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Background: Biomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role. Methods: This prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC). Results: Of 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p < 0.05) but also closely related to the severity of age-related white matter changes. Higher initial NIHSS score, severe white matter lesions, diabetes mellitus, and upregulated sNfL were significant predictors of END. Similarly, the multivariate logistic regression analysis results showed that elevated sNfL, a higher baseline NIHSS score, and severe white matter lesions were substantially linked with unfavorable outcomes for 3 months. Similarly, sNfL was valuable for the prediction of the 3 months of poor outcome (95%CI, 0.504-0.642, p = 0.044). Kaplan-Meier analysis shows that patients with elevated sNfL levels are more likely to reach combined cerebrovascular endpoints (log-rank test p < 0.05). Conclusion: This investigation suggests that sNfL can serve as a valuable biomarker for predicting END and 3-month poor functional outcomes after an IS and has the potential to forecast long-term cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Patients 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. Methods: We 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. Results: A 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 withMIS (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. Conclusion: Early neurological deterioration is common inminor 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. [ABSTRACT FROM AUTHOR]

Patients with intracerebral hemorrhage (ICH) often suffer from heterogeneous long-term neurological deficits, such as cognitive decline. Our ability to measure secondary brain injury to predict the long-term outcomes of these patients is limited. We investigated whether the blood neurofilament light chain (NfL) can monitor brain injury and predict long-term outcomes in patients with ICH. We enrolled 300 patients with first-episode ICH within 24 h recruited in the Chinese Cerebral Hemorrhage Mechanisms and Intervention study cohort from January 2019 to June 2020. Patients were prospectively followed up for 12 months. Blood samples were collected from 153 healthy participants. Plasma NfL levels determined using a single-molecule array revealed a biphasic increase in plasma NfL in ICH patients compared to healthy controls, with the first peak at around 24 h and a second elevation from day 7 through day 14 post-ICH. Plasma NfL levels were positively correlated with hemorrhage volume, National Institute of Health Stroke Scale, and Glasgow Coma Scale scores of ICH patients. Higher NfL concentration within 72 h after ictus was independently associated with 6- and 12-month worsened functional outcomes (modified Rankin Scale ≥ 3) and higher all-cause mortality. Magnetic resonance imaging and cognitive function evaluation were available for 26 patients at 6 months post-ICH, and NfL levels measured 7 days post-ictus correlated with decreased white matter fiber integrity and poor cognitive function at 6 months after stroke. These findings suggest that blood NfL is a sensitive marker for monitoring axonal injury post-ICH and can predict long-term functional ability and survival. [ABSTRACT FROM AUTHOR]

Background: Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients. Methods: NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry. Results: CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = − 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort. Conclusions: The observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis. [ABSTRACT FROM AUTHOR]

On the other hand, Hermansson et al. reported that plasma NfL did not correlate with serum creatinine among patients infected with HIV with a mean age of 40 years, suggesting that the relationship between blood NfL and renal function becomes more evident among older adults [[5]]. Here, we assessed admission levels of serum NfL (sNfL) in geriatric patients with COVID-19 with the aim to evaluate the ability of circulating NfL to improve COVID-19 mortality prediction alone and/or in association with other demographic, biochemical, and molecular circulating biomarkers. The minimum number of days for which patients in the recovered group remained hospitalized was one day, while the maximum hospital stay was 53 days for survived patients and 56 days for deceased patients. In conclusion, serum NfL could be associated with severe outcomes in geriatric patients affected by COVID-19, even if caution should be used when interpreting these findings in patients with impaired renal function. [Extracted from the article]

Background: Neurofilament light chain (NfL) in cerebrospinal fluid (CSF) is a biomarker of multiple sclerosis (MS). However, CSF sampling is invasive and has limited the clinical application. With the development of highly sensitive single-molecule assay, the accurate quantification of the very low NfL levels in blood become feasible. As evidence being accumulated, we performed a meta-analysis to evaluate the diagnostic and predictive value of blood NfL in MS patients. Methods: We performed literature search on PubMed, EMBASE, Web of Science and Cochrane Library from inception to May 31, 2022. The blood NfL differences between MS vs. controls, MS vs. clinically isolated syndrome (CIS), progressive MS (PMS) vs. relapsing-remitting MS (RRMS), and MS in relapse vs. MS in remission were estimated by standard mean difference (SMD) and corresponding 95% confidence interval (CI). Pooled hazard ratio (HR) and 95%CI were calculated to predict time to reach Expanded Disability Status Scale (EDSS) score≥4.0 and to relapse. Results: A total of 28 studies comprising 6545 MS patients and 2477 controls were eligible for meta-analysis of diagnosis value, and 5 studies with 4444 patients were synthesized in analysis of predictive value. Blood NfL levels were significantly higher in MS patients vs. age-matched controls (SMD = 0.64, 95%CI 0.44–0.85, P<0.001), vs. non-matched controls (SMD = 0.76, 95%CI 0.56–0.96, P<0.001) and vs. CIS patients (SMD = 0.30, 95%CI 0.18–0.42, P<0.001), in PMS vs. RRMS (SMD = 0.56, 95%CI 0.27–0.85, P<0.001), and in relapsed patients vs. remitted patients (SMD = 0.54, 95%CI 0.16–0.92, P = 0.005). Patients with high blood NfL levels had shorter time to reach EDSS score≥4.0 (HR = 2.36, 95%CI 1.32–4.21, P = 0.004) but similar time to relapse (HR = 1.32, 95%CI 0.90–1.93, P = 0.155) compared to those with low NfL levels. Conclusion: As far as we know, this is the first meta-analysis evaluating the diagnosis and predictive value of blood NfL in MS. The present study indicates blood NfL may be a useful biomarker in diagnosing MS, distinguishing MS subtypes and predicting disease worsening in the future. [ABSTRACT FROM AUTHOR]

Damage to axons is a core feature of ischemic stroke and cerebrovascular disease. The burden of axonal injury is correlated with the acute clinical deficits, the underlying burden of ischemic brain injury, the prognosis of recovery, and may be a meaningful therapeutic target for brain repair. Neurofilament light chain (NfL) has been identified as a blood-based biomarker that reflects neuroaxonal damage resulting from stroke. However, the utility of NfL as a blood-based biomarker in stroke is confounded by studies examining different temporal windows and patient populations. We conducted a systematic review and meta-analysis to verify the utility of blood NfL as a diagnostic, prognostic, and monitoring stroke biomarker. Nineteen studies reporting serum/plasma NfL values for a total of 4,237 distinct patients with stroke were identified. Using available summary data from the 10 studies that employed a common immunoassay platform, we utilized random effects linear mixed modeling and weighted averages to create a phasic model of serum/plasma NfL values in distinct time periods of acute stroke. Weighted averages show that blood NfL levels vary significantly across three distinct temporal epochs of acute (0–7 days), subacute (9–90 days), and chronic (>90 days) stroke with a steep peak in the early subacute period between 14 and 21 days after stroke. Blood NfL values can function as a diagnostic biomarker in distinguishing acute ischemic stroke from transient ischemic attack as well as amongst other cerebrovascular subtypes. Release of NfL into the bloodstream after stroke follows a distinct temporal dynamic that lags several weeks behind stroke onset and reliably associates with a stroke diagnosis despite some variability based on stroke subtype and severity. Identification of these temporal dynamics and the contribution of co- existent cerebrovascular disease states can improve the value of NfL as a stroke biomarker. [ABSTRACT FROM AUTHOR]

Objective. To explore associations of serum neurofilament light chain (sNfL) at admission with clinical deficits and the long-term prognosis of acute ischaemic stroke (AIS). Methods. We recruited 110 AIS patients with serum sampled at hospital arrival. The concentrations of sNfL were detected by a Simoa HD-1 analyser. We first investigated the determinants of sNfL levels at admission within the study population. Associations of sNfL levels with National Institutes of Health Stroke Scale (NIHSS) scores and modified Rankin Scale (mRS) scores were then tested. We further divided the patients into revascularized and nonrevascularized groups, and the associations of sNfL levels with NIHSS and mRS scores were assessed in these subgroups. Results. Age, sex, stroke history, and the time between the onset of illness and arrival at the hospital were independent influencing factors of sNfL levels within the study population. The sNfL levels at admission were correlated with the NIHSS scores 7 days after stroke (p = 0.004) across all subjects but showed no correlation with the NIHSS scores at admission (p = 0.293) or the mRS scores 6 months after stroke (p = 0.065). Further analysis revealed that in the nonrevascularized group of AIS patients, the sNfL levels at admission were positively correlated with NIHSS scores (NIHSS at admission, p = 0.005 ; NIHSS 7 days after stroke, p = 0.003) and negatively correlated with mRS scores (p = 0.011). Conclusion. sNfL levels at admission could be a potential biomarker for predicting clinical deficits and prognosis in the natural course of AIS. [ABSTRACT FROM AUTHOR]

Objectives: To test if the early kinetics of neurofilament light (NFL) in blood adds to the absolute values of NFL in the prediction of outcome, and to evaluate if NFL can discriminate individuals with severe hypoxic–ischemic brain injury (sHIBI) from those with other causes of poor outcome after out-of-hospital cardiac arrest (OHCA). Design and setting: Monocentric retrospective study involving individuals following non-traumatic OHCA between April 2014 and April 2016. NFL concentrations were determined on a SiMoA HD-1 device using NF-Light Advantage Kits. Participants: Of 73 patients screened, 53 had serum samples available for NFL measurement at three timepoints (after 3, 24, and 48 h of admission). Of these 53 individuals, 43.4% had poor neurologic outcome at discharge as assessed by Glasgow–Pittsburgh cerebral performance categories, and, according to a current prognostication algorithm, poor outcome due to sHIBI in 20.7%. Main outcome measure: Blood NFL and its early kinetics for prognostication of outcome and prediction of sHIBI after OHCA. Results: An absolute NFL > 508.6 pg/ml 48 h after admission, or a change in NFL > 494 pg/ml compared with an early baseline value predicted outcome, and discriminated severe sHIBI from other causes of unfavorable outcome after OHCA with high sensitivity (100%, 95%CI 70.0–100%) and specificity (91.7%, 95%CI 62.5–100%). Conclusions: Not only absolute values of NFL, but also early changes in NFL predict the outcome following OHCA, and may differentiate sHIBI from other causes of poor outcome after OHCA with high sensitivity and specificity. Our study adds to published data, overall corroborating that NFL measured in blood should be implemented in prognostication algorithms used in clinical routine. [ABSTRACT FROM AUTHOR]

Background: Mental health problems after acute ischemic stroke (AIS) have caused wide public concerns, and the study on early identification of these disorders is still an open issue. This study aims to investigate the predictive effect of circulating neurofilament light (NfL) on long-term mental health status of AIS patients. Methods: This study collected demographic information and mental health measurements from 304 AIS patients from May 1, 2016 to Dec 31, 2019. Baseline serum neurofilament light (NfL) was determined within 2 h since patient admission. Six months after AIS onset, the degree of symptoms of depression, anxiety, and insomnia was assessed by the Chinese versions of the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 7-item Insomnia Severity Index (ISI), respectively. Subjects were divided into the high NfL group and the low NfL group. Multivariate logistic regression analysis was performed to identify factors associated with these mental health problems. Results: The high NfL group had significantly higher PHQ-9, GAD-7, and ISI scores than the low NfL group. The prediction of serum NfL for major depression generated a sensitivity of 70.27%, a specificity of 67.79% and an AUC of 0.694. The prediction of serum NfL for anxiety generated a sensitivity of 69.23%, a specificity of 64.02%, and an AUC of 0.683. The prediction of serum NfL for insomnia generated a sensitivity of 75.00%, a specificity of 66.43% and an AUC of 0.723. Higher serum NfL was a risk factor of post-AIS depression [ORs (95% CI): 4.427 (1.918, 10.217)], anxiety [ORs (95% CI): 3.063 (1.939, 6.692)], and insomnia [ORs (95% CI): 4.200 (1.526, 11.562)]. Conclusions: These findings imply that circulating NfL might be a potential biomarker of long-term mental health problems after AIS. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) is a cytoskeletal protein component whose release into blood is indicative of neuronal damage. Tau is a microtubule-associated protein in neurons and strongly associated with overall brain degeneration. NfL and tau levels are associated with mortality in different neurological diseases, but studies in the general population are missing. We investigated whether NfL and tau serum levels could serve as prognostic markers for overall mortality in elderly individuals without pre-defined neurological conditions. Further, we investigated the cross-sectional associations between NfL, tau, neuropsychological functioning, and brain structures.Methods: In 1997, 385 inhabitants of Augsburg who were aged 65 years and older were included in the Memory and Morbidity in Augsburg Elderly (MEMO) study. They participated in a face-to-face medical interview including neuropsychological tests and magnetic resonance imaging (MRI) of the brain. NfL and tau were measured from non-fasting blood samples using highly sensitive single molecule array assays. To assess the prognostic accuracy of the biomarkers, concordance statistics based on the predicted 5-year survival probabilities were calculated for different Cox regression models. Associations between the biomarkers and the neuropsychological test scores or brain structures were investigated using linear or logistic regression.Results: NfL (HR 1.27, 95% CI [1.14-1.42]) and tau (1.20 [1.07-1.35]) serum levels were independently associated with all-cause mortality. NfL, but not tau, increased the prognostic accuracy when added to a model containing sociodemographic characteristics (concordance statistic 0.684 [0.612-0.755] vs. 0.663 [0.593-0.733]), but not when added to a model containing sociodemographic characteristics and brain atrophy or neuropsychological test scores. NfL serum levels were cross-sectionally associated with neuropsychological test scores and brain structures.Conclusions: The association between NfL serum levels and brain atrophy and neuropsychological performance in individuals without overt neurological disease is similar to that seen in patients with neurodegenerative diseases. These findings support the concept of a continuum of physiological aging and incipient, subclinical pathology, and manifest disease. NfL, but not tau, serum levels might serve as a prognostic marker for all-cause mortality if no other clinical information is available. [ABSTRACT FROM AUTHOR]

Background: Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT.Methods: We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3-6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage).Results: Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03-4.08), T2 (OR, 2.08; 95% CI, 1.05-4.01), and T3 (OR, 3.94; 95% CI, 1.44-10.79) were independent predictors of death or disability at 90 days.Conclusion: Among patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Plasma neurofilaments light chain (pNfL) is a marker of axonal injury. The purpose of this study was to examine the role of pNfL as a predictive biomarker for post-stroke cognitive impairment (PSCI). Methods: A prospective single-center observational cohort study was conducted at the General Hospital of Western Theater Command between July 1, 2017 and December 31, 2019. Consecutive patients ≥18 years with first-ever acute ischemic stroke (AIS) of anterior circulation within 24 h of symptom onset were included. PSCI was defined by the Montreal Cognitive Assessment (MOCA) (MOCA < 26) at 90 days after stroke onset. Results: A total of 1,694 patients [male, 893 (52.70%); median age, 64 (16) years] were enrolled in the cohort analysis, and 1,029 (60.70%) were diagnosed with PSCI. Patients with PSCI had significantly higher pNfL [median (IQR), 55.96 (36.13) vs. 35.73 (17.57) pg/ml; P < 0.001] than Non-PSCI. pNfL was valuable for the prediction of PSCI (OR 1.044, 95% CI 1.038–1.049, P < 0.001) after a logistic regression analysis, even after adjusting for conventional risk factors including age, sex, education level, NIHSS, TOAST classification, and infarction volume (OR 1.041, 95% CI 1.034–1.047, P < 0.001). The optimal cutoff value of the pNfL concentration was 46.12 pg/ml, which yielded a sensitivity of 71.0% and a specificity of 81.5%, with the area under the curve (AUC) at 0.785 (95% CI 0.762–0.808, P < 0.001). Conclusion: This prospective cohort study showed that the pNfL concentration within 48 h of onset was an independent risk factor for PSCI 90 days after an anterior circulation stroke, even after being adjusted for potential influencing factors regarded as clinically relevant. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1800020330. [ABSTRACT FROM AUTHOR]

Background: Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients.Methods: Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up.Results: Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06-3.87) and ICH (odds ratio 2.06, 95% CI 1.26-3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19-3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21-6.53) predicted incident ICH.Conclusions: In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Serum neurofilaments are markers of axonal injury. We investigated whether serum neurofilament light (sNfL) is a potential prognostic marker of functional outcome in Chinese patients with acute ischemic stroke (AIS). From May 2015 to December 2018, consecutive patients with AIS from the Department of Neurology of the Second Hospital of Jilin University were included. sNfL concentration was tested at baseline, and stroke severity was analyzed at admission using the NIHSS score. Functional outcome was assessed at discharge by the modified Rankin scale (mRS). The sNfL concentration was tested in 343 patients with a median value of 17.8 (IQR, 13.4–25.2) pg/ml. sNfL concentration paralleled lesion size (P = 0.035). At admission, 174 patients were defined as moderate-to-high stroke (NIHSS ≥ 5); the sNfL concentration in those patients were higher than that observed in patients with minor clinical severity [21.2 (IQR, 15.1–31.7) vs. 14.9 (11.8–19.4) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of moderate-to-high stroke increased by 202% (with the OR of 3.04 (95% CI 2.15–4.32), P < 0.001) and 102% [2.02 (1.10–3.16), P = 0.001), respectively. At discharge, 85 patients (24.8%) had poor functional outcome (mRS, 3–6); the sNfL concentration in those patients were higher than that observed in patients with good outcome [24.1 (IQR, 18.8–33.9) vs. 15.7 (11.9–21.8) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of poor outcome increased by 236% [with the OR of 3.36 (95% CI 2.23–5.06), P < 0.001] and 102% [2.29 (1.37–3.82), P < 0.001], respectively. The results show sNfL is meaningful blood biomarker to monitor stroke severity and functional outcome in ischemic stroke, suggesting that sNfL may play a role in stroke progression. [ABSTRACT FROM AUTHOR]

Increased sensitivity of methods assessing the levels of neurofilament light chain (NfL), a neuron-specific intermediate filament protein, in human plasma or serum, has in recent years led to a number of studies addressing the utility of monitoring NfL in the blood of stroke patients. In this review, we discuss that elevated blood NfL levels after stroke may reflect several different neurobiological processes. In the acute and post-acute phase after stroke, high blood levels of NfL are associated with poor clinical outcome, and later on, the blood levels of NfL positively correlate with secondary neurodegeneration as assessed by MRI. Interestingly, increased blood levels of NfL in individuals who survived stroke for more than 10 months were shown to predict functional improvement in the late phase after stroke. Whereas in the acute phase after stroke the injured axons are assumed to be the main source of blood NfL, synaptic turnover and secondary neurodegeneration could be major contributors to blood NfL levels in the late phase after stroke. Elevated blood NfL levels after stroke should therefore be interpreted with caution. More studies addressing the clinical utility of blood NfL assessment in stroke patients are needed before the inclusion of NfL in the clinical workout as a useful biomarker in both the acute and the chronic phase after stroke. [ABSTRACT FROM AUTHOR]