Welby et al.Dysphagia in 22q11.2 Deletion Syndrome 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.

Objectives/Hypothesis: The goal of this study was to objectively examine vocal fold (VF) motion dynamics after iatrogenic recurrent laryngeal nerve (RLN) injury in a mouse surgical model. Furthermore, we sought to identify a method of inducing injury with a consistent recovery pattern from which we can begin to evaluate spontaneous recovery and test therapeutic interventions.Study Design: Animal model. Methods: The right RLN in C57BL/6J mice was crushed for 30 seconds using an aneurysm clip with 1.3-N closing force. Transoral laryngoscopy enabled visualization of VF movement prior to surgery, immediately post-crush, and at two endpoints: 3 days (n = 5) and 2 weeks (n = 5). VF motion was quantified with our custom motion-analysis software. At each endpoint, RLN samples were collected for transmission electron microscopy for correlation with VF motion dynamics.Results: Our VF tracking software permitted automated quantification of several measures of VF dynamics, such as range and frequency of motion. By 2 weeks post-injury, the frequency of VF movement on the right (injured) side equaled the left, yet range of motion only partially recovered. These objective outcome measures enabled detection of VF dysfunction that persisted at 2 weeks post-crush. Transmission electron microscopy images revealed RLN degeneration 3 days post-crush and partial regeneration at 2 weeks, consistent with functional results obtained with automated VF tracking.Conclusions: Our motion-analysis software provides novel objective, quantitative, and repeatable metrics to detect and describe subtle VF dysfunction in mice that corresponds with underlying RLN degeneration and recovery. Adaptation of our tracking software for use with human patients is underway.

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The recurrent laryngeal nerve (RLN) is responsible for normal vocal‐fold (VF) movement, and is at risk for iatrogenic injury during anterior neck surgical procedures in human patients. Injury, resulting in VF paralysis, may contribute to subsequent swallowing, voice, and respiratory dysfunction. Unfortunately, treatment for RLN injury does little to restore physiologic function of the VFs. Thus, we sought to create a mouse model with translational functional outcomes to further investigate RLN regeneration and potential therapeutic interventions. To do so, we performed ventral neck surgery in 21 C57BL/6J male mice, divided into two groups: Unilateral RLN Transection (n = 11) and Sham Injury (n = 10). Mice underwent behavioral assays to determine upper airway function at multiple time points prior to and following surgery. Transoral endoscopy, videofluoroscopy, ultrasonic vocalizations, and whole‐body plethysmography were used to assess VF motion, swallow function, vocal function, and respiratory function, respectively. Affected outcome metrics, such as VF motion correlation, intervocalization interval, and peak inspiratory flow were identified to increase the translational potential of this model. Additionally, immunohistochemistry was used to investigate neuronal cell death in the nucleus ambiguus. Results revealed that RLN transection created ipsilateral VF paralysis that did not recover by 13 weeks postsurgery. Furthermore, there was evidence of significant vocal and respiratory dysfunction in the RLN transection group, but not the sham injury group. No significant differences in swallow function or neuronal cell death were found between the two groups. In conclusion, our mouse model of RLN injury provides several novel functional outcome measures to increase the translational potential of findings in preclinical animal studies. We will use this model and behavioral assays to assess various treatment options in future studies.

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