Abstract Details

Title Mapping White Matter Changes to Monitor Disease Progression in Multiple System Atrophy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-008

Objective We aimed to identify the white matter (WM) and grey matter (GM) abnormalities in multiple system atrophy (MSA) and assess the utility of longitudinal structural and diffusion changes as surrogate markers for tracking disease progression in MSA.

Background White matter abnormalities have been implicated in clinically relevant functional decline in MSA.

Design/Methods 27 participants with early MSA (15 with clinically predominant cerebellar (MSA-C) and 12 with clinically predominant parkinsonian features (MSA-P)) and 14 controls were enrolled as a part of our prospective, longitudinal study of synucleinopathies. Using structural magnetic resonance imaging (MRI) and diffusion MRI (diffusion tensor and neurite orientation and dispersion density imaging), we analyzed the whole and regional brain changes in these participants. We also evaluated temporal imaging trajectories based on up to 3 annual follow-up scans and assessed the impact of baseline diagnosis on these imaging biomarkers using mixed effect models.

Results MSA patients exhibited more widespread WM changes than GM, particularly in the cerebellum and brainstem, with greater severity in MSA-C. Structural and diffusion measures in the cerebellum and brainstem deteriorated with disease progression. Rates of progression of these abnormalities were similar in both MSA subtypes, reflecting increasing overlap of clinical features over time.

Conclusions WM abnormalities are core features of MSA disease progression and advance at similar rates in clinical MSA subtypes. Multimodal MRI imaging reveals novel insights into the distribution and pattern of brain abnormalities and their progression in MSA. Selected structural and diffusion measures may be useful for tracking disease progression in MSA clinical trials.

Authors/Disclosures
Sheela Raghavan PRESENTER	No disclosure on file
Timothy Lesnick	No disclosure on file
Anna Castillo	Anna Castillo has nothing to disclose.
Robert I. Reid	No disclosure on file
Angela Fought (Mayo Clinic)	Angela Fought has received personal compensation in the range of $500-$4,999 for serving as a Biostatistician on DSMB with Northwestern University.
Kaely Thostenson	No disclosure on file
Kohl Johnson Sparrman	No disclosure on file
Tonette Gehrking	Tonette Gehrking has nothing to disclose.
Jade Gehrking (Mayo Clinic, Neurology Dept)	Jade Gehrking has nothing to disclose.
David M. Sletten, MBA	Mr. Sletten has nothing to disclose.
Phillip A. Low, MD, FAAN (Mayo Clinic)	Dr. Low has nothing to disclose.
Wolfgang Singer, MD, FAAN (Mayo Clinic)	Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. The institution of Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Yoda. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. Dr. Singer has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ferrer. The institution of Dr. Singer has received research support from NIH. The institution of Dr. Singer has received research support from FDA. The institution of Dr. Singer has received research support from Michael J. Fox Foundation. Dr. Singer has received intellectual property interests from a discovery or technology relating to health care.
Prashanthi Vemuri, PhD (Mayo Clinic)	The institution of Dr. Vemuri has received research support from NIH.

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