Altered hypothalamic diffusivity in Parkinsonian autonomic dysfunction

Abstract

The pathophysiological basis of autonomic symptoms in Parkinson's disease remains incompletely understood. The hypothalamus plays a key regulatory role in autonomic function and has been shown to be affected in Parkinson's disease. Here, using diffusion magnetic resonance imaging, we investigated whether microstructural properties of the hypothalamus differ in Parkinson's disease patients with high compared to low autonomic symptom burden.Parkinson's disease patients with low (n=25) and high (n=25) autonomic symptom burden were identified from a larger pool, based on scores from a questionnaire assessing autonomic symptoms in Parkinson's disease (SCOPA-AUT). In each patient, we first segmented the hypothalamus manually, based on anatomical landmarks. Diffusivity measures were then extracted from the hypothalamus. Diffusivity measures calculated in the brainstem and the putamen were used to assess the specificity of the results.Relative to patients with low autonomic symptom burden, patients with high burden showed increased mean, axial, and radial diffusivity in the hypothalamus. In contrast, we did not find significant group differences in any of these measures extracted from the brainstem or the putamen.These results reveal consistent differences in the microstructural properties of the hypothalamus between patients with low and high autonomic symptom burden. Hypothalamic diffusivity properties can thus potentially be used as an imaging marker to assist in the identification of therapeutic targets for autonomic dysfunction in Parkinson's disease.