Demographic and clinical characteristics of our patients diagnosed with laryngeal dystonia

Laryngeal dystonia (LD) is a focal neurological dystonia characterized by intermittent and involuntary spasms caused by activation of the intrinsic laryngeal muscles during phonation, causing task-specific vocal fluency impairment [1]. LD is an uncommon form of dysphonia that does not include a phonatory organ disease or paralysis [2, 3]. Vocational incapacity and social isolation are the two most common distressing conditions caused by LD in patients [4, 5]. The pathophysiology of LD is inadequately comprehended, and the process of diagnosis presents challenges [6].

LD is characterized by its multifactorial etiology, and genetic variants are considered important risk factors for the development of this disorder. Nevertheless, traditional linkage studies in LD have been severely limited by low penetrance of dystonia, rare availability of large families, phenotypic discordance between affected family members, and late age at onset. While 12% of LD patients have a family history of dystonia [7], a specific gene for LD has not been identified. Among other forms of dystonia-causing gene mutations that have been identified, laryngeal involvement has been reported in patients with generalized and segmental dystonia who are carriers of the DYT1, DYT4, DYT6, DYT25, and DYT28 mutations [8]. Only 1 case of focal adductor LD (AdLD) with DYT25 (GNAL) mutation and without any other co-occurring forms of dystonia, a family history of dystonia, or other movement disorders has been reported to date [9]. Not only are the mutations in specific genes linked with dystonia but polymorphisms also play a role. While mutations of the TOR1A gene are responsible for early onset segmental dystonia that rarely involves laryngeal dystonia, polymorphisms in the same gene have been associated with adult-onset, primarily focal dystonia, including LD and even a decreased risk of developing dystonia.

Imaging studies have played a crucial role in investigating the specific pathophysiology of LD. In the study conducted by Walter et al., transcranial sonography revealed hyperechogenicity in the lenticular nucleus and caudate nucleus in 12 out of 14 patients with AdLD [10]. Subsequent neuroimaging studies have demonstrated that the pathophysiology of LD encompasses extensive alterations in both the function and structure of brain networks. These alterations affect not only the basal ganglia, but also higher-order motor and associative cortical regions, the thalamus, and the cerebellum [11]. Distinct symptoms in LD may be linked to disorder-specific network alterations [12]. Impaired brain plasticity and neurotransmission in LD also point to other mechanisms in dystonia pathophysiology, including abnormal dopaminergic and GABAergic function and maladaptive plasticity [13]. From a clinical point of view, the significance of variations in these regions is apparent from their diagnostic potential in the successful machine-learning classification of LD, achieving up to 98.8% accuracy in objectively diagnosing this disorder [14].

Despite the LD studies conducted in recent years, epidemiological data are insufficient due to the lack of studies observing the LD patient group in the long term. Although the diagnosis of LD can be challenging, the patient’s history, laryngoscopic examination, and phonatory characteristics of the voice often make the diagnosis. In a study by Hyodo et al. in Japan [15], the prevalence was 3.5–7.0/100,000, similar to that in Rochester (NY, USA) and Iceland[16]. Women were four times more likely to be affected than men. The mean age of onset varies between 40 and 50 years. Although rare, familial relationships have been shown in a few studies [17].

There are three forms of LD: adductor, abductor, and mixed. Adductor phenotype is the most common type (90–95%), in which intermittent glottal closure blocks expiratory airflow and causes a strained and hoarse voice quality with vocal interruptions. In abductor LD (AbLD), spasms of the intrinsic laryngeal abductor muscle open the vocal folds during speech, resulting in an intermittent breathy voice or aphonia [2‐4]. Mixed LD exhibits both vocal symptoms and is rarely seen.

Regardless of the subtype of LD, patients have difficulty speaking naturally and effectively, which has a significant impact on their professional and social communication [18, 19]. Some tactile or proprioceptive exercises, such as chewing or head bracing, can enhance speech for certain people [20]. The mechanism behind this behavior is unknown. Singing or laughing can boost speech fluency, possibly capitalizing on the task-specific character of dystonia [21].

Botulinum toxin (BT) injection into the laryngeal musculature is the most common and effective treatment method for LD. Surgery and voice therapy are other treatment options. BT inhibits acetylcholine release at the neuromuscular junction by reducing muscle activity. The target muscles are thyroarytenoid in AdLD patients and posterior cricoarytenoid in AbLD patients. Surgical interventions include type 2 thyroplasty [22, 23], thyroarytenoid myectomy [24, 25], and selective laryngeal denervation-reinnervation [26]. Voice therapy also aims to reduce strong glottal closure, but its effectiveness is limited.

There is currently no research on the prevalence of LD in Turkey. The objective of our study was to identify the demographic and clinical features of individuals with LD identified at our clinic which is among the few tertiary centers in Turkey that specialize in LD follow-up. Further research is necessary on LD prevalence, likely etiologies, treatment modalities, and diagnosis.

The sample population of the study consisted of patients diagnosed with LD who were followed at the Ear, Nose, and Throat Department of a tertiary medical center. The study was approved by a tertiary medical faculty Ethics Committee for Clinical Research on 27/10/2023 with number 09.2022.1449. Because the study was designed retrospectively, informed consent was not obtained from the patients. Descriptive statistic was used to present data. The study included patients who were diagnosed following admission and subsequently received treatment at our clinic. The diagnosis was made by a speech therapist and laryngologist with at least ten years of experience, employing a three-tiered technique as proposed by Ludlow et al. [27]. Firstly, screening questions were utilized to indicate potential LD. Secondly, a comprehensive speech examination was conducted to further assess and identify likely LD. Finally, the laryngoscopic examination was made for a definitive diagnosis. Neurologists also assessed the patients for potential coexisting movement disorder. A retrospective investigation was conducted on a cohort of 43 patients diagnosed with LD between January 2017 and July 2023. All patient data were obtained from past medical records and missing data was fulfilled with telesurveys. Sociodemographic characteristics of the patients, the age of symptom onset, and the time elapsed between the first onset of symptoms and the diagnosis were noted. Family history of dystonia-like symptoms and the existence of factors that trigger or alleviate symptoms were questioned. BT injections are the treatment of choice and are performed under local anesthesia with the help of laryngeal EMG. Each patient was questioned regarding the frequency of injections, the onset and peak days of injection effectiveness, and the length of injection effectiveness. Additionally, the dosage of injections was obtained from medical records.

The study included 43 patients and Table 1 summarizes the results. 19 (44%) were male and 24 (56%) were female. The patients' mean age at the time of diagnosis was 35.1 years (17–65 years). The mean age at the onset of the first symptoms in patients before diagnosis was 31.2 years (16–53 years). The average time from the first date of symptoms to the diagnosis of LD in our patients was 49.2 months (4–240 months), while this period was 42 months (4–120 months) for men and 64 months (6–240 months) for women. Thus, there was an approximately four-year delay from symptom onset to diagnosis in our study population. In our study, 40 participants (94%) had AdLD, and three (6%) had AbLD. Of the patients, nine (20%) reported experiencing a major stress or trauma that could affect their lives just before symptom onset. All patients were admitted to a hospital more than once until the diagnosis was made.

None of our patients had a family history of LD. Previous research has indicated a correlation between LD and an increased incidence of movement problems. With respect to movement disorders, 3 of our patients have co-existing vocal tremor. 2 out of the 43 patients had additional neurological disease, specifically peripheral nerve entrapments. In our study, 10 (%23) patients consumed alcohol daily basis and all patients who consumed alcohol claimed that their symptoms improved after alcohol consumption. Conversely, 24 (55%) patients reported worsening of their symptoms under emotional stress or anxiety. Our patients with AdLD undergo bilateral thyroarytenoid muscle (TA) botulinum toxin injections using a hollow-bore 27 gauge Teflon-coated EMG needle with EMG control. In the AdLD group, patients who did not achieve the intended outcome following the injection while being monitored by EMG, or in cases where EMG was not accessible, were given TA botulinum toxin injections employing flexible laryngoscopy in an office setting. Before administering the injections, patients received 5 cc of 2% lidocaine through the cricothyroid membrane to generate local anesthesia for the TA botulinum toxin injection process. On average, they receive 2.7 injections, with a minimum of 1 injection and a maximum of 20 injections. All of our data is based on injections of Botox^® (Allergan, Inc., Irvine, CA, USA). Our average dose is 1.5 U/0.1 ml per vocal fold. The findings for the entire adductor group indicate that the average time for the positive effects to start is 2.7 days. The average maximum effect occurs after 7 days, and the average length of improvement is 12 weeks. In the AbLD, we treated 3 patients with an average dose range of 2.5 U/0.1 ml units. given separately and spaced 2 weeks apart. The strategy for the AbLD group is to treat via posterior cricoarytenoid muscle (PCA) injections. They all received 1 injection for each PCA. In all three AbLD cases, the breathy voice persisted to some extent, despite a satisfactory reduction following the administration of the injection. The objective is to modify the dosage in subsequent injections.

This study analyzed the age, sex distribution, and clinical features of 43 patients diagnosed with LD at a single center in Turkey. The scarcity of research on the topic has resulted in a lack of relevant statistics regarding the prevalence of LD in Turkey. Therefore, it is necessary to conduct multicenter studies to establish the prevalence in Turkey. This study represents the largest cohort of Turkish patients diagnosed with LD at a single hospital thus far.

Although female predominance has been reported for the LD patient group in the literature, our study observed an almost equal distribution (M/F, 19/24). Studies have shown that movement disorders are associated with a higher rate in patients with LD. In our investigation, we detected concomitant vocal tremor in three cases, while the remaining individuals had isolated LD. While there has been a familial relationship in a small part of the studies on LD performed thus far, our study found no familial history in the LD patient population.

There is currently no standard diagnostic method for LD. The time elapsed between the onset of symptoms and diagnosis can take years. During this time, hospital admissions are seen more than once. Treatment is symptomatic therapy through BT chemodenervation. This is supported by a large body of literature confirming the efficacy of BT in many different studies, particularly in the uncomplicated adductor form of the disorder. Research into surgical treatment predates the development of BT therapy over a decade. However, its long-term effectiveness has not been proven, which points to the need for further research.