Barcelona Progressive Supranuclear Palsy (PSP) Registry: Clinical, Oculomotor, and Cerebrospinal Fluid Markers; from Suggestive to Definite Cases.

BACKGROUND

Timely and accurate diagnosis of progressive supranuclear palsy (PSP) remains challenging.

OBJECTIVE

To assess diagnostic certainty and progression biomarkers in the PSP spectrum from "suggestive of" (so-PSP) category as proxy of early disease, to definite (neuropathologically confirmed) cases.

METHODS

Multicenter, prospective, longitudinal study of 131 participants (so-PSP, n = 23; definite, n = 5) with oculometric (n = 47) and cerebrospinal fluid (CSF) biomarkers (n = 75), compared with control (n = 18) and Parkinson's disease (PD) subjects (n = 12).

RESULTS

Anti-saccade velocities were significantly reduced in so-PSP versus PD and controls. CSF α-synuclein seed amplification assay (asyn-SAA) was positive in 20% of PSP cases (vs. 100% PD and 0% controls). Longitudinally (median of 1.3 years), all probable/possible-PSP cases retained their diagnosis regardless of CSF asyn-SAA result. In so-PSP, worse saccades' variables and negative/low-fluorescence-positive asyn-SAA at baseline related to longitudinal diagnosis reinforcement. Clinical scales and neurofilament light chain (NfL) predicted shorter survival.

CONCLUSIONS

Quantitative oculometry and negative/low-fluorescence-positive CSF asyn-SAA predict diagnostic validation in so-PSP. In probable/possible-PSP, positive CSF asyn-SAA may suggest copathology, although confirmation requires larger pathological studies. © 2025 International Parkinson and Movement Disorder Society.