Laryngeal dystonia …

Movement Disorders

Updated 06.19.2024
Released 08.14.1995
Expires For CME 06.19.2027

Laryngeal dystonia (spasmodic dysphonia)

Authors: Tanya K Meyer MD, Rachel Jonas MD

See Contributor Disclosures

Editor: Robert Fekete MD

Laryngeal dystonia (spasmodic dysphonia)

In This Article

Quick Link

Introduction

Overview

A dystonia is characterized as involuntary muscle contractions. Dystonia can be divided into primary dystonia, in which there is no identified neurologic lesion, or a secondary dystonia, in which there is an identifiable lesion, such as lesions within the basal ganglia in Parkinson disease. Dystonia can also be focal, regional, or diffusely affect the entire body. Laryngeal dystonia, previously called spasmodic dysphonia, is a focal dystonia involving the intrinsic musculature of the larynx (thyroarytenoid, lateral cricoarytenoid, interarytenoid or posterior cricoarytenoid muscles). The more common type, adductor laryngeal dystonia, involves the muscles that adduct, or close, the vocal cords (thyroarytenoid, lateral cricoarytenoid, and interarytenoid muscles) and typically results in strained, strangled, effortful speech with breaks in phonation. Abductor laryngeal dystonia, which is less common, involves the paired posterior cricoarytenoid muscles, which are the only muscles that abduct, or open, the larynx for breathing. Abductor laryngeal dystonia generally causes breathy speech with voiceless pauses.

The task-specific nature of this condition means that the hyperfunctional muscular spasms occur with speech, but voice and function may be normal with other laryngeal activities, such as swallowing, coughing, laughter, yawning, and singing.

Laryngeal dystonia is typically diagnosed by history, listening to the voice, and laryngeal endoscopic videostroboscopy to exclude other disorders. Several causative genes have been identified for some forms of laryngeal dystonia, although it usually is idiopathic. As in other focal dystonia disorders, the mainstay of treatment for laryngeal dystonia is botulinum toxin injections into the affected musculature. Patients can experience side effects after botulinum toxin injections, although these are usually transient. Dosage of botulinum toxin is titrated to maximize improvement while minimizing side effects.

Key points

	• The diagnosis of laryngeal dystonia is made clinically based on perceptual voice evaluation combined with laryngeal endoscopy.
	• Adductor laryngeal dystonia typically results in strained, strangled, effortful speech with breaks in phonation.
	• Abductor laryngeal dystonia generally causes breathy speech with voiceless pauses.
	• Both adductor and abductor laryngeal dystonia are rare, with females more likely affected than males, although adductor laryngeal dystonia is more common than the abductor form.
	• The disorder was initially considered psychogenic, but subsequent studies have confirmed the neurogenic origin.
	• EMG-guided botulinum toxin injections into the intrinsic laryngeal musculature have become the mainstay of treatment for laryngeal dystonia.

Historical note and terminology

Laryngeal dystonia is a focal dystonia resulting in task-specific, action-induced spasm of the vocal cords. Historically, Tiberius Claudius Drusus Nero Germanicus, who became emperor of Rome 41 AD, has been suspected to have laryngeal dystonia (162). It was first described by Traube in 1871 as a “nervous hoarseness” in a young girl and assigned the label of spastic dysphonia (205). The patient only spoke with great effort, and “the laryngoscopic examination revealed spastic closure of the vocal cord, whereby the left arytenoid cartilage shifted in front of the right one while probably also the vocal cords were particularly overlapping of each other” (178). Schnitzler may be the first one to suspect organic etiology, in 1895, in two patients with “cramping of the vocal cord and forced voice” (181), who also had synkinesis of facial muscles and abnormal movements of the arms and legs (104). Schnitzler termed the condition “aphonia spastica” or spastic dysphonia. Due to the lack of other coexisting neurologic deficits, the disorder continued to be considered psychogenic (74; 178; 11). A century later, Aronson pointed out the wax and wane characteristic and proposed the term “spasmodic” instead of “spastic,” which implies rigidity (08; 09). Robe and colleagues were the first to postulate that this disorder was related to the central nervous system (163). Although, credit for reviving interest in laryngeal dystonia as a medical disorder belongs to Dedo with the proposed recurrent laryngeal nerve resection, which was a bold decision at the time when most of his contemporaries still believed in a psychiatric etiology (45).

Clinical manifestations

Presentation and course

The onset of laryngeal dystonia is insidious in most patients (84%), initially presenting as nonspecific hoarseness with gradual worsening of vocal quality over months to years (93; 07; 200). In a small proportion of patients, the onset is sudden (93). The most common inciting events identified by patients are stress, upper respiratory infection, pregnancy, and parturition (39; 05).

Laryngeal dystonia may be divided into three types (abductor laryngeal dystonia, adductor laryngeal dystonia, and mixed type laryngeal dystonia), depending on the specific intrinsic laryngeal muscles that are most affected. Adductor laryngeal dystonia is the most common form and accounts for up to 82% of cases (24). Abductor laryngeal dystonia occurs in 17% of cases, and the mixed type (both abductor and adductor laryngeal dystonia) is rare (25).

If the adductor muscles (thyroarytenoid, lateral cricoarytenoid, or interarytenoid muscles) are affected, then the laryngeal dystonia is termed “adductor laryngeal dystonia.” Quick glottic closure, because the adductor muscles spasm closed, interrupts airflow during phonation leading to breaks during vowels. The result is a classic strained, strangled speaking pattern (123). If the abductor musculature (posterior cricoarytenoid muscles) is affected, the laryngeal dystonia is termed “abductor laryngeal dystonia.” Patients have spasms when transitioning to a voice after a voiceless consonant. Prolonged vocal fold abduction during the voiceless consonant and spasms of the vocal cords in the open position prevent the rapid closure of the vocal cords during transition to vowels. The result is a breathy, effortful speaking pattern with poor generation of volume.

There is less consensus on the features of adductor laryngeal dystonia than the features of abductor laryngeal dystonia (124). Only 53% of 46 laryngeal dystonia specialists agreed that intermittent glottal stops were a feature of adductor laryngeal dystonia, and 47% agreed that patient report of speaking effort was a feature of adductor laryngeal dystonia. Of 46 laryngeal dystonia specialists, 97% agreed that intermittent breathy breaks are a feature of abductor laryngeal dystonia.

Tremor may coexist with dystonia in as many as one third of patients (108), although this is more common in females (152). Fine wire electromyography has revealed that both the thyroarytenoid and the lateral cricoarytenoid muscles might be affected in adductor laryngeal dystonia, even if the thyroarytenoid is more predominant (106). The thyroarytenoid and lateral cricoarytenoid muscles are equally involved in laryngeal dystonia with tremor (106).

Patients may have a mixed laryngeal dystonia with both adductor and abductor musculature affected, which may result in speech with both phonatory breaks from adductor spasms and breathy breaks from adductor spasms.

Laryngeal dystonia most commonly affects normal speech, typically in the normal talking range of pitch, volume, and speed. Laughing, whispering, screaming, and yawning may normalize the voice. Voice improvements also occur when the patient is taken by surprise or in sudden danger. These characteristics are likely related to the task-specific nature of dystonia. Vocal spams occur during speaking, but not during emotional vocalization (laughing, crying, shouting) because of the difference in the human vocalization system and human speech system. The neural systems involved in speech, which is learned, are likely not involved in emotional vocalization, which is an innate trait. The vocalization system includes the anterior cingulate, the periaqueductal gray, and the reticular system in the medulla and the laryngeal motor neurons in the nucleus ambiguous (97). On the other hand, the human speech system includes the laryngeal motor cortex to the laryngeal motor neurons in the nucleus ambiguous, the corticobulbar tract, the frontal opercular speech system, the primary motor cortex, the supplementary motor area, the posterior temporal gyrus, and the supramarginal gyrus (113; 191).

Some patients report that sensory tricks, such as touching the larynx, supporting the head, or lying down may improve speech. The fluency may also be improved by speaking in a higher pitch. Vacation often brings an improvement whereas stress can worsen vocal quality. Some patients report sedatives or consumption of alcohol reduce symptoms, although this is more characteristic of vocal tremor (103). Most patients report voice worsening with speaking in public or on the telephone (89).

Table 1. Factors Influencing Subjective Severity of Laryngeal Dystonia

	Relieving factor	Aggravating factor
Stress Talking on the telephone Louder speech Yawning Higher pitch Laughter Whisper Lower pitch Alcohol Strong statements Singing Softer speech Morning Prolonged talking Slower speech Swallowing Inspiratory speech	— — 23.7% 19.5% 18.9% 18.3% 14.8% 10.6% 10.1% 8.3% 7.7% 7.7% 7.7% 2.4% 2.4% 1.8% 1.2%	47.3% 29.6% 4.1% — — — — — 1.2% — 2.4% — — 5.3% — — —
(204)

Reports of task-specific laryngeal dystonia occurring only with singing (singer’s laryngeal dystonia) have also been described (24). Respiratory laryngeal dystonia results in laryngeal adductor spasms during respiration. Patients with this form of dystonia usually complain of dysphonia, but also dyspnea and inspiratory stridor, although not usually hypoxia (203).

Prognosis and complications

Laryngeal dystonia tends to emerge gradually in midlife and then reaches a plateau in terms of severity. Spontaneous remission has not been reported in laryngeal dystonia, which can be seen with cervical dystonia (128).

Untreated laryngeal dystonia may be associated with increased psychological comorbidity. A study of 44 patients with adductor laryngeal dystonia revealed substantial degrees of perceived handicap and low perceived control of the condition (98). Rates of anxiety and depression appear to be higher in patients with laryngeal dystonia and other voice disorders compared to the general population (216). In an analysis of 142 patients receiving botulinum toxin injections for laryngeal dystonia, anxiety was present in 13.4%, and depression was present in 2.8% (84).

Laryngeal dystonia can functionally affect work productivity (89). Patients with laryngeal dystonia report a 20% to 30% mean decrease in voice-related work productivity, which is ameliorated after treatment with botulinum toxin injections (141). The work productivity decreases are mainly in the form of presenteeism (140). Additionally, individuals with laryngeal dystonia reported seeking jobs without high voice demands and avoiding communication (16). However, a study using the Communication Participation Item Bank questionnaire showed that changes in communicative participation were not statistically significant, pre- and post-botulinum toxin treatment (58). The authors attributed this finding to demographic variables and different levels of access to care within their studied population.

Other studies show that treatment alters functional disability and quality of life. Hoogikyan and colleagues reported improvements in voice-related quality of life scores before and after treatment with botulinum toxin (80), although these results were not replicated in a study of individuals over the age of 65 (217).

However, botulinum toxin, the treatment for laryngeal dystonia, wears off after a variable period of time (2 to 6 months). Therefore, repeated treatment is needed, possibly lifelong. According to a national survey, most practitioners who provide botulinum toxin injections for laryngeal dystonia work at an academic care center (135). This may limit access to repetitive treatment and cause burden and loss of work productivity for those who live in more rural or remote areas.

Clinical vignette

Case 1. The patient in his late 40s was working in law enforcement and doing a sting operation at a warehouse location. On-site, there was a lot of construction dust. He began to have vocal difficulties that he felt were due to laryngitis from irritant exposure, but his voice did not return even when he moved to a different project location. His voice continued to deteriorate and became more strained and effortful. About 10 years later, he saw a speech-language pathologist with some improvement in his voice. He then noticed that while on amusement-park rides with his grandchildren, his voice was reproducibly normal. His speech-language pathologist accompanied him to the amusement park to witness this change in his voice and, thus, diagnosed him with laryngeal dystonia. He did not seek treatment until 2013 and was initially treated with 1 unit of botulinum toxin A to the bilateral thyroarytenoid muscles. He had significant breathiness and some difficulty with swallowing, and his dose was reduced. Currently, he receives an asymmetrical dose of 0.15 units of botulinum toxin A to one thyroarytenoid muscle and 0.25 units of botulinum toxin A to the contralateral thyroarytenoid muscle with vocal improvement from 40% to 50% normal function at baseline (when the effects of botulinum toxin have dissipated) to 80% to 90% of normal vocal function at the peak effect of the botulinum toxin injection with minimal breathiness or dysphagia.

Chronic constriction variant of adductor laryngeal dystonia

Patient diagnosed with chronic constriction variant of adductor laryngeal dystonia has a strained voice just before LEMG-guided botulinum toxin A injection. (Contributed by Dr. Tanya K Meyer.)
LEMG-guided botulinum toxin injection for laryngeal dystonia

Patient diagnosed with chronic constriction variant of adductor laryngeal dystonia undergoes LEMG-guided botulinum toxin A injection. (Contributed by Dr. Tanya K Meyer.)

Case 2. A 43-year-old female reported acute onset of voice changes in July 2016. She endorsed a strained effortful and “garbled” voice quality. She noted improvement in vocal quality with singing and with alcohol consumption. She was seen by her local ENT and referred to a speech-language pathologist and then further referred to the university for evaluation and management. As the vice president of her community college who frequently spoke to large groups, she had an extraordinary demand for voice use and quality in her vocational capacity. She was a nonsmoker and was otherwise healthy, with no other medical problems and no family history of neurologic disorders.

The patient was diagnosed with adductor laryngeal dystonia and initially treated with LEMG-guided botulinum toxin injections with a good effect. But after 2 years of treatment, she struggled with her injections causing too much initial breathiness and a shorter-than-desired duration of peak voicing. She was changed to an endoscopic approach to her injections and currently receives botulinum toxin injections to the bilateral thyroarytenoid and to the interarytenoid musculature. Her total dose is 2.5 units every 10 weeks of which she typically experiences 1 week of initial breathiness and mild dysphagia to liquids and 9 weeks of effect. She reports 4 weeks of peak voicing (90% to 100% of normal function), with a gradual decline to her baseline of 15% to 20% of normal function.

Adductor laryngeal dystonia voice at baseline

Voice of patient with adductor laryngeal dystonia at baseline before chemodenervation. (Contributed by Dr. Tanya K Meyer.)
Adductor laryngeal dystonia voice at peak after chemodenervation

Voice of patient with adductor laryngeal dystonia at peak voice 3 weeks after chemodenervation. (Contributed by Dr. Tanya K Meyer.)

Biological basis

Etiology and pathogenesis

Classifying laryngeal dystonia as a medical disorder rather than psychiatric is attributed to Dedo after a recurrent laryngeal nerve resection (45). Nevertheless, the etiological and pathophysiological mechanisms underlying laryngeal dystonia are not known. Histologic analysis of the recurrent laryngeal nerves in two patients who underwent recurrent laryngeal nerve resection revealed no apparent signs of either destruction or degeneration; however, the percentage of thin nerve fibers (diameter ranging from 5 to 10 microns) was higher than in normal controls (110). In another study, slight morphometric differences were found between the recurrent laryngeal nerve removed from patients with laryngeal dystonia and control recurrent laryngeal nerves in two groups, but these cannot explain causation of laryngeal dystonia (36).

Focal dystonias, such as laryngeal dystonia, are generally thought to be due to dysfunction in the basal ganglia. However, there is evidence to suggest that laryngeal dystonia is caused by abnormalities of large-scale brain networks, rather than due to pathology limited to the basal ganglia (67).

Postmortem brainstem examination in two patients with laryngeal dystonia revealed several neuropathological changes compared to controls (191). This included small clusters of inflammation in the reticular formation surrounding the solitary tract, spinal trigeminal nuclei, and in the pyramids in addition to neuronal degeneration and depigmentation in the substantia nigra and locus coeruleus.

Neurophysiological studies reveal that patients with adductor laryngeal dystonia have a shortened cortical silent period compared with healthy controls (171; 172; 199). Cortical silent period is the temporary interruption of electromyographic signal from a muscle with resulting interruption of voluntary muscle contraction after transcranial stimulation of the contralateral motor cortex, which is a way of measuring intracortical inhibition within the primary motor cortex. The laryngeal dystonia patient has abnormal blink reflex recovery, further pointing to a loss of inhibitory control (40). Loss of inhibitory control is also seen in many other focal dystonic conditions (151), and the underlying defect may be impaired inhibition at the cortical level leading to a decrease in the requirement for activation with voluntary motor commands (37). Measurements of excitability over the dominant primary motor cortex during “linguistic” and “non-linguistic” tasks following transcranial magnetic stimulation have been shown to differ in patients with laryngeal dystonia compared with healthy controls (199). Following treatment with botulinum toxin, there is restoration of these changes (199). A study utilizing EEG found excessively large synchronization between somatosensory and premotor cortical areas in patients with laryngeal dystonia (101).

Sharbrough and colleagues described abnormal auditory brainstem responses in 7 of 18 patients with laryngeal dystonia, indicating slower brainstem conduction along the auditory pathway (184). In another study of six patients with adductor laryngeal dystonia using the auditory brainstem response, five of six patients had a compromised capacity of the auditory brainstem to conduct impulses (64). In a study of 12 patients with laryngeal dystonia using three different auditory brainstem response parameters, 75% were abnormal. Three of the 12 had prolonged wave I–V interpeak latency, and seven had pathologic wave V latency shifts at a high stimulus rate (177). These findings were not confirmed by Middleton in a study of 14 patients with laryngeal dystonia with normal hearing (142).

Devous and colleagues suspected that in laryngeal dystonia, there was a dysfunction of cortical perfusion, cortical electrophysiology, or both, based on quantitative topographic electrophysiologic mapping and SPECT (50). Hirano and colleagues suggested that the functional deficit of the supplementary motor area might be related to laryngeal dystonia (78). Studying a 59-year-old male patient with adductor type laryngeal dystonia during phonation with PET, Hirano and colleagues noted remarkable activities during phonation in the left motor cortex, Broca area, cerebellum, and the auditory cortices, whereas the supplementary motor area was not activated. In normal subjects, significant activities were observed during vocalization in the supplementary motor area, whereas the auditory association area was not activated, even though the subjects heard their own voice (76). Similar to patients with laryngeal dystonia, normal subjects showed activation in the motor area, Broca area, and the cerebellum. The auditory association area was not activated during normal vocalization but came to be activated when the speaker’s own voice was distorted (76; 77), as is the case with the laryngeal dystonia strained voice. As the supplementary motor area is known to function for motor planning, programming (164) is usually activated in normal phonation, and damage of the supplementary motor area causes a severe disturbance of voluntary vocalization.

When functional MRI (fMRI) measurements were performed during vocal motor tasks in patients with laryngeal dystonia and compared with healthy volunteers, reduced activation of primary sensorimotor as well as premotor and sensory association cortices during vocalization in patients with laryngeal dystonia were noted (72). Another study utilizing fMRI found reduced functional connectivity between the left inferior parietal cortex, putamen, and bilateral premotor cortex (15).

Gray matter volume, cortical thickness, and brain activation on fMRI were increased in the laryngeal sensorimotor cortex, inferior frontal gyrus, superior or middle temporal and supramarginal gyri, and cerebellum in a study of 40 patients with laryngeal dystonia compared with controls (192). Phenotype-specific abnormalities have been reported in adductor and abductor forms of laryngeal dystonia on high-resolution MRI and diffusion-weighted imaging. Differences in cortical thickness and white matter fractional anisotropy were observed in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiate (20). In addition, genotype-specific abnormalities were seen between sporadic and familial cases in the left superior temporal gyrus, the supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus.

Lenticular nucleus hyperechogenicity has been observed on transcranial sonography in patients with laryngeal dystonia (213). A study examining a combination of independent component analysis and linear discriminant analysis of resting-state functional magnetic resonance imaging data found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with laryngeal dystonia compared with control subjects (14). In addition, differences in abnormal functional connectivity appeared to distinguish between the different clinical phenotypes of laryngeal dystonia, as well as between the genetic and sporadic forms. Differences in cortical surface area have also been described in subjects with laryngeal dystonia compared with control subjects in regions associated with sensorimotor integration, motor preparation, and motor execution, as well as in areas of processing of auditory and visual information (111).

In a PET study using [11C] raclopride (RAC) to assess striatal dopaminergic neurotransmission, patients with laryngeal dystonia demonstrated decreased RAC displacement during symptomatic speech production compared with controls, indicating decreased dopaminergic transmission (189). RAC displacement was increased during the unaffected task of asymptomatic tapping, possibly representing a compensatory adaptation of the nigrostriatal dopaminergic system.

Differential diagnosis

Confusing conditions

The differential diagnosis of laryngeal dystonia is broad and includes both organic disorders and functional disorders. Table 2 lists some differential diagnoses of laryngeal dystonia. Essential voice tremor and muscle tension dysphonia can cause voice breaks; thus, they can form the most important differential diagnoses.

Vocal tremor, a condition acoustically characterized by low-frequency oscillations in voice, can occur in isolation or as a component of essential tremor. Essential tremor is a progressive action tremor and consists of involuntary and rhythmic movements at 4 to 12 Hz of one or more antagonistic muscles or muscle groups. It affects approximately 1% of all people and nearly 5% of those older than 65 years (122). Eighteen to 30% of patients with essential tremor have a vocal tremor (197). The movement disorder in vocal tremor is rhythmic rather than spasmodic. In addition to the intrinsic laryngeal muscles, it often involves pharyngeal and strap muscles. Lundy and colleagues found that unlike laryngeal dystonia, tremor is more often marked by fluctuations in frequency rather than just in intensity (126).

Muscle tension dysphonia, a functional dysphonia, may also mimic the strained voice quality of abductor laryngeal dystonia (83). Evidence of consistent sound-specific phonatory breaks should raise suspicion of adductor spasmodic over muscle tension dysphonia. The hyperadduction of muscle tension dysphonia is generally sustained and is unlikely to be spasmodic. Although differences between muscle tension dysphonia and adductor laryngeal dystonia have been described on fiberoptic laryngoscopy, phonatory airflow measurement, and acoustic analysis, there is currently no single diagnostic test to differentiate these two disorders (169).

Careful auditory perceptual voice evaluation can help differentiate these diagnoses. One key difference is that neither vocal tremor nor muscle tension dysphonia demonstrate task specificity, whereas laryngeal dystonia does (present with talking as opposed to laughing and singing). The voice may deteriorate with stress in all conditions. Laryngeal endoscopy helps in the differential between laryngeal dystonia, vocal tremor, and muscle tension dysphonia; however, the diagnosis may be challenging in some cases. Even among experts, there can be notable variation when diagnosing patients with laryngeal dystonia, vocal tremor, or muscle tension dysphonia. In one study, international experts were asked to classify the vocal diagnosis of 178 patients across four different sites into 11 categories (124). The experts reviewed a portion of these patients’ video-laryngeal endoscopy and speech recordings, but due to a lack of diagnostic guidelines, there was poor interrater agreement regarding patient diagnoses.

In psychogenic dysphonia, another functional dysphonia, there are often several atypical characteristics, including loss of normal shouting, yawning, and laughing. Psychogenic dysphonia also does not present with tremor (119). In psychogenic dysphonia, the vocal symptoms are more often invariant across phonetic and most phonatory variables and not associated with sound prolongations or voice arrests (119). In one study, psychogenic speech and voice disorders were found to occur in 16.5% of 182 patients with psychogenic movement disorders. Among these patients, stuttering was the most common speech abnormality (n = 16, 53.3%), followed by speech arrests (n = 4, 13.3%), foreign accent syndrome (n = 2, 6.6%), hypophonia (n = 2, 6.6%), and dysphonia (n = 2, 6.6%) (11).

Vocal cord polyps or other mass lesions of the vocal cord can cause dysphonia characterized by strain and vocal breaks. These lesions would be visualized and diagnosed on laryngeal endoscopy.

There are also reports of stridor resulting from laryngeal dystonia, and in some cases, this may be misdiagnosed as asthma (204).

A form of dysphonia similar to laryngeal dystonia has also been described in dominantly inherited ataxia with dentate calcification, currently assigned the name “spinocerebellar ataxia type 20” (107).

Table 2. Differential Diagnosis for Laryngeal Dystonia

• Meige syndrome or part of generalized dystonia (133; 95)
• Wilson disease
• Huntington chorea
• Parkinson disease
• Essential tremors (121)
• Gilles de la Tourette syndrome (115)
• Spinocerebellar ataxia type 20 (107)
• Mitochondrial disease (157)
• Amyotrophic lateral sclerosis (168)
• Palatal myoclonus (56)
• Drug induced dysphonia (214)
• Tardive dyskinesia (06)
• Recurrent nerve paresis
• Strokes
• Vocal cord nodules or polyps
• Neoplasm
• Inflammation of the vocal cord (gastroesophageal reflux, rheumatoid arthritis)
• Infection of the vocal cord
• Trauma (63)
• Psychogenic dysphonia (176)
• Muscle tension dysphonia
• Asthma

Associated or underlying disorders

Laryngeal dystonia may occur as an isolated dystonia or as part of generalized dystonia (133; 95; 73; 03; 132; 156). Yet, most patients with laryngeal dystonia present only with the vocal dysfunction, without neurologic manifestations in other areas of the body (25). Most commonly, laryngeal dystonia occurs sporadically, and there are no associated or underlying disorders. Laryngeal dystonia less frequently occurs in the setting of segmental or generalized dystonia. The reported prevalence of extralaryngeal dystonia in patients with laryngeal dystonia varies from 5% to 14% (69; 152). In one series that included 901 patients with vocal involvement, 82.5% had primary dystonia and 17.5% had secondary dystonia (25). In another series, 15.8% of patients with laryngeal dystonia had spread of dystonia, all of whom developed cervical dystonia (19). In another study, patients with cough, disordinate breathing, paroxysmal sneezing, and hiccups were found to have a higher incidence of extralaryngeal dystonia (155).

Several causative genes have been identified in familial dystonic syndromes that cause generalized dystonia, which have risk of components of laryngeal dystonia (48). Careful clinical characterization of the dystonic syndrome allows accurate phenotype-genotype correlation and may assist in identifying an underlying genetic diagnosis. Despite these familial dystonic syndromes having components of laryngeal dystonia, genetic screening of patients with laryngeal dystonia targeted at mutations in TOR1A, THAP1, and TUBB4 has a low diagnostic yield (70; 48).

Gene	Gene function	Disease	Presentation	Reference
THAP1	Encodes a transcription factor that regulates endothelial cell proliferation	DYT6	Dystonia affecting the cervical, cranial, and upper limb musculature, often with laryngeal involvement. Mutations have also been identified in patients with early-onset generalized dystonia with laryngeal dystonia.	(23; 218) (55)
TOR1A	Encodes for a protein that is involved in cellular functions, such as protein folding, lipid metabolism, cytoskeletal organization, and nuclear polarity	DYT1	Dystonia of the limbs, notably sparing the craniofacial muscles initially and then spreading and progressing to severe generalized dystonia.	(62)
TUBB4	Encodes for a neuronally expressed tubulin, and mutations lead to basal ganglia and cerebellum atrophy	DYT4	Prominent spasmodic (“whispering”) dysphonia, which is distinct from abductor and adductor laryngeal dystonia, and associated craniocervical dystonia as well as a “hobby horse”–type gait.	(120)
ANO3	Encodes for calcium-gated chloride channels	DYT24	Craniocervical dystonia, including laryngeal dystonia and mild upper limb dystonia, notably additionally with tremor.	(195)
GNAL	Encodes a protein that mediated signaling within the olfactory epithelium	DYT25	Cervical dystonia, something with head tremor and laryngeal dystonia, although isolated laryngeal dystonia/laryngeal dystonia has also been described, and generalized dystonia occurs in about 10% of cases.	(12; 160)
KMT2B	Encodes a protein that methylates DNA and modifies the epigenome	DYTKMT2B	Progressive childhood-onset dystonia, with prominent cervical, cranial, and laryngeal dystonia. It is associated with typical facial features of an elongated face and bulbous nasal tip.	(139)

Other reported associations include neuroleptic exposure, either immediately or as part of the tardive syndrome (214; 06), mitochondrial disease (157), valproic acid administration (with improvement after discontinuation) (150), central pontine myelinosis (183), amyotrophic lateral sclerosis (168), psychogenic dysphonia (176; 11), late-onset laryngeal dystonia with low arylsulphatase A (134), essential tremor (121), palatal myoclonus (56), hereditary spastic paraplegia type 7 (71), multiple sclerosis (53), or trauma (63).

Diagnostic workup

Possibly because of the unfamiliarity of the disease, there is often a delay in diagnosis and patients are seen by multiple physicians prior to a definitive diagnosis. One study showed that patients had over a 4-year delay from initial presentation to a physician for vocal concerns to reaching a diagnosis of laryngeal dystonia (41). Another study from Japan showed that in 60% of patients, the diagnosis of laryngeal dystonia was delayed for more than 2 years (87).

Understanding of the nature of the symptoms, including onset, aggravating factors, alleviating factors, associated symptoms, duration of symptoms, and the character of symptoms is the focus of the history and helps lead to a correct diagnosis.

Table 3. Voice History and Symptoms of Laryngeal Dystonia

Onset of symptoms
	Sudden Progressive
Aggravating/alleviating factors
	Speaking Singing Stress Prolonged phonation
Associated symptoms
	Odynophonia Other neurologic signs Other systemic medical conditions
Character of symptoms
	Quality of voice
		Raspiness Breathiness Strain
	Flow
		Decreased breath support Decreased projection Decreased volume
	Control
		Loss of pitch control Voice breaks
(138)

History, physical examination, and laryngeal stroboscopy are all critical components of the diagnostic algorithm, but the most important component is the auditory perceptual evaluation of voice (138). The primary modality to assess laryngeal dystonia is by listening to the patient speak during conversational speech and during elicited speech tasks with either vowel or voiceless consonant predominant sentences (99). Listening to the patient reading sentences that are designed specifically to elicit either adductor or abductor spasms is also helpful. One should assess the fluidity of the voice, the quality of articulation, and the quality of the vocal signal. A normal voice should be smooth, without voice breaks or spasm.

Adductor laryngeal dystonia phrases or sentences would include words with vowels or voiced sounds such as:

	• “We eat eggs every evening.”
	• “Ambling down Rainy Island Avenue.”
	• Counting 80 to 85

Abductor laryngeal dystonia phrases or sentences would include words with vowels following a voiceless consonant (such as d, f, h, p, s or t). A breathiness is heard as a speaker transitions from a voiceless consonant to a voiced sound.

	• “Taxi!”
	• “The puppy bit the tape.”
	• “Hammy hit the hammer hard.”
	• Counting 60 to 65

Some clinicians have patients read the phonetically balanced “rainbow passage”:

When the sunlight strikes raindrops in the air, they act like a prism and form a rainbow. The rainbow is a division of white light into many beautiful colors. These take the shape of a long round arch, with its path high above, and its two ends apparently beyond the horizon. There is, according to legend, a boiling pot of gold at one end. People look, but no one ever finds it. When a man looks for something beyond his reach, his friends say he is looking for the pot of gold at the end of the rainbow… (61; 138).

Other measures of voice quality, which may provide further characterization of laryngeal dystonia, include the IINFVo (Impression, Intelligibility, Noise, Fluency, and Voicing) perceptual rating scale and the AMPEX (Auditory Model Based Pitch Extractor) acoustical analysis (186). Measurements in perceptual, acoustic, and self-assessment dimensions all demonstrate significant improvement in symptoms following botulinum toxin therapy, which is the standard of care. However, these three parameters were found to have poor intrinsic correlation; thus, a tridimensional approach may be preferable (49). Another study found that the latency between the initiation of thyroarytenoid electrical activity and the onset of phonation was significantly related to the severity of adductor laryngeal dystonia (43). The technique of airflow interruption may also provide additional quantitative information regarding laryngeal function in laryngeal dystonia (79). One study examining the perceptual structure of adductor laryngeal dystonia and the acoustic correlates of underlying perceptual factors identified a two-factor model of adductor laryngeal dystonia, characterized by hyperadduction and hypoadduction (35). Perceived ratings of roughness appeared to be most representative of the hyperadduction factor, whereas breathiness was most strongly associated with the hypoadduction factor. Onset of relative fundamental frequency measures were found to be related to perceived vocal effort in patients with adductor laryngeal dystonia in another study (57). Cepstral analysis and machine-learning algorithms have been able to distinguish between patients with laryngeal dystonia and controls and between pre- and post-botulinum toxin treated patients (198).

Although the primary modality to assess laryngeal dystonia is listening to the patient speak during conversational speech, a physical examination is essential for the evaluation. Attention should be paid to a complete neurologic examination. Laryngeal dystonia usually presents without other neurologic findings, so any tremor, weakness, or cranial nerve neuropathy should prompt further neurologic evaluation. In the setting of associated clinical features, such as segmental dystonia, tremor, or gait disturbance, careful clinical characterization of the phenotype may provide clues to an underlying genetic dystonic syndrome (see etiology and pathogenesis).

Spasms can be visualized during adductor and abductor laryngeal dystonia. Because laryngeal dystonia is a disorder of connected speech, transnasal rather than transoral laryngoscopy should be performed. In a study in which experts were provided videos, audios, and both, the diagnostic accuracy of laryngeal dystonia was 10%, 73%, and 73%, respectively (42). Based on this, laryngoscopy is most important for ruling out additional types of dysphonia diagnoses. Small vocal fold cysts and polyps may result in alteration of the voice, and stroboscopic examination may help determine the lesion’s contribution to the patient’s vocal complaints. The addition of a laryngeal stroboscopic assessment to the endoscopic imaging will allow a detailed evaluation of the vibratory function and architecture of the vocal folds, regardless of diagnosis.

Because spasms may be too quick to visualize on laryngoscopy, high-speed video endoscopy can help. Chen and colleagues were able to detect a rapid sustained adduction shortly after onset of phonation in a small sample of patients with adductor laryngeal dystonia compared to muscle tension dysphonia (38). Tsuji and colleagues described the findings of one patient with high-speed video laryngoscopy where there was a regular vibratory cycle followed by a spasm in which there was an increase in the closed phase and then a period in which the glottic cycle phases could not be identified (208).

Researchers have tried to identify modalities to diagnose laryngeal dystonia and differentiate it from muscle tension dysphonia, but these have not gained wide clinical use. One study suggested that the long-term average spectrum (LTAS), a tool that assesses the average amplitude spectrum across a selective frequency range and provides information on the spectral distribution of the speech signal over a period of time, may identify spectral noise differences between muscle tension dysphonia and adductor laryngeal dystonia in women (83). The use of neural network and support vector machine–based methods, in combination with a pattern recognition algorithm, has also been studied (179). Fine kinemetric analysis from high-speed digital imaging may assist in the clinical differentiation of adductor laryngeal dystonia and muscle tension dysphonia, although further studies are required (154).

Electromyography (EMG) measures muscle electrical activity in response to stimulation. In a study of patients with adductor laryngeal dystonia, Yang and colleagues found there were increased amplitudes of the motor unit recruitment potentials and evoked potentials of the thyroarytenoid muscles (219). Another study did not support this finding (211). When combined with acoustic channels, there may be a delay from the onset of the electrical activity on EMG with the onset of the acoustic output in laryngeal dystonia (188). A neurolaryngology study group in 2009 concluded that there is not enough evidence to support EMG being used as a diagnostic tool (29).

Management

Botulinum toxin. Botulinum toxin injections are the mainstay of treatment for laryngeal dystonia. Blitzer and colleagues performed the first botulinum toxin treatment on a patient with spasmodic dysphonia in 1986, and their work was confirmed by a subsequent double-blind study (26; 207). The American Academy of Otolaryngology-Head and Neck Surgery as well as the American Academy of Neurology endorses botulinum toxin as primary therapy for spasmodic dysphonia.

Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum that prevents the release of acetylcholine from the nerve ending at the neuromuscular junction. The result is a partial paralysis of the injected muscle. The toxin is made of a heavy and a light chain. The heavy chain allows the neurotoxin to be endocytosed into the neuron. Once within the neuron, the light chain binds to the SNARE proteins. SNARE proteins allow acetylcholine-containing vesicles to fuse at the nerve terminal to exocytose acetylcholine.

There are eight different types of toxins produced by Clostridium botulinum (A, B, C1, C2, D, E, F, and G). Type A is the most potent, and type B is the second most potent.

Five different botulinum toxin products are available on the market. Four of these toxins are botulinum toxin type A and include Botox® (Allergan, Inc., Irvine, California, United States), Dysport® (Ipsen Ltd., Slough, Berkshire, United Kingdom), Xeomin® (Merz Pharmaceuticals, United States), and CBTXA (China). Myobloc®/Neurobloc® (Solstice Neurosciences, Inc., South San Francisco, California, United States) is botulinum toxin type B. In the United States, the available preparations include Botox®, Xeomin®, and Myobloc®/NeuroBloc®.

Neutralizing antibodies to botulinum toxin can develop. Injections of botulinum toxin type B can be safely and effectively used in patients with antibodies to type A (01).

There are different techniques of laryngeal botulinum toxin injection. The most common is the EMG-guided percutaneous approach (143). Injections can also be performed using external landmarks, termed the “point-touch technique” (145). Injections under direct visualization, either by endoscopy or mirror examination, include a transoral approach (65), a percutaneous approach, and a transnasal approach (161). Others use laryngoscopic control in addition to EMG (207). A national survey of delivery methods of botulinum toxin injections for adductor laryngeal dystonia showed that an overwhelming majority (88%) of laryngologists use EMG guidance, 9% use anatomic landmarks, and very few (3%) use endoscopic guidance (185). Injections can be bilateral, unilateral, staggered, or with asymmetrical doses (136; 206; 210).

The thyroarytenoid muscle is most commonly injected for adductor laryngeal dystonia, although injections can be performed to any of the intrinsic laryngeal adductor muscles (thyroarytenoid, interarytenoid, lateral cricoarytenoid). Additionally, supraglottic injection of botulinum toxin to the false vocal folds is a treatment for adductor laryngeal dystonia (193). As there is only one muscle involved in vocal cord abduction, this muscle (the posterior cricoarytenoid) is injected for abductor laryngeal dystonia.

To perform the EMG-guided percutaneous approach to the thyroarytenoid muscle, a Teflon-coated injection needle is connected to the EMG machine. Typically, a 25-gauge needle is utilized. The needle is inserted just off midline (2–3 mm) through the space between the cricoid and thyroid cartilages, pointing towards the ipsilateral thyroarytenoid muscle. Bending the injection needle by 30 to 45 degrees can ease access to the muscle. The localization of the needle is verified by crisp motor unit potentials heard on EMG when the patient performs a long “/i/” (143; 32). The EMG activity is sustained during the phonation (75).

The EMG-guided percutaneous approach to the lateral cricoarytenoid muscle is similar to the EMG-guided percutaneous approach to the thyroarytenoid muscle. The needle is inserted further off midline in the cricothyroid space, at the junction of the cricoid cartilage and thyroid cartilage. After passing through the cricothyroid space, the needle is pointed towards the ipsilateral lateral cricoarytenoid muscle, and the location is confirmed with auditory feedback on the EMG machine during a sustained “/i/”. In this case, the EMG will show an increase and rapid drop-off in EMG activity, as the lateral cricoarytenoid muscle is responsible for the initial setting of the vocal cord position (75). A cadaver study showed that ultrasound-guided injection of the lateral cricoarytenoid muscle is feasible and precise (180).

Botulinum toxin injection into the interarytenoid muscle is additionally performed with EMG guidance. Topical anesthesia to the larynx is typically required, however. The needle is passed through the cricothyroid space and into the subglottis. A distinct air signal will be heard on the EMG when the needle is in the airway. The needle is then directed upwards towards the interarytenoid muscle. Insertional activity signal will be heard on the EMG machine when the muscle is entered, followed by recruitment activity during a sustained “/i/”.

Injections into the false vocal cords can be performed in various ways, all under direct visualization without EMG guidance. A flexible needle can be threaded through the working channel of a transnasal laryngoscope and the injection performed through this needle. However, this requires a large amount of liquid to prime the needle. Another approach is the peroral approach in which a flexible nasolaryngoscopy is performed to visualize the larynx. Then an orotracheal injector with a needle is passed perorally. The needle is visualized by the flexible laryngoscope and directed into the false vocal folds. Lastly, a thyrohyoid approach can be used in which a 25-gauge needle is advanced through the thyrohyoid membrane and under direct visualization with a flexible nasolaryngoscope; the needle is directed into the false vocal fold. In all approaches, the depth of injection is within the submucosal plane. This results in a bleb seen below the mucosa (193). Nasal anesthesia and decongestant are utilized during this procedure, in additional to laryngeal and airway anesthesia.

The injection of botulinum toxin into the posterior cricoarytenoid muscle for abductor laryngeal dystonia is more challenging. Injection techniques usually include translaryngeal EMG guidance and laryngeal rotation (27), endoscopic guidance (165), and transcricoid rostrum (136), or a combination approach. As opposed to confirming the position of the needle with a sustained “/i/”, the position within the posterior cricoarytenoid muscle is confirmed with crisp motor unit potentials heard on EMG when the patient sniffs, which further abducts the vocal cords.

In the translaryngeal EMG-guided approach to injection of the posterior cricoarytenoid, the needle is passed through the skin overlying the cricothyroid membrane, through the airway, and through the posterior cricoid plate into the posterior cricoarytenoid muscle. Visualization with laryngoscopy is often utilized to improve the accuracy of the injection. As the mucosa of the airway is violated, topical anesthesia to the glottis and subglottis is typically required.

For the laryngeal rotation technique, the physician rotates the larynx to expose the posterior aspect of the thyroid cartilage. The needle is passed posterior to the thyroid lamina, along the lower half of the thyroid cartilage/superior border of the cricoid cartilage, until the needle hits the posterior surface of the cricoid. EMG auditory feedback is used to confirm the position.

Typically, unilateral posterior cricoarytenoid muscle injections are performed. A major concern for bilateral injections is bilateral vocal fold abductor weakness and the consequent narrowing of the airway for adequate respiration. Simultaneous bilateral posterior cricoarytenoid injections have also shown success in improving vocal outcome measures (105). Successful outcomes have also been reported using an initial unilateral posterior cricoarytenoid muscle injection, followed by a contralateral injection after 2 weeks, if necessary (24).

Botulinum toxin doses. Doses of botulinum toxin used for the treatment of laryngeal dystonia vary depending on the practitioner and the brand of toxin used. In the early literature, the doses of botulinum toxin (Botox^®) into the thyroarytenoid muscle for adductor laryngeal dystonia ranged from 3.75 to 7.5 U for bilateral injections (34; 32; 33; 207) to 15 U for unilateral injections (143; 125). Up to 50 U per vocal cord has been used (96). Later literature and common practice have recommended the use of lower doses (30). In the authors’ experience, a chemodenervation-naive patient is started on botulinum toxin A at a dose of 0.5 to 1 unit in the bilateral thyroarytenoid muscle for the adductor laryngeal dystonia. This starting dose is based on Blitzer's original work (26). In one retrospective study of 126 patients, the mean dosage of onabotulinumtoxinA was 1.54 +/- 0.35 units per side (66).

Injection into the false vocal cords is typically at higher doses--anywhere from 5 to 10 units per false vocal fold (193).

The optimal dose of botulinum toxin varies between patients and does not appear to correlate with severity of laryngeal dystonia, age, or gender. In one study, BMI and overall health were correlated with a higher effective dose (220). Higher doses were required for symptom control in female patients with adductor laryngeal dystonia compared to males in one retrospective chart review, although the reasons for this observation are unclear (118). The dose of botulinum toxin required for the treatment of adductor laryngeal dystonia tends to remain stable over time (167). In one retrospective study, patients with adductor laryngeal dystonia who received long-term injections appeared to have an initial reduction followed by stabilization in their dosage (147). Those who have a fluctuating dosing trend tended to have a shorter interval between injections.

Patients are warned about potential coughing with liquids and breathy vocal quality, which typically last no more than a week. They are then instructed to return when their voice breaks start to worsen. At that time, at the authors’ institution, they are asked to judge their best voice on a scale of 0% to 100%, with 100% being a completely normal voice and 0% being no voice at all. They are then asked about any initial side effects and how long those symptoms lasted. At that point, the decision is made to increase or decrease the botulinum toxin dose or change the injection interval.

There appears to be a lower rate of resistance with botulinum toxin in laryngeal dystonia compared with other dystonias, and this may be related to the low antigen challenge associated with the low doses used (144).

Surgery. After recognition of the organic etiology of laryngeal dystonia, the development of recurrent laryngeal nerve resection confirmed the neurologic basis of the disease process. The first patient to undergo recurrent laryngeal nerve resection was a woman with a 17-year history of laryngeal dystonia who had been treated by more than 29 physicians from different specialties without improvement. Blocking of the recurrent nerve with lidocaine improved her spasm, whereas placebo injections did not improve the patient’s voice (45). After five repeated reproducible results with lidocaine, the patient underwent sectioning of the right recurrent laryngeal nerve with essentially normal voice within 1 week after the procedure, with the help of speech therapy.

Another less invasive procedure involved crushing the recurrent nerve, which initially appeared to be equally effective. Gross recurrent laryngeal nerve destruction is no longer a contemporary management for laryngeal dystonia, although this procedure is of great historical importance regarding the recognition that this disease has a neurologic and not psychiatric pathophysiology.

For adductor laryngeal dystonia, selective laryngeal adductor denervation-reinnervation (SLAD-R), first described in 1999 (18), involves selective denervation of the adductor branch of the recurrent laryngeal nerve. The distal nerve stumps are reinnervated with a nonlaryngeal nerve, generally the sternohyoid branches of the ansa cervicalis nerve (137).

Isshiki and colleagues offered an apparently mechanical solution to the problem of hyperadduction in adductor laryngeal dystonia with laryngeal framework surgery (92; 90). In this procedure, a lateralization laryngoplasty, or type II thyroplasty, is performed by means of a midline division and expansion of the thyroid cartilage.

Bilateral thyroarytenoid muscle myectomy is also used in the treatment of adductor laryngeal dystonia. Successful treatment of adductor laryngeal dystonia has also been reported in a small series of patients using selective lateral laser thyroarytenoid myotomy (86; 68). Sustained improvements in voice handicap index and GRBAS scale have been observed following endoscopic laser thyroarytenoid myoneurectomy (209; 68).

Surgical treatment for abductor laryngeal dystonia is more nuanced and has been less described in the literature. Bilateral vocal fold medialization, or type I thyroplasty, has been used by some.

Deep brain stimulation for adductor laryngeal dystonia is described for the treatment of laryngeal dystonia in a phase 1 clinical trial (81). A phase 2 clinical trial of deep brain stimulation for laryngeal dystonia is currently being conducted.

Other therapeutic modalities. Voice therapy has been reported to be helpful in conjunction with botulinum toxin treatment to retrain a long-term compensatory behavior superimposed on laryngeal dystonia (146), although this has not been consistent. Significant improvement with speech therapy may suggest an alternate diagnosis of muscle tension dysphonia (13). In a systematic review of 21 studies of voice therapy in patients with laryngeal dystonia, the adherence rate was quite low (about 60%) (131).

Although to a lesser degree than in the past, many patients with laryngeal dystonia are still subjected to psychiatric treatment. Psychotherapy is useful to help coping with social stresses, which can be considerable; the patient, however, needs to be made aware first that his or her condition is an organic disorder and to be treated accordingly either with botulinum toxin or surgery. Acupuncture has not been proven effective by expert raters, although Lee and colleagues found many patients reported subjective improvements in voice production (116). Electrical stimulation of the thyroarytenoid muscle was reported to improve symptoms in one small case series (158). An open-label study of sodium oxybate demonstrated reduced voice symptoms in alcohol-responsive laryngeal dystonia in those with and without coexistent voice tremor (170); unfortunately, the medication is expensive and only has a duration of up to 3 or 4 hours, which has limited more common clinical use (190).

Outcomes

As noted above, botulinum toxin injection is the mainstay of treatment for laryngeal dystonia, with positive outcomes. Treatment with botulinum toxin leads to a reduction in spasmodic contractions observed on video laryngoscopy (59). Yet, lower functional gain was noted in patients with dystonia in other body regions (130). A meta-analysis of 30, mostly single-blind studies, indicated moderate overall improvement as a result of botulinum toxin treatments (31). The Cochrane Collaboration Review noted that although only one study (207) out of the nearly 77 reports was double-blind and fulfilled their inclusion criteria, most of the studies had similarly positive effects (215). In one series of 131 patients, 67 of 574 injections (12%) were categorized as failures: failure was associated with injection by a new physician, the patient being a professional voice user, and a lack of breathiness in the voice after injection (221).

Improvement after injection with botulinum toxin for adductor laryngeal dystonia is realized an average of 2.4 days after injection; the average peak benefit occurs at 9 days post injection (28). For abductor laryngeal dystonia, the average onset of effect is 4.1 days, with a peak effect at 10 days.

For adductor laryngeal dystonia, the positive benefit of botulinum toxin injections lasts for approximately 15.1 weeks (28). The mean duration of benefit is 10.5 weeks for those with abductor laryngeal dystonia (28). Most insurance companies only allow for botulinum toxin injections every 3 months (four times per year). However, there are a considerable subset of patients who require short interval treatment to optimize their outcomes. In a study, 27.5% of patients required injections less than 90 days apart (short interval) while not showing an increased side effect profile (114). These patients were statistically younger than those who did not require short-interval botulinum toxin injections.

In the largest treatment series in 2010, patients with adductor laryngeal dystonia reported an improvement to 91.2% of normal with botulinum toxin injection (24). Treatment of abductor laryngeal dystonia was less satisfactory, with patients reporting an improvement to 70.3% of normal. Another study noted average subjective phonation improvement of 33% with adductor laryngeal dystonia (130). In another study examining outcomes of onabotulinumtoxinA, 88.1% of injection cycles for 328 patients with adductor laryngeal dystonia were noted to be maximally beneficial (153).

A meta-analysis showed significant improvement in several quality-of-life measures after treatment with botulinum toxin, including the Voice Handicap Index (VHI) and Voice-Related QoL scales (59; 60). Furthermore, patients on an established botulinum toxin injection routine have been shown to have high degrees of general and disease-specific self-efficacy, a concept that combines self-esteem and locus of control (85). Furthermore, the higher the self-efficacy, the lower the VHI and levels of anxiety and depression.

Possible complications from botulinum toxin injections into the thyroarytenoid musculature include breathiness, throat pain, and dysphagia. Initial functional decline following botulinum toxin injection was observed in 28.5% of cases (149). In a series of 1300 patients over 24 years of age, adductor injections were associated with a 25% risk of mild, transiently breathy voice and a 10% risk of transient coughing with drinking fluids. Breathy dysphonia has been reported to be as high as 50.9%, lasting on average 20 days (54). Local pain, bruising, and itch were reported in less than 1% of individuals (24). Rarely, bilateral abductor paralysis has been reported and is likely a result of toxin diffusion around the muscular process of the arytenoid to the posterior cricoarytenoid muscles (212).

There are some data to suggest that botulinum toxin is less effective in patients with concurrent vocal tremor (149). Patients with adductor laryngeal dystonia and associated vocal tremor may benefit from combined interarytenoid and thyroarytenoid muscle botulinum toxin injections (100). Botulinum toxin injections into the interarytenoid muscle have a 50% response rate in patients previously unresponsive to traditional injection sites (99).

Voice after supraglottic false vocal fold botulinum toxin injection for adductor laryngeal dystonia is significantly improved without the side effect of a period of a significantly breathy voice initially after injection (193).

Different protocols have been proposed for injecting botulinum toxin into the thyroarytenoid muscle, either unilaterally or bilaterally. Initial dosages of 1.25 units bilaterally of onabotulinumtoxinA resulted in a statistically significant shorter duration of breathiness without significant differences in clinical effectiveness or voice outcome in one study, compared with an initial dosage of 2.5 units bilaterally (166). Unilateral injection may result in fewer adverse events, such as breathiness or hoarseness (109; 21). Unilateral injections improve the performance ratio of strong voice interval divided by breathy voice interval (109). Upile and colleagues found that low-dose unilateral injections resulted in no significant difference in patient outcome in terms of voice duration, voice score, and complication rate when compared with bilateral injections (210). However, another study found that bilateral injections had a significantly higher proportion of patients than unilateral injections (36% vs. 33%, p=0.0228), with both greater than 3-month duration of effect and less than 2-week duration of side effects (52). Some studies have shown that the duration of benefit in men is significantly longer and with less swallowing difficulty after bilateral injections (129). Lee and colleagues found that alternating injections to the thyroarytenoid muscle was effective, with fewer side effects than bilateral injections, although the treatment effect was shorter (117). This was additionally supported by Stone and colleagues, who found that unilateral botulinum toxin injections reduce side effects without sacrificing improved voice outcomes, although with a shorter duration of improvement (196). Interestingly, they also studied bilateral injections with different doses to each side and found that this can extend the duration of effect, although with more side effects compared to a unilateral injection (196). Another study also found that the side effect profile was better for unilateral injections, but the authors concluded that bilateral injections had a better side effect/optimal effect profile (52).

Recurrent laryngeal nerve sectioning initially showed remarkable therapeutic results. Dedo reported the results of sectioning of the recurrent laryngeal nerve in 34 patients (45). Short- and mid-term results were good, with a recurrence rate of 10% to 15%, respectively (94; 46; 47). Long-term results showed a gradual decline in benefit from the procedure. Crushing of the recurrent laryngeal nerve also from widespread recurrence of symptoms had a success rate of 13% at 3 years (22).

The initial reports of selective laryngeal adductor denervation-reinnervation (SLAD-R) presented favorable results in 19 of 21 patients (18). Only one patient underwent further treatment with botulinum toxin postoperatively. Positive results using expert and untrained judge’s perceptual evaluation of the voice were also reported in a smaller series (04). Additional studies have also reported favorable results after a mean follow-up time of 7.5 years (137). Functional reinnervation of the vocal cord adductors by ansa cervicalis has been observed 10 years after successful SLAD-R surgery (44).

Isshiki reported success in a small series with informal judgments regarding voice quality by both patients and physicians after type II thyroplasty (92; 90). A further small study using laryngeal framework surgery also resulted in significant acoustic and aerodynamic improvement in adductor laryngeal dystonia (175). Follow-up after 2 to 5 years revealed unsatisfactory outcomes in 7 of 90 cases and were mainly attributed to inadequate technique and, in one case, an incorrect indication (173). Surgical mechanical faults appear to be the main cause of unsuccessful outcomes (91). Another long-term follow-up study (average of 41.3 months) following type II thyroplasty demonstrated sustained improvement in voice symptoms and quality of life (174).

One study found no difference in the postoperative Voice Handicap Index 10 score between patients who underwent bilateral thyroarytenoid muscle myectomy compared to those who received type II thyroplasty (148). Bilateral thyroarytenoid muscle myectomy appeared to improve strangulation, interruption, and tremor but worsened breathiness when compared to type II thyroplasty.

In one case series, six patients underwent vocal fold medialization via type 1 thyroplasty and demonstrated significant benefit on Voice Handicap Index (VHI) and Voice-Related Quality of Life (VR-QOL) measures. The four patients who had undergone the procedure at least 1 year prior to their survey reported a sustained benefit to their symptoms (51). One patient with staged bilateral posterior cricoarytenoid partial myoneurectomy demonstrated sustained benefit up to 8 years postoperatively (17).

Deep brain stimulation of the globus pallidus internus (GPi) resulted in improvement of segmental dystonia, including laryngeal dystonia in one patient, with maintenance of symptom control at 10-year follow-up (82). Some patients with primary dystonia with a component of laryngeal dystonia had no benefit to their laryngeal dystonia with GPi stimulation (88). One patient with essential tremor and adductor laryngeal dystonia had sustained benefit to her laryngeal dystonia with bilateral ventral intermediate (Vim) nucleus of the thalamus stimulation (127). Another patient with essential tremor and coincident adductor laryngeal dystonia treated with unilateral thalamic deep brain stimulation experienced significant improvement in vocal dysfunction with isolated Vim and combined Vim and ventral oralis anterior (Voa) nucleus of the thalamus (159). Honey and Kruger have reported promising results with bilateral thalamic deep brain stimulation (112; 81).

With regards to voice therapy, one study did not demonstrate additional benefits in patients receiving voice therapy compared to those receiving botulinum toxin alone or to those who received botulinum toxin with sham voice therapy (187). Further studies are required to confirm these results.

Laryngeal vibrotactile stimulation temporarily improved symptoms in 9 of 13 patients (102). This improvement was associated with a suppression of theta band power in the left somatosensory motor cortex, similar to what is seen during successful sensory tricks.

Media

References

01: Adler CH, Bansberg SF, Krein-Jones K, Hentz JG. Safety and efficacy of botulinum toxin type B (Myobloc) in adductor spasmodic dysphonia. Mov Disord 2004;19(9):1075-9. PMID 15372600
02: Adler CH, Edwards BW, Bansberg SF. Female predominance in spasmodic dysphonia. J Neurol Neurosurg Psychiatry 1997;63:688. PMID 9408119
03: Albanese A, Bhatia K, Bressman SB, et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord 2013;28(7):863-73. PMID 23649720
04: Allegretto M, Morrison M, Rammage L, Lau DP. Selective denervation: reinnervation for the control of adductor spasmodic dysphonia. J Otolaryngol 2003;32:185-9. PMID 12921138
05: Ankola A, Sulica L, Murry T. Laryngeal dystonia gravidarum: sudden onset of adductor spasmodic dysphonia in pregnancy. Laryngoscope 2013;123(12):3127-30. PMID 23712421
06: Armstrong L, Randal P. Spasmodic dysphonia, a rare form of tardive dystonia, induced by low-dose risperidone. Aust N Z J Psychiatry 2004;38:174. PMID 14961937
07: Aronson A. Clinical voice disorders: an interdisciplinary approach. New York: Thieme, 1990.
08: Aronson AE, Brown JR, Litin EM, Pearson JS. Spastic dysphonia. I. Voice, neurologic, and psychiatric aspects. J Speech Hear Disord 1968a;33:203-18. PMID 4385966
09: Aronson AE, Brown JR, Litin EM, Pearson JS. Spastic dysphonia. II. Comparison with essential (voice) tremor and other neurologic and psychogenic dysphonias. J Speech Hear Disord 1968b;33:219-31. PMID 5668051
10: Asgeirsson H, Jakobsson F, Hjaltason H, Jonsdottir H, Sveinbjornsdottir S. Prevalence study of primary dystonia in Iceland. Mov Disord 2006;21:293-8. PMID 16211610
11: Baizabal-Carvallo JF, Jankovic J. Speech and voice disorders in patients with psychogenic movement disorders. J Neurol 2015;262(11):2420-4. PMID 26194199
12: Balint B, Bhatia KP. Isolated and combined dystonia syndromes - an update on new genes and their phenotypes. Eur J Neurol 2015;22(4):610-7. PMID 25643588
13: Barkmeier-Kraemer JM, Clark HM. Speech-language pathology evaluation and management of hyperkinetic disorders affecting speech and swallowing function. Tremor Other Hyperkinet Mov (N Y) 2017;7:489. PMID 28983422
14: Battistella G, Fuertinger S, Fleysher L, Ozelius LJ, Simonyan K. Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia. Eur J Neurol 2016;23(10):1517-27. PMID 27346568
15: Battistella G, Simonyan K. Top-down alteration of functional connectivity within the sensorimotor network in focal dystonia. Neurology 2019;92(16):e1843-51. PMID 30918091
16: Baylor CR, Yorkston KM, Eadie TL. The consequences of spasmodic dysphonia on communication-related quality of life: a qualitative study of the insider's experiences. J Commun Disord 2005;38(5):395-419. PMID 15963338
17: Benito DA, Ferster AP, Sataloff RT. Bilateral posterior cricoarytenoid myoneurectomy for abductor spasmodic dysphonia. J Voice 2018;pii:S0892-1997(18)30148-6. PMID 30174222
18: Berke GS, Blackwell KE, Gerratt BR, Verneil A, Jackson KS, Sercarz JA. Selective laryngeal adductor denervation-reinnervation: a new surgical treatment for adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol 1999;108:227-31. PMID 10086613
19: Berman BD, Groth CL, Stefan HS, et al. Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study. J Neurol Neurosurg Psychiatry 2020;91(3):314-20. PMID 31848221
20: Bianchi S, Battistella G, Huddleston, et al. Phenotype- and genotype-specific structural alterations in spasmodic dysphonia. Mov Disord 2017;32(4):560-8. PMID 28186656
21: Bielamowicz S, Stager SV, Badillo A, Godlewski A. Unilateral versus bilateral injections of botulinum toxin in patients with adductor spasmodic dysphonia. J Voice 2002;16:117-23. PMID 12002878
22: Biller HF, Som ML, Lawson W. Laryngeal nerve crush for spastic dysphonia. Ann Otol Rhinol Laryngol 1979;88:531-2. PMID 475251
23: Blanchard A, Ea V, Roubertie A, et al. DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene. Hum Mutat 2011;32(11):1213-24. PMID 21793105
24: Blitzer A. Spasmodic dysphonia and botulinum toxin: experience from the largest treatment series. Eur J Neurol 2010;17(Suppl 1):28-30. PMID 20590805
25: Blitzer A, Brin MF. Laryngeal dystonia: a series with botulinum toxin therapy. Ann Otol Rhinol Laryngol 1991;100:85-9. PMID 1992905
26: Blitzer A, Brin MF, Fahn S, Lange D, Lovelace RE. Botulinum toxin (BOTOX) for the treatment of "spastic dysphonia" as part of a trial of toxin injections for the treatment of other cranial dystonias. Laryngoscope 1986;96:1300-1. PMID 3773633
27: Blitzer A, Brin MF, Stewart C, Aviv JE, Fahn S. Abductor laryngeal dystonia: a series treated with botulinum toxin. Laryngoscope 1992;102:163-7. PMID 1738288
28: Blitzer A, Brin MF, Stewart CF. Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): a 12-year experience in more than 900 patients. Laryngoscope 2015;125(8):1751-7. PMID 26200329
29: Blitzer A, Crumley RL, Dailey SH, et al. Recommendations of the Neurolaryngology Study Group on laryngeal electromyography. Otolaryngol Head Neck Surg 2009;140(6):782-93. PMID 19467391
30: Blitzer A, Sulica L. Botulinum toxin: basic science and clinical uses in otolaryngology. Laryngoscope 2001;111:218-26. PMID 11210864
31: Boutsen F, Cannito MP, Taylor M, Bender B. Botox treatment in adductor spasmodic dysphonia: a meta-analysis. J Speech Lang Hear Res 2002;45:469-81. PMID 12069000
32: Brin MF, Blitzer A, Fahn S, Gould W, Lovelace RE. Adductor laryngeal dystonia (spastic dysphonia): treatment with local injections of botulinum toxin (Botox). Mov Disord 1989;4:287-96. PMID 2811888
33: Brin MF, Blitzer A, Stewart C. Laryngeal dystonia (spasmodic dysphonia): observations of 901 patients and treatment with botulinum toxin. Adv Neurol 1998;78:237-52. PMID 9750921
34: Brin MF, Fahn S, Moskowitz C, et al. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Adv Neurol 1988;50:599-608. PMID 3400513
35: Cannito MP, Doiuchi M, Murry T, Woodson GE. Perceptual structure of adductor spasmodic dysphonia and its acoustic correlates. J Voice 2012;26(6):818.e5-13. PMID 23177751
36: Carlsoo B, Izdebski K, Dahlqvist A, Domeij S, Dedo HH. The recurrent laryngeal nerve in spastic dysphonia. A light and electron microscopic study. Acta Otolaryngol 1987;103:96-104. PMID 3564933
37: Chen R, Wassermann EM, Canos M, Hallett M. Impaired inhibition in writer's cramp during voluntary muscle activation. Neurology 1997;49:1054-9. PMID 9339689
38: Chen W, Woo P, Murry T. Vibratory onset of adductor spasmodic dysphonia and muscle tension dysphonia: a high-speed video study. J Voice 2018;pii:S0892-1997(18)30406-5. PMID 30595236
39: 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(10):2195-8. PMID 21898448
40: Cohen LG, Ludlow CL, Warden M, et al. Blink reflex excitability recovery curves in patients with spasmodic dysphonia. Neurology 1989;39:572-7. PMID 2927683
41: Creighton FX, Hapner E, Klein A, Rosen A, Jinnah HA, Johns MM. Diagnostic delays in spasmodic dysphonia: a call for clinician education. J Voice 2015;29(5):592-4. PMID 25873547
42: Daraei P, Villari CR, Rubin AD, et al. The role of laryngoscopy in the diagnosis of spasmodic dysphonia. JAMA Otolaryngol Head Neck Surg 2014;140(3):228-32. PMID 244557895
43: De Biase NG, Korn GP, Lorenzon P, et al. Dysphonia severity degree and phonation onset latency in laryngeal adductor dystonia. J Voice 2010;24(4):406-9. PMID 19766443
44: Deconde AS, Long JL, Armin BB, Berke GS. Functional reinnervation of vocal cords after selective laryngeal adductor denervation-reinnervation surgery for spasmodic dysphonia. J Voice 2012;26(5):602-3. PMID 22516313
45: Dedo HH. Recurrent laryngeal nerve section for spastic dysphonia. Ann Otol Rhinol Laryngol 1976;85:451-9. PMID 949152
46: Dedo HH, Izdebski K. Intermediate results of 306 recurrent laryngeal nerve sections for spastic dysphonia. Laryngoscope 1983a;93:9-16. PMID 6823180
47: Dedo HH, Izdebski K. Problems with surgical (RLN section) treatment of spastic dysphonia. Laryngoscope 1983b;93:268-71. PMID 6834947
48: de Gusmao CM, Fuchs T, Moses A, et al. Dystonia-causing mutations as a contribution to the etiology of spasmodic dysphonia. Otolaryngol Head Neck Surg 2016;155(4):624-8. PMID 27188707
49: Dejonckere PH, Neumann KJ, Moerman MB, Martens JP, Giordano A, Manfredi C. Tridimensional assessment of adductor spasmodic dysphonia pre- and post-treatment with botulinum toxin. Eur Arch Otorhinolaryngol 2012;269(4):1195-203. PMID 22210475
50: Devous MD Sr, Pool KD, Finitzo T, et al. Evidence for cortical dysfunction in spasmodic dysphonia: regional cerebral blood flow and quantitative electrophysiology. Brain Lang 1990;39:331-44. PMID 2224499
51: Dewan K, Berke GS. Bilateral vocal fold medialization: a treatment for abductor spasmodic dysphonia. J Voice 2019;33(1):45-8. PMID 29132808
52: Dharia I, Bielamowicz S. Unilateral versus bilateral botulinum toxin injections in adductor spasmodic dysphonia in a large cohort. Laryngoscope 2020;130(11):2659-62. PMID 31837152
53: Di Stadio A, Bernitsas E, Restivo DA, Alfonsi E, Marchese-Ragona R. Spasmodic dysphonia in multiple sclerosis treatment with botulin toxin a: a pilot study. J Voice 2018;pii:S0892-1997(18)30406-5. PMID 29650331
54: Dion GR, Nielsen SW. In-office laryngology injections. Otolaryngol Clin North Am 2019;52(3):521-36. PMID 30905566
55: Djarmati A, Schneider SA, Lohmann K, et al. Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study. Lancet Neurol 2009;8(5):447-52. PMID 19345148
56: Doody RS, Rosenfield DB. Spasmodic dysphonia associated with palatal myoclonus. Ear Nose Throat J 1990;69:829-32. PMID 2079007
57: Eadie TL, Stepp CE. Acoustic correlate of vocal effort in spasmodic dysphonia. Ann Otol Rhinol Laryngol 2013;122(3):169-76. PMID 23577569
58: Engelhoven AER, Zraick RI, Bursac Z, Tulunay-Ugur O, Hadden K. The effects of self-esteem, coping, and voice-related quality of life on communicative participation before and after BOTOX® treatment for spasmodic dysphonia. J Voice 2022;36(1):146.e5-16. PMID 32451253
59: Esposito M, Dubbioso R, Apisa P, Allocca R, Santoro L, Cesari U. Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin. Neurol Sci 2015;36(9):1679-82. PMID 25966878
60: Faham M, Ahmadi A, Silverman E, Harouni GG, Dabirmoghaddam P. Quality of life after botulinum toxin injection in patients with adductor spasmodic dysphonia; a systematic review and meta-analysis. J Voice 2019;S0892-1997(19):30184-5. PMID 31477348
61: Fairbanks G. Voice and articulation drillbook. 2nd edition. New York: Harper & Row, 1960:124-39.
62: Fan Y, Si Z, Wang L, Zhang L. DYT-TOR1A dystonia: an update on pathogenesis and treatment. Front Neurosci 2023;17:1216929. PMID 37638318
63: Finitzo T, Pool KD, Freeman FJ, et al. Spasmodic dysphonia subsequent to head trauma. Arch Otolaryngol Head Neck Surg 1987;113:1107-10. PMID 3497653
64: Finitzo-Hieber T, Freeman FJ, Gerling IJ, Dobson L, Schaefer SD. Auditory brainstem response abnormalities in adductor spasmodic dysphonia. Am J Otolaryngol 1982;3:26-30. PMID 7114388
65: Ford CN, Bless DM, Lowery JD. Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia. Otolaryngol Head Neck Surg 1990;103:752-8. PMID 2126097
66: French G, Bosch JD, Randall DR. Retrospective review of dosing trends in botulinum toxin injections for the treatment of adductor spasmodic dysphonia in a long-term cohort. J Otolaryngol Head Neck Surg 2020;49(1):4. PMID 31937363
67: Fuertinger S, Simonyan K. Connectome-wide phenotypical and genotypical associations in focal dystonia. J Neurosci 2017;37(31):7438-49. PMID 28674168
68: Gandhi S, Remacle M, Mishra P, Desai V. Vocal outcome after endoscopic thyroarytenoid myoneurectomy in patients with adductor spasmodic dysphonia. Eur Arch Otorhinolaryngol 2014;271(12):3249-54. PMID 24920326
69: Greene P, Kang UJ, Fahn S. Spread of symptoms in idiopathic torsion dystonia. Mov Disord 1995;10:143-52. PMID 7753056
70: Groen JL, Yildirim E, Ritz K, et al. THAP1 mutations are infrequent in spasmodic dysphonia. Mov Disord 2011;26(10):1952-4. PMID 21538522
71: Hall D, Stong N, Lippa N, Pitman MJ, Pullman SL, Levy OA. Spasmodic dysphonia in hereditary spastic paraplegia type 7. Mov Disord Clin Pract 2018;5(2):221-2. PMID 30746405
72: Haslinger B, Erhard P, Dresel C, Castrop F, Roettinger M, Ceballos-Baumann AO. "Silent event-related" fMRI reveals reduced sensorimotor activation in laryngeal dystonia. Neurology 2005;65:1562-9. PMID 16301482
73: Hattori H, Yoshikawa F, Sato H, Fujimine T. Spasmodic dysphonia in Meige syndrome responding to clonazepam. Intern Med 2011;50(18):2061-2. PMID 21921402
74: Heaver L. Spasmodic dysphonia: psychiatric considerations. Logos 1959;2:15-24.
75: Heman-Ackah YD, Mandel S, Manon-Espaillat R, Abaza MM, Sataloff RT. Laryngeal electromyography. Otolaryngol Clin North Am 2007;40(5):1003-23. PMID 17765693
76: Hirano S, Kojima H, Naito Y, et al. Cortical speech processing mechanisms while vocalizing visually presented languages. Neuroreport 1996;8:363-7. PMID 9051811
77: Hirano S, Kojima H, Naito Y, et al. Cortical processing mechanism for vocalization with auditory verbal feedback. Neuroreport 1997;8:2379-82. PMID 9243644
78: Hirano S, Kojima H, Naito Y, et al. Cortical dysfunction of the supplementary motor area in a spasmodic dysphonia patient. Am J Otolaryngol 2001;22(3):219-22. PMID 11351294
79: Hoffman MR, Jiang JJ, Rieves AL, McElveen KA, Ford CN. Differentiating between adductor and abductor spasmodic dysphonia using airflow interruption. Laryngoscope 2009;119(9):1851-5. PMID 19554636
80: Hogikyan ND, Wodchis WP, Spak C, Kileny PR. Longitudinal effects of botulinum toxin injections on voice-related quality of life (V-RQOL) for patients with adductory spasmodic dysphonia. J Voice 2001;15(4):576-86. PMID 11792036
81: Honey CR, Krüger MT, Almeida T, et al. Thalamic deep brain stimulation for spasmodic dysphonia: a phase i prospective randomized double-blind crossover trial. Neurosurgery 2021;89(1):45-52. PMID 33862624
82: Horisawa S, Ochiai T, Goto S, Nakajima T, Kawamata T, Taira T. Ten-year results of pallidal stimulation for cricopharyngeal dystonia with spasmodic dysphonia. Neurology 2017;88(2):211-3. PMID 27927934
83: Houtz DR, Roy N, Merrill RM, Smith ME. Differential diagnosis of muscle tension dysphonia and adductor spasmodic dysphonia using spectral moments of the long-term average spectrum. Laryngoscope 2010;120(4):749-57. PMID 20222024
84: Hu A, Hillel A, Zhao W, Meyer T. Anxiety and depression in spasmodic dysphonia patients. World J Otorhinolaryngol Head Neck Surg 2018;4(2):110-6. PMID 30101219
85: Hu A, Isetti D, Hillel AD, Waugh P, Comstock B, Meyer TK. Disease-specific self-efficacy in spasmodic dysphonia patients. Otolaryngol Head Neck Surg 2013;148(3):450-5. PMID 23300221
86: Hussain A, Shakeel M. Selective lateral laser thyroarytenoid myotomy for adductor spasmodic dysphonia. J Laryngol Otol 2010;124(8):886-91. PMID 20426891
87: Hyodo M, Hisa Y, Nishizawa N, et al. The prevalence and clinical features of spasmodic dysphonia: a review of epidemiological surveys conducted in Japan. Auris Nasus Larynx 2021;48(2):179-84. PMID 32861505
88: Isaias IU, Alterman RL, Tagliati M. Deep brain stimulation for primary generalized dystonia. Arch Neurol 2009;66(4):465-70. PMID 196364931
89: Isetti D, Meyer T. Workplace productivity and voice disorders: a cognitive interviewing study on presenteeism in individuals with spasmodic dysphonia. J Voice 2014;28(6):700-10. PMID 24972537
90: Isshiki N, Haji T, Yamamoto Y, Mahieu HF. Thyroplasty for adductor spasmodic dysphonia: further experiences. Laryngoscope 2001;111:615-21. PMID 11359129
91: Isshiki N, Sanuki T. Surgical tips for type II thyroplasty for adductor spasmodic dysphonia: modified technique after reviewing unsatisfactory cases. Acta Otolaryngol 2010;130(2):275-80. PMID 19513892
92: Isshiki N, Tsuji DH, Yamamoto Y, Iizuka Y. Midline lateralization thyroplasty for adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol 2000;109:187-93. PMID 10685572
93: Izdebski K, Dedo HH, Boles L. Spastic dysphonia: a patient profile of 200 cases. Am J Otolaryngol 1984;5:7-14. PMID 6534197
94: Izdebski K, Dedo HH, Shipp T, Flower RM. Postoperative and follow-up studies of spastic dysphonia patients treated by recurrent laryngeal nerve section. Otolaryngol Head Neck Surg 1981;89:96-101. PMID 6784090
95: Jankovic J, Ford J. Blepharospasm and orofacial-cervical dystonia: clinical and pharmacological findings in 100 patients. Ann Neurol 1983;13:402-11. PMID 6838174
96: Jankovic J, Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry 1990;53:633-9. PMID 2213039
97: Jurgens U. A study of the central control of vocalization using the squirrel monkey. Med Eng Phys 2002;24(7-8):473-7. PMID 12237042
98: Kaptein AA, Hughes BM, Scharloo M, Hondebrink N, Langeveld TP. Psychological aspects of adductor spasmodic dysphonia: a prospective population controlled questionnaire study. Clin Otolaryngol 2010;35(1):31-8. PMID 20447160
99: Kaye R, Blitzer A. Chemodenervation of the larynx. Toxins (Basel) 2017;9(11). PMID 29099066
100: Kendall KA, Leonard RJ. Interarytenoid muscle Botox injection for treatment of adductor spasmodic dysphonia with vocal tremor. J Voice 2011;25(1):114-9. PMID 20137891
101: Khosravani S, Mahnan A, Yeh IL, et al. Atypical somatosensory-motor cortical response during vowel vocalization in spasmodic dysphonia. Clin Neurophysiol 2019a;130(6):1033-40. PMID 30930193
102: Khosravani S, Mahnan A, Yeh IL, et al. Laryngeal vibration as a non-invasive neuromodulation therapy for spasmodic dysphonia. Sci Rep 2019b;9(1):17955. PMID 31784618
103: Kirke DN, Frucht SJ, Simonyan K. Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol 2015;262(6):1548-56. PMID 25929664
104: Kiml J. Experimental research on spastic dysphonia. Folia Phoniatr (Basel) 1965;17:241-300. PMID 14334148
105: Klein AM, Stong BC, Wise J, DelGaudio JM, Hapner ER, Johns MM 3rd. Vocal outcome measures after bilateral posterior cricoarytenoid muscle botulinum toxin injections for abductor spasmodic dysphonia. Otolaryngol Head Neck Surg 2008;139(3):421-3. PMID 18722224
106: Klotz DA, Maronian NC, Waugh PF, Shahinfar A, Robinson L, Hillel AD. Findings of multiple muscle involvement in a study of 214 patients with laryngeal dystonia using fine-wire electromyography. Ann Otol Rhinol Laryngol 2004;113:602-12. PMID 15330138
107: Knight MA, Gardner RJ, Bahlo M, et al. Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain 2004;127:1172-81. PMID 14998916
108: Koller WC, Busenbark K, Miner K. The relationship of essential tremor to other movement disorders: report on 678 patients. Essential Tremor Study Group. Ann Neurol 1994;35:717-23. PMID 8210229
109: Koriwchak MJ, Netterville JL, Snowden T, Courey M, Ossoff RH. Alternating unilateral botulinum toxin type A (BOTOX) injections for spasmodic dysphonia. Laryngoscope 1996;106:1476-81. PMID 8948606
110: Kosaki H, Iwamura S, Yamazaki I. Histologic study of the recurrent laryngeal nerve in spasmodic dysphonia. Otolaryngol Head Neck Surg 1999;120:129-33. PMID 9914563
111: Kostic VS, Agosta F, Sarro L, et al. Brain structural changes in spasmodic dysphonia: A multimodal magnetic resonance imaging study. Parkinsonism Relat Disord 2016;25:78-84. PMID 26876036
112: Kruger MT, Hu A, Honey CR. Deep brain stimulation for spasmodic dysphonia: a blinded comparison of unilateral and bilateral stimulation in two patients. Stereotact Funct Neurosurg 2020;98(3):200-5. PMID 32316007
113: Kuypers HG. Corticobular connexions to the pons and lower brain-stem in man: an anatomical study. Brain 1958; 81(3):364-88. PMID 13596471
114: Lagos-Villaseca A, Bhatt NK, Abdolhosseini P, et al. Assessment of patients receiving short-interval botulinum toxin chemodenervation treatment for laryngeal dystonia and essential tremor of the vocal tract. JAMA Otolaryngol Head Neck Surg 2023;149(7):615-20. PMID 37227721
115: Lang AE, Marsden CD. Spasmodic dysphonia in Gilles de la Tourette's disease. Arch Neurol 1983;40:51-2. PMID 6571713
116: Lee L, Daughton S, Scheer S, et al. Use of acupuncture for the treatment of adductor spasmodic dysphonia: a preliminary investigation. J Voice 2003;17:411-24. PMID 14513964
117: Lee SJ, Kang MS, Choi HS, Lim JY. Alternating unilateral versus bilateral injections of botulinum toxin for the treatment of adductor spasmodic dysphonia. Otolaryngol Head Neck Surg 2021;164(4):815-20. PMID 32957836
118: Lerner MZ, Lerner BA, Patel AA, Blitzer A. Gender differences in onabotulinum toxin A dosing for adductor spasmodic dysphonia. Laryngoscope 2017;127(5):1131-4. PMID 27633917
119: Leonard R, Kendall K. Differentiation of spasmodic and psychogenic dysphonias with phonoscopic evaluation. Laryngoscope 1999;109:295-300. PMID 10890782
120: Lohmann K, Wilcox RA, Winkler S, et al. Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene. Ann Neurol 2013;73(4):537-45. PMID 23595291
121: Lou JS, Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology 1991;41:234-8. PMID 1992367
122: Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord 2010;25(5):534-41. PMID 20175185
123: Ludlow CL. Treatment for spasmodic dysphonia: limitations of current approaches. Curr Opin Otolaryngol Head Neck Surg 2009;17(3):160-5. PMID 19337127
124: Ludlow CL, Domangue R, Sharma D, et al. Consensus-based attributes for identifying patients with spasmodic dysphonia and other voice disorders. JAMA Otolaryngol Head Neck Surg 2018;144(8):657-65. PMID 29931028
125: Ludlow CL, Naunton RF, Sedory SE, Schulz GM, Hallett M. Effects of botulinum toxin injections on speech in adductor spasmodic dysphonia. Neurology 1988;38:1220-5. PMID 3399071
126: Lundy DS, Roy S, Xue JW, Casiano RR, Jassir D. Spastic/spasmodic vs. tremulous vocal quality: motor speech profile analysis. J Voice 2004;18:146-52. PMID 15070235
127: Lyons MK, Boucher O, Evidente VGH. Spasmodic dysphonia and thalamic deep brain stimulation: long-term observations, possible neurophysiologic mechanism and comparison of unilateral versus bilateral stimulation. J Neurol Neurophysiol 2011;1:106.
128: Mainka T, Erro R, Rothwell J, Kühn AA, Bhatia KP, Ganos C. Remission in dystonia - systematic review of the literature and meta-analysis. Parkinsonism Relat Disord 2019;66:9-15. PMID 30898428
129: Maloney AP, Morrison MD. A comparison of the efficacy of unilateral versus bilateral botulinum toxin injections in the treatment of adductor spasmodic dysphonia. J Otolaryngol 1994;23:160-4. PMID 8064952
130: Marchese MR, D’Alatri L, Bentivoglio AR, Paludetti G. OnabotulinumtoxinA for adductor spasmodic dysphonia (ADSD): functional results and the role of dosage. Toxicon 2018;155:38-42. PMID 30315835
131: Marques Torbes TM, Zencke da Silva K, Dalbosco Gadenz C, Cassol M. Adherence of patients with dysphonia to voice therapy: systematic review. J Voice 2019;pii:S0892-1997(19)30004-9. PMID 31084942
132: Marras C, Lang A, van De Warrenburg BP, et al. Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and Movement Disorder Society Task Force. Mov Disord 2016;31(4):436-57. PMID 27079681
133: Marsden CD, Sheehy MP. Spastic dysphonia, Meige disease, and torsion dystonia. Neurology 1982;32:1202-3. PMID 6889708
134: Martinelli P, Montanari M, Ippoliti M, Mochi M, Sangiorgi S, Capocasa M. Familial spasmodic dysphonia with low arylsulphatase A (ASA) level. Acta Neurol Scand 1995;91:196-9. PMID 7793235
135: McGarey PO Jr, Simpson CB, Daniero JJ. Practice patterns and barriers in botulinum toxin injection for the treatment of voice disorders. J Voice 2022;36(1):113-8. PMID 32467003
136: Meleca RJ, Hogikyan ND, Bastian RW. A comparison of methods of botulinum toxin injection for abductory spasmodic dysphonia. Otolaryngol Head Neck Surg 1997;117:487-92. PMID 9374172
137: Mendelsohn AH, Berke GS. Surgery or botulinum toxin for adductor spasmodic dysphonia: a comparative study. Ann Otol Rhinol Laryngol 2012;121(4):231-8. PMID 22606926
138: Merati AL, Heman-Ackah YD, Abaza M, Altman KW, Sulica L, Belamowicz S. Common movement disorders affecting the larynx: a report from the neurolaryngology committee of the AAO-HNS. Otolaryngol Head Neck Surg 2005;133:654-65. PMID 16274788
139: Meyer E, Carss KJ, Rankin J, et al. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nat Genet 2017;49(2):223-37. PMID 27992417
140: Meyer TK, Hu A, Hillel AD. Voice disorders in the workplace: productivity in spasmodic dysphonia and the impact of botulinum toxin. Laryngoscope 2013;123(Suppl 6):S1-14. PMID 23818277
141: Meyer TK, Spiekerman C, Kaye R, et al. Association of laryngeal botulinum neurotoxin injection with work productivity for patients with spasmodic dysphonia. JAMA Otolaryngol Head Neck Surg 2021;147(9):804-10. PMID 34351425
142: Middleton ML, Wilson KM, Keith RW. Central auditory evaluation of patients with spasmodic dysphonia. Ear Nose Throat J 1997;76:710-5. PMID 9345814
143: 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;113:603-5. PMID 3566940
144: Mor N, Tang C, Blitzer A. Botulinum toxin in secondarily nonresponsive patients with spasmodic dysphonia. Otolaryngol Head Neck Surg 2016;155(3):458-61. PMID 27143711
145: Morzaria S, Damrose EJ. The point-touch technique for botulinum toxin injection in adductor spasmodic dysphonia: quality of life assessment. J Laryngol Otol 2011;125(7):714-8. PMID 21524329
146: Murry T, Woodson GE. Combined-modality treatment of adductor spasmodic dysphonia with botulinum toxin and voice therapy. J Voice 1995;9:460-5. PMID 8574315
147: Namin AW, Christopher KM, Eisenbeis JF. Botulinum toxin dosing trends in spasmodic dysphonia over a 20-year period. J Voice 2017;31(1):107-10. PMID 27005439
148: Nomoto M, Tokashiki R, Hiramatsu H, et al. The comparison of thyroarytenoid muscle myectomy and type II thyroplasty for spasmodic dysphonia. J Voice 2015;29(4):501-6. PMID 25737474
149: Novakovic D, Waters HH, D'Elia JB, Blitzer A. Botulinum toxin treatment of adductor spasmodic dysphonia: longitudinal functional outcomes. Laryngoscope 2011;121(3):606-12. PMID 21298641
150: Oh J, Park KD, Cho HJ, Choi KG, Jung SM. Spasmodic dysphonia induced by valproic acid. Epilepsia 2004;45:880-1. PMID 15230719
151: Panizza M, Lelli S, Nilsson J, Hallett M. H-reflex recovery curve and reciprocal inhibition of H-reflex in different kinds of dystonia. Neurology 1990;40:824-8. PMID 2330111
152: Patel AB, Bansberg SF, Adler CH, Lott DG, Crujido L. The Mayo Clinic Arizona spasmodic dysphonia experience: a demographic analysis of 718 patients. Ann Otol Rhinol Laryngol 2015;124(11):859-63. PMID 26024910
153: Patel PN, Kabagambe EK, Starkweather JC, et al. Outcomes of onabotulinum toxin a treatment for adductor spasmodic dysphonia and laryngeal tremor. JAMA Otolaryngol Head Neck Surg 2018;144(4):293-9. PMID 29423509
154: Patel RR, Liu L, Galatsanos N, Bless DM. Differential vibratory characteristics of adductor spasmodic dysphonia and muscle tension dysphonia on high-speed digital imaging. Ann Otol Rhinol Laryngol 2011;120(1):21-32. PMID 21370677
155: Payne S, Tisch S, Cole I, Brake H, Rough J, Darveniza P. The clinical spectrum of laryngeal dystonia includes dystonic cough: observations of a large series. Mov Disord 2014;29(6):729-35. PMID 24753288
156: Pedrero-Escalas MF, García-López I, Santiago-Pérez S, Vivancos F, Gavilán J. Clinical experience with patients with spasmodic dysphonia and primary Meige syndrome. Acta Otorrinolaringol Esp 2019;70(1):1-5. PMID 29716720
157: Peng Y, Crumley R, Ringman JM. Spasmodic dysphonia in a patient with the A to G transition at nucleotide 8344 in mitochondrial DNA. Mov Disord 2003;18:716-8. PMID 12784281
158: Pitman MJ. Treatment of spasmodic dysphonia with a neuromodulating electrical implant. Laryngoscope 2014;124(11):2537-43. PMID 24913352
159: Poologaindran A, Ivanishvili Z, Morrison MD, et al. The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits. J Neurosurg 2018;128:575-82. PMID 28304188
160: Putzel GG, Fuchs T, Battistella G, et al. GNAL mutation in isolated laryngeal dystonia. Mov Disord 2016;31(5):750-5. PMID 27093447
161: Rhew K, Fiedler DA, Ludlow CL. Technique for injection of botulinum toxin through the flexible nasolaryngoscope. Otolaryngol Head Neck Surg 1994;111:787-94. PMID 7991260
162: Rice JE. The emperor with the shaking head: Claudius' movement disorder. J R Soc Med 2000;93:198-201. PMID 10844890
163: Robe E, Brumlik J, Moore P. A study of spastic dysphonia. Neurologic and electroencephalographic abnormalities. Laryngoscope 1960;70:219-45. PMID 14437765
164: Roland PE, Larsen B, Lassen NA, Skinhoj E. Supplementary motor area and other cortical areas in organization of voluntary movements in man. J Neurophysiol 1980;43:118-36. PMID 7351547
165: Rontal M, Rontal E, Rolnick M, Merson R, Silverman B, Truong DD. A method for the treatment of abductor spasmodic dysphonia with botulinum toxin injections: a preliminary report. Laryngoscope 1991;101:911-4. PMID 1865744
166: Rosow DE, Parikh P, Vivero RJ, Casiano RR, Lundy DS. Considerations for initial dosing of botulinum toxin in treatment of adductor spasmodic dysphonia. Otolaryngol Head Neck Surg 2013;148(6):1003-6. PMID 23535709
167: Rosow DE, Pechman A, Saint-Victor S, Lo K, Lundy DS, Casiano RR. Factors influencing botulinum toxin dose instability in spasmodic dysphonia patients. J Voice 2015;29(3):352-5. PMID 25242042
168: Roth CR, Glaze LE, Goding GS Jr, David WS. Spasmodic dysphonia symptoms as initial presentation of amyotrophic lateral sclerosis. J Voice 1996;10:362-7. PMID 8943140
169: Roy N. Differential diagnosis of muscle tension dysphonia and spasmodic dysphonia. Curr Opin Otolaryngol Head Neck Surg 2010;18(3):165-70. PMID 20389245
170: Rumbach AF, Blitzer A, Frucht SJ, Simonyan K. An open-label study of sodium oxybate in Spasmodic dysphonia. Laryngoscope 2017;127(6):1402-7. PMID 27808415
171: Samargia S, Schmidt R, Kimberley TJ. Shortened cortical silent period in adductor spasmodic dysphonia: evidence for widespread cortical excitability. Neurosci Lett 2014;560:12-5. PMID 24333913
172: Samargia S, Schmidt R, Kimberley TJ. Cortical silent period reveals differences between adductor spasmodic dysphonia and muscle tension dysphonia. Neurorehabil Neural Repair 2016;30(3):221-32. PMID 26089309
173: Sanuki T, Isshiki N. Outcomes of type II thyroplasty for adductor spasmodic dysphonia: analysis of revision and unsatisfactory cases. Acta Otolaryngol 2009;129(11):1287-93. PMID 19863326
174: Sanuki T, Yumoto E. Long-term evaluation of type 2 thyroplasty with titanium bridges for adductor spasmodic dysphonia. Otolaryngol Head Neck Surg 2017;157(1):80-4. PMID 28463639
175: Sanuki T, Yumoto E, Minoda R, Kodama N. Effects of type II thyroplasty on adductor spasmodic dysphonia. Otolaryngol Head Neck Surg 2010;142(4):540-6. PMID 20304275
176: Sapir S. Psychogenic spasmodic dysphonia: a case study with expert opinions. J Voice 1995;9:270-81. PMID 8541970
177: Schaefer SD, Finitzo-Hieber T, Gerling IJ, Freeman FJ. Brainstem conduction abnormalities in spasmodic dysphonia. Ann Otol Rhinol Laryngol 1983;92:59-64. PMID 6824281
178: Schaefer SD, Freeman FJ. Spasmodic dysphonia. Otolaryngol Clin North Am 1987;20:161-78. PMID 3550593
179: Schlotthauer G, Torres ME, Jackson-Menaldi MC. A pattern recognition approach to spasmodic dysphonia and muscle tension dysphonia automatic classification. J Voice 2010;24(3):346-53. PMID 20346617
180: Schneider-Stickler B, Ho GY, Moriggl B. Ultrasound-guided injection into the lateral crico-arytenoid muscle: a pilot study. Eur Arch Otorhinolaryngol 2023;280(6):2877-83. PMID 36773100
181: Schnitzler J. Klinischer atlas der laryngologie nebst anleitung zur diagnose und therapie der krankheiten des kehlkopfes und der luftrohre. Wein/Leipzig: Braunmuller, 1895.
182: Schweinfurth JM, Billante M, Courey MS. Risk factors and demographics in patients with spasmodic dysphonia. Laryngoscope 2002;112:220-3. PMID 11889373
183: Seiser A, Schwarz S, Aichinger-Steiner MM, Funk G, Schnider P, Brainin M. Parkinsonism and dystonia in central pontine and extrapontine myelinolysis. J Neurol Neurosurg Psychiatry 1998;65:119-21. PMID 9667573
184: Sharbrough FW, Stockard JJ, Aronson AE. Brainstem auditory-evoked responses in spastic dysphonia. Trans Am Neurol Assoc 1978;103:198-201. PMID 757057
185: Shoffel-Havakuk H, Rosow DE, Lava CX, Hapner ER, Johns MM 3rd. Common practices in botulinum toxin injection for spasmodic dysphonia treatment: a national survey. Laryngoscope 2019;129(7):1650-6. PMID 30582627
186: Siemons-Luhring DI, Moerman M, Martens JP, Deuster D, Müller F, Dejonckere P. Spasmodic dysphonia, perceptual and acoustic analysis: presenting new diagnostic tools. Eur Arch Otorhinolaryngol 2009;266(12):1915-22. PMID 19866529
187: Silverman EP, Garvan C, Shrivastav R, Sapienza CM. Combined modality treatment of adductor spasmodic dysphonia. J Voice 2012;26(1):77-86. PMID 21292439
188: Simonyan K, Barkmeier-Kraemer J, Blitzer A, et al. Laryngeal dystonia: multidisciplinary update on terminology, pathophysiology, and research priorities. Neurology 2021;96(21):989-1001. PMID 33858994
189: Simonyan K, Berman BD, Herscovitch P, Hallett M. Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia. J Neurosci 2013;33(37):14705-14. PMID 24027271
190: Simonyan K, Frucht SJ, Blitzer A, Sichani AH, Rumbach AF. A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity. Sci Rep 2018;8(1):16111. PMID 30382161
191: Simonyan K, Ludlow CL, Vortmeyer AO. Brainstem pathology in spasmodic dysphonia. Laryngoscope 2010;120(1):121-4. PMID 19795469
192: Simonyan K, Ludlow CL. Abnormal structure-function relationship in spasmodic dysphonia. Cereb Cortex 2012;22(2):417-25. PMID 21666131
193: Simpson CB, Lee CT, Hatcher JL, Michalek J. Botulinum toxin treatment of false vocal folds in adductor spasmodic dysphonia: functional outcomes. Laryngoscope 2016;126(1):118-21. PMID 26467807
194: Soland VL, Bhatia KP, Marsden CD. Sex prevalence of focal dystonias. J Neurol Neurosurg Psychiatry 1996;60:204-5. PMID 8708656
195: Stamelou M, Charlesworth G, Cordivari C, et al. The phenotypic spectrum of DYT24 due to ANO3 mutations. Mov Disord 2014;29(7):928-34. PMID 24442708
196: Stone A, Powell ME, Hamers K, et al. Optimizing Botox regimens in patients with adductor spasmodic dysphonia and essential tremor of voice: a 31-year experience. Laryngoscope Investig Otolaryngol 2022;7(5):1499-505. PMID 36262464
197: Sulica L, Louis ED. Clinical characteristics of essential voice tremor: a study of 34 cases. Laryngoscope 2010;120(3):516-28. PMID 20066728
198: Suppa A, Asci F, Saggio G, et al. Voice analysis in adductor spasmodic dysphonia: objective diagnosis and response to botulinum toxin. Parkinsonism Relat Disord 2020;73:23-30. PMID 32222482
199: Suppa A, Marsili L, Giovannelli F, et al. Abnormal motor cortex excitability during linguistic tasks in adductor-type spasmodic dysphonia. Eur J Neurosci 2015;42(4):2051-60. PMID 26061279
200: Tanner K, Roy N, Merrill RM, Sauder C, Houtz DR, Smith ME. Spasmodic dysphonia: onset, course, socioemotional effects, and treatment response. Ann Otol Rhinol Laryngol 2011a;120(7):465-73. PMID 21859056
201: Tanner K, Roy N, Merrill RM, et al. Risk and protective factors for spasmodic dysphonia: a case-control investigation. J Voice 2011b;25(1):e35-46. PMID 20171836
202: Tanner K, Roy N, Merrill RM, Sauder C, Houtz DR, Smith ME. Case-control study of risk factors for spasmodic dysphonia: a comparison with other voice disorders. Laryngoscope 2012;122(5):1082-92. PMID 22253036
203: Tierney WS, Bryson PC, Nelson R, Kaplan SE, Benninger MS, Milstein CF. Respiratory laryngeal dystonia: characterization and diagnosis of a rare neurogenic disorder. Laryngoscope 2020;130(12):2843-6. PMID 32073668
204: Tisch SH, Brake HM, Law M, Cole IE, Darveniza P. Spasmodic dysphonia: clinical features and effects of botulinum toxin therapy in 169 patients--an Australian experience. J Clin Neurosci 2003;10:434-8. PMID 12852881
205: Traube L. Spastische form der nervoesen heiserkeit. Gesammelte beitraege zur pathologies und physiologie. Vol. 2. Berlin: Hirschwald, 1871.
206: Truong DD, Bhidayasiri R. Botulinum toxin therapy of laryngeal muscle hyperactivity syndromes: comparing different botulinum toxin preparations. Eur J Neurol 2006;13(Suppl 1):36-41. PMID 16417596
207: Troung DD, Rontal M, Rolnick M, Aronson AE, Mistura K. Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia. Laryngoscope 1991;101:630-4. PMID 2041443
208: Tsuji DH, Hachiya A, Dajer ME, Ishikawa CC, Takahashi MT, Montagnoli AN. Improvement of vocal pathologies diagnosis using high-speed videolaryngoscopy. Int Arch Otorhinolaryngol 2014;18(3):294-302. PMID 25992109
209: Tsuji DH, Takahashi MT, Imamura R, Hachiya A, Sennes LU. Endoscopic laser thyroarytenoid myoneurectomy in patients with adductor spasmodic dysphonia: a Pilot study on long-term outcome on voice quality. J Voice 2012;26(5):666.e7-12. PMID 21940146
210: Upile T, Elmiyeh B, Jerjes W, et al. Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor spasmodic dysphonia: a prospective study. Head Face Med 2009;5:20. PMID 19852852
211: Van Pelt F, Ludlow CL, Smith PJ. Comparison of muscle activation patterns in adductor and abductor spasmodic dysphonia. Ann Otol Rhinol Laryngol 1994;103(3):192-200. PMID 8122835
212: Venkatesan NN, Johns MM, Hapner ER, DelGaudio JM. Abductor paralysis after Botox injection for adductor spasmodic dysphonia. Laryngoscope 2010;120(6):1177-80. PMID 20513036
213: Walter U, Blitzer A, Benecke R, Grossmann A, Dressler D. Sonographic detection of basal ganglia abnormalities in spasmodic dysphonia. Eur J Neurol 2014;21(2):349-52. PMID 23581276
214: Warren J, Thompson P. Drug-induced supraglottic dystonia and spasmodic dysphonia. Mov Disord 1998;13:978-9. PMID 9827629
215: Watts CC, Whurr R, Nye C. Botulinum toxin injections for the treatment of spasmodic dysphonia. Cochrane Database Syst Rev 2004:CD004327. PMID 15266530
216: White LJ, Hapner ER, Klein AM, et al. Coprevalence of anxiety and depression with spasmodic dysphonia: a case-control study. J Voice 2012;26(5):667.e1-6. PMID 22209056
217: Wingate JM, Ruddy BH, Lundy DS, et al. Voice handicap index results for older patients with adductor spasmodic dysphonia. J Voice 2005;19(1):124-31. PMID 15766857
218: Xiromerisiou G, Houlden H, Scarmeas N, et al. THAP1 mutations and dystonia phenotypes: genotype phenotype correlations. Mov Disord 2012;27(10):1290-4. PMID 22903657
219: Yang Q, Xu W, Li Y, Cheng L. Value of laryngeal electromyography in spasmodic dysphonia diagnosis and therapy. Ann Otol Rhinol Laryngol 2015;124(7):579-83. PMID 25673120
220: Young DL, Halstead LA. Relationship of laryngeal botulinum toxin dosage to patient age, vitality, and socioeconomic issues. J Voice 2014;28(5):614-7. PMID 24954039
221: Zhao K, Guillaud M, Hu A. Factors associated with failure of botulinum toxin injection in adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol 2020;129(10):996-1002. PMID 32468829

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Tanya K Meyer MD

Dr. Meyer of the University Washington has no relevant financial relationships to disclose.
See Profile
Rachel Jonas MD

Dr. Jonas of the University of Washington Medical Center has no relevant financial relationships to disclose.
See Profile

Editor

Robert Fekete MD

Dr. Fekete of New York Medical College received consultation fees from Acadia Pharmaceutical, Acorda, Adamas/Supernus Pharmaceuticals, Amneal/Impax, Kyowa Kirin, Lundbeck Inc., Neurocrine Inc., and Teva Pharmaceutical, Inc.
See Profile

Former Authors

Christopher F O'Brien MD
Andrew Blitzer MD DDS
Jean Verheyden MD
Daniel D Truong MD
Roongroj Bhidayasiri MD MRCP
Ainhi Ha PhD BSc FRACP MBBS
Steven Bellows MD
Craig H Zalvan MD

Patient Profile

Age range of presentation: 40 to 65+ years
Sex preponderance: female>male, >2:1
Heredity: Heredity may be a factor
Population groups selectively affected: None selectively affected
Occupation groups selectively affected: None selectively affected

ICD & OMIM codes

ICD-10: Other diseases of larynx: J38.7

Dysphonia: R49.0

Laryngeal spasm: J38.5

Dystonia: G24.9
ICD-11: Other specified primary dystonia: 8A02.0Y

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Laryngeal dystonia (spasmodic dysphonia)

Associated Disorders

Tardive syndrome
Mitochondrial disease
Valproic acid administration
Central pontine myelinosis
Amyotrophic lateral sclerosis
- Psychogenic dysphonia
- Late-onset laryngeal dystonia with low arylsulphatase A
- Essential tremor
- Palatal myoclonus
- Hereditary spastic paraplegia type 7
- Multiple sclerosis
- Trauma

Differential Diagnosis

Essential voice tremor
Muscle tension dysphonia
Vocal tremor
Meige syndrome or part of generalized dystonia
Wilson disease
- Huntington chorea
- Parkinson disease
- Essential tremors
- Gilles de la Tourette syndrome
- Spinocerebellar ataxia type 20
- Mitochondrial disease
- Amyotrophic lateral sclerosis
- Palatal myoclonus
- Drug-induced dysphonia
- Tardive dyskinesia
- Recurrent nerve paresis
- Stroke
- Vocal cord nodules or polyps
- Neoplasm
- Inflammation of the vocal cord (eg, gastroesophageal reflux, rheumatoid arthritis)
- Infection/laryngitis
- Trauma
- Psychogenic dysphonia
- Asthma

Also Relevant

Blepharospasm
Botulinum toxin treatment of neurologic disorders
Childhood movement disorders
Primary dystonia
Psychogenic movement disorders
- Rating scales of movement disorders

Laryngeal dystonia (spasmodic dysphonia)

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. Factors Influencing Subjective Severity of Laryngeal Dystonia

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Table 2. Differential Diagnosis for Laryngeal Dystonia

Associated or underlying disorders

Diagnostic workup

Table 3. Voice History and Symptoms of Laryngeal Dystonia

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Hemifacial spasm

Wilson disease

Neuroacanthocytosis

Restless legs syndrome

Dementia in Parkinson disease

ALS-like disorders of the Western Pacific

Sleep-related leg cramps

Sleep and cerebral degenerative disorders

This is an article preview.
Start a Free Account
to access the full version.