Objective: To investigate the association between autonomic symptom burden and hypothalamic functional connectivity in patients with MSA.

Background: Multiple system atrophy (MSA) is a progressive neurodegenerative condition characterized clinically by the combination of parkinsonism, cerebellar ataxia, autonomic dysfunction, and pyramidal system dysfunction. Autonomic symptoms are often very prominent, and thought to be primarily related to deterioration in the brainstem and sympathetic chain. Hypothalamic structural and functional changes are well documented in MSA[1]. The hypothalamus plays an important role in autonomic function[2], and altered functional connectivity between the hypothalamus and the striatum in Parkinson’s disease patients with higher burden of autonomic symptoms has previously been demonstrated by our group[3].

Method: We enrolled patients with probable or possible MSA seen at the UNC Neurology clinic for their care. Participants completed the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT), Montreal Cognitive Assessment (MoCA), and underwent brain MRI including T1 and rs-fMRI sequences. We employed seed-to-voxel analysis, with seeds in the left and right hypothalamus, to investigate patterns of functional connectivity between the hypothalamus and other brain structures associated with SCOPA-AUT scores. Results were corrected for multiple comparisons.

Results: We enrolled 11 participants into this study. Mean disease duration was 6.5 years (range 1.5-13 years), mean SCOPA-AUT score was 26.3 (range 10-34). We found alterations in functional connectivity between the left and right hypothalamus and the brainstem, inferior temporal gyrus, subcallosal cortex, anterior cingulate gyrus, parahippocampal gyrus, cerebellum, paracingulate gyri, and the subcallosal cortex, in association with increased SCOPA-AUT.

Conclusion: We present the first investigation, to our knowledge, of the association of autonomic symptom burden with rs-fMRI measures in MSA. We found alterations of functional connectivity between the hypothalamus and many known cortical and subcortical CNS autonomic centers in association with elevated autonomic symptom burden in MSA.

References: 1. Benarroch, E.E., et al., Differential involvement of hypothalamic vasopressin neurons in multiple system atrophy. Brain, 2006. 129(Pt 10): p. 2688-96. 2. Sklerov, M., E. Dayan, and N. Browner, Functional neuroimaging of the central autonomic network: recent developments and clinical implications. Clin Auton Res, 2018. 3. Dayan, E., M. Sklerov, and N. Browner, Disrupted hypothalamic functional connectivity in patients with PD and autonomic dysfunction. Neurology, 2018. 90(23): p. e2051-e2058.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hypothalamic-functional-connectivity-correlates-with-autonomic-symptom-burden-in-patients-with-multiple-system-atrophy/