Spasmodic dysphonia and voice tremor: an analysis of the neuropathophysiology, clinical features and treatment options

Abstract

Spasmodic dysphonia (SD) is a focal laryngeal dystonia that affects speech production. It is a rare disease that can remain undiagnosed and untreated in many. It usually develops in midlife and is socially and occupationally disabling. It can be sub-classified into adductor SD (ADSD), abductor SD (ABSD) and mixed SD. In one -third of patients, SD is also associated with vocal tremor (SD/VT). This further complicates the diagnosis, as this element of the disease has a more variable response to the gold standard of management Botulinum toxin (BoNT) than SD alone. The reasons for this are unclear, but a lack of the full understanding of the aetiology, pathophysiology and clinical features of SD with or without VT (SD+/-VT) certainly contribute.Whilst there has been some recent progress made in understanding the brain functional and structural alterations of SD, there has been no commensurate progress in understanding the VT component of SD/VT. As such this prevents the true understanding of the nature of SD+/-VT, and thus improved management of the disorder. Therefore the first aim of this work was to determine specific brain abnormalities contributing to both SD and SD/VT, via examining functional and structural brain abnormalities in 20 SD vs. 20 SD/VT vs. healthy controls (HV), using functional MRI (fMRI) during symptomatic speech production, voxel based morphometry (VBM) and diffusion weighted imaging (DWI). This revealed that both SD and SD/VT groups showed increased activation in the sensorimotor cortex, inferior frontal (IFG) and superior temporal gyri (STG), putamen and ventral thalamus, as well as deficient activation in the inferior parietal cortex and middle frontal gyrus (MFG). Common structural alterations were observed in the IFG and putamen, which were further coupled with functional abnormalities in both patient groups (Coordinates at the peak of significant clusters are given in the AFNI standard Talairach-Tournoux space at an FWE-corrected p ≤ 0.05). Abnormal activation in the left putamen was correlated with SD onset (r = 0.61, p = 0.004), whereas SD/VT onset was associated with right putaminal volumetric changes (r = -0.48, p = 0.032). These and further findings explored in the thesis demonstrate that SD and SD/VT, are heterogeneous disorders at different ends of the same clinical spectrum, with each disorder carrying a characteristic neural signature, which may potentially help the development of differential markers for these two conditions.The secondary aim of this Masters, was to explore some of the clinical characteristics of SD+/-VT. It has been acknowledged anecdotally that the symptoms of both SD and SD/VT respond positively to the consumption of alcohol. This has been published in the setting of VT alone, however it has never been formally explored in the setting of SD. Therefore the secondary aim of this work was to conduct a cross sectional online survey of patients with SD and SD/VT in order to 3 ascertain their degree of alcohol consumption and the effect it has on their sym...