几丁质管桥接喉返神经缺损的实验研究

为在恢复神经再支配手术治疗喉返神经损伤所致的喉麻痹中,探索一种新的可避免神经误向支配的方法,采用非神经生物材料几了质管,桥接狗喉返神经干的缺损,并用自体神经移植作为对照组.术后5个月,组织学、组织化学和电生理等检测,显示两组动物的喉内肌皆获得神经再支配.实验组术侧声带较明显恢复了和健侧一致的内收和外展运动,甲杓肌(Thyroarytenoid,TAM)和环杓后肌(Posterior cricoarytenoid musdes,PCAM)也分别出现了相应的生理性自发肌电;对照组的术侧声带无明显的运动,TAM和PCAM则在呼气期和吸气期均出现不规则的持续密集自发肌电.提示几丁质桥接喉返神经干缺损可使其定向性再生,选择性支配喉内肌.     

Experimental Study on Reinnervation of Vocal Cord Adductors With the Ansa Cervicalis

The purpose of this study was to reestablish the adduction of the paralyzed vocal cord through reinnervation of the adductor muscles for unilateral vocal cord paralysis. In nine dogs, the adductor branch of the recurrent laryngeal nerve was anastomosed to the main branch of the ansa cervicalis. Six months later, various techniques of observation showed that seven of nine cases had excellent to good adduction during whining. Adduction was caused by reinnervation of the adductor muscles from the ansa cervicalis as demonstrated by laryngeal spontaneous and evoked electromyography, contraction tension, and various histologic findings. Therefore, the new technique could be a good treatment of unilateral vocal cord paralysis.     

喉内收及外展肌选择性再神经支配的实验研究

选用犬１５只，随机分成三组，进行了选择性再神经支配喉内收肌及外展肌功能重建的观察。两个实验组术侧声带最初恢复内收时间为术后３个月，最初恢复外展时间为术后４个月，术后６个月，所有实验组动物的术侧声带均恢复了良好的内收及外展运动，并得到肌电图、肌收缩力及神经肌肉组织化学检查的证实。实验结果表明，同时重建麻痹的声带内收及外展功能是可行且有效的。     

Laryngeal reinnervation for unilateral traumatic recurrent laryngeal nerve injuries]

OBJECTIVE: To investigate 5 procedures of laryngeal reinnervation for unilateral vocal cord paralysis induced by traumatic recurrent laryngeal nerve injury. METHODS: 35 cases were selected for our study, all patients had unilateral recurrent laryngeal nerve injury, including 8 for nerve decompression, 6 for end to end anastomosis of recurrent laryngeal nerve, 16 for main branch of ansa cervicalis anastomosis to recurrent laryngeal nerve, 3 for nerve muscular pedicle and 2 for nerve implantation. All cases have been subjected to preoperative and postoperative voice recording, acoustic analysis, videolaryngoscopy, strobscopy and electromyography. RESULTS: It is found the adductory and abductory motion of the vocal cord restored in 5 cases with less than 4 months course who received nerve decompression. Although functional motion of vocal cord was not seen in two patients who received nerve decompression with a course longer than 4 months and one less than 4 months, and in all cases who received ansa cervicalis anastomosis and end to end anastomosis of recurrent laryngeal nerve, these procedures resulted in medialization of vocal cord and the mass and tension of the reinnervated vocal cord may become much the same as the contralateral normal vocal cord, thus resuming symmetric vibration of the vocal cords and physiological phonation. Nerve muscular pedicle technique and nerve implantation enabled adductory muscles to be reinnervated, thus improving severe hoarseness, but they didn't restore normal voice. CONCLUSIONS: (1) Nerve decompression seems to be the best procedure in laryngeal reinnervation; (2) Main branch of ansa cervicalis technique raises satisfactory reinnervation of adductor muscles; (3) Selection of the laryngeal reinnervation protocols should depend on the course, severity and type of nerve injury.     

Effects of arytenoid adduction on laryngeal function following ansa cervicalis nerve transfer for vocal fold paralysis in an in vivo canine model

Laryngeal reinnervation with the ansa cervicalis has been proposed as a treatment for human unilateral vocal fold paralysis (UVFP). This study tested the assumption that results from reinnervation could be improved if combined with medialization surgery. Six canine subjects underwent recurrent laryngeal nerve section and reinnervation with a branch of the ansa cervicalis. After reinnervation, vocal function was assessed before and after arytenoid adduction. Although laryngeal function improved significantly following reinnervation, results were significantly enhanced by the addition of medialization surgery. The implications for the treatment of human unilateral vocal fold paralysis are discussed.     

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.     

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.     

Laryngeal reinnervation with the hypoglossal nerve. I. Physiology, histochemistry, electromyography, and retrograde labeling in a canine model.

This study was performed to determine whether the hypoglossal nerve (cranial nerve XI [XII]) would serve as a useful donor for laryngeal reinnervation by anastomosis to the recurrent laryngeal nerve (RLN). Twenty hemilarynges in 10 dogs were studied prospectively after XII-RLN anastomosis (group A; n = 5), split XII-RLN anastomosis (group B; n = 3), XII-RLN anastomosis with a 2-cm interposition graft (group C; n = 2), no treatment (group D; n = 5), RLN section (group E; n = 2), or ansa cervicalis-RLN anastomosis (group F; n = 3). Spontaneous activity was observed monthly by infraglottic examination through permanent tracheostomies and was recorded by electromyography. Laryngeal adductory pressure and induced phonation were obtained by stimulating the RLN while passing a pressure transducer balloon or humidified air through the glottis. At sacrifice, the laryngeal muscles were stained for adenosine triphosphatase to determine the ratio of type I to type II fibers. Retrograde labeling of the brain stem was performed with horseradish peroxidase. Infraglottic examination at 6 months showed a full range of adductory motion in groups A and B during the swallow reflex, comparable with that in group D. Groups C and F showed good bulk and tone, but little spontaneous motion. Group E remained paralyzed. Stimulation of the transferred nerves caused more activity in groups A and B than in the other groups; groups C and F partially adducted at high levels. The laryngeal adductory pressure responses of groups A and B were similar to those of group D. The XII-reinnervated larynges were capable of producing normal induced phonation. Retrograde labeling of the RLN showed that the reinnervating axons originated only in the hypoglossal nucleus. Electromyography of the reinnervated adductor muscles confirmed spontaneous activity in the dogs (awake). Histochemical analysis confirmed slow-to-fast transformation of both the posterior and lateral cricoarytenoid muscles, indicating that significant reinnervation occurred. We conclude that the hypoglossal nerve functions well as a donor for adductory reinnervation of the larynx.     

Improvement of respiratory compromise through abductor reinnervation and pacing in a patient with bilateral vocal fold impairment

Objectives/Hypothesis.

To determine whether respiratory compromise from bilateral vocal fold impairment (paralysis) can be objectively alleviated by reinnervation and pacing.

Methods.

A patient with paramedian vocal folds and synkinesis had a tracheotomy for stridor after bilateral laryngeal nerve injury and Miller Fisher syndrome. One posterior cricoarytenoideus (PCA) received a nerve‐muscle pedicle fitted with a perineural electrode for pacemaker stimulation. The airway was evaluated endoscopically and by spirometry for up to 1 year.

Results.

Bilateral vocal fold patency during quiet breathing was reversed to active vocal fold adduction during tracheal occlusion. Peak inspiratory flows (PIFs) were significantly higher (P < .001) after reinnervation. PIFs and glottic apertures increased further under stimulation (42 Hz, 1–4 mA, 42–400 μsec). although the differences were not significant.

Conclusions.

Based on our preliminary data, PCA reinnervation and pacing offer promise for amelioration of respiratory compromise after paradoxical adduction in bilateral vocal fold impairment. Laryngoscope, 2010     

Physiologic motion after vocal cord reinnervation: A preliminary study

This study attempted to reestablish physiologic vocal cord motion, rather than synkinesis, to a rein-nervated vocal cord. One mongrel dog underwent a division and reanastomosis of the anterior branch of the right recurrent laryngeal nerve and simultaneous separation and reimplantation of a posterior division nerve-muscle pedicle into the posterior cricoarytenoid muscle. After 21 weeks, spontaneous physiologic vocal cord movement and electromyographic (EMG) activity were recorded during respiratory obstruction and laryngeal mechanical stimulation. Acoustic measures and histologic data are also presented from the reinnervated and normal vocalis muscle and from the recurrent laryngeal nerve. This study demonstrated that physiologic vocal cord motion can be achieved after laryngeal reinnervation using this technique.     

Spontaneous laryngeal reinnervation after recurrent laryngeal or vagus nerve injury

OBJECTIVES: The status of innervation in patients with laryngeal paralysis is somewhat controversial. Electromyographic activity has been frequently documented in the laryngeal muscles of patients with laryngeal paralysis, and animal experiments report a strong propensity for reinnervation after laryngeal nerve injury. However, a study of intraoperative electromyography performed in patients during reinnervation surgery failed to document activity with stimulation of the recurrent laryngeal nerve (RLN). Noting the long-observed differences in the symptoms of patients with vagus nerve injury and those with RLN injury, I hypothesized that reinnervation is influenced by the site of nerve injury. METHODS: Cats were sacrificed at various intervals after resection of 1 cm of either the RLN or the vagus nerve, without any attempt to repair the nerve. RESULTS: Four months after RLN resection, distal nerve biopsy revealed unmyelinated axons scattered through fibrous tissue. By 6 months, myelinated axons were organized, and electromyographic and histologic examination showed preferential reinnervation of the thyroarytenoid muscle. After vagotomy, the RLN was fibrotic and no axons were present. Both the thyroarytenoid and posterior cricoarytenoid muscles were fibrotic and had no electromyographic activity. CONCLUSIONS: The results confirm the strong propensity for laryngeal reinnervation after RLN injury, but not after vagus nerve injury. Preferential reinnervation of adductor muscles may account for a medial position of the paralyzed vocal fold.     

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.     

甲状腺手术喉返神经损伤规律及治疗的探讨

目的 探讨甲状腺手术喉返神经损伤的规律及中早期神经减压的疗效。方法 甲状腺手术喉返神经损伤单侧声带麻痹87例,其中行喉返神经探查65例,非手术治疗22例。探查术中观察喉返神经损伤部位、类型、程度及神经肌肉形态;对缝扎、粘连伤行神经减压治疗14例。治疗前后以喉镜、嗓音声学参数、肌电图检查等评价治疗效果。结果 探查发现喉返神经被缝线结扎、瘢痕粘连压迫、断离分别占43％(28/65)、9％(6/65)、48％(31/65)。损伤部位以近环甲关节处多见,占75％(49/65);甲状腺中下部占25％(16/65)。病程半年以内者喉内肌及损伤处远端神经干萎缩并不严重,病程越长萎缩变性越明显。神经切断伤上述改变较缝扎伤及压迫伤更为明显;但病程18个月喉内肌仍可见肌纤维组织结构。病程3个月内神经减压10例中9例声带恢复了不同程度的内收及外展功能;病程3个月以内1例、3-5个月4例神经减压术后声带未恢复运动,但均恢复了正常的肌张力、肌体积,声带振动及黏膜波对称,嗓音亦恢复正常。非手术治疗组声嘶有改善,但嗓音未恢复正常,声带亦未恢复运动。结论 通过喉返神经探查初步揭示甲状腺手术喉返神经损伤的规律,中早期喉返神经减压术能恢复声带生理性运动功能。     

甲状腺手术喉返神经损伤规律及治疗的探讨

目的探讨甲状腺手术喉返神经损伤的规律及中早期神经减压的疗效。方法甲状腺手术喉返神经损伤单侧声带麻痹87例，其中行喉返神经探查65例，非手术治疗22例。探查术中观察喉返神经损伤部位、类型、程度及神经肌肉形态；对缝扎、粘连伤行神经减压治疗14例。治疗前后以喉镜、嗓音声学参数、肌电图检查等评价治疗效果。结果探查发现喉返神经被缝线结扎、瘢痕粘连压迫、断离分别占43％(28／65)、9％(6／65)、48％(31／65)。损伤部位以近环甲关节处多见，占75％(49／65)；甲状腺中下部占25％(16／65)。病程半年以内喉内肌及损伤处远端神经干萎缩并不严重，病程越长萎缩变性越明显。神经切断伤上述改变较缝扎伤及压迫伤更为明显；但病程18个月喉内肌仍可见肌纤维组织结构。病程3个月内神经减压10例中9例声带恢复了不同程度的内收及外展功能；病程3个月以内1例、3—5个月4例神经减压术后声带未恢复运动，但均恢复了正常的肌张力、肌体积，声带振动及黏膜波对称，嗓音亦恢复正常。非手术治疗组声嘶有改善，但嗓音未恢复正常，声带亦未恢复运动。结论通过喉返神经探查初步揭示甲状腺手术喉返神经损伤的规律，中早期喉返神经减压术能恢复声带生理性运动功能。     

Combined arytenoid adduction and laryngeal reinnervation in the treatment of vocal fold paralysis

OBJECTIVE/HYPOTHESIS: Glottal closure and symmetrical thyroarytenoid stiffness are two important functional characteristics of normal phonatory posture. In the treatment of unilateral vocal cord paralysis, vocal fold medialization improves closure, facilitating entrainment of both vocal folds for improved phonation, and reinnervation is purported to maintain vocal fold bulk and stiffness. A combination of medialization and reinnervation would be expected to further improve vocal quality over medialization alone. STUDY DESIGN: A retrospective review of preoperative and postoperative voice analysis on all patients who underwent arytenoid adduction alone (adduction group) or combined arytenoid adduction and ansa cervicalis to recurrent laryngeal nerve anastomosis (combined group) between 1989 and 1995 for the treatment of unilateral vocal cord paralysis. Patients without postoperative voice analysis were invited back for its completion. A perceptual analysis was designed and completed. METHODS: Videostroboscopic measures of glottal closure, mucosal wave, and symmetry were rated. Aerodynamic parameters of laryngeal airflow and subglottic pressure were measured. A 2-second segment of sustained vowel was used for perceptual analysis by means of a panel of voice professionals and a rating system. Statistical calculations were performed at a significance level of P = .05. RESULTS: There were 9 patients in the adduction group and 10 patients in the combined group. Closure and mucosal wave improved significantly in both groups. Airflow decreased in both groups, but the decrease reached statistical significance only in the adduction group. Subglottic pressure remained unchanged in both groups. Both groups had significant perceptual improvement of voice quality. In all tested parameters the extent of improvement was similar in both groups. CONCLUSION: The role of laryngeal reinnervation in the treatment of unilateral vocal cord paralysis remains to be established.     

Modulation of myosin heavy chains in rat laryngeal muscle

OBJECTIVES: To test the hypothesis that myosin heavy chain (MHC) composition is a biological marker indicative of appropriate and functional reinnervation. STUDY DESIGN: Age-matched adult rats were randomized for prospective study under three experimental conditions. METHODS: In adult rats, three experimental conditions were surgically created, including transient recurrent laryngeal nerve (RLN) crush injury, RLN transection and repair, and cricoarytenoid joint fixation with intact RLN. Animals were survived for 30, 90, and 180 days. At each interval, vocal fold mobility was assessed by rigid microlaryngoscopy. Laryngeal electromyography (EMG) was performed before euthanasia. The thyroarytenoid and posterior cricoarytenoid muscles were then excised, each muscle was processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and MHC composition was determined. RESULTS: Thirty days after nerve crush injury, three of six animals regained vocal fold mobility and normal MHC composition. Impaired vocal fold motion in three of six animals was associated with MHC composition characteristic of denervation. At 90 and 180 days, normal vocal fold motion and normal MHC composition were observed in all animals. Following nerve transection and repair, impaired vocal fold motion and MHC composition characteristic of denervation were observed in all animals, despite evidence of reinnervation on EMG. Following joint fixation, alteration in MHC composition consistent with denervation was observed only at 30 days, as was evident in the nerve crush model. CONCLUSION: Temporary injury and vocal fold immobilization result in transient shifts in MHC composition. Nerve transection and repair result in persistent alteration of MHC composition and vocal fold dysfunction. The expression of normal MHC composition is dependent on the condition of appropriate neural contact and functional reinnervation.     

Thyroarytenoid muscle maintains normal contractile force in chronic vocal fold immobility.

BACKGROUND: Denervation of skeletal muscle typically results in irreversible denervation atrophy over time. This finding has generated controversy as to the efficacy of reinnervation procedures for chronic vocal fold immobility related to recurrent laryngeal nerve injury. OBJECTIVE: To test the hypothesis that chronic vocal fold immobility after recurrent laryngeal nerve injury does not result in diminished maximal isometric force generation in the thyroarytenoid muscle. STUDY DESIGN: Adult random-bred cats underwent either unilateral laryngeal denervation (n = 6) or sham surgery (n = 6). After 6 months, videolaryngoscopy was performed followed by in vitro measurement of maximal isometric tetanic force produced by the thyroarytenoid muscle. RESULTS: All animals in the denervation group showed right vocal fold paralysis after the initial denervation operation; none of these animals had return of appropriately phased movement with respiration. Four had intermittent disorganized twitching movements. One had these movements plus an occasional weak adduction, and one had no movement. Normal vocal fold mobility was observed in 6 of 6 animals undergoing sham surgery. The maximal isometric tetanic force measured from the thyroarytenoid muscle in the sham group was 438 mN (+/-92 mN standard deviation [SD]). The maximal isometric tetanic force measured from the thyroarytenoid muscle in the chronically immobile group was 405 mN (+/-107 mN SD). Differences were not statistically significant. CONCLUSION: Maximal isometric force in the thyroarytenoid muscle is not diminished in chronic vocal fold immobility after recurrent laryngeal nerve injury. We conclude that the possibility for restoration of contractile force to the chronically immobile thyroarytenoid muscle exists. This finding supports the pursuit of reinnervation procedures in the treatment of chronic vocal fold immobility.     

Paradoxical vocal fold motion: respiratory retraining to manage long-term symptoms

Paradoxical vocal fold motion (PVFM) is a laryngeal disorder characterized by abnormal adduction of the vocal folds during respiration. It is caused by a multitude of etiologies and their interactions. In the current study, a 24-year-old female patient with a 12-year complaint of shortness of breath was diagnosed with paradoxical vocal fold motion following nasal endoscopy, spirometry testing and detailed case history analysis. She had no history or indication of laryngopharyngeal reflux or chronic cough. She performed respiratory retraining exercises three to four times daily for a period of four weeks, and continued daily exercises for two additional months as needed. After four weeks of treatment, abnormal vocal fold adduction continued to be seen on endoscopy and the patient was mildly symptomatic. One month post-treatment, there was no abnormal vocal fold adduction and the patient reported rare shortness of breath. At three months post-treatment, there was no abnormal vocal fold adduction and the patient no longer reported shortness of breath. She reported normal breathing with no symptoms one year later. The results suggest that non-pulmonary related shortness of breath treated with respiratory retraining can effectively eliminate dyspnea in patients with long term breathing difficulties caused by paradoxical vocal fold motion. Resolution may require treatment over an extended period of time.     

Artificial restoration of voice. I: Experiments in phonatory control of the reinnervated canine larynx

Coordinated electronic pacing of implanted nerve pedicles into paralyzed laryngeal muscles has allowed selective dynamic control of abduction, adduction, and elongation of the vocal cords. Modifications of the original circuit in a cervical muscle model has added fine tuning to basic "all-or-none" pacing. Rehabilitation of phonation illustrated the sophisticated nature of voice and the need for restoration of fine tuning. Five mongrel dogs received nerve-muscle pedicles into the thyroarytenoideus, cricothyroideus, and posterior cricothyroideus after denervation of one hemilarynx. Following appropriate reinnervation time, pedicles and intact recurrent laryngeal nerves were injected with currents of variable amplitudes and pulse widths to achieve graded vocal fold control while air was blown intratracheally towards the glottic chink. Videoscopic and spectral analyses indicated that artificial phonation could be restored to frequencies measured in the normal state. These experiments suggested that rehabilitation of the impaired voice by servocontrol might eventually be feasible.     

Echo-Planar Magnetic Resonance Imaging of Deglutitive Vocal Fold Closure: Normal and Pathologic Patterns of Displacement

Abnormalities of vocal fold closure during deglutition predispose to aspiration due to impairment of airway protection. Conventional assessment of deglutitive vocal fold motion with laryngoscopy does not permit visualization through a complete adduction-abduction cycle. We determined spatiotemporal patterns of deglutitive vocal fold adduction through echo-planar magnetic resonance imaging in 15 normal volunteers and 6 patients with vocal fold paralysis. In normal volunteers, deglutitive vocal fold adduction was synchronized with laryngeal elevation, with complete vocal fold closure at the apex. Patients with unilateral vocal fold paralysis demonstrated reduced elevation and medial movement of the involved vocal fold. At maximal laryngeal elevation the uninvolved vocal fold attained a position superior to the paralyzed fold, resulting in level differences and an interglottic gap. Patients with bilateral vocal fold paralysis demonstrated reduced elevation and medial movement of both vocal folds. These findings indicate that normal and abnormal patterns of vocal fold displacement can be distinguished noninvasively through the use of echo-planar imaging. Laryngoscope, 106:568-572, 1996