Role of Botulinum toxin injection in the treatment of spasmodic dysphonia: Experience in Bangladesh Medical University

The impact of the disordered voice on standard work productivity measures and employment trends is difficult to quantify; this is in large part due to the heterogeneity of the disease processes. Spasmodic dysphonia (SD), a chronic voice disorder, may be a useful model to study this impact. Self-reported work measures (worked missed, work impairment, overall work productivity, and activity impairment) were studied among patients receiving botulinum toxin (BTX) treatments for SD. It was hypothesized that there would be a substantial difference in work-related measures between the best and worst voicing periods. In addition, job types, employment shifts, and vocal requirements during the course of vocal disability from SD were investigated for each individual, and the impact of SD on these patterns was studied. A total of 145 patients with SD, either adductor or abductor, who were established in routine therapeutic BTX injections agreed to participate in a self-administered questionnaire study. Seventy-two participants were currently working and provided highly detailed information on work-related measures. Their answers characterized the effect of SD on their employment status, productivity at work, activity impairment outside of work, employment retention or change, and whether the individual perceived that BTX therapy affected these measures. Patients were asked to complete the Work Productivity and Activity Impairment (WPAI) instrument to determine these measures for their best and worst voicing weeks over the duration since their previous BTX injection. Voice-specific quality of life instruments (Voice Handicap Index-10) and perceptual assessments (Consensus Auditory Perceptual Evaluation of Voice) were elicited to provide correlations of work measures with patient-perceived voice handicap and clinician-perceived voice quality. Cross-sectional analysis using self-administered questionnaire. A total of 108 patients reported ever working during their diagnosis and treatment of SD, and 72 patients were currently working and had undergone BTX therapy for at least 1 year at the time of the analysis. Currently employed patients reported a mean 4.4% decrease in work missed (absenteeism), a 28.1% decrease in work impairment (presenteeism), a 29.4% decrease in work productivity, and a 21.4% decrease in activity impairment (P <.001) in their best, as compared to their worst voicing period over their last BTX injection cycle. Presenteeism accounted for the major component of the percent work productivity impairment calculation. There was neither apparent shift in job categories nor any change in the vocal demands of their employment over the course of their disease. Among patients that have worked during their diagnosis of SD, greater than 98% report that BTX injections helped them at work. Patients with SD reported that their vocal dysfunction caused a significant negative effect on work productivity and increase in activity impairment. There was a significant improvement in their voice-related work parameters from their worst to best voicing periods over their last BTX injection cycle. Patients undergoing long-term BTX treatment report a positive effect of this treatment in their workplace. Spasmodic dysphonia is a meaningful model in which to study the effects of voice disorders on work productivity and employment patterns.

This paper reviews a 12-year experience in more than 900 patients with spasmodic dysphonia who have been treated with botulinum toxin. This is a retrospective analysis of patients with adductor spasmodic dysphonia (strain-strangled 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. 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. 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. 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.

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 (BT) is a currently used treatment for spasmodic dysphonia (SD) and other related focal dystonias. The goal of this study is to provide a basis for using the rat larynx to objectively assess physiological and histological effects of BT. Dosages and volumes of BT injection were varied and three physiological parameters were measured. These measures included: optical density of PAS-stained laryngeal muscle after electrical stimulation, which is an indirect measure of denervation, spontaneous laryngeal muscle activity, and laryngeal movement. A new microlaryngoscopic technique was developed, which made it possible to observe and manipulate the rat larynx endoscopically. Laryngeal movement and electromyographic (EMG) measures were made prior to injection and 3 days following BT injections of various dosages and volumes. Optical density measures were made 3 days after injection. Significant reductions in vocal fold motion and spontaneous laryngeal muscle activity as a function of increased BT dosage were observed. In addition, the optical density of PAS-stained laryngeal muscle after electrical stimulation was increased following BT injection. Significant volume effects in optical density were observed in the lateral thyroarytenoid and lateral cricoarytenoid muscles on the contralateral side. The rat laryngeal model is suitable for assessing BT effects. In addition, the three physiological variables provided useful and reliable measures of laryngeal function. It is the authors' intention to use the rat laryngeal model to further examine the physiological and histological effects of BT with the goal of developing new methods for the treatment of patients with SD and other focal dystonias.

Adductor spasmodic dysphonia (ADSD) is a focal dystonia treated most commonly by chemodenervation of the thyroarytenoid (TA) muscles with botulinum toxin. Currently, there are no consensus guidelines regarding this treatment and the management of ADSD. The objective of this study was to assess current practice patterns among physicians who treat ADSD. A cross-sectional survey study was conducted regarding treatment choices and specific technical aspects of injection technique and botulinum toxin use. The study population consisted of laryngologists from the Canadian Society of Otolaryngology-Head and Neck Surgery and laryngologists obtained from the American Laryngological Association member database and the American Academy of Otolaryngology-Head and Neck Surgery Neurolaryngology Study Group. An overall response rate of 13% was achieved, with a high absolute number of physicians who manage ADSD responding (n = 37). Most respondents treat ADSD by injecting botulinum toxin type A (Botox) through the cricothyroid membrane submucosally at a mode starting dose of 2.5 units per TA muscle using electromyographic guidance with or without fibre-optic laryngoscopy every 3 to 4 months, with the frequency of reinjection being based on patient symptomatology. There is much variability with regard to starting injection dose, alternate treatments for ADSD, unilateral versus bilateral injections, and guidance technique. Most physicians (36 of 37) share one vial among more than one patient, and some (7 of 37) freeze a reconstituted vial that has remaining toxin for reuse at a later time. There is considerable variability in treatment practices for the management of ADSD. Further study is warranted to define an optimal therapeutic paradigm.

Background and Purpose: The aim of our study is to evaluate the effect of botulinum toxin in patients of adductor spasmodic dysphonia (SD) with and without voice tremor. Methods: We used botulinum toxin A (BTX-A, Botox®) in treating 10 patients with adductor SD. Among them, 6 patients were presenting simple adductor SD, 4 patients were presenting adductor SD and prominent voice tremor. The features of their voices were evaluated blindly by another neurologist, by a speech pathologist, and by an otolarygologist with direct videoendoscopic observation before and after treatment. Guided with EMG, a dose of 15 to 20 units of BTX-A was injected into the unilateral thyroarytenoid muscle. Results: We obtained a significant improvement of voice quality in 5 out of 6 simple adductor SD patients. The benefits commenced at a mean of 5 days (range; 4-6 days). The median duration of peak effects was 4 weeks (range: 3-6 weeks). The remaining 1 patient had only mild effects. The videoendoscopic parameters also showed a significant improvement in correlation with the clinical effect. Four adductor SD patients associated with dominant voice tremor did not improve, especially in the tremor component. Conclusion: We have proved that BTX-A is an effective treatment for simple adductor SD, but not for adductor SD with prominent voice tremor. We suggest that a videoendoscopic evaluation is valuable for selecting the patients with adductor SD, particularly complicated with voice tremor.

Since laryngeal botulinum toxin (BTX) injections have become the treatment of choice for spasmodic dysphonia, the purpose of this study was to examine its effects on the stability of the upper vocal tract as compared to the effects on glottic stability. Two different acoustic methods were used to analyze voice samples from 16 patients with adductor-type spasmodic dysphonias before and after BTX therapy and from a normal control group. Independent acoustic analyses were used to determine laryngeal and upper vocal tract stability. The results showed significantly higher values for the standard deviation of fundamental frequency (SDF0), reflecting laryngeal instability, for the patient group than for the control group and an impressive improvement for the patients after BTX therapy. Further, the equally high values of SDF0 for the initial second and a second from the midsegment of phonation were differentially reduced by BTX therapy, resulting in a normal pattern of laryngeal stability during sustained phonation. The variability of the first and second formants, reflecting upper vocal tract instability, showed higher values for the patients compared with the control group, but this difference was not statistically significant. The present findings showed that BTX injections to the thyroarytenoid muscle had no discernible effect on stability of the upper vocal tract.

CONTACT OBJECTIVES: Botulinum toxin therapy (BTX) for adductor spasmodic dysphonia (ADSD) requires re-injection. The dosing effects after prolonged treatment are not well reported. We report our ten-year experience in the utilization of BTX in ADSD STUDY DESIGN: Retrospective chart review METHODS: From a database of 182 ADSD patients from 1997-2008 treated with BTX, we pulled a subset of 87 patients receiving BTX for greater than 3 visits (average 10.27 visits, range 3-40). We analyzed duration of effect, dosing effects and changes in administration technique. RESULTS: This study group was predominantly female (3:1), presenting at mean age 60. All BTX was administered with laryngeal electromyographic guidance. The average starting dose was 2.28 units (range 1.25 – 3.75). The average dose per injection was 2.15 units (range 0.25-12.5) with an average time interval of 5.6 months between visits. Patients reached a stable dosing regimen at an average of 1.34 months, with 75% optimized after the first visit. There was a trend towards increased average dosage for patients during their 15th treatment visit and up (p=0.14), with increased variation in effect (SD 0.95 vs 1.36). Average time interval between visits tended to decrease over time. Patients who began treatment at older ages in the 6th and 7th tended to require decreasing dosages over time. 10 out of 87 patients progressed to unilateral injections after an average of 12.5 treatment visits, with 70% efficacy. CONCLUSIONS: Botulinum therapy in ADSD is stable and safe. Prolonged treatment over 15 visits may require changes in dosing and technique. Unilateral injections provide an effective alternative to bilateral injection. Name: Nina Chinosornvatana, MD Organization: Mount Sinai Hospital Email: nchinos@gmail.com •Patient positioned supine with neck slightly extended. Laryngeal electromyography (LEMG) ground and reference electrodes are placed. Neck prepped. •Botulinum toxin diluted to 100 units per 4cc of injectable bacteriostatic saline. 1cc tuberculin syringe fixed to LEMG monopolar electrode injector needle. •Needle inserted through the skin just off of midline at the level of the cricothyroid membrane. Needle advanced superolaterally towards the targeted thyroarytenoid muscle. •LEMG used to verify placement of needle into thyroarytenoid muscle, showing increased muscle action potential complexes with phonation and cough. •Starting dosage administered is 2.5 units to each side. Subsequent dosing is determined dependent on prior dosage and its effectiveness. • Botulinum therapy was shown to have prolonged efficacy, with successful injections administered at upper limits of 80 injections, 40 visits, and 10 years. This is consistent with BTX’s proven record of safety and efficacy in the literature. To date, there are no reports of mortality attributed to BTX treatment in the literature. 7 The most common adverse effect has been temporary excessive breathiness from overinjection. •We recommend 2.5 units to each thyroarytenoid muscle as an effective starting dose with use of laryngeal electromyographic guidance. Reported rates of starting dosage administration vary; our 70% efficacy rate after the first visit compares favorably to other reported series. 6,7 •We saw an increase in dosage variability in patients receiving prolonged treatment beyond 15 visits, with a trend towards increased average dosing. Other series have reported decreases in dosing requirements over time without resistance. 7 We therefore recommend vigilant attention to changes in dosing requirement or technique in patients over 15 visits, with consideration of unilateral injections as an alternative to bilateral injection. •Unilateral injections have been reported to be successful in a wide range of doses, from 2.5u – 30u. 9 Comparisons to bilateral injections have shown similar efficacy, with some reports of decreased side effect profiles. 10 Our experience confirms unilateral administration as a useful and effective alternative to bilateral injection. •Adductor spasmodic dysphonia (ADSD) is an idiopathic focal dystonia of the intrinsic laryngeal adductor musculature. Spasms most frequently affect the thyroarytenoid muscles, but can also involve the lateral cricoarytenoid and interarytenoids, resulting in overforceful vocal fold closure. •Clinically, ADSD presents with strangulated strained vocal quality, and is characterized by repetitive breaks in phonation and pitch, requiring increased effort during speech. ADSD is triggered by speech, in particular, voiced sounds. 1 •Treatment options for ADSD include speech therapy, recurrent laryngeal nerve sectioning2,3 , partial thyroarytenoid myectomy4, anterior commissure release, and botulinum administration. The use of botulinum remains the gold standard treatment due to its effectiveness, reliability, and high safety profile.5 •Chemodenervation with botulinum requires reinjection. Because there is significant variability in patient response and toxin delivery, individualization of treatment is necessary for optimal effect. Adductor Spasmodic Dysphonia

Quality of Life After Botulinum Toxin Injection in Patients With Adductor Spasmodic Dysphonia; a Systematic Review and Meta-analysis

Spasmodic dysphonia (SD) is a rare disease caused by focal dystonia in the laryngeal muscles. The adductor type SD (AdSD), which affects the thyroarytenoid (TA) muscle, is found in 80% of all SD patients. For them, voice therapy and medication are less effective and definitive surgical treatment has not been established yet. Botulinum toxin injection is considered the gold standard treatment. However, patients require regular injections every 3-6 months whenever the effect of botulinum toxin disappears. Therefore, it is essential that injecting botulinum toxin is safe, comfortable, and accurate. Injections are usually performed under the guidance of electromyography or laryngoscopy. Ultrasonography (US) is a familiar device to otorhinolaryngologists and has recently been used to evaluate the laryngeal structures. While US has been used only for diagnosis, it can also be used for treatment. Here, we describe a novel technique that can be used to inject botulinum toxin into the TA muscle via trans-cartilaginous approach under the guidance of US for the treatment of AdSD.

Simultaneous Botox and Augmentation Injection Laryngoplasty in Patients With Adductor Spasmodic Dysphonia (ASD) and Tremor

Background: Adductor spasmodic dysphonia (ASD) is a voice disorder characterized by strained, stuttering-like voice (involuntary disruptions of voice). Botulinum toxin (BT) injection of the vocal folds (VFs) is the treatment of choice, however, the doses and method of injection are variable. Objectives: The aim of this study is to assess the effect of BT injection on the voices of the patients having ASD. Patients and Methods: Twelve patients with ASD treated bilaterally with VF BT injection in the office under local anesthesia. Each patient evaluated by laryngoscopic examination, acoustic analysis, and voice handicap index. Results: All patients improved markedly regarding laryngoscopic, acoustic, and self-assessment parameters. Conclusion: BT can be used effectively for the treatment of ASD and improving phonatory (voice) and quality of patients' life.

Botulinum toxin

This special issue of Disability and Rehabilitation reports contemporary applications of Botulinum toxin for managing muscle overactivity and associated muscle imbalance. Clostridium botulinum, a gram-positive anaerobic bacterium, produces a potent poison, Botulinum toxin, which, when ingested, can induce transient muscle weakness, which in severe cases can be life-threatening. Despite this potential risk, minute doses of the purified neurotoxin confer an option for efficacious treatment of painful muscle spasms, focal muscle overactivity, and muscle imbalance of neurological and musculoskeletal origin. Intramuscular injection with therapeutic preparations of Botulinum toxin decreases contractile activity by blocking acetylcholine release at the neuromuscular junction, rendering the muscle relatively weakened for a variable period until the nerve terminal has recovered. In many conditions treated using Botulinum toxin injection, the main goal is to achieve a balance between the activity of a tight/short/overactive agonist and a weak/lengthened/inhibited antagonist, with synergistic muscles often contributing in a variety of complex ways. This special issue addresses a range of conditions where the main goal of treatment is to achieve a better balance of muscle function and, as a consequence, better movement control. In the preface to this material, Dr Alan Scott, describes the development of the therapeutic application of this toxin based upon pioneering studies using Botulinum toxin type A in monkeys and subsequently in humans to treat strabismus. From these fundamental origins, clinical applications have broadened extensively and continue to expand. Some of these applications are highlighted in sections within this issue and give insights into indications, efficacy and future issues for the therapeutic use of Botulinum toxin. The pharmacological basis for Botulinum toxin is reviewed by Dressler and Benecke who describe the versatility of its applications; including the potential to block cholinergic neuromuscular innervation of intraand extrafusal muscle fibres as well as cholinergic autonomic innervation of sweat, lacrimal, and salival glands and smooth muscles. In general it would appear that long-term clinical application does not produce additive adverse effects, although the potential for autoimmunity remains a problem in some applications. The development of commercial preparations of Botulinum toxin type B has offered options for individuals with auto-resistance and there is some evidence that this serotype may be more efficacious in the treatment of autonomic disorders. The role of Botulinum toxin injection in the management of axial and cervical dystonia is reviewed by Benecke and Dressler. Intramuscular injection of Botulinum toxin has revolutionalized the treatment of this group of conditions. Precise identification of dystonic muscles and careful quantification of their involvement is necessary to optimize patient outcomes. Sheean reports on the pathophysiology of the excessive and inappropriate muscle contractions which occur during fine motor tasks in individuals with focal task specific hand dystonia; and the efficacy of Botulinum toxin therapy, at least in the short term, in conjunction with other therapeutic approaches for this cohort. Gracies and colleagues provide an overview of the role of Botulinum toxin therapy in the management of muscle imbalance in the lower limb in adult onset central nervous system injury/dysfunction. These authors point to the key interactions between muscle overactivity, adaptive shortening and loss of strength

Spasmodic dysphonia (SD) is a rare neurological disorder that impairs phonatory function by triggering involuntary and intermittent contractions of the intrinsic laryngeal muscles. SD is classified into three types: adductor SD (AdSD), abductor SD (AbSD), and mixed SD. Of these, AdSD accounts for 90–95% of disease; younger females are predominantly affected. Botulinum toxin injection into the laryngeal muscles is safe, minimally invasive, and very effective. Here, we review the history of clinical research for SD conducted in Japan. The first use of botulinum toxin injection therapy to treat SD in Japan was by Kobayashi et al. in 1989. The group developed an objective mora (syllable) method to evaluate SD severity. Recently, we conducted a placebo-controlled, randomized, double-blinded clinical trial of botulinum toxin therapy for AdSD and an open-label trial for AbSD to obtain the approval of such therapy by the Japanese medical insurance system. The mora method revealed significant voice improvement and the evidence was of high quality. Additionally, a clinical trial of type 2 thyroplasty using titanium bridges confirmed the efficacy and safety of such therapy. These studies broadened the SD treatment options and have significantly benefited patients.