Reconstruction of laryngeal function for recurrent laryngeal nerve paralysis: historical view, advancement of latest investigations and a preliminary experiment.

Historical investigations of the functional restoration for recurrent laryngeal nerve paralysis are reviewed and some advancement in recent studies are introduced. A preliminary experiment is reported in which the ansa hypoglossi and the sternothyroid muscle pedicle was implanted into the denervated posterior cricoarytenoid muscle in dogs. From these experiments we have concluded that the ansa hypoglossi and sternothyroid muscle pedicle, which has been shown to transmit efferent inspiratory bursts, is capable of restoring function to the paralyzed posterior cricoarytenoid muscle in some dogs.     

Functional results after experimental reinnervation of the posterior cricoarytenoid muscle in dogs

The purpose of the present investigation was to test and compare three different types of experimental posterior cricoarytenoid (PCA) muscle reinnervation. Dogs were subjected to reinnervation by the recurrent nerve itself (self-reinnervation) (n = 6), by the ansa cervicalis nerve (n = 5) or by the phrenic nerve (n = 5). In all but three of the self-reinnervation cases the adductor branch of the nerve was cut and ligated. Three to seven months postoperatively--depending upon the experimental approach--the animals were anesthetized and the function of the vocal cords was tested, visually evaluated and photographed. In the self--reinnervated larynges there were no observable movements on the reinnervated side during quiet inspiration, while during forced inspiration there were small but inconsistent movements. In the larynges reinnervated by the ansa cervicalis nerve no movements could be observed on the reinnervated side during either quiet or forced respiration. In four out of five larynges reinnervated by the phrenic nerve there were larger excursions on the reinnervated side as compared to the normal side during quiet respiration. During forced inspiration the excursions increased on both sides, but relatively more on the normal side. In all experiments indirect electrical stimulation gave large excursions on the experimental side indicating successful reinnervation. It is concluded that the phrenic nerve appears to be the best alternative if reinnervation of the PCA muscle in paralyzed larynges is attempted.     

Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization

OBJECTIVE: To determine if selective reinnervation of the cricothyroid muscle could be achieved with muscle-nerve-muscle neurotization. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three consecutive patients with high vagal lesions that resulted in unilateral laryngeal paralysis. INTERVENTIONS: Patients underwent laryngeal reinnervation with ansa hypoglossi to recurrent laryngeal nerve anastomosis. In addition, patients underwent selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization technique. MAIN OUTCOME MEASURES: Objective and subjective improvement in voice quality and electromyographic evidence of selective reinnervation of the cricothyroid muscle. RESULTS: All patients recovered normal or near-normal speaking voice and had normal objective measures of voice quality. They also showed electromyographic evidence of cricothyroid muscle reinnervation. CONCLUSION: The muscle-nerve-muscle neurotization technique was successful in providing selective reinnervation of the cricothyroid muscle in our 3 patients.     

A histochemical evaluation of experimentally reinnervated canine laryngeal muscles

Sixteen dogs underwent different types of experimental reinnervation procedures of the posterior cricoarytenoid (PCA) muscle - reinnervation by the recurrent nerve itself (self-reinnervation) (n = 6), by the ansa cervicalis nerve (n = 5) or by the phrenic nerve (n = 5). After functional evaluation the normal left and the reinnervated right PCA muscles were removed for histochemical analysis. Cryostat sections were incubated for actomyosin ATPase, NADH-TR and alpha-GPDH. All muscles showed microscopical evidence of successful reinnervation. There was a slight change in the muscle fiber type composition in the reinnervated muscle as compared to the normal side. Incubations for the NADH-TR and alpha-GPDH showed less staining intensity in the reinnervated muscles. The histochemical differences between normal and reinnervated muscles were small, however, and probably of minor importance with regard to the function of the muscles.     

Contractile properties of canine thyroarytenoid muscle reinnervated from the ansa cervicalis

In an attempt to obtain data on the contractile properties of vocal fold muscle reinnervated from the ansa cervicalis, we severed the recurrent nerve and connected its distal stump to the ansa cervicalis by an end-to-end anastomosis in a series of dogs. Each dog was allowed to heal for 5 months. Then the section of the thyroid cartilage on which the vocal fold muscle inserted was detached, connected to an isometric force transducer, and activated by indirect stimulation successively on both the operated and unoperated sides. A series of twitch contractions was recorded from each side. In two dogs no contractile response was obtained. In the three others, the twitch contraction time was increased significantly, by 23% to 60%. In two of three dogs, the operated muscle was significantly weaker than the unoperated muscle. The reinnervated thyroarytenoid muscle changed its speed in the direction of the donor sternothyroid muscle.     

Recurrent nerve/ansa cervicalis nerve anastomosis: a treatment alternative in unilateral recurrent nerve paralysis.

Sectioning of the right recurrent nerve was done in 5 mongrel dogs under general anaesthesia. The distal stump was anastomosed with the ansa cervicalis nerve branch to the sternothyroid muscle. Three to 5 months later the vocal cord movements during light and very light anaesthesia were videorecorded. Under light anaesthesia contraction and medial bulging of the reinnervated right vocal cord occurred in 4 of the dogs. Under very light anaesthesia there was also some adduction of the right vocal cord in these 4 dogs. The right recurrent nerve was then sectioned proximally to the anastomosis and stimulated electrically. In all 5 dogs we observed that electrical stimulation produced a strong adduction of the right vocal cord. Histochemistry of the right vocal and posterior cricoarytenoid muscles showed that reinnervation had taken place. The study indicates that in cases of unilateral vocal cord paralysis an anastomosis between the ansa cervalalis and the recurrent nerve will result in improved phonatory function of the affected vocal cord.     

Motion-specific laryngeal reinnervation using muscle-nerve-muscle neurotization

There is no current treatment method that can reliably restore physiologic movement to a paralyzed vocal fold. The purposes of this study were to test the hypotheses that 1) muscle-nerve-muscle (M-N-M) neurotization can be induced in feline laryngeal muscles and 2) M-N-M neurotization can restore movement to a paralyzed vocal fold. Muscle-nerve-muscle neurotization can be defined as the reinnervation of a denervated muscle via axons that are induced to sprout from nerves within an innervated muscle and that then traverse a nerve graft interposed between it and the target denervated muscle. A paralyzed laryngeal muscle could be reinnervated by axons from its contralateral paired muscle, thus achieving motion-specific reinnervation. Eighteen adult cats were divided into sham, hemilaryngeal-denervated, and M-N-M-reinnervated thyroarytenoid muscle groups. Five of the 6 reinnervated animals had histologic evidence of axons in the nerve graft, 4 of the 6 had evoked electromyographic evidence of crossed reinnervation, and 1 of the 6 had a return of appropriately phased adduction. This technique has great potential and should be further investigated.     

Recurrent Nerve/Ansa Cervicalis Nerve Anastomosis: A Treatment Alternative in Unilateral Recurrent Nerve Paralysis

Sectioning of the right recurrent nerve was done in 5 mongrel dogs under general anaesthesia. The distal stump was anastomosed with the ansa cervicalis nerve branch to the sternothyroid muscle. Three to 5 months later the vocal cord movements during light and very light anaesthesia were videorecorded. Under light anaesthesia contraction and medial bulging of the reinnervated right vocal cord occurred in 4 of the dogs. Under very light anaesthesia there was also some adduction of the right vocal cord in these 4 dogs. The right recurrent nerve was then sectioned proximally to the anastomosis and stimulated electrically. In all 5 dogs we observed that electrical stimulation produced a strong adduction of the right vocal cord. Histochemistry of the right vocal and posterior cricoarytenoid muscles showed that reinnervation had taken place. The study indicates that in cases of unilateral vocal cord paralysis an anastomosis between the ansa cervicalis and the recurrent nerve will result in improved phonatory function of the affected vocal cord.     

Newer technique of laryngeal reinnervation: superior laryngeal nerve (motor branch) as a driver of the posterior cricoarytenoid muscle

This report analyzes the experience gained using two different techniques to reinnervate the paralyzed vocal cord. In the neurotization group, the superior laryngeal nerve (SLN) motor branch-cricothyroid muscle pedicle was used to reinnervate the posterior cricoarytenoid muscle. In the direct nerve anastomosis group, the SLN was anastomosed to the abductor branch of the recurrent laryngeal nerve (RLN), and the ansa hypoglossi (AH) to the adductor branch of the RLN. A third group of animals (control) had the right RLN sectioned without any anastomosis. About 5 to 6 months postoperatively the animals were killed painlessly and evaluated. The neurotization group revealed vocal fold mobilization on the right side to have an average of about half of the mobility of the left, normal side. After the RLN and SLN on the left were severed as well as the AH bilaterally, the vocal cord mobility was reduced to about one fourth. The direct nerve anastomosis group showed about fourfold less vocal cord mobility than the neurotization group. After the SLN, RLN, and AH were severed bilaterally, the control group showed no vocal cord mobility. The neurotization technique has been selected for further experimentation in human adults.     

Recovery of inspiratory abduction of the paralyzed vocal cords after bilateral reinnervation of the cricoarytenoid muscles by one single branch of the phrenic nerve

The aim of this study was to provide the bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by the superior root of the right phrenic nerve. In six adult cats, the right phrenic root was anastomosed to the distal stump of the transected recurrent laryngeal nerve (RLN) on the same side. The RLN adductor branch was then cut and anastomosed to a nerve graft whose end was carried contralaterally and sutured to the left RLN or to the left PCA muscle. The phrenic fibers regrowing along the RLN abductor branch reinnervated the right PCA muscle and restored the inspiratory abduction of the right vocal cord in all the animals. In five of the six cats, the fibers regenerated through the RLN adductor branch and the graft reached the left PCA muscle and also restored the inspiratory opening of the larynx on the left side. Histological nerve examination revealed a fairly symmetrical distribution of the regenerated phrenic axons to the right and left PCA muscles.     

Electromyography of the infrahyoid muscles - part 1: normal findings]

BACKGROUND: The infrahyoid muscles (IHM) are very useful as a neurovascular myofascial flap in plastic reconstructive surgery of the upper aerodigestive tract, especially for restoration of the muscular component in larger tongue defects. As a base for further postoperative investigations on the function of transferred IHM this first part of the study describes the physiological function and the electromyographical features of the IHM. METHODS: In 17 patients with cancer of the upper aerodigestive tract the sternohyoid and sternothyroid muscles and in additionally eight patients the upper part of the omohyoid muscle were studied electromyographically. Muscular activity was recorded at various movements and maximal voluntary innervation. In ten healthy volunteers the motor unit potentials (MUP) during light voluntary innervation of these muscles were studied. RESULTS: In both muscles we found the steadist and strongest muscular activity at isometric head bending and yaw opening, in the omohyoid muscle also at head rotation. At swallowing and breathing in (2/3) of the cases muscular activity could be recorded. Amplitudes and electromyographic charge pattern in comparison were diminished. Phonation und tongue movements showed no noticable muscular activity. Analysis of the MUP in 10 healthy volunteers showed a mean amplitude of 274 +/- 59 microV and a mean duration of 8.5 +/- 0.6 ms. CONCLUSIONS: The presented study demonstrates that EMG of the IHM are recorded best while head bending, yaw opening and head rotation. Since there is no interchange of nerve fibres between the hypoglossal nerve and the cervical ansa it should be possible to differentiate between original tongue muscles and transferred muscles in electromyographic studies of myofascial flaps after tongue reconstruction.     

膈神经替代喉返神经修复治疗双侧声带麻痹

目的 探讨膈神经喉返神经吻合和内收肌支环杓后肌植入术（膈神经手术）治疗双侧喉返神经损伤声带麻痹的有效性、可行性。方法 第二军医大学长海医院耳鼻咽喉科1999年8月－2001年7月治疗外伤性双侧喉返神经损伤声带麻痹6例。病程1周－18个月，一侧作膈神经手术，而另一侧作颈袢肌蒂环杓后肌植入术。手术前后电子喉镜、频闪喉镜观察声门大小、声珲运动、振动情况，噪音声学参数分析，喉肌电力产检查评价手术效果。结果 术后2－3周检查发现4例声门较术前增大2－3mm，但声带固定不动，2例无明显改善。术后6个月5例膈神经修复侧均恢复了较大幅度的吸气性声带外展功能，外展幅度可达3－5mm，而肌蒂植入侧仅轻微外展或固定不动，幅度均在1mm以内。此5例均顺利拔管，并能承受较大强度的体力活动，1例仍在随访中。术后4个月6例肌电图检查显示膈神经修复侧自发、诱发电位均明显大于肌蒂植入侧，自发电活动与肋间肌基本同步，而较肌蒂植入侧延迟100－200ms。声音估价显示3例声嘶术后较术前好转，2例无变化。术后半年肺功能均恢复正常。结论 膈神经喉返神经吻合内收肌支环杓后肌植入术安全可行，较颈袢肌蒂植入术更能有效地恢复声带吸气性外展运动，值得临床推广应用。     

Study on contractile properties of the posterior cricoarytenoid muscle after delayed reinnervation]

To study date on the contractile properties of posterior cricoarytenoid muscle after delayed reinnervation of different reinnervated methods. Twenty four dogs were reinnervated at 0,4,5,6,10 and 12 month interval following recurrent laryngeal nerve via the phrenic nerve anastomosed to the recurrent laryngeal nerve after cutting the adductor branch and ansa cervicalis-sternothyroid muscle pedicle implanted into the posterior cricoarytenoid muscle. After 6 months, a series of contractions were recorded from each side in twenty living dogs. The results showed that contractile force of reinnervated muscle decreased gradually with the time of denervation, but contractile force of muscle was no significantly difference between reinnervated side of nerve anastomosed group in 4 months after denervated and normal side, and it was significantly difference between nerve anastomosed group and nerve-muscle pedicle implanted group at some time of delayed reinnervation. The contractile time of reinnervated side of two operated groups was similar to that of normal side. The conclusion demonstrated that the contractile properties can indicate exactly reinnervated degree of muscle, and the earlier reinnervation was performed, the better curative effect was.     

Muscle transfer for laryngeal paralysis. Restoration of inspiratory vocal cord abduction by phrenic-omohyoid transfer

Omohyoid muscle transfer to the denervated posterior cricoarytenoid muscle (PCA) was performed in three monkeys. The transposed omohyoid muscle was reinnervated by the phrenic nerve by performing nerve anastomosis prior to muscle transfer. The muscles were sutured over the denervated ipsilateral PCA muscle to allow for neurotization of the denervated PCA muscle in such a way as to reproduce the directional vector of PCA contraction, eg, to mimic the directional pull of the PCA muscle. The muscle flaps were found to be long enough to reach the contralateral PCA muscle, confirming that the technique might be used ultimately for bilateral simultaneous PCA reinnervation. Each animal achieved reinnervation. The superiorly based omohyoid muscle flap was found to more closely emulate the size and orientation of the underlying PCA muscle. Electromyography, videolaryngoscopy, and histologic examination were used to confirm the results. The procedure has the potential for PCA muscle replacement in long-standing cases of paralysis with PCA denervation atrophy as well as for reinnervating a denervated PCA muscle.     

Innervation of the paralyzed laryngeal muscles by phrenic motoneurons. A quantitative study by light and electron microscopy.

In the cat, inspiratory opening of the paralyzed glottis recovered after unilateral or bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by phrenic axons. The morphometric analysis of the regenerated recurrent laryngeal nerves (RLNs), showed that proliferation was abundant; 4 months after the nerve anastomosis, more than 500 myelinated axonal branches repopulated the RLNs. The mean diameter of motor axons (3.5 to 5.0 microns) was lower than in normal phrenic and RLN (8 to 10 microns), and the mean internode length was about half that of the normal RLN. Histochemical examination of the PCA muscle revealed that muscle fiber composition (44% type I and 56% type II muscle fiber) was fairly similar to that of normal PCA. The contraction time of the reinnervated muscles was as long as 60 msec at the time of movement recovery, but it shortened to 25 to 30 msec when the reinnervation time increased. These anatomical and functional results support the choice of the phrenic nerve for laryngeal reinnervation.     

Experimental laryngeal reinnervation by phrenic nerve implantation into the posterior cricoarytenoid muscle

Under general anaesthesia, 5 dogs underwent sectioning of the right recurrent nerve followed by implantation of the phrenic nerve into the posterior cricoarytenoid (PCA) muscle. Some 6-7 months later the dogs were sacrificed after registration of vocal cord motility. Still photographs and movie film of the larynx were taken during quiet and forced respiration and at electrical stimulation of the implanted phrenic nerve. The PCA and vocal muscles were removed for histochemical studies. We found practically no abductory movement of the vocal cord on the reinnervated side, either during quiet or forced respiration. During forced inspiration there was, however, a slight medial bowing of the right vocal cord. At electrical stimulation there was a sphincteric movement of the entire larynx. Histochemistry showed a reinnervation picture of both the PCA and the vocal muscles on the experimental side. The conclusion drawn from this study is that axonal escape, probably from the implantation site, results in an unwanted reinnervation of laryngeal adductor muscles, which neutralize the abducting effect of the PCA muscle during inspiration. This method therefore does not seem to be suitable as a treatment alternative for bilateral recurrent nerve paralysis.     

Experimental laryngeal reinnervation by phrenic nerve implantation into the posterior cricoarytenoid muscle

Under general anaesthesia, 5 dogs underwent sectioning of the right recurrent nerve followed by implantation of the phrenic nerve into the posterior cricoarytenoid (PCA) muscle. Some 6-7 months later the dogs were sacrificed after registration of vocal cord motility. Still photographs and movie film of the larynx were taken during quiet and forced respiration and at electrical stimulation of the implanted phrenic nerve. The PCA and vocal muscles were removed for histochemical studies. We found practically no abductory movement of the vocal cord on the reinnervated side, either during quiet or forced respiration. During forced inspiration there was, however, a slight medial bowing of the right vocal cord. At electrical stimulation there was a sphincteric movement of the entire larynx. Histochemistry showed a reinnervation picture of both the PCA and the vocal muscles on the experimental side. The conclusion drawn from this study is that axonal escape, probably from the implantation site, results in an unwanted reinnervation of laryngeal adductor muscles, which neutralize the abducting effect of the PCA muscle during inspiration. This method therefore does not seem to be suitable as a treatment alternative for bilateral recurrent nerve paralysis.     

Extension of neuromuscular pedicles and direct nerve implants in the rabbit

Extension of neuromuscular pedicles and direct nerve implants was investigated in ten rabbits. All rabbits underwent facial nerve resection bilaterally. In five rabbits a neuromuscular pedicle, based on the ansa cervicalis nerve, was implanted into the denervated mentalis muscle unilaterally. On the opposite side, reinnervation was attempted using a neuromuscular pedicle with an interposed nerve graft. In the other five rabbits, reinnervation was attempted using a direct nerve implant on one side and a direct nerve implant extended with a nerve graft on the opposite side. Evoked electromyographic muscle tension and histologic studies were used to evaluate reinnervation. Functional neuromuscular units were consistently produced with neuromuscular pedicles, direct nerve implants, and extended direct nerve implants, while extended neuromuscular pedicles failed to produce detectable reinnervation.     

Neurotization of pectoralis major myocutaneous flap by the hypoglossal nerve in tongue reconstruction: clinical and experimental observations

Recently, neurotization has been proposed for providing mobility to the pectoralis major, or other myocutaneous flap in lingual reconstruction following total glossectomy. The development of an active tongue-like structure may offer the patient higher potential for rehabilitation of speech and deglutition. The purpose of this thesis is to report experimental and clinical observations on neurotization of the pectoralis major myocutaneous flap. The pectoralis major myoflap of 16 rats was reinnervated by either a hypoglossal nerve pedicle of hypoglossal-genioglossus muscle neuromuscular pedicle. Functional flap reinnervation was confirmed in eight of the 16 animals. The author's clinical experience with reconstruction of the tongue utilizing neurotized pectoralis major myocutaneous flap is presented.     

一侧膈神经上根选择性神经再支配环杓后肌的实验研究

目的 探讨一侧膈神经上根选择性神经再支配环杓后肌的可行性和有效性.方法 8只健康雄性青年Beagle犬作为实验动物,全麻下切断Beagle犬左侧膈神经上根与左侧喉返神经,两断端通过游离神经桥接的方式吻合,并将同侧喉返神经内收肌支切断并植入同侧环杓后肌中;右侧不做任何处理,作为正常对照侧.于手术前、神经修复术后即刻、术后6个月分别行电子喉镜和喉肌电图检查,在最后一次检查后处死动物,取双侧环杓后肌和喉内段喉返神经行组织学检查并与对侧比较.结果 术前8只犬的双侧声带运动正常,术后即刻左侧声带固定,术后6个月均恢复了吸气性外展运动.术前8只犬双侧环杓后肌均能记录到自发肌电位,并引出诱发电位;术后即刻左侧环杓后肌呈电静息,未记录到诱发电位;术后6个月均能记录到自发肌电位,并引出诱发电位,而且两种电位幅度分别与术前比较差异均无统计学意义(均为P>0.05).环杓后肌Masson染色示两侧肌肉纤维相对截面积、胶原纤维相对截面积、肌肉/胶原纤维截面积比差异均无统计学意义(均为P>0.05).喉内段喉返神经甲苯胺蓝染色后示神经纤维分布较均匀密集,且左右两侧喉返神经有髓神经纤维数量差异无统计学意义(P>0.05).结论 左侧膈神经上根选择性神经再支配环杓后肌能有效避免神经错向再生,恢复声带的生理性外展运动.