Combined CSF α-SYN RT-QuIC, CSF NFL and midbrain-pons planimetry in degenerative parkinsonisms: From bedside to bench, and back again.

Introduction Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs: multiple system atrophy[MSA], progressive supranuclear palsy[PSP], corticobasal degeneration[CBD]) remains challenging. Lately, cerebrospinal fluid (CSF) studies of neurofilament light-chain (N...

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Authors: Compta, Yaroslau, Painous Martí, Cèlia, Soto Gimeno, Marta, Pulido Salgado, Marta, Fernández Sánchez, Manel, Cámara Lorenzo, Ana, Sánchez, V., Bargalló Alabart, Núria, Caballol, Núria, Pont-Sunyer, Claustre, Buongiorno, Maria Teresa, Martín, Nuria, Basora Macaya, Misericordia, Tió, Montserrat, Giraldo, Darly M., Pérez Soriano, Alexandra, Zaro, I., Muñoz, Esteban, Martí Domènech, Ma. Josep, Valldeoriola Serra, Francesc
Format: article
Status:Versión aceptada para publicación
Publication Date:2022
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/228015
Online Access:https://hdl.handle.net/2445/228015
Access Level:Open access
Keyword:Imatges per ressonància magnètica
Malaltia de Parkinson
Marcadors bioquímics
Líquid cefalorraquidi
Magnetic resonance imaging
Parkinson's disease
Biochemical markers
Cerebrospinal fluid
Description
Summary:Introduction Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs: multiple system atrophy[MSA], progressive supranuclear palsy[PSP], corticobasal degeneration[CBD]) remains challenging. Lately, cerebrospinal fluid (CSF) studies of neurofilament light-chain (NFL) and RT-QuIC of alpha-synuclein (α-SYN) have shown promise, but data on their combination with MRI measures is lacking. Objective (1) to assess the combined diagnostic ability of CSF RT-QuIC α-SYN, CSF NFL and midbrain/pons MRI planimetry in degenerative parkinsonisms; (2) to evaluate if biomarker-signatures relate to clinical diagnoses and whether or not unexpected findings can guide diagnostic revision. Methods We collected demographic and clinical data and set up α-SYN RT-QuIC at our lab in a cross-sectional cohort of 112 participants: 19 control subjects (CSs), 20PD, 37MSA, 23PSP, and 13CBD cases. We also determined CSF NFL by ELISA and, in 74 participants (10CSs, 9PD, 26MSA, 19PSP, 10CBD), automatized planimetric midbrain/pons areas from 3T-MRI. Results Sensitivity of α-SYN RT-QuIC for PD was 75% increasing to 81% after revisiting clinical diagnoses with aid of biomarkers. Sensitivity for MSA was 12% but decreased to 9% with diagnostic revision. Specificities were 100% against CSs, and 89% against tauopathies raising to 91% with diagnostic revision. CSF NFL was significantly higher in APs. The combination of biomarkers yielded high diagnostic accuracy (PD vs. non-PD AUC = 0.983; MSA vs. non-MSA AUC = 0.933; tauopathies vs. non-tauopathies AUC = 0.924). Biomarkers-signatures fitted in most cases with clinical classification. Conclusions The combination of CSF NFL, CSF RT-QuIC α-SYN and midbrain/pons MRI measures showed high discriminant ability across all groups. Results opposite to expected can assist diagnostic reclassification.

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