Association of admission serum levels of neurofilament light chain and in-hospital mortality in geriatric patients with COVID-19.
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ABSTRACT:
SUBMITTER: Marchegiani F
PROVIDER: S-EPMC9483416 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Association of admission serum levels of neurofilament light chain and in-hospital mortality in geriatric patients with COVID-19.
Marchegiani Francesca F Recchioni Rina R Marcheselli Fiorella F Di Rosa Mirko M Sabbatinelli Jacopo J Matacchione Giulia G Giuliani Angelica A Ramini Deborah D Stripoli Pierpaolo P Biscetti Leonardo L Pelliccioni Giuseppe G Sarzani Riccardo R Spannella Francesco F Cherubini Antonio A Corsonello Andrea A Procopio Antonio Domenico AD Bonfigli Anna Rita AR Bonafè Massimiliano M Lattanzio Fabrizia F Olivieri Fabiola F
Journal of neurology 20220916 1
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Project description:BackgroundThe aim was to evaluate the diagnostic potential of serum neurofilament light chain (sNfL) measurements in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).MethodssNfL levels were determined by single molecule array assay in a retrospective cross-sectional cohort of 144 patients with systemic lupus erythematosus (SLE). After log-transformation of sNfL levels, mean sNfL levels were compared between NPSLE patients and SLE patients without neuropsychiatric disease using Student's t test. Furthermore, the association of different neuropsychiatric manifestations with sNfL levels was assessed using a one-way analysis of variance (ANOVA) with post hoc analysis. Associations of sNfL with clinical and laboratory parameters were assessed by correlation and multiple linear regression analysis.ResultsNPSLE patients (n = 69) had significantly higher sNfL levels than SLE patients without neuropsychiatric disease manifestations (n = 75; mean difference: 0.13, 95% CI: 0.04-0.22, p = 0.006). With regard to the category of NPSLE manifestation, mean sNfL levels were only increased in NPSLE patients with focal central nervous system (CNS) involvement (n = 45; mean difference: 0.16, 95% CI: 0.02-0.30, p = 0.019), whereas mean sNfL levels of NPSLE patients with diffuse CNS and peripheral nervous system involvement did not differ from those of SLE patients without neuropsychiatric manifestations. Age and serum creatinine concentrations were identified as relevant contributors to sNfL levels.ConclusionsNfL is a promising, easily accessible biomarker for neuropsychiatric involvement in SLE patients and might therefore complement the diagnostic workup of SLE patients with suspected involvement of the nervous system.
| S-EPMC8543555 | biostudies-literature
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.
| S-EPMC6745051 | biostudies-literature
Project description:Background and purposeNeurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment.MethodsUsing a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]).ResultsSerum NfL levels were elevated in both SVD samples (P<1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R2=0.52, P=1.2e-09; sporadic SVD, R2=0.21, P<1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R2=0.27, P=7.6e-05; sporadic SVD, R2=0.06, P=4.8e-08), focal neurological symptoms (CADASIL, NIHSS, P=4.2e-05) and disability (CADASIL, mRS, P=3.0e-06).ConclusionsWe found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.
| S-EPMC6007291 | biostudies-literature
Project description:BackgroundBoth frailty and elevated serum neurofilament light chain (sNfL) levels are linked to cognitive impairment. However, evidence of their relationship is lacking, and whether it was mediated by renal function was unknown. This study aimed to investigate the association between frailty and sNfL levels in a representative U.S. population, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship.MethodsData from 1,782 participants aged 20-75 years in the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed. Frailty was assessed using a 49-item frailty index, and participants were categorized as non-frail, pre-frail, or frail. sNfL levels were measured using acoustic emission technology. Multivariable linear regression models and restricted cubic spline analyses were employed to examine the associations between frailty, eGFR, and sNfL levels. Mediation analysis was conducted to evaluate the role of eGFR in the frailty-sNfL relationship.ResultsThe prevalence of pre-frailty and frailty was 45.39 and 11.60%, respectively. A significant positive association was observed between frailty score and sNfL levels (adjusted β: 39.97, SE: 11.07, p = 0.003), with a linear relationship confirmed by restricted cubic spline analysis. Frail individuals had significantly higher sNfL levels compared to non-frail participants (adjusted β: 11.86, SE: 5.42, p = 0.04). eGFR was negatively associated with sNfL levels (adjusted β: -0.23, SE: 0.05, p < 0.001). Mediation analysis revealed that eGFR accounted for 12.52% of the total effect of frailty on sNfL levels (p < 0.0001).ConclusionThis study demonstrates a significant association between frailty and elevated sNfL levels in a representative U.S. population, with eGFR partially mediating this relationship. These findings suggest that sNfL may serve as a potential biomarker for frailty-related neuronal damage and highlight the importance of kidney function in this association. Further research is warranted to explore the clinical implications of these findings in frailty assessment and management strategies.
| S-EPMC11502322 | biostudies-literature
Project description:BackgroundSerum neurofilament light chain (sNfL) is a biomarker for neuro-axonal injury.ObjectivesTo assess sNfL's utility as a diagnostic marker for Lyme neuroborreliosis (LNB).MethodsWe compared serum and CSF NfL levels in LNB patients and age-matched controls. Age-adjusted NfL values were used in receiver operating characteristic (ROC) analysis.DesignRetrospective cohort study.ResultsEighty-six patients (30 LNB, 29 with-, and 27 without neurological disorders) were included. Compared to individuals without neurological disease, LNB patients showed increased serum (median (interquartile range, IQR): 36.3 pg/ml (19.3-112.0) vs 20 pg/ml (12.9-37.3), p < 0.001) and CSF NfL levels (median (IQR): 1000.0 pg/ml (286.0-6471.0) vs 182 pg/ml (99.3-474.0), p < 0.001). NfL concentrations were similar in LNB and other neurological disorders. ROC analysis of age-adjusted sNfL and CSF NfL levels showed areas under the curve of 0.78 (95% confidence interval (CI): 0.66-0.89) and 0.83 (95% CI: 0.71-0.94), respectively.ConclusionsNfL concentrations lack sufficient diagnostic capability for LNB diagnosis.
| S-EPMC11752212 | biostudies-literature
Project description:ObjectiveGiven the continued spread of coronavirus 2, the early predictors of coronavirus disease 19 (COVID-19) associated mortality might improve patients' outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuronal injury, have been observed in severe COVID-19 patients. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality.MethodsWe measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID-19 patients.ResultsIn cohort 1, we found significantly elevated NfL levels only in critically ill COVID-19 patients. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following the two other prognostic markers of COVID-19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between ALC and LDH abnormalities and subsequent rise of NfL implicate that the multi-organ failure is the most likely cause of neuronal injury in severe COVID-19 patients. The addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3.InterpretationA substantial increase in serum/plasma NfL reproducibly enhanced COVID-19 mortality prediction. Combined with other prognostic markers, such as ALC and LDH that are routinely measured in ICU patients, NfL measurements might be useful to identify the patients at a high risk of COVID-19-associated mortality, who might still benefit from escalated care.
| S-EPMC9082006 | biostudies-literature
Project description:Given the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), early predictors of coronavirus disease 19 (COVID-19) mortality might improve patients’ outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuro-axonal injury, have been observed in patients with severe COVID-19. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality. We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID-19 patients. In cohort 1, we found significantly elevated NfL levels only in critically ill COVID-19 patients compared to healthy controls. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following two other prognostic markers of COVID-19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between LDH and ALC abnormalities and subsequent rise of NfL implicate multi-organ failure as a likely cause of neuronal injury at the later stages of COVID-19. Addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. In conclusion, although substantial increase in serum/plasma NfL reproducibly enhances COVID-19 mortality prediction, NfL has clinically meaningful prognostic value only close to death, which may be too late to alter medical management. When combined with other prognostic biomarkers, rising longitudinal NfL measurements triggered by LDH and ALC abnormalities would identify patients at risk of COVID-19 associated mortality who might still benefit from escalated care.
| S-EPMC8786234 | biostudies-literature
Project description:Background and aimsPatients infected with SARS-CoV-2 range from asymptomatic, to mild, moderate or severe disease evolution including fatal outcome. Thus, early predictors of clinical outcome are highly needed. We investigated markers of neural tissue damage as a possible early sign of multisystem involvement to assess their clinical prognostic value on survival or transfer to intensive care unit (ICU).MethodsWe collected blood from 104 patients infected with SARS-CoV-2 the day of admission to the emergency room and measured blood neurofilament light chair (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and total tau protein levels.ResultsWe found that NfL, GFAP, and tau were significantly increased in patients with fatal outcome, while NfL and UCH-L1 in those needing ICU transfer. ROC and Kaplan-Meier curves indicated that total tau levels at admission accurately predict mortality.ConclusionsBlood neural markers may provide additional prognostic value to conventional biomarkers used to predict COVID-19 outcome.
| S-EPMC8108733 | biostudies-literature
Project description:ObjectiveTo assess the value of annual serum neurofilament light (NfL) measures in predicting 10-year clinical and MRI outcomes in multiple sclerosis (MS).MethodsWe identified patients in our center's Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study enrolled within 5 years of disease onset, and with annual blood samples up to 10 years (n = 122). Serum NfL was measured using a single molecule array (SIMOA) assay. An automated pipeline quantified brain T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) from year 10 high-resolution 3T MRI scans. Correlations between averaged annual NfL and 10-year clinical/MRI outcomes were assessed using Spearman's correlation, univariate, and multivariate linear regression models.ResultsAveraged annual NfL values were negatively associated with year 10 BPF, which included averaged year 1-5 NfL values (unadjusted P < 0.01; adjusted analysis P < 0.01), and averaged values through year 10. Linear regression analyses of averaged annual NfL values showed multiple associations with T2LV, specifically averaged year 1-5 NfL (unadjusted P < 0.01; adjusted analysis P < 0.01). Approximately 15-20% of the BPF variance and T2LV could be predicted from early averaged annual NfL levels. Also, averaged annual NfL levels with fatigue score worsening between years 1 and 10 showed statistically significant associations. However, averaged NfL measurements were not associated with year 10 EDSS, SDMT or T25FW in this cohort.InterpretationSerum NfL measured during the first few years after the clinical onset of MS contributed to the prediction of 10-year MRI brain lesion load and atrophy.
| S-EPMC6292183 | biostudies-literature
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.
| S-EPMC10034185 | biostudies-literature