Primary Nonselective Laryngeal Reinnervation in Iatrogenic Acute Recurrent Laryngeal Nerve Injury: Case Series and Literature Review

Abstract

Treating an acutely injured recurrent laryngeal nerve by primary nonselective laryngeal reinnervation (LR) during thyroidectomy is encouraged to minimize postoperative morbidity. Performing a concurrent transoral temporary injection laryngoplasty (IL) may improve the patient’s voice while waiting for the effect of successful reinnervation. Chronological multidimensional voice outcomes (qualitative and quantitative) and combination of the primary nonselective LR with concurrent transoral IL were not explicitly demonstrated in previous cases that published the literature. In this study, the authors presented the multidimensional voice parameters of 3 patients undergoing primary nonselective LR with concurrent IL during thyroidectomy. The parameters were measured at different time points (2 weeks and 1, 3, 6, and 12 months) following the surgery. Laryngeal electromyography was done at 1 to 2 months and 12 months postsurgery. The results showed that the voices, qualitatively and quantitatively, were within normal range at within 3 months postintervention. The parameters were slightly beyond the normal limit at 3 months and returned to normal at 6 months postintervention and beyond. The LEMG depicted evidence of successful reinnervation in which the motor unit was normal comparable to the opposite normal vocal fold.

Keywords

laryngoplasty recurrent laryngeal nerve vocal fold palsy reinnervation neurorrhaphy primary intervention

Introduction

Recurrent laryngeal nerve (RLN) injury is a known complication of thyroid surgery and confers a great burden of morbidity to the patients.¹ The incidence of permanent RLN paralysis following thyroidectomy is 0.3% to 3%, which is considered significant despite the advancement in surgical techniques and intraoperative nerve monitoring.^1,2 The injury could be due to resection of thyroid malignancy or unexpected injury during manipulation.¹ It is commonly manifested as asthenic breathy voice, aspiration, dysphagia, and dyspnea, resulting in poor quality of life (QoL).³ Type I thyroplasty with or without arytenoid adduction and nonselective laryngeal reinnervation (LR) are common procedures performed in permanent unilateral vocal fold paralysis (UVFP), with particular attention to the latter, which can be in form of either RLN-to-RLN neurorrhaphy, free nerve grafting (FNG), or ansa cervicalis-to-RLN neurorrhaphy (ansa-to-RLN).^4-7 The aim of nonselective LR is to restore innervation and preserve the tone and bulk of vocal fold.^5,8,9

Surgeons must be equipped to treat an acutely injured RLN in operating theatre, by which primary interventions will minimize postoperative morbidity.¹⁰ Ignoring acute injury of RLN intraoperatively will affect the QoL while waiting for the delayed intervention in treating the glottic insufficiency.¹¹ Nonselective LR is a procedure that can be done in the same setting once transection of RLN was identified as the procedure does not require fine-tuning of the voice unlike type I thyroplasty.^10,12,8 Concurrent temporary injection laryngoplasty (IL) will improve the voice while waiting for the effect of reinnervation.^13,7 The effectiveness of primary nonselective LR in patients undergoing thyroidectomy has been reported in the published case series.^12,8 However, they lacked in documentation of chronological multidimensional voice outcomes progress. And to the authors’ knowledge, none of the primary nonselective LR cases were combined with IL or the procedure was not explicitly described.

In this study, the authors demonstrated the chronological progress of voice in 3 patients undergoing primary nonselective LR with concurrent transoral IL, in an acute RLN transection during thyroidectomy. The trend of voice improvement, postsurgery at different time points, was shown using a multidimensional voice outcome measures. A nonsystematic literature review on primary nonselective LR was discussed.

Case Report

Five patients had received primary nonselective LR and transoral IL during thyroid surgery in a tertiary center. The IL material used was Juvederm (hyaluronic acid). Three consecutive patients who had complete data set were included in this report. The demography, thyroid pathology, risk factor for RLN injury, and technique of surgery for these patients are summarized in Table 1. All patients had normal vocal fold and swallowing function preoperatively. None of the patients complained of aspiration or shortness of breath following the surgery.

Table 1.

Summary of the Demography of the Patients, Thyroid Pathology, Risk Factor for RLN Injury, and Technique of Nonselective LR.

Patient	Age (year old/gender)	Thyroid pathology	Risk factor	Nonselective LR technique	Injection laryngoplasty (same setting)
A	57/female	Multinodular goiter with retrosternal extension	Retrosternal extension	RLN-RLN	Performed
B	34/female	Papillary thyroid carcinoma	Malignancy	Ansa-RLN	Performed
C	29/male	Multinodular goiter	none	Ansa-RLN	Performed

Abbreviations: LR, laryngeal reinnervation; RLN-RLN, recurrent laryngeal nerve to recurrent laryngeal nerve neurorrhaphy; ansa-RLN, ansa cervicalis to RLN neurorrhaphy.

There were 2 surgical techniques employed in this case report, ansa-RLN and RLN-RLN neurorrhaphy. When the ipsilateral of proximal and distal trunk of the injured RLN were identified, nontension end-to-end repair was performed without using a cable graft. However, if only the distal trunk of injured RLN was available, the ansa-RLN technique was opted in which the neurorrhaphy was performed between the sternohyoid or sternothyroid branch of the ansa cervicalis and the distal main trunk of the RLN.^7,14

Outcome Measures

Flexible endoscopy was performed for all patients to evaluate the mobility of the vocal folds, preoperatively and postoperatively. The endoscopy confirmed that all patients had UVFP postoperatively. Two patients had right UVFP, whereas the third patient had left UVFP. Laryngeal electromyography (LEMG) was performed for all patients at 1 month postoperatively, and 2 patients (patient A and patient C) had it done at 12 months postsurgery. The LEMG was assessed qualitatively using Koufman classification.¹⁵ The patients’ voices were assessed using multidimensional voice outcomes: (1) Bahasa Malaysia version of voice handicap index-10 (mVHI-10),¹⁶ (2) maximum phonation time (MPT), and (3) acoustic analysis. The acoustic analysis, including jitter%, shimmer%, and noise-to-harmonic ratio (NHR), was measured using OperaVOX.¹⁷ The voices were assessed at 2 weeks and 1, 3, 6, and 12 months postoperatively. The overall dysphonia, roughness, and breathiness scale of GRBAS scale and laryngostroboscopic evaluation were not reported here because of the small samples for assessment of inter- and intrarater agreement in evaluating the subjective parameters.

Results

All parameters (mVHI-10, MPT, jitter%, shimmer%, and NHR) for the 3 patients’ voices were within normal limit at all time points postprimary nonselective LR and IL (Table 2), except at 3 months. At this time point, generally most of voice parameters were slightly beyond normal range. The progress of voice assessments at different time points was depicted in graphs in Figures 1 to 5. The mVHI-10 was of within normal limit at all time points, but at 3 months, the mVHI-10 was slightly beyond score of 11 for patient B and patient C. Among the 3 patients, the objective voice parameters (shimmer, NHR, and MPT) for patient A who had RLN-RLN neurorrhaphy showed the worst outcomes within 6 months postintervention, although the VHI-10 and jitter were within normal limit (Figures 1 -5).

Table 2.

Summary of Voice and Acoustic Analysis.

Parameter	Time	A	B	C
VHI-10	2 weeks	0	0	0
	1 month	0	2	11
	3 months	0	12	15
	6 months	2	1	2
	12 months	0	1	1
Jitter%	2 weeks	0.6172	0.8900	0.7055
	1 month	3.0120	1.4447	0.6746
	3 months	5.6219	0.8893	2.1103
	6 months	0.8886	0.5539	1.8964
	12 months	0.8160	0.5639	0.7775
Shimmer%	2 weeks	3.6208	4.8300	7.7005
	1 month	9.9869	5.7900	4.2909
	3 months	14.0458	4.8285	8.2048
	6 months	6.9353	2.0286	5.3587
	12 months	4.2291	2.0288	3.5415
Noise-to-harmonic ratio	2 weeks	0.0117	0.0222	0.1290
	1 month	0.1155	0.0542	0.0813
	3 months	0.2221	0.0167	0.3080
	6 months	0.0525	0.0056	0.0620
	12 months	0.0676	0.0066	0.0370
Maximum phonatory time (seconds)	2 weeks	14.0	14.8	14.1
	1 month	8.9	13.2	17.0
	3 months	6.6	14.8	12.9
	6 months	9.7	14.8	18.0
	12 months	11.1	18.9	21.0

Figure 1.

Postoperative subjective analysis using VHI-10 questionnaire.

Figure 2.

Preoperative and postoperative jitter%.

Figure 3.

Preoperative and postoperative shimmer%.

Figure 4.

Preoperative and postoperative noise-to-harmonic ratio.

Figure 5.

Preoperative and postoperative maximum phonatory time in seconds.

The LEMG of the paralyzed TA-LCA complex, at within 1 to 2 months postintervention, showed neuropathic changes in which the Koufman classifications for the LEMG tracings for patients A, B, and C were of grades III, V, and III, respectively. Patient B had active denervation changes with absent recruitment of motor unit; in contrast, patients A and C showed reinnervation changes as early as 2 months postoperation. At 12 months postintervention, patient A and patient C showed normal motor unit recruitment with Koufman classification of grade 1 for both mobile and immobile vocal folds.

Discussion

Injury to the RLN results in loss of productivity and significant morbidity; thus, surgeons obligated to strive to protect the nerve and optimize management when injury occurs. Nonselective LR is an approach to restore the connection of motor neurons with denervated laryngeal muscles.² It can be performed primarily on table during the acute injury or delayed that would requires second general anaesthesia.¹⁰ Although favorable voice outcomes was reported in both primary and delayed nonselective LR, the latter may affect the QoL of the patients tremendously while waiting the procedure to be done.^12,7 The delayed intervention may lead to the development of compensatory mechanism, which results in hyperfunctional behaviors, such as anteroposterior or lateral compression of the false vocal folds.¹¹

The proposed surgical techniques in primary nonselective LR in acutely injured RLN during thyroidectomy include ansa-RLN, RLN-RLN, FNG, and vagus-RLN.^12,8,9 Following these interventions, the nerve can regenerate randomly with some adductor axons innervating abductor muscles, resulting in synkinesis to provide muscle tension, bulk, and favorable position of the vocal fold. However, due to the synkinetic reinnervation, the return of vocal fold mobility will not be achieved due to the abnormal and counterproductive movements.^1,3 An important factor to consider at the point of embarking this surgery is that surgeon must ascertain that the RLN injury is unilateral instead of bilateral, as the latter may results with a median or paramedian position of vocal folds, thus causing airway obstruction and tracheostomy may be required.¹⁸

The authors reviewed published papers that focused on primary nonselective LR. The review that included 5 papers is summarized in Table 3. All papers concluded that this procedure is recommended as it improved the patients’ voices to near-normal or normal voice by 6 months postintervention.^12,19,20 The most common surgical technique employed was ansa-RLN, followed by RLN-RLN.^13,8 Most authors recommend either surgical technique because the voice improvement was reported to be earlier compared to FNG and vagus-RLN.^12,8 Hence, when the end-to-end repair is not possible, using ansa cervicalis as the donor nerve is encouraged.^12,8 However, none of the papers reported the employment of concomitant transoral IL and there was also lack of standardization of time points in measuring the voice outcomes.^{12,8,21,19,20} Only 1 paper included a multidimensional voice outcome measures, but the assessment was performed after 6 months of intervention; thus, the progress of voice improvement within 6 months postintervention was not depicted.¹² The results of LEMG to support the evidence of reinnervation were also not reported.

Table 3.

Summary of 5 Papers That Report and Discussed the Voice Outcomes of Nonselective LR in Acutely Injured RLN During Thyroidectomy.

Author (date)	n^a	Surgical technique (n)	IL	Outcome measures	Outcomes
Miyauchi (1998)	34	Ansa-RLN (19) RLN-RLN (5) FNG (8) Vagus-RLN (2)	Nil	MPT	There was no standardized time point for voice evaluation. Improvement of MPT within 2 to 5 months postintervention that was best in ansa-RLN and RLN-RLN. Improvement in vagus-RLN patients took the longest up to 12 months.⁸
Chou (2003)^b	8	RLN-RLN	Nil	All are subjective parameters that are mainly perceptual evaluation	Voice evaluation was performed at 3 and 6 months postintervention. Normal voice is achieved at 6 months postintervention.
Sanuki (2010)^c	6 (group 2)	Ansa-RLN (1) RLN-RLN (1) FNG (4)	Nil	Perceptual evaluation, MPT, MFR, laryngostroboscope	Did not document the voice outcomes at different time points postoperatively. The voices after 6 months showed within normal range voice outcomes.
Dzodic (2015)	16	Ansa-RLN (11) RLN-RLN (5)	Nil	Unvalidated subjective evaluation.	There was no standardized time point for voice evaluation. The patients achieved good or better phonation within 6 to 12 months postintervention.²⁰
Lee (2018)^d	19	Ansa-RLN (12) RLN-RLN (7)	Nil	Acoustic, aerodynamic, perceptual, stroboscopic, and voice handicap index (VHI) evaluations.	The voice outcomes measured at 12, 24, and 36 months. The voice improved at 12 months and remains stable at 24 and 36 months. The early trend of voice outcomes cannot be elicited.

Abbreviations: ansa-RLN, ansa to RLN neurorrhaphy; RLN-RLN, RLN-to-RLN neurorrhaphy; FNG, free nerve grafting; vagus-RLN, vagus-to-RLN neurorrhaphy; IL, injection laryngoplasty.

^a n indicates the number of patients with acute RLN injury who received primary nonselective LR.

^b This study included 8 patients who had acute RLN injury during thyroidectomy, 4 received primary nonselective LR and 4 did not have any procedures perform to treat the acute RLN injury. There was significant improvement of voice outcomes in the first, whereas for the latter group, the voices remained the same and the patients have to undergo medialization laryngoplasty.¹⁹

^c This study actually included 12 patients, 6 had preoperative UVFP (group 1) and 6 had preoperative normal voice with acute RLN injury intraoperatively (group 2). There was no significant difference of voice outcomes between the 2 groups after 6 months of primary nonselective LR.¹²

^d This study included 43 patients with post-thyroidectomy permanent UVFP underwent IL (group 1) under local anesthesia and 19 patients who underwent primary nonselective LR (group 2). Both groups yielded statistically significant voice improvements at 36 months postoperatively. But primary nonselective LR yielded showed better voice outcomes than IL.²¹

The effect of reinnervation in reestablishment of muscle tension and bulk generally occurred with 3 to 6 months after the intervention.^13,21 Therefore, employing concurrent transoral IL with primary nonselective LR is recommended.¹³ This will minimize the effect of glottic insufficiency caused by UVFP while waiting for the onset of effect of reinnervation. The biomaterial used for IL is preferably the temporary type like hyaluronic acid because it was reported to be remained in vivo for 6 to 12 months and maintained the function for 3 to 4 months.²²

The present 3 cases had undergone both primary nonselective LR and concurrent IL using hyaluronic acid. The results showed that the voices, qualitatively and quantitatively, remained within normal range at within 3 months postintervention. The voice outcomes were slightly beyond the normal limit at 3 months and returned to normal at 6 months postintervention. The slight deterioration of voice at 3 months may indicate the resorption of hyaluronic acid in the paraglottic space. Subsequently, the voice returns to normal due to the effect of reinnervation.¹³ The evidence of reinnervation was supported by the presented LEMG results. As previously revealed, small case series have documented that RLN-RLN or FNG resulted in favorable synkinetic reinnervation, approximately 70% to 75% of the time.² Ansa-to-RLN neurorrhaphy is an ideal option that was proven to yield 98% to 99% successful reinnervation.^1,2

The authors recommend future prospective larger study including patients undergoing primary nonselective LR and transoral temporary IL in the same setting, employing multidimensional voice outcome measures at a standardized time points postoperatively. Therefore, the authors suggest that a routine consent of possibility of primary nonselective LR and transoral IL is taken for all patients undergoing thyroidectomy, especially those with higher risk of RLN injury.

Conclusions

The present 3 cases demonstrated good voice outcomes within 12 months following a primary nonselective LR with concomitant temporary transoral IL in unilateral acute injury of RLN during thyroidectomy. The results, which were supported by evidence of successful reinnervation on LEMG at 12 months postintervention, may indicate that the active intervention with combination of both surgical treatments alleviates postoperative morbidity. Larger longitudinal data with standardized multidimensional voice outcomes are recommended to study the benefit achieved during the period before the onset of reinnervation effect.

Footnotes

Authors’ Note

Verbal informed consent was obtained from the patient(s) for their anonymized information to be published in this article.

Acknowledgments

The authors thank Professor Martin Birchall of University College London for his contribution on introducing the last author on the nonselective LR technique.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Marina Mat Baki

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