Vocal Cord Dysfunction

Communication by voice depends on symmetrical vibrations within the vocal folds (VFs) and is indispensable for various occupations. VF scarring is one of the main reasons for permanent dysphonia and results from injury to the unique layered structure of the VFs. The increased collagen and decreased hyaluronic acid within VF scars lead to a loss of pliability of the VFs and significantly decreases their capacity to vibrate. As there is currently no definitive treatment for VF scarring, regenerative medicine and tissue engineering have become increasingly important research areas within otolaryngology. Several recent reviews have described the problem of VF scarring and various possible solutions, including tissue engineered cells and tissues, biomaterial implants, stem cells, growth factors, anti-inflammatory cytokines antifibrotic agents. Despite considerable research progress, these technical advances have not been established as routine clinical procedures. This review focuses on emerging techniques for restoring VF pliability using various approaches. We discuss our studies on interactions among adipose-derived stem/stromal cells, antifibrotic agents, and VF fibroblasts using an in vitro model. We also identify some obstacles to advances in research.

Vocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis.

Objective(s)To systematically synthesize published evidence on paradoxical vocal fold motion associated with confirmed central or peripheral neurological disorders, with emphasis on neuroanatomic correlations, clinical presentation, management strategies, and treatment outcomes.MethodsA systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO. Six databases (PubMed/MEDLINE, Embase, Scopus, Cochrane Library, ScienceDirect, and Google Scholar) were searched from inception to December 2025. Studies reporting PVFM associated with a confirmed neurological disorder in patients of any age were included. Eligible designs comprised case reports, case series, and observational studies. Data extraction was performed using predefined criteria, and risk of bias was assessed using Joanna Briggs Institute (JBI) critical appraisal tools and the ROBINS-I framework.ResultsEleven studies were included, enrolling 102 patients, of whom 42 (19 pediatric, 23 adult) had paradoxical vocal fold motion in association with a confirmed neurological disorder. Neurological etiologies encompassed brainstem malformations, epilepsy, cerebral palsy, neuromuscular junction disorders, basal ganglia diseases, neurodegenerative disorders, and ion-channelopathies. The review design precluded estimation of the prevalence of neurological causes among all PVFM cases; within individual cohorts, neurological disease was identified in 54% of infants with PVFM, and paradoxical vocal fold motion was documented in 33% of patients with multiple system atrophy. Six of the nine studies with classifiable etiologies involved reversible or treatable conditions and three involved progressive neurodegenerative disease, although most individual patients fell into the latter group because the neurodegenerative cohorts were larger. Treatment directed at the underlying neurological disorder resulted in substantial improvement or resolution in most reversible cases, whereas symptoms often persisted in progressive diseases.ConclusionPVFM is frequently associated with organic neurological disorders and should be recognized as a manifestation of disrupted neural control rather than solely a functional condition. Early neurological evaluation and disease-specific management may improve outcomes, particularly in atypical or refractory presentations.