Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants

Jennifer L. Whitwell, Nirubol Tosakulwong, Hugo Botha, Farwa Ali, Heather M. Clark, Joseph R. Duffy, Rene L. Utianski, Chase A. Stevens, Stephen D. Weigand, Christopher G. Schwarz, Matthew L. Senjem, Clifford R. Jack, Val J. Lowe, J. Eric Ahlskog, Dennis W. Dickson, Keith A. Josephs

Research output: Contribution to journalArticle

Abstract

Background and purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. Materials and methods: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. Results: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. Conclusion: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of disease spread through the brain. These findings will be important in the development of appropriate neuroimaging biomarkers for the different PSP variants.

Original languageEnglish (US)
Article number102152
JournalNeuroImage: Clinical
Volume25
DOIs
StatePublished - 2020

Fingerprint

Progressive Supranuclear Palsy
Brain
Subthalamic Nucleus
Globus Pallidus
Motor Cortex
Prostaglandins F

Keywords

  • Atypical
  • Flortaucipir
  • MRI
  • PET
  • PSP

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants. / Whitwell, Jennifer L.; Tosakulwong, Nirubol; Botha, Hugo; Ali, Farwa; Clark, Heather M.; Duffy, Joseph R.; Utianski, Rene L.; Stevens, Chase A.; Weigand, Stephen D.; Schwarz, Christopher G.; Senjem, Matthew L.; Jack, Clifford R.; Lowe, Val J.; Ahlskog, J. Eric; Dickson, Dennis W.; Josephs, Keith A.

In: NeuroImage: Clinical, Vol. 25, 102152, 2020.

Research output: Contribution to journalArticle

Whitwell, Jennifer L. ; Tosakulwong, Nirubol ; Botha, Hugo ; Ali, Farwa ; Clark, Heather M. ; Duffy, Joseph R. ; Utianski, Rene L. ; Stevens, Chase A. ; Weigand, Stephen D. ; Schwarz, Christopher G. ; Senjem, Matthew L. ; Jack, Clifford R. ; Lowe, Val J. ; Ahlskog, J. Eric ; Dickson, Dennis W. ; Josephs, Keith A. / Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants. In: NeuroImage: Clinical. 2020 ; Vol. 25.
@article{c3e41a40e6224fc7b791b19890b4fd82,
title = "Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants",
abstract = "Background and purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. Materials and methods: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. Results: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. Conclusion: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of disease spread through the brain. These findings will be important in the development of appropriate neuroimaging biomarkers for the different PSP variants.",
keywords = "Atypical, Flortaucipir, MRI, PET, PSP",
author = "Whitwell, {Jennifer L.} and Nirubol Tosakulwong and Hugo Botha and Farwa Ali and Clark, {Heather M.} and Duffy, {Joseph R.} and Utianski, {Rene L.} and Stevens, {Chase A.} and Weigand, {Stephen D.} and Schwarz, {Christopher G.} and Senjem, {Matthew L.} and Jack, {Clifford R.} and Lowe, {Val J.} and Ahlskog, {J. Eric} and Dickson, {Dennis W.} and Josephs, {Keith A.}",
year = "2020",
doi = "10.1016/j.nicl.2019.102152",
language = "English (US)",
volume = "25",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants

AU - Whitwell, Jennifer L.

AU - Tosakulwong, Nirubol

AU - Botha, Hugo

AU - Ali, Farwa

AU - Clark, Heather M.

AU - Duffy, Joseph R.

AU - Utianski, Rene L.

AU - Stevens, Chase A.

AU - Weigand, Stephen D.

AU - Schwarz, Christopher G.

AU - Senjem, Matthew L.

AU - Jack, Clifford R.

AU - Lowe, Val J.

AU - Ahlskog, J. Eric

AU - Dickson, Dennis W.

AU - Josephs, Keith A.

PY - 2020

Y1 - 2020

N2 - Background and purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. Materials and methods: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. Results: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. Conclusion: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of disease spread through the brain. These findings will be important in the development of appropriate neuroimaging biomarkers for the different PSP variants.

AB - Background and purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. Materials and methods: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. Results: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. Conclusion: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of disease spread through the brain. These findings will be important in the development of appropriate neuroimaging biomarkers for the different PSP variants.

KW - Atypical

KW - Flortaucipir

KW - MRI

KW - PET

KW - PSP

UR - http://www.scopus.com/inward/record.url?scp=85077647592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077647592&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2019.102152

DO - 10.1016/j.nicl.2019.102152

M3 - Article

AN - SCOPUS:85077647592

VL - 25

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

M1 - 102152

ER -