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      Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis

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          Abstract

          Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration.

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          Awaji diagnostic algorithm increases sensitivity of El Escorial criteria for ALS diagnosis.

          Mamede de Carvalho, Michael Swash (2009)
          We have tested the sensitivity of a recently published approach to combining clinical and EMG data in the 'research diagnosis' of ALS, in 55 consecutive patients clinically diagnosed with ALS. The application of this 'Awaji algorithm' to the revised El Escorial diagnostic criteria for diagnosis of ALS achieved a diagnostic sensitivity of 95% for definite ALS compared with 18% using the clinical El Escorial criteria and 53% when the EMG criteria as defined in the El Escorial criteria, were applied to the same dataset. This increased sensitivity was particularly relevant for bulbar onset patients (sensitivity improved from 38% to 87%) and for patients with El Escorial clinically possible ALS (from 50% to 86%). We suggest that, in future, investigators and triallists should use the Awaji algorithm superimposed onto the El Escorial criteria, in selecting patients for research studies.
          Article 0 comments Cited 68 times – based on 0 reviews     Review now
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            NF-L in cerebrospinal fluid and serum is a biomarker of neuronal damage in an inducible mouse model of neurodegeneration.

            Catherine Pech, Stéphanie Hamon, Véronique Blanchard-Bregeon … (2017)
            Accumulation of neurofilaments (NFs), the major constituents of the neuronal cytoskeleton, is a distinctive feature of neurological diseases and several studies have shown that soluble NFs can be detected in the cerebrospinal fluid (CSF) of patients with neurological diseases, such as multiple sclerosis and frontotemporal dementia. Here we have used an inducible transgenic mouse model of neurodegeneration, CamKII-TetOp25 mice, to evaluate whether NF-L levels in CSF or blood can be used as a biochemical biomarker of neurodegeneration. Induction of p25 transgene brain expression led to increase in CSF and serum NF-L levels that correlated with ongoing neurodegeneration. Switching off p25 prevented further increases in both CSF and serum NF-L levels and concomitantly stopped the progression of neurodegeneration. The levels of CSF NF-L detected in p25 mice are about 4-fold higher than the CSF levels detected in patients with chronic neurodegenerative diseases, such as symptomatic FTD (bvFTD). In addition, our data indicate that the NF-L detected in CSF is most likely a cleaved form of NF-L. These results suggest that CSF and serum NF-L are of interest to be further explored as potential translational dynamic biomarkers of neurodegeneration or as pharmacodynamics biomarkers at least in preclinical animal studies.
            Article 0 comments Cited 33 times – based on 0 reviews     Review now
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              Benefit of the Awaji diagnostic algorithm for amyotrophic lateral sclerosis: a prospective study.

              Philip van den Broek, Charlotte Smetcoren, Wim Robberecht … (2011)
              Early and accurate diagnosis of amyotrophic lateral sclerosis (ALS) is important for patient care and for entry in clinical trials. Retrospective studies suggest that the use of the Awaji algorithm for the diagnosis of ALS is more sensitive for early diagnosis than the currently used revised El Escorial criteria. We prospectively compared the revised El Escorial criteria with the Awaji algorithm in patients seen with suspected ALS at the University Hospitals Leuven between January 2008 and April 2010. Out of 200 patients referred for the diagnosis of ALS, 66% and 85% could be categorized to definite or probable ALS at first presentation according to the revised El Escorial and the Awaji algorithm, respectively (p 50% reduction of patients not eligible for clinical trial entry. Application of the Awaji algorithm made the diagnosis of ALS more likely by at least 1 diagnostic category in 25.7% of patients and identified at least 1 additional region with electrodiagnostic signs of ongoing lower motor neuron loss in 46.4% of electrodiagnostic investigations. Application of the Awaji algorithm did not result in a single false-positive diagnosis of ALS in this study. Our data demonstrate that the Awaji algorithm is significantly more sensitive compared to the revised El Escorial criteria, without resulting in false-positive diagnoses of ALS. It should therefore be used in clinical trials. Copyright © 2011 American Neurological Association.
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                Author and article information

                Journal
                Title: Neuropathology and Applied Neurobiology
                Abbreviated Title: Neuropathol Appl Neurobiol
                Publisher: Wiley
                ISSN: 03051846
                Publication date (Electronic): July 18 2018
                Affiliations
                [1 ]Laboratory for Molecular Neurobiomarker Research; Department of Neurosciences; KU Leuven; Leuven Belgium
                [2 ]Department of Chronic Disease, Metabolism and Ageing; KU Leuven; Leuven Belgium
                [3 ]Laboratory Medicine; University Hospitals Leuven; Leuven Belgium
                [4 ]Laboratory of Neurobiology; Department of Neurosciences; KU Leuven and Center for Brain & Disease Research VIB Leuven; Leuven Belgium
                [5 ]Department of Neurology; Neuromuscular Reference Centre; University Hospitals Leuven; Leuven Belgium
                [6 ]Laboratory for Neuroimmunology; Department of Neurosciences; KU Leuven; Leuven Belgium
                [7 ]Department of Neurosurgery; Neuromuscular Reference Centre; University Hospitals Leuven; Leuven Belgium
                [8 ]Research Group Experimental Neurosurgery and Neuroanatomy; KU Leuven; Department of Neurosciences; Leuven Belgium
                [9 ]Laboratory for Muscle diseases and Neuropathies; Department of Neurosciences; KU Leuven; Leuven Belgium
                [10 ]Alzheimer Research Centre KU Leuven; Leuven Institute of Neuroscience and Disease; Leuven Belgium
                [11 ]Department of Geriatric Medicine; University Hospitals Leuven; Leuven Belgium
                Article
                DOI: 10.1111/nan.12511
                SO-VID: 3404ad60-b76f-437d-857e-baab14509d53
                Copyright © © 2018
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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