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

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.

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.

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
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Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein-Buendel Incorporated, Medimmune/Viela Bio, Medday, Merck/Serono, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Regeneron, Reckover Pharmaceuticals, Roche, TG Therapeutics.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics,Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc.. Dr. Cutter has received personal compensation in the range of $500-$4,999 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.
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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.
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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 Pharma. Dr. Standaert has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Gray Matter Technologies. 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 Department of Defense. The institution of Dr. Standaert has received research support from National Institutes of Health. 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 Speaker with Case Western Reserve. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Consultant with California Pacific Medical Center. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Course Instructor with International Parkinson Disease and Movement Disorders Society. 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 received personal compensation in the range of $500-$4,999 for serving as a Consultant with Parkinson Study Group. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Speaker with UCSD. Dr. Standaert has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with Warren Alpert Foundation. 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.