Faculty Bibliography

PURPOSE OF REVIEW: Over the past decade, substantial insight into the biological function of the tumor suppressors neurofibromin (NF1) and Merlin (NF2) has been gained. The purpose of this review is to highlight some of the major advances in our understanding of the biology of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) as they relate to the development of novel therapies for these disorders. RECENT FINDINGS: The development of increasingly sophisticated preclinical models over the recent years has provided the platform from which to rationally develop molecular targeted therapies for both NF1 and NF2-related tumors, such as within the Department of Defense-sponsored Neurofibromatosis Clinical Trials Consortium. SUMMARY: Clinical trials with molecular-targeted therapies have become a reality for neurofibromatosis patients, and hold substantial promise for improving the morbidity and mortality of individuals affected with these disorders.

OBJECTIVE: To describe the clinical outcomes of patients undergoing serial observation for vestibular schwannoma (VS) and identify factors that may predict tumor growth or hearing loss. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was conducted of patients seen at a tertiary care medical center between 2002 and 2013 with an International Classification of Diseases-9 diagnosis code of 225.1. Patients electing observation as initial management, with at least two documented imaging results, were included. Exclusion criteria comprised bilateral VS, diagnosis of neurofibromatosis type 2, and neoplasms other than VS. Decline in serviceable hearing, tumor growth, and changes in management strategy were recorded. Survival analysis to assess median time to outcomes and multiple logistic regression analyses were performed. RESULTS: A total of 94 patients met inclusion criteria. While undergoing observation, 22.3% of patients underwent a change in management strategy to microsurgical excision or stereotactic radiotherapy. For patients with initial serviceable hearing, 24.3% observed a decline to a nonserviceable level. No significant clinical factors were identified to predict changes in hearing. Survival analysis revealed that an estimated 69.1% of patients electing observation as initial management continued to do so at 5 years. Imbalance or disequilibrium at presentation was found to be associated with an increased adjusted odds ratio (OR) (OR 2.96; 95% confidence interval, 1.03-8.50; P = 0.04) for tumor growth. CONCLUSION: Serial observation of VS is a viable treatment strategy for selected patients, with two-thirds of patients electing to continue this management option after 5 years. Disequilibrium as a presenting symptom may be associated with subsequent tumor growth. LEVEL OF EVIDENCE: 4. Laryngoscope, 2015.

This study aims to identify educational and training modalities that dentists in Puerto Rico (PR) believe will increase the quality and quantity of opportunistic oral cancer screening examinations (OCS) in dental offices on the island. The study was conducted in three phases: a systematic search of relevant literature, an expert review and consensus panel, and focus groups (FG) involving PR general dentists. To increase OCS by dentists in PR, the FG participants proposed a small group, hands-on OCS training, an integrated oral cancer course, and readily available videos, photographs, and computer simulations to further demonstrate OCS performance and facilitate differential diagnosis. OCS training requirements for licensure and re-licensure, improving OCS dentist-patient communication skills, and establishment of an oral lesion referral center were also viewed favorably. In conclusion, general dentists in our FGs believed the quality and quantity of OCS in Puerto Rico can be increased through the application of specific continuing education and training modalities.

OBJECTIVES: True vocal fold (TVF) paralysis is a common cause of neonatal stridor and airway obstruction, though bilateral TVF paralysis is seen less frequently. Rare cases of familial congenital TVF paralysis have been described with implied genetic origin, but few genetic abnormalities have been discovered to date. The purpose of this study is to describe a novel chromosomal translocation responsible for congenital bilateral TVF immobility. METHODS: The charts of three patients were retrospectively reviewed: a 35 year-old woman and her two children. The mother had bilateral TVF paralysis at birth requiring tracheotomy. Her oldest child had a similar presentation at birth and also required tracheotomy, while the younger child had laryngomalacia without TVF paralysis. Standard karyotype analysis was done using samples from all three patients and the parents of the mother, to assess whether a chromosomal abnormality was responsible. RESULTS: Karyotype analysis revealed the same balanced translocation between chromosomes 5 and 14, t(5;14) (p15.3, q11.2) in the mother and her two daughters. No other genetic abnormalities were identified. Neither maternal grandparent had the translocation, which appeared to be a spontaneous mutation in the mother with autosomal dominant inheritance and variable penetrance. CONCLUSIONS: A novel chromosomal translocation was identified that appears to be responsible for familial congenital bilateral TVF paralysis. While there are other reports of genetic abnormalities responsible for this condition, we believe this is the first describing this particular translocation.

Sensory feedback is crucial for learning and performing many behaviors, but its role in the execution of complex motor sequences is poorly understood. To address this, we consider the forebrain nucleus HVC in the songbird, which contains the premotor circuitry for song production and receives multiple convergent sensory inputs. During singing, projection neurons within HVC exhibit precisely timed synaptic events that may represent the ongoing motor program or song-related sensory feedback. To distinguish between these possibilities, we recorded the membrane potential from identified HVC projection neurons in singing zebra finches. External auditory perturbations during song production did not affect synaptic inputs in these neurons. Furthermore, the systematic removal of three sensory feedback streams (auditory, proprioceptive, and vagal) did not alter the frequency or temporal precision of synaptic activity observed. These findings support a motor origin for song-related synaptic events and suggest an updated circuit model for generating behavioral sequences.

Background Tracheobronchopathia osteochondroplastica is a rare benign and often indolent disease. We report the first case of tracheobronchopathia osteochondroplastica (TBO) presenting as acute hypercarbic respiratory failure due to superimposed subglottic submucosal abscess. Case Report A 27-year-old man presented to the emergency department in respiratory distress that required mechanical ventilation for acute hypercarbic respiratory failure. Upon extubation the next day, stridor was elicited with ambulation. Spirometry revealed fixed upper airway obstruction. Neck imaging showed a 2.8x2.0x4.0 cm partially calcified subglottic mass with cystic and solid component obstructing 75% of the airway. Surgical exploration revealed purulent drainage upon elevation of the thyroid isthmus and an anterolateral cricoid wall defect in communication with a subglottic submucosal cavity. Microbiology was negative for bacteria or fungi. Pathology showed chondro-osseous metaplasia compatible with tracheobronchopathia osteochondroplastica (TBO). The patient received a course of antibiotics and prophylactic tracheostomy. Since tracheostomy removal 3 days later, the patient remains asymptomatic. Conclusions Tracheobronchopathia osteochondroplastica is a rare disease with usually benign clinical course and incidental diagnosis. It may present as acute hypercarbic respiratory failure when subglottic infection is superimposed.

INTRODUCTION: In-office laryngeal procedures present an alternative to the risks and costs associated with general anesthesia. However, the inherent control afforded by the operative theater is decreased potentially increasing the risk of complications. Many patients undergoing these procedures have traditional surgical risk factors, such as antithrombotic (AT) medical therapy. We sought to quantify complication rates for in-office procedures as a function of AT therapy. METHODS: A retrospective review of 127 diverse, in-office laryngeal procedures was performed and patients were then stratified based on AT medication status and type of procedure. The primary dependent variables were intraoperative and postoperative complications. Additionally, in those patients undergoing procedures with the goal of voice improvement, Voice Handicap Index (VHI)-10 scores were used to quantify the success of the procedure as a function of AT therapy. RESULTS: Of the 127 procedures, 27 procedures (21.2%) involved patients on some form of AT agent that was not ceased for the procedure. Across all patients, no intraoperative complications were encountered, irrespective of therapeutic status. Three postoperative complications were noted; all in patients not on AT therapy. A statistically significant improvement in VHI-10 scores was noted across all patients, irrespective of AT status. CONCLUSIONS: AT medications do not appear to increase the risk of complications associated with in-office laryngeal procedures. Furthermore, AT therapy seemed to have no negative impact on the voice outcomes of patients undergoing procedures for voice improvement.

In the zebra finch, singing behavior is driven by a sequence of bursts within premotor neurons located in the forebrain nucleus HVC (proper name). In addition to these excitatory projection neurons, HVC also contains inhibitory interneurons with a role in premotor patterning that is unclear. Here, we used a range of electrophysiological and behavioral observations to test previously described models suggesting discrete functional roles for inhibitory interneurons in song production. We show that single HVC premotor neuron bursts are sufficient to drive structured activity within the interneuron network because of pervasive and facilitating synaptic connections. We characterize interneuron activity during singing and describe reliable pauses in the firing of those neurons. We then demonstrate that these gaps in inhibition are likely to be necessary for driving normal bursting behavior in HVC premotor neurons and suggest that structured inhibition and excitation may be a general mechanism enabling sequence generation in other circuits.