Is intraoperative neural monitoring necessary for exploration of the superior laryngeal nerve?

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Is intraoperative neural monitoring necessary for exploration of the superior laryngeal nerve? Mehmet Uludag, MD,a Nurcihan Aygun, MD,a Kinyas Kartal, MD,a Evren Besler, MD,a and Adnan Isgor, MD,b Istanbul, Turkey

Background. We aimed to evaluate the contribution of intraoperative neuromonitoring to the visual and functional identification of the external branch of the superior laryngeal nerve and the effect on postoperative voice changes. Methods. The prospective data of 221 patients (183 women, 38 men) who underwent thyroid operation with intraoperative neuromonitoring for exploration of the external branch of the superior laryngeal nerve were evaluated retrospectively. The surface endotracheal tube–based Medtronic NIM3 (Medtronic, Jacksonville, FL) intraoperative neuromonitoring device was used. The function of the external branch of the superior laryngeal nerve was evaluated by cricothyroid muscle twitch. Additionally, the contribution of the external branch of the superior laryngeal nerve to vocal cord adduction was evaluated using electromyographic records. Results. A total of 374 (95.2%) of 393 external branch of the superior laryngeal nerves were identified; 145 (36.9%) external branch of the superior laryngeal nerves were identified visually before being stimulated with a probe, and 130 (33.1%) external branch of the superior laryngeal nerves were identified visually after being identified with a probe. Although 99 (25.2%) external branch of the superior laryngeal nerves were identified with a probe, they were not visualized. Intraoperative neuromonitoring provided meaningful contributions to visual (P = .001) and functional (P = .001) identification of the external branch of the superior laryngeal nerve. Positive electromyographic responses were recorded from 257 external branch of the superior laryngeal nerves (68.7%). After the patients with recurrent laryngeal nerve palsy were excluded, voice changes were detected in 6 (3.3%) of 184 patients with identified external branch of the superior laryngeal nerves and 3 (20%) of 15 patients in whom at least 1 external branch of the superior laryngeal nerve could not be identified with intraoperative neuromonitoring. Conclusion. Intraoperative neuromonitoring provided an important contribution to the visual and functional identification of the external branch of the superior laryngeal nerve. Intraoperative neuromonitoring is a helpful adjunct for identifying the external branch of the superior laryngeal nerve. (Surgery 2016;j:j-j.) From the Department of General Surgery,a Sisli Hamidiye Etfal Training and Research Hospital, and the Department of General Surgery,b Bahcesehir University Medical Faculty, Istanbul, Turkey

The authors declare that this study has received no financial support. There were no financial or professional associations between the authors and the commercial company that supplied the nerve-monitoring product. All authors have agreed to the manuscript’s content. All authors warrant that the submitted article is original and has not been submitted to another journal for publication, has not been published elsewhere, or if published in whole or in part, all permissions were granted for publication in Surgery. Presented at the First World Congress of Neural Monitoring in Thyroid and Parathyroid Surgery, September 17–19, 2015, Krakow, Poland.

Accepted for publication October 6, 2016. Reprint requests: Mehmet Uludag, MD, Department of General Surgery, Sisli Hamidiye Etfal Training and Research Hospital Sisli Hamidiye Etfal E gitim ve Arastirma Hastanesi, Genel Cerrahi Klini gi, Kat: 4, C Blok, Halaskargazi Cad. Etfal Sk., Sisli, Istanbul 34371, Turkey. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2016.10.026

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ALTERED PHONATION is among the most common problems after thyroid operation. Preservation of the recurrent laryngeal nerve (RLN) alone is not sufficient to prevent voice impairment and maintain normal vocal cord function.1 The external branch of the superior laryngeal nerve (EBSLN) must also be preserved along with the RLN. The EBSLN innervates the cricothyroid muscle (CTM), which is responsible for the tension of the vocal folds during pitch elevation.2 Injury to the EBSLN, however, can occur during the dissection and clamping of the superior thyroid vessels. This injury causes CTM paralysis, impairing the production of high tones and altering the voice’s fundamental frequency, which is especially problematic for women and professional singers.3 Intraoperative neuromonitoring (IONM) has gained widespread acceptance as an adjunct to the gold standard of visual identification of the RLN.4 In contrast to routine dissection of the RLN, many surgeons tend to routinely avoid exposing and identifying the EBSLN.5 The rate of IONM use for exploration of the EBSLN, however, has been increasing.6 Although large, randomized studies comparing the identification of the EBSLN between visualization alone and the addition of IONM have been reported in the literature,3,7,8 most have compared 2 separate groups consisting of visual identifications and those with the use of IONM. All of the studies found that the use of IONM was superior; however, none of these studies verified that the structure visually identified as the EBSLN was actually the genuine EBSLN. Unlike these studies, we have confirmed every EBSLN-like anatomic structure with IONM and aimed to evaluate the contribution of the IONM to visual and functional identification of the EBSLN and its effects on voice changes. PATIENTS AND METHODS The prospective data of patients who underwent thyroid surgery with IONM for exploration of the EBSLN between July 2012 and March 2015 were evaluated retrospectively. Each side of the neck was considered a separate entity. The exclusion criteria consisted of secondary operation, thyroid cancer with massive extrathyroidal extension, intentional nerve transection due to cancer invasion, and failure to assess EBSLN function due to technical issues. Four patients were excluded from the study due to the technical problems, such as detachment of the electrodes (2 of 4) and blasting of the fuse of the interface-connector box (2 of 4).

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The study was approved from the Institutional Review Board of Sisli Etfal Training and Research Hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in this study. IONM and operative techniques. The NIM 3.0 Nerve Monitoring System (Medtronic Xomed, Jacksonville, FL) and an endotracheal surface electrode were used to test the nerve intraoperatively. Each patient was administered general anesthesia with a low-dose, short-acting neuromuscular blockade (rocuronium 0.3 mg/kg) and intubated with a Medtronic Xomed Nerve Integrity Monitor Standard Reinforced Electromyography Endotracheal Tube (size 6.0, 7.0, or 8.0). After patient positioning, proper tube positioning was confirmed by the tap test or by direct visualization, and the tube was secured with tape.4 A sterile, single-use, pulse-generated monopolar stimulator probe (Medtronic Xomed) was used for nerve stimulation within the operative field. The IONM setup, applications, and data interpretation of RLN monitoring were in compliance with International Nerve Monitoring guidelines.4,5 Standard IONM was performed as a 4-step procedure (V1, R1, R2, V2). The amplitude of the electromyography (EMG) waveform from the endotracheal surface electrode during IONM was defined as the adductor motor function of the vocal cords, whose main adductor is the thyroarytenoid muscle. The EBSLN function was assessed by CTM twitch. Both an auditory signal and a clear glottal EMG waveform with EBSLN stimulation were obtained in some cases. Positive stimulation was defined as both the audible alarm and the achievement of a recognizable EMG waveform amplitude that was >100 mV for both RLN and EBSLN. The thyroidectomy technique was described in detail in our previous study.9 After the vagus nerve was identified, the nerve was stimulated with a stimulator probe (V1) and evaluated by an EMGevoked waveform from the vocal cord to confirm the absence of muscle paralysis before identification of the EBSLN. Superior thyroid pole dissection was performed before or after lateral gland mobilization. The upper pole was retracted laterally and caudally to expand the sternothyroidlaryngeal triangle (SLT) (Fig 1, A), the limits of which are as follows: medially, the inferior

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Fig 1. (A) The upper pole was retracted laterally and caudally to expand the sternothyroid-laryngeal triangle (yellow arrow indicates the sternothyroid-laryngeal triangle, black arrow shows the direction of traction). (B) After the EBSLN was visually identified clearly in the sternothyroid-laryngeal triangle, it was confirmed with a monopolar stimulator probe (blue image). (C) The stimulator probe (blue image) was used to rule out entrapment of the EBSLN prior to division of vascular structures. CTM, Cricothyroid muscle; D, dissector; EBSLN, external branch of the superior laryngeal nerve; IPCM, inferior pharyngeal constrictor muscle; SHM, sternohyoid muscle; SHM-cut, cut sternohyoid muscle; STA, superior thyroid artery; STM, sternothyroid muscle; T, thyroid; TC, thyroid cartilage; THM, thyrohyoid muscle; Tr, trachea. (Color version of this figure is available online.)

pharyngeal constrictor muscle (IPCM) and CTM; anteriorly, the sternothyroid muscle; and laterally, the superior thyroid pole.10 The superior pole is gradually separated from the overlying strap muscle. In patients with an enlarged gland or a short neck, the strap muscles were transected with a LigaSure (Covidien, Mansfield, MA) at one-third of the superior edge to provide better exposure and dissection of the superior thyroid pedicle.5,11 The avascular space between the superior pole and CTM was dissected bluntly to obtain better operative control and exposure of the SLT, which harbors the EBSLN. The EBSLN was searched for in the SLT. After the EBSLN was clearly visually identified in the SLT, it was confirmed with a monopolar stimulator probe via CTM twitch assessment (Fig 1, B, Fig 2). If positive waveforms were detected during that stimulation, they were recorded. If the EBSLN could not be identified visually, a stimulator probe was used to search for it under the laryngeal head of the sternothyroid muscle, which is a good landmark for the course of the EBSLN and over the IPCM, on which the EBSLN follows an oblique path down toward the CTM.8 When the EBSLN could not be identified with a probe, the fibers of the IPCM were not dissected to identify the nerve visually, and no more dissection was performed near the upper lobe vessels. A stimulator probe was applied to the CTM, and repetitive contractions of the CTM were seen. Division of the superior pedicle was achieved by individual ligation and division of the vessels of the pedicle on the thyroid capsule.

Fig 2. The EBSLN was identified and stimulated in the sternothyroid-laryngeal triangle EBSN, External branch of the superior laryngeal nerve; SHM, sternohyoid muscle; STM, sternothyroid muscle; STP, superior thyroid pole. (Color version of this figure is available online.)

While managing the superior pole dissection, each portion of the pedicle tissue was stimulated with a probe to ensure that the EBSLN was not trapped during the maneuvers of clamping or cauterization (Fig 1, C). After dividing the superior thyroid vessels, we stimulated the EBSLN with a

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Fig 3. Cernea classification (A) type 1, (B) type 2a, (C) type 2b (A, The upper edge of the superior thyroid pole; B, 1 cm above the upper edge of the superior thyroid pole; B’, <1 cm above the upper edge of the superior thyroid pole; CCA, common carotid artery; EBSN, external branch of the superior laryngeal nerve; STA, superior thyroid artery; T, thyroid). (Color version of this figure is available online.)

probe cranially to the division point of the vessels to confirm its integrity. Anatomic classification of the EBSLN. Various anatomic classification systems for the EBSLN have been proposed, including the Cernea, Friedman, Kierner, and Selvan classifications.5 The Cernea classification is the most widely accepted and is based on the potential risk of injury to the EBSLN during thyroidectomy. It describes the EBSLN as 1 of 3 types with regard to its relation to the superior thyroid vessels and superior thyroid pole. Type 1 EBSLN crosses the superior thyroid vessels >1 cm above the upper edge of the superior pole, while the type 2A nerve crosses the vessels <1 cm above the upper edge of the superior thyroid pole. The type 2B nerve crosses the superior thyroid vessels below the upper edge of the superior thyroid pole12 (Fig 3). Friedman classification does not focus on the superior thyroid vessels; the main focus of this classification is the course of the EBSLN through IPCM. Three variations of the Friedman classification have been defined for the main trunk of the EBSLN before its insertion into the CTM. In the type I variation, it runs its whole course superficially or laterally to the IPC muscle, descending with the superior thyroid vessels until it terminates in the CTM. In the type 2 variation, the EBSLN penetrates deep to the IPCM, approximately 1 cm proximal to the inferior constrictor-cricothyroid junction. In the type 3 variation, nerves penetrate

under the superior most fiber of the IPCM, remaining covered by this muscle throughout its course to the CTM13 (Fig 4). Friedman classification was not aimed to replace the Cernea classification and should be considered as a complementary classification system, useful for intraoperative identification of the EBSLN. Since we started to evaluate the EBSLNs accordance with both the Cernea and Friedman systems after September 2014, 65 patients (113 EBSLNs) presented according to these classification systems. Evaluation of vocal cord function. The patients underwent routine pre- and postoperative (within 2 days) direct laryngoscopy conducted by an independent laryngologist. For patients with documented postoperative vocal cord palsy, repeated examinations were performed on the 15th day and at the first, second, fourth, and sixth months postoperatively until complete recovery of vocal cord function. RLN palsy was determined to be permanent when no evidence of recovery was found within 6 months postoperation. Evaluation of voice complaints. All the patients were reviewed by the surgery team on the 15th day postoperation. Any voice changes, such as hoarseness or weakness, inability to produce high-pitched sounds, reduction of the vocal range requiring additional effort to speak, and vocal fatigue at the end of the day were recorded. The patients with voice changes were clinically assessed at the first,

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Fig 4. Friedman classification (A) type 1, (B) type 2, (C) type 3. CTM, Cricothyroid muscle; E, esophagus; EBSLN, external branch of the superior laryngeal nerve; IBSLN, internal branch of the superior laryngeal nerve; IPCM, inferior pharyngeal constrictor muscle; RLN, recurrent laryngeal nerve; STP, superior thyroid pole; T, thyroid; TC, thyroid cartilage; Tr, trachea. (Color version of this figure is available online.)

second, fourth, and sixth months postoperation by the same operative team. The primary end point was to evaluate the visual identification rate of the EBSLN and the contribution of IONM to the visual and functional identification of the EBSLN. The secondary end point was to evaluate the effect of EBSLN identification on the clinical voice change complaints of the patients without RLN paralyses. Statistical analyses. The incidence of nerve events was calculated based on the number of nerves at risk. Differences between continuous and categorical variables were assessed with the MannWhitney U test and Fisher exact test and by the v2 test, respectively. RESULTS The study included the data of 221 patients (183 women, 38 men) with a mean age of 45.9 ± 12.5 years (range, 18–75 years) and 393 neck sides. The operative indications and procedures performed are presented in Tables I and II. The methods used for EBSLN identification are described in Table III. A total of 374 (95.2%) of 393 EBSLNs were identified. Nineteen EBSLNs (4.8%) were not able to be identified in 17 patients (15 unilateral and 2 bilateral); 275 (70%) of 393 EBSLNs were visualized; 145 (36.9%) EBSLNs were identified visually before being stimulated with a probe, and 130

(33.1%) EBSLNs were identified visually after being identified with a probe. Although 99 (25.2%) EBSLNs were identified with a probe, they were not visualized. The IONM provided a significant contribution to visual (P = .001) and functional (P = .001) identification of the EBSLN. Additionally, positive EMG responses were recorded from 257 (68.7%) of 374 EBSLNs. The EMG waveform amplitudes obtained from the RLNs and EBSLNs were 907 ± 604 mV (range, 314–2990 mV) and 172 ± 72 mV (range, 100– 361 mV), respectively, and the difference was significant (P < .001). No positive signals were obtained from the proximal parts of the 7 (1.8%) of 393 EBSLNs, however, although they were visually intact at the end of the operation. The distribution of the final 113 EBSLNs according to the Cernea and Friedman classifications is shown in Table III. Vocal cord palsy. All the vocal cord paralyses detected were unilateral. Nineteen (4.8%) temporary and 3 (0.8%) permanent RLN paralyses (RLNP) were detected. Postoperative voice changes. Voice changes were reported by 31 patients clinically (Table IV). Voice changes were detected in all patients who had temporary and permanent vocal cord paralyses. Twenty cases of 22 RLNP, including 17 temporary and 3 permanent paralyses, were detected in the patients whose EBSLNs were identified with

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Table I. Indications for operation Indication Benign nodular goiter MNG Recurrent goiter Solitary nodule Fine needle aspiration biopsy Bethesda III–IV Bethesda V Bethesda VI Histopathologically diagnosed malignancy Hyperthyroidism Toxic MNG Toxic adenoma Graves’ disease

No. of patients 81 6 7 29 18 33 7

25 4 11

MNG, Multinodular goiter.

Table II. The operative procedure performed Operative intervention Bilateral approach TT TT+CLND TT+CLND+LD Unilateral approach L

No. of patients 143 22 7 49

CLND, Central lymph node dissection; L, lobectomy; LD, lateral dissection; TT, total thyroidectomy.

Table III. The Cernea and Friedman classification of the 113 EBSLNs Classification Cernea classification Cernea type 1 Cernea type 2a Cernea type 2b Friedman classification Friedman type 1 Friedman type 2 Friedman type 3

n (%) 35 (31) 68 (60) 10 (9) 66 (59) 14 (12) 33 (30)

IONM, and the remaining 2 cases of RLNP occurred in patients who had at least one EBSLN that could not be identified with IONM. The vocal cord functions and voice change complaints of the patients with temporary RLNP recovered. The voice change complaints of the patients with permanent paralysis decreased but did not completely recover. After the patients with RLNP excluded, voice changes were detected in 6 (3.3%) of 184 patients with identified EBSLNs and 3 (20%) of 15

patients in whom at least 1 EBSLN could not be identified with IONM. Voice changes were detected in 7 patients with identified EBSLNs who had loss of signal from the proximal parts of the EBSLNs at the end of their operations. Six of these patients had ipsilateral normal vocal cord function and 1 had ipsilateral temporary RLNP. The voice complaints of 9 patients improved within 4 months postoperatively (Table IV). DISCUSSION The EBSLN, which is in close proximity to the superior thyroid vessels, is one of the major anatomic structures at risk during thyroid operation. No standard technique to preserve the EBSLN or uniform consensus on the operative protocol for identification of the EBSLN exist.14 Several techniques have been described to avoid EBSLN injury during superior thyroid vessels dissection and ligation, including peripheral ligation of the individual branches of the superior thyroid vessels only on the thyroid capsule, identification of the nerve before ligation of the vessels, and the use of either a nerve stimulator or IONM.3,5,7,15 A standardization of IONM technique, operative training, specific experience, and an interdisciplinary collaboration between operative and anesthesiology teams are necessary for optimal use of this technique.16 However, the surgeons did not entirely avoid especially technical problems during the initial stage of IONM use. The results of some of the studies indicate that in order to be an expert of the basic techniques of neuromonitoring and minimize technical problems, 50 to 100 tyhroidectomies with IONM have to be performed. The most common technical problems involved are improper positioning of the surface electrodes on the endotracheal tube in relation to the vocal cords.16-18 The technical problems encountered during EBSLN monitoring are more rare when compared to RLN monitoring. The EBSLN function is primarily evaluated by the CTM and, therefore, the positioning of the endotracheal tube and the recording electrodes do not affect the EBSLN evaluation. In the current study, the technical problems are #2%. Technical problems, such as the displacement of the grounding electrodes, could be prevented if treated more carefully at the beginning of the operation. Absence of the electrical current in the operative field could be arising from the blasting of the

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Table IV. The distribution of vocal cord function and voice change of the patients with/without identified EBSLNs

Normal vocal cord function Voice change No voice change Total Vocal cord palsy Voice change Temporarary RLNP Permanent RLNP No voice change Total

Patients with identified EBSLNs n = 204

Patients with $1 EBSLN not identified n = 17

6 (3.3%)* 178 184

3 (20%) 12 15

20 17* 3 0 20

2 2 0 0 2

*Voice changes were detected in 7 patients with identified EBSLNs who had loss of signal from the proximal parts of the EBSLNs at the end of their operations. Six of these patients had ipsilateral normal vocal cord function and 1 had ipsilateral temporary RLNP.

fuse of the interface-connector box. In this case, the monitoring system should be restarted after the renovation of the fuse. Prolonged neuromuscular blockage, various stimulator probe malfunctions (probe, probe wire, or probe ground), blood, or fascia covering the stimulated nerve segment, insufficient probe-nerve contact, and transient neuropraxis of the EBSLN are the other technical problems that can be encountered during the monitoring.4,5 A cardinal principle of any operation is identifying a structure in order to avoid injury to it.19 The visual identification rate of the EBSLNs at risk was only 36.9% in the present study, which is lower than the rates reported in the literature. In our opinion, the reason for the difference was that we did not divide the strap muscles routinely to expose the SLT. The EBSLN identification rate was 34.1% in another study similar to ours in which the sternothyroid muscles were not divided,7 but the rate has been as high as 80%–88% in other studies in which sternothyroid muscle division was performed to improve visual control of the EBSLN.20-22 The visual identification rate of the EBSLN after being identified with IONM, however, increased to 70%, which is closer to the rates reported in studies including routine division of the strap muscles. In most cases of a normally sized or only slightly enlarged gland, strap muscle division is not required.5 The functional identification rate of EBSLN with IONM is 95.2% and consistent with those reported in the other studies, as ranging from 83% to 100%.7,8,11,21 Hurtado-Lopez et al21 found an odd ratio value implying that it is 10-times more feasible to identify EBSLN with IONM than to identify it visually.

In our study, IONM provided meaningful contributions to visual (P = .001) and functional (P = .001) identification and also to mapping of the EBSLN. Our results demonstrated that both visual and functional identification rates of the EBSLN similar to those of other studies with routine division of the strap muscles could also be achieved using IONM without routine division of these muscles. Although our study was not a randomized, 2-group study design, it could provide substantial contributions by confirming the visually identified structure as the EBSLN with IONM. This is important because Selvan et al23 showed that nonneural fibers or tendinous fibers of the regional musculature could be mistaken for the EBSLN. Although most of the RLNs could be visually identified, approximately 20% of the EBSLNs could not be visually identified due to their subfascial course on the IPCM, requiring microdissection for identification.13,24 Although 25.2% of all the EBSLNs were identified with IONM, they were not visualized in the present study. Additionally, 30% of the last 113 EBSLNs had a subfascial/intramuscular course on the IPC muscle toward the CTM (Friedman type 3), and 12% of the 113 EBSLNs penetrated the IPC muscle in the lower portion so that only the distal part of the nerve had a course beneath the fibers of this muscle (Friedman type 2). The EBSLNs were also classified according to the Cernea classification based on the nerve’s potential injury risk; the distribution of the last 113 nerves with regard to types 1, 2a, and 2b were 31%, 60%, and 9%, respectively. The distribution rates of EBSLNs according to the Cernea classification have been reported in the literature with results varying from 17% to 60%

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for type 1, 17% to 59% for type 2a, and 10% to 56% for type 2b.3,20-22,25 The different results might be due to various factors, such as the race or height of the person, weight of the thyroid gland, identification type of the EBSLN visually or with the use of IONM, and the extent of the study. Mostly, the Cernea type 2b but also both types 2a and 2b EBSLNs were at risk during the superior thyroid vessel dissection due to their close course to the superior pole.3 In the present study, nearly 2/3 of the EBSLNs were prone to risk of injury due to their crossing with vessels within 1 cm the upper edge of the superior pole. The EMG waveform amplitude represents the vocal cord adductor function. Motor interconnectivity between the RLN and the EBSLN allows for EMG activity to be detected by monitoring action potentials of the thyroarytenoid muscle, especially in the anterior third of the vocal cord.26 The distant fibers of the EBSLN penetrate the 2 heads of the CTM extending to the anterior portion of the thyroarytenoid muscle and connect with the RLN. This connection has been described as the “human communicating nerve.”27 This nerve was identified in 41% to 85% of humans in anatomic dissection studies.27,28 The human communicating nerve transmits the stimulation impulse from the EBSLN to the endolaryngeal musculature, allowing for action potential measurement through IONM.11 In addition to the observed cricothyroid twitch, several studies have recently found that EMG amplitudes (less than those of RLN) could be obtained from the vocal cords by EBSLN stimulation in 70% to 80% of cases.7,29 They found that EMG amplitudes with EBSLN stimulation are approximately one-third of ipsilateral RLN amplitudes Similar to these studies, we achieved EMG responses from 68.7% of the EBSLNs identified with IONM and the mean amplitude was 172 ± 72 mV, which was less than that of RLNs (907 ± 604 mV). Darr et al11 could identify all the EBSLNs and observed quantifiable EMG responses in 100% of cases using a novel endotracheal tube with larger surface electrode. They found that the EMG responses from the vocal cords had a great variability and that tube position might influence the EMG waveform amplitudes, likely due to the fact that the EBSLN innervates primarily the anterior onethird of the vocal cord. While gross CTM twitch is quite evident at operation and is a useful operative maneuver, this twitch is not quantifiable data. Quantifiable EMG responses can add to gross CTM twitch as a tool to optimally monitor EBSLN.

Surgery j 2016 Darr et al11 suggested that EMG data acquired through IONM may furthermore aid in distinguishing between neuropraxic states and prognosticating postoperative neural function. The reported prevalence of EBSLN injury given the limited data in the literature has varied widely from 0% to 58% due to the lack of a standard protocol to detect EBSLN injury and the use of different postoperative evaluation methods.30 Jansson et al31 evaluated the EMG responses of the CTMs after thyroidectomy without EBSLN identification intraoperatively and found temporary EBSLN injury in 58% and permanent injury in 3.8% of the patients. Cernea et al3 found an incidence between 12% and 28% of injury when the EBSLN was not identified intraoperatively, and some of these injuries were permanent, as confirmed by long-term EMG evaluation. They detected no EBSLN injury in the patients, however, whose EBSLNs were identified and confirmed with IONM. Barcyznski et al7 compared visualization with neuromonitoring for the identification of the EBSLN in their randomized, controlled, prospective study, and they found that IONM also reduced the prevalence of transient, but not permanent, EBSLN injury in monitored versus nonmonitored groups (1.0% vs 5%, respectively; P = .02); it reduced the risk of early, but not permanent, changes following thyroidectomy. Glower et al22 found voice change complaints in 17 (6.8%; 7 with RLNP and 10 without RLNP) of 251 patients whose EBSLNs were identified with IONM. Hortado Lopez et al21 evaluated the effect of IONM use to the risk of EBSLN injury and detected no alterations in postoperative laryngoscopy and subjective voice assessment. The combination of proper usage of IONM, anatomic knowledge, and operative experience will facilitate the identification of the EBSLN. In 1998, Kierner et al32 proposed a classification similar to the Cernea system, adding a fourth type of the EBSLN descending dorsal to the superior thyroid artery and only crossing the branches of the superior thyroid artery immediately above the upper pole of the thyroid gland. This type was found in 14% of the EBSLNs in their study of cadaver dissection. They stated that its identification is more difficult because in these cases the nerve descends more dorsally than one would expect. In our study, we were not able to identify approximately 5% of the EBSLNs with IONM. These nerves can be of Friedman type III, which are located under the fibers of IPCM, or Kierner type IV. Due to these anatomic variations, the

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insufficient probe-nerve contact may be the reason for not identifying the EBSLN. We did not perform extended dissection for the nerves that could not be identified visually and/or with IONM to avoid the increase in potential risk of EBSLN injury during the dissection. The voice changes rate of the patients in our study with at least one EBSLN unidentified was higher than that of the patients with all EBSLNs identified by IONM, excluding the patients with RLNP (20% vs 3.3%). Although the voice change complaints of the patients without RLNP were multifactorial in origin, they were more likely to be related to EBSLN injury and included inability to produce high-pitched sounds and vocal fatigue at the end of the day. Additionally, 6 (3.3%) patients with EBSLNs identified via IONM had loss of signal on the proximal parts of the EBSLNs after dissection, supporting the hypothesis that the voice change complaints were due to the EBSLN injury. The voice change complaints were all temporary in patients whose EBSLNs were identified with IONM. Thus, we believe that the contribution of IONM may play an important role for the preservation of the EBSLN. Voice change in patients with undetectable nerves may be related with the Kierner type 4 classification of these EBSLNs. We suggest that nerve injury may be in 2 different ways in Kierner type 4. First, the nerve passes through the branches of the superior thyroid artery during the inferolateral traction of the superior pole, which causes a tractional trauma; second, thermal damage is caused by the usage of energy-based devices (EBD) during the superior pole vessel ligation. Thermal damage also may be the reason for voice impairments in patients whose EBSLNs were anatomically intact and visually identified but have a loss of signaling when stimulated from the proximal edge of the nerve. We think that not using EBD close to the visually and/or functionally identified EBSLNs may contribute to the preservation of these nerves. Traction and thermal injury are the most common mechanisms of RLN injury during thyroid procedures. EBDs are widely used in thyroid operation, and recent studies determined that EBDs can be safely used 2–3 mm away from the RLN without causing EMG signal changes.33,34 EBDs can increase the risk of collateral iatrogenic heat injury to the adjacent structures, including the EBSLN, the RLN, and the parathyroid glands, especially in cases in which the nerve could not be found.5 We suggest that, in cases in which the EBSLNs could not be identified,

conventional techniques should be preferred in the ligation of the vessels instead of the EBDs. Also, according to the our clinical practice, vascular or tubular anatomic structures can be ligated on the thyroid capsule if CTM twitch is detected only after the direct stimulation of the CTM, while there is no evidence of CTM twitch when these structures are stimulated by the probe. The present study had several limitations. First, the study was retrospective, although the data were collected prospectively. The anatomic variations in the last 65 (113 EBSLNs) of 221 patients were recorded according to the Cernea and Friedman classifications. One of the major limitations is that the standard postoperative voice assessment methods (such as the subjective voice handicap index) or EMG of the CTM were not applied in the patients. The only definitive method of diagnosing EBSLN injury is via postoperative CTM EMG.8 In conclusion, IONM provided an important contribution to the visual and functional identification of the EBSLN. IONM is a helpful adjunct for identifying the EBSLN. Despite several studies performed previously in this field, it is a fact that more prospective, randomized studies should be performed in this field for demonstrating the effect of intraoperative IONM in preventing the EBSLN injuries and showing its effect on postoperative voice impairments. REFERENCES 1. Masuoka H, Miyauchi A, Higashiyama T, Yabuta T, Fukushima M, Ito Y, et al. Prospective randomized study on injury of the external branch of the superior laryngeal nerve during thyroidectomy comparing intraoperative nerve monitoring and a conventional technique. Head Neck 2015;37:1456-60. 2. Sanders I, Wu BL, Mu L, Li Y, Biller HF. The innervation of the human larynx. Arch Otolaryngol Head Neck Surg 1993; 119:934-9. 3. Cernea CR, Ferraz AR, Furlani J, Monteiro S, Nishio S, Hojaij FC, et al. Identification of the external branch of the superior laryngeal nerve during thyroidectomy. Am J Surg 1992;164:634-69. 4. Randolph GW, Dralle H, International Intraoperative Monitoring Study Group, Abdullah H, Barczynski M, Bellantone R, et al, Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: international standards guideline statement. Laryngoscope 2011;121(suppl 1):S1-16. 5. Barczy nski M, Randolph GW, Cernea CR, Dralle H, Dionigi G, Alesina PF, et al. International Neural Monitoring Study Group. External branch of the superior laryngeal nerve monitoring during thyroid and parathyroid surgery: International Neural Monitoring Study Group standards guideline statement. Laryngoscope 2013;123(suppl 4):S1-14. 6. Barczy nski M, Randolph GW, Cernea C, International Neural Monitoring Study Group in Thyroid and Parathyroid Surgery, International survey on the identification and

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