic injury.We aim to provide a new idea for diagnosing and treating hypothalamus injury.Methods: This study enrolled the patients with sellar region tumors involving the hypothalamus who were treated at the Affiliated Hospital of Qingdao University and underwent surgical treatment from June 2020 to May 2021.The changes in autonomic nerve function during the perioperative period were evaluated by the patients’ HRV and 24-hour urinary VMA contents.Among HRV parameters,sympathetic nervous system index(SNS index),normalized low frequency(LFnu),and low frequency/high frequency(LF/HF)reflect sympathetic nervous system activity;parasympathetic nervous system index(PNS index),high frequency(HF)and normalized high frequency(HFnu)reflect parasympathetic nervous system activity.The degree of postoperative hypothalamus injury was assessed by the brain MRI images of the patients more than three months after the operation,and the patients were divided into grade 0(no damage)group,grade 1(mild damage)group,and grade 2(severe damage)group.The HRV parameters and 24 h urine VMA content were compared between the three groups before and after surgery to clarify the changes in autonomic nerve function in patients with hypothalamic injury.The prognosis of the patients was followed up and scored using the prognostic assessment scale.The correlation between the autonomic nervous function status with the patients’ prognosis was clarified by statistical analysis.Results: From June 2020 to May 2021,257 patients with sellar region tumors received surgical treatment at the Neurosurgery Department of the Affiliated Hospital of Qingdao University.After screening by inclusion and exclusion criteria,64 patients were enrolled in the study,which included 38 cases of nonfunctional pituitary adenomas(59.38%),10 cases of craniopharyngiomas(15.63%),6 cases of meningiomas(9.38%),5 cases of Rathke cleft cyst(7.81%),2 cases of chordomas(3.12%),1 case of lymphoma(1.56%),1 case of germ cell tumor(1.56%),and 1 case of Ewing’s sarcoma(1.56%).According to the degree of postoperative hypothalamus injury,patients were divided into three groups,including the grade 0 group(n = 36),grade 1 group(n = 18),and grade 2 group(n = 10).Analysis results of sympathetic nerve parameters in HRV showed that the SNS index of patients in the three groups was significantly different on day 1(p=0.010)and day 5(p=0.008)after surgery,and the patients in the grade 2 group were significantly lower than those in grade 1 and 0group.The LFnu of patients in the three groups was statistically different on day 2(p=0.004)and day 5(p=0.008)after surgery.On day two after surgery,the patients in the grade 2group were significantly lower than those in the grade 0 group.Patients in the grade 1 group were significantly lower than those in the grade 0 group on day five after surgery.There were statistical differences in LF/HF in the three groups on day 2(p=0.006)and day 5(p=0.008)after surgery,and the patients in the grade 2 group were significantly lower than those in the grade 0 group on day two after surgery.Patients in grade 1 and 2 groups were significantly lower than those in the grade 0 group on day five after surgery.Analysis result of parasympathetic nerve parameters in HRV showed that the PNS index of patients in the three groups was statistically different on day 1(p=0.004)and day 5(p=0.024)after surgery,and the grade 2 group was significantly higher than the grade 1 and 0 groups on the day one after surgery.Patients in the grade 2 group were significantly higher than those in the grade 0 group on day five after surgery.The HFnu in the three groups was statistically different on day 2(p=0.004)and day 5(p=0.008)after surgery,and the grade 2 group was significantly higher than the grade 0 group on day two after surgery.Patients in the grade 1group were significantly higher than those in the grade 0 group on day five after surgery.The HF in the grade 2 group tended to be higher than those in the grade 0 and 1 groups after surgery but were not statistically significant.The 24 h urinary VMA content of patients in the three groups was statistically different on day 1(p<0.001),day 2(p<0.001),and day5(p<0.001)after surgery,and further inter-group comparison showed that the 24 h urinary VMA content of patients in grade 2 group was significantly lower than that in grade 0 group and grade 1 group.Correlation analysis between autonomic nerve parameters and prognosis:there was no statistical significance between SNS index on day five after surgery and prognosis score,r=-0.242,p=0.054.There was a negative correlation between 24 h urinary VMA content on day five after surgery and the patient’s prognosis score,r=-0.304,p=0.015.There was a positive correlation between the PNS index on day five after surgery and the patient’s prognosis score,r=0.315,p=0.011.Conclusion: After sellar region tumor surgery,there was no obvious abnormality in autonomic nerve activity in patients with mild hypothalamic injury,but sympathetic nerve activity was weakened,and parasympathetic nerve activity was enhanced in patients with severe hypothalamic injury.Poor prognosis was negatively correlated with sympathetic nerve activity and positively correlated with parasympathetic nerve activity.Diagnosis and treatment of autonomic nerve dysfunction are expected to improve the treatment dilemma of patients with hypothalamic injury.