Scientific Updates
Focal White Matter Changes in Spasmodic Dysphonia: A Combined Diffusion Tensor Imaging and Neuropathological Study
Authors: Kristina Simonyan, Fernanda Tovar-Moll, John Ostuni, Mark Hallett, Victor F. Kalasinsky, Michael R. Lewin-Smith, Elisabeth J. Rushing, Alexander O. Vortmeyer, Christy L. Ludlow
The full article on this study was published in Brain (2008): 131(2), 447-459,
Abstract
Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 spasmodic dysphonia patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus and cerebellar white and grey matter in the patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions, containing calcium, phosphorus and iron, in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus and cerebellum in the postmortem brain tissue from one patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization, limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of spasmodic dysphonia (r=0.509, p=0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of this disorder.
Lay Summary of Research
Spasmodic Dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are known, the brain abnormalities underlying this voice disorder remain unknown. Using magnetic resonance imaging (MRI) available in most hospitals, no brain abnormalities are seen in persons with SD. However, when some specialized techniques were used, referred to as Diffusion Tensor Imaging (DTI), we found structural brain differences in patients with SD in comparison with normal speakers. This study compared 20 SD patients and 20 healthy subjects using this specialized technique. The connecting pathways in the brain from the cortex down to the brain stem region, where the neurons controlling the laryngeal muscles can be found, were measured on both sides of the brain. In this study, the connecting pathway on the right side of the brain from the cortex to the brainstem showed some thinning suggesting that some of the fibers from cortical neurons going to the brainstem were either injured or losing their myelin covering.
We also studied a brain that was donated by an SD patient and their family and compared it with brains of people who had normal speech. No gross abnormalities could be seen in the brain of the SD patient in comparison with the three controls. However, when we closely examined the region that showed abnormalities on brain imaging with DTI, we found some thinning in the same region—the right internal capsule, which carries fibers from the laryngeal motor cortical region towards the brainstem motor nuclei for laryngeal muscle control. In addition, in regions of the basal ganglia, thalamus and cerebellum we also found clusters of mineral accumulations, which contained calcium, phosphorus, and iron. This indicates that some abnormal processes have occurred in the brains of persons with SD but does not tell us what caused those abnormalities.
This study is important because it is the first time we have found abnormalities that may underlie the development of the voice disorder in persons with spasmodic dysphonia. The next step will be to determine what has caused these abnormalities to occur. Studies of abnormalities in proteins that may have produced the build up of these deposits in the brain will be required to unravel the cause of SD.
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Focal White Matter Changes in Spasmodic Dysphonia: A Combined Diffusion Tensor Imaging and Neuropathological Study
Authors: Kristina Simonyan, Fernanda Tovar-Moll, John Ostuni, Mark Hallett, Victor F. Kalasinsky, Michael R. Lewin-Smith, Elisabeth J. Rushing, Alexander O. Vortmeyer, Christy L. Ludlow
The full article on this study was published in Brain (2008): 131(2), 447-459,
Abstract
Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 spasmodic dysphonia patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus and cerebellar white and grey matter in the patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions, containing calcium, phosphorus and iron, in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus and cerebellum in the postmortem brain tissue from one patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization, limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of spasmodic dysphonia (r=0.509, p=0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of this disorder.
Lay Summary of Research
Spasmodic Dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are known, the brain abnormalities underlying this voice disorder remain unknown. Using magnetic resonance imaging (MRI) available in most hospitals, no brain abnormalities are seen in persons with SD. However, when some specialized techniques were used, referred to as Diffusion Tensor Imaging (DTI), we found structural brain differences in patients with SD in comparison with normal speakers. This study compared 20 SD patients and 20 healthy subjects using this specialized technique. The connecting pathways in the brain from the cortex down to the brain stem region, where the neurons controlling the laryngeal muscles can be found, were measured on both sides of the brain. In this study, the connecting pathway on the right side of the brain from the cortex to the brainstem showed some thinning suggesting that some of the fibers from cortical neurons going to the brainstem were either injured or losing their myelin covering.
We also studied a brain that was donated by an SD patient and their family and compared it with brains of people who had normal speech. No gross abnormalities could be seen in the brain of the SD patient in comparison with the three controls. However, when we closely examined the region that showed abnormalities on brain imaging with DTI, we found some thinning in the same region—the right internal capsule, which carries fibers from the laryngeal motor cortical region towards the brainstem motor nuclei for laryngeal muscle control. In addition, in regions of the basal ganglia, thalamus and cerebellum we also found clusters of mineral accumulations, which contained calcium, phosphorus, and iron. This indicates that some abnormal processes have occurred in the brains of persons with SD but does not tell us what caused those abnormalities.
This study is important because it is the first time we have found abnormalities that may underlie the development of the voice disorder in persons with spasmodic dysphonia. The next step will be to determine what has caused these abnormalities to occur. Studies of abnormalities in proteins that may have produced the build up of these deposits in the brain will be required to unravel the cause of SD.