Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a type of focal dystonia affecting the intrinsic laryngeal muscles during speech [1]. LD is a rare, idiopathic disease with unknown exact incidence or prevalence. It has been reported that the prevalence of LD is up to 35 per 100,000 people in the general population [1]; however, in some countries, the prevalence was reported to be lower (i.e., Iceland and Japan). Similar to other forms of isolated or focal dystonia (e.g., hand dystonia, cervical dystonia, blepharospasms, and oromandibular dystonia), the pathophysiology of LD is regarded as multifactorial. Recent reports define dystonia as a neural network disorder with alterations in brain structure, function, and neurotransmission ^[2][3][4][2,3,4]. The basal ganglia with thalamus and cerebellum are regarded as the core of structural and functional disorganization, while reduced availability of striatal dopamine D₂/D₃ receptors decreases the inhibitory activity within the indirect basal ganglia pathway, leading to hyperexcitability of the thalamus ^[2][4][2,4].

The two most common types of LD are adductor LD and the relatively rare abductor LD. The condition is characterized by task specificity and selective speech impairment with preserved whispering, breathing, laughing, crying, and yawning [1]. Adductor LD is characterized by a strained-strangled voice quality with intermittent voice breaks during vowel production (phonation task), while abductor LD is characterized by intermittent breathy voice breaks occurring predominantly on voiceless consonants [1]. However, some patients may exhibit a combination of both adductor and abductor spasms, leading to a mix of strained and breathy voice qualities. Caucasians and women are significantly more affected, while the average age of symptom onset is 40 years [1]. Symptoms can appear gradually, but a sudden onset is recorded in 45% of cases [5]. In 82.4% of cases, the disorder remains focal, but patients may later develop other dystonia types, such as cranial or generalized dystonia [5]. Approximately 25.3% of LD patients have a positive family history of dystonia, and 11.8% of them have some other movement disorder, indicating a genetic predisposition for LD [1]. Specific extrinsic factors show a correlation with the development of LD. Chronic stimuli of the upper respiratory system in the form of frequent infections, gastroesophageal reflux disease, and inhaled irritants increase the risk of developing LD. Psychiatric conditions such as depression, anxiety, and stress are a risk factor [6]. Approximately 43–46% of LD patients reported emotional trauma before symptom onset. Emotional trauma immediately before symptoms have been found in 43–46% of LD subjects [6]. People who frequently use their voice, e.g., singers and professors, constitute a risk population [1]. The LD diagnosis is made by a multidisciplinary team examination that includes a laryngologist, a speech and language therapist, and a neurologist. Due to the lack of strict diagnostic guidelines and still unknown pathophysiological mechanisms involved in LD, the diagnosis is delayed an average of 5.5 years from the onset of symptoms, and the multidisciplinary team experts agree with diagnosis only in 34% of cases [1]. In the differential diagnosis, one must include other disorders that cause laryngeal spasms, such as essential vocal tremors and muscle tension dysphonia ^[7][8][7,8]. Both voice tremor and muscle tension dysphonia are present in approximately one-third of LD individuals [1]. The main differentiating factor of LD from other diseases is the symptom occurrence during voice production/phonation and speech ^[1][5][1,5]. The standard treatments for LD have typically included botulinum toxin injections, speech/voice therapy, and, in some cases, surgical interventions (ENT and neurosurgical procedures). Botulinum toxin injection into specific laryngeal muscles is the standard primary therapeutic option leading to functional voice improvement and improved voice-related quality of life of LD subjects ^[9][10][9,10]. Botulinum toxin blocks the release of acetylcholine from nerve terminals. Three compounds of botulinum toxin type A (Botox^®, Dysport^®, and Xeomin^®) and type B (NeuroBloc^®) are commercially available for LD treatment [9]. The recommendation for botulinum toxin injection in adductor LD is the thyroarytenoid (TA) muscle (bilateral or unilateral) with Botox^®/1–5 MU, Xeomin^®/10–40 MU, and Dysport^® per side, while for treatment of abductor LD the posterior cricoarytenoid (CT) muscle (bilateral or unilateral) is recommended by applying Botox^®/2.5–5 MU, Xeomin^®/20–40 MU, or Dysport^® per side [9]. Thereby, botulinum toxin causes flaccid paralysis of the muscle about 48 h after injection; however, its effect is transient [9]. A significant proportion of patients require repeat procedures, and some patients might experience transient dysphagia after administration of botulinum toxin injection.

Besides standard treatment management of LD, some individuals with LD explore alternative therapies such as acupuncture, yoga, or relaxation techniques to manage stress, which can exacerbate symptoms. While these approaches may provide some relief, their efficacy is not well-established through scientific research. New theoretical views and treatment approaches like transcranial magnetic stimulation (TMS) [11] and laryngeal vibration over the laryngeal muscles are present in recent attempts in the treatment of LD [12].

Contrary to the non-invasive nature of rTMS, invasive deep brain stimulation (DBS) of globus pallidus internus (GPi) or subthalamic nucleus (STN) has been approved by the FDA for the treatment of drug-refractory generalized, segmental, cervical dystonia, hemi dystonia, and essential tremor [1]. It has to be pointed out that no current DBS findings are reported for isolated focal LD treatment, except for patients with essential tremor and coincident LD in whom DBS of the thalamus’s ventral intermediate (VIM) nucleus was targeted ^[13][14][15][29,30,31].

In a 79-year-old woman with the essential tremor of the dominant right upper limb and LD, unilateral left thalamic VIM stimulation (DBS on) significantly improved LD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and voice-related quality of life (VRQOL) (p < 0.01) ^[15][31]. The patient’s voice was evaluated with the stimulation turned off for 14 days and on for 14 days. The unilateral left electrode’s stimulation parameters were Case +, contacts, 0 off, 1-, 2 off, 3 off, pulse width 90 ms, frequency 185 Hz, and voltage 3.0 V.

Krüger et al. ^[14][30] presented an 85-year-old woman, right-handed, with essential tremor of the limbs and LD, and a 73-year-old man with mixed left-handedness with essential limb tremor and LD. The female patient underwent bilateral VIM nucleus DBS, with DBS parameters: left VIM case +, contacts 0 off, 1(−), 2, and 3 off, frequency 185 Hz, pulse width 90 µs, and amplitude 2.8 V; right VIM case off, 8 and 9 off, 10(+) and 11(−)frequency 185 Hz, pulse width 90 µs, and amplitude 2.5 V. The male patient underwent bilateral VIM nucleus DBS with the following parameters: left VIM case (+), contacts 0 (−), 1, 2, and 3 off, frequency 185 Hz, pulse width 60 µs, voltage 1.6 V; right Vim case +, contacts 8 off, 9 -, 10 and 11 off, frequency 185 Hz, pulse width 60 µs, and voltage 2.5 V. In the female patient, the OMNI—Vocal Effort Scale (OMNI-VES) ^[16][32] showed the most improvement (80%) with both DBS sides on. With just the left DBS side turned on, a 60% improvement was achieved, whereas only a 20% improvement occurred with just the right DBS side on. The results were similar to the Unified Spasmodic Dysphonia Rating Scale (USDRS) ^[17][33] total score and four of the USDRS subcategories (overall, voice arrest, voice tremor, and voice intelligibility). In the mixed left-handed patient, the OMNI-VES also showed that the most improvement (71%) was achieved with bilateral DBS sides on. With the right DBS side on, a 57% improvement was achieved, whereas a 14% improvement occurred with the left DBS side on.

Evidente et al. ^[13][29] presented three patients with essential tremor and LD with bilateral VIM nucleus DBS. The first patient was a 74-year-old, right-handed woman with hand tremor and LD. The programming settings were as follows: for the left VIM, settings were case (+), 0(−), 3.9 volts, 90 µs, and 180 Hz; for the right VIM, settings 11(+), 8(−), 3.7 volts, 90 µs, and 180 Hz. The patient subjectively assessed her voice, noting that she could easily phonate with no vocal tremor. The second patient was a 71-year-old, right-handed woman with hand tremor, blepharospasm, and LD, and the programming settings were as follows: for the left VIM, settings were 3(+), 0(−), 2.7 volts, 60 µs, and 180 Hz; for the right VIM, settings were 11(+), 8(−), 2.4 volts, 60 µs, and 180 Hz. The patient subjectively assessed the voice quality as better in the stimulated state. The third patient was a 65-year-old, left-handed man presenting with bilateral hand tremor and LD with the following stimulator settings: for the left VIM, settings were 3(+), 0(−), 3.7 volts, 90 µs, and 185 Hz; for the right VIM, settings were 11 (+), 8(−), 3.7 volts, 90 V, and 185 Hz. The patient reported improved LD symptoms and vocal tremor in the stimulation state.

Lastly, according to the literature findings on 5 September 2023, one observational prospective cohort study is underway (ClinicalTrials.gov Identifier: NCT05506085) to apply DBS of GPi in treating 12 LD individuals. The estimated study completion (ClinicalTrials.gov Identifier: NCT05506085) is reported to be 1 May 2024.

ENT surgical procedures include selective laryngeal adductor denervation–reinnervation surgery ^{[18][19][20][21]}[34,35,36,37], bilateral vocal fold medialization ^[22][38], TA muscle myectomy/myoneurectomy ^{[23][24][25][26][27]}[39,40,41,42,43], and type II thyroplasty (TPII) ^[28][29][30][44,45,46].

Selective denervation disunites the adductor recurrent laryngeal nerve at its insertion into the TA and the lateral CT muscles, with the proximal stump exteriorized to prevent regeneration, and the ansa cervicalis nerve is anastomized to prevent the regeneration of recurrent laryngeal nerve axons to the TA and the lateral CT muscles. Selective laryngeal adductor denervation–reinnervation surgery for adductor LD can provide relief from voice breaks in patients with LD refractory to botulinum toxin injection ^[18][19][34,35]. Inspecting the laryngeal adductor denervation–reinnervation surgery, a total of 43 LD patients’ findings were reported ^{[18][19][20][21]}[34,35,36,37].

Regarding the treatment of abductor LD, botulinum toxin injection is often unsuccessful, and surgical options include bilateral vocal fold medialization ^[22][38]. Type I thyroplasty is performed under local anesthesia using a silastic implant designed to medialize the vocal folds in six patients with abductor LD ^[22][38]. The authors reported a reduction in voice breaks ^[22][38].

A bilateral TA muscle myectomy surgical approach under microlaryngoscopy was described by Nakamura et al. ^[27][43] in seven patients with adductor LD. The postoperative breathy voice was reported as the disadvantage of the method. Partial myectomy of the TA muscle and neurectomy of the thyroarytenoid branch of the inferior laryngeal nerve resulted in long-term improvement of vocal quality of 15 patients with adductor LD ^[25][26][41,42]. Furthermore, Benito et al. ^[23][39] reported the utility of the bilateral posterior CT partial myoneurectomy in the treatment of a single male patient with abductor LD who had no improvement after six botulinum toxin injections over 21 months. During the postoperative period, the patient reported improved quality of life with breathy voice breaks.

A long-term evaluation of thyroplasty type II with titanium bridges revealed patient satisfaction with the postoperative voice status and a significant improvement in VHI sore postoperatively in a total of 54 patients from two published studies by the same research group ^[28][29][44,45]. Thyroplasty type II (midline lateralization) procedure was performed for the first time by Isshiki et al. ^[30][46] in a single female patient with adductor LD with restored voice with no recurrence of symptoms 17 months postoperatively. Nomoto et al. ^[24][40] compared the TA muscle myectomy and thyroplasty type II in 65 adductor LD patients, concluding that the TA muscle myectomy tends to improve strangulation, interruption, and tremor on the VHI scale ^[31][47]; however, postoperative VHI scores did not differ between the TA muscle myectomy and thyroplasty type II procedures ^[24][40].