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     

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.     

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.     

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.     

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.     

Botulinum toxin A injection under electromyographic guidance for treatment of spasmodic dysphonia

Spasmodic dysphonia is a disabling voice condition caused by a chronic neurological disorder of central motor processing. Present therapy is directed at relief of symptoms rather than cure. Botulinum toxin type A injection into the thyroarytenoid muscle has become the pre-eminent approach for treatment of adductor spasmodic dysphonia. Botulinum toxin A injections can be performed in an out-patient setting under electromyographic guidance. We present our experience with 153 injections in 14 patients with adductor spasmodic dysphonia over a 10-year period. We demonstrate that the electromyography signal is a reliable prognostic indicator in terms of efficacy, and that patients' subjective opinion is a valid indicator of treatment success and future treatment strategy.     

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.     

Singer's dystonia: first report of a variant of spasmodic dysphonia

OBJECTIVES: We discuss the phonatory characteristics of a previously undescribed focal laryngeal dystonia present in the singing voice. METHODS: We performed a retrospective chart review of 5 patients with singer's dystonia at a neurolaryngology referral center. RESULTS: Four patients reviewed demonstrated phonatory characteristics consistent with adductor spasmodic dysphonia present in their singing voice. One patient demonstrated abductor spasmodic dysphonia in the singing voice. Each patient initially exhibited normal connected speech in conversational voicing. The treatment protocol and outcome are discussed, including the use of botulinum toxin. CONCLUSIONS: Singer's dystonia is a previously undescribed neurologic disorder that should be understood by those who treat voice performers and voice disorders.     

Effects of Botulinum Toxin Type A Injections on Aerodynamic Measures of Spasmodic Dysphonia

The effects of botulinum toxin type A (BOTOX^®) injections on aerodynamic measures of phonation were examined in 30 patients with adductor spasmodic dysphonia. Patients received bilateral injections of 2.5 U of botulinum toxin type A in each thyroarytenoid muscle. Measures of air pressure, average airflow, coefficient of variation (CV) of airflow, and laryngeal resistance were obtained before the injections and at 2 and 10 weeks after the injections. These measures were also obtained from 12 normal subjects. Compared with normal subjects, the spasmodic dysphonia patients had significantly higher preinjection values for air pressure, CV of airflow, and laryngeal resistance. At 2 and 10 weeks after the botulinum toxin type A injections, the spasmodic dysphonia patients showed a significant increase in the average airflow values and a significant decrease in the CV of airflow values and the laryngeal resistance values. At 10 weeks after the injections, the values for the three measures began to approach the preinjection values. It is concluded that these aerodynamic measures of phonation can provide useful measures of treatment outcome in adductor spasmodic dysphonia.     

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.     

Botox treatment in adductor spasmodic dysphonia: a meta-analysis.

Over the years many studies have been conducted to document the treatment effects of Botulinum toxin type A in adductor spasmodic dysphonia. The results of these studies have led to the view that overall Botulinum toxin treatment is moderately effective. This study reviews efficacy research qualitatively and quantitatively to determine the extent to which this conclusion is fully supported by the data. Although the data indicate moderate overall improvement as a result of Botulinum toxin treatment, they also suggest significant variation across patients, measurements, and treatment conditions. This result, together with methodological limitations and lack of standardization in BT efficacy research, justifies caution when making inferences regarding BT treatment benefit in adductor spasmodic dysphonia.     

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.     

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     

Perceptual analyses of spasmodic dysphonia before and after treatment

OBJECTIVE: To evaluate expert listeners' perceptions of voice and fluency in persons with adductor spasmodic dysphonia (ADSD) before and after treatment with botulinum toxin type A (Botox), as a function of initial severity of the disorder (while controlling for patients' age at injection). DESIGN: Simple before-and-after trial with blinded randomized listener judgments. SETTING: Ambulatory care clinic at a single medical center. PARTICIPANTS: Forty-two consecutive patients with ADSD who underwent examination, with a 3- to 6-week follow-up, after initial botulinum toxin type A injection. There were also 42 age- and sex-matched healthy control subjects. INTERVENTIONS: Injections of botulinum toxin type A into the thyroarytenoid muscle(s). MAIN OUTCOME MEASURES: Computer-implemented visual analog scaling judgments of voice quality and speech fluency made by expert listeners under psychoacoustically controlled conditions. RESULTS: Response to botulinum toxin type A varied markedly as a function of pretreatment severity of ADSD. More severe initial symptoms exhibited greater magnitudes of improvement. Patients with mild dysphonia did not exhibit pretreatment to posttreatment change. Following treatment, voice and fluency remained significantly (P<.05) poorer in ADSD than in healthy speakers. Older patients exhibited less improvement than younger patients when the effect of initial severity was statistically controlled. CONCLUSIONS: Voice quality and fluency improved for most patients following treatment, but older patients and those with milder dysphonia exhibited the least optimal responses to the procedure. Patients who were profoundly impaired demonstrated the greatest amount of improvement. Computer-implemented visual analog scaling provided a reliable clinical tool for determining treatment-related changes in those with ADSD.     

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.     

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.     

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     

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.     

Longitudinal follow-up of adductor spasmodic dysphonia patients after botulinum toxin injection: quality of life results

OBJECTIVE: Botulinum toxin injections are used routinely to treat patients with adductor spasmodic dysphonia. After an initial "breathy phase," most patients experience improvement for a few weeks to months and then a gradual decline until their next injection. In this study, voice-related quality of life (VRQOL) data were collected at 4 week intervals through one to three injection cycles in an attempt to quantify the proportion of each cycle during which patients experience meaningful benefit. STUDY DESIGN: Prospective, nonrandomized case series. METHODS: Patients receiving stable-dose botulinum injections for adductor spasmodic dysphonia were invited to participate. Voice recordings and clinical outcomes data were collected by telephone every 4 weeks throughout each injection cycle. Quality of life data were normalized for cycle length and interpolated to generate composite curves. RESULTS: Twenty-two patients completed data collection for at least one full injection cycle. The average cycle was 25.9 weeks; the mean age was 59.8 years. On a 100-point scale, the total VRQOL scores peaked at 77.4, at 30% of the cycle, then gradually declined. The social-emotional (SE) subscale scores were significantly better than the physical subscale scores (P < .05). The total VRQOL score exceeded 75 during only 14% of the cycle (52.6% for SE subscores, 0% for physical subscores). If the threshold is lowered to 70, the total VRQOL exceeded this level during 54.6% of the cycle (69.6% for SE subscores, 44.1% for physical subscores). For the 11 patients completing three full injection cycles, there were no significant differences between the three cycles, and the mean VRQOL scores were similar to the values given above. At the beginning and end of each cycle, the total VRQOL scores averaged 52.8 (56.0 for SE subscale, 50.7 for physical subscale). CONCLUSION: Although botulinum toxin injections provide significant improvement for these patients, the initial breathy phase and the late declining phase add up to a significant proportion of each cycle spent with a reduced quality of life. At best, the total VRQOL averaged below 80%. This longitudinal study provides a unique look at the effect of this condition and its treatment on these patients' lives. A suitable long-term treatment for this condition is needed to eliminate the cyclical voice results experienced with the botulinum toxin injection approach.     

Selective denervation: reinnervation for the control of adductor spasmodic dysphonia

OBJECTIVES: The objective of this study was to evaluate the efficacy of a new surgical procedure for adductor spasmodic dysphonia (AddSD). This surgery involves the bilateral selective division of the adductor branches of the recurrent laryngeal nerves with immediate reinnervation of the distal nerve trunks with branches of the ansa cervicalis (selective denervation-reinnervation). METHODS: Our first six patients to undergo this procedure were enrolled in the study. All patients suffered from AddSD and had previously received botulinum toxin A (Botox, Allergen, Markham, ON) therapy. Patients were recorded preoperatively and all underwent the same surgical procedure performed by the same lead surgeon. All patients were surveyed postoperatively and then re-recorded. Expert and untrained judges undertook perceptual evaluation of voice quality. Voice samples were also objectively evaluated for aphonic voice breaks. RESULTS: No major surgical complications were noted. Patient satisfaction was excellent, and five of the six patients no longer require botulinum toxin therapy. In five of the six patients, the majority of untrained and expert listeners perceived the postoperative voice to be superior. Objectively, the rate of aphonic voice breaks was also reduced in five of the six patients.