Serum NFL discriminates Parkinson disease from atypical parkinsonisms

Neurology ◽  
2019 ◽  
Vol 92 (13) ◽  
pp. e1479-e1486 ◽  
Author(s):  
Tainá M. Marques ◽  
Anouke van Rumund ◽  
Patrick Oeckl ◽  
H. Bea Kuiperij ◽  
Rianne A.J. Esselink ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Single Molecule ◽  
Predictive Value ◽  
Clinical Symptoms ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Clinical Diagnoses

ObjectiveTo investigate the diagnostic value of serum neurofilament light chain (NFL) in patients with clear signs of parkinsonism but whose specific diagnosis was yet uncertain.MethodsSerum samples were collected from patients with clear signs of parkinsonism but with uncertain diagnosis at the inclusion. Clinical diagnoses of Parkinson disease (PD) and atypical parkinsonism disorders (APDs) were established after 3 years of follow-up and updated again after a maximum of 12 years in case longer follow-up data were available. Serum NFL was quantified by single molecule array in patients with PD (n = 55) and APD (n = 29, multiple system atrophy = 22, progressive supranuclear palsy = 7) and 53 nonneurologic controls.ResultsSerum NFL levels were elevated and differentiated the APD group (mean 23.8 ± 10.3 ng/L) from PD (mean 10.4 ± 4.9 ng/L) and controls (mean 11.5 ± 6.5 ng/L, p < 0.0001) with accuracy levels up to 91% (sensitivity = 86% and specificity = 85%). Serum NFL strongly correlated with CSF NFL levels (r = 0.72, p < 0.0001) in all groups and with age in PD (r = 0.78, p < 0.0001) and controls (r = 0.66, p < 0.0001). In our cohort, the probability of having APD was 76% (positive predictive value) and of having PD 92% (negative predictive value).ConclusionSerum NFL levels are markedly elevated in APD compared to PD and discriminate APDs from PD with high accuracy. Serum NFL may be a useful clinical biomarker to identify APD, even at stages when clinical symptoms are not yet conclusive.Classification of evidenceThis study provides Class II evidence that serum NFL levels accurately discriminate APDs from PD.

Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD

Neurology ◽  
2019 ◽  
Vol 93 (13) ◽  
pp. e1299-e1311 ◽  
Author(s):  
Mitsuru Watanabe ◽  
Yuri Nakamura ◽  
Zuzanna Michalak ◽  
Noriko Isobe ◽  
Christian Barro ◽  
...  
Keyword(s):  
Disease Activity ◽  
Single Molecule ◽  
Multivariate Analyses ◽  
Serum Levels ◽  
Strongly Correlated ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Disability Status ◽  
Spectrum Disorders

ObjectiveTo test the hypothesis that serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), which are an intermediate astrocyte and neuron filaments, respectively, are clinically useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorders (NMOSD).MethodsLevels of GFAP and NfL in serum (sGFAP and sNfL, respectively) and in CSF samples were measured in healthy controls (HCs) (n = 49; 49 serum samples), patients with NMOSD (n = 33; 42 CSF and 102 serum samples), and patients with multiple sclerosis (MS) (n = 49; 53 CSF and 91 serum samples) by ultrasensitive single-molecule array assays. Association of sGFAP and sNfL levels with clinical parameters was determined.ResultsFor both GFAP and NfL, CSF and serum levels were strongly correlated. Both were higher in the serum of patients with NMOSD than in HCs (both p < 0.001). Moreover, sGFAP was higher in NMOSD than in MS (median 207.7 vs 121.1 pg/mL, p < 0.001). In NMOSD, sGFAP concentration increased after recent relapse (540.9 vs 152.9 pg/mL, p < 0.001). Multivariate analyses indicated that sGFAP and sNfL were associated with Expanded Disability Status Scale score in NMOSD (p = 0.026 and p < 0.001, respectively). Higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS with a sensitivity of 73.0% and a specificity of 75.8%.ConclusionssGFAP and sNfL are likely to be good biomarkers of disease activity and disability, and the sGFAP/sNfL quotient at relapse is a potential diagnostic marker for NMOSD.

scholarly journals Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽  
2017 ◽  
Vol 89 (20) ◽  
pp. 2108-2114 ◽  
Author(s):  
Thomas Gattringer ◽  
Daniela Pinter ◽  
Christian Enzinger ◽  
Thomas Seifert-Held ◽  
Markus Kneihsl ◽  
...  
Keyword(s):  
Single Molecule ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease

Objective:To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.Methods:In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.Results:Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up.Conclusions:Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

scholarly journals Detection of Cerebrospinal Fluid Neurofilament Light Chain as a Marker for Alpha-Synucleinopathies

2021 ◽  
Vol 13 ◽  
Author(s):  
Sezgi Canaslan ◽  
Matthias Schmitz ◽  
Anna Villar-Piqué ◽  
Fabian Maass ◽  
Karin Gmitterová ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Clinical Symptoms ◽  
Alpha Synuclein ◽  
Test System ◽  
Marker Protein ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Different Types

Alpha-synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are a class of neurodegenerative diseases. A diagnosis may be challenging because clinical symptoms partially overlap, and there is currently no reliable diagnostic test available. Therefore, we aimed to identify a suitable marker protein in cerebrospinal fluid (CSF) to distinguish either between different types of alpha-synucleinopathies or between alpha-synucleinopathies and controls. In this study, the regulation of different marker protein candidates, such as alpha-synuclein (a-Syn), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total tau (tau) in different types of alpha-synucleinopathies, had been analyzed by using an ultrasensitive test system called single-molecule array (SIMOA). Interestingly, we observed that CSF-NfL was significantly elevated in patients with DLB and MSA compared to patients with PD or control donors. To differentiate between groups, receiver operating characteristic (ROC) curve analysis resulted in a very good diagnostic accuracy as indicated by the area under the curve (AUC) values of 0.87–0.92 for CSF-NfL. Furthermore, we observed that GFAP and tau were slightly increased either in DLB or MSA, while a-Syn levels remained unregulated. Our study suggests NfL as a promising marker to discriminate between different types of alpha-synucleinopathies or between DLB/MSA and controls.

Absence of attack-independent neuroaxonal injury in MOG antibody-associated disease: Longitudinal assessment of serum neurofilament light chain

2021 ◽  
pp. 135245852110637
Author(s):  
Jae-Won Hyun ◽  
So Yeon Kim ◽  
Yeseul Kim ◽  
Na Young Park ◽  
Ki Hoon Kim ◽  
...  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Single Molecule ◽  
Light Chain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Acidic Protein ◽  
Healthy Controls ◽  
Longitudinal Assessment ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

To evaluate the occurrence of attack-independent neuroaxonal and astrocytic damage in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) levels were longitudinally measured in 102 sera using a single-molecule array assay. Sera from 15 adults with relapsing MOGAD with available longitudinal samples for the median 24-month follow-up and 26 age-/sex-matched healthy controls were analyzed. sNfL levels were significantly elevated in all clinical attacks, where the levels decreased below or close to cut-off value within 6 months after attacks. sNfL levels were consistently low during inter-attack periods. In contrast, sGFAP levels did not increase in most clinical attacks and remained low during follow-up. Significant neuroaxonal damage was observed at clinical attacks, while attack-independent neuroaxonal and astrocytic injury was absent in MOGAD.

scholarly journals Neurofilament light chain predicts disease activity in relapsing-remitting MS

2017 ◽  
Vol 5 (1) ◽  
pp. e422 ◽  
Author(s):  
Kristin N. Varhaug ◽  
Christian Barro ◽  
Kjetil Bjørnevik ◽  
Kjell-Morten Myhr ◽  
Øivind Torkildsen ◽  
...  
Keyword(s):  
Disease Activity ◽  
Single Molecule ◽  
Light Chain ◽  
Interferon Beta ◽  
Serum Levels ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Relapsing Remitting

Objective:To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS).Methods:A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models.Results:NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9–52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1–48.5) compared with those without (28.0 pg/mL, IQR 21.9–36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8–35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.Conclusion:Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity.ClinicalTrials.gov identifier:NCT00360906.

scholarly journals Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa

2016 ◽  
Vol 54 (10) ◽  
Author(s):  
Jens Kuhle ◽  
Christian Barro ◽  
Ulf Andreasson ◽  
Tobias Derfuss ◽  
Raija Lindberg ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Neurological Diseases ◽  
Cytoskeletal Proteins ◽  
Response To Treatment ◽  
Analytical Sensitivity ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

AbstractBackground:Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are specific cytoskeletal proteins of neurons and their quantification has shown encouraging results as a biomarker for axonal injury.Methods:We aimed at comparing a widely used conventional ELISA for Nf light chain (NfL) with an electrochemiluminescence-based method (ECL assay) and a newly developed single-molecule array (Simoa) method in clinically relevant cerebrospinal fluid (CSF) and serum samples.Results:Analytical sensitivity was 0.62 pg/mL for Simoa, 15.6 pg/mL for the ECL assay, and 78.0 pg/mL for the ELISA. Correlations between paired CSF and serum samples were strongest for Simoa (r=0.88, p<0.001) and the ECL assay (r=0.78, p<0.001) and weaker for ELISA measurements (r=0.38, p=0.030). CSF NfL measurements between the platforms were highly correlated (r=1.0, p<0.001). Serum NfL levels were highly related between ECL assay and Simoa (r=0.86, p<0.001), and this was less visible between ELISA-ECL assay (r=0.41, p=0.018) and ELISA-Simoa (r=0.43, p=0.013). Multiple sclerosis (MS) patients had significantly higher serum NfL levels than controls when measured with Simoa (p=0.001) but not with the other platforms.Conclusions:We found Simoa to be more sensitive than ELISA or the ECL assay. Our results support the feasibility of quantifying NfL in serum; the results correlate with the more-established CSF NfL test. The highly sensitive Simoa technology deserves further studies in larger patient cohorts to clarify whether serum NfL could be used in the future to measure disease severity and determine prognosis or response to treatment interventions in neurological diseases.

scholarly journals Implications of extreme serum neurofilament light chain levels for the management of patients with relapsing multiple sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110019
Author(s):  
Sinah Engel ◽  
Maria Protopapa ◽  
Falk Steffen ◽  
Vakis Papanastasiou ◽  
Christoforos Nicolaou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Single Molecule ◽  
Light Chain ◽  
Clinical Symptoms ◽  
Threshold Value ◽  
Sample Collection ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
The Mean

Background: Serum neurofilament light chain (sNfL) is a promising biomarker to complement the decision-making process in multiple sclerosis (MS) patients. However, although sNfL levels are able to detect disease activity and to predict future disability, the growing evidence has not yet been translated into practicable recommendations for an implementation into clinical routine. Methods: The observation of a patient with extensive inflammatory activity in magnetic resonance imaging (MRI) along with an extremely high sNfL level in the absence of any clinical symptoms prompted us to investigate common characteristics of our MS patients with the highest sNfL levels in a retrospective cohort study. The 97.5th percentile was chosen as a cut-off value because the mean sNfL level of the resulting extreme neurofilament light chain (NfL) cohort corresponded well to the sNfL level of the presented case. Patient characterization included clinical and MRI assessment with a focus on disease activity markers. sNfL levels were determined by single molecule array. Results: The 97.5th percentile of our MS cohort (958 sNfL measurements in 455 patients) corresponded to a threshold value of 46.1 pg/ml. The mean sNfL level of the extreme sNfL cohort ( n = 24) was 95.6 pg/ml (standard deviation 68.4). Interestingly, only 15 patients suffered from a relapse at the time point of sample collection, whereas nine patients showed no signs of clinical disease activity. sNfL levels of patients with and without relapse did not differ [median 81.3 pg/ml (interquartile range [IQR] 48.0–128) versus 80.2 pg/ml (IQR 46.4–97.6), p = 0.815]. The proportion of patients with contrast-enhancing lesions was high and also did not differ between patients with and without relapse (92.9% versus 87.5%, p = 0.538); 78.9% of the patients not receiving a high-efficacious therapy had ongoing disease activity during a 2-year follow-up. Conclusion: Extremely high sNfL levels are indicative of subclinical disease activity and might complement treatment decisions in ambiguous cases.

scholarly journals Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19

Neurology ◽  
2020 ◽  
Vol 95 (12) ◽  
pp. e1754-e1759 ◽  
Author(s):  
Nelly Kanberg ◽  
Nicholas J. Ashton ◽  
Lars-Magnus Andersson ◽  
Aylin Yilmaz ◽  
Magnus Lindh ◽  
...  
Keyword(s):  
Single Molecule ◽  
Severe Disease ◽  
Plasma Concentrations ◽  
Neuronal Injury ◽  
Cns Injury ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Plasma Biomarkers

ObjectiveTo test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.MethodsWe recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.ResultsThe patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.ConclusionWe show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19–related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.

scholarly journals CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Mette Scheller Nissen ◽  
Matias Ryding ◽  
Anna Christine Nilsson ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Demyelinating Disease ◽  
Demyelinating Diseases ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Array Technology ◽  
National Cohort ◽  
Activity Marker

Background and ObjectivesThe two most common autoimmune encephalitides (AE), N-methyl-D-Aspartate receptor (NMDAR) and Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis, have been known for more than a decade. Nevertheless, no well-established biomarkers to guide treatment or estimate prognosis exist. Neurofilament light chain (NfL) has become an unspecific screening marker of axonal damage in CNS diseases, and has proven useful as a diagnostic and disease activity marker in neuroinflammatory diseases. Only limited reports on NfL in AE exist. We investigated NfL levels at diagnosis and follow-up in NMDAR and LGI1-AE patients, and evaluated the utility of CSF-NfL as a biomarker in AE.MethodsPatients were included from the National Danish AE cohort (2009-present) and diagnosed based upon autoantibody positivity and diagnostic consensus criteria. CSF-NfL was analyzed by single molecule array technology. Clinical and diagnostic information was retrospectively evaluated and related to NfL levels at baseline and follow-up. NMDAR-AE patients were subdivided into: idiopathic/teratoma associated or secondary NMDAR-AE (post-viral or concomitant with malignancies/demyelinating disease).ResultsA total of 74 CSF samples from 53 AE patients (37 NMDAR and 16 LGI1 positive) were included in the study. Longitudinal CSF-NfL levels was measured in 21 patients. Median follow-up time was 23.8 and 43.9 months for NMDAR and LGI1-AE respectively. Major findings of this study are: i) CSF-NfL levels were higher in LGI1-AE than in idiopathic/teratoma associated NMDAR-AE at diagnosis; ii) CSF-NfL levels in NMDAR-AE patients distinguished idiopathic/teratoma cases from cases with other underlying etiologies (post-viral or malignancies/demyelinating diseases) and iii) Elevated CSF-NfL at diagnosis seems to be associated with worse long-term disease outcomes in both NMDAR and LGI1-AE.DiscussionCSF-NfL measurement may be beneficial as a prognostic biomarker in NMDAR and LGI1-AE, and high CSF-NfL could foster search for underlying etiologies in NMDAR-AE. Further studies on larger cohorts, using standardized methods, are warranted.

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

2020 ◽  
Vol 58 (2) ◽  
pp. 261-267 ◽  
Author(s):  
Claus Vinter Bodker Hviid ◽  
Tua Gyldenholm ◽  
Signe Voigt Lauridsen ◽  
Niels Hjort ◽  
Anne-Mette Hvas ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Single Molecule ◽  
Light Chain ◽  
Characteristic Curve ◽  
Clinical Status ◽  
Scoring Systems ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

AbstractBackgroundNeurofilament 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.

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