Is There a Plateau to the Learning Curve for Acoustic Neuroma Resection?-Experience and Outcomes from a Single Interdisciplinary Team Over Thirty Years.

Objective The evolution of acoustic neuroma (AN) care continues to shift focus on balancing optimized tumor resection and control with preservation of neurological function. Prior learning curve analyses of AN resection have demonstrated a plateau between 20 and 100 surgeries. In this study of 860 consecutive AN surgeries, we investigate the presence of an extended learning curve tail for AN resection. Methods A retrospective cohort study of AN resections by a single interdisciplinary team between 1988 and 2018 was performed. Proportional odds models and restricted cubic splines were used to determine the association between the timing of surgery and odds of improved postoperative outcomes. Results The likelihood of improved postoperative House-Brackmann (HB) scores increased in the first 400 procedures, with HB 1 at 36% in 1988 compared with 79% in 2004. While the probability of a better HB score increased over time, there was a temporary decrease in slope of the cubic spline between 2005 and 2009. The last 400 cases continued to see improvement in optimal HB outcomes: adjusted odds of HB 1 score were twofold higher in both 2005 to 2009 (adjusted odds ratio [aOR]: 2.11, 95% confidence interval [CI]: 1.38-3.22, p < 0.001) and 2010 to 2018 (aOR: 2.18, 95% CI: 1.49-3.19, p < 0.001). Conclusion In contrast to prior studies, our study demonstrates the steepest growth for learning, as measured by rates of preservation of facial function outcomes (HB 1), occurs in the first 400 AN resections. Additionally, improvements in patient outcomes continued even 30 years into practice, underlining the importance of lifelong learning.

Occipital Neuralgia following Acoustic Neuroma Resection.

Background While postoperative outcomes of acoustic neuroma (AN) resection commonly consider hearing preservation and facial function, headache is a critical quality of life factor. Postoperative headache is described in the literature; however, there is limited discussion specific to occipital neuralgia (ON) following AN resection. Objective The aim of this study is to investigate the effectiveness of conservative management and surgery. Methods We conducted a retrospective review of 872 AN patients who underwent resection at our institution between 1988 and 2017 and identified 15 patients (1.9%) that met International Classification of Headache Disorders criteria for ON. Results Of the 15 ON patients, surgical approaches included 13 (87%) retrosigmoid (RS), one (7%) translabyrinthine (TL), and one (7%) combined RS + TL. Mean clinical follow-up was 119 months (11-263). Six (40%) patients obtained pain relief through conservative management, while the remaining nine (60%) underwent surgery or ablative procedure. Three (38%) patients received an external neurolysis, four (50%) received a neurectomy, one (13%) had both procedures, and one (13%) received two C2 to 3 radio frequency ablations. Of the nine patients who underwent procedural ON treatment, seven (78%) patients achieved pain relief, one patient (11%) continued to have pain, and one patient (11%) was lost to follow-up. Of the six patients whose pain was controlled with conservative management and nerve blocks, five (83%) found relief by using neuropathic pain medication and one (17%) found relief on nonsteroidal anti-inflammatory drug. Conclusion Our series demonstrates success with conservative management in some, but overall a minority (40%) of patients, reserving decompression only for refractory cases.

Stage-dependent effects of intermittent hypoxia influence the outcome of hippocampal adult neurogenesis.

Over one billion adults worldwide are estimated to suffer from sleep apnea, a condition with wide-reaching effects on brain health. Sleep apnea causes cognitive decline and is a risk factor for neurodegenerative conditions such as Alzheimer's disease. Rodents exposed to intermittent hypoxia (IH), a hallmark of sleep apnea, exhibit spatial memory deficits associated with impaired hippocampal neurophysiology and dysregulated adult neurogenesis. We demonstrate that IH creates a pro-oxidant condition that reduces the Tbr2+ neural progenitor pool early in the process, while also suppressing terminal differentiation of adult born neurons during late adult neurogenesis. We further show that IH-dependent cell-autonomous hypoxia inducible factor 1-alpha (HIF1a) signaling is activated in early neuroprogenitors and enhances the generation of adult born neurons upon termination of IH. Our findings indicate that oscillations in oxygen homeostasis, such as those found in sleep apnea, have complex stage-dependent influence over hippocampal adult neurogenesis.

Neonatal apneic phenotype in a murine congenital central hypoventilation syndrome model is induced through non-cell autonomous developmental mechanisms.

Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B. Some CCHS patients suffer mainly from deficiencies in CO2 and/or O2 respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations in CCHS. In the developing murine neuroepithelium, Phox2b is expressed in three discrete progenitor domains across the dorsal-ventral axis, with different domains responsible for producing unique autonomic or visceral motor neurons. Restricting the expression of mutant Phox2b to the ventral visceral motor neuron domain induces marked newborn apnea together with a significant loss of visceral motor neurons, RTN ablation, and preBötzinger complex dysfunction. This finding suggests that the observed apnea develops through non-cell autonomous developmental mechanisms. Mutant Phox2b expression in dorsal rhombencephalic neurons did not generate significant respiratory dysfunction, but did result in subtle metabolic thermoregulatory deficiencies. We confirm the expression of a novel murine Phox2b splice variant which shares exons 1 and 2 with the more widely studied Phox2b splice variant, but which differs in exon 3 where most CCHS mutations occur. We also show that mutant Phox2b expression in the visceral motor neuron progenitor domain increases cell proliferation at the expense of visceral motor neuron development. We propose that visceral motor neurons may function as organizers of brainstem respiratory neuron development, and that disruptions in their development result in secondary/non-cell autonomous maldevelopment of key brainstem respiratory neurons.

Pediatric vestibular schwannomas: case series and a systematic review with meta-analysis.

OBJECTIVE: Sporadic unilateral vestibular schwannomas are rare in the pediatric population. Little has been reported in the literature on the presentation, tumor size, response to surgical treatment, and recurrence rates in these younger patients. The authors' goal was to describe their institutional experience with pediatric sporadic vestibular schwannomas and to conduct a meta-analysis of the existing literature to provide further insight into the presentation, tumor characteristics, and surgical outcomes for these rare tumors to help direct future treatment strategies. METHODS: The authors performed a retrospective review of all patients 21 years of age or younger with unilateral vestibular schwannomas and without neurofibromatosis type 2 who underwent resection by the senior authors between 1997 and 2019. A systematic review of the literature and meta-analysis was also performed by entering the search terms "pediatric" and "vestibular schwannoma" or "acoustic neuroma," as well as "sporadic" into PubMed. Presentation, treatment, clinical outcomes, and follow-up were analyzed. RESULTS: Fifteen patients were identified at the authors' institution, ranging in age from 12 to 21 years (mean 16.5 years). Common presenting symptoms included hearing loss (87%), headache (40%), vertigo (33%), ataxia (33%), and tinnitus (33%). At the time of surgery, the mean tumor size was 3.4 cm, with four 1-cm tumors. Four patients had residual tumor following their first surgery, 3 (75%) of whom had significant radiographic regrowth that required further treatment. The literature review identified an additional 81 patients from 26 studies with patient-specific clinical data available for analysis. This resulted in a total of 96 reported patients with an overall average age at diagnosis of 12.1 years (range 6-21 years) and an average tumor size of 4.1 cm. CONCLUSIONS: Pediatric vestibular schwannomas present similarly to those in adults, although symptoms of mass effect are more common, as these tumors tend to be larger at diagnosis. Some children are found to have small tumors and can be successfully treated surgically. Residual tumors in pediatric patients were found to have a higher rate of regrowth than those in their adult counterparts.

Effect of Institutional Volume on Acoustic Neuroma Surgical Outcomes: State Inpatient Database 2009-2013.

BACKGROUND: Evolving technologies and health care quality metrics have altered treatment algorithms for acoustic neuromas (ANs), increasing trends toward observation and radiosurgery, with proportionate declines in use of microsurgery. A correlation between increasing surgical volumes and superior outcomes has been investigated previously in numerous surgical diseases, including AN. OBJECTIVE: To re-evaluate the volume-outcome relationship of AN resection in a changing health care system, with evolving treatment strategies. METHODS: Patients who underwent AN resection between 2009 and 2013 were retrospectively identified in the State Inpatient Database subset of the Healthcare Cost and Utilization Project. Generalized linear mixed-effect models were used to assess odds of various outcome measures (length of stay [LOS], discharge disposition, and facial nerve or severe clinical complications). Institutions were grouped into low-volume centers (1-6 cases/year) and high-volume centers (HVC; ≥31 cases/year) for analysis. RESULTS: A total of 1873 patients underwent AN resection between 2009 and 2013 with a mean age of 50.1 ± 14.1 years (±standard deviation). For each additional case treated annually, patients were 2% (odds ratio [OR], 0.98; 95% confidence interval, 0.96-0.99) less likely to experience a severe complication (P = 0.004). Each additional case also trended toward a decreased rate of facial nerve complications and nonroutine discharge. Inpatient LOS was also shorter for patients at HVCs (median, 4 vs. 5 days; P < 0.001). CONCLUSIONS: Despite a relative decline in microsurgery compared with previous eras, care at HVCs is still associated with superior short-term outcomes, such as decreased LOS, facial nerve or other severe complications, and nonroutine discharges.

Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone.

Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Moreover, MCH cerebrospinal fluid (CSF) levels increase prior to nocturnal feeding and following chemogenetic activation of MCH-producing neurons. Utilizing a dual viral vector approach, additional results reveal that selective activation of putative CSF-projecting MCH neurons increases food intake. In contrast, food intake was reduced following immunosequestration of MCH endogenously present in CSF, indicating that neuropeptide transmission through the cerebral ventricles is a physiologically relevant signaling pathway for energy balance control. Collectively these results suggest that neural-CSF volume transmission signaling may be a common neurobiological mechanism for the control of fundamental behaviors.

Angiographic "Blush" After Stereotactic Radiosurgery Ablation of Residual Arteriovenous Malformation in Pediatric Patient: Case Report and Review of Literature.

INTRODUCTION: While surgical resection remains a primary treatment for accessible arteriovenous malformations (AVMs), stereotactic radiosurgery (SRS) has become thoroughly integrated into the AVM armamentarium; however, delayed sequelae of this treatment have become evident with increased long-term follow-up. To our knowledge, this is the second case of an aberrant local arterial angiographic blush without early venous drainage or an associated lesion following AVM SRS. CASE DESCRIPTION: An 8-year-old female presented with a ruptured 4-cm right medial frontal periventricular Spetzler-Martin grade 3 AVM with isolated intraventricular hemorrhage. She underwent subtotal resection followed by SRS. Six years later, diagnostic cerebral angiography demonstrated a prominent arterial-phase filling microvasculature without early venous drainage in the region of the irradiated residual AVM nidus. CONCLUSION: Although there is a paucity of information on angiographic blush following AVM SRS, consensus in the literature suggests that without early venous drainage, these lesions appear to pose an insignificant threat to the patient. These angiographic findings may be on a spectrum of delayed cerebrovascular radiation changes, and thus indefinite follow-up may be considered, especially in pediatric patients.