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.
N1 - Publisher Copyright:
© 2019 The Authors
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
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U2 - 10.1016/j.nicl.2019.102152
DO - 10.1016/j.nicl.2019.102152
M3 - Article
C2 - 31935638
AN - SCOPUS:85077647592
SN - 2213-1582
VL - 25
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 102152
ER -