Is the Phenotype Designation by PSP-MDS Criteria Stable Throughout the Disease Course and Consistent With Tau Distribution?

Javier Sánchez-Ruiz De Gordoa,Blanca Acha,Miren Roldán,Paula Tellechea-Aramburo,Victoria Zelaya,Maite Mendioroz,Arkaitz Galbete,Valle Coca,Carlos López-Molina,M Elena Erro

doi:10.3389/fneur.2022.827338

Javier Sánchez-Ruiz De Gordoa, Blanca Acha + Show 8 more

Open Access

https://doi.org/10.3389/fneur.2022.827338

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Abstract

IntroductionThe MDS-PSP criteria have shown high sensitivity for the PSP diagnosis, but do not discriminate the phenotype diversity. Our purpose was to search for anatomopathological differences among PSP phenotypes resulting from the application of the MDS-PSP criteria comparing with the previous ones.MethodsThirty-four PSP cases from a single brain bank were retrospectively classified according to the criteria used by Respondek et al. in 2014 and the PSP-MDS criteria at 3 years (MDS-3y), 6 years (MDS-6y) and at the last clinical evaluation before death (MDS-last). Semiquantitative measurement of total, cortical and subcortical tau load was compared. For comparative analysis, PSP-Richardson syndrome and PSP postural instability were grouped (PSP-RS/PI) as well as the PSP atypical cortical phenotypes (PSP-Cx).ResultsApplying the Respondek's criteria, PSP phenotypes were distributed as follow: 55.9% PSP-RS/PI, 26.5% PSP-Cx, 11.8% PSP-Parkinsonism (PSP-P), and 5.9% PSP-Cerebellum. PSP-RS/PI and PSP-Cx had a higher total tau load than PSP-P; PSP-Cx showed a higher cortical tau load than PSP-RS/PI and PSP-P; and PSP-RS/PI had a higher subcortical tau load than PSP-P. Applying the MDS-3y, MDS-6y and MDS-last criteria; the PSP-RS/PI group increased (67.6, 70.6 and 70.6% respectively) whereas the PSP-Cx group decreased (8.8, and 8.8 and 11.8%). Then, only differences in total and subcortical tau burden between PSP-RS/PI and PSP-P were observed.InterpretationAfter the retrospective application of the new MDS-PSP criteria, total and subcortical tau load is higher in PSP-RS/PI than in PSP-P whereas no other differences in tau load between phenotypes were found, as a consequence of the loss of phenotypic diversity.

Highlights

The movement disorders society (MDS)-Progressive supranuclear palsy (PSP) criteria have shown high sensitivity for the PSP diagnosis, but do not discriminate the phenotype diversity
After applying the MDS-3y criteria, PSP phenotypes were distributed as follow: 67.6% PSP-RS/PI (47.1% PSP-RS and 20.6% PSP-PI), 17.6% PSPU, 8.8% PSP-Cx (8.8% PSP-predominant speech/language disorder (PSP-SL)) and 5.9% PSP-predominant parkinsonism (PSP-P)
The new MDS-PSP classification [8] resulted from the need to establish sensitive and specific clinical criteria for the diagnosis of the different PSP phenotypes that have been described after the 1996 definition of the Neurological Disorders and Stroke (NINDS)-PSP criteria [2], which are very specific for the PSP-RS phenotype, but very insensitive for the atypical variants

Summary

Introduction

The MDS-PSP criteria have shown high sensitivity for the PSP diagnosis, but do not discriminate the phenotype diversity. NINDS-PSP criteria have low sensitivity for the diagnosis of the atypical PSP phenotypes that have been described throughout the last 20 years, especially in early stages of the disease [3,4,5,6,7] For this reason, the movement disorders society (MDS) has recently reformulated PSP diagnostic criteria [8]. The new MDS-PSP criteria categorize PSP symptoms into four clinical domains: ocular motor, postural instability, akinesia and cognitive dysfunction Different combinations of these symptoms have defined various PSP phenotypes: PSP-RS, PSP-predominant postural instability (PSPPI); PSP-predominant ocular motor dysfunction (PSP-OM); PSP-predominant parkinsonism (PSP-P); PSP-progressive gait freezing (PSP-PGF); PSP-predominant corticobasal syndrome (PSP-CBS); PSP-predominant frontal presentation (PSP-F) and PSP-predominant speech/language disorder (PSP-SL)

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