Brain Advance Access originally published online on December 14, 2007
Brain 2008 131(2):447-459; doi:10.1093/brain/awm303
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Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study
1Laryngeal and Speech Section, Medical Neurology Branch, 2Neuroimmunology Branch, 3Clinicial Neurosciences Program, 4Human Motor Control Section, Medical Neurology Branch, 5Department of Environmental and Infectious Disease Sciences, 6Department of Neuropathology and Ophthalmic Pathology, Armed Forces Institute of Pathology and 7Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health
Correspondence to: Kristina Simonyan, MD, PhD, Laryngeal and Speech Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 5D38, Bethesda, MD 20892-1416, USA E-mail: simonyak{at}ninds.nih.gov
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.
Key Words: laryngeal dystonia; corticobulbar tract; basal ganglia; neuroimaging; neuropathology
Abbreviations: ABSD, abductor spasmodic dysphonia; ADSD, adductor spasmodic dysphonia; CBT/CST, corticobulbar/corticospinal tract; CV, coefficient of variance; DTI, diffusion tensor imaging; FA, fractional anisotropy; HV, healthy volunteer; ROI, region of interest; SD, spasmodic dysphonia; SEM-EDXA, scanning electron microscopy with energy dispersive X-ray analysis; TBSS, tract-based spatial statistics
Received May 10, 2007. Revised November 20, 2007. Accepted November 22, 2007.
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