Plasma neurofilament light chain is associated with mortality after spontaneous intracerebral hemorrhage

Abstract

BackgroundNeurofilament light chain (NfL) is a neuron-specific biomarker with prognostic ability in several types of central nervous system injuries. This study investigates if plasma NfL (pNfL) is elevated early after spontaneous intracerebral hemorrhage (ICH) and whether such elevation reflects disease severity and day-30 outcome.MethodspNfL was quantified by single molecule array analysis in 103 reference subjects (RS) and in samples from 37 patients with ICH obtained on admission to hospital and at 24-h follow-up. The primary outcome was day-30 mortality. Clinical status on admission was evaluated by standardized scoring systems.ResultsMedian pNfL among RS was 9.6 (interquartile range [IQR] 6.2) pg/mL. Upon admission, ICH patients had pNfL of 19.8 (IQR 30.7) pg/mL increasing to 35.9 (IQR 44.5) pg/mL at 24 h (all, p < 0.001). On admission, pNfL was higher among ICH non-survivors than survivors (119.2 [IQR 152.6] pg/mL vs. 15.7 [IQR 19.6] pg/mL, p < 0.01) and this difference was observed also on 24 h follow-up (195.1 [IQR 73.9] pg/mL vs. 31.3 [IQR 27.8] pg/mL, p < 0.01). The area under the receiver operating characteristic curve (ROC AUC) for discrimination of day-30 mortality was significant on admission (AUC = 0.83, 95% confidence interval [CI]: 0.56–1.0) and increased on 24-h follow-up (AUC = 0.93, 95% CI: 0.84–1.0). The odds ratio (OR) for death, by each quartile increase in pNfL was significant both on admission (OR = 4.52, 95% CI: 1.32–15.48) and after 24-h follow-up (OR = 9.52, 95% CI: 1.26–71.74).ConclusionsPNfL is associated with day-30 mortality after spontaneous ICH when early after the ictus.

Serum neurofilament light and tau as prognostic markers for all-cause mortality in the elderly general population—an analysis from the MEMO study

“…Our results show that in population-based settings, NfL and tau serum levels can be used to identify individuals at higher risk of mortality (reflected by the hazard ratios above one) that are clinically normal, relative to a reference group. Our data establish a continuum of predictive value for NfL between subclinical morbidity and individuals with neurological disease [6][7][8]. Moreover, none of the patient-or population-based studies so far investigated the influence of NfL on absolute risks.…”

“…Moreover, NfL CSF levels are associated with mortality of patients with parkinsonism [2], mitochondrial disease [3], and other neurodegenerative diseases [4,5]. Similarly, this is the case for higher NfL serum levels in patients with sporadic Creutzfeldt-Jakob disease [6], after ischaemic stroke [7] and after spontaneous intracerebral haemorrhage [8].…”

Plasma neurofilament light predicts mortality in patients with stroke

“…Consequently, determining the prognostic utility of blood neurofilament proteins has become an important endeavor in the stroke field. To date, studies aimed at addressing this question have chiefly concentrated on acute cerebral infarction (ACI) (14)(15)(16)(17)(18)(19)(20)(21)(22), with far fewer investigations examining blood neurofilament in SAH (13,23) or ICH (24,25). In aggregate, findings from these studies are encouraging but nonetheless highlight the need for more intensive investigations on hemorrhagic stroke and on the interstudy discrepancies that must be addressed if blood neurofilament proteins are to be successfully translated to the clinic.…”

“…In aggregate, findings from these studies are encouraging but nonetheless highlight the need for more intensive investigations on hemorrhagic stroke and on the interstudy discrepancies that must be addressed if blood neurofilament proteins are to be successfully translated to the clinic. For instance, associations of blood neurofilament with functional outcomes and, in the case of ACI, with infarct volumes were observed in only some of the studies in which such correlations were examined (13)(14)(15)(16)(17)(19)(20)(21)(22)(23)(24)(25)(26).…”

Neurofilament Light Chain as A Biomarker for Brain Metastases

“…The quantification of NfL levels has previously been described [ 26 ]. In short, the NF-light ® assay was established on the ultra-sensitive Simoa™ HD-1 platform (Quanterix © , Lexington, MA, USA) [ 12 ].…”