Intra-Operative Detection of a Left-Sided Non-Recurrent Laryngeal Nerve During Vagus Nerve Stimulator Implantation

medicina

Case Report Intra-Operative Detection of a Left-Sided Non-Recurrent Laryngeal Nerve during Vagus Nerve Stimulator Implantation

Jason John Labuschagne 1,2,3,* and Niels Hammer 4,5,6,*

1 Netcare Unitas Hospital, Centurion 0140, South Africa 2 Department of Neurosurgery, University of Witwatersrand, Johannesburg 2193, South Africa 3 Department of Pediatric Neurosurgery, Nelson Mandela Children’s Hospital, Johannesburg 2193, South Africa 4 Department of Macroscopic and Clinical Anatomy, Medical University of Graz, 8010 Graz, Austria 5 Department of Trauma, Orthopedic and Plastic Surgery, University Hospital of Leipzig, 04109 Leipzig, Germany 6 Fraunhofer Institute for Machine Tools and Forming Technology, 01187 Dresden, Germany * Correspondence: [email protected] (J.J.L.); [email protected] or [email protected] (N.H.); Tel.: +43-316-38571100 (N.H.)

Received: 22 August 2020; Accepted: 18 September 2020; Published: 23 September 2020

Abstract: Left sided non-recurrent laryngeal nerves (NRLN) are very rarely observed during surgery in the head and neck region. Arising directly from the cervical aspect of the vagus nerve, the NRLN lies in a vulnerable position distant from its normal location. NRLNs are normally associated with embryological branchial arch aberrations and subsequent vascular anomalies. The anomalous course of the NRLN makes it more susceptible to injury during surgery in the neck region. Knowledge of this anatomical variant will reduce the potential for injury and resultant vocal cord paralysis. During microsurgical dissection of the carotid sheath for the implantation of a vagus nerve stimulator in a 19-year-old female patient with refractory epilepsy, a moderate-sized branch of the main vagus nerve trunk was identified postero-medially within the carotid sheath. Intra-operative stimulation of this nerve resulted in a compound muscle evoked potential from the left vocal cord. Thus, this branch was confirmed to be a left-sided NRLN. The patient had no associated vascular anomalies. This is first reported case of a left-sided NRLN found during VNS insertion. Awareness of the possibility of an NRLN is imperative to prevent iatrogenic injury. A medial location of the vagus nerve within the carotid sheath should alert the surgeon to the possible presence of an NRLN. The absence of fourth branchial arch remnant anomalies is not a guarantee as to the absence of a left-sided NRLN. The addition of intra-operative nerve monitoring for vagus nerve stimulator (VNS) implantation procedures should be strongly considered to help avoid iatrogenic injury.

Keywords: nerve stimulation; non-recurrent laryngeal nerve; seizure treatment; vagus nerve; vagal trunk; variational anatomy

1. Introduction Left sided non-recurrent laryngeal nerves (NRLN) are very rarely observed during surgery in the head and neck region. In “non-anomalous” cases, the right recurrent laryngeal nerve (RLN) arises from the right vagus nerve anterior to the ﬁrst part of the subclavian artery, it then hooks around the right subclavian artery and ascends towards the tracheo-oesophageal groove before entering the larynx [1]. On the left side, the RLN is given oﬀ by vagus at the inferior border of the arch of the aorta, it then passes inferior to the arch of the aorta, immediately lateral to the ligamentum arteriosum,

Medicina 2020, 56, 489; doi:10.3390/medicina56100489 www.mdpi.com/journal/medicina Medicina 2020, 56, x FOR PEER REVIEW 2 of 5 it then passes inferior to the arch of the aorta, immediately lateral to the ligamentum arteriosum, and Medicina 2020, 56, 489 2 of 6 ascends in the tracheo-oesophageal groove to the larynx [1]. Non-recurrent laryngeal nerves arise directly from the cervical aspect of the vagus nerve to enter the larynx directly without first descendingand ascends to in the the thoracic tracheo-oesophageal level. NRLNs groove have tobeen the reported larynx [1 ].in Non-recurrentonly 0.3–0.8% laryngeal[2] of the nervespopulation arise ondirectly the right from side, the cervical and they aspect are extremely of the vagus rare nerve on th toe enterleft side, the larynxwith a directly reported without incidence ﬁrst of descending less than 0.004%to the thoracic [2]. Indeed, level. to NRLNsour knowledge, have been only reported four ca inses only of left-sided 0.3–0.8% NRLNs [2] of the have population been reported on the [3]. right side,The and anomalous they are extremely course of rare the onNRLN the leftmakes side, it withmore a susceptible reported incidence to injury of during less than surgery 0.004% in the [2]. neckIndeed, region. to our Knowledge knowledge, of only both four the cases normal of left-sided anatomy NRLNs and anatomical have been reportedvariants [of3]. the recurrent laryngealThe anomalous nerve should course serve of to the reduce NRLN iatrogenic makes itmore injury susceptible to the nerve. to injury We report during a case surgery of a inleft the NRLN neck discoveredregion. Knowledge during vagus of both nerve the st normalimulator anatomy implantation and anatomical (VNS). variants of the recurrent laryngeal nerve should serve to reduce iatrogenic injury to the nerve. We report a case of a left NRLN discovered 2.during Case vagusReport nerve stimulator implantation (VNS).

2. CaseA 19-year-old Report female patient with drug-resistant epilepsy, who was not considered a suitable candidate for resective epilepsy surgery, was offered vagal nerve stimulation for seizure control. SurgeryA 19-year-old was performed female patient under with general drug-resistant anaesthesia epilepsy, after whothe administration was not considered of intravenous a suitable antibioticscandidate forand resective under strict epilepsy aseptic surgery, protocol. was o Theffered patient vagal nervewas placed stimulation supine for with seizure the control.head in the midlineSurgery and a wasslightly performed extended under position. general A horizontal anaesthesia neck afterincision the was administration made at the level of intravenous of the mid larynx,antibiotics halfway and under between strict asepticthe clavicle protocol. and Themastoi patientd process. was placed The supinesternocleidomastoid with the head in muscle the midline was dissectedand a slightly along extended its anterior position. aspect A horizontaland retracted neck posteriorly. incision was A made combination at the level of ofsharp the midand larynx, blunt dissectionhalfway between was used the to clavicle expose and a 4-cm mastoid long process. segmen Thet of the sternocleidomastoid carotid sheath. The muscle fibrous was connective dissected tissuealong itsof the anterior sheath aspect was opened and retracted with atraumatic posteriorly. forceps A combination by splitting of the sharp fibres and of blunt the sheath dissection medially was andused laterally to expose to a reveal 4-cm longthe contents segment of the carotidcarotid sheath.sheath. TheFurther fibrous dissection connective was tissue performed of the sheathunder wasmicroscopic opened withvisualisation. atraumatic (Zeiss, forceps Kinevo by splitting 900, Carl the Zeiss fibres AG, of the Oberkochen, sheath medially Germany). and laterally to reveal the contentsDuring ofdissection the carotid of the sheath. carotid Further sheath, dissection a moderat wase-sized performed branch under of the microscopic main vagus visualisation. nerve trunk (Zeiss,was identified Kinevo postero-medially 900, Carl Zeiss AG, wi Oberkochen,thin the carotid Germany). sheath (Figure 1). Vessel loops were placed around the proximalDuringdissection and distal ofends the of carotid the main sheath, vagal amoderate-sized trunk and around branch the proximal of the main portion vagus of nerve the medial trunk wasbranch. identified Intra-operative postero-medially stimulation within (0.3 themA carotid monopolar sheath stimulation) (Figure1). Vesselwas delivered loops were by a placed commercially around availablethe proximal neurostimu and distallator ends (Medtronic of the main NIM vagal® Eclipse, trunk Minneapolis, and around the MN, proximal USA) to portion the vagus ofthe trunk medial and tobranch. the medial Intra-operative branch. The stimulation vocal cord (0.3 responses mA monopolar were stimulation)recorded by wasa commercially delivered by available a commercially EMG ® embeddedavailable neurostimulator endotracheal tube (Medtronic device used NIM to deEclipse,tect vocal Minneapolis, cord responses MN, USA)(Medtronic to the NIM vagus® Flex, trunk EMG and Tube,to the Minneapolis, medial branch. MN, The USA). vocal Stimulation cord responses of the werecommon recorded trunk by and a commerciallymedial branch available both elicited EMG a ® compoundembedded endotrachealmuscle evoked tube potential device from used the to left detect vocal vocal cord. cord A similar responses latency (Medtronic period of NIM 6 ms Flex,was detectedEMG Tube, following Minneapolis, stimulation MN, USA). of both Stimulation the trunk of and the the common medial trunk branch; and however, medial branch the amplitude both elicited of thea compound compound muscle muscle evoked potential potential was approximately from the left vocal halfcord. when A the similar vagal latency trunk periodwas stimulated of 6 ms was as opposeddetected followingto the medial stimulation branch stimulation. of both the trunk and the medial branch; however, the amplitude of the compoundThe VNS muscle coils potentialof the VNS was Stimulator approximately (AspireSR, half when model the 106, vagal Cyberonics trunk was Inc. stimulated Houston, as TX, opposed USA) wereto the placed medial around branch the stimulation. main vagal trunk, away from the branching point. (Figure 2).

Figure 1. Intra-operative images images showing showing an an aberrant aberrant br branchanch (small (small white white arrow) of the left vagus nerve (large white arrow) in the cervical sheath identiﬁedidentified asas aa non-recurrentnon-recurrent laryngeallaryngeal nerve.nerve.

Medicina 2020, 56, 489 3 of 6

The VNS coils of the VNS Stimulator (AspireSR, model 106, Cyberonics Inc. Houston, TX, USA) were placed around the main vagal trunk, away from the branching point. (Figure2). Medicina 2020, 56, x FOR PEER REVIEW 3 of 5

Figure 2. Vagus nerve stimulator (VNS) electrode placed around the main vagal trunk (white arrow) with the aberrant branch displaced medially at the branching point (white arrowhead) on the left side.

The leadlead wirewire was was passed passed subcutaneously subcutaneously to anto an infraclavicular infraclavicular subcutaneous subcutaneous pocket. pocket. Then, Then, the lead the waslead attachedwas attached to the to implantable the implantable pulse generator.pulse genera Theretor.were There no were cardiac no responsescardiac responses to intra-operative to intra- testoperative stimulation. test stimulation. The wound The was wound closed was in anatomical closed in layers.anatomical The patientlayers. hadThe nopatient intra-operative had no intra- nor post-operativeoperative nor post-operative complications. complications. A routine chest A routin X-raye chest was performedX-ray was performed as part of as the part pre-operative of the pre- workup,operative andworkup, this didand notthis demonstratedid not demonstrate evidence evi ofdence situs of invertus situs invertus or a right-sided or a right-sided aortic aortic arch. Additionalarch. Additional investigations investigations for vascular for vascular anomalies anomalies were notwere performed. not performed. The patient was seen for regular follow-up visits. During follow up, a structured questionnaire designed to elicit anyany laryngopharyngeallaryngopharyngeal symptomssymptoms waswas administered.administered. The patient presented no evidence of vagal nerve dysfunction. At At six-mont six-monthh follow follow up, up, she she had had responded responded well well to to the VNS, with a reduction inin seizureseizure frequencyfrequency andand severity.severity.

3. Discussion To ourour knowledge,knowledge, this this is is the the first first reported reported case case of of an an NRLN NRLN in thein the setting setting of VNS of VNS implantation implantation and oneand ofone the of fewthe casesfew cases in which in which the coursethe course of the of NRLNthe NRLN is described is described both both within within the carotidthe carotid sheath sheath and onceand once exiting exiting the sheath. the sheath. According According to our knowledge,to our know it isledge, also theit is first also reported the first case reported to demonstrate case to thedemonstrate benefit of the standard benefit intra-operative of standard intra-operativ nerve monitoringe nerve (IONM) monitoring in the (IONM) setting in of the VNS setting implantation of VNS inimplantation delineating in anatomical delineating variations anatomical in variations this region in and this the region potential and the of IONMpotential to of assist IONM in avoiding to assist iatrogenicin avoiding injury. iatrogenic injury. Embryologically, the recurrent laryngeal nerves (RLNs), also frequently referred to as the “inferior“inferior laryngeallaryngeal nerves”, are derived from the VI branchial arch and have a horizontal course. course. Subsequently, the V and distal portion of the VI branchialbranchial arches regress bilaterally, and the RLNs remain anchoredanchored toto structures structures that that develop develop from from the the IV IV branchial branchial arch: arch: the the aortic aortic arch arch on theon the left left and and the subclavianthe subclavian artery artery on the on right the right [4,5]. [4,5]. As the As heart the he descendsart descends and the and neck the elongates,neck elongates, the nerves the nerves are pulled are intopulled an into intrathoracic an intrathoracic position, position, and therefore, and therefor they neede, they to assumeneed to a assume recurrent a recurrent course. The course. recurrent The laryngealrecurrent laryngeal nerves (RLNs) nerves run (RLNs) a diff erentrun a coursedifferent on course each side. on each On theside. right, On the they right, arise they from arise the rightfrom vagusthe right nerve vagus anterior nerve toanterior the first to partthe first of the part subclavian of the subclavian artery. Then, artery. the Then, right the RLN right hooks RLN around hooks thearound right the subclavian right subclavian artery and artery ascends and towards ascend thes towards tracheo-oesophageal the tracheo-oesophageal groove before groove entering before the larynxentering [1 ].the On larynx the left [1]. side, On thethe RLN left side, is given the oRLNff by vagusis given at off the by inferior vagus border at theof inferior the arch border of the of aorta. the Thearch leftof RLNthe aorta. passes The inferior left RLN to the passes arch of inferior the aorta, to immediatelythe arch of the lateral aorta, to theimmediately ligamentum lateral arteriosum, to the andligamentum ascends inarteriosum, the tracheo-oesophageal and ascends in groovethe trac toheo-oesophageal the larynx [1]. groove to the larynx [1]. The NRLN is a rare anomaly in which the NRLN branches off the cervical vagal trunk to enter the larynx directly from within the carotid sheath, without first descending to the thoracic level. It has been reported in only 0.3–0.8% [2] of the population on the right side, and it is extremely rare on the left side, with a reported incidence of less than 0.004% [2]. Indeed, to our knowledge, only four cases of left-sided NRLNs have been reported [3]. Three types of NRLN have previously been distinguished [6]: type 1 NRLNs arise directly from the vagus and run together with the vessels of the superior thyroid peduncle; type 2a NRLNs follow

Medicina 2020, 56, 489 4 of 6

The NRLN is a rare anomaly in which the NRLN branches off the cervical vagal trunk to enter the larynx directly from within the carotid sheath, without first descending to the thoracic level. It has been reported in only 0.3–0.8% [2] of the population on the right side, and it is extremely rare on the left side, with a reported incidence of less than 0.004% [2]. Indeed, to our knowledge, only four cases of left-sided NRLNs have been reported [3]. Three types of NRLN have previously been distinguished [6]: type 1 NRLNs arise directly from the vagus and run together with the vessels of the superior thyroid peduncle; type 2a NRLNs follow a transverse path parallel to and over the trunk of the inferior thyroid artery; and type 2b NRLNs follow a transverse path parallel to and under the trunk or between the branches of the inferior thyroid artery. The case presented here is an example of a type 1 NRLN. Most descriptions of the NRLN describe the path of the nerve once it exits the carotid sheath, as this is of most relevance to thyroid and parathyroid surgery. Very little is described regarding NRLN anatomy within the carotid sheath. Gurleyik [7] described a case of a right-sided NRLN discovered during a total thyroidectomy in which they followed the NRLN back into the carotid sheath and found that the length of the nerve from its origin, the trunk of the vagus nerve, to the laryngeal entry point was 4 cm. In this case report of Gurleyik [7], the trunk of the vagus nerve ran parallel and antero-medially within the carotid sheath. The association between the vagus nerve being located medially, within the carotid sheath, to the common carotid and the presence of a NRLN is emphasised by Toniato et al. [6], who describe this medial location of the vagal trunk as a “pilot light” to the possible presence of an NRLN. However, this medial location is not an absolute, as Coady et al. [8] described a case of a left NRLN in a patient undergoing a carotid endarterectomy in which the vagus nerve was anterolateral to the carotid artery and the NRLN crossed anterior to the carotid to reach the larynx. In the present case, the vagus trunk was in a postero-medial location to the common carotid. Generally speaking, the non-recurrence of the right laryngeal nerve results from a vascular anomaly during embryonic development of the aortic arches, with the resultant absence of the innominate artery and the formation of an aberrant right subclavian artery, the so-called arteria lusoria, which arises directly from the aorta left of the midline and crosses the oesophagus. For non-recurrence of the left-sided laryngeal nerve, a triad of fourth branchial arch remnant anomalies are required: a right-sided aortic arch with an associated situs inversus; a right-sided ligamentum arteriosum, and a left subclavian artery with a lusoria course [9]. However, up to 11% of reported right-sided NRLNs are not associated with a subclavian artery abnormality [10]. To our knowledge, only one case [8] prior to the currently presented case has been reported of a left NRLN without an associated vascular anomaly. The current case had no evidence of fourth branchial arch anomalies. The embryological pathogenesis of an NRLN with an associated vascular anomaly is understood, but the presence of the variant nerve without the accompanying vascular anomaly “remains a mystery” [10]. Some authors have challenged the viability of an NRLN without a branchial arch anomaly [9,11,12] and have noted that “the origin of the non-recurrent nerve was never confirmed as the vagus nerve” [12]. Raffaelli et al. [9] posit that an NRLN in the patients without vascular anomaly is in fact a “false NRLN”. This “false NRLN” is thought to be an anastomotic nerve between the sympathetic chain and the RLN that has a similar diameter and size as an NRLN [13]. In their manuscript, Tateda et al. [3] reported a case of NRLN without a vascular anomaly, in whom vocal cord mobility was proven by intra-operative nerve stimulation of the NRLN. If in this case it was a “false NRLN”, it would imply that the sympathetic trunk is involved in vocal cord function, which has never been shown to be the case [3]. Likewise, in the case presented here, IONM confirmed a compound action potential from the left vocal cord implying a “true” NRLN. As far as we are aware, this is the first reported case of an NRLN in the setting of VNS therapy. Despite the widespread use of intra-operative nerve monitoring (IONM) in head and neck endocrine surgery [14,15], IONM is not routine practice for VNS insertion, with few surgical units [16] describing its use to minimise voice-related side effects. Interestingly, Dolezel et al. [11] reported that the use of IONM in thyroid surgery increased the prevalence of NRLN detection, yet it decreased the incidence of Medicina 2020, 56, 489 5 of 6 post-operative palsy. Our unit uses IONM as standard practice, and in the current case, its availability was invaluable in confirming the presence of the NRLN.

4. Conclusions Awareness of the possibility of an NRLN within the carotid sheath during VNS implantation or any other surgery involving dissection of the carotid sheath is imperative to prevent iatrogenic injury to the vagus nerve and its branches. A medial location of the vagus nerve within the carotid sheath should alert the surgeon to the possible presence of an NRLN. The absence of fourth branchial arch remnant anomalies is not a guarantee as to the absence of a left-sided NRLN. The addition of IONM for VNS implantation procedures should be strongly considered to help avoid iatrogenic injury.

Ethical Considerations: The Human Research Ethics Committee of the University of the Witwatersrand approved the presentation of the case report (reference number M190610, date: 28 June 2019). Author Contributions: Conceptualization, methodology, original draft preparation, writing—review and editing, J.J.L. and N.H. All authors have read and agreed to the published version of the manuscript. Funding: We acknowledge support from the German Research Foundation (DFG) (http://www.dfg.de/en/) and the University Leipzig within the program of funding Open Access Publishing. Conﬂicts of Interest: The authors declare no conﬂict of interest.

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