Spasmodic Dysphonia: Let’s Look at That Again Thomas Murry, New York, New York Summary: G. Paul Moore influenced the study of spasmodic dysphonia (SD) with his 1960 publication that examined the neurological, medical, and vocal fold behavior in a group of patients with adductor spasmodic dysphonia (ADSD). This review of advances in the diagnosis and treatment of SD follows a time line of research that can be traced in part to the early work of Moore et al. This article reviews the research in ADSD over the past 50 plus years. The capstone events that brought SD to its present day level of management by laryngologists and speech-language pathologists are highlighted. A look to the future to understand more of the disorder is offered for this debilitating disorder. Key Words: G. Paul Moore–Adductor spasmodic dysphonia–Botulinum toxin. INTRODUCTION Spasmodic dysphonia (SD) is a disorder of speech and voice in which irregular and uncontrolled vocal spasms interrupt the normal speech flow. Irregular voice breaks, effortful phonation, and breathiness are thought to start out gradually and then progress slowly before becoming chronic.1–3 Using high-speed motion pictures, Moore4 described SD as an intermittent squeezing of the vocal folds disrupting the flow of speech. Early reports of this disorder (also called spastic dysphonia [SD]) were thought to be psychosomatic.5 For almost 100 years, the literature persisted on categorizing this disorder as a personality disorder managed by counseling and voice therapy. However, there is now sufficient evidence to show that SD is a task-specific focal dystonia of the larynx consisting of disruptions in the speech and voice.6,7 Since the early work of Moore and others, two major types of SD have emerged. Adductor spasmodic dysphonia (ADSD) is characterized by interruptions in the closure of voice during speech. Abductor spasmodic dysphonia (ABSD) is characterized by breathy interruptions of ongoing phonation. A small percentage of patients have signs of both ADSD and ABSD. This discussion will focus primarily on ADSD and the research and treatments that have evolved over the last 55 years to manage this disorder. EARLY YEARS OF ADSD The history relating SD to G. Paul Moore dates back to the early 1960s and reflects the character of Moore’s clinical and scientific acumen. He was often found in the voice laboratory to say ‘‘Let’s look at that again.’’ His interest in ‘‘spastic’’ dysphonia derived from his continuing approach to understanding the biomechanics and neurological functions of the larynx, specifically the vocal folds, and to find evidence that would guide the treatment of patients. He indicated that early experimental work suggested that the cause may be neurological. Moore developed a strong interest in SD based on the early work of Berendes8 who described many of the characteristics of the speech Accepted for publication March 17, 2014. The G. Paul Moore Lecture, 42nd Annual Symposium: Care of the Professional Voice, Philadelphia, PA, June 1, 2013. From the Department of Otolaryngology—Head and Neck Surgery, Weill Cornell Medical College, New York, New York. Address correspondence and reprint requests to Thomas Murry, Department of Otolaryngology—Head and Neck Surgery, Weill Cornell Medical College, 1305 York Avenue, 5th Floor, New York, NY 10021. E-mail: [email protected] Journal of Voice, Vol. -, No. -, pp. 1-6 0892-1997/$36.00 Ó 2014 The Voice Foundation http://dx.doi.org/10.1016/j.jvoice.2014.03.007
of individuals that now have been documented to be associated with SD. Another early investigator of SD, Arnold,9 originally felt that SD was because of primitive subcortical centers acting without inhibition in patients with known personality problems.9 Nonetheless, in 1959, despite these early suggestions that there may be a neurological basis for the disorder, there was still a persistent belief that disruptions in personality had a strong relationship to the disorder. In 1960, Robe et al10 reported on 10 patients diagnosed with SD ranging from 6 months to 15 years. The subjects completed questionnaires, had thorough ear, nose, and throat examinations as well as neurological examinations, and they also underwent electroencephalograms. All these patients had signs of central nervous system abnormalities. Their signs included irregular discharges in the right temporalparietal region in nine of the 10 subjects, four subjects with familial neurological diseases, eight with transient leg or arm weakness, and other conditions such as parasthesias in the hands, arms, or legs. Several of the subjects reported the onset associated with a sickness such as an upper respiratory disease or with stressful events leading up to the onset of the condition. Robe et al10 concluded that SD was a phonatory disorder resulting from a disturbance in neural function and possible neural structure. This was the first study to present clinical neurological evidence that SD was linked to a neurological disorder. This work of Moore et al opened up new avenues of study with the hope that treatment options would follow. Soon after the classic work of Moore et al, Aronson et al11 identified two types of the disorders, adductor consisting of strained and strangled speech production and abductor, an intermittent breathiness. They suggested that these disorders demonstrated a somewhat different movement pattern in the larynx than the rigidity of spastic muscles, hence the term spasmodic dysphonia (either adductor spasmodic dysphonia, ADSD or abductor spasmodic dysphonia, ABSD). These terms have been used consistently since 1968. In the 1960s, several studies reported on various behavioral treatment attempts despite the trend at that time toward a neurological basis. Rethi12 suggested inspiratory and expiratory phonation exercises similar to those used to treat stuttering. Bloch13 examined the neuropsychological aspects of the disorder in an attempt to identify patterns of behavior that may contribute to the disorder and therefore be amenable to medical treatment and counseling. Their results did not show long-term positive outcomes. Although the evidence for a neurological basis of SD began to mount in the 1960s, it was not until 1976 that direct evidence
2 was presented to show that SD was a neurological disorder. Dedo temporarily paralyzed the recurrent laryngeal nerve (RLN), and a significant improvement in voice quality resulted. Dedo14 reported the sectioning of the RLN in 34 patients with ADSD. Izdebski et al15 reported that with postoperative voice therapy, all subjects exhibited some improvement and approximately one-half of the group returned to a near normal voice but with less overall volume. Dedo et al16 subsequently found that through histological analysis of the RLN, patients with ADSD had significantly more abnormalities compared with age-matched controls. The finding of a change in the speech and voice after resection of the RLN led others to try it. However, sectioning of the RLN was not universally accepted, and later Aronson17 reported that in some subjects the long-term results were poor.
THE BOTULINUM TOXIN ERA The findings by Dedo14,16 and Robe et al10 encouraged other investigators to look more closely at the disorder. Electromyographic results of Kiml,18 Tluchowski,19 as well as Caraceni and Zibordi20 identified abnormalities in the peripheral nerve or in the corticonuclear tracts suggesting that a neurological abnormality exists in patients with spastic speech. These findings were later supported with studies by Sellin et al,21 Rosenfield et al,22 Jankovic,23 and Dolly et al24 that paved the way for the treatment of the dystonic movement of the larynx with botulinum toxin (BTX), a neurotoxin of which the most potent type is type A. Jankovic23 demonstrated the usefulness of BTX in the treatment of Meige symptoms, which are associated with ADSD in a percentage of cases. Early patients’ reports of treatment with BTX were encouraging.25 Blitzer et al26 reported on the first large case series treated with BTX. Initially, BTX was used primarily for ADSD, but later reports of treatment for ABSD followed.26 BTX has since been reported to be safe for the treatment of ADSD and ABSD and has been used to manage SD for the past 30 years. The speech and voice abnormalities of SD achieved greater recognition in the 1980s and 1990s; thanks to the success generated by the work of Dedo14,15 and successful use of BTX as a treatment. However, descriptions and assessments of ADSD remained primarily subjective with perceptual terms such as ‘‘strained-strangled’’ and ‘‘effortful phonation’’ predominant in the literature. Numerous studies of functional outcomes in the voice and speech of patients with SD before and after BTX treatments followed as its use became accepted. Investigators have examined the pre- to post-BTX findings of acoustic, aerodynamic, and perceptual studies in demonstrating the positive voice changes after BTX injections. Treatment of ADSD with BTX over the past 30 years has demonstrated improvements in the acoustic, aerodynamic, and perceptual characteristics of the voice. The results are based on numerous methods of treatment (bilateral injection vs unilateral injection) and various measures obtained from sustained and spoken speech samples. Table 1 summarizes the acoustic and physiological findings. Investigators have found that after BTX injection, there was no significant change in fundamental frequency,
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TABLE 1. A Summary of the Acoustic and Physiological Findings From Studies That Reported Pre- and Post-BTX Results Parameter Vowels Fo Jitter Shimmer Harmonic/noise ratio Subglottic pressure Airflow rate Voice breaks Tremor Speech Mean Fo Speech rate Airflow rate Voice breaks
Findings Unchanged pre vs post BTX Lower post BTX Lower post BTX Lower post BTX Lower post BTX Higher post BTX Near normal 2 wk post BTX Fewer post BTX Improved post BTX Unchanged pre vs post BTX Faster post BTX Higher post BTX Fewer post BTX
jitter, shimmer, signal-to-noise ratio (SNR), and maximum phonation time.27–36 Data from connected speech by Cannito et al35 demonstrated that although overall fundamental frequency did not change after BTX treatment, the number of low frequency events and the SNR were significantly different after treatment compared with pretreatment. Moreover, the variation in fundamental frequency and the SNR were related to listener judgments of voice quality. Investigators did find significant post-BTX changes in the prosodic aspects of speech, namely, the number of voice breaks, time to read a sentence or paragraph, and control of speech intensity.2,28–30,32 Despite the lack of statistical evidence in some of the forgoing studies, the general conclusions from the postBTX data imply an improvement in communication and a closer relationship to normal speech and voice acoustic parameters. Fewer investigators studied the physiological measures associated with treatment using BTX. Airflow measures obtained by Zwirner et al29 and also by Murry and Woodson37 before BTX injection in patients with ADSD were found to be lower than age-matched normal subjects. However, Adams et al36,38 in two different groups found airflow rates to be within normal range before BTX injections. After BTX injection, airflow rate changes increased significantly for the first few weeks and then stabilized to near normal flow rates after the initial period.29,36–38 Physiological measures based on electromyography (EMG) have been studied by Ludlow39 as well as Davidson and Ludlow.40 Based on their EMG findings, Davidson and Ludlow40 suggest that motor unit reorganization may continue long after the effects of the BTX injection dissipate. As might be expected, perceptual studies of ADSD show significant changes after BTX injection. However, it is unsure if the perceptual changes after BTX treatment are related to temporal aspects of the speech or specific acoustic and physiological properties of the voice signal or some combination of the
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changes. Cannito et al41 found a weak positive relationship between voice quality and the combination of frequency variation and SNR measures. Silverman et al42 found that the perceived severity of the dysphonia in ADSD was related primarily to the amount of aperiodicity and the number of voice breaks. Similar to that found by Cannito et al, the perceptual relationships identified by Silverman, and also by Dejonkere et al,43 accounted for only a portion of the variance of the perceptual data. Thus, there remains a need to understand the effects of BTX changes in ADSD on listeners’ perception of voice quality after treatment.
SURGICAL APPROACHES TO THE TREATMENT OF ADSD At the same time, although the use of BTX gained wide acceptance by some, others were not completely satisfied with this treatment method as BTX required frequent injections, relationships between dose and response were unpredictable, and occasional transient swallowing problems occurred. In addition, there was a postinjection period of up to 2 weeks in which the voice was breathy and thus limited communication. As a result, others took a look at the treatment of ADSD and considered surgical procedures that might be useful. In 1980, Isshiki44 reported on a thyroplasty procedure, identified as type II thyroplasty, which divided and widened the thyroid cartilage at the midline thus reducing the squeeze effect of the vocal folds in ADSD. Although this procedure did not gain enthusiasm for the treatment of ADSD in the United States because of the more accessible use of BTX, it nonetheless stimulated interest among surgeons to look for other avenues of treatment for ADSD. Chan et al45 reported on 13 patients with the diagnosis of ADSD who were previously treated successfully with BTX and then were recruited for type II thyroplasty as described by Isshiki. Self-rating assessment of the degree of severity and vocal effort were recorded and compared with the BTX treatment. Patients’ self-assessments and long-term followups were not supportive of the procedure; only five patients reported some degree of satisfaction with the procedure. As knowledge of neural function of the larynx and specifically the vocal folds increased and the growing acceptance of ADSD as a neurological voice disorder evolved, other surgical treatments were explored. Although BTX was successful in reducing laryngeal spasms and patients were generally satisfied with the injections, speech was not normal after BTX injection and more importantly, the speech and voice fluctuated as the BTX wore off. An early animal study reported by Genack et al46 showed that thyroarytenoid (TA) myectomy resulted in reduced vocal fold closure but with vocalization remaining. Other investigations followed this work on patients with ADSD. Although the results by various investigators demonstrated the elimination of severe constrictions and in some cases improved scores on the Voice Handicap Index and other assessment tools, patients remained with a weak voice for protracted periods.47 Weeds et al48 reported on the long-term results of RLN avulsion in 18 patients. Although the patients’ voices remained
3 weak in volume, 16 of the 18 had no recurrence of spasms after 3 years. In patients who were followed longer, they also found that several of those who were offered medialization thyroplasty for their weak voices had a recurrence of spasms despite previous absence of spasms for more than 3 years.48 Following the early surgical options previously mentioned, investigators began to look at ways to reduce the closing force of the vocal folds to reduce the spasm effect in patients with ADSD. Iwamura49,50 reported that the EMG findings of patients with SD showed that the percentage of thin motor fibers in the TA muscle is greater in patients with ADSD than in control subjects. By removing part of the TA muscle and thus reducing the number of thin motor fibers, they found a reduction or elimination in the spasms. The work of Iwamura was followed by Berke et al51 who reported on selective adductor denervation surgery (SLAD-R). Earlier, Green and Berke52 studied the effects of hyperadduction in canines and the effects of denervation. The SLAD-R procedure reduces the force of the closing phase of vibration because of weakening of the TA muscle. Long-term results of the procedure reported by Chhetri et al53 showed that patients had reduced or eliminated the spasms, had lower Voice Handicap Index scores, and were generally satisfied with the results compared with previous treatments with BTX. They reported that patients achieved long-term spasm-free voice with breathiness lasting the first 3–6 months after the surgery. Mendelsohn and Berke54 found that as long as 14 years after the SLAD-R procedure, patients were more satisfied with their voices than when they were previously treated with BTX. Although the SLAD-R procedure is generally no longer used nowadays, the long-term data of Chhetri et al53 as well as Mendelsohn and Berke54 suggest that it is a viable treatment for ADSD, and it represents an alternative to the regular treatments of BTX with its accompanying voice changes as the BTX wears off.
THE CURRENT ERA The pathogenesis of ADSD remains unknown at this time, but a neurological basis including endogenous and exogenous factors is now supported by the literature.55 That is not to say that patients with ADSD do not have psychological issues. It is well known that when patients with ADSD speak under stress, their voice disorders are judged to be more severe than when they hum a tune. Moreover, any significant illness is usually associated with psychological or psychosocial factors. Murry et al56 obtained self-ratings of depression, state anxiety (a temporary anxiety associated with a task such as speaking), and trait anxiety from patients before and after BTX injection. Before BTX treatment, patients exhibited mildly elevated scores of depression and state anxiety but no trait anxiety compared with subjects with other voice disorders. In addition, the BTX pretreatment scores were similar to those in patients with other neuropsychological disorders. The findings were interpreted to suggest that the state of speaking in patients with ADSD before BTX treatment was the basis for anxiety in the 16 of 32 patients who reported elevated state but not trait anxiety. Improvement in speech after BTX resulted in lower scores on all measures.
4 White et al57 recently found that patients with ADSD had no greater scores on depression and anxiety scales than patients with other voice disorders. The current era has increased the understanding of changes that occur in ADSD as a result of chemical and surgical treatments. Currently, there is also an increasing understanding of factors that contribute to the risk and onset of the disorder. Thus, although chemical and surgical procedures offer alternatives to managing ADSD, a better model for management might include an understanding of the factors leading to the disorder. Furthermore, there remains a need to explore these factors for ADSD and ABSD. Perceptual studies have shown that ADSD is characterized by hyperadduction and hypoadduction. High subglottic pressures associated with sudden adduction followed by high airflow associated with voice breaks are the prominent aerodynamic findings correlated with perceptual judgments of ADSD. BTX helps to reduce both these characteristics. After surgical or BTX treatment, episodic high subglottic pressures decrease, airflow rates return to near normal values, and listeners perceive the voice as more normal than before BTX.29,45 Epidemiological studies have recently contributed to a better understanding of factors that are prominently related to ADSD. Izdebski et al15 were the first to explore factors that were associated with ADSD in a group of 200 patients. They found patients with ADSD had extensive histories of voice use and voice use under stress. Schweinfurth et al58 used a questionnaire to evaluate demographics, educational level, work history, and life events in 168 patients and compared their findings to relatives of the patients. They found a 65% history of measles and mumps in the ADSD group compared with the relatives of patients with ADSD. Recently, Tanner55 used an extensive questionnaire with 150 ADSD patients and 136 patients with other structural, neurological, or functional voice disorders. Several factors were significant in the ADSD group. Those included a personal history of cervical dystonia, sinus, and throat illnesses, mumps, dust exposure, rubella, and extensive voice use. They also found a family or extended family history of voice disorders, vocal tremor, ocular disease, and meningitis. Table 2 summarizes the risk factors identified by the works from five different groups reporting on large numbers of subjects. These multifactorial findings of risks and environmental factors are supported by studies of other focal dystonias.59,60 Although clinical observations have suggested that more women than men develop ADSD, the implications for this finding are not clear. Moreover, although some patients associate their onset with a particular event, others do not. Childs et al61 reviewed the records of 350 patients treated in two different centers. Her group found that 80% were females and 2% of them had a history of other focal dystonias. In a subset of those 350 patients who were able to identify the onset of ADSD, 92 of the patients identified a gradual onset of the problem, whereas 77 patients characterized their onset as sudden (developing within 1 week). Fifty-nine of those patients with a sudden onset identified the onset trigger. The most common trigger in all patients was stress. Other frequently identified
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TABLE 2. Summary of Risk Factors Identified in Patients With Diagnosis of ADSD by Investigators Who Studied Large Groups Characteristic Middle decades of life Female Stress event in life Injury outside the vocal tract Childhood measles and mumps Upper respiratory infection Family history of essential tremor Family history of other neurological disease Cervical dystonia Sinus and throat illnesses Family history of meningitis Pregnancy and parturition
Reference 15,55,58 5,15,55,61 15,55,58,61 15 15,55,58 55,61 15,55 15,55,58 55 15,55 55 61
triggers were upper respiratory infection, pregnancy and parturition, and postintubation for surgery. The findings of Childs et al and others (Table 2) suggest that stress may be a relevant psychological factor that requires further investigation (or as Moore would say ‘‘Let’s look at that again’’). One of the sudden onset factors that Childs et al61 identified was pregnancy and parturition. Ankola et al62 examined five subjects in this group in more detail. They found that this group that was significantly younger than others in the sudden onset group of Childs et al had significantly increased avocational voice use during their pregnancy (they were full-time used) and had other risk factors such as a history of viral infection or sinus infection at the time of ADSD onset compared with a nonpregnant age-matched group. The authors concluded that hoarseness or dysphonia during or shortly after pregnancy may be a risk factor for ADSD, especially in those who continue to work or who are using their voice extensively. Clinicians should be aware of these issues to appropriately counsel and treat hoarseness during pregnancy.
SUMMARY The management of ADSD has evolved from a diagnostic framework of psychological factors to a neurological basis. The pioneering work of G. Paul Moore played a significant role in that evolution. His early work identified neurological factors present in patients with SD. After Moore’s initial work, clinicians and investigators in a variety of disciplines have spent the past 55 years trying to understand the epidemiology, pathogenesis, and treatment methods that improve the voice and speech of patients with ADSD. Studies of the anatomy, physiology, and histology of patients with ADSD have led to an understanding that this disorder is not a psychological disorder but a movement disorder of the larynx, a focal dystonia. Surgical approaches that emanated from early histological studies have provided patients with alternative treatments. Surgical results from TA myectomy to RLN avulsion and to SLADR have shown improvement for extended periods. Although
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most surgical treatments have the drawbacks of the need for general anesthesia, depend on the skills of the surgeon, and the acceptance by the patients, they offer a long-term approach to voice improvement compared with BTX, which is generally required every 3–4 months. Acoustic and aerodynamic studies predominantly during the 1980s and 1990s provided information about the changes in ADSD after treatment with BTX. The 2007 National Institutes of Health multidisciplinary panel reported in 2008 on the research priorities in ADSD and found that, among other areas, the identification of risk factors that contribute to the onset of the disorders was highly needed. The study of risk factors that has gone on and been refined over the past 30 years now provides today’s clinicians with useful information in counseling patients with ADSD. The use of BTX has been the main treatment approach for the past 35 years. The procedure is done in the office without general anesthesia, requires no preparation on the part of the patient, and has been shown to improve speech and voice significantly from the patient’s point of view and that of the listeners. The combined treatment of voice therapy and BTX has produced mixed results, and additional prospective studies of combined BTX-voice therapy are needed to determine the value of post-BTX therapy. The need to understand central processes in ADSD remains. ADSD is likely multifactorial in etiology and pathophysiology. Tremors exist with ADSD in some patients and not in others. Some patients experience both ADSD and ABSD symptoms; extensive voice use under stress appears to help identify ADSD in some patients. Future studies of ADSD are required to examine the epidemiological and pathophysiological factors in ADSD and the intersection of those factors with other exogenous and endogenous risks for the disorder. Genetic studies of families with various focal dystonias including ADSD should be directed to add further information to improve the management of this debilitating disorder.
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5 10. Robe E, Brumlick J, Moore GP. A study of spastic dysphonia. Neurologic and electroencephalographic abnormalities. Laryngoscope. 1960;70: 219–245. 11. Aronson AE, Brown JR, Litin EM, Pearson JS. Spastic dysphonia. I. Voice, neurologic, and psychiatric aspects. J Speech Hear Disord. 1968;33: 203–218. 12. Rethi A. On the treatment of stuttering and of spastic dysphonia with inspiratory and expiratory phonation. Monatsschr Ohrenheilkd Laryngorhinol. 1965;99:240–246. 13. Bloch P. Neuro-psychiatric aspects of spastic dysphonia. Folia Phoniatr (Basel). 1965;17:301–364. 14. Dedo HH. Recurrent laryngeal nerve section for spastic dysphonia. Ann Otol Rhinol Laryngol. 1976;85:451–459. 15. Izdebski K, Dedo HH, Boles L. Spastic dysphonia: a patient profile of 200 cases. Am J Otolaryngol. 1984;5:7–14. 16. Dedo HH, Izdebski K, Townsend JJ. Current evidence for the organic etiology of spastic dysphonia. Otolaryngology. 1978;86:875–880. 17. Aronson AE, DeSanto LW, Salassa JR. Adductor spastic dysphonia: three years after recurrent laryngeal nerve resection. Laryngoscope. 1983;93: 1–8. 18. Kiml J. Experimental research on spastic dysphonia. Folia Phoniatr (Basel). 1965;17:241–300. 19. Tluchowski W. Electromyographic studies of the cricothyroid and sternothyroid muscles in functional dysphonia. Folia Phoniatr (Basel). 1965; 17:179–184. 20. Caraceni T, Zibordi F. Electromyography in neural pathology of the larynx. Rev Otoneuroophtalmol. 1965;37:65–91. 21. Sellin LC, Polak RL, Thesleff S. Acetylcholine content and release in denervated or botulinum poisoned rat skeletal muscle. J Physiol. 1981; 319:253–259. 22. Rosenfield DB, Miller RH, Jankovic J. Spasmodic dysphonia: a neurological movement disorder. Neurology. 1984;34(suppl 1):148. 23. Jankovic J. Cranial-cervical cystonia. In: Appel SH, ed. Current Neurology6. Chicago, IL: Year Book Medical Publishers, Inc.; 1986: 153–176. 24. Dolly JO, Black JD, Williams RS. Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization. Nature. 1984;307:457–460. 25. Miller RH, Woodson GE, Jankovic J. Botulinum toxin injection of the vocal fold for spasmodic dysphonia: a preliminary report. Arch Otolaryngol Head Neck Surg. 1987;113:603–605. 26. Blizter A, Brin MF, Stewart C, et al. Laryngeal botulinum toxin injections for disabling stuttering in adults. Neurology. 1994;44:2262–2266. 27. Woodson GE, Zwirner P, Murry T, Swenson MR. Functional assessment of patient with spasmodic dysphonia. J Voice. 1992;6:338–343. 28. Zwirner P, Murry T, Swenson M, Woodson GE. Acoustic changes in spasmodic dysphonia after botulinum toxin injection. J Voice. 1991;5:78–84. 29. Zwirner P, Murry T, Swenson M, Woodson GE. Effects of botulinum toxin therapy in patients with adductor spasmodic dysphonia: acoustic, aerodynamic, and videoendoscopic findings. Laryngoscope. 1992;102: 400–406. 30. Ford CN, Bless DM, Patel NY. Botulinum toxin treatment of spasmodic dysphonia: techniques, indications, efficacy. J Voice. 1992;6:370–376. 31. Rhew K, Fiedler DA, Ludlow CL. Technique for injection of botulinum toxin through the flexible nasolaryngoscope. Otolaryngol Head Neck Surg. 1994;111:787–794. 32. Wong DL, Adams SG, Irish JC, et al. Effect of neuromuscular activity on the response to botulinum toxin injections in spasmodic dysphonia. J Otolaryngol. 1995;24:209–216. 33. Adams SG, Hunt EJ, Charles DA, Lang AE. Unilateral versus bilateral botulinum toxin injections in spasmodic dysphonia: acoustic and perceptual results. J Otolaryngol. 1993;22:171–175. 34. Shonweiler R, Wohlfarth K, Dengler R, Ptok M. Supraglottal injection of botulinum toxin type A in adductor type spasmodic dysphonia with both intrinsic and extrinsic hyperfunction. Laryngoscope. 1998;108:55–63. 35. Cannito MP, Woodson GE, Murry T, Bender B. Perceptual analysis of spasmodic dysphonia before and after treatment. Arch Otolaryngol Head Neck Surg. 2004;130:1393–1399.
6 36. Adams SG, Hunt EJ, Durkin LC, et al. Comparison of botulinum toxin injection procedures in adductor spasmodic dysphonia. J Otolaryngol. 1995; 24:345–351. 37. Murry T, Woodson GE. Combined-modality treatment of adductor spasmodic dysphonia with botulinum toxin and voice therapy. J Voice. 1995; 9:460–465. 38. Adams SG, Durkin LC, Irish JC, Wong DL, Hunt EJ. Effects of botulinum toxin type A injections on aerodynamic measures of spasmodic dysphonia. Laryngoscope. 1996;106:296–300. 39. Ludlow CL. Treatment of speech and voice disorders with botulinum toxin. JAMA. 1990;264:2671–2675. 40. Davidson BJ, Ludlow CL. Long-term effects of botulinum toxin injection in spasmodic dysphonia. Ann Otol Rhinol Laryngol. 1996;105:33–42. 41. Cannito MP, Doiuchi M, Murry T, Woodson GE. Perceptual structure of adductor spasmodic dysphonia and its acoustic correlates. J Voice. 2012; 26:818.e5–818.e13. 42. Silverman EP, Garvan C, Rahul S, Sapienza CM. Combined modality treatment of adductor spasmodic dysphonia. J Voice. 2012;26:77–86. 43. Dejonkere P, Martens JP, Moerman M, et al. Spasmodic dysphonia, perceptual, and acoustic analysis: presenting new diagnostic tools. Eur Arch Otorhinolaryngol. 2009;266:1915–1922. 44. Isshiki N. Recent advances in phonosurgery. Folia Phoniatr (Basel). 1980; 32:119–154. 45. Chan SW, Baxter M, Oates J, Yorston A. Long-term results of type II thyroplasty for adductor spasmodic dysphonia. Laryngoscope. 2004;114: 1604–1608. 46. Genack SH, Woo P, Colton RH, Goyette D. Partial thyroarytenoid myectomy: an animal study investigating a proposed new treatment for adductor spasmodic dysphonia. Otolaryngol Head Neck Surg. 1993;108:256–264. 47. Nakamura K, Muta H, Watanabe Y, Mochizuki R, Yoshida T, Suzuki M. Surgical treatment for adductor spasmodic dysphonia—efficacy of bilateral thyroarytenoid myectomy under microlaryngoscopy. Acta Otolaryngol. 2008;128:1348–1353. 48. Weeds DT, Netterville JL, Jewett BS, et al. Long-term follow-up of recurrent laryngeal nerve avulsion for the treatment of spastic dysphonia. Ann Otol Rhinol Laryngol. 1996;105:592–601.
Journal of Voice, Vol. -, No. -, 2014 49. Iwamura S. Spasmodic dysphonia. Otolaryngol Head Neck Surg. 1986;2: 497–500. 50. Iwamura S. An EMG study of spastic dysphonia; spastic or spasmodic. J Otolaryngol Jpn. 1991;94:1495–1496. 51. Berke GS, Blackwell KE, Gerratt RR, et al. Selective laryngeal adductor denervation-reinnervation: a new surgical treatment for adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol. 1999;108:227–231. 52. Green DC, Berke GS. An in vivo canine model for testing treatment effects in laryngeal hyperadduction disorders. Laryngoscope. 1990;100:1229–1235. 53. Chhetri DK, Berke GS, Mendelsohn AH, Blumin JH. Long-term follow-up results of selective laryngeal adductor denervation-reinnervation surgery for adductor spasmodic dysphonia. Laryngoscope. 2006;116:635–642. 54. Mendelsohn AH, Berke GS. Surgery or botulinum toxin for adductor spasmodic dysphonia: comparative study. Ann Otol Rhinol Laryngol. 2012;121: 231–238. 55. Tanner K. Epidemiologic advances in spasmodic dysphonia. Am Speech Lang Hear Assoc. 2012;22:104–111. 56. Murry T, Cannito MP, Woodson GE. Spasmodic dysphonia: emotional states and botulinum toxin treatment. Arch Otolaryngol Head Neck Surg. 1994;120:310–316. 57. White LJ, Hapner ER, Klein AM. Coprevalence of anxiety and depression with spasmodic dysphonia: a case-control study. J Voice. 2012;26:667. e1–667.e6. 58. Schweinfurth JM, Billante M, Courey MS. Risk factors and demographics in patients with spasmodic dysphonia. Laryngoscope. 2002;112:220–223. 59. Frucht SJ. Focal task-specific dystonia in musicians. Adv Neurol. 2004;94: 225–230. 60. Leube B, Kessler KR, Goecke T, Auburger G, Benecke R. Frequency of familial inheritance among 488 index patients with idiopathic focal dystonia and clinical variability in a large family. Mov Disord. 1997;12:1000–1006. 61. Childs L, Rickert S, Murry T, Blitzer A, Sulica L. Patient perceptions of factors leading to spasmodic dysphonia: a combined clinical experience of 350 patients. Laryngoscope. 2011;121:2195–2198. 62. Ankola A, Sulica L, Murry T. Laryngeal dystonia gravidarum: sudden onset of adductor spasmodic dysphonia in pregnancy. Laryngoscope. 2013;123: 3127–3130.
of individuals that now have been documented to be associated with SD. Another early investigator of SD, Arnold,9 originally felt that SD was because of primitive subcortical centers acting without inhibition in patients with known personality problems.9 Nonetheless, in 1959, despite these early suggestions that there may be a neurological basis for the disorder, there was still a persistent belief that disruptions in personality had a strong relationship to the disorder. In 1960, Robe et al10 reported on 10 patients diagnosed with SD ranging from 6 months to 15 years. The subjects completed questionnaires, had thorough ear, nose, and throat examinations as well as neurological examinations, and they also underwent electroencephalograms. All these patients had signs of central nervous system abnormalities. Their signs included irregular discharges in the right temporalparietal region in nine of the 10 subjects, four subjects with familial neurological diseases, eight with transient leg or arm weakness, and other conditions such as parasthesias in the hands, arms, or legs. Several of the subjects reported the onset associated with a sickness such as an upper respiratory disease or with stressful events leading up to the onset of the condition. Robe et al10 concluded that SD was a phonatory disorder resulting from a disturbance in neural function and possible neural structure. This was the first study to present clinical neurological evidence that SD was linked to a neurological disorder. This work of Moore et al opened up new avenues of study with the hope that treatment options would follow. Soon after the classic work of Moore et al, Aronson et al11 identified two types of the disorders, adductor consisting of strained and strangled speech production and abductor, an intermittent breathiness. They suggested that these disorders demonstrated a somewhat different movement pattern in the larynx than the rigidity of spastic muscles, hence the term spasmodic dysphonia (either adductor spasmodic dysphonia, ADSD or abductor spasmodic dysphonia, ABSD). These terms have been used consistently since 1968. In the 1960s, several studies reported on various behavioral treatment attempts despite the trend at that time toward a neurological basis. Rethi12 suggested inspiratory and expiratory phonation exercises similar to those used to treat stuttering. Bloch13 examined the neuropsychological aspects of the disorder in an attempt to identify patterns of behavior that may contribute to the disorder and therefore be amenable to medical treatment and counseling. Their results did not show long-term positive outcomes. Although the evidence for a neurological basis of SD began to mount in the 1960s, it was not until 1976 that direct evidence
2 was presented to show that SD was a neurological disorder. Dedo temporarily paralyzed the recurrent laryngeal nerve (RLN), and a significant improvement in voice quality resulted. Dedo14 reported the sectioning of the RLN in 34 patients with ADSD. Izdebski et al15 reported that with postoperative voice therapy, all subjects exhibited some improvement and approximately one-half of the group returned to a near normal voice but with less overall volume. Dedo et al16 subsequently found that through histological analysis of the RLN, patients with ADSD had significantly more abnormalities compared with age-matched controls. The finding of a change in the speech and voice after resection of the RLN led others to try it. However, sectioning of the RLN was not universally accepted, and later Aronson17 reported that in some subjects the long-term results were poor.
THE BOTULINUM TOXIN ERA The findings by Dedo14,16 and Robe et al10 encouraged other investigators to look more closely at the disorder. Electromyographic results of Kiml,18 Tluchowski,19 as well as Caraceni and Zibordi20 identified abnormalities in the peripheral nerve or in the corticonuclear tracts suggesting that a neurological abnormality exists in patients with spastic speech. These findings were later supported with studies by Sellin et al,21 Rosenfield et al,22 Jankovic,23 and Dolly et al24 that paved the way for the treatment of the dystonic movement of the larynx with botulinum toxin (BTX), a neurotoxin of which the most potent type is type A. Jankovic23 demonstrated the usefulness of BTX in the treatment of Meige symptoms, which are associated with ADSD in a percentage of cases. Early patients’ reports of treatment with BTX were encouraging.25 Blitzer et al26 reported on the first large case series treated with BTX. Initially, BTX was used primarily for ADSD, but later reports of treatment for ABSD followed.26 BTX has since been reported to be safe for the treatment of ADSD and ABSD and has been used to manage SD for the past 30 years. The speech and voice abnormalities of SD achieved greater recognition in the 1980s and 1990s; thanks to the success generated by the work of Dedo14,15 and successful use of BTX as a treatment. However, descriptions and assessments of ADSD remained primarily subjective with perceptual terms such as ‘‘strained-strangled’’ and ‘‘effortful phonation’’ predominant in the literature. Numerous studies of functional outcomes in the voice and speech of patients with SD before and after BTX treatments followed as its use became accepted. Investigators have examined the pre- to post-BTX findings of acoustic, aerodynamic, and perceptual studies in demonstrating the positive voice changes after BTX injections. Treatment of ADSD with BTX over the past 30 years has demonstrated improvements in the acoustic, aerodynamic, and perceptual characteristics of the voice. The results are based on numerous methods of treatment (bilateral injection vs unilateral injection) and various measures obtained from sustained and spoken speech samples. Table 1 summarizes the acoustic and physiological findings. Investigators have found that after BTX injection, there was no significant change in fundamental frequency,
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TABLE 1. A Summary of the Acoustic and Physiological Findings From Studies That Reported Pre- and Post-BTX Results Parameter Vowels Fo Jitter Shimmer Harmonic/noise ratio Subglottic pressure Airflow rate Voice breaks Tremor Speech Mean Fo Speech rate Airflow rate Voice breaks
Findings Unchanged pre vs post BTX Lower post BTX Lower post BTX Lower post BTX Lower post BTX Higher post BTX Near normal 2 wk post BTX Fewer post BTX Improved post BTX Unchanged pre vs post BTX Faster post BTX Higher post BTX Fewer post BTX
jitter, shimmer, signal-to-noise ratio (SNR), and maximum phonation time.27–36 Data from connected speech by Cannito et al35 demonstrated that although overall fundamental frequency did not change after BTX treatment, the number of low frequency events and the SNR were significantly different after treatment compared with pretreatment. Moreover, the variation in fundamental frequency and the SNR were related to listener judgments of voice quality. Investigators did find significant post-BTX changes in the prosodic aspects of speech, namely, the number of voice breaks, time to read a sentence or paragraph, and control of speech intensity.2,28–30,32 Despite the lack of statistical evidence in some of the forgoing studies, the general conclusions from the postBTX data imply an improvement in communication and a closer relationship to normal speech and voice acoustic parameters. Fewer investigators studied the physiological measures associated with treatment using BTX. Airflow measures obtained by Zwirner et al29 and also by Murry and Woodson37 before BTX injection in patients with ADSD were found to be lower than age-matched normal subjects. However, Adams et al36,38 in two different groups found airflow rates to be within normal range before BTX injections. After BTX injection, airflow rate changes increased significantly for the first few weeks and then stabilized to near normal flow rates after the initial period.29,36–38 Physiological measures based on electromyography (EMG) have been studied by Ludlow39 as well as Davidson and Ludlow.40 Based on their EMG findings, Davidson and Ludlow40 suggest that motor unit reorganization may continue long after the effects of the BTX injection dissipate. As might be expected, perceptual studies of ADSD show significant changes after BTX injection. However, it is unsure if the perceptual changes after BTX treatment are related to temporal aspects of the speech or specific acoustic and physiological properties of the voice signal or some combination of the
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changes. Cannito et al41 found a weak positive relationship between voice quality and the combination of frequency variation and SNR measures. Silverman et al42 found that the perceived severity of the dysphonia in ADSD was related primarily to the amount of aperiodicity and the number of voice breaks. Similar to that found by Cannito et al, the perceptual relationships identified by Silverman, and also by Dejonkere et al,43 accounted for only a portion of the variance of the perceptual data. Thus, there remains a need to understand the effects of BTX changes in ADSD on listeners’ perception of voice quality after treatment.
SURGICAL APPROACHES TO THE TREATMENT OF ADSD At the same time, although the use of BTX gained wide acceptance by some, others were not completely satisfied with this treatment method as BTX required frequent injections, relationships between dose and response were unpredictable, and occasional transient swallowing problems occurred. In addition, there was a postinjection period of up to 2 weeks in which the voice was breathy and thus limited communication. As a result, others took a look at the treatment of ADSD and considered surgical procedures that might be useful. In 1980, Isshiki44 reported on a thyroplasty procedure, identified as type II thyroplasty, which divided and widened the thyroid cartilage at the midline thus reducing the squeeze effect of the vocal folds in ADSD. Although this procedure did not gain enthusiasm for the treatment of ADSD in the United States because of the more accessible use of BTX, it nonetheless stimulated interest among surgeons to look for other avenues of treatment for ADSD. Chan et al45 reported on 13 patients with the diagnosis of ADSD who were previously treated successfully with BTX and then were recruited for type II thyroplasty as described by Isshiki. Self-rating assessment of the degree of severity and vocal effort were recorded and compared with the BTX treatment. Patients’ self-assessments and long-term followups were not supportive of the procedure; only five patients reported some degree of satisfaction with the procedure. As knowledge of neural function of the larynx and specifically the vocal folds increased and the growing acceptance of ADSD as a neurological voice disorder evolved, other surgical treatments were explored. Although BTX was successful in reducing laryngeal spasms and patients were generally satisfied with the injections, speech was not normal after BTX injection and more importantly, the speech and voice fluctuated as the BTX wore off. An early animal study reported by Genack et al46 showed that thyroarytenoid (TA) myectomy resulted in reduced vocal fold closure but with vocalization remaining. Other investigations followed this work on patients with ADSD. Although the results by various investigators demonstrated the elimination of severe constrictions and in some cases improved scores on the Voice Handicap Index and other assessment tools, patients remained with a weak voice for protracted periods.47 Weeds et al48 reported on the long-term results of RLN avulsion in 18 patients. Although the patients’ voices remained
3 weak in volume, 16 of the 18 had no recurrence of spasms after 3 years. In patients who were followed longer, they also found that several of those who were offered medialization thyroplasty for their weak voices had a recurrence of spasms despite previous absence of spasms for more than 3 years.48 Following the early surgical options previously mentioned, investigators began to look at ways to reduce the closing force of the vocal folds to reduce the spasm effect in patients with ADSD. Iwamura49,50 reported that the EMG findings of patients with SD showed that the percentage of thin motor fibers in the TA muscle is greater in patients with ADSD than in control subjects. By removing part of the TA muscle and thus reducing the number of thin motor fibers, they found a reduction or elimination in the spasms. The work of Iwamura was followed by Berke et al51 who reported on selective adductor denervation surgery (SLAD-R). Earlier, Green and Berke52 studied the effects of hyperadduction in canines and the effects of denervation. The SLAD-R procedure reduces the force of the closing phase of vibration because of weakening of the TA muscle. Long-term results of the procedure reported by Chhetri et al53 showed that patients had reduced or eliminated the spasms, had lower Voice Handicap Index scores, and were generally satisfied with the results compared with previous treatments with BTX. They reported that patients achieved long-term spasm-free voice with breathiness lasting the first 3–6 months after the surgery. Mendelsohn and Berke54 found that as long as 14 years after the SLAD-R procedure, patients were more satisfied with their voices than when they were previously treated with BTX. Although the SLAD-R procedure is generally no longer used nowadays, the long-term data of Chhetri et al53 as well as Mendelsohn and Berke54 suggest that it is a viable treatment for ADSD, and it represents an alternative to the regular treatments of BTX with its accompanying voice changes as the BTX wears off.
THE CURRENT ERA The pathogenesis of ADSD remains unknown at this time, but a neurological basis including endogenous and exogenous factors is now supported by the literature.55 That is not to say that patients with ADSD do not have psychological issues. It is well known that when patients with ADSD speak under stress, their voice disorders are judged to be more severe than when they hum a tune. Moreover, any significant illness is usually associated with psychological or psychosocial factors. Murry et al56 obtained self-ratings of depression, state anxiety (a temporary anxiety associated with a task such as speaking), and trait anxiety from patients before and after BTX injection. Before BTX treatment, patients exhibited mildly elevated scores of depression and state anxiety but no trait anxiety compared with subjects with other voice disorders. In addition, the BTX pretreatment scores were similar to those in patients with other neuropsychological disorders. The findings were interpreted to suggest that the state of speaking in patients with ADSD before BTX treatment was the basis for anxiety in the 16 of 32 patients who reported elevated state but not trait anxiety. Improvement in speech after BTX resulted in lower scores on all measures.
4 White et al57 recently found that patients with ADSD had no greater scores on depression and anxiety scales than patients with other voice disorders. The current era has increased the understanding of changes that occur in ADSD as a result of chemical and surgical treatments. Currently, there is also an increasing understanding of factors that contribute to the risk and onset of the disorder. Thus, although chemical and surgical procedures offer alternatives to managing ADSD, a better model for management might include an understanding of the factors leading to the disorder. Furthermore, there remains a need to explore these factors for ADSD and ABSD. Perceptual studies have shown that ADSD is characterized by hyperadduction and hypoadduction. High subglottic pressures associated with sudden adduction followed by high airflow associated with voice breaks are the prominent aerodynamic findings correlated with perceptual judgments of ADSD. BTX helps to reduce both these characteristics. After surgical or BTX treatment, episodic high subglottic pressures decrease, airflow rates return to near normal values, and listeners perceive the voice as more normal than before BTX.29,45 Epidemiological studies have recently contributed to a better understanding of factors that are prominently related to ADSD. Izdebski et al15 were the first to explore factors that were associated with ADSD in a group of 200 patients. They found patients with ADSD had extensive histories of voice use and voice use under stress. Schweinfurth et al58 used a questionnaire to evaluate demographics, educational level, work history, and life events in 168 patients and compared their findings to relatives of the patients. They found a 65% history of measles and mumps in the ADSD group compared with the relatives of patients with ADSD. Recently, Tanner55 used an extensive questionnaire with 150 ADSD patients and 136 patients with other structural, neurological, or functional voice disorders. Several factors were significant in the ADSD group. Those included a personal history of cervical dystonia, sinus, and throat illnesses, mumps, dust exposure, rubella, and extensive voice use. They also found a family or extended family history of voice disorders, vocal tremor, ocular disease, and meningitis. Table 2 summarizes the risk factors identified by the works from five different groups reporting on large numbers of subjects. These multifactorial findings of risks and environmental factors are supported by studies of other focal dystonias.59,60 Although clinical observations have suggested that more women than men develop ADSD, the implications for this finding are not clear. Moreover, although some patients associate their onset with a particular event, others do not. Childs et al61 reviewed the records of 350 patients treated in two different centers. Her group found that 80% were females and 2% of them had a history of other focal dystonias. In a subset of those 350 patients who were able to identify the onset of ADSD, 92 of the patients identified a gradual onset of the problem, whereas 77 patients characterized their onset as sudden (developing within 1 week). Fifty-nine of those patients with a sudden onset identified the onset trigger. The most common trigger in all patients was stress. Other frequently identified
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TABLE 2. Summary of Risk Factors Identified in Patients With Diagnosis of ADSD by Investigators Who Studied Large Groups Characteristic Middle decades of life Female Stress event in life Injury outside the vocal tract Childhood measles and mumps Upper respiratory infection Family history of essential tremor Family history of other neurological disease Cervical dystonia Sinus and throat illnesses Family history of meningitis Pregnancy and parturition
Reference 15,55,58 5,15,55,61 15,55,58,61 15 15,55,58 55,61 15,55 15,55,58 55 15,55 55 61
triggers were upper respiratory infection, pregnancy and parturition, and postintubation for surgery. The findings of Childs et al and others (Table 2) suggest that stress may be a relevant psychological factor that requires further investigation (or as Moore would say ‘‘Let’s look at that again’’). One of the sudden onset factors that Childs et al61 identified was pregnancy and parturition. Ankola et al62 examined five subjects in this group in more detail. They found that this group that was significantly younger than others in the sudden onset group of Childs et al had significantly increased avocational voice use during their pregnancy (they were full-time used) and had other risk factors such as a history of viral infection or sinus infection at the time of ADSD onset compared with a nonpregnant age-matched group. The authors concluded that hoarseness or dysphonia during or shortly after pregnancy may be a risk factor for ADSD, especially in those who continue to work or who are using their voice extensively. Clinicians should be aware of these issues to appropriately counsel and treat hoarseness during pregnancy.
SUMMARY The management of ADSD has evolved from a diagnostic framework of psychological factors to a neurological basis. The pioneering work of G. Paul Moore played a significant role in that evolution. His early work identified neurological factors present in patients with SD. After Moore’s initial work, clinicians and investigators in a variety of disciplines have spent the past 55 years trying to understand the epidemiology, pathogenesis, and treatment methods that improve the voice and speech of patients with ADSD. Studies of the anatomy, physiology, and histology of patients with ADSD have led to an understanding that this disorder is not a psychological disorder but a movement disorder of the larynx, a focal dystonia. Surgical approaches that emanated from early histological studies have provided patients with alternative treatments. Surgical results from TA myectomy to RLN avulsion and to SLADR have shown improvement for extended periods. Although
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most surgical treatments have the drawbacks of the need for general anesthesia, depend on the skills of the surgeon, and the acceptance by the patients, they offer a long-term approach to voice improvement compared with BTX, which is generally required every 3–4 months. Acoustic and aerodynamic studies predominantly during the 1980s and 1990s provided information about the changes in ADSD after treatment with BTX. The 2007 National Institutes of Health multidisciplinary panel reported in 2008 on the research priorities in ADSD and found that, among other areas, the identification of risk factors that contribute to the onset of the disorders was highly needed. The study of risk factors that has gone on and been refined over the past 30 years now provides today’s clinicians with useful information in counseling patients with ADSD. The use of BTX has been the main treatment approach for the past 35 years. The procedure is done in the office without general anesthesia, requires no preparation on the part of the patient, and has been shown to improve speech and voice significantly from the patient’s point of view and that of the listeners. The combined treatment of voice therapy and BTX has produced mixed results, and additional prospective studies of combined BTX-voice therapy are needed to determine the value of post-BTX therapy. The need to understand central processes in ADSD remains. ADSD is likely multifactorial in etiology and pathophysiology. Tremors exist with ADSD in some patients and not in others. Some patients experience both ADSD and ABSD symptoms; extensive voice use under stress appears to help identify ADSD in some patients. Future studies of ADSD are required to examine the epidemiological and pathophysiological factors in ADSD and the intersection of those factors with other exogenous and endogenous risks for the disorder. Genetic studies of families with various focal dystonias including ADSD should be directed to add further information to improve the management of this debilitating disorder.
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