Spasmodic dysphonia (SD) is a focal dystonia affecting the neural control of the laryngeal musculature for speech production. Although the clinical symptoms of SD have been described, the underlying pathological mechanisms remain unknown. Treatment strategies are of short benefit and expensive.
Muscle tension dysphonia (MTD) is considered a behavioral voice disorder because many cases benefit from behavioral therapy. The etiology of this vocal misuse disorder remains unknown but is not considered neurological and is thought to differ from SD.
Vocal tremor (VT) is a form of benign essential tremor. In less severely affected persons, vocal tremor is action-induced and occurs during vocalization only. In more severe cases, the tremor can be present also during exhalation and whispering and affect other structures, such as the velum and pharynx. This is also considered a neurological disorder but may differ in character from SD. Both these disorders can co-occur with SD but can also occur independently.
The anatomical characteristics of pre- and postmortem brains in patients with SD, MTD and VT and healthy volunteers will be investigated using imaging and neurohistological techniques to provide insight into the pathogenesis of SD. Identification of the neuropathological basis of SD and how it differs from other voice disorders would enhance our understanding of the neurological basis of SD.
OBJECTIVES:
Our objective in this study is to investigate anatomical and morphological characteristics of premortem and postmortem brains from persons with SD, and determine how it differs from other voice disorders such as MTD and VT using magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and neurohistological techniques.
STUDY POPULATION:
We plan to examine persons referred with a diagnosis of SD, MTD, and VT to confirm whether they have symptoms of the disorder and to identify research volunteers who are without neurological, psychiatric, or head and neck disorders. The research volunteers could be spouses of persons with SD, MTD, and VT without a familial relationship.
DESIGN:
This is a natural history study. In the premortem part of the study persons with SD, MTD, and VT and research volunteers will be screened for eligibility for the study. Brain MRI using a 3T scanner will be performed for volumetric reconstruction of gray matter on the first 60 participants in both the patient and research volunteer groups. In addition, high-resolution MRI using 7T scanner will be obtained to identify focal structural differences on individual basis in the same 20 SD patients compared to 20 controls. DTI will be conducted for visualization of white matter tracts in 25 subjects per group. The remaining subjects will only undergo the screening and anatomical MRI scans prior to brain donation.
In the postmortem phase, the study will employ MRI of the postmortem brain specimens for diagnostic purposes. Brain and laryngeal tissue will be processed histologically to quantify morphological abnormalities between the two groups. Because it is estimated that about 48% of subjects who participate in the main MRI study will also grant consent for brain/larynx donation, maximum of additional 30 subjects per group are to be recruited for the study. Many of the previous patients who have participated in Laryngeal and Speech Section protocols in the past will be contacted to determine if they would be interested in participating.
OUTCOME MEASURES:
1. Premortem imaging techniques will determine if there are differences in the brain anatomy of patients with SD compared to MTD, VT and to research volunteers:
1. Volumetric reconstruction of gray matter regions involved in voice production;
2. Visualization of the white matter tracts between brain regions of interest.
2. Postmortem MRI will identify discrepancies between premortem and postmortem brains of the same persons with SD in comparisons to MTD, VT and to research volunteers.
3. Microscopic examination of brain sections will determine whether abnormalities can be found in the cortical and subcortical regions involved in voice production in persons with SD that differ from patients with MTD and VT.
4. Microscopic examination of the larynx will determine distribution of motor and sensory nerve endings in persons with SD and in patients with MTD and VT and controls.
