The Effect of Immediate Microsurgical Resection of Vestibular Schwannoma on Hearing Preservation.

OBJECTIVE: Evaluate for differences in postoperative hearing in patients who undergo immediate versus delayed hearing preservation microsurgical resection of vestibular schwannomas (VS). STUDY DESIGN: Retrospective single-institution cohort study spanning November 2017 to November 2021. SETTING: Single-institution tertiary care hospital. PATIENTS: Sporadic VS in patients with American Academy of Otolaryngology-Head and Neck Surgery hearing classification A or B, with tumor size less than or equal to 2 cm and undergoing hearing preservation microsurgical resection. INTERVENTIONS: Delayed surgical intervention defined by time from first diagnostic MRI to date of surgery being greater than 3 months. MAIN OUTCOME MEASURES: Preoperative and postoperative audiometric performance. RESULTS: In total, 193 patients met inclusion criteria. Within the cohort, 70 (36%) proceeded with surgery within 3 months of diagnostic MRI with a mean observation time of 62 days, whereas 123 (63%) underwent surgery after 3 months with a mean observation time of 301 days. There was no difference in preoperative hearing between the two groups with word recognition score 99% in early intervention group and 100% in delayed intervention group ( p = 0.6). However, 64% of those who proceeded with immediate surgery had successful hearing preservation, compared to a 42% of those who had delayed intervention ( p < 0.01). In a multivariable logistic regression accounting for preoperative word recognition score, tumor size, and age at diagnosis, the odds of hearing preservation were lower in those who delayed surgery compared to immediate surgery (odds ratio, 0.31; 95% confidence interval, 0.15-0.61). CONCLUSIONS: Patients who underwent microsurgical resection within 3 months of diagnosis demonstrated a hearing preservation advantage compared to those who did not. Findings of this study highlight the counseling challenges associated with the timing of surgical treatment of VS in patients presenting with good preoperative hearing and small tumors.

The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.

Background: The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function. Methods: To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1Vip; Vax1fl/fl:VipCre). Results: We found that Vax1Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1Vip males and females presented with a shortened circadian period in locomotor activity and ex vivo SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes Bmal1 and Per2. Interestingly, Vax1Vip females presented with increased expression of arginine vasopressin (Avp) in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1Vip mice, we assessed GnRH sensitivity to a kisspeptin challenge in vivo. We found that GnRH neurons in Vax1Vip females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1Vip males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1Vip mice were fertile and generated litters comparable in size and frequency to controls. Conclusion: Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons.