Gene therapy for laryngeal paralysis

OBJECTIVES: The surgical options for laryngeal paralysis only achieve static changes of vocal fold position. Laryngeal reinnervation procedures have had little impact on the return of dynamic laryngeal function. The development of a new treatment for laryngeal paralysis, aimed at the return of dynamic function and neurologic restoration and regeneration, is necessary. METHODS: To assess the possibility of gene therapy for laryngeal paralysis aiming for the return of dynamic laryngeal function, we investigated the therapeutic effects of gene therapy using rat laryngeal paralysis models. RESULTS: In a rat vagal nerve avulsion model, we transferred glial cell line-derived neurotrophic factor (GDNF) gene into the nucleus ambiguus using an adenovirus vector. Two and 4 weeks after the GDNF gene transfer, a significantly larger number of surviving motoneurons was observed. These neuroprotective effects of GDNF gene transfer were enhanced by simultaneous brain-derived neurotrophic factor gene transfer. In a rat recurrent laryngeal nerve crush model, we transferred GDNF gene into recurrent laryngeal nerve fibers after crush injury. Two and 4 weeks after GDNF gene transfer, we observed significantly faster nerve conduction velocity and better vocal fold motion recovery. CONCLUSIONS: These results indicate that gene therapy could be a future treatment strategy for laryngeal paralysis. Further studies will be necessary to demonstrate the safety of the vector before clinical application.     

单侧声带麻痹的外科治疗

目的比较颈袢喉返神经吻合术与声带外侧自体软骨充填术、声带脂肪注射术的疗效。方法单侧声带麻痹143例,病程6个月至12年。行颈袢与喉返神经吻合术(A组)89例：声带外侧自体软骨充填术(B组)25例;声带自体脂肪注射术(C组)29例。治疗前后以电子喉镜、频闪喉镜、声音评估和嗓音声学参数分析等评价治疗效果。结果A组术后术侧声带均内移至正中位,肌体积增大,发音时声带突明显内收,声门后裂隙消失,声带振动及黏膜波均恢复对称性,声门闭合良好：嗓音恢复正常86例。3例接近正常;声学五参数频率微拢、振幅微拢、标准化嗓音能量、基频及最长声时平均值均在正常范围内,前三项明显小于术前,后两项明显大于术前,差异均具有非常显著性。B组及C组术后声带均不同程度内移,但声带均无运动,声门后裂隙仍较明显。B、C组术后声嘶有不同程度好转,声学前三参数平均值均明显小于术前,最长声时明显大于术前,差异均具有显著性：而基频手术前后差异无显著性。B、C组的声学参数前三项均明显大于A组,而基频及最长声时明显小于A组,差异均具有显著性。B、C组间的声学五参数差异无显著性意义。结论单侧声带麻痹以神经修复术疗效最佳;声带外侧充填术及声带脂肪注射术也有治疗效果,不适合神经修复者仍可选用：脂肪注射术往往须多次注射方能维持疗效。     

Selective laryngeal adductor denervation-reinnervation: a new surgical treatment for adductor spasmodic dysphonia

During the past decade, botulinum toxin (Botox) has emerged as the accepted treatment for adductor spasmodic dysphonia (ASD). This therapy, which produces bilateral weakness of the thyroarytenoid muscle, undoubtedly produces physiologic effects that are beneficial to patients with ASD. However, it also has important limitations, including the need for repeated injections, the unpredictable relationship between dosage and response, and the possibility of short-term swallowing and voice problems. In this study, we will report our preliminary experience with a new surgical treatment for ASD. In this new procedure, the adductor branch of the recurrent laryngeal nerve is selectively denervated bilaterally, and its distal nerve stumps are reinnervated with branches of the ansa cervicalis nerve. Each of the patients was followed for at least 12 months; the median follow-up is 36 months. The outcome of the operation in 21 consecutive patients is reported. Nineteen of the 21 patients were judged to have an overall severity of dysphonia that was "absent to mild" following the procedure. Only 1 patient underwent further treatment with Botox postoperatively. The implications of this new procedure for ASD are discussed.     

Pediatric vocal fold paralysis: a long-term retrospective study

OBJECTIVE: To review our experience of pediatric vocal fold paralysis (VFP), with particular emphasis on etiological factors, associated airway pathologic conditions, and treatment and prognostic outcomes. DESIGN: Retrospective case review of a cohort of patients presenting with VFP. SETTING: Tertiary referral center. PATIENTS: A consecutive sample of 102 patients presenting with VFP to Great Ormond Street Hospital for Children, London, England, over a 14-year period from 1980 to 1994. RESULTS: There was an almost equal distribution of unilateral (52% [n = 53]) and bilateral (48% [n = 49]) VFP. Iatrogenic causes (43% [n = 44]) formed the largest group, followed by idiopathic VFP (35% [n = 36]), neurological causes (16% [n = 16]), and finally birth trauma (5% [n = 5]). Associated upper airway pathologic conditions were noted in 66% (n = 23) of patients who underwent tracheotomy. Tracheotomy was necessary in only 57% (n = 28) of children with bilateral VFP. Prognosis was variable depending upon the cause, with neurological VFP having the highest rate of recovery (71% [5/7]) and iatrogenic VFP the lowest rate (46% [12/26]). CONCLUSION: Recovery after an interval of up to 11 years was seen in idiopathic bilateral VFP; this has significant implications when considering lateralization procedures in these patients.     

Pediatric laryngeal sarcoidosis

Numerous cases of sarcoidosis, but few cases of well-documented laryngeal involvement, have been reported in the pediatric literature. Isolated laryngeal involvement is a most unusual presentation of sarcoidosis. Such a case is reported here, along with a review of laryngeal sarcoidosis in the pediatric population. Differential diagnosis, diagnostic evaluation, and treatment options are discussed. Intralesional steroid injection provides local therapy with fewer complications than systemic steroids.     

Pediatric vocal cord paralysis

Pediatric vocal cord paralysis accounts for approximately 10% of all congenital laryngeal lesions. Early detection of these neurogenic disorders is based upon a high index of suspicion and is important to prevent catastrophes during periods of acute respiratory embarrassment. This paper reviews the symptoms, etiology and management of unilateral and bilateral vocal cord paralysis as it pertains to this age group. A case is presented of a neonate with vocal cord paralysis and associated hydrocephalous and meningomyelocele to illustrate many of the problems associated with pediatric laryngeal paralysis.     

Evolving concepts of laryngeal paralysis

Accepted concepts of the pathophysiology and treatment of laryngeal paralysis have changed over the years. It has long been observed that symptoms of laryngeal paralysis vary greatly, both between patients and over time. There have been various theories to explain these differences. This article reviews how these ideas have changed over time as research has produced new information. Currently, the most popular view is that the laryngeal nerve regenerates after injury, albeit incompletely and inconsistently, and that variations in symptoms and laryngeal posture can be accounted for by muscle activity.     

Hereditary congenital laryngeal abductor paralysis

We discuss the cases of a mother and daughter with paralysis of laryngeal abduction at birth as an isolated symptom. These patients are compared with other known families with congenital abductor paralysis, and inferences are made about the cause and mechanism of the disorder. A plan of diagnosis and management is presented.     

Recurrent laryngeal nerve paralysis: anatomy and etiology

Etiologies of adult vocal paralysis are varied by the site of the lesion as well as the extent and cause of the damage. Most large series point to surgery and neoplastic causes for recurrent nerve paralysis. A detailed history is important when working up a patient with this voice disorder.Knowledge of the anatomy of the head, neck, and chest as well as the mechanisms behind vocal fold paralysis is essential in the evaluation and treatment of recurrent nerve paralysis. Many of the surgical and traumatic causes of hoarseness are from compression type injuries. Recovery is dependent on the type, extent, and site of nerve lesion. Familiarity with this data allows the otolaryngologist to tailor management to suit each patient with vocal fold paralysis.     

Endoscopic vocal cord medialization: a new surgical technique without neck incision for laryngeal palsy

Different types of surgery have been reported for glottal insufficiency due to unilateral vocal cord paralysis. We recently developed a new surgical technique of fascia implantation known as vocal cord medialization. This new method achieves a wide glottal gap during phonation, without the use of an external approach. This new technique is described in detail herein, together with the satisfactory results we obtained in six cases of unilateral vocal cord paralysis with a wide glottal gap during phonation. We recommend this technique in cases of unilateral vocal cord paralysis in which both a satisfactory clinical result and an aesthetically pleasing cosmetic result are required.     

Pediatric laryngeal trauma: a case series at a tertiary children's hospital

Background

Pediatric blunt or sharp laryngotracheal injuries are infrequent because of the softer cartilages and the protection of the prominent mandible. These injuries usually occur secondary to striking furniture or via the “clothesline” injury.

Methods

We present five cases of pediatric laryngotracheal injury (thyroid cartilage, true vocal cords, cricoid cartilage, cricotracheal junction, and posterior tracheal wall).

Results

We examined the need for intubation, need for tracheostomy, length of intubation, length of hospital stay, interval until direct laryngoscopy, use of steroids, post-injury swallowing, and post-injury phonation.

Discussion

Three of the five patients were intubated either prior to arrival or upon arrival to the emergency department. Two of the patients underwent direct laryngoscopy on the day of arrival. Three patients received steroids. CT (computed tomography) was not helpful in diagnosis or decision regarding treatment. The patients with thyroid cartilage fracture, cricoid cartilage fracture, cricotracheal separation, and posterior tracheal wall tear required open repair. The tracheal wall injury, cricoid fracture, and cricotracheal separation were repaired with sutures and the thyroid cartilage fracture with a plate and screws. One tracheal stent was placed. Two open repairs were performed within 24 h of injury. The patient with posterior tracheal wall injury experienced persistent dysphagia and dysphonia, which may have been secondary to intraoperative dissection.

Conclusion

Dyspnea was not necessarily indicative of the severity of injury in our patients. CT added little information about the integrity of the larynx not already known by physical examination. Open repair was usually indicated for the blunt neck injuries in our series. Oral intubation proved less difficult than tracheostomy in our patient with cricoid cartilage fracture.