Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension

Jay A. van Gerpen, Rana Hanna Al-Shaikh, Philip W. Tipton, Zbigniew K. Wszolek, Ryan J. Uitti, Tanis J. Ferman, Dennis W. Dickson, Eduardo E. Benarroch, Wolfgang Singer, Jeremy K. Cutsforth-Gregory, Michael G. Heckman, Danielle E. Brushaber, Keith A. Josephs, Phillip A. Low, J. Eric Ahlskog, William P. Cheshire

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology. METHODS: Autopsy-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. RESULTS: The 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. CONCLUSION: Our 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.

Original languageEnglish (US)
Pages (from-to)e1339-e1347
JournalNeurology
Volume93
Issue number14
DOIs
StatePublished - Oct 1 2019

Fingerprint

Progressive Supranuclear Palsy
Orthostatic Hypotension
Adrenergic Agents
Multiple System Atrophy
Lewy Body Disease
Autopsy
Synucleins
REM Sleep Behavior Disorder
Blood Pressure
Movement Disorders
Cardiovascular System
Pathology
Pressure

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

van Gerpen, J. A., Al-Shaikh, R. H., Tipton, P. W., Wszolek, Z. K., Uitti, R. J., Ferman, T. J., ... Cheshire, W. P. (2019). Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension. Neurology, 93(14), e1339-e1347. https://doi.org/10.1212/WNL.0000000000008197

Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension. / van Gerpen, Jay A.; Al-Shaikh, Rana Hanna; Tipton, Philip W.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Ferman, Tanis J.; Dickson, Dennis W.; Benarroch, Eduardo E.; Singer, Wolfgang; Cutsforth-Gregory, Jeremy K.; Heckman, Michael G.; Brushaber, Danielle E.; Josephs, Keith A.; Low, Phillip A.; Ahlskog, J. Eric; Cheshire, William P.

In: Neurology, Vol. 93, No. 14, 01.10.2019, p. e1339-e1347.

Research output: Contribution to journalArticle

van Gerpen, JA, Al-Shaikh, RH, Tipton, PW, Wszolek, ZK, Uitti, RJ, Ferman, TJ, Dickson, DW, Benarroch, EE, Singer, W, Cutsforth-Gregory, JK, Heckman, MG, Brushaber, DE, Josephs, KA, Low, PA, Ahlskog, JE & Cheshire, WP 2019, 'Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension', Neurology, vol. 93, no. 14, pp. e1339-e1347. https://doi.org/10.1212/WNL.0000000000008197
van Gerpen, Jay A. ; Al-Shaikh, Rana Hanna ; Tipton, Philip W. ; Wszolek, Zbigniew K. ; Uitti, Ryan J. ; Ferman, Tanis J. ; Dickson, Dennis W. ; Benarroch, Eduardo E. ; Singer, Wolfgang ; Cutsforth-Gregory, Jeremy K. ; Heckman, Michael G. ; Brushaber, Danielle E. ; Josephs, Keith A. ; Low, Phillip A. ; Ahlskog, J. Eric ; Cheshire, William P. / Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension. In: Neurology. 2019 ; Vol. 93, No. 14. pp. e1339-e1347.
@article{87417b3f52704c96b922d98da0406360,
title = "Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension",
abstract = "OBJECTIVE: To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology. METHODS: Autopsy-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. RESULTS: The 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. CONCLUSION: Our 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.",
author = "{van Gerpen}, {Jay A.} and Al-Shaikh, {Rana Hanna} and Tipton, {Philip W.} and Wszolek, {Zbigniew K.} and Uitti, {Ryan J.} and Ferman, {Tanis J.} and Dickson, {Dennis W.} and Benarroch, {Eduardo E.} and Wolfgang Singer and Cutsforth-Gregory, {Jeremy K.} and Heckman, {Michael G.} and Brushaber, {Danielle E.} and Josephs, {Keith A.} and Low, {Phillip A.} and Ahlskog, {J. Eric} and Cheshire, {William P.}",
year = "2019",
month = "10",
day = "1",
doi = "10.1212/WNL.0000000000008197",
language = "English (US)",
volume = "93",
pages = "e1339--e1347",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "14",

}

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.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - OBJECTIVE: To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology. METHODS: Autopsy-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. RESULTS: The 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. CONCLUSION: Our 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 - OBJECTIVE: To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology. METHODS: Autopsy-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. RESULTS: The 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. CONCLUSION: Our 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

VL - 93

SP - e1339-e1347

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 14

ER -