Magnetic Resonance Imaging and Neurofilament Light in the Differentiation of Parkinsonism

Derek B Archer; Trina Mitchell; Roxana G Burciu; Jing Yang; Salvatore Nigro; Aldo Quattrone; Andrea Quattrone; Andreas Jeromin; Nikolaus R McFarland; Michael S Okun; David E Vaillancourt

doi:10.1002/mds.28060

Magnetic Resonance Imaging and Neurofilament Light in the Differentiation of Parkinsonism

Mov Disord. 2020 Aug;35(8):1388-1395. doi: 10.1002/mds.28060. Epub 2020 May 1.

Authors

Derek B Archer¹, Trina Mitchell¹, Roxana G Burciu², Jing Yang³, Salvatore Nigro⁴, Aldo Quattrone^{4

5}, Andrea Quattrone⁶, Andreas Jeromin⁷, Nikolaus R McFarland^{8

9}, Michael S Okun^{8

9

10}, David E Vaillancourt^{1

8

9

11}

Affiliations

¹ Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
² Department of Kinesiology and Applied Physiology, College of Health Sciences, University of Delaware, Newark, Delaware, USA.
³ Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
⁴ Neuroscience Centre, Magna Graecia University, Catanzaro, Italy.
⁵ Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy.
⁶ Institute of Neurology, Department of Medical Sciences, Magna Graecia University, Catanzaro, Italy.
⁷ Quanterix, Corporation, Lexington, Massachusetts, USA.
⁸ Fixel Institute for Neurological Disease, College of Medicine, University of Florida, Gainesville, Florida, USA.
⁹ Department of Neurology, University of Florida, McKnight Brain Institute, Gainesville, Florida, USA.
¹⁰ Department of Neurosurgery, University of Florida, McKnight Brain Institute, Gainesville, Florida, USA.
¹¹ J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA.

Abstract

Objective: Accurate diagnosis is particularly challenging in Parkinson's disease (PD), multiple system atrophy (MSAp), and progressive supranuclear palsy (PSP). We compare the utility of 3 promising biomarkers to differentiate disease state and explain disease severity in parkinsonism: the Automated Imaging Differentiation in Parkinsonism (AID-P), the Magnetic Resonance Parkinsonism Index (MRPI), and plasma-based neurofilament light chain protein (NfL).

Methods: For each biomarker, the area under the curve (AUC) of receiver operating characteristic curves were quantified for PD versus MSAp/PSP and MSAp versus PSP and statistically compared. Unique combinations of variables were also assessed. Furthermore, each measures association with disease severity was determined using stepwise multiple regression.

Results: For PD versus MSAp/PSP, AID-P (AUC, 0.900) measures had higher AUC compared with NfL (AUC, 0.747) and MRPI (AUC, 0.669), P < 0.05. For MSAp versus PSP, AID-P (AUC, 0.889), and MRPI (AUC, 0.824) measures were greater than NfL (AUC, 0.537), P < 0.05. We then combined measures to determine if any unique combination provided enhanced accuracy and found that no combination performed better than the AID-P alone in differentiating parkinsonisms. Furthermore, we found that the AID-P demonstrated the highest association with the MDS-UPDRS (R_adj² -AID-P, 26.58%; NfL,15.12%; MRPI, 12.90%).

Conclusions: Compared with MRPI and NfL, AID-P provides the best overall differentiation of PD versus MSAp/PSP. Both AID-P and MRPI are effective in differentiating MSAp versus PSP. Furthermore, combining biomarkers did not improve classification of disease state compared with using AID-P alone. The findings demonstrate in the current sample that the AID-P and MRPI are robust biomarkers for PD, MSAp, and PSP. © 2020 International Parkinson and Movement Disorder Society.

Keywords: MRI; Parkinson's disease; multiple system atrophy; neurofilament light; progressive supranuclear palsy.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Diagnosis, Differential
Humans
Intermediate Filaments
Magnetic Resonance Imaging
Multiple System Atrophy* / diagnostic imaging
Parkinsonian Disorders* / diagnostic imaging
Supranuclear Palsy, Progressive* / diagnostic imaging

Abstract

Publication types

MeSH terms

Grants and funding