Objective: To evaluate the phenotypical convergence phenomena among a cohort of different PSP variants. We also aimed to evaluate the possible correlations of the regional glucose metabolism between variants.

Background: An accurate diagnosis of PSP is still a clinical challenge, especially at early stages, when the phenotypes are heterogeneous. Thus, clinical variants were defined in the current MDS-PSP criteria[1]. However, there is increasing evidence that as the disease progresses, many patients with a diagnosis of variants of PSP develop ocular and/or postural features.

Method: We performed a retrospective, multicenter, cohort study of 72 PSP patients who were referred for an FDG-PET scan (final clinical diagnosis based on the MDS-PSP criteria & MAX rules)[2]: PSP-RS, n=47; PSP-P variant, n=17; and PSP-PGF, n=8. Phenotypical convergence was assessed in two ways: Firstly, we studied the temporal expression of the main clinical domains defined in the criteria using time-to-event analyses. Secondly, we studied the longitudinal evolution of the diagnostic certainty level and the PSP variant diagnosis according to the criteria. Additionally, to evaluate the correlation of regional glucose metabolism between variants we performed a Volume-of-Interest analysis.

Results: Patients with a final diagnosis of PSP-RS showed a more aggressive disease with shorter disease duration at FDG-PET without differences in motor or functional scores (Table 1). Through the follow-up, we observed a tendency to clinically converge to phenotypes linked to higher diagnostic certainty. Interestingly, the different variants showed a parallel clinical progression with differences in time of onset regarding the oculomotor (OM) and postural instability (PI) domains. Compared to RS, PSP-P patients showed a delayed onset on both, OM and PI domains, and PSP-PGF showed a similar onset on PI but a delayed onset on OM domain (Table 2- Fig. 1). Furthermore, the regional glucose metabolism was strongly correlated between PSP subtypes (Fig. 2).

Conclusion: Despite initial clinical heterogeneity among PSP variants, we observe a trend to converge towards a fully symptomatic stage which encompasses OM dysfunction, PI, and, in most cases, a dysexecutive/behavioral syndrome. Moreover, the regional glucose metabolism was strongly correlated between PSP subtypes, which supports the longitudinal clinical parallelism detected among them.

References: [1] G.U. Höglinger, G. Respondek, M. Stamelou, C. Kurz, K.A. Josephs, A.E. Lang, B. Mollenhauer, U. Müller, C. Nilsson, J.L. Whitwell, T. Arzberger, E. Englund, E. Gelpi, A. Giese, D.J. Irwin, W.G. Meissner, A. Pantelyat, A. Rajput, J.C. van Swieten, C. Troakes, A. Antonini, K.P. Bhatia, Y. Bordelon, Y. Compta, J.-C. Corvol, C. Colosimo, D.W. Dickson, R. Dodel, L. Ferguson, M. Grossman, J. Kassubek, F. Krismer, J. Levin, S. Lorenzl, H.R. Morris, P. Nestor, W.H. Oertel, W. Poewe, G. Rabinovici, J.B. Rowe, G.D. Schellenberg, K. Seppi, T. van Eimeren, G.K. Wenning, A.L. Boxer, L.I. Golbe, I. Litvan, Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria, Mov. Disord. 32 (2017) 853–864. doi:10.1002/mds.26987. [2] M. Grimm, G. Respondek, M. Stamelou, T. Arzberger, L. Ferguson, E. Gelpi, A. Giese, M. Grossman, D.J. Irwin, A. Pantelyat, A. Rajput, S. Roeber, J.C. Swieten, C. Troakes, A. Antonini, K.P. Bhatia, C. Colosimo, T. Eimeren, J. Kassubek, J. Levin, W.G. Meissner, C. Nilsson, W.H. Oertel, I. Piot, W. Poewe, G.K. Wenning, A. Boxer, L.I. Golbe, K.A. Josephs, I. Litvan, H.R. Morris, J.L. Whitwell, Y. Compta, J. Corvol, A.E. Lang, J.B. Rowe, G.U. Höglinger, How to apply the movement disorder society criteria for diagnosis of progressive supranuclear palsy, Mov. Disord. 34 (2019) 1228–1232. doi:10.1002/mds.27666.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-variants-of-psp-phenotypical-convergence-and-its-relationship-with-the-brain-glucose-metabolism/