Laryngeal dystonia: Phenomenology, genetics, and management.

Laryngeal dystonia is a task-specific movement disorder causing abnormal movement of the adductor or abductor muscles of the vocal folds. In 1984, Blitzer pioneered the first use of onabotulinum toxin A to treat this disorder. Over 1400 patients were diagnosed with laryngeal dystonia in the last thirty years. In this paper, we summarize their clinical and endoscopic findings as well as treatment results. We also summarize the underlying genetics of the disorder. 82% of patients were diagnosed with adductor type laryngeal dystonia and 17% of patients manifested an abductor laryngeal dystonia. Patients with adductor dystonia were treated with toxin to the thyroarytenoid muscles and those with abductor dystonia were treated with toxin to the posterior cricoarytenoid muscle. All patient achieved greater than 70% improvement in percent normal function. Laryngeal dystonia is a rare movement disorder of the larynx with an incidence of approximately 35.1 per 100,000 individuals (Simonyan et al., 2021). Presently, there is no cure for laryngeal dystonia, but botulinum toxin has shown significant success in treating the symptoms of the disorder.

The pluripotential evolution and journey of Botox (onabotulinumtoxinA).

Clinical use of onabotulinumtoxinA evolved based on strategic, hypothesis-driven applications, as well as serendipitous observations by physicians and patients. The success of onabotulinumtoxinA in blepharospasm and strabismus led to its study in other head and neck dystonias, followed by limb dystonia, tremor, and spasticity. The aesthetic use of onabotulinumtoxinA followed initial reports from patients of improved facial lines after injections for facial dystonias and hemifacial spasm. Although patients with dystonias and spasticity regularly reported that their local pain improved after injections, onabotulinumtoxinA was not systematically explored for chronic migraine until patients began reporting headache improvements following aesthetic injections. Clinicians began assessing onabotulinumtoxinA for facial sweating and hyperhidrosis based on its inhibition of acetylcholine from sympathetic cholinergic nerves. Yet another line of research grew out of injections for laryngeal dystonia, whereby clinicians began to explore other sphincters in the gastrointestinal tract and eventually to treatment of pelvic sphincters; many of these sphincters are innervated by autonomic nerves. Additional investigations in other autonomically mediated conditions were conducted, including overactive bladder and neurogenic detrusor overactivity, achalasia, obesity, and postoperative atrial fibrillation. The study of onabotulinumtoxinA for depression also grew out of the cosmetic experience and the observation that relaxing facial muscle contractions associated with negative emotions may improve mood. For approved indications, the safety profile of onabotulinumtoxinA has been demonstrated in the formal development programs and post-marketing reports. Over time, evidence has accumulated suggesting clinical manifestations of systemic effects, albeit uncommon, particularly with high doses and in vulnerable populations. Although onabotulinumtoxinA is approved for approximately 26 indications across multiple local regions, there are 15 primary indication uses that have been approved in most regions, including the United States, Europe, South America, and Asia. This review describes many uses for which AbbVie has not sought and/or received regulatory approval and are mentioned for historical context only.

Treatment of glabellar lines with Botox (onabotulinumtoxinA): Development, insights, and impact.

OnabotulinumtoxinA is an injectable medication that produces muscle relaxation through local chemical denervation at the neuromuscular junction. Discovery of onabotulinumtoxinA's aesthetic benefits occurred serendipitously in the 1980s at the intersection of several medical disciplines, including ophthalmology, neurology, otolaryngology, and dermatology. Patients receiving onabotulinumtoxinA for blepharospasm, hemifacial spasm, and dystonia noticed their periorbital wrinkles disappearing, particularly frown lines between the eyebrows called glabellar lines (GL). Aesthetic use of onabotulinumtoxinA necessitated rigorous training programs and vigilant monitoring by Allergan. Approval for the GL indication was based on 2 similarly designed, double-blind, randomized, multicenter clinical studies. Subjects with moderate to severe GL receiving onabotulinumtoxinA achieved significantly greater improvement in GL severity than those receiving placebo. In subsequent studies, more than 80% of subjects were satisfied with onabotulinumtoxinA treatment through day 60, and many reported looking approximately 4 years younger at weeks 4 and 12 than at baseline. OnabotulinumtoxinA has a rapid onset of action, and peak effect occurs between 30 and 60 days. The median duration of response for dynamic GL in the initial studies was 120 days and response progressively improved with subsequent treatments. OnabotulinumtoxinA was well tolerated, and the 2 most common adverse events, headache and blepharoptosis, tended to decrease in frequency with repeat treatment. The novel use of onabotulinumtoxinA for treating GL was an important step in addressing the clinical need for a noninvasive, straightforward, office-based procedure for facial lines that also left patients extremely satisfied with its treatment effects and represented the beginning of its widespread use for numerous aesthetic indications.

Metformin for the Treatment of Recurrent Respiratory Papillomatosis.

OBJECTIVES: Metformin is an oral agent used for the management of type 2 diabetes. As a result of its ability to alter cellular metabolic requirements, metformin also possesses antiproliferative properties. Metformin has been shown to reduce mutagenesis in several malignancies, however has never been described as a treatment option for recurrent respiratory papillomatosis (RRP). The aim of this study is to present a case series of non-diabetic patients with adult-onset RRP who were treated with metformin. METHODS: Case series. RESULTS: Five patients (age 48 ± 17.82, range 35-68, 4 males, 1 female) were identified with a history of laryngeal RRP who were treated with 500 mg of metformin twice daily. Follow-up time ranged from 11 to 105 months. Two patients had spontaneous regression of RRP lesions within months of starting metformin. Four patients had reduced time intervals between surgical procedures after starting metformin. All patients tolerated metformin well with only minor side effects of self-limiting light-headedness, facial flushing or gastrointestinal upset. CONCLUSION: Metformin is a low-risk medication that was used to reduce progression and burden of disease in 5 patients with RRP. Further studies should investigate the sole or adjunct use of metformin for treatment of RRP.

IncobotulinimtoxinA (Xeomin) for the treatment of adductor laryngeal dystonia: A prospective, open-label clinical trial.

OBJECTIVES: Demonstrate an understanding of incobotulinumtoxinA efficacy in the treatment of adductor spasmodic dysphonia (SD). Understand that incobotulinumtoxinA can successfully be used as an alternative to onabotulinumtoxinA and for secondary non-responders. METHODS: We conducted a prospective open-label trial from 2016 until 2019 regarding the use of incobotulinimtoxinA for the treatment of adductor spasmodic dysphonia. Exclusion criteria included pregnant/nursing women, botulinum toxin for other indications, known allergy, neuromuscular or systemic diseases, use of aminoglycoside antibiotics, substance abuse, litigation regarding prior therapy, or other confounding conditions. Sixty-four injection sessions with completed with sixteen patients who were enrolled in the study and underwent EMG-guided incobotulinumtoxinA injections to the thyroarytenoid (TA) muscle using a hollow monopolar Teflon-coated needle via a trans-cricothyroid membrane approach. Dosages to each TA muscle were recorded and patients completed a Voice Handicap Index-10 (VHI-10), a validated worksheet regarding their perceived percent of normal function (PNF) following treatment, and a side effect profile. Outcomes were analyzed using the paired t-test. RESULTS: For primary transitioners to incobotulinimtoxinA, VHI-10 scores and best percent normal function did not significantly change. For non-responders, VHI-10 decreased from 32.5 on Botox to 19.5 on incobotulinimtoxinA and best PNF increased from 37.6 to 90 %, which was statistically significant. Transient side effects included breathiness. CONCLUSIONS: Our study demonstrates that incobotulinimtoxinA may be used successfully for adductor SD either as first line treatment or in secondary non-responders to onabotulinumtoxinA.

Laryngeal, Pharyngeal and Respiratory Involvement in Palatal Tremor.

OBJECTIVE: To present cases of atypical palatal tremor (PT) and showcase the variable phenomenology of this condition. STUDY DESIGN: Retrospective case series. RESULTS: PT, or palatal myoclonus, is a movement disorder characterized by brief, involuntary rhythmic muscular contractions of the soft palate. Variants of PT have been described and include synchronous tremors in other branchial arch derivatives including the larynx, pharynx, neck, face, jaw, ocular and also respiratory and trunk muscles. We present 3 cases, including clinical videos, of atypical PT with extra-palatal manifestations, in addition to a brief discussion of the pathophysiology and management of this condition. CONCLUSION: Variations of PT are of interest to the practicing otolaryngologist as the clinical spectrum of this condition is wide and can present with laryngeal, pharyngeal, respiratory and other head and neck manifestations.

Oromandibular Dystonia: A Clinical Examination of 2,020 Cases.

Objective: The goal of this study is to better characterize the phenotypic heterogeneity of oromandibular dystonia (OMD) for the purpose of facilitating early diagnosis. Methods: First, we provide a comprehensive summary of the literature encompassing 1,121 cases. Next, we describe the clinical features of 727 OMD subjects enrolled by the Dystonia Coalition (DC), an international multicenter cohort. Finally, we summarize clinical features and treatment outcomes from cross-sectional analysis of 172 OMD subjects from two expert centers. Results: In all cohorts, typical age at onset was in the 50s and 70% of cases were female. The Dystonia Coalition cohort revealed perioral musculature was involved most commonly (85%), followed by jaw (61%) and tongue (17%). OMD more commonly appeared as part of a segmental dystonia (43%), and less commonly focal (39%) or generalized (10%). OMD was found to be associated with impaired quality of life, independent of disease severity. On average, social anxiety (LSA score: 33 ± 28) was more common than depression (BDI II score: 9.7 ± 7.8). In the expert center cohorts, botulinum toxin injections improved symptom severity by more than 50% in ~80% of subjects, regardless of etiology. Conclusions: This comprehensive description of OMD cases has revealed novel insights into the most common OMD phenotypes, pattern of dystonia distribution, associated psychiatric disturbances, and effect on QoL. We hope these findings will improve clinical recognition to aid in timely diagnosis and inform treatment strategies.

Association of Laryngeal Botulinum Neurotoxin Injection With Work Productivity for Patients With Spasmodic Dysphonia.

Importance: A disordered voice can affect an individual across both work and non-work-related life domains. There is insufficient research on the effect of spasmodic dysphonia or its treatment with botulinum neurotoxin (BoNT) injections on work productivity. Objective: To assess whether employed patients with spasmodic dysphonia experience voice-related work productivity impairment before BoNT injection, and had a 10% or greater improvement in productivity 1 month after treatment with BoNT injection. Design, Setting, and Particpants: This prospective case series carried out in 2 laryngology outpatient clinics from November 1, 2015, to August 30, 2018 included a consecutive sample of adult employed patients diagnosed with spasmodic dysphonia. Analysis was conducted between November 1, 2015, to July 31, 2018. Exposures: Treatment with BoNT injection into the intrinsic laryngeal musculature. Main Outcomes and Measures: Eligible participants completed the following validated outcomes instruments immediately before and 1 month after outpatient laryngeal BoNT injection: the Work Productivity and Activity Impairment instrument (WPAI), Voice Handicap Index (VHI), and WorkHoarse. Demographic, comorbidity, and occupational voice use data were also collected at baseline. The changes in outcome measures (primary, WPAI Work Productivity Impairment domain) were tested using a paired 2-tailed t test. Exploratory subgroup analyses were analyzed with multivariable linear regression, adjusting for demographic, comorbidity, and voice use variables. Results: Of the 101 patients enrolled, 75 completed the study. The mean (SD) age of the 75 completing participants was 55.7 (11.8) years and 53 (71%) were women. The participants who completed the study had mean (SD) voice-related work productivity impairment of 43% (27%) at baseline and 22% (23%) at 1 month after BoNT injection (difference, 20% [27%] improvement; 95% CI, 14%-27%; effect size, 0.74). Conclusions and Relevance: This case series study found that employed patients with spasmodic dysphonia reported voice-related work productivity impairment, which improved significantly 1 month after treatment with BoNT injection. The association of spasmodic dysphonia with voice-related work productivity appeared greater in women than men with comparable outcomes with BoNT treatment, but this exploratory sex-associated difference requires independent validation.

Laryngeal Dystonia: Multidisciplinary Update on Terminology, Pathophysiology, and Research Priorities.

OBJECTIVE: To delineate research priorities for improving clinical management of laryngeal dystonia, the NIH convened a multidisciplinary panel of experts for a 1-day workshop to examine the current progress in understanding its etiopathophysiology and clinical care. METHODS: The participants reviewed the current terminology of disorder and discussed advances in understanding its pathophysiology since a similar workshop was held in 2005. Clinical and research gaps were identified, and recommendations for future directions were delineated. RESULTS: The panel unanimously agreed to adopt the term "laryngeal dystonia" instead of "spasmodic dysphonia" to reflect the current progress in characterizations of this disorder. Laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonia. Its etiology remains unknown, whereas the pathophysiology likely involves large-scale functional and structural brain network disorganization. Current challenges include the lack of clinically validated diagnostic markers and outcome measures and the paucity of therapies that address the disorder pathophysiology. CONCLUSION: Research priorities should be guided by challenges in clinical management of laryngeal dystonia. Identification of disorder-specific biomarkers would allow the development of novel diagnostic tools and unified measures of treatment outcome. Elucidation of the critical nodes within neural networks that cause or modulate symptoms would allow the development of targeted therapies that address the underlying pathophysiology. Given the rarity of laryngeal dystonia, future rapid research progress may be facilitated by multicenter, national and international collaborations.

Safety and Feasibility of a Novel Esophageal Balloon for Circumferential Cytologic Sampling.

OBJECTIVES: A prior publication introduced the Strome-Blitzer balloon's ability to obtain circumferential esophageal cytologic sampling. This GLP study was requisite for FDA approval to determine if equivalent cell capture and cellularity was observed with the balloon compared to surface sampling brushes and to determine the balloon's usability for naive otolaryngologists. METHODS: Three naïve users tested the Hobbs brush and Strome-Blitzer balloon on 4 Yorkshire swine. Four anatomical sites were sampled, beginning distally and ending proximally. In 2 animals, the balloon was used first distally and in the remaining 2, 4 new Hobbs brushes were used distally first. Moving proximally, the balloon and brushes were sequentially alternated. In follow-the-leader fashion, the balloon was introduced trans-orally followed by an endoscope to the desired site. The balloon was inflated exposing the abrasive strips to contact the esophageal mucosa. Moving the balloon 1 to 2 cm superiorly and inferiorly effected circumferential cell capture. The balloon was collapsed and removed, preserving the cellularity. The Hobbs brush was passed through the scope's channel. Four brushes, 1 per quadrant, obtained the samples at an anatomical site. The balloon was rated as pass/fail on the following: delivery, kinking, usability, and malfunction. A blinded veterinary pathologist evaluated the cytology. RESULTS: There was no device malfunction, mucosal trauma, or difficulty with device use. Balloon cytologic samples were comparable in cellularity and quality to the brush. CONCLUSION: A single balloon sampling was comparable to 4 brushes in capturing diagnostically relevant cellular volumes and architecture. Naïve users easily performed the procedures after reading the guidelines. LEVEL OF EVIDENCE: 3.

Botulinum Toxin for the Treatment of Motor and Phonic Tics: A Case Report.

OBJECTIVE: To present a unique approach to the treatment of motor and phonic tics. PATIENT: A 26-year-old male presented with motor and phonic tics including grunting, coughing, and throat clearing. INTERVENTION: The patient was treated with 2.5 units of onabotulinum toxin A (BoNT) to the facial mimetic musculature and 2.5 units to each supraglottic musculature via a transthyrohyoid membrane approach under fiberoptic visualization. RESULTS: The patient experienced reduction in the frequency, intensity, and interference with daily life of motor and phonic tics on the Yale Global Tic Severity Scale (YGTSS). CONCLUSION: This patient experienced subjective and objective decreases in tic severity using a unique approach in the treatment of phonic tics. Results suggest a novel approach in the treatment of phonic tics and bolster the data regarding safe and effective use of BoNT for tic disorder. LEVEL OF EVIDENCE: Level V, case report.

Impact of an Upper Respiratory Tract Infection on Botulinum Toxin Efficacy in Spasmodic Dysphonia Patients.

OBJECTIVE: To determine whether the presence of a concomitant upper respiratory tract infection (URI) impacts upon Botulinum toxin (BoNT) efficacy in spasmodic dysphonia (SD) patients. STUDY DESIGN: Case series and literature review. METHODS: All SD patients with a concurrent URI, presenting for BoNT therapy at a clinical research center from November 2016 to December 2017 were included. A total of 12 patients were identified. Patients were followed for at least two BoNT treatment cycles (approximately 6 months). The primary outcome measure was efficacy of the initial BoNT injection and the secondary outcome measure was the efficacy of the subsequent BoNT injection. RESULTS: All subjects had adductor type SD (ADSD). There were 10 females and two males with a median age of 55 years (±19.5). All patients were well established on a consistent BoNT treatment regime, with an average administered dose of 1.0 unit (range 0.2-1.80 units). Bilateral injections were administered to 10 patients. Regarding the primary outcome measure, five failed to have any response to BoNT (41.7%), four had a partial response (33.3%), and three had a positive response to treatment (25.0%). When patients had their follow-up injection in the absence of URI symptoms, 11 patients had a positive response to treatment (91.7%). CONCLUSION: While the interplay between illness and BoNT efficacy is yet to be elucidated, we report that some patients are affected. We recommend that SD patients presenting for BoNT administration with a concomitant URI, should be counseled that their treatment might have decreased effect. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1746-1749, 2020.

Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks.

BACKGROUND: Botulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks. METHODS: Adults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs). RESULTS: In total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by -0.16 and -0.17, respectively, at the end-of-study visit. Subjects' GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%). CONCLUSIONS: Data support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.

SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea.

OBJECTIVE: This pivotal phase III study, SIAXI, investigated the efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea due to Parkinson disease (PD), atypical parkinsonism, stroke, or traumatic brain injury (TBI). METHODS: Adult patients with PD (70.7%), atypical parkinsonism (8.7%), stroke (19.0%), or TBI (2.7%) were randomized (2:2:1) to double-blind treatment with placebo (n = 36), or total doses of incobotulinumtoxinA 75 U (n = 74) or 100 U (n = 74), in a single treatment cycle. The coprimary endpoints were change in unstimulated salivary flow rate from baseline to week 4, and patients' Global Impression of Change Scale score at week 4. Adverse events were recorded throughout. RESULTS: A total of 184 patients were randomized. Both incobotulinumtoxinA dose groups showed reductions in mean unstimulated salivary flow rate at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.004). Patients' Global Impression of Change Scale scores also improved at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.002). A lasting effect was observed at week 16 post injection. The most frequent treatment-related adverse events in the incobotulinumtoxinA 75 U and 100 U groups were dry mouth (5.4% and 2.7% of patients) and dysphagia (2.7% and 0.0% of patients). CONCLUSIONS: IncobotulinumtoxinA 100 U is an effective and well-tolerated treatment of chronic sialorrhea in adults. CLINICALTRIALSGOV IDENTIFIER: NCT02091739. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that incobotulinumtoxinA reduces salivary flow rates in patients with chronic sialorrhea due to PD, atypical parkinsonism, stroke, or TBI.

Interesting case of late Gore-Tex extrusion following medialization laryngoplasty.

A 65-year-old female presented with a foreign body sensation following an asthmatic attack associated with severe coughing. Six years earlier, the patient underwent medialization laryngoplasty (ML), which was complicated by a small tear (2 mm) in the right ventricle. One year following this, the patient developed Gore-Tex extrusion but elected only for partial removal. Healing was complete until 5 years later; on examination, the patient had evidence of Gore-Tex extrusion through the right ventricle. Implant extrusion is a recognized complication of ML. This case demonstrates several important surgical steps that can benefit otolaryngologists at all stages of their surgical career. Laryngoscope, 129:1420-1422, 2019.

A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity.

Oral medications for the treatment of dystonia are not established. Currently, symptoms of focal dystonia are managed with botulinum toxin injections into the affected muscles. However, the injection effects are short-lived and not beneficial for all patients. We recently reported significant clinical improvement of symptoms with novel investigational oral drug, sodium oxybate, in patients with the alcohol-responsive form of laryngeal focal dystonia. Understanding the mechanism of action of this promising oral agent holds a strong potential for the development of a scientific rationale for its use in dystonia. Therefore, to determine the neural markers of sodium oxybate effects, which may underlie dystonic symptom improvement, we examined brain activity during symptomatic speech production before and after drug intake in patients with laryngeal dystonia and compared to healthy subjects. We found that sodium oxybate significantly attenuated hyperfunctional activity of cerebellar, thalamic and primary/secondary sensorimotor cortical regions. Drug-induced symptom improvement was correlated with decreased-to-normal levels of activity in the right cerebellum. These findings suggest that sodium oxybate shows direct modulatory effects on disorder pathophysiology by acting upon abnormal neural activity within the dystonic network.

Unearthing a consistent bilateral R1 component of the laryngeal adductor reflex in awake humans.

OBJECTIVE: The laryngeal adductor reflex (LAR) is an essential tracheobronchial protective mechanism resulting in vocal fold adduction to laryngeal stimulation. It was thought to consist of an early ipsilateral R1 component and a later, bilateral but highly centrally modulated R2 component. We recently demonstrated that bilateral R1 responses are robustly present in humans under general anesthesia. We herein give evidence that the R1 response is also bilateral in awake humans and is likely the primary component responsible for initiating the LAR. METHODS: Seven volunteers were included (3 males, 4 females). The reflex was elicited by direct percutaneous monopolar needle stimulation of the internal superior laryngeal nerve. Electromyography traces from bilateral lateral cricoarytenoid muscles were recorded using hookwire electrodes. Reflex responses to variations in stimulus intensity and duration were evaluated. RESULTS: Bilateral R1 responses were recorded in all patients, even during deep inspiration when the vocal folds were maximally abducted. R1, but not R2, responses increased linearly in amplitude, with sequential increases in both stimulation intensity (1-8 mA) and duration (100-500 µsec) (Pearson correlation 0.94). CONCLUSION: Contradicting over 40 years of research, we demonstrate that the R1 LAR component is consistently bilateral in awake humans. It increases linearly with stimulus intensity and is unaffected by conscious state suggesting minimal central control. These findings may provide a means to objectively stratify patients for risk of laryngeal aspiration, even in unconscious states, and its potentially cardinal role in disease states such as laryngospasm and sudden infant death needs to be reevaluated. LEVEL OF EVIDENCE: 4. Laryngoscope, 2581-2587, 2018.

Dacryocystorhinostomy with a thulium:YAG laser-a case series.

We conducted a retrospective chart review of 27 patients-7 men and 20 women, aged 47 to 94 years (mean: 71.3)-with symptomatic epiphora secondary to dacryostenosis who had undergone thulium: YAG (Tm:YAG) laser dacryocystorhinostomy (DCR). Among them, dacryostenosis had been documented in 35 eyes by dacryocystography. The Tm:YAG procedure involved the administration of local anesthesia, after which a 600-µm laser fiber was inserted into the lacrimal canaliculi and then into the nasolacrimal duct. Under endoscopic visualization, the DCR was performed anterior and inferior to the middle turbinate, which created an opening. Silicone stents were then inserted and tied intranasally. In the immediate postoperative period, all 27 patients noted initial improvement. During a follow-up of 22 days to 25 months (mean: 11.3 mo), 24 of the 27 patients (89%) remained symptom-free, while the remaining 3 patients (11%) experienced a treatment failure and required revision surgery. To the best of our knowledge, only two articles on thulium laser therapy for DCR have been previously published, both approximately 25 years ago; both involved the use of a thulium along with holmium and chromium in cadavers. As far as we know, our case series is the largest in the English-language literature that has documented the use of the thulium in laser therapy for DCR, and it is the only in vivo study. We found that DCR with the Tm:YAG laser was an effective and affordable option for patients with symptomatic epiphora secondary to lacrimal obstruction.

Central voice production and pathophysiology of spasmodic dysphonia.

OBJECTIVE: Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). DATA SOURCES: Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. REVIEW METHODS: Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. RESULTS: Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. CONCLUSION: Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. LEVEL OF EVIDENCE: NA.Laryngoscope, 128:177-183, 2018.