Serum Neurofilament Light Chain in NMOSD and Related Disorders: Comparison According to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies Status

Background Neurofilament light chain (NF-L) levels reflect axonal damage in different conditions, including demyelinating disorders. Objectives We aimed to compare serum NF-L levels in patients with aquaporin-4 antibodies (AQP4-Ab), myelin oligodendrocyte antibodies (MOG-Ab) and seronegative cases with neuromyelitis optica spectrum disorders and related disorders. Methods We analysed AQP4-Ab and MOG-Ab with cell-based assay and NF-L with ultrasensitive electrochemiluminescence immunoassay. Results Median NF-L levels were increased in 25 AQP4-Ab-positive patients (59 pg/ml) as compared with 22 MOG-Ab-positive cases (25 pg/ml), 52 seronegative patients (18 pg/ml), 25 multiple sclerosis patients (12 pg/ml) and 14 healthy controls (12 pg/ml). Conclusions Increased serum levels of NF-L in patients with AQP4-Ab or MOG-Ab might reflect an ongoing axonal damage and a more malignant disease course.

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Serum levels of neurofilament light chain, neuron-specific enolase and S100 calcium-binding protein B during acute bacterial meningitis: a prospective cohort study

Infectious Diseases ◽

10.1080/23744235.2021.1883730 ◽

2021 ◽

pp. 1-11

Author(s):

Mads Hjortdal Grønhøj ◽

Tobias Sejbaek ◽

Rasmus Würgler Hansen ◽

Lykke Larsen ◽

Morten Dahl ◽

...

Keyword(s):

Cohort Study ◽

Bacterial Meningitis ◽

Light Chain ◽

Calcium Binding ◽

Neuron Specific Enolase ◽

Serum Levels ◽

Acute Bacterial Meningitis ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

S100 Calcium Binding Protein

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

Neurology ◽

10.1212/wnl.0000000000008160 ◽

2019 ◽

Vol 93 (13) ◽

pp. e1299-e1311 ◽

Cited By ~ 21

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.

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CSF Neurofilament light chain level predicts axonal damage in cerebral vasculitis

Annals of Clinical and Translational Neurology ◽

10.1002/acn3.790 ◽

2019 ◽

Vol 6 (6) ◽

pp. 1134-1137 ◽

Cited By ~ 2

Author(s):

Marc Pawlitzki ◽

Michaela Butryn ◽

Florian Kirchner ◽

Jacqueline Färber ◽

Oliver Beuing ◽

...

Keyword(s):

Light Chain ◽

Cerebral Vasculitis ◽

Axonal Damage ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Chain Level

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Thirty years after anorexia nervosa onset, serum neurofilament light chain protein concentration indicates neuronal injury

European Child & Adolescent Psychiatry ◽

10.1007/s00787-020-01657-7 ◽

2020 ◽

Author(s):

Elisabet Wentz ◽

Sandra Rydberg Dobrescu ◽

Lisa Dinkler ◽

Carina Gillberg ◽

Christopher Gillberg ◽

...

Keyword(s):

Anorexia Nervosa ◽

Single Molecule ◽

Light Chain ◽

Axonal Degeneration ◽

Neuronal Injury ◽

Serum Levels ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

National Patient ◽

History Of

Abstract Little is known about the long-term consequences of anorexia nervosa (AN) in terms of possible brain neuronal injury. We aimed at investigating whether women with adolescent-onset AN exhibit increased serum levels of neurofilament light chain protein (NfL), a biomarker for neuronal injury, compared with matched controls at 30-year follow-up. Blood samples were collected from 34 women with adolescent-onset AN and 38 matched healthy comparison women (COMP), at a mean age of 44 years (range 38–48 years). NfL was measured in serum using the in-house single molecule array (Simoa) method. The individuals were asked whether they or their parents had been diagnosed with dementia. The Swedish National Patient Register was searched for diagnoses related to dementia. Serum NfL concentrations were significantly higher in the AN group (AN 27.7 pg/ml; COMP 19.0 pg/ml; p = 0.041). When individuals with medical/neurological disorders in the AN and COMP groups were excluded, there was a statistically non-significant trend towards higher concentrations in the AN group (AN 27.4 pg/ml; COMP 18.8 pg/ml; p = 0.060). None of the participants had been diagnosed with dementia. There was no significant correlation between serum NfL and AN duration (r = 0.15). There was a moderate negative correlation between the serum NfL concentration and the current BMI in the AN group (r = 0.44). This is the first time that serum NfL has been assessed in middle-aged women with a history of adolescent-onset AN. The results suggest that there might be increased axonal degeneration as a sequel of AN. Individuals remaining underweight had higher serum NfL concentrations than those with a normal/high BMI. Additional studies are needed to confirm increased serum NfL concentrations in individuals recovered from AN. There is a need for further study of axonal degeneration as a consequence of AN.

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Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod

Multiple Sclerosis Journal ◽

10.1177/1352458517715132 ◽

2017 ◽

Vol 24 (8) ◽

pp. 1046-1054 ◽

Cited By ~ 73

Author(s):

Fredrik Piehl ◽

Ingrid Kockum ◽

Mohsen Khademi ◽

Kaj Blennow ◽

Jan Lycke ◽

...

Keyword(s):

Single Molecule ◽

Light Chain ◽

Detection Threshold ◽

Therapy Response ◽

Serum Levels ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Post Marketing ◽

Highly Correlated ◽

Ms Therapy

Background: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). Objective: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. Methods: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort ( n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL). Results: Mean NFL pg/mL (standard deviation ( SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated ( n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod ( n = 243), mean NFL pg/mL ( SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10−6), and levels remained stable at 24 months (13.2 (6.2)). Conclusion: NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response.

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Neurofilament Light Chain Levels Are Associated with Disease Activity Determined by No Evident Disease Activity in Multiple Sclerosis Patients

European Neurology ◽

10.1159/000515806 ◽

2021 ◽

pp. 1-8

Author(s):

Jarmila Szilasiová ◽

Jaroslav Rosenberger ◽

Miriam Fedičová ◽

Pavol Mikula ◽

Peter Urban ◽

...

Keyword(s):

Multiple Sclerosis ◽

Magnetic Resonance ◽

Disease Activity ◽

Sensitivity And Specificity ◽

Light Chain ◽

Operating Characteristics ◽

Disability Score ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Multiple Sclerosis Patients

Introduction: There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). Methods: Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). Results: Levels of pNfL were significantly higher in MS patients than in healthy controls (p < 0.001). From a total of 159 patients, 80 (50.3%) achieved NEDA-3 status, while 79 (49.7%) patients showed evident disease activity (EDA) status. pNfL were significantly lower in the NEDA-3 group than in the EDA group (pNfL mean 7.06 pg/mL [standard deviation (SD) 2.37] vs. pNfL mean 13.04 pg/mL [SD 7.07]) (p < 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, p < 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, p < 0.001). Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.

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Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

10.1101/2021.04.21.21255887 ◽

2021 ◽

Author(s):

Henning H. Rise ◽

Synne Brune ◽

Claudia Chien ◽

Tone Berge ◽

Steffan D. Bos ◽

...

Keyword(s):

Multiple Sclerosis ◽

Single Molecule ◽

Brain Network ◽

Axonal Damage ◽

Base Line ◽

Lesion Volume ◽

Neurofilament Light Chain ◽

Random Factor ◽

Neurofilament Light ◽

Multiple Sclerosis Patients

AbstractThe pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient’s white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, β = 0.03, p = 0.02), age (t = 5.01, β = 0.32, p < 5.5 × 10−7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, β = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = −1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

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Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458518765666 ◽

2018 ◽

Vol 25 (5) ◽

pp. 678-686 ◽

Cited By ~ 62

Author(s):

Nelly Siller ◽

Jens Kuhle ◽

Muthuraman Muthuraman ◽

Christian Barro ◽

Timo Uphaus ◽

...

Keyword(s):

Multiple Sclerosis ◽

Single Molecule ◽

Light Chain ◽

Neuronal Damage ◽

Axonal Damage ◽

Lesion Volume ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Magnetic Resonance Imaging Mri ◽

Brain Parenchymal

Background: Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood. Objective: To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS. Methods: sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months). Results: Baseline sNfL correlated significantly with T2 lesion volume ( r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased ( r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL ( r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels. Conclusion: sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.

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Neurofilament light chain as a biomarker in neurological disorders

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-320106 ◽

2019 ◽

Vol 90 (8) ◽

pp. 870-881 ◽

Cited By ~ 90

Author(s):

Lorenzo Gaetani ◽

Kaj Blennow ◽

Paolo Calabresi ◽

Massimiliano Di Filippo ◽

Lucilla Parnetti ◽

...

Keyword(s):

Light Chain ◽

Neurological Disorders ◽

Neurological Diseases ◽

Cerebrovascular Diseases ◽

Axonal Damage ◽

Neurofilament Light Chain ◽

Future Directions ◽

Neurofilament Light ◽

Prognostic Assessment ◽

Potential Applications

In the management of neurological diseases, the identification and quantification of axonal damage could allow for the improvement of diagnostic accuracy and prognostic assessment. Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large calibre myelinated axons. Its levels increase in cerebrospinal fluid (CSF) and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including inflammatory, neurodegenerative, traumatic and cerebrovascular diseases. New immunoassays able to detect biomarkers at ultralow levels have allowed for the measurement of NfL in blood, thus making it possible to easily and repeatedly measure NfL for monitoring diseases’ courses. Evidence that both CSF and blood NfL may serve as diagnostic, prognostic and monitoring biomarkers in neurological diseases is progressively increasing, and NfL is one of the most promising biomarkers to be used in clinical and research setting in the next future. Here we review the most important results on CSF and blood NfL and we discuss its potential applications and future directions.

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