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.     

A comparison of injection techniques using botulinum toxin injection for treatment of the spasmodic dysphonias

The benefit duration and side effects following effective treatment of spasmodic dysphonia or voice tremor using botulinum toxin injection were studied following 477 open trial unilateral or bilateral injections provided to 178 patients. A comparison of unilateral and bilateral injections in male and female patients with adductor spasmodic dysphonia demonstrated an increased benefit duration following unilateral injections in women, longer periods of breathiness in men than in women following bilateral or unilateral injections, and a trend for reduced benefit durations following repeated treatments using bilateral injections. Outcomes were similar in the adductor spasmodic dysphonia and vocal tremor groups following thyroarytenoid injection while benefit durations were reduced and side effects lasted longer in patients with abductor spasmodic dysphonia following cricothyroid injections. Long-term benefit > 1 year occurred in 12.3% of patients following injection.     

Analysis of factors affecting botulinum toxin results in spasmodic dysphonia

This study was designed to investigate how variations in patterns of injection could improve the efficacy of botulinum toxin injections in relieving the symptoms of adductor spasmodic dysphonia. A total of 64 adductor spasmodic dysphonia patients who were injected using indirect laryngoscopic localization (for a total of 426 injections) were analyzed retrospectively using their own subjective data on duration of voice improvement, optimal voice improvement, breathiness side effects, and intervals between treatments. Injection to both the thyroarytenoid (TA) and the lateral cricoarytenoid (LCA) simultaneously gave the best voice results; the overall improvement from baseline was the longest lasting, and the period during which the voice was the best was the longest lasting. TA + LCA also gave the shortest duration of undesirable breathiness side effect. On the basis of these data, it seems reasonable to recommend that initial botulinum toxin therapy for adductor spasmodic dysphonia patients should be a single unilateral injection placed strategically at the posterior portion of the TA and directed toward the LCA so that both muscle groups are affected.     

Treatment of spasmodic dysphonia (laryngeal dystonia) with local injections of Botulinum toxin

In 1984 the authors performed the first laryngeal injection of Botulinum toxin for laryngeal dystonia via percutaneous, electromyographically guided technique. Since that time we have treated 450 patients with adductor spasmodic dysphonia, abductor spasmodic dysphonia, and adductor breathing dystonia. In general, the adductor patients received bilateral injections of 1.25 U to 3.75 U, obtaining greater than 90% of normal voice. The abductor patients received unilateral or staged bilateral injections of the posterior cricoarytenoid muscles with 0.6 to 3.75 U, obtaining 70% of normal function. We have found laryngeal injections of Botulinum toxin to be safe and effective therapy for the symptoms of laryngeal dystonia (spasmodic dysphonia).     

Technique of percutaneous EMG-guided botulinum toxin injection of the larynx for spasmodic dystonia

Percutaneous electromyography (EMG)-guided technique of botulinum toxin (BT) injection of the larynx evolved from similar techniques for extraocular muscle injection in strabismus, as well as from experience with diagnostic laryngeal EMG. This technique permits rapid accurate injection of BT into the laryngeal muscles. Although usually injected into the thyroarytenoid muscle, BT can also be directed to the posterior cricoarytenoid and cricothyroid muscles. Complications are minimal and of short duration.     

Functional reinnervation of vocal folds after selective laryngeal adductor denervation-reinnervation surgery for spasmodic dysphonia

Selective laryngeal adductor denervation-reinnervation surgery (SLAD-R) offers a viable surgical alternative for patients with adductor spasmodic dysphonia refractory to botulinum toxin injections. SLAD-R selectively denervates the symptomatic thyroarytenoid muscle by dividing the distal adductor branch of the recurrent laryngeal nerve (RLN), and preventing reinnervation, by the proximal RLN and maintaining vocal fold bulk and tone by reinnervating the distal RLN with the ansa cervicalis. We present a patient who had previously undergone successful SLAD-R but presented 10 years postoperatively with a new regional dystonia involving his strap muscles translocated to his reinnervated larynx by his previous ansa-RLN neurorraphy. The patient's symptomatic vocal fold adduction resolved completely on division of the ansa-RLN neurorraphy confirming successful selective functional reinnervation of vocal fold adductors by the ansa cervicalis.     

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     

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.     

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.     

Botulinum toxin treatment of spasmodic dysphonia: Techniques, indications, efficacy

A group of 58 patients with spasmodic dysphonia (SD) was treated perorally or transcutaneously with botulinum toxin (BT), and followed for at least 6 months. Most were treated by peroral injection using indirect laryngoscopy to facilitate precise placement. An effort was made to disperse the toxin over the entire thyroarytenoid muscle in order to affect the greatest number of motor end-plates using the smallest possible effective dose. Severely symptomatic patients with primarily adductor SD had the best results. A potentiation effect is suggested by analysis of a subpopulation of patients, mostly injected unilaterally, for whom the outcome was more favorable for those who had had prior injections. One-month postinjection studies reflect significant improvement in measured readings of a standard passage, and this is consistent with the subjective and perceptual improvements noted. There were no severe complications. Peroral injection seems inadvisable for patients with mixed or abductor SD as well as for those with an uncontrollable gag reflex.     

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.     

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.     

The dystonic larynx

“Spastic Dysphonia” or spasmodic dysphonia has been shown to be a focal laryngeal form of dystonia. Review of our 2556 cases of dystonia and 562 cases of laryngeal dystonia reveals similar male/female ratio, Jewish/non-Jewish ratio, family history, EMG data, and percent focal, segmental and general cases to be the same. Patients with the adductor form have a staccato, jerky, squeezed, labored, hoarse or groaning voice. In the abductor form, patients have a breathy, effortful voice with aphonic, whispered segments of speech. Compensatory forms may confuse the diagnosis. Fiberoptic videostroboscopy, EMG, and voice spectrograms are very useful for diagnosis.     

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.     

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     

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

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 Effect of Botulinum Toxin A on the Vocal Symptoms of Spastic Dysarthria: A Case Study

The vocal symptoms of spastic dysarthria and spasmodic dysphonia have many similar features. Botulinum toxin has been used effectively to treat spasmodic dysphonia. This study was designed to determine what vocal changes occur in an individual with spastic dysarthria following Botulinum toxin A injection into the thyroarytenoid muscles. Measures were obtained preinjection and three times postinjection. Acoustic and aerodynamic results were comparable to those reported for individuals with spasmodic dysphonia. The most marked change was increased DC airflow. Despite persistent breathiness, the participant reported great satisfaction with the result, particularly because of her more appropriate loudness. In addition, everyday listeners perceived significantly less listener burden and more relaxed and pleasant vocal quality postinjection.     

Electroglottographic tracking of phonatory response to botox™

Botox injection into the thyroarytenoid muscle is thought to alter the glottal competence and laryngeal adduction of patients with adductor spasmodic dysphonia (ADSD). Hypofunctional responses to treatment have been rated subjectively and inferred from postinjection breathy voice, aphonia, midline glottal gap, or subclinical aspiration. Clinical experience suggests that temporary hypofunction varies in duration and severity among patients. This study used electroglottographic measures to examine changes over time in glottal competence during the relatively stable phonation produced by 5 patients with ADSD. Hierarchical linear modeling was used to test 3 hypotheses: (a) that reduced laryngeal adduction would occur during the first 3 weeks postinjection, followed by a reversal; (b) that patients' hypofunctional response curves would differ one from another; and (c) that changes in adduction, if present, would be related to changes in severity ratings of ADSD symptoms. For 3 participants, significant hypoadduction occurred after injection and reversed toward preinjection level over an 8-week period. Two participants demonstrated a flat or increasing vocal fold contact response curve during the early postinjection period. Observations were consistent with the previously reported differences and possibly complex relation between the resolution of breathy hypofunction and ultimate return of ADSD symptoms.