Date: Monday, June 5, 2017
Session Title: Parkinsonism, MSA, PSP (Secondary and Parkinsonism-Plus)
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: To investigate whether the level of CSF Neurofilament Light Chain (NFL) can predict the speed of disease progression in patients with Progressive Supranuclear Palsy (PSP).
Background: Measuring clinical progression in neurodegenerative conditions is central to defining the effects of therapeutic intervention and disease biology. There is a need for reliable disease progression biomarkers to complement clinical rating scales such as the PSP rating scale (PSPRS). Predicting disease progression with such biomarkers may enable better powered clinical trials, and give insights into the mediators of progression. This study builds on recent work which has shown that serial measurements of CSF NFL can reliably track disease progression (1), whilst plasma NFL at baseline predicts the severity of subsequent progression (2).
Methods: A prospective cohort of 90 patients and 29 healthy controls were recruited from a single specialist Neurology centre between June 2011 and December 2013. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PSP (n=29), CBS (n=10), MSA (n=29), PD (n=5) and AD (n=17). Baseline NFL concentration was measured using standard enzyme-linked immunosorbent assay (ELISA). Patients were followed up longitudinally to obtain a total disease duration (date of disease onset to date of death/date of censoring). Survival was analysed using Kaplan-Meier survival and Cox regression analyses.
Results: As previously reported, the mean CSF NFL concentration was higher in the atypical parkinsonian syndrome group (PSP, CBS and MSA) vs PD, AD and healthy controls (2507.2ng/ml vs 1116.0ng/ml, 1429.9ng/ml and 630.6ng/ml). By dividing the PSP subjects into high and low CSF NFL groups based on the median CSF NFL concentration of 2217ng/ml, we found that the high CSF NFL group were over 5 times more likely to die during the monitored time period (hazard ratio 5.75, p = 0.02, 95% CI 1.35-24.43), when corrected for gender, age and disease duration at testing and disease severity at testing according to the baseline PSPRS score.
Conclusions: Our results suggest that baseline CSF NFL levels can predict future disease progression. Our aim is to replicate these findings in both CSF and plasma in a larger cohort using ultrasensitive methods of protein biomarker detection.
References: 1) Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 13, 676-685 (2014).
2) Rojas JC, Karydas A, Bang J, et al. Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol 3, 216-225 (2016).
To cite this abstract in AMA style:E. Jabbari, J. Woodside, H. Morris. Can the level of CSF Neurofilament Light Chain predict disease progression in Progressive Supranuclear Palsy? [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/can-the-level-of-csf-neurofilament-light-chain-predict-disease-progression-in-progressive-supranuclear-palsy/. Accessed December 11, 2023.
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