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     

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.     

Alternating Unilateral Botulinum Toxin Type A (BOTOX®) Injections for Spasmodic Dysphonia

Injection of botulinum toxin type A (BOTOX^®) into both thyroarytenoid muscles is an accepted treatment for spasmodic dysphonia. The authors of this study identified patients who could not tolerate the interval of breathy voice that immediately follows bilateral injections. These patients were offered a protocol in which the injection side was alternated on subsequent treatments. Eighteen patients who received at least two bilateral injections and two unilateral injections were reviewed. Alternating unilateral injections yielded a shorter breathy interval by an average of 12.7 days (P=.0007) and a shorter duration of return of spasmodic symptoms by an average of 26.0 days (P=.0006). Compared with bilateral injections, alternating unilateral injections yielded an average(median) of 3.2 more days of strong voice per day of breathy voice (P=.001). However, unilateral injections had a shorter average interval of strong voice (27.4 days; P=.007), as well as a slightly higher failure rate (4.9% vs. 1.1%). The authors conclude that alternating unilateral botulinum toxin type A injections are useful in patients with spasmodic dysphonia who have difficulty with the breathy voice that follows bilateral injection.     

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 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.     

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.     

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.     

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.     

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.     

Contemporary management of spasmodic dysphonia

PURPOSE OF REVIEW: To review current concept in spasmodic dysphonia management. RECENT FINDINGS: The standard of care for spasmodic dysphonia in 2004 remains botulinum toxin chemodenervation for symptomatic management. This is supported by a large body of literature attesting to its efficacy in many different hands, particularly for the adductor form of the disorder. New surgical approaches await the crucial test of time, in view of historical difficulties in achieving long-term benefit via recurrent nerve section, and currently, surgery is best reserved for the rare patient who does not benefit or cannot tolerate botulinum toxin injections. Despite efforts to refine both surgical and botulinum toxin treatment, symptom relief in abductor spasmodic dysphonia and dystonia with tremor remains suboptimal. SUMMARY: Spasmodic dysphonia is a disorder of the central nervous system rather than the larynx, and as in other forms of dystonia, interventions at the end organ have not offered a definitive cure. The pathophysiology underlying dystonia is becoming better understood as a result of discoveries in genetically based forms of the disorder, and this approach is the most promising avenue to a long-term solution.     

Laryngeal dystonia: a series with botulinum toxin therapy

Laryngeal dystonia is a syndrome characterized by action-induced, involuntary spasms of the laryngeal muscles. Most patients have involvement of the adductor laryngeal muscles producing uncontrolled spasms during phonation, and a "strain-strangle" speech pattern commonly termed "spastic dysphonia." Other patients have involvement of the abductor muscles producing "whispering dysphonia." Rare patients have paradoxical vocal cord motion during respiration with adductor spasms on inspiration. Over the past 5 years we have used botulinum toxin (BOTOX) to treat more than 200 patients with laryngeal dystonia. This group includes patients with adductor involvement (phonatory dystonia, recurrent laryngeal nerve section failure, respiratory dystonia) and those with abductor involvement (whispering dystonia). Patients received benefit within 24 to 72 hours, with sustained improvement for 2 to 9 months with an average of 4 months. Patients improved to an average of 90% of normal function. Clinically significant adverse effects included extended breathy dysphonia and mild choking on fluids. BOTOX has become our treatment of choice for dystonic conditions of the larynx.     

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.     

Results of using botulism toxin in the treatment of spasmodic dysphonia

Spasmodic Dysphonia (SD) is a dystonia involving laryngeal musculature thus causing a characteristic voice disorder. Two main types of SD have been described. The adductor type is the commonest and it is characterized by a strain-strangle, choked voice. The abductor type can be distinguished from the previous one by episodes of a blown and whispering voice, interrupting speech. Botulism toxin (BTX) has demonstrated to be the most effective treatment for this condition. Thirty patients diagnosed of SD (twenty-nine adductor type/one abductor type) were included. Their degree of dysphonia was evaluated using both functional and visual-analogue scales. They were treated with BTX vocal cord injections using a percutaneous technique under EMG guidance. Improvements up to a 100% of the normal vocal function were obtained, with an average of 82% in the adductor type. The adverse effects were mild and transient. Hypophonia affected 61.3% of patients lasting an average of 11.3 days. Dysphagia was reported in 44.1% of cases lasting an average of 5.8 days.     

Safety of simultaneous bilateral botulinum toxin injections for abductor spasmodic dysphonia

OBJECTIVE: To review the safety of simultaneous bilateral posterior cricoarytenoid muscle botulinum toxin injections. DESIGN: Retrospective case series review. SETTING: Tertiary care academic clinic. PATIENTS: Twenty-one patients with abductor spasmodic dysphonia. INTERVENTIONS: Patients received 100 simultaneous bilateral posterior cricoarytenoid muscle botulinum toxin injections for isolated abductor spasmodic dysphonia over a 6-year period. MAIN OUTCOME MEASURES: Major and minor complications, injection dosing, and demographics. RESULTS: The total bilateral botulinum toxin injection dose per session ranged from 2.50 to 7.50 U, and the average total bilateral dose per patient was 4.70 U. There were no major complications, and minor complications were self-limited. There was a 5% incidence of significant dyspnea and a 2% incidence of dysphagia, and all patients were treated conservatively. The average doses at which dyspnea and dysphagia occurred were 4.97 and 5.56 U, respectively. CONCLUSIONS: This case series demonstrates that simultaneous bilateral posterior cricoarytenoid muscle botulinum toxin injection is safe up to the highest doses reported. Complications with this approach are consistent with those previously reported using other methods. Prospective studies on vocal outcome measures are needed for simultaneous bilateral posterior cricoarytenoid muscle botulinum toxin injections to evaluate the efficacy of this technique.     

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.     

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.     

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.     

Treatment of adductor-type spasmodic dysphonia by surgical myectomy: a preliminary report

OBJECTIVES: Despite the belief that it represents a central neurologic dysfunctional process, adductor-type spasmodic dysphonia without tremor is usually effectively treated by injection of botulinum toxin A; however, in most cases such injections must be repeated every few months. A promising new surgical procedure is herein reported. METHODS: Under local anesthesia with intravenous sedation, a large laryngoplasty window is created, and under direct vision with intraoperative voice monitoring, fibers from the thyroarytenoid and lateral cricoarytenoid muscles are removed until breathiness occurs. The two sides are staged; that is, one side is done at a time, with surgery on the second side being performed 3 to 6 months after that on the first side, if needed. RESULTS: This was a retrospective, unblinded study of 5 patients who underwent myectomy of the thyroarytenoid and lateral cricoarytenoid muscles. The preliminary results show improved voice fluency in all patients at 5 to 19 months of follow-up. There was no period of prolonged breathiness or dysphagia in any of the patients, and there were no surgical complications. CONCLUSIONS: Myectomy of the thyroarytenoid and lateral cricoarytenoid muscles is a promising new surgical treatment for adductor-type spasmodic dysphonia that may effectively mimic "permanent" botulinum toxin injections.     

Listening: the key to diagnosing spasmodic dysphonia

Spasmodic dysphonia (SD) is a focal dystonia of the larynx. Adductor spasmodic dysphonia (ADSD) involves the laryngeal adductor muscles, and symptoms of vocal roughness, staccato-like sounds, and stops in phonation. Abductor spasmodic dysphonia (ABSD) affects the laryngeal abductor muscles, resulting in a breathy or whispered voice quality and voice breaks. SD has a significant impact on the quality of life. This article discusses symptoms of SD and the standard treatment of SD.