Objective: To investigate whether functional connectivity of the hypothalamus can distinguish multiple system atrophy from Parkinson disease.

Background: Multiple system atrophy parkinsonian subtype (MSA-P) and Parkinson disease (PD) are neurodegenerative diseases that can be difficult to distinguish clinically. A common feature among PD patients misdiagnosed with MSA-P is autonomic dysfunction[1]. Prior studies have looked at structural changes on MRI in MSA patients but are limited by variable sensitivity and specificity[2]. We have previously shown that changes in resting state functional MRI (rs-fMRI) in central autonomic regulation regions, centered around the hypothalamus, are associated with the degree of autonomic dysfunction in PD patients[3]. Functional neuroimaging studies of central autonomic structures in MSA patients have not been published. Our preliminary data suggests that fMRI can be used to differentiate MSA-P from PD.

Method: We enrolled 11 subjects with MSA from patients at the UNC Neurology clinic. rs-fMRI and clinical data for 22 PD subjects were obtained from the Parkinson’s Progression Markers Initiative database, an open-access database of early PD patients. We used seed-to-voxel analysis, placing seeds in the left and right hypothalamus (HTH), to investigate patterns of functional connectivity between the HTH and other brain structures, correcting for multiple comparisons.

Results: Mean age and range of MSA and PD subjects was 68.8 (61-80) and 69.5 (53-79) years, respectively. Mean disease duration and range for MSA and PD subjects was 6.9 (1.5-13) and 3.7 (1-22) years, respectively. MSA subjects had significantly stronger functional connectivity between the HTH and ipsilateral insular region as compared to PD subjects in both the left and right hemispheres. A comparator analysis placing seeds in the cerebellum revealed reduced functional connectivity between the cerebellum and the ipsilateral caudate in MSA subjects as compared to PD subjects.

Conclusion: Preliminary analysis of functional connectivity of the HTH shows differences in MSA subjects as compared to age matched PD subjects. These results suggest that rs-fMRI could be used as a tool to help distinguish between the two diseases. Part of these data were presented previously in an abstract at the 2018 American Autonomic Society annual meeting [Oct 2018].

References: [1] Koga, S., et al., When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology, 2015. 85(5): p. 404-12. [2] Bajaj, S., et al., Diffusion-weighted MRI distinguishes Parkinson disease from the parkinsonian variant of multiple system atrophy: A systematic review and meta-analysis. PLoS One, 2017. 12(12): p. e0189897. [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/differences-in-resting-state-fmri-distinguish-multiple-system-atrophy-and-parkinson-disease/