ABSTRACT
Background Progressive supranuclear palsy (PSP) is clinically heterogeneous. Clinical diagnostic criteria were revised in 2017, to increase sensitivity and operationalize the diagnosis of PSP Richardson’s syndrome (PSP-RS) and “variant” syndromes (vPSP).
Objectives To determine the (1) sensitivity and specificity of the 1996 NINDS-SPSP and 2017 MDS-PSP criteria; (2) false positive rates in frontotemporal dementia with frontotemporal lobar degeneration (FTLD); and (3) clinical evolution of variant PSP syndromes (vPSP).
Methods Retrospective multicenter review of 108 neuropathologically-confirmed PSP patients and 81 patients with other forms of FTLD: 38 behavioral variant frontotemporal dementia (bvFTD), 14 non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), and 29 corticobasal degeneration (CBD), Sensitivity and specificity of the MDS-PSP criteria were compared to the NINDS-SPSP criteria at baseline. In a subset of cases, the timing and frequency of clinical features were compared across groups over six years.
Results Sensitivity for recognition of probable and possible PSP pathology was higher by MDS-PSP criteria (72.2-100%) than NINDS-SPSP criteria (48.1-61.1%). Specificity was higher by NINDS-SPSP criteria (97.5-100%) than MDS-PSP criteria (53.1-95.1%). False positives by MDS-PSP criteria were few for bvFTD (10.5-18.4%) but common for CBD and nfvPPA (fulfilling “suggestive of’ PSP). Most vPSP cases developed PSP-RS-like features within six years, including falls and supranuclear gaze palsy, distinguishing frontal presentations of PSP from bvFTD, and speech/language presentations of PSP from nfvPPA.
Conclusions The 2017 MDS-PSP criteria successfully identify PSP, including variant phenotypes. This independent validation of the revised clinical diagnostic criteria strengthens the case for novel therapeutic strategies against PSP to include variant presentations.
Footnotes
Financial disclosure/Conflict of interest: Nothing to declare
Funding sources: James B. Rowe is supported by the Wellcome Trust (103838). The Cambridge Brain bank is supported by the National Institute for Health Research Biomedical Research Centre. Günter Höglinger was funded by the Deutsche Forschungsgemeinschaft (DFG, HO2402/6-2 & Munich Cluster for Systems Neurology SyNergy). Yaroslau Compta was funded by the CERCA Programme of the Generalitat de Laura Molina-Porcel is supported by the “Fundació Marató de TV3” Grant (20141610). Irene Litvan research is supported by the US National Institutes of Health 5P50 AG005131-31, 5T35HL007491,1U01NS086659 and 1U54NS092089-01; Parkinson Study Group, Michael J Fox Foundation, AVID Pharmaceuticals, C2N Diagnostics/Abbvie and Bristol-Myers Squibb/Biogen. She was a member of the Abbvie advisory board, Biotie/Parkinson Study Group Medical Advisory Board, and Toyama Pharmaceuticals consultant. She receives her salary from the University of California San Diego and as Chief Editor of Frontiers in Neurology. Cases contributed were participants in the ENGENE-PSP study funded by US National Institutes of Health 5R01AG024040.
