Minimally Invasive Murine Laryngoscopy for Close-Up Imaging of Laryngeal Motion during Breathing and Swallowing.

The larynx is an essential organ in mammals with three primary functions - breathing, swallowing, and vocalizing. A wide range of disorders are known to impair laryngeal function, which results in difficulty breathing (dyspnea), swallowing impairment (dysphagia), and/or voice impairment (dysphonia). Dysphagia, in particular, can lead to aspiration pneumonia and associated morbidity, recurrent hospitalization, and early mortality. Despite these serious consequences, existing treatments for laryngeal dysfunction are largely aimed at surgical and behavioral interventions that unfortunately do not typically restore normal laryngeal function, thus highlighting the urgent need for innovative solutions. To bridge this gap, we have been developing an experimental endoscopic approach to investigate laryngeal dysfunction in murine (i.e., mouse and rat) models. However, endoscopy in rodents is quite challenging due to their small size relative to current endoscope technology, anatomical differences in the upper airway, and the necessity for anesthesia to optimally access the larynx. Here, we describe a novel transoral laryngoscopy approach that permits close-up, unobstructed video imaging of laryngeal motion in mice and rats. Critical steps in the protocol include precise anesthesia management (to prevent overdosing that abolishes swallowing and/or risks respiratory distress-related mortality) and micromanipulator control of the endoscope (for stable video recording of laryngeal motion by a single researcher for subsequent quantification). Importantly, the protocol can be performed over time in the same animals to study the impact of various pathological conditions specifically on laryngeal function. A novel advantage of this protocol is the ability to visualize airway protection during swallowing, which is not possible in humans due to epiglottic inversion over the laryngeal inlet that obstructs the glottis from view. Rodents therefore provide a unique opportunity to specifically investigate the mechanisms of normal versus pathological laryngeal airway protection for the ultimate purpose of discovering treatments to effectively restore normal laryngeal function.

Cricoid abscess presenting as progressive dyspnea.

Laryngeal abscess, especially in the posterior larynx and cricoid region, is a rare entity with potential for high morbidity and mortality. The most common etiologies for such abscesses include trauma, prolonged intubation, and supraglottic infection. This case report describes a patient with cricoid abscess of unknown etiology but with a remote history of trauma and intubation. He initially presented with progressive dyspnea and hoarseness, with no signs or symptoms consistent with infection. The report describes airway management techniques and a unique approach to draining the posterior cricoid fluid collection.

A Mouse Model of Dysphagia After Facial Nerve Injury.

OBJECTIVE: Dysphagia is common following facial nerve injury; however, research is sparse regarding swallowing-related outcomes and targeted treatments. Previous animal studies have used eye blink and vibrissae movement as measures of facial nerve impairment and recovery. The purpose of this study was to create a mouse model of facial nerve injury that results in dysphagia to enhance translational research outcomes. STUDY DESIGN: Prospective animal study. METHODS: Twenty C57BL/6J mice underwent surgical transection of the main trunk (MT) (n = 10) or marginal mandibular branch (MMB) (n = 10) of the left facial nerve. Videofluoroscopic swallow study (VFSS) assays for drinking and eating were performed at baseline and 14 days postsurgery to quantify several deglutition-related outcome measures. RESULTS: VFSS analysis revealed that MT transection resulted in significantly slower lick and swallow rates during drinking (P ≤ .05) and significantly slower swallow rates and longer inter-swallow intervals during eating (P ≤ .05), congruent with oral and pharyngeal dysphagia. After MMB transection, these same VFSS metrics were not statistically significant (P > .05). CONCLUSION: The main finding of this study was that transection of the facial nerve MT leads to oral and pharyngeal stage dysphagia in mice; MMB transection does not. These results from mice provide novel insight into specific VFSS metrics that may be used to characterize dysphagia in humans following facial nerve injury. We are currently using this surgical mouse model to explore promising treatment modalities such as electrical stimulation to hasten recovery and improve outcomes following various iatrogenic and idiopathic conditions affecting the facial nerve. LEVEL OF EVIDENCE: NA Laryngoscope, 131:17-24, 2021.

Positive Margins in Cutaneous Melanoma of the Head and Neck: Implications for Timing of Reconstruction.

OBJECTIVE: The aim of this study is to identify clinicopathologic features associated with positive margins after surgical treatment of cutaneous melanoma of the head and neck (CMHN). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: A retrospective analysis of the National Cancer Database was performed of patients diagnosed with CMHN between 2004 and 2016. Univariate and multivariate analyses examining the association of clinicopathologic features with positive margins were performed via logistic regression analysis. RESULTS: A total of 101,560 patients met inclusion criteria. The incidence of positive margins was 5.0% (5128/101,560). Patients were significantly more likely to have positive margins with the following: increasing age (P < .001; odds ratio [OR], 1.028; 95% CI, 1.026-1.031), the lip subsite (P < .001; OR, 1.664; 95% CI, 1.286-2.154), the eyelid subsite (P < .001; OR, 2.380; 95% CI, 1.996-2.838), the face subsite (P < .001; OR, 1.215; 95% CI, 1.133-1.302), the lentigo maligna/lentigo maligna melanoma subtype (P = .019; OR, 1.099; 95% CI, 1.016-1.188), the desmoplastic subtype (P < .001; OR, 1.455; 95% CI, 1.261-1.680), the spindle cell subtype (P = .006; OR, 1.276; 95% CI, 1.073-1.516), and advanced pT classification. Patients with male sex (P < .001; OR, 0.733; 95% CI, 0.687-0.782) and without ulceration (P < .001; OR, 0.803; 95% CI, 0.736-0.876) were significantly less likely to have positive margins. CONCLUSION: The following have been identified as clinicopathologic features associated with positive margins after surgical treatment of CMHN: increasing age, female sex, the lip subsite, the eyelid subsite, the face subsite, ulceration, the lentigo maligna/lentigo maligna melanoma subtype, the desmoplastic subtype, the spindle cell subtype, and increasing pT classification.

Persistent Feeding and Swallowing Deficits in a Mouse Model of 22q11.2 Deletion Syndrome.

Disrupted development of oropharyngeal structures as well as cranial nerve and brainstem circuits may lead to feeding and swallowing difficulties in children with 22q11. 2 deletion syndrome (22q11DS). We previously demonstrated aspiration-based dysphagia during early postnatal life in the LgDel mouse model of 22q11DS along with disrupted oropharyngeal morphogenesis and divergent differentiation and function of cranial motor and sensory nerves. We now ask whether feeding and swallowing deficits persist in adult LgDel mice using methods analogous to those used in human patients to evaluate feeding and swallowing dysfunction. Compared to wild-type mice, videofluoroscopic swallow study revealed that LgDel mice have altered feeding and swallowing behaviors, including slower lick rates, longer inter-lick intervals, and longer pharyngeal transit times with liquid consistency. Transoral endoscopic assessment identified minor structural anomalies of the palate and larynx in one-third of the LgDel mice examined. Video surveillance of feeding-related behaviors showed that LgDel mice eat and drink more frequently. Furthermore, LgDel animals engage in another oromotor behavior, grooming, more frequently, implying that divergent craniofacial and cranial nerve structure and function result in altered oromotor coordination. Finally, LgDel mice have significantly increased lung inflammation, a potential sign of aspiration-based dysphagia, consistent with results from our previous studies of early postnatal animals showing aspiration-related lung inflammation. Thus, oromotor dysfunction, feeding, and swallowing difficulties and their consequences persist in the LgDel 22q11DS mouse model. Apparently, postnatal growth and/or neural plasticity does not fully resolve deficits due to anomalous hindbrain, craniofacial, and cranial nerve development that prefigure perinatal dysphagia in 22q11DS. This new recognition of persistent challenges with feeding and swallowing may provide opportunities for improved therapeutic intervention for adolescents and adults with 22q11DS, as well as others with a history of perinatal feeding and swallowing disorders.

Beta-adrenergic antagonist effects on a novel cognitive flexibility task in rodents.

Previous work examining animal models of cognitive flexibility have focused on tasks where animals are required to shift between cues in order to reach a food reward from among a limited set of choices. Performance by nonhuman animals on these tasks, including reversal learning, intradimensional set-shifting, and extradimensional set-shifting, are affected by pharmacological action on serotonergic, dopaminergic, and alpha-adrenergic, but not beta-adrenergic receptors. However, beta-adrenergic antagonists, such as propranolol, are widely utilized for conditions such as test anxiety. Propranolol improves performance in humans during cognitive flexibility tasks where there is a broad set of potential solutions. The current investigation utilized a digging task where the rodent must develop a novel solution in order to obtain a reward. Similar to the effects observed in humans, propranolol improved performance on this task, while not affecting performance on set-shifting tasks, as with previous animal studies. This may allow future investigation of the neurobiological mechanism by which propranolol affects context-specific anxiety, and could provide insight into the neurobiology of creativity.