The Swallowing Side Effects of Botulinum Toxin Type A Injection in Spasmodic Dysphonia

Botulinum toxin type A (BOTOX®) injection of the thyroarytenoid muscle is used to control speech symptoms in patients with adductor spasmodic dysphonia. Transient difficulty in swallowing liquids is a common treatment side effect. Laryngeal movement durations were measured during swallowing in 13 adductor spasmodic dysphonia patients undergoing treatment and in 6 normal control subjects in order to determine the following: 1. whether, prior to the injection, laryngeal movement durations were longer in the spasmodic dysphonia patients than in the control subjects; 2. whether movement durations increased following the injections; 3. whether preinjection swallowing difficulties related to postinjection swallowing measurements and postinjection patient reports of swallowing problems. A piezoelectric movement transducer was shown to be accurate for noninvasive measurement of laryngeal movement duration in relation to muscle onset and offset for hyoid elevation and relaxation. Before botulinum toxin type A injection, no significant differences in swallowing duration were found between the patient and control groups. Four patients with swallowing complaints prior to injection had longer laryngeal movement durations than the other spasmodic dysphonia patients and the control subjects. Following injection, laryngeal movement durations increased in the patients with spasmodic dysphonia, and eight patients reported dysphagia for an average of 2 weeks. Relationships were found between the patients' initial reports of swallowing problems and increased laryngeal movement durations before and after botulinum toxin type A injection. Those patients initially reporting swallowing difficulties had severe dysphagia for 2 weeks after the injection. Patient reports of dysphagia prior to injection may indicate a greater likelihood of significant dysphagia following thyroarytenoid injection with botulinum toxin type A.     

Long-term therapy for spasmodic dysphonia: acoustic and aerodynamic outcomes

OBJECTIVE: To evaluate the long-term aerodynamic, acoustic, and electromyographic effects of serial botulinum toxin (BT) injections in patients with adductor spasmodic dysphonia. DESIGN: Two-year, nonrandomized, controlled, before-after study. SETTING: Ambulatory care clinic at a single academic medical center. PATIENTS: A convenience sample of 91 patients with adductor spasmodic dysphonia evaluated and treated during 2 years and 64 age- and sex-matched controls. INTERVENTIONS: Injections of BT into the thyroarytenoid muscles in conjunction with electromyographic evaluation and acoustic and aerodynamic evaluation before and after serial BT injections. MAIN OUTCOME MEASURES: Translaryngeal airflow, jitter, shimmer, signal-to-noise ratio, fundamental frequency, standard deviation of fundamental frequency, maximum phonation time, and inappropriate muscle activity by electromyography. RESULTS: Translaryngeal airflow, jitter, and shimmer improved significantly after serial BT treatments and showed sustained improvement over time. Fundamental frequency, standard deviation of fundamental frequency, and signal-to-noise ratio did not change significantly after BT treatment. Electromyographic data suggested decreased inappropriate muscle activity with repeated BT injections. CONCLUSION: Treatment with BT provides ongoing relief of voice perturbations in patients with adductor spasmodic dysphonia who undergo long-term cumulative therapy.     

Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): A 12-year experience in more than 900 patients

Objectives: This paper reviews a 12-year experience in more than 900 patients with spasmodic dysphonia who have been treated with botulinum toxin. Study Design: This is a retrospective analysis of patients with adductor spasmodic dysphonia (strainstrangled voice), abductor spasmodic dysphonia (whispering voice), and adductor breathing dystonia (paradoxical vocal fold motion), all of whom have been treated with botulinum toxin injections for relief of symptom. Methods: All of the patients were studied with a complete head and neck and neurologic examination; fiberoptic laryngostroboscopy; acoustic and aerodynamic measures; and a speech evaluation including the Universal spasmodic dysphonia rating scale. Some were given electromyography. All patients received botulinum toxin injections into the affected muscles under electromyographic guidance. Results: The adductor patients had an average benefit of 90% of normal function lasting an average of 15.1 weeks. The abductor patients had an average benefit of 66.7% of normal function lasting an average of 10.5 weeks. Adverse effects included mild breathiness and coughing on fluids in the adductor patients, and mild stridor in a few of the abductor patients. Conclusion: Botulinum toxin A injection of the laryngeal hyperfunctional muscles has been found over the past 12 years to be the treatment of choice to control the dystonic symptoms in most patients with spasmodic dysphonia. Laryngoscope, 108:1435–1441, 1998     

A,comparison of bilateral and unilateral botulinum toxin treatments for spasmodic dysphonia

Summary To assess the efficacy of bilateral or unilateral botulinum treatments for spasmodic dysphonia we injected botulinum toxin (type A) into the thyroarytenoid muscle of 24 patients with adductor type spasmodic dysphonia. Eleven patients underwent unilateral procedures and 13 bilateral procedures. Samples of sustained phonation were analyzed acoustically by a computer-assisted method and the air flow rates determined. All tests were conducted 1 week before injection and 1 week and 1 month after treatment. With unilateral injection, improvements in acoustic parameters occurred as early as 1 week after treatment. With bilateral injections, only the voice break factor was significantly reduced after 1 week, while standard deviations of fundamental frequency, jitter, shimmer and signal-to-noise-ratios were reduced 1 month after treatment. In comparison with unilateral injections, the mean air flow rate was twice as high 1 week after bilateral injections, with no significant differences found 1 month after treatment. Clinically, both injection modes resulted in the reduction of laryngeal spasms as early as within 48 h after injection.Portions of this work were presented at the 63th Annual Meeting of the German Society of Oto-Rhino -Laryngology-Head and Neck Surgery, Garmisch-Partenkirchen, 30 May–3 June 1992     

Botulinum toxin for the treatment of spasmodic dysphonia

Spasmodic dysphonia is a focal laryngeal dystonia. Laryngeal dystonia presents as: adductor spasmodic dysphonia with the characteristic strain-strangle voice; abductor spasmodic dysphonia with hypophonia and breathy breaks in connected speech; and adductor respiratory dystonia with paradoxical vocal fold motion and intermittent stridor. Current treatment with periodic laryngeal intramuscular injections of botulinum toxin A has allowed patients to function more normally. In this article, the authors' treatment paradigm and experience in treating over 900 patients with laryngeal dystonia are discussed.     

痉挛性发音障碍诊断及治疗的研究

目的对痉挛性发音障碍患者临床特点,喉肌电图表现,疗效进行分析,探讨痉挛性发音障碍诊断及治疗特点。方法对22例痉挛性发音障碍患者治疗前后症状、嗓音声学特征,频闪喉镜下声带状态,喉肌电图特征进行分析;根据不同分型,应用肉毒素A行特定肌肉注射并观察疗效。结果22例痉挛性发音障碍患者中,内收肌型18例(81 8% ),外展肌型4例(18 2% )。内收肌型患者发音嘶哑,音质紧张、言语中断,发音时声带过度内收,杓间区明显,伴局部震颤; 2例患者发音时还同时伴有舌及软腭震颤;肌电图甲杓肌运动单位电位(motorunitpotential,MUP)振幅明显增加(P<0 01),干扰相呈密集束状放电,募集活动异常活跃,幅度明显增大(700~2500μV)。4例外展肌型患者发音低哑、震颤,气息声明显,发音时声门闭合不良;环杓后肌MUP振幅明显增加,在374~538μV间,募集活动异常活跃,幅度增大(3000~5000μV)。内收肌型患者应用肉毒素A进行甲杓肌注射,单侧剂量大于2 5U疗效明显。症状开始改善时间为注射后6h~2d,平均( x±s,下同)为( 1 4±0 8)d, 2周时最为明显,肌电图及喉肌诱发电位显示药物作用完全,注射肌肉失神经支配。疗效维持8~24周,平均维持(15 2±4 9)周,副作用包括不同程度的发音气息声,声门闭合不良,吞咽不适,饮水呛咳。外展肌型患者采用环杓后肌     

Findings of multiple muscle involvement in a study of 214 patients with laryngeal dystonia using fine-wire electromyography

Although perceptual and stroboscopic data help in diagnosing and classifying laryngeal dystonia, these measures do not aid the voice clinician in targeting which specific muscles to treat with botulinum toxin. Most patients achieve smoother, less effortful voicing with standard injection regimens. However, there is a notable failure rate. We performed fine-wire electromyography on 214 consecutive patients with laryngeal dystonia. We correlated voice ratings, stroboscopy data, and fine-wire electromyography data. Videostroboscopy was successful in visually demonstrating most of the audible findings in isolated vocal tremor, but it was much less successful in identifying breaks alone or a combination of breaks and tremor. Fine-wire electromyography revealed that the thyroarytenoid muscle was significantly more likely than the lateral cricoarytenoid muscle to be the predominant muscle associated with adductor spasmodic dysphonia, and that the thyroarytenoid and lateral cricoarytenoid muscles were equally likely to be predominantly involved in tremor spasmodic dysphonia. In addition, several patients in both the adductor spasmodic dysphonia and the tremor spasmodic dysphonia groups presented with interarytenoid muscle predominance. All of the intrinsic laryngeal muscles are capable of being the predominant muscle in laryngeal dystonia, and there are patterns of muscle abnormalities that differ between adductor spasmodic dysphonia and tremor spasmodic dysphonia. Some of the failures in treating adductor spasmodic dysphonia with botulinum toxin, and the greater difficulty with success in treating patients with tremor spasmodic dysphonia, are due to failure to deliver toxin to the appropriate muscles.     

Effects of botulinum toxin therapy in patients with adductor spasmodic dysphonia: acoustic, aerodynamic, and videoendoscopic findings.

Botulinum toxin has been previously reported to be successful in the treatment of spasmodic dysphonia. To objectively document results, 11 patients with adductor spasmodic dysphonia who received unilateral treatment of the thyroarytenoid muscle were studied. Acoustic analyses and airflow rates during sustained phonation and flexible videoendoscopy were performed prior to, 1 week and 1 month after injection. 1. Acoustic parameters demonstrated significant voice improvement, although abnormal characteristics remained. 2. Mean airflow rates were increased 1 week after injection with almost normal values 1 month later. 3. Videolaryngoscopy showed an effective reduction of intrinsic laryngeal muscle hyperfunction with less effect on extrinsic muscle activity. Interrelations between videolaryngoscopic rating scores, acoustic results and aerodynamic results are discussed.     

Die Behandlung laryngealer Bewegungsstörungen mit Botulinumtoxinen

Laryngeal dystonia (spasmodic dysphonia) is a movement disorder characterised by involuntary contractions of the laryngeal muscles involved in vocalisation. The introduction of botulinum toxin (BTX) in the treatment of laryngeal dystonia had a major clinical impact due to the striking improvement of symptoms. Most patients with severe types of spasmodic dysphonia are treated with injections of botulinum toxin type A. For patients with a resistance against type A toxin there is a new hypercleaned type A toxin or type B available. Research on type F toxin is also underway. In this article, the history of botulinum toxin, its therapeutic activity and possibilities for its use are described.     

Resistance to botulinum toxin injections for spasmodic dysphonia

A known complication of botulinum toxin injections in the treatment of dystonia has been the occasional development of resistance. This has been seen primarily with patients who receive injections for torticollis. We report on 2 patients who, after several years of receiving injections for spasmodic dysphonia, developed clinical resistance by failing to have expected voice improvement after receiving laryngeal reinjection. One of the 2 patients demonstrated antibodies to botulinum toxin by mouse neutralization bioassay. The second patient had negative bioassay results but had no clinical response to the test toxin injection of facial muscles. These cases demonstrate that, although uncommon, resistance to botulinum toxin injections can occur in the treatment of spasmodic dysphonia. We offer suggestions to limit this complication.     

Botulinum toxin management of adductor spasmodic dysphonia after failed recurrent laryngeal nerve section

This study examined botulinum toxin type A (BTX-A) treatment of adductor spasmodic dysphonia patients who had previously undergone recurrent laryngeal nerve section that failed to control symptoms. Information was retrieved from records of patients treated by our group between 1984 and 1999. Complete records with standardized outcome measurements were available for 181 BTX-A injection sessions in 16 patients who had had nerve section. These were compared to previously published information regarding 4,621 sessions in 639 adductor spasmodic dysphonia patients also treated by our group. Treatment with BTX-A resulted in significant improvement in voice function in the studied patients (change, 38.2% +/- 24.5%; p < .0001). The onset of effect took place approximately 2.3 days after treatment, and the peak effect about 10.0 days after treatment. The therapeutic effect lasted 14.1 weeks on the average. These features were not significantly different from those observed in adductor spasmodic dysphonia patients as a whole. The incidence of complications was also comparable. However, lower baseline and peak posttreatment perceptions of voice function in the nerve section group were statistically significant (baseline, 45.6% +/- 23.0% versus 52.4% +/- 22.0%; peak, 83.8% +/- 16.4% versus 89.7% +/- 13.0%; both p < .001). We conclude that BTX-A is effective in the treatment of adductor spasmodic dysphonia in patients who have had recurrent nerve section. However, nerve section may adversely affect perceived voice function and may make botulinum toxin therapy less satisfactory. Because of this finding, and because of the unusual pathological features of the focal dystonias, irreversible means of treating adductor spasmodic dysphonia should be approached with caution.     

Diagnostic and therapeutic difficulties in laryngeal dystonia

Spasmodic dysphonia is a focal laryngeal dystonia. It presents as: adductor spasmodic dysphonia with the strain-strangle voice; abductor spasmodic dysphonia with whispering voice and breathy breaks in connected speech; and adductor respiratory dystonia with paradoxical vocal fold movements and stridor. It is most commonly treated by the intramuscular injection of botulinum toxin. In this article, the authors discuss difficulties in making diagnosis and treatment in patients with laryngeal dystonia concerning their own cases.     

Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia

The treatment of adductor spasmodic dysphonia using botulinum toxin A was conducted in 13 patients as a double-blind, placebo-controlled study. Patients were diagnosed independently by an interdisciplinary team consisting of speech pathologists, an otolaryngol-ogist, and a neurologist. The toxin or saline was injected into each thyroarytenoid muscle under electro-myographic and laryngoscopic guidance. Botulinum toxin A markedly reduced perturbation, decreased fundamental frequency range, and improved the spectrographic characteristics of the voice. Fundamental frequency and phonation time remained unchanged. Patients injected with botulinum toxin A noticed significant improvement in their voices in comparison with the placebo-treated group. Excessive breathiness of the voice occurred in two patients, and mild bleeding in one patient in the botulinum toxin A-treated group. Injection with saline resulted in edema of the vocal cord in one patient. Botulinum toxin A proved to be an effective and safe treatment of adductor spasmodic dysphonia.     

Effects of botulinum toxin on pathophysiology in spasmodic dysphonia

To determine the mechanism of symptom relief with treatment by botulinum toxin injection in persons with adductor spasmodic dysphonia (ADSD), we evaluated the effects of unilateral thyroarytenoid muscle injections on both injected and noninjected muscles in 10 subjects with ADSD, using electromyography on both sides of the larynx before and after treatment. The subjects' speech symptoms were reduced (p = .005) 2 weeks following injection, when the electromyographic study occurred. Muscle activation levels and the numbers of spasmodic muscle bursts decreased significantly (p < or = .03) postinjection in both the injected and noninjected muscles. The reductions in laryngeal muscle bursts correlated with symptom reduction (r > or = .7) in all muscles. Reductions in laryngeal muscle bursts did not relate to either absolute or normalized levels of muscle activity before or after botulinum toxin injection. The results suggest that changes in the central pathophysiology are responsible for changes in speech symptoms following treatment.     

Laryngeal spasm and tracheostomy after hydroxyapatite injection laryngoplasty

IntroductionAdductor spasmodic dysphonia (Ad-SD) is usually treated by botulinum toxin injection into the thyroarytenoid muscles. In older patients, atrophy of these muscles is responsible for glottic leak, causing presbyphonia and is managed by vocal fold medialization using autologous fat or hydroxyapatite (HA). We report the first case of uncontrollable laryngeal spasm requiring tracheostomy after hydroxyapatite injection laryngoplasty in a patient with spasmodic dysphonia and presbyphonia.Case reportAn 83-year-old man had been treated for Ad-SD by botulinum toxin injections every six months for 14 years. Due to severely disabling glottic leak, autologous fat injection laryngoplasty was then successfully performed. Six months later, following recurrence of severe hypophonia, hydroxyapatite injection was performed, subsequently complicated by immediate acute respiratory distress secondary to adductor laryngeal spasm requiring reintubation and tracheostomy. The postoperative course was marked by gradual recovery of vocal fold mobility with decannulation on day 12.DiscussionThis case allows a discussion of the possible pathophysiological mechanisms responsible for adductor laryngeal spasm. Vocal fold medialization procedures should be performed with caution in patients with Ad-SD.     

Increased stability of airflow following botulinum toxin injection.

OBJECTIVES: The purpose of this study was to determine whether stability of airflow, as well as mean airflow, increased following botulinum toxin injection to laryngeal and extralaryngeal muscles in persons with spasmodic dysphonia (SD), some with associated vocal tremor (VT). STUDY DESIGN: Aerodynamic data were collected from five subjects before and at 2, 4, and 8 weeks after they received treatment by each of two different arms in an injection protocol in a crossover study. One arm of the protocol involved treatment of the thyroarytenoid muscles only. The other arm involved treatment of both the thyroarytenoid muscles and the strap muscles. METHODS: Measures of mean airflow and coefficient of variation (COV) of airflow during phonation were obtained. A decrease in the COV of airflow would indicate increased stability of phonatory airflow. RESULTS: Before treatment, all subjects with SD/VT exhibited mean airflows that were similar to controls. The COV of airflow ranged from normal to substantially elevated. Following botulinum injection, mean airflow characteristically increased and COV of airflow decreased. CONCLUSIONS: This finding suggests there is a change in the type, as well as the level, of activity in the muscles of speech production following botulinum toxin injection. The increase in airflow stability identified could be due to increased stability of the laryngeal system and possibly of the respiratory system as well.     

Dosierung von Botulinumtoxin Typ B bei spasmodischer Dysphonie vom Adduktortyp

Today, most patients with severe adductor type spasmodic dysphonia are treated with repeated injections of botulinum toxin type A (BTA). It is known that patients who have been treated for many years and have received a high cumulative dosage may develop antibodies against BTA, making them "resistant" to further injections. For these patients, botulinum toxin type B (BTB, NeuroBloc) is considered to be a new chance to continue the treatment. When changing to BTB, one has to find an "equivalent dosage" which is estimated for cervical dystonia to be 25-33-fold of the previous Botox dosage and the 10-13-fold for the previous Dysport dosage. We report on a 62 year old female patient with antibodies against BTA. For maximum care, the first injection of BTB was performed with the sixfold of the previous Dysport dosage, which was almost the half of the needed dosage predicted from experience with cervical dystonia. The relief only lasted 3 weeks and was therefore disappointing. For the subsequent injections, we consulted Sataloff who also had one patient with antibodies treated with BTB. Based on his personnel advice, we chose the 30-fold dosage, which was effective for 3 months, resulting in improvements to voice quality (both psychoacoustic rating and acoustic measures), voice "quantity" (voice range profiles), aerodynamics (maximum phonation time, phonation quotient), and voice handicap. As with Sataloff et al. (2002), we found that the dosage of BTB probably has to be much higher than in cervical dystonia.     

Histology of nerves and muscles in adductor spasmodic dysphonia

To elucidate the etiology and pathophysiology of spasmodic dysphonia, we examined the adductor branch of the recurrent laryngeal nerve and the lateral cricoarytenoid muscle from 9 consecutive patients with this disorder who were previously treated with botulinum toxin. Histologic examination revealed average muscle fiber diameters ranging from 21 to 57 microm. Botulinum toxin treatment-related muscle atrophy was observed up to 5 months after injection. Endomysial fibrosis was present in all samples. Histochemical analysis in 8 patients revealed type 2 fiber predominance in 7 patients and fiber type grouping in 2. Type-specific muscle fiber size changes were not present. Nerve samples were examined in plastic sections. In 8 patients the nerves contained homogeneous, large-diameter myelinated nerve fibers and sparse small fibers. One patient had a relatively increased proportion of small myelinated nerve fibers. Overall, the nerve fiber diameter was slightly larger in patients than in controls. These findings may implicate the central nervous system in the pathophysiology of adductor spasmodic dysphonia.     

Effects of botulinum toxin on vocal tract steadiness in patients with spasmodic dysphonia

Since laryngeal botulinum toxin (BTX) injections have become the treatment of choice for spasmodic dysphonia, the purpose of this study was to examine its effects on the stability of the upper vocal tract as compared to the effects on glottic stability. Two different acoustic methods were used to analyze voice samples from 16 patients with adductor-type spasmodic dysphonias before and after BTX therapy and from a normal control group. Independent acoustic analyses were used to determine laryngeal and upper vocal tract stability. The results showed significantly higher values for the standard deviation of fundamental frequency (SDFO), reflecting laryngeal instability, for the patient group than for the control group and an impressive improvement for the patients after BTX therapy. Further, the equally high values of SDFO for the initial second and a second from the midsegment of phonation were differentially reduced by BTX therapy, resulting in a normal pattern of laryngeal stability during sustained phonation. The variability of the first and second formants, reflecting upper vocal tract instability, showed higher values for the patients compared with the control group, but this difference was not statistically significant. The present findings showed that BTX injections to the thyroarytenoid muscle had no discernible effect on stability of the upper vocal tract.Presented in part at the 65th Annual Meeting of the German Society of Oto-Rhino-Laryngology-Head and Neck Surgery, Chemnitz, 14–18 May 1994 and the First World Voice Congress in Oporto, Portugal, 9–13 April 1995     

Management of supraglottic squeeze in adductor spasmodic dysphonia: a new technique

OBJECTIVES: Spasmodic dysphonia is a disabling disorder of the voice characterized primarily by involuntary disruptions of phonation. Botulinum toxin injections of the thyroarytenoid muscles have been the treatment of choice for adductor spasmodic dysphonia (ADSD). We describe a new technique to address the problem of compensatory or supraglottic hyperadduction in some of these patients. STUDY DESIGN: Case series. METHODS: Four patients with ADSD with sphincteric supraglottic contraction were seen for evaluation of botulinum toxin injection. On fiberoptic exam, it was noted that they had type I hyperadduction of the true vocal cords with a significant type III, and/or type IV hyperadduction of the supraglottis. After standard management of the thyroarytenoid muscles, the strained/strangled voice continued. On fiberoptic exam it was noted that the vocal folds were weakened, but the supraglottic hyperfunction persisted. The patients were treated by speech therapists to unload their supraglottis without success. All patients then had their oblique portion of the lateral cricoarytenoid muscles injected with botulinum toxin A through a thyrohyoid approach. This was done in the office under electromyographic control. RESULTS: On follow-up, all patients demonstrated improvement in the quality of their voices (as compared to thyroarytenoid injections alone). CONCLUSIONS: We describe a new technique for injection of the supraglottic portion of the lateral cricoarytenoid muscles. We demonstrate this can be done safely and successfully in an office setting with electromyography control.