Neuropathological validation of the MDS-PSP criteria with PSP and other frontotemporal lobar degeneration

Gazzina, S.; Respondek, G.; Compta, Y.; Allinson, K. S.; Spillantini, M. G.; Molina-Porcel, L.; Guasp-Verdaguer, M.; Moftakhar, S.; Reich, S. G.; Hall, D.; Litvan, I.; Hoeglinger, G.; Rowe, J. B.

doi:10.1101/520510

bioRxiv · 10.1101/520510

Neuropathological validation of the MDS-PSP criteria with PSP and other frontotemporal lobar degeneration

Gazzina, S.·Respondek, G.·Compta, Y.·Allinson, K. S.·Spillantini, M. G.·Molina-Porcel, L.·Guasp-Verdaguer, M.·Moftakhar, S.·Reich, S. G.·Hall, D.·Litvan, I.·Hoeglinger, G.·Rowe, J. B.

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Abstract

BackgroundProgressive supranuclear palsy (PSP) is clinically heterogeneous. Clinical diagnostic criteria were revised in 2017, to increase sensitivity and operationalize the diagnosis of PSP Richardsons syndrome (PSP-RS) and \"variant\" syndromes (vPSP).\n\nObjectivesTo 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).\n\nMethodsRetrospective 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.\n\nResultsSensitivity 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.\n\nConclusionsThe 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.

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Gazzina, S., Respondek, G., Compta, Y., Allinson, K. S., Spillantini, M. G., Molina-Porcel, L., Guasp-Verdaguer, M., Moftakhar, S., Reich, S. G., Hall, D., Litvan, I., Hoeglinger, G., Rowe, J. B.. 2019-01-15. Neuropathological validation of the MDS-PSP criteria with PSP and other frontotemporal lobar degeneration. https://doi.org/10.1101/520510

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