TY - JOUR
T1 - Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension
AU - Van Gerpen, Jay A.
AU - Al-Shaikh, Rana Hanna
AU - Tipton, Philip W.
AU - Wszolek, Zbigniew K.
AU - Uitti, Ryan J.
AU - Ferman, Tanis J.
AU - Dickson, Dennis W.
AU - Benarroch, Eduardo E.
AU - Singer, Wolfgang
AU - Cutsforth-Gregory, Jeremy K.
AU - Heckman, Michael G.
AU - Brushaber, Danielle E.
AU - Josephs, Keith A.
AU - Low, Phillip A.
AU - Ahlskog, J. Eric
AU - Cheshire, William P.
N1 - Funding Information:
The authors acknowledge the financial support of the Mayo Clinic in Florida Focused Research Team.
Funding Information:
J. van Gerpen receives funding from the Florida Focused Research Team. R. Hanna Al-Shaikh receives funding from the Florida Focused Research Team and Donald G. and Jodi P. Heeringa. P. Tipton reports no disclosures relevant to the manuscript. Z. Wszolek is partially supported by Mayo Clinic Center for Regenerative Medicine, the Sol Goldman Charitable Trust, Donald G. and Jodi P. Heeringa, and Abbvie and Biogen medication trials. R. Uitti reports no disclosures relevant to the manuscript. T. Ferman is partially supported by NIH P50-AG16574, NIH P50-NS72187-01, and the Man-gurian Foundation for LBD research. D. Dickson reports no disclosures relevant to the manuscript. E. Benarroch is a sec-tioneditorforNeurology®. W. Singer, J. Cutsforth-Gregory, M. Heckman, and D. Brushaber report no disclosures relevant to the manuscript. K. Josephs is supported by NIH R01 AG37491 (principal investigator), R01 NS89757 (principal investigator), and R01 DC14942 (principal investigator). P. Low, J. Ahlskog, and W. Cheshire report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© 2019 American Academy of Neurology.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - ObjectiveTo evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology.MethodsAutopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic.ResultsThe absence of orthostatic hypotension (OH) was the strongest autonomic parameter that distinguished PSP from α-synucleinopathies (0% vs 69%, p < 0.0001). Tests of adrenergic failure, which distinguish neurogenic OH, also differentiated PSP from other groups. These included the pressure recovery time (p = 0.0008), adrenergic impairment score (p = 0.001), and magnitude of change of systolic (p = 0.0002) and diastolic (p = 0.0001) blood pressures (BPs) during upright tilt. In addition, REM sleep behavior disorder was seen less frequently (p = 0.006) in PSP (33%) compared to MSA (87%) and LBD (90%). Antemortem clinical diagnostic accuracy for these phenotypically variable disorders was 57% for PSP and 83% for α-synucleinopathies.ConclusionOur results suggest that the cardiovascular adrenergic system, which sustains BP during standing, is relatively unaffected, if not spared, in PSP. These findings increase our understanding of the clinical signature of PSP and have the potential to improve diagnostic accuracy in atypical parkinsonisms by distinguishing PSP from the α-synucleinopathies.
AB - ObjectiveTo evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology.MethodsAutopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic.ResultsThe absence of orthostatic hypotension (OH) was the strongest autonomic parameter that distinguished PSP from α-synucleinopathies (0% vs 69%, p < 0.0001). Tests of adrenergic failure, which distinguish neurogenic OH, also differentiated PSP from other groups. These included the pressure recovery time (p = 0.0008), adrenergic impairment score (p = 0.001), and magnitude of change of systolic (p = 0.0002) and diastolic (p = 0.0001) blood pressures (BPs) during upright tilt. In addition, REM sleep behavior disorder was seen less frequently (p = 0.006) in PSP (33%) compared to MSA (87%) and LBD (90%). Antemortem clinical diagnostic accuracy for these phenotypically variable disorders was 57% for PSP and 83% for α-synucleinopathies.ConclusionOur results suggest that the cardiovascular adrenergic system, which sustains BP during standing, is relatively unaffected, if not spared, in PSP. These findings increase our understanding of the clinical signature of PSP and have the potential to improve diagnostic accuracy in atypical parkinsonisms by distinguishing PSP from the α-synucleinopathies.
UR - http://www.scopus.com/inward/record.url?scp=85072790587&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072790587&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000008197
DO - 10.1212/WNL.0000000000008197
M3 - Article
C2 - 31484717
AN - SCOPUS:85072790587
SN - 0028-3878
VL - 93
SP - E1339-E1347
JO - Neurology
JF - Neurology
IS - 14
ER -