scholarly journals Serum Neurofilament Light Chain: A Marker of Nervous System Damage in Myopathies

2021 ◽  
Vol 15 ◽  
Author(s):  
Annika Saak ◽  
Pascal Benkert ◽  
Katja Akgün ◽  
Eline Willemse ◽  
Jens Kuhle ◽  
...  
Keyword(s):  
Nervous System ◽  
Disease Control ◽  
Light Chain ◽  
Neuronal Damage ◽  
Control Group ◽  
Molecular Defect ◽  
Type I ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
System Involvement

Purpose: Neurofilament light chain in serum (sNfL) has been suggested as a biomarker for the assessment of neuroaxonal damage. Since NfL are not expressed in muscle, elevated sNfL in patients with primary myopathies suggest additional nervous system involvement. To verify this hypothesis, we measured sNfL in a series of patients with myopathies.Methods: sNfL were determined in 62 patients with molecular proven primary myopathies in whom some nervous system involvement may be predicted: myotonic dystrophy type I and II (DM I, II) and mitochondrial disease. In addition, sNfL were measured in 8 patients with facioscapulohumeral muscular dystrophy (FSHD) and in a disease control group caused by genetic defects exclusively expressed in muscle.Results: sNfL values were significantly elevated in the DM I, the DM II and the mitochondrial group, with FSHD patients showing the lowest sNfL elevations. sNfL levels in the disease control group were not different from the healthy controls. A significant correlation between repeat length and sNfL levels was found in the DM I patients, but not in the DM II patients. Mitochondrial patients with encephalopathy showed significantly higher sNfL concentrations compared to patients with only muscular symptoms.Conclusion: sNfL levels are elevated in myopathies with, based on the underlying molecular defect or clinical features, established nervous system involvement, i.e., myotonic dystrophies and mitochondrial disorders. sNfL were also raised in FSHD, where involvement of the nervous system is not usually clinically apparent. Thus, sNfL concentrations may serve as a biomarker for additional neuronal damage in primary myopathies.

scholarly journals Neurofilament light chain level in plasma extracellular vesicles and Parkinson’s disease

2020 ◽  
Vol 13 ◽  
pp. 175628642097591
Author(s):  
Chen-Chih Chung ◽  
Lung Chan ◽  
Jia-Hung Chen ◽  
Oluwaseun Adebayo Bamodu ◽  
Chien-Tai Hong
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Extracellular Vesicles ◽  
Light Chain ◽  
Rating Scale ◽  
Neuronal Damage ◽  
Control Group ◽  
Motor Symptoms ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background: Neurofilament light chain (NfL) is essential for axonal maintenance and reflects neuronal damage. Extracellular vesicles (EVs), especially exosomes, secreted by cells into the blood, are emerging as novel biomedical research platforms of physiological and pathological processes. The present study investigated the possible association between plasma EV NfL and Parkinson’s disease (PD). Methods: One hundred and sixteen patients with mild to moderate PD and 46 non-PD, neurological controls were recruited, and their clinical motor symptoms and cognitive function were evaluated. Plasma EVs were isolated using an exoEasy kit, and immunomagnetic reduction assay was used to assess EV NfL level. Statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant. Results: The isolated plasma EVs were validated according to size and the presence of specific surface markers. Compared with the neurological control group, the levels of plasma EV NfL in patients with PD were not significantly different (PD: 9.42 ± 3.89, control: 9.53 ± 3.62 pg/mL plasma, p = 0.71). On the other hand, plasma EV NfL in patients with PD trendwise correlated with the severity of akinetic rigidity ( p = 0.05). PD patients with optimal EV NfL (lowest quartile) had 6.66 ± 2.08 lower Unified Parkinson’s Disease Rating Scale-III score after adjustment for age, sex, and disease duration. Conclusion: Plasma EV NfL levels did not distinguish patients with PD from the neurological control group. The possible correlation between plasma EV NfL with the severity of motor symptoms within the PD patients, especially with akinetic rigidity, was noted. Further clinical validation of the blood EV NfL by a longitudinal follow-up study of PD patients is warranted.

scholarly journals Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

2021 ◽  
Vol 11 (2) ◽  
pp. 238
Author(s):  
Keld-Erik Byg ◽  
Helle H. Nielsen ◽  
Tobias Sejbaek ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chain ◽  
Plasma Levels ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Fluid Levels

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

scholarly journals No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach

2021 ◽  
pp. 100056
Author(s):  
Jasmini ALAGARATNAM ◽  
Wolfgang STÖHR ◽  
Jamie TOOMBS ◽  
Amanda HESLEGRAVE ◽  
Henrik ZETTERBERG ◽  
...  
Keyword(s):  
Light Chain ◽  
Neuronal Damage ◽  
Hiv Cure ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ngoc Dung Le ◽  
Lukas Muri ◽  
Denis Grandgirard ◽  
Jens Kuhle ◽  
David Leppert ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Pneumococcal Meningitis ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Health Concern ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Inflammatory Phase

Abstract Background Pneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM). Methods Eleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively. Results In ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics. Conclusion Current results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.

scholarly journals Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives

2021 ◽  
pp. 000486742110586
Author(s):  
Dhamidhu Eratne ◽  
Shorena Janelidze ◽  
Charles B Malpas ◽  
Samantha Loi ◽  
Mark Walterfang ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Light Chain ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
First Episode ◽  
Treatment Resistant ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
First Degree Relatives ◽  
Frontotemporal Dementias

Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine ( n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine ( n = 13), and age- and sex-matched controls ( n = 59). Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman’s r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia ( r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight ( r = −0.305, 95% confidence interval: [−0.504, −0.076]). Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode.

scholarly journals Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

2021 ◽  
pp. 1-7
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

scholarly journals Serum neurofilament light chain as outcome marker for intensive care unit patients

2020 ◽  
Author(s):  
Anna Lena Fisse ◽  
Kalliopi Pitarokoili ◽  
David Leppert ◽  
Jeremias Motte ◽  
Xiomara Pedreiturria ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Central Nervous System ◽  
Nervous System ◽  
Intensive Care ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Icu Patients ◽  
Neurofilament Light ◽  
The Central Nervous System

Abstract Objective Neurofilament light chain (NfL) in serum indicates neuro-axonal damage in diseases of the central and peripheral nervous system. Reliable markers to enable early estimation of clinical outcome of intensive care unit (ICU) patients are lacking. The aim of this study was to investigate, whether serum NfL levels are a possible biomarker for prediction of outcome of ICU patients. Methods Thirty five patients were prospectively examined from admission to ICU until discharge from the hospital or death. NfL levels were measured longitudinally by a Simoa assay. Results NfL was elevated in all ICU patients and reached its maximum at day 35 of ICU treatment. Outcome determined by modified Rankin Scale at the end of the follow-up period correlated with NfL level at admission, especially in the group of patients with impairment of the central nervous system (n = 25, r = 0.56, p = 0.02). Conclusion NfL could be used as a prognostic marker for outcome of ICU patients, especially in patients with impairment of the central nervous system.

scholarly journals CSF Neurofilament Light Chain Concentrations Predict Outcome in Bacterial Meningitis

2021 ◽  
Vol 9 (1) ◽  
pp. e1123
Author(s):  
Nora Chekrouni ◽  
Thijs M. van Soest ◽  
Matthijs C. Brouwer ◽  
Eline A.J. Willemse ◽  
Charlotte E. Teunissen ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Light Chain ◽  
Neuronal Damage ◽  
Area Under The Curve ◽  
Case Fatality ◽  
High Serum ◽  
Unfavorable Outcome ◽  
Index Test ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Background and ObjectivesNeurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquired bacterial meningitis.MethodsWe measured NfL concentration CSF samples from a prospective cohort study of adults with community-acquired bacterial meningitis in The Netherlands and determined associations between NfL CSF concentrations, clinical characteristics, and outcome in multivariate analyses. We identified independent predictors of an unfavorable outcome (Glasgow Outcome Scale scores 1–4) by logistic regression.ResultsCSF NfL concentrations were evaluated in 429 episodes of 425 patients with community-acquired bacterial meningitis. The median age of 429 episodes was 62 years (interquartile range, 50–69 years). Of note, 290 of 422 (68%) episodes presented with an altered mental status (Glasgow Coma Scale score < 14). Most common causative pathogens were Streptococcus pneumoniae (73%), Neisseria meningitidis (7%), and Listeria monocytogenes (5%). The overall case fatality rate was 62 of 429 (15%), and unfavorable outcome occurred in 57 (37%) of 429 episodes. In multivariate analysis, predictors of unfavorable outcome were older age (OR 1.03, 95% CI 1.01–1.05), cranial nerve palsy (OR 4, 95% CI 1.6–10.3), high serum C-reactive protein concentration (OR 1.3, 95% CI 1.01–1.05), and high CSF NfL concentration (OR 1.5, 95% CI 1.07–2.00). CSF NfL concentrations were higher in patients presenting with focal cerebral deficits (717 pg/mL [416–1,401] vs 412 pg/mL [278–731]; p < 0.001). The area under the curve (AUC) for predicting unfavorable outcome in bacterial meningitis of CSF NfL concentration was 0.69 (95% CI, 0.64–0.74).DiscussionCSF NfL concentration is independently associated with unfavorable outcome in adults with community-acquired bacterial meningitis, suggesting that CSF NfL concentration may be a useful biomarker for prognostic assessment in bacterial meningitis.Classification of EvidenceCan the level of NfL in CSF (the index test) predict unfavorable outcome in patients with bacterial meningitis, in a cohort of bacterial meningitis patients with a favorable and unfavorable outcome? This study provides Class II evidence that NfL level in CSF is a moderate predictor, with the AUC for predicting unfavorable outcome in bacterial meningitis being 0.69 (95% CI, 0.64–0.74).

scholarly journals Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

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