Langenbecks Arch Surg DOI 10.1007/s00423-016-1376-5
RAPID COMMUNICATIONS
Innervation of the human cricopharyngeal muscle by the recurrent laryngeal nerve and external branch of the superior laryngeal nerve Mehmet Uludag 1 & Nurcihan Aygun 1 & Adnan Isgor 2
Received: 9 November 2015 / Accepted: 24 January 2016 # Springer-Verlag Berlin Heidelberg 2016
Abstract Purpose The major component of the upper esophageal sphincter is the cricopharyngeal muscle (CPM). We assessed the contribution of the laryngeal nerves to motor innervation of the CPM. Methods We performed an intraoperative electromyographic study of 27 patients. The recurrent laryngeal nerve (RLN), vagus nerve, external branch of the superior laryngeal nerve (EBSLN), and pharyngeal plexus (PP) were stimulated. Responses were evaluated by visual observation of CPM contractions and electromyographic examination via insertion of needle electrodes into the CPM. Results In total, 46 CPMs (24 right, 22 left) were evaluated. PP stimulation produced both positive visual contractions and electromyographic (EMG) responses in 42 CPMs (2080 ± 1583 μV). EBSLN stimulation produced visual contractions of 28 CPMs and positive EMG responses in 35 CPMs (686 ± 630 μV). Stimulation of 45 RLNs produced visible contractions of 37 CPMs and positive EMG activity in 41 CPMs (337 ± 280 μV). Stimulation of 42 vagal nerves resulted in visible contractions of 36 CPMs and positive EMG responses in 37 CPMs (292 ± 229 μV). Motor activity was noted in 32 CPMs by both RLN and EBSLN stimulation, 9 CPMs by RLN stimulation, and 3 CPMs by EBSLN stimulation; 2 CPMs exhibited no response. Conclusions This is the first study to show that the EBSLN contributes to motor innervation of the human CPM. The
* Mehmet Uludag [email protected]
1
General Surgery, Sisli Hamidiye Etfal Training and Research Hospital, Department of General Surgery, Istanbul, Turkey
2
General Surgery, Bahcesehir University Medical Faculty, Department of General Surgery, Istanbul, Turkey
RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively. Keywords Cricopharyngeal muscle . Recurrent laryngeal nerve . External branch of the superior laryngeal nerve . Pharyngeal plexus
Introduction The upper esophageal sphincter is a high-pressure zone that s ep a r a t es t h e p h ar y nx f r o m t h e e s o p h a gu s . T h e cricopharyngeal muscle (CPM) is the most definitive component of this sphincter [1]. The upper esophageal sphincter is closed at rest, because the CPM is tonically contracted; demonstrating electromyographic (EMG) activity at baseline [2]. During a swallow, the CPM relaxes to allow the upper esophageal sphincter to open and a bolus to pass into the esophagus. The CPM may also play an important non-swallow role, namely regulation of upper esophageal sphincter closure. Increased upper esophageal sphincter pressure and CPM EMG activity have been found during inhalation, exhalation, and phonation [3, 4] (Figs. 1, 2, and 3). Motor innervation of the CPM has been debated for decades and needs to be further studied. Different animal and human anatomical studies have suggested that the CPM may be innervated by a single nerve such as the pharyngeal plexus (PP), glossopharyngeal nerve, cervical sympathetic ganglion, external branch of the superior laryngeal nerve (EBSLN) [5], or recurrent laryngeal nerve (RLN) [6]. Alternatively, the CPM may be innervated by the union of two or more of these nerves, such as the PP and RLN [7–9]; RLN and its sympathetic anastomoses with the middle cervical ganglion [10]; RLN and EBSLN [11, 12]; or the glossopharyngeal nerve, RLN, and EBSLN [13]. When Sasaki et al. [14] reviewed the literature, they realized that there may be several sources of confusion contributing to neuroanatomic controversy: the
Langenbecks Arch Surg Fig. 1 a A pair of needle electrodes inserted into both the CPM and CTM for the electromyographic study and the demonstration of the EBSLN stimulation with the stimulator probe (CPM cricopharyngeal nerve, CTM cricothyroid muscle, EBSLN external branch of the superior laryngeal nerve, STA superior thyroid artery). b Evoked amplitudes from the CPM (channel 4), CT muscle (channel 3), and left vocal cord (channel 1) with the stimulation of the EBSLN
use of non-human models; observational misinterpretation of small-diameter, overlapping nerve fibers; and the lack of realtime validation of motor projections. Voice symptoms after thyroidectomy are well-known implications of laryngeal nerve (RLN and EBSLN) injuries. Laryngeal nerve injuries frequently lead to swallowing problems [15, 16]. In recent years, intraoperative neural monitoring (IONM) during thyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. IONM can be used to identify and evaluate the functions of both the RLN and EBSLN. The functions of other
laryngeal muscles can also be evaluated by the various channels in multichannel IONM systems, excluding the two channels already evaluating vocal cord functionality. The CPM and cricothyroid muscle (CTM) are the muscles present in the dissection field during thyroidectomy. The function of the EBSLN is evaluated with CTM twitch on stimulation via IONM during thyroidectomy. The potential use of visual observation of CPM contractions with RLN and/or EBSLN stimulation caught our attention. The presence of real-time EMG studies in the literature is more limited than the controversial anatomical studies on CPM innervation [14, 17]. CPM
Langenbecks Arch Surg Fig. 2 a A pair of needle electrodes inserted into both the CPM and CTM for the electromyographic study and the demonstration of the RLN stimulation with the stimulator probe (CPM cricopharyngeal muscle, CTM cricothyroid muscle, RLN recurrent laryngeal nerve, STA superior thyroid artery, CCA common carotid artery, VN vagus nerve, IJV internal jugular vein, ITA inferior thyroid artery). b Evoked amplitudes from the CPM (channel 4) and right vocal cord (channel 2) with the stimulation of the right vagus nerve and RLN. The electromyographic responses were recorded with a pair of needle electrodes inserted into the CPM. The vagus nerve and recurrent laryngeal nerve were stimulated at 1 mA
innervation by the EBSLN was not detected in one study evaluating the function of the EBSLN [14]. In the present study, we evaluated the CPM innervation pattern by the RLN and EBSLN in vivo using IONM during thyroidectomy.
Materials and methods We studied a consecutive series of 27 patients (19 female, 8 male; 46 neck sides) who underwent thyroid surgery with IONM from February to April of 2015. Each side of the neck operated on was considered a separate entity in our study. The
demographic profile of each patient and the anatomy and neuromonitoring data of the RLN and EBSLN were documented at the end of each operation and recorded in a prospective database. The exclusion criteria were preoperative RLN palsy, thyroid cancer with massive extrathyroidal extension, intentional nerve transection because of cancer invasion, and failure to assess nerve function because of the technical issues. All patients underwent routine direct laryngoscopy by an independent laryngologist preoperatively and within 2 days postoperatively. RLN palsy was determined to be permanent,
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stimulated the EBSLN with a probe at a point cranial to the ligation of the vessels to confirm the integrity of the EBSLN. After dissection of the superior pole, the RLN was identified and fully dissected till its entry through the larynx under the CPM.
Neuromonitoring of CPM
Fig. 3 A pair of needle electrodes inserted into both the CPM and CTM for the electromyographic study and the demonstration of the stimulation point of PP at the posterolateral side of the superior thyroid arteries among the fibers of the inferior pharyngeal constrictor muscle at the posterior border of the thyroid lamina. (CPM cricopharyngeal muscle, CTM cricothyroid muscle, EBSLN external branch of the superior laryngeal nerve, STA superior thyroid artery, PP pharyngeal plexus, IPCM inferior pharyngeal constrictor muscle)
when there was no evidence of recovery within 6 months postoperatively. IONM technique The four-channel NIM 3.0 Nerve Monitoring System (Medtronic Xomed, Jacksonville, FL, USA) was used intraoperatively. All monitoring setup, applications, and data interpretation were in compliance with the International Neural Monitoring Guidelines [18]. The patient was placed under general anesthesia with low-dose, short-acting neuromuscular blockade (rocuronium, 0.3 mg/kg) and intubated with a size 6.0 to 8.0 endotracheal tube (NIM Standard Reinforced EMG endotracheal tube; Medtronic Xomed). The endotracheal tube electrodes (left vocal cord—channel 1, right vocal cord— channel 2), probe electrode, and grounding electrodes were plugged into the interface-connector box. Surgical technique Thyroidectomy and/or central neck dissection was performed using a 4 to 6 cm collar transverse incision. All the patients underwent total extracapsular thyroidectomy. During the superior pole dissection, the sternothyroidlaryngeal triangle was exposed with blunt dissection and searched for the EBSLN with a monopolar stimulating probe via CTM twitch assessment. An auditory signal and a clear EMG waveform with EBSLN stimulation were obtained in some cases. After ligating the superior thyroid vessels, we
EMG recordings were accomplished with a pair of needle electrodes inserted into the CTM and midportion of the CPM, located on the superior side of the RLN. These needle electrodes were plugged into the third and fourth channels of interface-connector box, respectively, at the end of the thyroidectomy. We evaluated the innervation pattern of the CTM in another study and found that the EBSLN is the main supplier of the CTM, and the EMG findings of the CTM were used to confirm this in the present study. The EMG responses of the CPM and CTM were analyzed and validated by considering the following conditions based on the studies of Faaborg-Anderson [19] and Martin-Oviedo et al. [20]. A positive response had to be at least four times greater than that of the uninnervated muscle. In our study, the mean response in the contralateral CPM was 19.1 μV with stimulation of the EBSLN, and a positive evoked response was defined as ≥100 μV. The EBSLN, PP, RLN, and vagus nerves were stimulated with a monopolar stimulator probe at 1 mA. The constant points of neural stimulations were standardized. EBSLN was stimulated at a point that is located 2 cm proximally to the nerve’s entry point to the CTM. PP was stimulated at the same level of EBSLN’s stimulation point at the posterolateral side of the superior thyroid vessels. PP is found with the monopolar stimulator probe among the fibers of the inferior pharyngeal constrictor muscle at the posterior border of the thyroid cartilage lamina. RLN was stimulated at a distance of 2 cm proximally, before it enters the larynx. In case of RLN branching, the main trunk and each branch were stimulated and evaluated by an EMG-evoked waveform. The EBSLN, RLN, vagus nerve, and PP were stimulated with a monopolar stimulator probe at 1 mA. The stimulation duration was set at 100 μs, and the current was set at a frequency of 4 Hz. While stimulating these nerves, the ipsilateral and contralateral CPMs were visually observed for possible contractions, and EMG recordings were obtained with the four-channel neuromonitoring system.
Statistical analysis All amplitude data are presented as mean and standard deviation (min–max). Visual movement and positive EMG response values are expressed as frequency and percentage.
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Results In total, 27 patients (19 female, 8 male; mean age, 45.8 years; range, 33–70 years) including 46 neck sides (24 right, 22 left) and CPMs were evaluated. The indications for surgical procedures were benign thyroid disorders (euthyroid, n = 12; hyperthyroid, n = 6); cytologically diagnosed disorders on fineneedle aspiration biopsy classified as Bethesda IV, V, or VI (n = 8); and histopathologically diagnosed malignant thyroid disease (n =1). Surgical procedures were total thyroidectomy (n = 19) including central neck dissection in two patients, lobectomy (n = 6), completion thyroidectomy (n = 1), and lobectomy with parathyroidectomy (n = 1). The visual contractions and positive EMG responses obtained with stimulation of the nerves are shown in Table 1. No EMG responses were obtained on one side with both RLN and vagus nerve stimulations in one patient with primary signal loss. EMG responses were not obtained with vagus nerve stimulation but obtained with RLN stimulation in two patients with ipsilateral transient signal loss. EMG motor activity was achieved in 32 (70 %) CPMs by both RLN and EBSLN stimulations, in 9 (20 %) CPMs by only RLN stimulation, and in 3 (6 %) CPMs by only EBSLN stimulation; 2 (4 %) CPMs showed no response. One of the last two CPMs exhibited no EMG response because of primary signal loss with RLN stimulation. Sixteen (34.8 %) branching RLNs of 46 RLNs were detected. The median branching distance was 1 cm (range 0.5– 3 cm). Positive EMG responses were obtained from CPMs with the stimulation of the anterior branches of 13 RLNs out of 16 branched RLNs. No motor activity was detected with the posterior branch stimulation. No signal was accomplished from neither the main trunks nor the anterior or posterior branches of the two branched RLNs. CPM motor innervation was evaluated electromyograpically on 31 neck sides with the stimulation of the contralateral vagus nerve, RLN, EBSLN, and PP, in 16 out of 19 bilaterally operated patients. No positive EMG responses were achieved from any of the 31 CPMs with the stimulation of the contralateral nerves. The CPM contraction was obtained only ipsilaterally. One patient had partial and one had complete transient vocal cord paralysis that resolved within 15 days and 2 months after the procedure, respectively.
Discussion The CPM is the major component of the upper esophageal sphincter. Different opinions exist regarding the anatomy and physiology of the motor nerve supply of the CPM. To our knowledge, only two studies have evaluated the motor innervation of the CPM both electrophysiologically and functionally during an operation [14, 17].
Our study has demonstrated that the PP always functionally contributes to motor innervation of the CPM. This finding is in compliance with the anatomical findings of previous human studies [7–9]. The RLN reportedly has a motor contribution to most (91 %) CPMs based on the EMG responses obtained by RLN stimulation. The EBSLN has been found to contribute to the motor innervation in 76 % of CPMs. The innervation of CPM was ipsilateral with both the EBSLN and/or RLN. The visual contractions of CPMs detected by both RLN and EBSLN stimulation may be weaker than those detected by EMG, because visual contractions may not be observed in muscles recorded with low amplitudes. Sasaki et al. [14] performed microdissection in 9 of 27 patients undergoing total laryngectomy for endolaryngeal cancer and real-time EMG CPM evaluation with PP, RLN, EBSLN, and sympathetic plexus stimulation. The authors demonstrated dual ipsilateral innervation of the CPM by the PP and RLN, segmental projection of the RLN to the anterior and PP projection to the posterior motor unit, absence of a sympathetic or EBSLN contribution, and absence of contralateral innervation. Brok et al. [17] examined the contribution of the RLN and PP to the motor nerve innervation of the CPM and inferior pharyngeal constrictor muscles with intraoperative EMG. The authors reported that the RLN contributes to the motor innervation of the CPM. Additionally, positive evoked EMG potentials of the CPM were obtained with PP stimulation in three of seven patients. The authors observed innervation of the inferior pharyngeal constrictor muscle by both the RLN and PP in all patients. Halum et al. [21] compared the EMG data of the CPM with the simultaneous EMG findings of the ipsilateral pharyngeal and laryngeal muscles at a neurology clinic in 2006. They suggested an extremely high correlation between the innervation status of the CPM and that of the inferior pharyngeal constrictor muscle (same innervation status in 27 of 28 studies). This was followed by observation of a correlation between the innervation status of the CPM and CTM (same innervation status in 40 of 50 studies) and of the CPM and thyroarytenoid muscle (same innervation status in 31 of 50 studies). These findings alone suggest that the PP plays the greatest role in CPM innervation, followed by the SLN and RLN. To the best of our knowledge, the current study is the most extensive study to evaluate the innervation of the CPM with real-time EMG. This study is also the first to demonstrate the functional contribution of the EBSLN to the motor innervation of the CPM with intraoperative EMG. Our EMG findings contrast those reported by Sasaki et al. [14], who demonstrated the absence of an EBSLN contribution to the CPM. The EBSLN was not tested in the physiological study by Brok et al. [17]. The anatomical findings of previous animal [5, 11] and human [12, 13] studies of the contribution of the EBSLN to the CPM innervation support our functional results. While the results of our study and that of Sasaki et al. [14] are similar in terms of the contribution of the PP to the motor
Langenbecks Arch Surg Table 1 Visible contractions and evoked amplitudes of the CPM with stimulation of the PP, EBSLN, RLN, and vagus nerve
Nerve
N
Visible contractions
Positive EMG response
EMG amplitude mean ± SD, μV (min–max)
PP EBSLN
46 46
46 (100 %) 28 (61 %)
46 (100 %) 35 (76 %)
2080 ± 1583 (101–8041) 686 ± 630 (100–2923)
RLN Vagus nerve
45 43
37 (82 %) 36 (84 %)
41 (91 %) 37 (86 %)
337 ± 280 (100–1556) 292 ± 229 (101–1077)
CPM cricopharyngeal muscle, PP pharyngeal plexus, EBSLN external branch of superior laryngeal nerve, RLN recurrent laryngeal nerve, EMG electromyography, SD standard deviation
innervation of all CPMs, Brok et al. [17] reported that the PP functionally contributes to the CPM in fewer than half of cases. Although the contribution of the RLN to the innervation of the CPM was 100 % in the two above mentioned studies, it was 91 % in our study. We found rates of contribution of the PP and EBSLN to the innervation of the CPM similar to those found by Halum et al. [21] (100.0 vs. 96.5 % and 76.0 vs. 80.0 %, respectively), although theirs was a clinical trial. Their rate of RLN contribution to the CPM innervation was lower than that in our study and the other physiologic study (17) (62 vs. 91 vs. 100 %, respectively). The differences in the physiologic results are similar to the different opinions among the anatomical studies in the literature. The neuroanatomic variance in the area of the larynx and upper esophageal sphincter is an enough reason to state that anatomic dissection, even with physiologic correlation, may not readily elucidate the innervation of the CPM [21]. Studies based on anatomic dissection of canine models have revealed that the CPM is supplied by the pharyngeal branch of the vagus nerve [22] or by the vagus and sympathetic nerves [23]. Lund and Andran [24] reported that the PP is the main supplier of nerve fibers to all pharyngeal muscles excluding the stylopharyngeal muscle. Hwang et al. [11] suggested that the CPM is innervated by terminal branches of the RLN and PP or by the PP of the vagus nerve. Other researchers have suggested that the CPM is also innervated by the EBSLN in different animal models [5, 11]. Human anatomical studies have also demonstrated differing sources of CPM innervation. Steinberg et al. [8] found that the CPM is supplied by the branches of the RLN and their sympathetic anastomoses with the middle cervical ganglion. Other investigators have found that the CPM receives input from the PP and RLN [7–9]. Mu and Sanders [8] reported that the CPM receives its innervation from below via the RLN and from above via the PP. Most recently, in 2007, Mu and Sanders [13] found that in addition to the PP and RLN, the EBSLN also supplies branches to innervate the CPM. Prades et al. [12] suggested that the posterior part of the CPM is supplied by the RLN and the anterior part of the CPM is supplied by the lateral branch of the SLN.
CPM innervation may also vary according to the anastomosis between the nerves. By general consensus, the pharyngeal branches of the glossopharyngeal and vagus nerves communicate to form the PP [9, 25]. Mu and Sanders [13] mapped the entire human PP with Sihler’s stain. They found that the adult human PP mainly comprises the pharyngeal branches of the glossopharyngeal and vagus nerves with less contribution from the EBSLN and the sympathetic nerve fibers derived from the superior ganglion [12]. Some studies have observed connections between the RLN and PP in the CPM [8, 9, 13]. The communications of the PP with the external and internal branches and main trunk of the SLN were sometimes found [9]. The loops were found between the cervical sympathetic chain and the SLN or its branches [26, 27]. Connections between the RLN and the internal or external branch of the SLN have been documented in 15 to 100 % cases in a variety of dissection studies [28]. Sanuda et al. [29] found that at least two anastomoses (the Galen anastomosis and the arytenoid plexus) appeared in 21 % of hemilarynges, and 79 % of cases had three or more anastomoses between the RLN and branches of the SLN. Maranillo et al. [30] demonstrated one or more communicating branches between the EBSLN and RLN in 85 % of 103 human cadaver larynges. Electrical stimulation of one of these nerves that communicates with another may result in stimulation of any interconnected muscle, regardless of its innervation source [12]. The RLN and EBSLN were stimulated at the level of their main trunks in the current study. We found that EMG motor activity was achieved by both RLN and EBSLN stimulation in 70 % of the CPMs evaluated. This finding suggests that the various anastomoses between the nerves may also contribute to the motor innervation of the CPM. The RLN and EBSLN are inevitably at risk during surgery of the neck, skull base, and chest [31]. Thyroid surgery is the most common cause of injury to the RLN and EBSLN [32]. Injury to one or both of these nerves may disturb various voice, airway, and swallowing functions [33]. These symptoms may be related to injury to the extrinsic perithyroidal neural plexus, which innervates the pharyngeal and laryngeal structures [15, 16]. The thyroid surgeon must be familiar with the laryngeal neuroanatomy and various manifestations of
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laryngeal nerve injuries [33]. Nerve injuries may alter the swallowing function depending on the complex motor innervation of the CPM. Therefore, during thyroidectomy, preservation of the laryngeal nerves is equally as important for the innervation of the CPM and other pharyngeal muscles as for the innervation of the intrinsic laryngeal muscles.
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Conclusion
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This is the first report to provide evidence that the EBSLN functionally contributes to the motor innervation of the human CPM. The RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively.
8.
Authors’ contributions Study conception and design: Mehmet Uludag Acquisition of data: Nurcihan Aygun Analysis and interpretation data: Mehmet Uludag, Nurcihan Aygun, Adnan Isgor Drafting of manuscript: Mehmet Uludag, Nurcihan Aygun Critical revision of manuscript: Mehmet Uludag, Adnan Isgor
10.
Compliance with ethical standards 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 Langenbeck’s Archives of Surgery.
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Conflicts of interest The authors declare that they have no conflict of interest.
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Funding None.
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Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee 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. This prospective study was approved by the Institutional Review Board of Sisli Hamidiye Etfal Training and Research Hospital.
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Informed consent Informed consent was obtained from all individual participants included in the study. 19.
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Innervation of the human cricopharyngeal muscle by the recurrent laryngeal nerve and external branch of the superior laryngeal nerve Mehmet Uludag 1 & Nurcihan Aygun 1 & Adnan Isgor 2
Received: 9 November 2015 / Accepted: 24 January 2016 # Springer-Verlag Berlin Heidelberg 2016
Abstract Purpose The major component of the upper esophageal sphincter is the cricopharyngeal muscle (CPM). We assessed the contribution of the laryngeal nerves to motor innervation of the CPM. Methods We performed an intraoperative electromyographic study of 27 patients. The recurrent laryngeal nerve (RLN), vagus nerve, external branch of the superior laryngeal nerve (EBSLN), and pharyngeal plexus (PP) were stimulated. Responses were evaluated by visual observation of CPM contractions and electromyographic examination via insertion of needle electrodes into the CPM. Results In total, 46 CPMs (24 right, 22 left) were evaluated. PP stimulation produced both positive visual contractions and electromyographic (EMG) responses in 42 CPMs (2080 ± 1583 μV). EBSLN stimulation produced visual contractions of 28 CPMs and positive EMG responses in 35 CPMs (686 ± 630 μV). Stimulation of 45 RLNs produced visible contractions of 37 CPMs and positive EMG activity in 41 CPMs (337 ± 280 μV). Stimulation of 42 vagal nerves resulted in visible contractions of 36 CPMs and positive EMG responses in 37 CPMs (292 ± 229 μV). Motor activity was noted in 32 CPMs by both RLN and EBSLN stimulation, 9 CPMs by RLN stimulation, and 3 CPMs by EBSLN stimulation; 2 CPMs exhibited no response. Conclusions This is the first study to show that the EBSLN contributes to motor innervation of the human CPM. The
* Mehmet Uludag [email protected]
1
General Surgery, Sisli Hamidiye Etfal Training and Research Hospital, Department of General Surgery, Istanbul, Turkey
2
General Surgery, Bahcesehir University Medical Faculty, Department of General Surgery, Istanbul, Turkey
RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively. Keywords Cricopharyngeal muscle . Recurrent laryngeal nerve . External branch of the superior laryngeal nerve . Pharyngeal plexus
Introduction The upper esophageal sphincter is a high-pressure zone that s ep a r a t es t h e p h ar y nx f r o m t h e e s o p h a gu s . T h e cricopharyngeal muscle (CPM) is the most definitive component of this sphincter [1]. The upper esophageal sphincter is closed at rest, because the CPM is tonically contracted; demonstrating electromyographic (EMG) activity at baseline [2]. During a swallow, the CPM relaxes to allow the upper esophageal sphincter to open and a bolus to pass into the esophagus. The CPM may also play an important non-swallow role, namely regulation of upper esophageal sphincter closure. Increased upper esophageal sphincter pressure and CPM EMG activity have been found during inhalation, exhalation, and phonation [3, 4] (Figs. 1, 2, and 3). Motor innervation of the CPM has been debated for decades and needs to be further studied. Different animal and human anatomical studies have suggested that the CPM may be innervated by a single nerve such as the pharyngeal plexus (PP), glossopharyngeal nerve, cervical sympathetic ganglion, external branch of the superior laryngeal nerve (EBSLN) [5], or recurrent laryngeal nerve (RLN) [6]. Alternatively, the CPM may be innervated by the union of two or more of these nerves, such as the PP and RLN [7–9]; RLN and its sympathetic anastomoses with the middle cervical ganglion [10]; RLN and EBSLN [11, 12]; or the glossopharyngeal nerve, RLN, and EBSLN [13]. When Sasaki et al. [14] reviewed the literature, they realized that there may be several sources of confusion contributing to neuroanatomic controversy: the
Langenbecks Arch Surg Fig. 1 a A pair of needle electrodes inserted into both the CPM and CTM for the electromyographic study and the demonstration of the EBSLN stimulation with the stimulator probe (CPM cricopharyngeal nerve, CTM cricothyroid muscle, EBSLN external branch of the superior laryngeal nerve, STA superior thyroid artery). b Evoked amplitudes from the CPM (channel 4), CT muscle (channel 3), and left vocal cord (channel 1) with the stimulation of the EBSLN
use of non-human models; observational misinterpretation of small-diameter, overlapping nerve fibers; and the lack of realtime validation of motor projections. Voice symptoms after thyroidectomy are well-known implications of laryngeal nerve (RLN and EBSLN) injuries. Laryngeal nerve injuries frequently lead to swallowing problems [15, 16]. In recent years, intraoperative neural monitoring (IONM) during thyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. IONM can be used to identify and evaluate the functions of both the RLN and EBSLN. The functions of other
laryngeal muscles can also be evaluated by the various channels in multichannel IONM systems, excluding the two channels already evaluating vocal cord functionality. The CPM and cricothyroid muscle (CTM) are the muscles present in the dissection field during thyroidectomy. The function of the EBSLN is evaluated with CTM twitch on stimulation via IONM during thyroidectomy. The potential use of visual observation of CPM contractions with RLN and/or EBSLN stimulation caught our attention. The presence of real-time EMG studies in the literature is more limited than the controversial anatomical studies on CPM innervation [14, 17]. CPM
Langenbecks Arch Surg Fig. 2 a A pair of needle electrodes inserted into both the CPM and CTM for the electromyographic study and the demonstration of the RLN stimulation with the stimulator probe (CPM cricopharyngeal muscle, CTM cricothyroid muscle, RLN recurrent laryngeal nerve, STA superior thyroid artery, CCA common carotid artery, VN vagus nerve, IJV internal jugular vein, ITA inferior thyroid artery). b Evoked amplitudes from the CPM (channel 4) and right vocal cord (channel 2) with the stimulation of the right vagus nerve and RLN. The electromyographic responses were recorded with a pair of needle electrodes inserted into the CPM. The vagus nerve and recurrent laryngeal nerve were stimulated at 1 mA
innervation by the EBSLN was not detected in one study evaluating the function of the EBSLN [14]. In the present study, we evaluated the CPM innervation pattern by the RLN and EBSLN in vivo using IONM during thyroidectomy.
Materials and methods We studied a consecutive series of 27 patients (19 female, 8 male; 46 neck sides) who underwent thyroid surgery with IONM from February to April of 2015. Each side of the neck operated on was considered a separate entity in our study. The
demographic profile of each patient and the anatomy and neuromonitoring data of the RLN and EBSLN were documented at the end of each operation and recorded in a prospective database. The exclusion criteria were preoperative RLN palsy, thyroid cancer with massive extrathyroidal extension, intentional nerve transection because of cancer invasion, and failure to assess nerve function because of the technical issues. All patients underwent routine direct laryngoscopy by an independent laryngologist preoperatively and within 2 days postoperatively. RLN palsy was determined to be permanent,
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stimulated the EBSLN with a probe at a point cranial to the ligation of the vessels to confirm the integrity of the EBSLN. After dissection of the superior pole, the RLN was identified and fully dissected till its entry through the larynx under the CPM.
Neuromonitoring of CPM
Fig. 3 A pair of needle electrodes inserted into both the CPM and CTM for the electromyographic study and the demonstration of the stimulation point of PP at the posterolateral side of the superior thyroid arteries among the fibers of the inferior pharyngeal constrictor muscle at the posterior border of the thyroid lamina. (CPM cricopharyngeal muscle, CTM cricothyroid muscle, EBSLN external branch of the superior laryngeal nerve, STA superior thyroid artery, PP pharyngeal plexus, IPCM inferior pharyngeal constrictor muscle)
when there was no evidence of recovery within 6 months postoperatively. IONM technique The four-channel NIM 3.0 Nerve Monitoring System (Medtronic Xomed, Jacksonville, FL, USA) was used intraoperatively. All monitoring setup, applications, and data interpretation were in compliance with the International Neural Monitoring Guidelines [18]. The patient was placed under general anesthesia with low-dose, short-acting neuromuscular blockade (rocuronium, 0.3 mg/kg) and intubated with a size 6.0 to 8.0 endotracheal tube (NIM Standard Reinforced EMG endotracheal tube; Medtronic Xomed). The endotracheal tube electrodes (left vocal cord—channel 1, right vocal cord— channel 2), probe electrode, and grounding electrodes were plugged into the interface-connector box. Surgical technique Thyroidectomy and/or central neck dissection was performed using a 4 to 6 cm collar transverse incision. All the patients underwent total extracapsular thyroidectomy. During the superior pole dissection, the sternothyroidlaryngeal triangle was exposed with blunt dissection and searched for the EBSLN with a monopolar stimulating probe via CTM twitch assessment. An auditory signal and a clear EMG waveform with EBSLN stimulation were obtained in some cases. After ligating the superior thyroid vessels, we
EMG recordings were accomplished with a pair of needle electrodes inserted into the CTM and midportion of the CPM, located on the superior side of the RLN. These needle electrodes were plugged into the third and fourth channels of interface-connector box, respectively, at the end of the thyroidectomy. We evaluated the innervation pattern of the CTM in another study and found that the EBSLN is the main supplier of the CTM, and the EMG findings of the CTM were used to confirm this in the present study. The EMG responses of the CPM and CTM were analyzed and validated by considering the following conditions based on the studies of Faaborg-Anderson [19] and Martin-Oviedo et al. [20]. A positive response had to be at least four times greater than that of the uninnervated muscle. In our study, the mean response in the contralateral CPM was 19.1 μV with stimulation of the EBSLN, and a positive evoked response was defined as ≥100 μV. The EBSLN, PP, RLN, and vagus nerves were stimulated with a monopolar stimulator probe at 1 mA. The constant points of neural stimulations were standardized. EBSLN was stimulated at a point that is located 2 cm proximally to the nerve’s entry point to the CTM. PP was stimulated at the same level of EBSLN’s stimulation point at the posterolateral side of the superior thyroid vessels. PP is found with the monopolar stimulator probe among the fibers of the inferior pharyngeal constrictor muscle at the posterior border of the thyroid cartilage lamina. RLN was stimulated at a distance of 2 cm proximally, before it enters the larynx. In case of RLN branching, the main trunk and each branch were stimulated and evaluated by an EMG-evoked waveform. The EBSLN, RLN, vagus nerve, and PP were stimulated with a monopolar stimulator probe at 1 mA. The stimulation duration was set at 100 μs, and the current was set at a frequency of 4 Hz. While stimulating these nerves, the ipsilateral and contralateral CPMs were visually observed for possible contractions, and EMG recordings were obtained with the four-channel neuromonitoring system.
Statistical analysis All amplitude data are presented as mean and standard deviation (min–max). Visual movement and positive EMG response values are expressed as frequency and percentage.
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Results In total, 27 patients (19 female, 8 male; mean age, 45.8 years; range, 33–70 years) including 46 neck sides (24 right, 22 left) and CPMs were evaluated. The indications for surgical procedures were benign thyroid disorders (euthyroid, n = 12; hyperthyroid, n = 6); cytologically diagnosed disorders on fineneedle aspiration biopsy classified as Bethesda IV, V, or VI (n = 8); and histopathologically diagnosed malignant thyroid disease (n =1). Surgical procedures were total thyroidectomy (n = 19) including central neck dissection in two patients, lobectomy (n = 6), completion thyroidectomy (n = 1), and lobectomy with parathyroidectomy (n = 1). The visual contractions and positive EMG responses obtained with stimulation of the nerves are shown in Table 1. No EMG responses were obtained on one side with both RLN and vagus nerve stimulations in one patient with primary signal loss. EMG responses were not obtained with vagus nerve stimulation but obtained with RLN stimulation in two patients with ipsilateral transient signal loss. EMG motor activity was achieved in 32 (70 %) CPMs by both RLN and EBSLN stimulations, in 9 (20 %) CPMs by only RLN stimulation, and in 3 (6 %) CPMs by only EBSLN stimulation; 2 (4 %) CPMs showed no response. One of the last two CPMs exhibited no EMG response because of primary signal loss with RLN stimulation. Sixteen (34.8 %) branching RLNs of 46 RLNs were detected. The median branching distance was 1 cm (range 0.5– 3 cm). Positive EMG responses were obtained from CPMs with the stimulation of the anterior branches of 13 RLNs out of 16 branched RLNs. No motor activity was detected with the posterior branch stimulation. No signal was accomplished from neither the main trunks nor the anterior or posterior branches of the two branched RLNs. CPM motor innervation was evaluated electromyograpically on 31 neck sides with the stimulation of the contralateral vagus nerve, RLN, EBSLN, and PP, in 16 out of 19 bilaterally operated patients. No positive EMG responses were achieved from any of the 31 CPMs with the stimulation of the contralateral nerves. The CPM contraction was obtained only ipsilaterally. One patient had partial and one had complete transient vocal cord paralysis that resolved within 15 days and 2 months after the procedure, respectively.
Discussion The CPM is the major component of the upper esophageal sphincter. Different opinions exist regarding the anatomy and physiology of the motor nerve supply of the CPM. To our knowledge, only two studies have evaluated the motor innervation of the CPM both electrophysiologically and functionally during an operation [14, 17].
Our study has demonstrated that the PP always functionally contributes to motor innervation of the CPM. This finding is in compliance with the anatomical findings of previous human studies [7–9]. The RLN reportedly has a motor contribution to most (91 %) CPMs based on the EMG responses obtained by RLN stimulation. The EBSLN has been found to contribute to the motor innervation in 76 % of CPMs. The innervation of CPM was ipsilateral with both the EBSLN and/or RLN. The visual contractions of CPMs detected by both RLN and EBSLN stimulation may be weaker than those detected by EMG, because visual contractions may not be observed in muscles recorded with low amplitudes. Sasaki et al. [14] performed microdissection in 9 of 27 patients undergoing total laryngectomy for endolaryngeal cancer and real-time EMG CPM evaluation with PP, RLN, EBSLN, and sympathetic plexus stimulation. The authors demonstrated dual ipsilateral innervation of the CPM by the PP and RLN, segmental projection of the RLN to the anterior and PP projection to the posterior motor unit, absence of a sympathetic or EBSLN contribution, and absence of contralateral innervation. Brok et al. [17] examined the contribution of the RLN and PP to the motor nerve innervation of the CPM and inferior pharyngeal constrictor muscles with intraoperative EMG. The authors reported that the RLN contributes to the motor innervation of the CPM. Additionally, positive evoked EMG potentials of the CPM were obtained with PP stimulation in three of seven patients. The authors observed innervation of the inferior pharyngeal constrictor muscle by both the RLN and PP in all patients. Halum et al. [21] compared the EMG data of the CPM with the simultaneous EMG findings of the ipsilateral pharyngeal and laryngeal muscles at a neurology clinic in 2006. They suggested an extremely high correlation between the innervation status of the CPM and that of the inferior pharyngeal constrictor muscle (same innervation status in 27 of 28 studies). This was followed by observation of a correlation between the innervation status of the CPM and CTM (same innervation status in 40 of 50 studies) and of the CPM and thyroarytenoid muscle (same innervation status in 31 of 50 studies). These findings alone suggest that the PP plays the greatest role in CPM innervation, followed by the SLN and RLN. To the best of our knowledge, the current study is the most extensive study to evaluate the innervation of the CPM with real-time EMG. This study is also the first to demonstrate the functional contribution of the EBSLN to the motor innervation of the CPM with intraoperative EMG. Our EMG findings contrast those reported by Sasaki et al. [14], who demonstrated the absence of an EBSLN contribution to the CPM. The EBSLN was not tested in the physiological study by Brok et al. [17]. The anatomical findings of previous animal [5, 11] and human [12, 13] studies of the contribution of the EBSLN to the CPM innervation support our functional results. While the results of our study and that of Sasaki et al. [14] are similar in terms of the contribution of the PP to the motor
Langenbecks Arch Surg Table 1 Visible contractions and evoked amplitudes of the CPM with stimulation of the PP, EBSLN, RLN, and vagus nerve
Nerve
N
Visible contractions
Positive EMG response
EMG amplitude mean ± SD, μV (min–max)
PP EBSLN
46 46
46 (100 %) 28 (61 %)
46 (100 %) 35 (76 %)
2080 ± 1583 (101–8041) 686 ± 630 (100–2923)
RLN Vagus nerve
45 43
37 (82 %) 36 (84 %)
41 (91 %) 37 (86 %)
337 ± 280 (100–1556) 292 ± 229 (101–1077)
CPM cricopharyngeal muscle, PP pharyngeal plexus, EBSLN external branch of superior laryngeal nerve, RLN recurrent laryngeal nerve, EMG electromyography, SD standard deviation
innervation of all CPMs, Brok et al. [17] reported that the PP functionally contributes to the CPM in fewer than half of cases. Although the contribution of the RLN to the innervation of the CPM was 100 % in the two above mentioned studies, it was 91 % in our study. We found rates of contribution of the PP and EBSLN to the innervation of the CPM similar to those found by Halum et al. [21] (100.0 vs. 96.5 % and 76.0 vs. 80.0 %, respectively), although theirs was a clinical trial. Their rate of RLN contribution to the CPM innervation was lower than that in our study and the other physiologic study (17) (62 vs. 91 vs. 100 %, respectively). The differences in the physiologic results are similar to the different opinions among the anatomical studies in the literature. The neuroanatomic variance in the area of the larynx and upper esophageal sphincter is an enough reason to state that anatomic dissection, even with physiologic correlation, may not readily elucidate the innervation of the CPM [21]. Studies based on anatomic dissection of canine models have revealed that the CPM is supplied by the pharyngeal branch of the vagus nerve [22] or by the vagus and sympathetic nerves [23]. Lund and Andran [24] reported that the PP is the main supplier of nerve fibers to all pharyngeal muscles excluding the stylopharyngeal muscle. Hwang et al. [11] suggested that the CPM is innervated by terminal branches of the RLN and PP or by the PP of the vagus nerve. Other researchers have suggested that the CPM is also innervated by the EBSLN in different animal models [5, 11]. Human anatomical studies have also demonstrated differing sources of CPM innervation. Steinberg et al. [8] found that the CPM is supplied by the branches of the RLN and their sympathetic anastomoses with the middle cervical ganglion. Other investigators have found that the CPM receives input from the PP and RLN [7–9]. Mu and Sanders [8] reported that the CPM receives its innervation from below via the RLN and from above via the PP. Most recently, in 2007, Mu and Sanders [13] found that in addition to the PP and RLN, the EBSLN also supplies branches to innervate the CPM. Prades et al. [12] suggested that the posterior part of the CPM is supplied by the RLN and the anterior part of the CPM is supplied by the lateral branch of the SLN.
CPM innervation may also vary according to the anastomosis between the nerves. By general consensus, the pharyngeal branches of the glossopharyngeal and vagus nerves communicate to form the PP [9, 25]. Mu and Sanders [13] mapped the entire human PP with Sihler’s stain. They found that the adult human PP mainly comprises the pharyngeal branches of the glossopharyngeal and vagus nerves with less contribution from the EBSLN and the sympathetic nerve fibers derived from the superior ganglion [12]. Some studies have observed connections between the RLN and PP in the CPM [8, 9, 13]. The communications of the PP with the external and internal branches and main trunk of the SLN were sometimes found [9]. The loops were found between the cervical sympathetic chain and the SLN or its branches [26, 27]. Connections between the RLN and the internal or external branch of the SLN have been documented in 15 to 100 % cases in a variety of dissection studies [28]. Sanuda et al. [29] found that at least two anastomoses (the Galen anastomosis and the arytenoid plexus) appeared in 21 % of hemilarynges, and 79 % of cases had three or more anastomoses between the RLN and branches of the SLN. Maranillo et al. [30] demonstrated one or more communicating branches between the EBSLN and RLN in 85 % of 103 human cadaver larynges. Electrical stimulation of one of these nerves that communicates with another may result in stimulation of any interconnected muscle, regardless of its innervation source [12]. The RLN and EBSLN were stimulated at the level of their main trunks in the current study. We found that EMG motor activity was achieved by both RLN and EBSLN stimulation in 70 % of the CPMs evaluated. This finding suggests that the various anastomoses between the nerves may also contribute to the motor innervation of the CPM. The RLN and EBSLN are inevitably at risk during surgery of the neck, skull base, and chest [31]. Thyroid surgery is the most common cause of injury to the RLN and EBSLN [32]. Injury to one or both of these nerves may disturb various voice, airway, and swallowing functions [33]. These symptoms may be related to injury to the extrinsic perithyroidal neural plexus, which innervates the pharyngeal and laryngeal structures [15, 16]. The thyroid surgeon must be familiar with the laryngeal neuroanatomy and various manifestations of
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laryngeal nerve injuries [33]. Nerve injuries may alter the swallowing function depending on the complex motor innervation of the CPM. Therefore, during thyroidectomy, preservation of the laryngeal nerves is equally as important for the innervation of the CPM and other pharyngeal muscles as for the innervation of the intrinsic laryngeal muscles.
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Conclusion
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This is the first report to provide evidence that the EBSLN functionally contributes to the motor innervation of the human CPM. The RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively.
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Authors’ contributions Study conception and design: Mehmet Uludag Acquisition of data: Nurcihan Aygun Analysis and interpretation data: Mehmet Uludag, Nurcihan Aygun, Adnan Isgor Drafting of manuscript: Mehmet Uludag, Nurcihan Aygun Critical revision of manuscript: Mehmet Uludag, Adnan Isgor
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Compliance with ethical standards 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 Langenbeck’s Archives of Surgery.
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Conflicts of interest The authors declare that they have no conflict of interest.
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Funding None.
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Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee 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. This prospective study was approved by the Institutional Review Board of Sisli Hamidiye Etfal Training and Research Hospital.
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Informed consent Informed consent was obtained from all individual participants included in the study. 19.
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