Objective:

Background:

Markers of neuronal and glial injury have been adapted for monitoring disease activity and injury in individuals with neurodegenerative and neuroinflammatory disorders. There are currently no biomarkers that inform on disease activity, prognosis, and treatment in NS.

Design/Methods:

This is a prospective, observational study to study biomarkers of inflammation and neuronal injury with associated clinical outcome measures in patients with NS. Plasma concentrations of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, Ubiquitin carboxy-terminal hydrolase L1 (UCHL-1) in patients with NS (Possible, probable, and definite) and healthy controls (HC) using Quanterix SIMOA were evaluated. Ongoing collection and statistical analysis will aim to report longitudinal analysis correlated with clinical progression. 

Results:

To date, plasma from 16 NS patients  has been collected; age(x ̅=55.8 SD=8.3) percent female(50.0%). Cross-sectional analysis of 8 plasma based samples from patients with NS shows a mean plasma concentrations of NfL, GFAP, and UCH-L1 were elevated in  NS patients compared to HCs of similar sex and age distribution (n=8 NS; 8 HC): NFL (26.4 v. 4.3 pg/ml, p = 0.0030 ), GFAP (137.4 v. 32.5 pg/ml, p < 0.0002 ), UCH-L1 (26.1 v. 5.0 pg/mL, p = 0.0030). Plasma tau levels were not different (1.9 v. 2.9 pg/mL, p = 0.1304). In NS patients CSF concentrations were as follows: NfL (x ̅=4252.8 pg/ml; SD=5625.1), GFAP (x ̅=10289.9 pg/ml; SD=4125.6), UCH-L1 (x ̅=2667.5 pg/ml; SD=1425.3), tau (x ̅=52.8 pg/ml; SD=22.9). Ongoing longitudinal analysis correlating to clinical outcome measures include modified Rankin Scale and Expanded Disability Status Scale.

Conclusions:

Preliminary results show plasma NfL, GFAP, and UCHL-1 levels are elevated in NS at the time of their disease onset. Additional inflammatory markers with cytokine analysis and longitudinal studies to correlate biomarkers for disease progression are ongoing.