Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

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Excerpt

The clinical course of multiple sclerosis (MS) is highly variable, ranging from rapidly reversible episodes of impairment to severe disability within months after disease onset. Focal inflammation, chronic diffuse neuronal damage, and failure of repair or compensation all contribute to the development of permanent disability.1 Biomarkers reflecting tissue damage and allowing the monitoring of subclinical disease activity are highly desirable for assessment of therapeutic response and prediction of disability in both clinical studies and management of individual patients.2
Together with the medium and heavy subunits, neurofilament light chain (NfL) represents one of the scaffolding proteins of the neuronal cytoskeleton and is released in the extracellular space following axonal damage.3 NfL levels are increased in the cerebrospinal fluid (CSF) of MS patients as well as in degenerative and traumatic neurological diseases (eg, dementia, amyotrophic lateral sclerosis, and spinal cord injury).4 CSF NfL levels are further increased during relapses and are positively associated with magnetic resonance imaging (MRI) lesion load and disability scores in MS.10 Noteworthy, CSF NfL levels have also been shown to be a marker of treatment response in this disease.13 However, lumbar punctures are relatively invasive procedures, limiting the value of CSF NfL in routine clinical settings.
A commercially available enzyme‐linked immunosorbent assay (ELISA; UmanDiagnostics, Umeå, Sweden) can be used to measure CSF NfL, but is not recommended for blood measurements. Using an electrochemiluminescence (ECL)‐based assay, we have found increased serum NfL (sNfL) concentrations in clinically isolated syndrome (CIS) and MS patients.11 However, these studies were limited by the still relatively low sensitivity of the assay.20 A novel single‐molecule array (Simoa) assay has shown 126‐ and 25‐fold higher sensitivity than the ELISA and ECL assays, respectively.20 This high sensitivity allows a more accurate quantification of the low sNfL concentrations expected in healthy controls (HC) and can help to better differentiate abnormal from normal values. Recent studies using this assay have shown that sNfL levels are increased in patients suffering from acute brain damage or chronic neurodegenerative disorders.22
This study had several aims: (1) to obtain a pilot estimate of the distribution of sNfL concentrations in HC and to investigate the potential influence of age and gender; (2) to compare paired sNfL and CSF NfL levels in MS patients; (3) to investigate the association between sNfL and number of T2 and contrast‐enhancing lesions in brain and spinal cord; (4) to investigate the association between sNfL and clinical features, including occurrence of relapses, worsening of disability, and treatment status; and (5) to test whether elevated sNfL levels can predict later disease activity and disability worsening.

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