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

Abstract

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.

© 2021 American Academy of Neurology.

Figures

Figure 1. Standard Clinical Management and Clinical Characteristics and of Laryngeal Dystonia

(A) The current standard clinical management of laryngeal dystonia. The patient undergoes multiple assessments by several specialists until the final diagnosis can be reached, often delaying the overall time-to-diagnosis for several years. Multidisciplinary team evaluations of a patient are recommended to facilitate the diagnosis and initiate the treatment. (B) Clinical diagnosis is based on a syndromic approach, using (C) a combination of case history, auditory-perceptual characteristics, and laryngeal/neurologic examinations. Red bars in (B) indicate different stages in the diagnostic process when the clinical decision is refined based on additional evaluations. AD = autosomal dominant; ABLD = abductor form of laryngeal dystonia; ADLD = adductor form of laryngeal dystonia; LD = laryngeal dystonia; MTD = muscle tension dysphonia; VT = voice tremor.

Figure 2. Risk Factors for the Development of Laryngeal Dystonia

(A) Dystonia-associated polygenic risk and the contribution of different gene ontology terms to the enrichment score based on data described in Ref. 17. (B) Distribution of laryngeal dystonia-associated biological and extrinsic risk factors based on data described in Ref. 3.

Figure 3. Characteristic Brain Alterations in Laryngeal Dystonia

(A) Schematic of large-scale neural network alterations in laryngeal dystonia, with associations between regional changes, clinical features, endophenotypic traits, genetic mutations, polygenic risk, and extrinsic risk. The timeline shows the evolution of understanding of the pathophysiology of dystonia from a basal ganglia disorder to a functional and structural neural network disorder. This figure was modified from Ref. 24 to represent the neuroimaging literature in laryngeal dystonia. (B) Common features of large-scale neural network disorganization in patients across different phenotypes and genotypes of laryngeal dystonia (middle circular plot) and the distinct features of the large-scale network architecture based on the disorder phenotype and genotype. The figure was modified from Ref. 45. The inner circle in each graph represents the network hubs (red—connector hubs; yellow—provincial hubs); the outer circle in each group represents high-influence network nodes; lines represent connections of each node with the network. For detailed information on network node/hub participation, see original research study. ABLD = abductor form of laryngeal dystonia; ADLD = adductor form of laryngeal dystonia.