Objective: (1) to assess the combined diagnostic ability of CSF NFL, CSF RT-QuIC α-SYN and midbrain/pons MRI measures in degenerative parkinsonisms; (2) to interpret results opposed to initial diagnosis and evaluate if biomarker-signatures can assist diagnostic reclassification.

Background: 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.

Method: 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. 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%, raising to 91%, against tauopathies. CSF NFL was significantly higher in APs. Combination of biomarkers provided a high diagnostic value (PD vs. non-PD AUC 0.983; MSA vs. non-MSA AUC 0.933; PSP vs. non-PSP AUC 0.924). Biomarkers-signatures fitted in most cases with clinical classification.

Conclusion: 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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MDS Abstracts - https://www.mdsabstracts.org/abstract/combined-csf-%ce%b1-syn-rt-quic-csf-nfl-and-midbrain-pons-planimetry-in-degenerative-parkinsonisms-from-bedside-to-bench-and-back-again/