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

ABSTRACT: Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stroke and brain infarcts. During a follow-up of 3603 person-years, 133 (16.3%) individuals developed incident stroke, including ischemic and hemorrhagic. The HR (95%CI) of incident stroke was 1.28 (95%CI 1.10-1.50) per 1 standard deviation (SD) increase of log10 NfL serum levels. Compared to participants in the first tertile of NfL (i.e., lower levels), the risk of stroke was 1.68 times higher (95%CI 1.07-2.65) in those in the second tertile and 2.35 times higher (95%CI 1.45-3.81) in those in the third tertile of NfL. NfL levels were also positively associated with brain infarcts; 1-SD in log10 NfL levels was associated with 1.32 (95%CI 1.06-1.66) higher odds of one or more brain infarcts. These results suggest that NfL may serve as a biomarker of stroke in older adults.

SUBMITTER: Dhana A

PROVIDER: S-EPMC10081967 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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

Dhana Anisa A DeCarli Charles C Aggarwal Neelum T NT Dhana Klodian K Desai Pankaja P Evans Denis A DA Rajan Kumar B KB

European journal of epidemiology 20230303 4

Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stro ...[more]

PMID: 36867286

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Project description:ObjectivesPatients with minor ischemic stroke (MIS) frequently suffer from early neurological deterioration (END) and become disabled. Our study aimed to explore the association between serum neurofilament light chain (sNfL) levels and END in patients with MIS.MethodsWe conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score 0-3] admitted within 24 h from the onset of symptoms. sNfL levels were measured at admission. The primary outcome was END, defined as an increase in the NIHSS score by ≥2 points within 5 days after admission. Univariate and multivariate analyses were performed to explore the risk factors associated with END. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between sNfL levels and END.ResultsA total of 152 patients with MIS were enrolled, of which 24 (15.8%) developed END. The median sNfL level was 63.1 [interquartile range (IQR), 51.2-83.4] pg/ml on admission, which was significantly higher than that of 40 age- and sex-matched healthy controls (median 47.6, IQR 40.8-56.1 pg/ml; p < 0.001). Patients with MIS with END had a higher level of sNfL (with ND: median 74.1, IQR 59.5-89.8 pg/ml; without END: median 61.2, IQR 50.5-82.2 pg/ml; p = 0.026). After adjusting for age, baseline NIHSS score, and potential confounding factors in multivariate analyses, an elevated sNfL level (per 10 pg/mL) was associated with an increased risk of END [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.04-1.77; p = 0.027). Stratified analyses and interaction tests demonstrated that the association between sNfL and END did not change by age group, sex, baseline NIHSS score, Fazekas' rating scale, hypertension, diabetes mellitus, intravenous thrombolysis, and dual antiplatelet therapy in patients with MIS (all p for interaction > 0.05). END was associated with an increased risk of unfavorable outcomes (modified Rankin scale score ranging from 3 to 6) at 3 months.ConclusionEarly neurological deterioration is common in minor ischemic stroke and is associated with poor prognosis. The elevated sNfL level was associated with an increased risk of early neurological deterioration in patients with minor ischemic stroke. sNfL might be a promising biomarker candidate that can help to identify patients with minor ischemic stroke at high risk of neurological deterioration, for reaching individual therapeutic decisions in clinical practice.

Project description:ImportanceUnrecognized demyelinating events often precede the clinical onset of multiple sclerosis (MS). Identification of these events at the time of occurrence would have implications for early diagnosis and the search of causal factors for the disease.ObjectiveTo assess whether serum neurofilament light chain (sNfL) levels are elevated before the clinical MS onset.Design, setting, and participantsNested case-control study among US military personnel who have serum samples stored in the US Department of Defense Serum Repository. Serum samples were collected from 2000 to 2011; sNfL assays and data analyses were performed from 2018 to 2019. We selected 60 case patients with MS who either had 2 samples collected before onset (mean follow-up, 6.3 years) or 1 sample collected before and 1 after onset (mean follow-up, 1.3 years), among 245 previously identified case patients. For each case, we randomly selected 1 of 2 previously identified control individuals matched by age, sex, race/ethnicity, and dates of sample collection. The sample size was chosen based on the available funding.ExposuresSerum NfL concentrations measured using an ultrasensitive single-molecule array assay (Simoa).Main outcomes and measurementsLog-transformed sNfL concentrations in case patients and control individuals compared using conditional logistic regression and linear mixed models.ResultsMean age at baseline was 27.5 years, and 92 of 120 participants (76.7%) were men. Serum NfL levels were higher in case patients with MS compared with their matched control individuals in samples drawn a median of 6 years (range, 4-10 years) before the clinical onset (median, 16.7 pg/mL; interquartile range [IQR], 12.6-23.1 pg/mL vs 15.2 pg/m; IQR, 10.3-19.9 pg/mL; P = .04). This difference increased with decreasing time to the case clinical onset (estimated coefficient for interaction with time = 0.063; P = .008). A within-person increase in presymptomatic sNfL levels was associated with higher MS risk (rate ratio for ≥5 pg/mL increase, 7.50; 95% CI, 1.72-32.80). The clinical onset was associated with a marked increase in sNfL levels (median, 25.0; IQR, 17.1-41.3 vs 45.1; IQR, 27.0-102.7 pg/mL for presymptomatic and postonset MS samples; P = .009).Conclusions and relevanceThe levels of sNfL were increased 6 years before the clinical MS onset, indicating that MS may have a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.

Project description:ImportancePrognostication of neurologic outcome after cardiac arrest is an important but challenging aspect of patient therapy management in critical care units.ObjectiveTo determine whether serum neurofilament light chain (NFL) levels can be used for prognostication of neurologic outcome after cardiac arrest.Design, setting and participantsProspective clinical biobank study of data from the randomized Target Temperature Management After Cardiac Arrest trial, an international, multicenter study with 29 participating sites. Patients were included between November 11, 2010, and January 10, 2013. Serum NFL levels were analyzed between August 1 and August 23, 2017, after trial completion. A total of 782 unconscious patients with out-of-hospital cardiac arrest of presumed cardiac origin were eligible.ExposuresSerum NFL concentrations analyzed at 24, 48, and 72 hours after cardiac arrest with an ultrasensitive immunoassay.Main outcomes and measuresPoor neurologic outcome at 6-month follow-up, defined according to the Cerebral Performance Category Scale as cerebral performance category 3 (severe cerebral disability), 4 (coma), or 5 (brain death).ResultsOf 782 eligible patients, 65 patients (8.3%) were excluded because of issues with aliquoting, missing sampling, missing outcome, or transport problems of samples. Of the 717 patients included (91.7%), 580 were men (80.9%) and median (interquartile range [IQR]) age was 65 (56-73) years. A total of 360 patients (50.2%) had poor neurologic outcome at 6 months. Median (IQR) serum NFL level was significantly increased in the patients with poor outcome vs good outcome at 24 hours (1426 [299-3577] vs 37 [20-70] pg/mL), 48 hours (3240 [623-8271] vs 46 [26-101] pg/mL), and 72 hours (3344 [845-7838] vs 54 [30-122] pg/mL) (P < .001 at all time points), with high overall performance (area under the curve, 0.94-0.95) and high sensitivities at high specificities (eg, 69% sensitivity with 98% specificity at 24 hours). Serum NFL levels had significantly greater performance than the other biochemical serum markers (ie, tau, neuron-specific enolase, and S100). At comparable specificities, serum NFL levels had greater sensitivity for poor outcome compared with routine electroencephalogram, somatosensory-evoked potentials, head computed tomography, and both pupillary and corneal reflexes (ranging from 29.2% to 49.0% greater for serum NFL level).Conclusions and relevanceFindings from this study suggest that the serum NFL level is a highly predictive marker of long-term poor neurologic outcome at 24 hours after cardiac arrest and may be a useful complement to currently available neurologic prognostication methods.

Dataset Information

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

Publications

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

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