The effect of patient factors on response outcomes toBotox treatment of spasmodic dysphonia

Injection of botulinum toxin (Botox) into the laryngeal muscleshas become the treatment of choice for controlling the symptoms of spasmodic dysphonia (SD). Currently, no specific battery of objective tests to assess the outcome is universally accepted. The purpose of this study was to investigate demographic, clinical, and treatment factors with voice outcome following Botox injection. Sixty-eight patients with adductor SD who underwent at least one Botox injection during a 5-year period were studied. Voice outcome measures were made from patient self-reporting scales and included overall vocal quality, length of response, and duration of breathiness. Vocal quality was significantly correlated with the underlying severity of vocal symptoms prior to treatment, incidence of breathiness and unilateral versus bilateral injection. The length of response was greater in males and following bilateral injections. An increased period of breathiness significantly correlated with bilateral injections.     

Combined-modality treatment of adductor spasmodic dysphonia with botulinum toxin and voice therapy

A combined-modality treatment program consisting of botulinum toxin injection (Botox) and voice therapy was used to treat 17 subjects diagnosed with adductor spasmodic dysphonia (ADD SD). Ten subjects with ADD SD served as the control and were given Botox only. Voice therapy after Botox injection was directed toward reducing the hyperfunctional vocal behaviors, primarily glottal overpressure at voice onset and anterior-posterior squeezing. The results indicated that subjects who underwent combined-modality treatment maintained significantly higher mean airflow rates for significantly longer periods. Moreover, there was a carryover effect in these patients when they received Botox only. Adductor spasmodic dysphonia is treated most effectively when intrinsic laryngeal muscle spasms are reduced or eliminated by Botox injection and extrinsic hyperfunctional vocal behaviors are treated with voice therapy     

Does botulinum toxin alter laryngeal secretionsand mucociliary transport?

Localized botulinum toxin injection disrupts cholinergic transmissionand has potential to cause focal dysautonomia. Mucociliary transport and laryngeal secretions are thought to be mediated in part by autonomic, cholinergic transmission. We questioned whether patients who receive Botox® injection for adductor spasmodic dysphonia (ADSD) report postinjection symptoms possibly related to altered mucociliary clearance or laryngeal secretions. Medical histories, audiotaped interviews, and symptom ratings were retrospectively examined for 29 patients with ADSD who were followed after one or more Botox injections. Patients had received bilateral, percutaneous Botox injections of 2.5 units using an EMG-guided approach. One or more weeks after injection, four patients reported either burning, tickling, or irritation of the larynx/throat, excessive thick secretions, or dryness. Symptoms recurred with subsequent injections in two patients and were not associated with swallowing difficulty. These symptoms are consistent with, but not diagnostic of, the known effects of botulinum toxin on cholinergic, autonomic transmission.     

Analysis of spasmodic dysphonia by aerodynamic and laryngostroboscopic measurements

Sequential assessment of laryngeal function using laryngostroboscopy and phonatory air flow assessment was carried out in 18 patients with spasmodic dysphonia (SD). Comparison was made between findings in patients before treatment (n = 18), after unilateral recurrent nerve block by lidocaine (n = 6), after bilateral injections of botulinum toxin (Botox) (n = 13), and prior to Botox reinjection (n = 3). Unilateral nerve block resulted in higher mean phonatory airflows than after bilateral Botox injections. Both unilateral nerve block and Botox injections increased fluctuant or alternating flow source (AC); however, unilateral nerve block resulted in more unmodulated airflow leakage. Phonation time on a single breath was longer than with Botox injection. Bilateral Botox injections resulted in better glottal closure, fewer instances of vocal fold level differences, and, better vocal fold vibrations with phase symmetry, as determined by laryngostroboscopy. Partial bilateral denervation using Botox resulted in laryngeal function, which appeared to be intermediate between that of tightly squeezed pretreatment status and a breathy voice with incomplete adduction after unilateral nerve block. Of all treatments assessed, bilateral partial denervation by Botox appeared to be the most physiologic in restoring normal vocal fold vibratory function and airflow.     

Voice Handicap Index Results for Older Patients with Adductor Spasmodic Dysphonia

Adductor spasmodic dysphonia (ADSD) adversely affects a speaker's ability to effectively communicate. For many individuals suffering with ADSD, botulinum toxin (Botox) is the chosen treatment to remediate the symptoms. Although Botox's effects on symptom remediation have been examined before, patient perception of improvement post-Botox has been examined less frequently. Further, no studies have addressed the symptomatic changes in older adults that occur after Botox treatment. The Voice Handicap Index (VHI) was used as the instrument to assess older patient's (>65 years) perception of how ADSD impacts certain areas of their life pre- and post-Botox injection. The outcome of the VHI was related to a clinical judgment of voice severity. Participants also completed the Social Readjustment Rating Scale (SRRS) to examine overall stress level, and the outcome of the SRRS was correlated to postinjection VHI scores. Results indicated no significant correlation between VHI scores and voice severity or SRRS ratings. The current study suggests further study of voice outcomes with older adults with ADSD is needed.     

Botulinum toxin injection in the treatment of vocal fold paralysis associated with multiple sclerosis: A case report

Botulinum toxin has been demonstrated clinically to be an effective treatment for a variety of laryngeal problems, most notably spasmodic dysphonia. As in other movement disorders, the theory behind the injection of this substance in the larynx has been a weakening of the vocal fold musculature to relieve uncoordinated and spasmodic movement of the vocal folds, presumably rebalancing the forces within the intralaryngeal musculature. Recently, this concept was applied to help reposition the arytenoid cartilage in acute and longstanding anteromedial cricoarytenoid dislocations. This same concept may apply to the paralyzed vocal fold. In support of this idea, a number of investigators have shown that immobile, clinically paralyzed vocal folds may still have partial voluntary motor unit activity. This voluntary activation may not produce clinically evident movement but may be sufficient to produce tone within the fold. If the voluntary motor units in the abductor musculature of the paralyzed fold are weakened with botulinum toxin, the continued pull of the functioning adductor musculature may be sufficient to medialize the paralyzed fold. This idea has been supported by animal experiments, which have shown that botulinum toxin may affect the ability of the fold to rebalance itself. With this evidence in mind, a patient with fold immobility secondary to multiple sclerosis was treated in an attempt at laryngeal rebalancing, using botulinum toxin to medialize the fold. However, instead of simply having the fold return fixed to the midline, the patient regained normal laryngeal mobility and voice. While it is unclear whether the botulinum toxin alone was responsible, the coincidence of this occurrence certainly requires reporting. This paper is a report of the first successful treatment of vocal fold paralysis using botulinum toxin to treat vocal fold fixation in a patient with multiple sclerosis.     

Botulinum toxin

The National Institutes of Health Consensus Development Conference on Clinical Use of Botulinum Toxin brought together neurologists, ophthalmologists, otolaryngologists, speech pathologists, and other health care professionals as well as the public to address the mechanisms of action of botulinum toxin, the indications and contraindications for botulinum toxin treatment, the general principles of technique of injection and handling for its safe and effective use, and the short-term and long-term side effects and complications of therapy. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel recommended that (a) botulinum toxin therapy is safe and effective for treating strabismus, blepharospasm, hemifacial spasm, adductor spasmodic dysphonia, jaw-closing oromandibular dystonia, and cervical dystonia; (b) botulinum toxin is not curative in chronic neurological disorders; (c) the safety of botulinum toxin therapy during pregnancy, breast feeding, and chronic use during childhood is unknown; (d) the long-term effects of chronic treatment with botulinum toxin remain unknown; and (e) botulinum toxin should be administered by committed interdisciplinary teams of physicians and related health care professionals with appropriate instrumentation. The full text of the consensus panel's statement follows.     

The treatment of essential voice tremor with botulinum toxin A: A longitudinal case report

The purpose of this study was to evaluate the effects of bilateral botulinum toxin injection into the thyroarytenoid (TA) muscles of a patient with essential voice tremor. Acoustic and aerodynamic data were collected weekly over a 16-week period. Flexible nasolaryngoscopy was performed prior to injection and 2, 6, 10, and 16 weeks postinjection. Perceptual analyses of the acoustic and nasolaryngoscopic data were performed. A reduction in frequency tremor and, to a lesser extent, amplitude tremor was observed during the 1-10 week period. Estimated laryngeal resistance decreased after injection and was accompanied in perceptual measures by a reduction in vocal effort, laryngeal tremor, and supraglottic hyperfunction. Essential voice tremor can be successfully attenuated with bilateral percutaneous injection of botulinum toxin A into the vocalis muscle.     

Bilateral vocal fold paralysis: an unsual treatment with botulinum toxin

We presented a patient with bilateral vocal fold paralysis treated with intralaryngeal Botox injection to improve the glottal airway. The use of Botox in this manner has not been previously reported and highlights the value and role of intralaryngeal Botox in changing the configuration of the glottis. The concept and various approaches for using Botox to alter pathologic vocal fold position is reviewed and discussed.     

Botulinum Toxin Type B for Treatment of Spasmodic Dysphonia: A Case Report

Although treatment with botulinum toxin type A (BTXA) has become the standard of care for most patients with laryngeal dystonia, its use is limited by the development of resistance to the toxin in some patients. Botulinum toxin type B (BTXB) has been found to be safe and effective in the treatment of cervical dystonia, but it has not been used previously to treat spasmodic dysphonia. Our experience with BTXB in a patient who developed resistance to BTXA suggests that BTXB may be safe and effective for the treatment of laryngeal dystonia, as well.     

Botulinum Toxin Therapy for Abductor Spasmodic Dysphonia

Botulinum toxin has been widely accepted as an effective therapy for controlling the symptoms of adductor spasmodic dysphonia (ADSD). Reported experience with botulinum treatment for abductor spasmodic dysphonia (ABSD) has been less impressive. Factors that may impair outcomes for ABSD include differences in the pathophysiology of ADSD and ABSD and limitation of maximal dose from airway restriction with posterior cricoarytenoid muscle (PCA) weakness. We report our experience with botulinum injection of the PCA with an asymmetric dose escalation protocol, based on clinical observations that in ABSD, abductor spasms are often stronger on one side, usually the left. The nondominant side was injected with 1.25 units. Dominant side dose began at 5 units, with step-wise increments of 5 units per week until one of three endpoints was reached: Elimination of breathy voice breaks, complete abductor paralysis of the dominant side, or airway compromise. Fourteen of 17 patients achieved good or fair voice, with dominant-side doses ranging from 10 to 25 units. Exercise intolerance limited PCA dose in two patients. One patient had persisting breathiness that improved with medialization thyroplasty. Asymmetric botulinum toxin injection into PCA muscles can suppress abductor spasm in patients with ABSD, but breathiness may persist, because of inadequate glottal closure.     

Adductor spasmodic dysphonia: case reports withacoustic analysis following botulinum toxin injection and acupuncture

We analyzed frequency and duration parameters of voice and speech in two men with adductor spasmodic dysphonia (SD). One was treated with botulinum toxin injection; the other received acupuncture therapy. Im provement after acupuncture therapy in terms of standard deviation of fundamental frequency, acoustic perturbation measurements, durational measurements of voice and speech, and spectrographic analysis was comparable to the results achieved with botulinum toxin injection. Voice and speech parameters were stable I year after acupuncture therapy.     

Immunologic Characterization of Spasmodic Dysphonia Patients Who Develop Resistance to Botulinum Toxin

The immune status of six spasmodic dysphonia patients who became resistant to botulinum toxin was compared to that of a series of patients who remained responsive. The two groups were similar in terms of age, sex, and cumulative dose of toxin. Five of the resistant patients had a significant titer of anti-botulinum toxin IgG antibodies, as determined by enzyme-linked immunosorbent assay (ELISA). These same five resistant patients had a circulating titer of anti-heavy chain antibodies, but only three of these patients had a circulating titer of anti-light chain antibodies, as determined by Western blotting. By contrast, none of the responsive patients had antibodies against the holotoxin or its two chains. Interestingly, two of the resistant patients also had a low circulating titer of anti-botulinum toxin IgA antibodies. None of the responsive patients was IgA-positive. The cumulative dose of botulinum toxin administered to resistant patients was lower than that customarily associated with emergence of immunity in dystonia patients.     

Longitudinal Effects of Botulinum Toxin Injections on Voice-Related Quality of Life (V-RQOL) for Patients with Adductory Spasmodic Dysphonia

Adductory spasmodic dysphonia is a focal dystonia of laryngeal muscles. Patients with this disorder typically have severe vocal difficulties, with significant functional, social, and emotional consequences. There is no widely accepted cure for this condition, however, botulinum toxin injections of the thyroarytenoid muscles are considered by most voice clinicians to be the state of the art treatment. Based on extensive experience treating patients for adductory spasmodic dysphonia, we feel that traditional means of voice assessment do not adequately measure either the disease severity or the treatment outcomes. That is, listening to or acoustically analyzing limited phonatory samples does not capture the functional, social, and emotional consequences of this disorder. These consequences will be reflected in a patient's voice-related quality of life (V-RQOL). Using a validated voice outcomes instrument, the V-RQOL Measure, the purpose of this study was to quantify longitudinal changes in the V-RQOL of patients with adductory spasmodic dysphonia who are undergoing botulinum toxin injections. Twenty-seven consecutive new patients presenting with dysphonia to our institution during an 18-month period were diagnosed with adductory spasmodic dysphonia, and treated patients were evaluated prospectively using the V-RQOL Measure. Results indicated that (1) V-RQOL was initially very low for these patients, (2) botulinum toxin injections improved it significantly for each injection cycle studied, and (3) the magnitude of the treatment effect appears to change across injections.     

Functional assessment of patients with spasmodic dysphonia

Assessment of function in patients with spasmodic dysphonia is necessary to confirm diagnosis, plan therapy, predict response, and assess effectiveness of treatment. This task is difficult because symptom severity fluctuates, the test environment is artificial, and the objective parameters used to measure vocal function may not adequately reflect the handicap experienced by the patient. Available methods for assessing these patients are reviewed and the utility of each considered, particularly in managing patients with botulinum toxin therapy. Assessment should include a battery of tests, including subjective perceptual ratings and direct physical measurements.     

Practice parameter: laryngeal electromyography (an evidence-based review)

This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders, including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. Thirty-three of the 584 articles met the predefined inclusion criteria. The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the two techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications.     

Laryngeal Botulinum Toxin Injection: Can It Be a Cause of Obstructive Sleep Apnea as an Adverse Effect?

Spasmodic dysphonia is a chronic voice disorder that is characterized by involuntary spasms of the laryngeal muscles during speech production. Botulinum toxin injection into to the laryngeal muscles is the most common and effective treatment of choice for symptoms of spasmodic dysphonia. We present a 44-year-old man with adductor spasmodic dysphonia who was diagnosed as having upper airway obstruction in a polysomnographic examination during sleep after a botulinum toxin injection.     

Botulinum Toxin in the Management of Laryngeal Tics

SUMMARY: The objective of the study was to demonstrate the utility of botulinum toxin (BTX; Botox: Allergan Pharmaceuticals, Irvine, CA) type A injections for symptom reduction in laryngeal tics. The study consisted of case studies and literature review. Case histories of two patients with laryngeal tics are presented. Treatment was administered using BTX type A injected into the thyroarytenoid muscles using electromyographic guidance or via direct laryngoscopy. Treatment outcomes were measured using clinical rating scales with a range from 0 (no response) to 4 (maximal response). A subjective assessment of reduction in premonitory sensations was recorded. Subject 1 was a 49-year-old female with onset of laryngeal tic (throat clearing) at 46 years. She received six injections over 24 months. The lowest effective dose was 1.25 units bilaterally, producing complete resolution of the tic behavior (peak effect of 4/4) and reduction of the premonitory sensations. The median duration of benefit was 13 weeks. Subject 2 was a 14-year-old male with Gilles de la Tourette syndrome with laryngeal symptoms including throat clearing, barking, and crowing. He received three injections, with the lowest effective dose of 0.625 units bilaterally. He achieved marked reduction (peak effect of 3/4) of the throat clearing, barking, and crowing behaviors. There was also substantial reduction of the premonitory sensations. The median duration of benefit was 10 weeks. The cases presented herein are examples of successful treatment with low-dose BTX type A to reduce the symptoms of laryngeal tics, leading to improved quality of life. These cases add to the relatively small number of similar patients reported in the literature, and support the use of chemical neuromuscular blockade for treatment of laryngeal tic symptoms.     

Paradoxical vocal fold motion: Presentation and treatment options

Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.     

Use of flexible fiberoptic laryngoscopy to assess patients with spasmodic dysphonia

Flexible videolaryngoscopy was used to study 38 patients with spasmodic dysphonia, rating excessive activation of intrinsic laryngeal muscles, extrinsic muscle hyperfunction, tremor, and dystonic movements. Seventeen patients were also studied after unilateral botulinum toxin injection. Dysfunction varied greatly; however, discrete patterns could not be identified. Functional status correlated significantly with the total score of all pathologic indicators, but not with any single parameter. Botulinum toxin was highly effective in reducing intrinsic laryngeal muscle activation, but did not always improve tremor. Extrinsic laryngeal muscle hyperfunction was not significantly affected by the toxin