Low Clinical Sensitivity and Unexpectedly High Incidence for Neuropathologically Diagnosed Progressive Supranuclear Palsy (PSP)
Erika Driver-Dunckley1, Nathaniel Dunckley2, Nan Zhang1, Geidy Serrano3, Lucia Sue3, Holly Shill4, Shyamal Mehta1, Christine Belden3, cecilia tremblay3, Alireza Atri3, Charles Adler1, Thomas Beach3
1Mayo Clinic Arizona, 2Saguaro High School, 3Banner Sun Health Research Institute, 4Barrow Neurology Clinics
Objective:
Determine the prevalence, incidence, and clinical diagnostic accuracy for neuropathologically-diagnosed PSP.
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.
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.