Focal white matter changes in spasmodic dysphonia: a combined diffusion tensor imaging and neuropathological study

TLDR

Spasmodic dysphonia is a neurological disorder marked by involuntary laryngeal muscle spasms during speech, yet its underlying pathophysiology remains unknown. The study aims to identify disorder‑specific brain abnormalities in spasmodic dysphonia patients using a combined diffusion tensor imaging and postmortem histopathology approach. Diffusion tensor imaging was employed to detect white‑matter changes and to guide targeted neuropathological examination of the affected regions. DTI revealed reduced fractional anisotropy in the right internal capsule genu and increased diffusivity in the corticobulbar/corticospinal tract, lentiform nucleus, ventral thalamus, and cerebellar white/grey matter, and postmortem analysis confirmed axonal loss, demyelination, and mineral deposits in these areas, with changes correlating with symptom severity and suggesting a role in the disorder’s pathophysiology.

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.