Magnetic Resonance Imaging and Neurofilament Light in the Differentiation of Parkinsonism

Abstract

A BS TRACT: 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 adj 2-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.

TAF1 Transcripts and Neurofilament Light Chain as Biomarkers for X‐linked Dystonia‐Parkinsonism

“…Our results are consistent with the knowledge that XDP is a disease of basal ganglia neurodegeneration 1‐4,9 . This adds XDP to the list of atypical parkinsonian syndromes with increased plasma NfL 24,29,30 …”

“…[1][2][3][4]9 This adds XDP to the list of atypical parkinsonian syndromes with increased plasma NfL. 24,29,30 Although NfL may be a nonspecific biomarker of neurodegeneration in XDP, it may still be useful in monitoring disease onset and progression in presymptomatic and symptomatic patients under therapeutic treatment. TAF1 dysregulation acts as a disease-specific biomarker that makes it an attractive readout for target engagement by new therapies, particularly those targeting TAF1 expression and splicing regulation.…”

“…23,28 Specifically, it has been shown to be useful in the differential diagnoses of parkinsonian disorders. 24,29,30 Clinically, XDP is diagnosed in patients with signs of dystonia and parkinsonism who have a positive history of affected relatives and maternal ancestry from Panay island. 2 Cell-based and biofluid-based disease-specific biomarkers will be needed to understand disease mechanisms, predict progression, and serve as noninvasive readouts for novel therapeutics.…”

“…Through the development of a highly sensitive fourth‐generation single molecule array, SiMoA (Quanterix Corporation, Billerica, MA), for detection in blood, 27,28 NfL has been reported in different neurodegenerative diseases as a blood‐based biomarker correlating with disease status, progression, and outcomes in different neurological diseases 23,28 . Specifically, it has been shown to be useful in the differential diagnoses of parkinsonian disorders 24,29,30 …”

Differentiating PSP from MSA using MR planimetric measurements: a systematic review and meta-analysis

“…For the M/P, overall sensitivity and specificity reached 84.1% (95% CI 77.2-89.2%) and 89.2% (95% CI 81.8-93.8%), respectively, with a positive LR of 8.13 (median 7.76, 95% CI 4.390-14.00), a negative LR of 0.183 (median 0.179; 95% CI 0.118-0.269), and a DOR of 48.700 (median 43.50; 95% CI 17.200-110.00). In detail, all of the included studies (Oba et al 2005;Archer et al 2020;Mangesius et al 2018;Möller et al 2017;Sjöström et al 2020;Sakamoto et al 2020;Quattrone et al 2008;Constantinides et al 2018) assessed the MRPI and M/P in clinically diagnosed PSP or MSA, which likely overestimates the sensitivity of the diagnostic test by excluding patients with suspected disease but an unconfirmed diagnosis (i.e. difficult-to-diagnose patients, QUA-DAS-2 signalling question for inappropriate exclusion (Whiting et al 2011)).…”