Local Neurotoxins for Prevention of Laryngeal Synkinesis after Recurrent Laryngeal Nerve Injury

McRae, Bryan R.; Kincaid, John C.; Illing, Elisa A.; Hiatt, Kelly; Hawkins, Jan F.; Halum, Stacey L.

doi:10.1177/000348940911801210

Cited by 15 publications

(24 citation statements)

References 32 publications

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“…With unilateral UVFP, to prevent or counteract synkinesis, either the total number of axons innervating the adductor muscles must be increased, or the number of aberrant nerve fibers innervating the abductor muscle (posterior cricoarytenoid [PCA] muscle) must be reduced. As a neurotoxic agent, vincristine has been shown to inhibit neural regeneration in a rat post‐traumatic nerve injury model . In another rat study, we found paclitaxel to be equally as effective as vincristine for preventing reinnervation of a denervated muscle …”

Section: Introductionmentioning

confidence: 76%

“…Vincristine administration in the setting of chemotherapy has been associated with toxicity including neutropenia, neuropathy, and a small therapeutic window . Although low‐dose administration of vincristine following vocal fold paralysis may avoid toxicity and achieve the desired effects, paclitaxel provides an alternative with a possibly wider therapeutic index . Additionally, prior studies have demonstrated that paclitaxel and vincristine have no effect after reinnervation has occurred .…”

Section: Discussionmentioning

confidence: 99%

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Paclitaxel inhibits post‐traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model

2016

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Section: Introductionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Paclitaxel inhibits post‐traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model

2016

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“…Selective prevention of reinnervation of a specific muscle following a nerve injury was originally conceived as a way to reduce laryngeal synkinesis . Other clinical applications are possible.…”

Section: Discussionmentioning

confidence: 99%

“…Yian et al showed that vincristine prevented facial nerve recovery into a target muscle after a transection injury with primary neurorrhaphy, which may have led to enhanced reinnervation of adjacent muscle groups as well as a reduction in synkinetic muscle activity . Studies by McRae et al in a rat larynx model, and by Paniello in a canine larynx model, both confirmed that vincristine is effective in blocking neural regeneration when administered to the posterior cricoarytenoid muscle.…”

Section: Introductionmentioning

confidence: 94%

Prevention of post‐traumatic reinnervation with microtubule inhibitors

2015

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Objective/Hypothesis Functional recovery after a recurrent laryngeal nerve or facial nerve injury may be impaired due to aberrant reinnervation. Previous work in a rat peripheral nerve injury model found vincristine to be a potent inhibitor of reinnervation, and it has since been used to effectively block neural regeneration in other animal models. However, vincristine’s narrow therapeutic index may limit its utility; therefore, another microtubule inhibitor, paclitaxel, which has a higher therapeutic index, was tested. Study Design Animal (rat) study. Methods After controlled injury to the rat posterior tibial (PT) nerve, the gasctrocnemius/soleus complex was injected with saline (control, n=14), vincristine (n=30), or paclitaxel (n=20). Injections without a crush injury were performed using saline (n=5) or paclitaxel (n=9). The functional recovery (FR) of the posterior tibial nerve was assessed using walking track analysis. Results At six weeks, controls had already recovered to baseline (FR=1.0) while the paclitaxel group had FR =0.724 ±0.064 and the vincristine group had FR =0.709 ±0.078. At six months the paclitaxel rats had FR = 0.798 ±0.167 and the vincristine rats had FR =0.754 ±0.240. These differences were significantly different from baseline, but the two agents were not different from each other. Paclitaxel did not affect the FR in the absence of a nerve injury. Conclusion Intramuscular paclitaxel and vincristine both significantly inhibit regeneration of the PT nerve after crush injury for at least 6 months. Potential clinical uses of inhibition of reinnervation are discussed. Level of Evidence NA

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“…{8} McRae et al independently confirmed that vincristine effectively blocked reinnervation in a rat RLN injury model. {9}…”

Section: Introductionmentioning

confidence: 99%

Effect on Laryngeal Adductor Function of Vincristine Block of Posterior Cricoarytenoid Muscle 3 to 5 Months After Recurrent Laryngeal Nerve Injury

Paniello

Park

2015

Ann Otol Rhinol Laryngol

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Objectives It has been shown, in a canine model, that a single injection of vincristine into the PCA muscle at the time of recurrent laryngeal nerve (RLN) injury effectively blocks its reinnervation and results in improved adductor strength. But clinically, such injuries are usually diagnosed weeks or months after onset. Vincristine injection does not affect a muscle that is already innervated; thus, there is a limited time frame following RLN injury during which a vincristine injection could effectively improve ultimate laryngeal adductor functional recovery. A series of delayed injections were performed in a canine model and results assessed. Study Design Animal (canine) experiment. Methods The RLN was transected and repaired, and vincristine (0.4 mg) was injected into the PCA muscle at the time of injury (n=12), or at 3, 4, and 5 months later (n=8 each study group). Six months after RLN injury, laryngeal adductor function was measured. Results of vincristine injection without RLN injury (n=6), and longer-term (12 months) follow-up for time zero injections (n=4), are also reported. Results The animals injected at time zero had better adductor function than non-injected controls, as reported previously, and this result was further increased at 12 months. The 3-month delay gave results similar to the time zero group. The 5-month delay group showed no vincristine benefit, and the 4-month delay group gave an intermediate result. Vincristine to the PCA had no effect on adductor function when the RLN was left intact. Plasma levels showed 19% of injected vincristine reached systemic circulation, which was cleared within 69 hours. Conclusions Vincristine injection of the PCA muscle after RLN injury, which blocks this functional recovery. The window of opportunity to apply this treatment closes by four months after RLN injury in the canine model. Human RLN recovery follows a similar time course and can reasonably be expected to have a similar therapeutic window.

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Local Neurotoxins for Prevention of Laryngeal Synkinesis after Recurrent Laryngeal Nerve Injury

Abstract: Low-dose VNC injections appear to be relatively safe and effective in selectively inhibiting spontaneous aberrant reinnervation after RLN injury in an animal model.

Cited by 15 publications

References 32 publications

Paclitaxel inhibits post‐traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model

Paclitaxel inhibits post‐traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model

Prevention of post‐traumatic reinnervation with microtubule inhibitors

Effect on Laryngeal Adductor Function of Vincristine Block of Posterior Cricoarytenoid Muscle 3 to 5 Months After Recurrent Laryngeal Nerve Injury

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