Abstract Details

Title Imaging Identifies Distinct Brainstem Phenotypes in Early Parkinson’s Disease

Topic Movement Disorders

Presentation(s) S41 - Imaging in Movement Disorders (4:03 PM-4:14 PM)

Poster/Presentation
Number 004

Objective

We designed a study, using DWI, to identify pathologic features in the brainstem in early PD (within 1 year of diagnosis), and determine which of these features predict later development of gait dysfunction.

Background Dense brainstem pathology in neuronal perikarya and related axonal populations is present at diagnosis in Parkinson’s disease (PD). A lack of reliable imaging markers of brainstem disease hinders the development of insight into phenotypic variability in symptoms, and prognosis in PD. Diffusion weighted imaging (DWI) can evaluate both cellular fluid partitioning and directional information in gray and white matter. DWI therefore can potentially identify pathologic features in the brainstem associated with progression.

Design/Methods

Directionality and fluid partitioning measures were derived from DWI of 101 individuals with early PD and 56 healthy controls. We compared these measures in PD patients at the time of diagnosis to controls, and to measure of clinical progression.

Results

A decrease in the intracellular fluid partition in the substantial nigra and the mesencephalic locomotor region at onset (predominantly gray matter regions) is associated with early development of postural instability and gait dysfunction. Conversely, altered radial diffusion in adjacent white matter is more predictive of a diagnosis of PD relative to health controls, but is not a predictor of later gait dysfunction.

Conclusions Two PD populations that can be detected at diagnosis, one with primarily white matter/axonal disease and a second, more rapidly progressive, population with both axonal and gray matter disease. These populations have different prognoses. Our approach provides a pathway towards using MR to detect early, prognostic, neurodegenerative changes in diseases of the brain

Authors/Disclosures
Frank Skidmore, MD PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for onsulting or Advisory Boards: Alexion, Antisense Therapeutics/Percheron, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Genzyme, Genentech, Immunic, Klein-Buendel Incorporated, Kyverna Therapeutics, Inc. , Linical, Merck/Serono, Noema, Neurogenesis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Revelstone Consulting, Roche, SAB Biotherapeutics, Sapience Therapeutics, Scott&Scott LLP, Tenmile.. Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Data and Safety Monitoring Boards: Applied Therapeutics, AI therapeutics, AMO Pharma, Argenx, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb, CSL Behring, Cynata Therapeutics, DiamedicaTherapeutics, Horizon Pharmaceuticals, Immunic, Inhibrix, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Merck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Holdings, Prothena Biosciences, Novartis, Pipeline Therapeutics (Contineum), Regeneron, Sanofi-Aventis, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Anthony P. Nicholas, MD, PhD (University of Alabama at Birmingham)	Dr. Nicholas has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Fenwick. Dr. Nicholas has received publishing royalties from a publication relating to health care.
	No disclosure on file
Mark W. Albers, MD, PhD (Massachusetts General Hospital)	An immediate family member of Dr. Albers has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Aromha. Dr. Albers has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Aromha. Dr. Albers has stock in Berkshire Hathaway. Dr. Albers has stock in Curis. The institution of Dr. Albers has received research support from NIH. Dr. Albers has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Rand Swenson, MD, PhD (Geisel School of Medicine At Dartmouth)	No disclosure on file
Hemant Tiwari	No disclosure on file
	No disclosure on file
David G. Standaert, MD, PhD, FAAN (Univ of Alabama - Dept of Neurology)	Dr. Standaert has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie, Inc. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curium. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Standaert has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS/Pharmacy. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HanAll Biopharma. Dr. Standaert has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for F. Hoffman LaRoche. Dr. Standaert has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Aventis. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance, Inc. Dr. Standaert has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for International Parkinson and Movement Disorder Society. The institution of Dr. Standaert has received research support from Abbvie, Inc. The institution of Dr. Standaert has received research support from American Parkinson Disease Association. The institution of Dr. Standaert has received research support from National Institutes of Health. The institution of Dr. Standaert has received research support from F. Hoffman LaRoche. Dr. Standaert has received publishing royalties from a publication relating to health care. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with National Institutes of Health. Dr. Standaert has a non-compensated relationship as a Chair, Scientific Advisory Board with American Parkinson Disease Association that is relevant to AAN interests or activities.

��ɫ��

��ɫ��