Unilateral vocal-fold paralysis is a major complication from thyroid surgery and commonly results from trauma to the recurrent laryngeal nerve (RLN). The loss of tone in the intrinsic muscles of the larynx due to RLN injury can eliminate voice, produce breathing difficulties, and significantly increase risk for aspiration. For crush injuries o the RLN, the only treatment is watchful waiting for spontaneous regeneration of axons and reinnervation of laryngeal muscles. For transected RLNs, the preferred treatment is surgical anastomosis of nerve segments followed by the same hopes for spontaneous regeneration and reinnervation. Both treatments can restore muscle tone, but reinnervation is inefficient and takes many months. Even then, purposeful movement of the vocal folds and complete glottic closure are not restored because of synkinesis from aberrant reinnervation, but, as long as there is reinnervation, laryngeal function can be further improved with surgical manipulation of laryngeal muscles. In this project, we will develop tools for producing controlled injury and test the efficacy of a simple, safe pharmacological treatment to significantly accelerate reinnervation.
In Aim 1, we will develop quantitatively reproducible RLN crush injuries and quantitative techniques for the study of resulting vocal fold paralysis and functional reinnervation.
In Aim 2, we will test the hypothesis that continuous lithium administration accelerates reinnervation after RLN crush injury. Lithium modulates glycogen synthase kinase 3 in the neurotrophin pathway and promotes growth-cone activity and neurite extension. For both aims, functional outcomes will be monitored at regular intervals by vocalization analysis, plethysmography, quantitative video laryngoscopy, and larynx electromyography. The results of this multidisciplinary collaboration between physicians and basic scientists will have direct practical clinical impact on the treatment of patients with unilateral vocal-fold paralysis. The quantitative tools for nerve injury and functional assessment, and the pharmacological treatment to accelerate axonal sprouting and reinnervation will have significant impact on all types of peripheral nerve injury.

Public Health Relevance

Paralysis of the vocal cords in the larynx or 'voice box' frequently results from accidental injury to the recurrent laryngeal nerve (RLN) in the neck and causes difficulties with breathing and speaking. Current methods for surgical RLN repair are unsatisfactory, as the recovery of larynx function is slow and incomplete, and no drug treatments are available. Our project will use rats to pursue two goals: First, develop a well defined and reproducible procedure for RLN injury. Second, test whether the administration of lithium during a months-long recovery period promotes recovery of larynx function after RLN injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DC013629-01A1
Application #
8824373
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
2014-12-01
Project End
2016-11-30
Budget Start
2014-12-01
Budget End
2015-11-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
040796328
City
Brooklyn
State
NY
Country
United States
Zip Code
11203