Serum neurofilament light chain, brain infarcts, and the risk of stroke: a prospective population-based cohort study

Dhana, Anisa; DeCarli, Charles; Aggarwal, Neelum T.; Dhana, Klodian; Desai, Pankaja; Evans, Denis A.; Rajan, Kumar B.

doi:10.1007/s10654-023-00978-6

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…">NfL, a neuron‐specific cytoplasmic protein that is highly expressed in CNS myelinated axons. Plasma NfL levels rise promptly with cerebral infarction and arterial stenoses, including in small vessel disease 22,34,35 . Elevated levels may persist for more than 1 year following acute cerebral infarction 36 …”

Section: Methodsmentioning

confidence: 99%

“…19,20 Studies of blood-based brain biomarkers for cerebral infarcts in non-SCA adults, for example neurofilament light chain (NfL), have demonstrated their potential utility for detecting and prospectively tracking stroke-related brain injury, including by recent systemic review and metaanalysis. [22][23][24][25] Clinically, NfL is increasingly used for conditions of central nervous system (CNS) neuronal injury, although currently not infarcts. 26,27 Higher levels are associated with more severe brain injury.…”

Section: Introductionmentioning

confidence: 99%

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Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

et al. 2023

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SummaryCerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI‐MRA) in sub‐Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood‐based brain biomarkers of cerebral infarcts have been identified in non‐SCA adults. Using plasma samples from a well‐characterized cross‐sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI‐detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4‐plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron‐specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non‐SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI‐detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI‐detected infarcts after adjusting for sex and age. All non‐SCA controls and SCA participants lacking MRI‐detected infarcts had low NfL levels. These data suggest potential utility of plasma‐based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

et al. 2023

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Exploring the correlation between paediatric narcolepsy and serum neurofilament light chain levels: An exploratory study

Li,

Sun,

Chen

2024

European Journal of Paediatric Neurology

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Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation

Aulin,

Sjölin,

Lindbäck

et al. 2024

Circulation

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BACKGROUND: Biomarkers reflecting brain injury are not routinely used in risk assessment of stroke in atrial fibrillation (AF). Neurofilament light chain (NFL) is a novel biomarker released into blood after cerebral insults. We investigated the association between plasma concentrations of NFL, other biomarkers, and risk of stroke and death in patients with AF not receiving oral anticoagulation. METHODS: For this observational study, baseline plasma samples were available from 3077 patients with AF randomized to aspirin in ACTIVE A (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events; 2003 to 2008) and AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment; 2007 to 2009). Median follow-up was 1.5 years. NFL was analyzed with a Single Molecule Array (Simoa). Associations with outcomes (total stroke or systemic embolism, ischemic stroke, cardiovascular death, and all-cause death) were explored with Cox regression models. RESULTS: In the combined cohort, the median NFL level was 16.9 ng/L (interquartile range, 11.1–26.5 ng/L), the median age was 71 years, 58% were men, and 13% had a history of previous stroke. NFL was associated with older age, higher creatinine, lower body mass index, previous stroke, female sex, and diabetes but not cardiac rhythm. Higher NFL was associated with a higher risk of stroke or systemic embolism (n=206) independently of clinical characteristics (hazard ratio, 1.27 [95% CI, 1.10–1.46] per doubling of NFL) and other biomarkers (hazard ratio, 1.18 [95% CI, 1.01–1.37]) and including in patients without previous stroke (hazard ratio, 1.23 [95% CI, 1.02–1.48]). NFL was also independently associated with cardiovascular (n=219) and all-cause (n=311) death. The C index for stroke using only NFL was 0.642, on par with the currently used clinical risk scores. Addition of information on NFL improved discrimination in a model also including clinical information, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and high-sensitivity cardiac troponin T, yielding a C index of 0.727. CONCLUSIONS: NFL reflects overt and covert episodes of cerebral ischemia and improves risk assessment of stroke and death in patients with AF without oral anticoagulation, including in patients without previous stroke. The combination of NFL with information on age, history of stroke, and other biomarkers should be explored as a future avenue for stroke risk assessments in patients with AF.

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Serum neurofilament light chain, brain infarcts, and the risk of stroke: a prospective population-based cohort study

Cited by 5 publications

References 35 publications

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

Exploring the correlation between paediatric narcolepsy and serum neurofilament light chain levels: An exploratory study

Neurofilament Light Chain and Risk of Stroke in Patients With Atrial Fibrillation

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