Serum neurofilament light is sensitive to active cerebral small vessel disease

Abstract

Objective: To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.

Methods: In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.

Results: Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1-11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)-related lesions at follow-up.

Conclusions: Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

© 2017 American Academy of Neurology.

Figures

Figure 1. Correlation between baseline serum NfL levels and duration between stroke symptom onset and blood sampling (rs = 0.51, p < 0.0001)

NfL = neurofilament light chain protein.

Figure 2. Longitudinal dynamics of serum NfL levels for 49 patients with RSSI with available data for all 3 time points

IQR = interquartile range; NfL = neurofilament light chain protein; RSSI = recent small subcortical infarct.

Figure 3. Serial MRI scans of a patient with CSVD-related lesions at both follow-up scans

(A) Index RSSI at baseline (red arrow), which evolved into a lacune at the 3-month follow-up MRI (B, H, green arrow) and remained unchanged at 15 months (C, I, green arrow). On the 3-month follow-up MRI, the patient had a newly evolved lacunar infarct in the left centrum semiovale (green arrow, E), which was not present at baseline (D). Two more lacunar lesions in the right centrum semiovale (F, white arrow) and right periventricular region (I, white arrow) occurred between the first and second follow-ups at 15 months. Note that panel A shows a diffusion-weighted MRI sequence, while all other panels (B–I) are fluid-attenuated inversion recovery scans. Newly evolved lesions at the 3-month follow-up are indicated by green arrows. Lesions that occurred between 3 and 15 months are indicated by white arrows. NfL levels in this patient were 212.34 (baseline), 676.59 (3-month follow-up), and 84.17 (15-month follow-up) pg/mL. CSVD = cerebral small vessel disease; RSSI = recent small subcortical infarct.