HSC Section 6 Nov2016 Green Book

adequate. 17 However, all of the parameters of vocal func- tion assessment, including perceptual evaluation, objec- tive acoustic analysis, and aerodynamics parameter MPT, showed that denervation duration was an influen- tial factor to the surgical outcome of laryngeal reinner- vation. Data of postoperative motor-unit recruitment also support the vocal function results. The perceptual and acoustic parameters showed no significant difference postoperatively among patients with denervation inter- vals of less than 24 months, and the parameter values in these patients were better than those in patients with longer denervation intervals. These results indicate that delayed reinnervation is still effective. There are several reasons that may support delayed laryngeal reinnerva- tion. There may be an inherent cellular mechanism for preserving the structure of denervated laryngeal muscles. 20 Johns et al. found that 6 months after RLN resection there was no significant difference in maximal isometric force of the TA muscle between the experimen- tal and control cats, 21 possibly due to spontaneous regeneration of the RLN. Our previous study indicated a strong tendency for regeneration in the RLN following injury, which may at least partially reinnervate the laryngeal muscle, helping to maintain its structural integrity and function and to alleviate excessive muscle atrophy and fibrosis. 16 In addition, laryngeal muscle stem cells provide persistent regenerative potential for delayed laryngeal reinnervation for up to 2 years after denervation, as revealed by our previous study. 22 The population of activated muscle stem cells in the laryn- geal muscles may be more resistant to apoptosis than those in limb muscles, which may contribute to regener- ative myogenesis in denervated laryngeal muscles through compensatory mechanisms. 22 Nevertheless, after 2 years of denervation, the sur- gical outcomes were less favorable in the present study, although most postoperative parameters in these patients showed improvement compared with the corre- sponding preoperative values. As fixation of the cricoary- tenoid joint was precluded preoperatively in these cases, the compromise of the recovery of voice quality might have been due to insufficient laryngeal reinnervation, which was confirmed by postoperative EMG. One cause of poor functional recovery after exces- sive long-term muscle denervation is the failure of many regenerating axons to elongate and/or make synaptic connections with denervated muscle fibers. The ability of nerve sheaths to support axon regeneration to long-term denervated muscle fibers may progressively deteriorate because of: a decrease in the number of Schwann cells to a level that cannot provide adequate support for regen- erating axons 23 ; degeneration and collagenization of endoneurial tubes, which may obstruct axonal regenera- tion 24 ; and an inability of the basal lamina to be renewed without Schwann cell–axon contact. 25 These factors contribute to a profound reduction in the number of axons that eventually reach denervated muscles. 26 Another possible explanation is occupation of the dener- vated muscle end plates by axons coming from adjacent nerves or by fibers of autonomous origin, precluding delayed reinnervation. 27 In addition, muscle fiber

surgery is usually postponed for at least 6 months to allow for possible spontaneous recovery or compensation from the contralateral vocal fold. However, the studies on regeneration of other peripheral nerves showed that the degree of functional reinnervation lessens as the period of denervation increases; and there appears to be a time range beyond which effective reinnervation declines dramatically. 13 But a significant body of evi- dence indicates that this does not necessarily apply to the larynx. 8,14,15 Clinical and experimental evidences have demonstrated that spontaneous regeneration com- monly takes place after RLN injuries. 16–18 Although this type of reinnervation is usually nonfunctional and sel- dom occurs with laryngeal mobility (termed subclinical reinnervation), it can help to halt or even reverse muscle atrophy and/or fibrosis caused by denervation. 16 There- fore, the researchers think that denervation duration does not affect the surgical outcome of laryngeal reinner- vation in a linear fashion. However, so far we have not seen any report regarding the stratification analysis of denervation duration on the laryngeal reinnervation effect. Thus, it is of great clinical importance to explore whether the same situation in the regeneration of other peripheral nerves also happens to the recurrent laryn- geal nerve—that regeneration capacity declines progres- sively as the denervation duration increases. Delayed reinnervation procedures have proven effective after peripheral nerve injury in animal experi- ments. For example, selective reinnervation of the poste- rior cricoarytenoid muscle with a phrenic nerve transfer has been feasible after a 9-month delay in cat models; however, functional recovery was less successful than with immediate reinnervation. 14 We previously reported that laryngeal reinnervation is still possible to some degree, even after an 18-month denervation period in dogs; however, the degree of RLN regeneration is less than those with an 8-month denervation period. 8 In the clinical studies, Maronian et al. reported on nine patients, eight of whom had an interval between RLN injury and surgery that exceeded 12 months. These patients had a normal or improved voice after laryngeal reinnervation. The longest denervation interval in that series was 9 years, and the postoperative voice in that case was improved. 15 Olson et al. reported excellent acoustic and perceptual results in patients with the maximal interval of 6 years between injury and sur- gery. 19 Our study of a large sample of UVFP patients, in which the longest denervation course was more than 3 years, confirmed that delayed reinnervation can be effec- tive. 4 Nevertheless, the relationship between denerva- tion duration and degree of functional recovery of the laryngeal muscle in UVFP patients remains to be elucidated. Results of the present study showed that there was no significant difference with regard to glottal closure among the three groups. This was probably due to a lack of standardization of inspiratory effort while the patients were undergoing videostroboscopy examination. In addi- tion, a difference in the vertical plane of the vocal folds can result in a significant glottic gap, even when the apparent closure as viewed from above seems

Laryngoscope 124: August 2014

Li et al.: Denervated Duration on Reinnervation for UVFP

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