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ABSTRACT: OBJECTIVES/HYPOTHESIS: To quantitate postdeglutitive residue and determine its association with paralysis duration (≤6 vs. ≥6 months) in patients with idiopathic unilateral vocal fold paralysis (UVFP). STUDY DESIGN: Primary institutional retrospective review. METHODS: Twenty patients (mean age, 72 years) with idiopathic UVFP and 13 patients (mean age, 66 years) with isolated recurrent laryngeal nerve paralysis (RLNP) who underwent videofluoroscopic swallow studies (VFSSs) were included. Vallecular and pyriform sinus (PS) residues in the anteroposterior view were analyzed quantitatively. In both regions, the symmetry of the affected versus nonaffected sides between patients with idiopathic UVFP and RLNP were compared. Residual differences between short- versus long-term paralysis duration in idiopathic UVFP patients alone were also evaluated. RESULTS: The affected PS of the idiopathic group demonstrated significantly increased residue (P = .007) as compared with the nonaffected PS, but with no significant difference with respect to the vallecula (P = .183). There was no significant difference in the RLNP group. When compared with RLNP patients, the idiopathic group showed significantly increased residue on the affected PS (P = .002), but differences in the vallecular residue were nonsignificant. Pharyngeal residue and the duration of paralysis in idiopathic UVFP patients were not significantly different. CONCLUSIONS: Idiopathic UVFP patients were more likely to demonstrate increased residue and asymmetry toward the involved region as compared with RLNP patients, suggesting that nerve involvement in idiopathic UVFP may not be exclusive to the RLN. Laryngoscope, 2013.
The Laryngoscope 05/2013; · 1.75 Impact Factor
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ABSTRACT: Although numerous causative genes for hereditary hearing loss have been identified, there are no fundamental treatments for this condition. Herein, we describe a novel potential treatment for genetic hearing loss. Because mutations or deletions in the connexin (Cx) genes are common causes of profound congenital hearing loss in both humans and mice, we investigated whether gene supplementation therapy using the wild-type Cx gene could cure hearing loss. We first generated inner ear-specific connexin 30 (Cx30)-deficient mice via the transuterine transfer of Cx30-targeted short hairpin RNA (shRNA-Cx30) into otocysts. The inner ear-specific Cx30-deficient mice mimicked homozygous Cx30-deficient mice both histologically and physiologically. Subsequently, we cotransfected the shRNA-Cx30 and the wild-type Cx30 gene. The cotransfected mice exhibited Cx30 expression in the cochleae and displayed normal auditory functions. Next, we performed the transuterine transfer of the wild-type Cx30 gene into the otocysts of homozygous Cx30-deficient mice, thereby rescuing the lack of Cx30 expression in the cochleae and restoring auditory functioning. These results demonstrate that supplementation therapy with wild-type genes can restore postnatal auditory functioning. Moreover, this is the first report to show that Cx-related genetic hearing loss is treatable by in vivo gene therapy.Molecular Therapy (2013); doi:10.1038/mt.2013.62.
Molecular Therapy 04/2013; · 6.87 Impact Factor
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ABSTRACT: We established an animal model of recurrent laryngeal nerve reinnervation with persistent vocal fold immobility following recurrent laryngeal nerve injury.
In 36 rats, the left recurrent laryngeal nerve was transected and the stumps were abutted in a silicone tube with a 1-mm interspace, facilitating regeneration. The mobility of the vocal folds was examined endoscopically 5, 10, and 15 weeks later. Electromyography of the thyroarytenoid muscle was performed. Reinnervation was assessed by means of a quantitative immunohistologic evaluation with anti-neurofilament antibody in the nerve both proximal and distal to the silicone tube. The atrophy of the thyroarytenoid muscle was assessed histologically.
We observed that all animals had a fixed left vocal fold throughout the study. The average neurofilament expression in the nerve both distal and proximal to the silicone tube, the muscle area, and the amplitude of the compound muscle action potential recorded from the thyroarytenoid muscle on the treated side increased significantly (p < 0.05) over time, demonstrating regeneration through the silicone tube.
Recurrent laryngeal nerve regeneration through a silicone tube produced reinnervation without vocal fold mobility in rats. The efficacy of new laryngeal reinnervation treatments can be assessed with this model.
The Annals of otology, rhinology, and laryngology 01/2013; 122(1):49-53. · 1.05 Impact Factor
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ABSTRACT: Intraorbital foreign bodies (IOFBs) are usually accompanied by notable skin wounds and/or ocular wounds, and often there is a clear history of a penetrating object. We report herein on a patient who had an asymptomatic IOFB for 30 years. To the best of our knowledge, there is only one other case of a patient with an IOFB for a longer asymptomatic period after the injury. IOFBs may be overlooked because a small penetrating wound may be accompanied by no signs of inflammation for many decades as in this patient's clinical course.
Auris, nasus, larynx 11/2012; · 0.58 Impact Factor
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ABSTRACT: Abstract Conclusions: Three different types of glottal configuration in unilaterally paralyzed larynx were proposed by utilizing three-dimensional computed tomographic (3DCT) images. This new classification might facilitate understanding of the behavior of the affected vocal fold in terms of vocal function. Objectives: To develop a classification of glottal configuration in unilateral vocal fold paralysis (UVFP) based on the thickness and location of the vocal folds utilizing 3DCT and to compare each type of configuration with vocal function. Methods: Thirty-seven consecutive patients with UVFP underwent CT during phonation and inhalation. 3D endoscopic and coronal images on two occasions were produced. Maximum phonation time and mean airflow rate were also measured. Results: Three types of glottal configuration were proposed. The thickness of the affected vocal fold during phonation was equal to or slightly thinner than the healthy fold in 10 patients (type A). The affected fold of the remaining 27 was thin during phonation; they were further classified into types B and C. In type B, the affected fold remained thin during phonation and inhalation (n = 12). Type C was allocated to those showing one or two paradoxical movements of the affected fold (n = 15). Those with type A showed significantly better vocal function.
Acta oto-laryngologica 11/2012; · 0.98 Impact Factor
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ABSTRACT: OBJECTIVES/HYPOTHESIS: To evaluate the impact of nimodipineon reinnervation of the long-term denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle flap (NMP) implantation. STUDY DESIGN: Quantitative histologic and physiologic assessments. METHODS: Using 120 Wistar rats, we performed NMP implantation at different times after transection of the left recurrent laryngeal nerve (RLN). Sixty animals received nimodipine treatment (NIMO [+] group), and the remaining 60 animals received no nimodipine treatment (NIMO [-] group). As a control, an additional 28 animals were subjected only to transection of the left RLN (DNV group). Subgroups were assigned based on the period after RLN transection (0 [immediate], 8, 16, and 32 weeks). In the DNV group, we assessed histologically the muscle area, axons, neuromuscular junctions (NMJs), and myosin heavy chains (MyHC) type IIA and IIB in the TA muscle. In the NIMO (-) and NIMO (+) groups, histologic assessments and evoked electromyography were performed on the TA muscle at 10 weeks post-NMP implantation. RESULTS: In 8-week interval subgroups, the muscle fiber area and the number of NMJs in the NIMO (+) group were significantly greater than in the NIMO (-) group (P < 0.05, each). In the 0-week and 32-week interval subgroups, the muscle fiber subtype changed significantly, from IIA to IIB (P < 0.01 and P < 0.05, respectively); and, at all time-points the muscle fiber area, number of NMJs, and action potentials in the TA muscle tended to be greater in the NIMO (+) group than in the NIMO (-) group. CONCLUSIONS: Nimodipine expedited the effects of NMP implantation on reinnervation of the long-term denervated TA muscle. Laryngoscope, 2012.
The Laryngoscope 09/2012; · 1.75 Impact Factor
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ABSTRACT: Arytenoid adduction (AA) as surgical treatment for unilateral vocal fold paralysis (UVFP) is associated with higher morbidity from airway complications due to postoperative laryngeal edema compared with other laryngeal framework surgeries. The aim of this study was to evaluate postoperative laryngeal edema after AA using a new videolaryngoscopic (VL) scoring assessment.
Prospective case series.
Nineteen patients with UVFP (14 males and five females; mean age, 56 years) who were treated with AA alone or combined with ansa cervicalis (AA/AC) nerve anastomosis or nerve-muscle pedicle (AA/NMP) flap implantation were evaluated. Laryngeal edema was assessed by VL scoring for 10 days postoperatively. Degree of edema was scored in three subsites: the membranous vocal fold, arytenoid mound, and pyriform sinus on the operated side. Statistical significance was defined as P < .05.
No patient experienced postoperative airway compromise. Interexaminer reliability was generally high (Spearman r > 0.75). The mean degree of edema increased steadily from postoperative day (POD) 1 to 3, peaking on POD 3 at all subsites. It then declined significantly from POD 3 to 7 (P < .05) and gradually through POD 10. The maximum degree of edema, maximum edema time, and operative time were not correlated significantly at any subsite. Maximum edema time and surgery type (AA vs. AA/AC or AA/NMP) were not correlated at any subsite.
Inter-rater reliability for the proposed VL scoring was significant at all subsites. The VL findings suggest that AA alone or AA combined with reinnervation showed maximum laryngeal edema on POD 3 but added no significant morbidity.
The Laryngoscope 03/2012; 122(5):1104-8. · 1.75 Impact Factor
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ABSTRACT: To determine whether nimodipine, an L-type voltage-operated calcium channel antagonist that is an accelerator of axonal regeneration following peripheral nerve injury, can expedite reinnervation of denervated rat thyroarytenoid (TA) muscle following nerve-muscle pedicle (NMP) flap implantation.
A quantitative histologic and physiologic assessment of the TA muscle following NMP flap implantation, with or without nimodipine treatment.
Using 72 Wistar rats, we performed a transection on the left recurrent laryngeal nerve, followed by NMP flap implantation. Thirty-six animals received nimodipine treatment (NIMO [+] group), and the remaining 36 animals received no nimodipine treatment (NIMO [-] group). As a control, 18 animals were subjected only to transection of the left recurrent laryngeal nerve. We performed a histologic assessment for muscle area, axon, nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA muscle and electromyography at 2, 4, and 10 weeks after surgery.
Muscle area, ratio of the number of NTs to that of AchRs (NT/AchR ratio), and evoked action potential in the TA muscle were significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05) at 4 weeks. At 10 weeks, the NT/AchR ratio was significantly greater in the NIMO (+) group than in the NIMO (-) group (P < .05).
We found that nimodipine accelerated reinnervation of the denervated TA muscle following NMP flap implantation.
The Laryngoscope 03/2012; 122(3):606-13. · 1.75 Impact Factor
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ABSTRACT: X-linked agammaglobulinemia (XLA) is caused by a mutation in the Bruton tyrosine kinase, leading to an arrest in B cell development. Consequently, patients with XLA show significant decreases in gammaglobulin. Here, we describe a child with postmeningitic deafness and XLA who underwent a cochlear implantation. His psychomotor development had been normal and his congenital immunodeficiency was noticed only postoperatively. Immunoglobulin replacement treatment was started, but he still suffered repeated infections. Eventually, his cochlear implant was removed. A preoperative check of immunological status might be advisable in postmeningitic patients undergoing cochlear implantation to reduce the risk of postoperative infectious complications.
Auris, nasus, larynx 02/2012; 39(6):638-40. · 0.58 Impact Factor
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ABSTRACT: To evaluate the long-term efficacy of arytenoid adduction (AA) combined with ansa cervicalis-recurrent laryngeal nerve anastomosis (ACN-RLN) in the treatment of unilateral vocal fold paralysis.
Retrospective review of clinical records.
Institutional practice.
Nine patients with severe paralytic dysphonia with large glottal gap were included. Voice outcome was followed up over 24 months postoperatively. One patient did not attend the 24-month evaluation.
All patients underwent AA + ACN-RLN. The ansa cervicalis nerve to the sternohyoid muscle was used as the donor nerve.
Maximum phonation time (MPT), pitch range, harmonics-to-noise ratio (HNR), and perceptual voice quality were evaluated preoperatively and postoperatively at 1 to 3 months, 6 to 8 months, 12 to 14 months, and 24 months.
All parameters improved significantly after surgery and continued to improve over the 24-month period. The MPT continued to improve over time (P = .01, P = .006, and P = .001 when comparing the 1- to 3-month evaluation with the 6- to 8-month, 12- to 14-month, and 24-month evaluations, respectively). Also, pitch range and HNR showed significant, steady improvement over the 24-month duration of the study. Perceptual voice quality markedly improved at 24 months compared with the 1- to 3-month, 6- to 8-month, and 12- to 14-month follow-ups (P = .004, P = .005, and P = .02, respectively, for grade overall, and P = .004, P = .008, and P = .02, respectively, for breathiness grade).
Treatment with AA + ACN-RLN provides near-normal vocal function in the 24-month follow-up. Therefore, this method could be a successful surgical treatment for severe paralytic dysphonia.
Archives of otolaryngology--head & neck surgery 01/2012; 138(1):60-5. · 1.92 Impact Factor
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ABSTRACT: Regeneration of nerve fibers in the thyroarytenoid (TA) muscle occurred actively after damage on the recurrent laryngeal nerve (RLN) compared with the vagus nerve (VN). However, remyelination did not occur after damage on the RLN.
To determine the regeneration process of nerve fibers in the TA muscle following transection and immediate anastomosis of the RLN or VN.
Three types of animal model were prepared: an RLN anastomosis model (RLNa), a VN anastomosis model (VNa), and a peroneal nerve anastomosis model (PNa). Animals were sacrificed at five time points following the procedure. The modulation of axons, myelin sheaths, Schwann cells (SCs), nerve terminals (NTs), and acetylcholine receptors (AchRs) in the TA or tibialis anterior muscles was examined by immunohistochemical analysis. The ratios of the expression areas in axons, myelin sheaths, and SCs, and the number of NTs and AchRs in the treated (T) and untreated (U) sides (T/U) were evaluated.
At 18 weeks, the T/U ratios of expression in RLNa, VNa, and PNa were 68.5, 0, and 100.4%, respectively, in axons; 0, 0, and 97.6% in myelin sheaths; 53.7, 0, and 93.6% in SCs; 61.0, 0, and 96.4% in NTs; and 99.4, 67.0, and 101.2% in AchRs.
Acta oto-laryngologica 12/2011; 132(3):305-13. · 0.98 Impact Factor
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ABSTRACT: Nerve-muscle pedicle (NMP) implantation was effective in the recovery of atrophic changes in the denervated thyroarytenoid (TA) muscle in aged rats.
To evaluate the effects of NMP implantation on the denervated TA muscle in aged rats.
Wistar rats aged 20 months and 8 weeks were respectively divided into two groups in which the left recurrent laryngeal nerve (RLN) was transected without (aged/young DNV group) or with (aged/young NMP group) NMP implantation. The aged DNV and NMP groups were further divided into two subgroups, based on the period after RLN transection (10 or 20 weeks). In the DNV groups, we assessed the area of muscle and the number of neuromuscular junctions (NMJs) histologically. In the NMP groups, we performed electromyography and histological assessments. For electromyography, we stimulated the transferred nerve and evaluated the muscle action potentials (MAPs) of the TA muscle.
The muscle areas in the aged NMP groups were significantly larger than those in the aged DNV groups. More NMJs were found in aged NMP groups compared with aged DNV groups. MAPs were seen in all NMP animals. No significant differences were observed between the aged and young NMP groups in histological and physiological assessments.
Acta oto-laryngologica 11/2011; 132(2):210-7. · 0.98 Impact Factor
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ABSTRACT: The mouse otocyst, an anlage of the inner ear, is an attractive experimental target for developing treatment modalities for congenital inner ear diseases and for studying inner ear development. Poly-arginine (6-12 residues) is a cell-penetrating peptide and can be used to deliver cargo into cells. Here, we achieved transutero delivery of enhanced green fluorescent protein (EGFP) fused to a nine-arginine peptide into mouse embryonic otocysts. The EGFP signal was detected both in the lining cells of the otocysts and in their vicinity at 18 h post injection. Mice injected with EGFP fused to a nine-arginine peptide had normal auditory and vestibular functions. These data suggest that protein transduction using poly-arginine may be a useful alternative strategy to commonly used gene delivery methods for delivering therapeutically relevant molecules to the developing inner ear.
Neuroreport 10/2011; 22(18):994-9. · 1.66 Impact Factor
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ABSTRACT: Our objective was to evaluate the efficacy of modified nerve-muscle pedicle (NMP) flap transfer combined with arytenoid adduction (AA) (AA + modified NMP) for treatment of unilateral vocal fold paralysis. The patterns of voice outcome assessed using phonatory function tests and auditory perceptual judgments were followed-up for 2 years.
Prospective study.
Thirteen subjects among those presented with paralytic dysphonia between March 2002 and December 2008 were treated with AA + modified NMP. The voice outcomes (six objective and two subjective voice parameters) were evaluated preoperatively and in four different time points postoperatively over 2-years duration.
All voice parameters showed initial postoperative improvement. Moreover, five parameters showed significant continuous improvement over the 2-year follow-up (maximum phonation time, pitch range, shimmer, and grade overall and breathiness of the grade-roughness-breathiness-asthenia-strain scale (GRBAS), whereas two parameters revealed continuous improvement over the first 12 to 14 months after surgery (mean flow rate and harmonics-to-noise ratio).
AA + modified NMP improves both short- and long-term voice outcomes in unilateral vocal fold paralysis patients. Therefore, AA + modified NMP is an effective surgical combination for the treatment of severe paralytic dysphonia.
The Laryngoscope 05/2011; 121(5):1018-22. · 1.75 Impact Factor
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Otolaryngology Head and Neck Surgery 04/2011; 145(5):874-5. · 1.72 Impact Factor
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ABSTRACT: We investigated whether implantation of an ansa cervicalis nerve (ACN)-muscle pedicle into the thyroarytenoid (TA) muscle is efficacious in the presence of partial recurrent laryngeal nerve (RLN) innervation.
We studied a total of 36 rats. Twelve of the rats served as positive and negative control animals. In the remaining 24 rats, the left RLN was transected, a 1-mm piece of nerve was removed, and the stumps were abutted in silicone tubes (STs), inducing partial RLN regeneration. Twelve of the ST-treated rats underwent this procedure alone, and the other 12 rats had a nerve-muscle pedicle (NMP) implanted into the left TA muscle 5 weeks after ST treatment. At 15 weeks, reinnervation was assessed by histologic evaluation of the TA muscle and by electromyography with stimulation of the RLNs and ACNs.
The muscle area, the number of nerve terminals, the number of acetylcholine receptors, and the ratio of nerve terminals to acetylcholine receptors were significantly greater (p < 0.05) in the NMP group than in the ST group. Electromyography elicited TA muscle compound action potentials upon stimulation of the RLNs and ACNs.
In rats, NMP implantation is efficacious for reducing atrophic changes in the TA muscle in the presence of partial RLN innervation.
The Annals of otology, rhinology, and laryngology 12/2010; 119(12):823-9. · 1.05 Impact Factor
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ABSTRACT: To overcome the demerits of conventional postoperative aural packing, we developed a useful protocol for postoperative stenting of the external auditory canal after middle ear surgery which enables transcanal drainage and simultaneously allows for visual inspection and treatment of the canal, as necessary.
Twenty-four surgeries, 21 patients underwent tympanoplasty with a postaural incision. At the end of all surgical procedures, the external auditory canal was packed with a 0.3mm thickness rolled, tapered silastic sheet (RTSS) with antibiotic ointment applied to one surface. The inserted RTSSs were removed at 5-10 days postoperatively. We assessed the efficacy and the reliability of the RTSS.
In 23 ear surgeries on 20 patients, we achieved successful postoperative ear packing utilizing our RTSS. With these patients, the tympanic membrane and the external auditory meatus were able to be observed immediately after the completion of the stenting during the surgery and the removal of the gauze over the operated ear at Day 1 to Day 3 postoperatively. During 4 surgeries with ventilation tube insertion to the tympanic membrane, there was secretion through the inserted ventilation tube which was easy to suction. In one surgery, on one patient, additional packing materials were utilized once only during a sandwich graft myringoplasty. No patients showed any harmful effects during the postoperative period.
The useful and reliable RTSS, with antibiotic ointment applied to one surface, has several positive advantages that the conventional packing methods do not.
Auris, nasus, larynx 12/2010; 37(6):680-4. · 0.58 Impact Factor
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ABSTRACT: To describe a new technique of nerve-muscle pedicle (NMP) flap implantation combined with arytenoid adduction (AA) to treat dysphonia due to unilateral vocal fold paralysis and to examine postoperative vocal function.
Retrospective review of clinical records.
Tertiary academic center.
Twenty-two consecutive patients underwent NMP flap implantation with AA and were followed up short term over a period of 1 to 6 months (mean, 2.9 months) and long term over a period of 7 to 36 months (mean, 21.4 months).
An NMP flap was made using an ansa cervicalis branch and a piece of the sternohyoid muscle. A window was opened in the thyroid ala at the level of the vocal fold. Then, AA was performed and the NMP flap was securely implanted onto the thyroarytenoid muscle through the window under microscopic guidance.
The maximum phonation time, mean airflow rate, pitch range, and acoustic parameters (jitter, shimmer, and harmonics to noise ratio) were evaluated before surgery and twice after surgery.
All parameters improved significantly after surgery (P < .01). The measurements for maximum phonation time, mean airflow rate, and harmonics to noise ratio were within normal ranges after surgery. Furthermore, the maximum phonation time and jitter were significantly improved after long-term follow-up compared with early postoperative measurements (P < .01 and P < .05, respectively).
Precise harvest of an NMP flap and its placement directly onto the thyroarytenoid muscle combined with AA provided excellent vocal function. The NMP method may have played a certain role in the improvement of postoperative vocal function, although further study with electromyographic examination is required to clarify the innervation status of the thyroarytenoid muscle.
Archives of otolaryngology--head & neck surgery 10/2010; 136(10):965-9. · 1.92 Impact Factor
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ABSTRACT: Type II thyroplasty, or laryngeal framework surgery, is based on the hypothesis that the effect of adductor spasmodic dysphonia (AdSD) on the voice is due to excessively tight closure of the glottis, hampering phonation. Most of the previous, partially effective treatments have aimed to relieve this tight closure, including recurrent laryngeal nerve section or avulsion, extirpation of the adductor muscle, and botulinum toxin injection, which is currently the most popular. The aim of this study was to assess the effects of type II thyroplasty on aerodynamic and acoustic findings in patients with AdSD.
Case series.
University hospital.
Ten patients with AdSD underwent type II thyroplasty between August 2006 and December 2008. Aerodynamic and acoustic analyses were performed prior to and six months after surgery. Mean flow rates (MFRs) and voice efficiency were evaluated with a phonation analyzer. Jitter, shimmer, the harmonics-to-noise ratio (HNR), standard deviation of the fundamental frequency (SDF0), and degree of voice breaks (DVB) were measured from each subject's longest sustained phonation sample of the vowel /a/.
Voice efficiency improved significantly after surgery. No significant difference was found in the MFRs between before and after surgery. Jitter, shimmer, HNR, SDF0, and DVB improved significantly after surgery.
Treatment of AdSD with type II thyroplasty significantly improved aerodynamic and acoustic findings. The results of this study suggest that type II thyroplasty provides relief from voice strangulation in patients with AdSD.
Otolaryngology Head and Neck Surgery 04/2010; 142(4):540-6. · 1.72 Impact Factor
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ABSTRACT: Unilateral vocal fold paralysis (UVFP) is one of the most serious problems in conducting surgery for thyroid cancer. Different treatments are available for the management of UVFP including intracordal injection, type I thyroplasty, arytenoid adduction, and laryngeal reinnervations. The effects of immediate recurrent laryngeal nerve (RLN) reconstruction during thyroid cancer surgery with or without UVFP before the surgery were evaluated with videostroboscopic, aerodynamic, and perceptual analyses. All subjects experienced postoperative improvements in voice quality. Particularly, aerodynamic analysis showed that the values for all patients entered normal ranges in both patients with and without UVFP before surgery. Immediate RLN reconstruction has the potential to restore a normal or near-normal voice by returning thyroarytenoid muscle tone and bulk seen with vocal fold denervation. Immediate RLN reconstruction is an efficient and effective approach to the management of RLN resection during surgery for thyroid cancer.
Journal of Oncology 01/2010; 2010:846235.
