Abstract Details

Title Low Clinical Sensitivity and Unexpectedly High Incidence for Neuropathologically Diagnosed Progressive Supranuclear Palsy (PSP)

Topic Movement Disorders

Presentation(s) S51 - Movement Disorders: Tremor, Parkinsonism, and Non-motor Symptoms (3:30 PM-3:42 PM)

Poster/Presentation
Number 001

Background The clinical diagnosis of PSP remains difficult due to the variability in the presenting phenotypes. Often the diagnosis of PSP is not made until autopsy. A recent update of consensus neuropathological criteria for PSP allows an improved assessment of clinical diagnostic accuracy.

Objective Determine the prevalence, incidence, and clinical diagnostic accuracy for neuropathologically-diagnosed PSP.

Design/Methods All subjects were enrolled in the in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP) and had annual standardized research clinical assessments as well as comprehensive neuropathological examinations after death. A subset of subjects who lacked dementia or parkinsonism at enrollment were used to calculate the PSP incidence rate. The Rainwater neuropathological criteria were used to define PSP while clinical findings were used to separate subjects into incidental PSP (iPSP) and clinically manifest PSP based on the presence or absence of parkinsonism or dementia. Prevalence and incidence rates were calculated.

Results

Of 954 autopsy cases, 101 met Rainwater criteria for the neuropathologic diagnosis of PSP. 87 of these were termed clinicopathological PSP while 14 were iPSP. The prevalence of clinicopathologically-defined PSP subjects in the entire autopsy dataset was 9.1% while the incidence rate was estimated at 780 per 100,000 persons per year, roughly 50-fold or more greater than most previous clinically-determined PSP incidence estimates. A clinical diagnosis of PSP was 99.6% specific but only 9.2% sensitive based on first examination, and 99.3% specific and 20.7% sensitive based on the final clinical exam. Of the clinicopathologically-defined PSP cases, 35/87 (~40%) had no form of parkinsonism at first assessment while this decreased to 18/83 (21.7%) at final assessment.

Conclusions Our study confirms a high specificity but low sensitivity for the clinical diagnosis of PSP. The low clinical sensitivity for PSP is likely primarily responsible for previous underestimates of the PSP population incidence rate.

Authors/Disclosures
Erika Driver-Dunckley, MD, FAAN PRESENTER	Dr. Driver-Dunckley has nothing to disclose.
	No disclosure on file
Nan Zhang	No disclosure on file
Geidy Serrano	No disclosure on file
	No disclosure on file
Holly A. Shill, MD, FAAN (Barrow Neurology Clinics)	Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Biogen. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for KeifeRx. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis Precision Medicine. Dr. Shill has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fasikl Inc.
Shyamal Mehta, MD, PhD, FAAN (Mayo Clinic, Arizona)	Dr. Mehta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Adamas Pharma. Dr. Mehta has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Mehta has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CNS Ratings.
Christine Belden	No disclosure on file
Cecilia Tremblay (Banner Sun Health Research Institute)	No disclosure on file
Alireza Atri, MD, PhD (Banner Sun Health Research Institute)	Dr. Atri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prothena. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Atri has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novo Nordisk. Dr. Atri has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Atri has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lunbeck. The institution of Dr. Atri has received research support from National Institute of Aging (NIA). The institution of Dr. Atri has received research support from AZ Department of Health Services. The institution of Dr. Atri has received research support from Gates Ventures. The institution of Dr. Atri has received research support from Multiple companies, universities & consortia for contracted clinical trials to institution. The institution of Dr. Atri has received research support from Washington University in St. Louis. The institution of Dr. Atri has received research support from Foundation for NIH. The institution of Dr. Atri has received research support from ACTC/NIH. Dr. Atri has received publishing royalties from a publication relating to health care.
Charles H. Adler, MD, PhD, FAAN (Mayo Clinic Arizona)	Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Adler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CND Life Sci. Dr. Adler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precon. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. The institution of Dr. Adler has received research support from NIH. The institution of Dr. Adler has received research support from Michael J. Fox Foundation. The institution of Dr. Adler has received research support from Arizona Biomedical Research Commission. Dr. Adler has received publishing royalties from a publication relating to health care.
Thomas Beach (Banner Sun Health Research Institute)	Thomas Beach has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vivid Genomics. Thomas Beach has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics. The institution of Thomas Beach has received research support from National Institutes of Health. The institution of Thomas Beach has received research support from Michael J Fox Foundation . The institution of Thomas Beach has received research support from State of Arizona.