Does botulinum toxin type A alter the consequences of recurrent laryngeal nerve transection in the rat model?

  • Author / Creator
    Jomah, Mohammed A
  • Introduction: Laryngeal paralysis (LP) is a disorder that impacts significantly the health and the quality of life of patients. It causes a dysfunction of vocal folds (VF) movement as a result of affection of the laryngeal neural supply. While several theories have been proposed to explain the pathophysiology, synkinesis or misdirected re-innervation of laryngeal muscles is the currently accepted mechanism. Several experimental treatments to restore VF functional mobility have been proposed. However, most of them were unsuccessful due to the persistence of synkinesis. Injection of neurotoxins into laryngeal muscles was used to overcome this problem, but unfortunately did not restore functional mobility, and was associated with significant side effects. Only one animal experiment previously tested botulinum toxin type A (BTX-A) injections into laryngeal muscles, and resulted in widening the laryngeal inlet, although recovery of function was not assessed. In a study on children with LP, BTX-A was injected into external laryngeal muscles and resulted in recovery of function in nearly all of them. This study and others suggested that toxin’s action at the neuromuscular junction, may be not be the only one at play, and that other promising sites of action (e.g. central) can reverse the synkinetic phenomenon. Objective: To investigate whether an injection of BTX-A into external laryngeal muscles enhances the recovery of laryngeal function, in laryngeal paralysis rat model. Methods: A single blind randomized controlled animal study (Sprague Dawley rats) with surgically induced LP was conducted. After transection of the right recurrent laryngeal nerve (RLN), a BTX-A or normal saline was injected into the intervention or the control group’s cricothyroid, sternothyroid and sternohyoid muscles. Under general intravenous anesthesia, laryngoscopy and LEMG recordings from thyroarytenoid (TA), cricothyroid (CT) and posterior cricoarytenoid (PCA) muscles were performed before, immediately and four to six weeks after transection of RLN. LEMG activity of each muscle was graded (0-4), according to the amplitude and relation to the phase of respiration. VF movement on laryngoscopy was graded as normal, partially mobile, or immobile. Main Outcome Measures: Primary: Difference between median LEMG grades of the two groups. Secondary: 1- difference between the proportions of recovered and persistently paralyzed VF in the two groups, 2- Difference between the medians of burst amplitude and duration on LEMG in the two groups. Results: Twenty-four Sprague Dawley rats were randomized. Only nineteen animals were available for the final evaluation. LEMG analysis showed a statistically significant difference between the median LEMG grades of right PCA (p= 0.02, 95% CI 0.017-0.023). The median grade for the intervention group (n=10) was 4 (25th%=2.75, 75th%=4), and for the control group (n=4) was 1 (25th%=0.25, 75th%=3.25). No difference was found in the TA median grades. Recovery of movement was observed in four out of nine animals, and four out of ten animals of the intervention group (p 1.00). No statistically significant difference was found between the amplitude and the burst durations between the two groups. Conclusions: BTX-A appears to enhance the phasic activity of the laryngeal abductor muscle in the rat model at the short-term. However, this was not translated into functional VF movement. Further work will be necessary to clarify the impact on clinically significant mobility.

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  • Graduation date
  • Type of Item
  • Degree
    Master of Science
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    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Surgery
  • Specialization
    • Experimental Surgery
  • Supervisor / co-supervisor and their department(s)
    • El-Hakim, Hamdy (Departments of Surgery & Paediatrics)
  • Examining committee members and their departments
    • Churchill, Thomas (Department of Surgery)
    • Dicken, Bryan (Department of Surgery)
    • El-Hakim, Hamdy (Departments of Surgery & Paediatrics)
    • Daniel, Sam (Department of Paediatric surgery/ McGill University)