Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults

Hviid, Claus Vinter Bødker; Knudsen, Cindy Soendersoe; Parkner, Tina

doi:10.1080/00365513.2020.1730434

Cited by 102 publications

(92 citation statements)

References 29 publications

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“…The TTM trial included patients without any age limit and included patients with a non-shockable initial rhythm, whereas the COMAC-ARE trial only included patients younger than 80 years, with a shockable initital rhythm and patients with time to ROSC less than 45 min. Moreover, in the current study we have used a new commercially available kit for measuring NfL, while the Moseby-Knappe study used a custom-made assay [27,28]. The AUROC values of NfL are very high at 24 h from CA.…”

Section: Discussionmentioning

confidence: 97%

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

et al. 2020

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Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO 2), arterial oxygen tension (PaO 2), and mean arterial pressure (MAP). Methods: We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1-2 and poor outcome as CPC 3-5. Results: Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11-31) pg/ml in patients with good outcome and 2343 (587-5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97-1.00) at 24 h, 0.98 (0.97-1.00) at 48 h, and 0.98 (0.95-1.00) at 72 h. NfL concentrations were lower in the higher MAP (80-100 mmHg) group than in the lower MAP (65-75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO 2 and PaO 2 targets did not associate with NfL levels. Conclusions: NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.

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Section: Discussionmentioning

confidence: 97%

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

et al. 2020

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“…Because the study group comprised participants aged 60 years and older, these findings are not necessarily generalizable to all age groups. The sample size of the HC group was underpowered to detect a correlation coefficient smaller than 0.4 and the age distribution was narrow due to the Japanese system of mandatory retirement at the age of 65 while previous studies reported the correlation coefficient between age and blood NfL to be 0.32-0.59 [30][31][32] . The association of blood NfL with renal function is confirmed in two distinct clinical groups, but the probability of confounding by comorbidities of diabetes such as peripheral neuropathy cannot be excluded, because we did not analyze the association with severities of comorbidities of diabetes in the DM group.…”

Section: Discussionmentioning

confidence: 99%

Renal function is associated with blood neurofilament light chain level in older adults

Akamine

Marutani

Kanayama

et al. 2020

Sci Rep

137

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Neurofilament light chain (NfL) is a novel biomarker of neurodegenerative diseases. It is detectable in the peripheral blood, allowing low-invasive assessment of early signs of neurodegeneration. The level of NfL gradually increases with age; however, what other factors affect it remains unclear. The present study examined the association between blood NfL level and renal function among healthy participants undergoing a health check (n = 43, serum NfL) and patients with diabetes mellitus (n = 188, plasma NfL). All participants were 60 years of age or older; none were diagnosed with dementia. In each group, levels of blood NfL and serum creatinine significantly correlated (coefficient r = 0.50, 0.56). These associations remained statistically significant even after adjustment for age, sex, and body mass index. These findings indicate that blood NfL level might be partially affected by renal function. We recommend measuring renal function for a more precise evaluation of neuroaxonal damage, in particular, among older adults.

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“…Ultimately, our study confirms the results of another study published just recently. In this reference sample study, the authors evaluated a subgroup of twelve serum samples for pre-analytical properties and found a stability of 95% for three-day storage at room temperature and 92% after three freeze-thaw cycles compared to standardized conditions 22 . www.nature.com/scientificreports/ It is exciting to notice an increase in research invested in the study of intrinsic factors influencing sNfL concentrations in health and disease.…”

Section: Discussionmentioning

confidence: 99%

Serum neurofilament light chain withstands delayed freezing and repeated thawing

Altmann

Leutmezer

Zach

et al. 2020

Sci Rep

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Serum neurofilament light chain (sNfL) and its ability to expose axonal damage in neurologic disorders have solicited a considerable amount of attention in blood biomarker research. Hence, with the proliferation of high-throughput assay technology, there is an imminent need to study the pre-analytical stability of this biomarker. We recruited 20 patients with common neurological diagnoses and 10 controls (i.e. patients without structural neurological disease). We investigated whether a variation in pre-analytical variables (delayed freezing up to 24 h and repeated thawing/freezing for up to three cycles) affects the measured sNfL concentrations using state of the art Simoa technology. Advanced statistical methods were applied to expose any relevant changes in sNfL concentration due to different storing and processing conditions. We found that sNfL concentrations remained stable when samples were frozen within 24 h (mean absolute difference 0.2 pg/ml; intraindividual variation below 0.1%). Repeated thawing and re-freezing up to three times did not change measured sNfL concentration significantly, either (mean absolute difference 0.7 pg/ml; intraindividual variation below 0.2%). We conclude that the soluble sNfL concentration is unaffected at 4–8 °C when samples are frozen within 24 h and single aliquots can be used up to three times. These observations should be considered for planning future studies.

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Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults

Cited by 102 publications

References 29 publications

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Renal function is associated with blood neurofilament light chain level in older adults

Serum neurofilament light chain withstands delayed freezing and repeated thawing

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