Serum neurofilament light chain levels are correlated with the infarct volume in patients with acute ischemic stroke

June Woo Ahn, Jaechun Hwang, Myunghoon Lee, Jae Hyoung Kim, Hee-Jin Cho, Ho-Won Lee, Mi-Yeon Eun, June Woo Ahn, Jaechun Hwang, Myunghoon Lee, Jae Hyoung Kim, Hee-Jin Cho, Ho-Won Lee, Mi-Yeon Eun

Abstract

Neurofilament light chains (NfLs) are promising biomarkers of neuroaxonal damage in stroke patients. We investigated the correlations between NfL levels and infarct volume, initial stroke severity, and functional outcomes at discharge in patients with acute ischemic stroke. We prospectively included 15 patients with first-ever acute ischemic stroke and 8 age- and sex-matched healthy controls without other neurological disorders. Serum NfL levels were measured using the single-molecule array (Simoa) technique twice within 24 hours of admission (NfL1D) and on the seventh hospital day (NfL7D) in patients with stroke and once in healthy controls. We assessed the infarct volume on diffusion-weighted magnetic resonance imaging using the free software ITK-SNAP. Serum NfL1D levels in stroke patients were significantly higher (28.4 pg/mL; interquartile range [IQR], 43.0) than in healthy controls (14.5 pg/mL; IQR, 3.2; P = .005). Temporal pattern analyses demonstrated that NfL7D levels were increased (114.0 pg/mL; IQR, 109.6) compared to NfL1D levels in all stroke patients (P = .001). There was a strong correlation between NfL7D levels and infarct volume (R = 0.67, P = .007). The difference between NfL1D and NfL7D (NfLdiff levels) was strongly correlated with the infarct volume (R = 0.63; P = .013). However, there was no statistically significant correlation between NfL levels and the initial stroke severity or functional outcomes at discharge. NfL levels in the subacute stage of stroke and the NfL difference between admission and 7th day of hospital were correlated with infarct volume in patients with acute ischemic stroke.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1.
Figure 1.
Selection of patient population with acute ischemic stroke.
Figure 2.
Figure 2.
Serum NfL levels in the study population. (A) NfL levels in healthy controls and patients with acute ischemic stroke (HD 1 and HD 7) using the Mann–Whitney U-test. (B) Temporal pattern of NfL levels in every patient using the Wilcoxon signed-rank test. HD = hospital day, NfL = neurofilament light chain, NfLHC = neurofilament light chain in healthy controls, NfL1D = neurofilament light chain within 24 h of admission in patients, NfL7D = neurofilament light chain on the seventh hospital day.
Figure 3.
Figure 3.
Correlation between serum NfL levels and infarct volume, initial NIHSS score, and discharge mRS. Analysis was conducted using Spearman rank correlation analysis. * means P < .05; ** means P < .01; *** means P < .001. NfL = neurofilament light chain, NIHSS = National Institutes of Health Stroke Scale, mRS = modified rankin scale.

References

    1. Gaetani L, Blennow K, Calabresi P, et al. . Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90:870–81.
    1. Yuan A, Nixon RA. Neurofilament proteins as biomarkers to monitor neurological diseases and the efficacy of therapies. Front Neurosci. 2021;15:689938.
    1. Lewczuk P, Ermann N, Andreasson U, et al. . Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther. 2018;10:71.
    1. Thebault S, Abdoli M, Fereshtehnejad SM, et al. . Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Sci Rep. 2020;10:10381.
    1. Verde F, Steinacker P, Weishaupt JH, et al. . Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2019;90:157–64.
    1. Shahim P, Politis A, van der Merwe A, et al. . Neurofilament light as a biomarker in traumatic brain injury. Neurology. 2020;95:e610–e22.
    1. De Marchis GM, Katan M, Barro C, et al. . Serum neurofilament light chain in patients with acute cerebrovascular events. Eur J Neurol. 2018;25:562–8.
    1. Onatsu J, Vanninen R, Jakala P, et al. . Serum neurofilament light chain concentration correlates with infarct volume but not prognosis in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2019;28:2242–9.
    1. Pedersen A, Stanne TM, Nilsson S, et al. . Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction. J Neurol. 2019;266:2796–806.
    1. Tiedt S, Duering M, Barro C, et al. . Serum neurofilament light: a biomarker of neuroaxonal injury after ischemic stroke. Neurology. 2018;91:e1338–e47.
    1. Nielsen HH, Soares CB, Hogedal SS, et al. . Acute neurofilament light chain plasma levels correlate with stroke severity and clinical outcome in ischemic stroke patients. Front Neurol. 2020;11:448.
    1. Uphaus T, Bittner S, Groschel S, et al. . NfL (neurofilament light chain) levels as a predictive marker for long-term outcome after ischemic stroke. Stroke. 2019;50:3077–84.
    1. Yushkevich PA, Piven J, Hazlett HC, et al. . User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability. Neuroimage. 2006;31:1116–28.
    1. Peng Y, Li Q, Qin L, et al. . Combination of serum neurofilament light chain levels and MRI markers to predict cognitive function in ischemic stroke. Neurorehabil Neural Repair. 2021;35:247–55.
    1. Traenka C, Disanto G, Seiffge DJ, et al. . Serum neurofilament light chain levels are associated with clinical characteristics and outcome in patients with cervical artery dissection. Cerebrovasc Dis. 2015;40:222–7.
    1. Gattringer T, Pinter D, Enzinger C, et al. . Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology. 2017;89:2108–14.
    1. Jayaraj RL, Azimullah S, Beiram R, Jalal FY, et al. . Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation. 2019;16:142.
    1. Kuhle J, Barro C, Andreasson U, et al. . Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med. 2016;54:1655–61.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다