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Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS.

ABSTRACT: In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum.Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the follow-up period of 1 year. Levels of neurofilament light polypeptide (NF-L), glial fibrillary acidic protein, microtubule-associated protein tau, and S100 calcium binding protein B were measured in the CSF, and NF-L was also quantified in serum at each time point.One month after neurosurgical trauma, there was a distinct peak in NF-L concentration in both CSF and serum. In contrast, the biomarkers S100 calcium binding protein B, glial fibrillary acidic protein, and microtubule-associated protein tau did not show any significant changes. NF-L levels in both CSF and serum peaked at 1 month post surgery, returning to baseline after 6 to 9 months. A strong correlation was observed between the concentrations of NF-L in CSF and serum.The NF-L level, in CSF and serum, appears to be both a sensitive and specific marker for white matter axonal injury. This makes NF-L a valuable tool with which to evaluate acute white matter axonal damage in a clinical setting. Serum analysis of NF-L may become a convenient way to follow white matter axonal damage longitudinally.NCT01719159.

SUBMITTER: Bergman J

PROVIDER: S-EPMC4972001 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS.

Bergman Joakim J Dring Ann A Zetterberg Henrik H Blennow Kaj K Norgren Niklas N Gilthorpe Jonathan J Bergenheim Tommy T Svenningsson Anders A

Neurology(R) neuroimmunology & neuroinflammation 20160802 5

<h4>Objective</h4>In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum.<h4>Methods</h4>Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the ...[more]

PMID: 27536708

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Project description:BackgroundImpaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.MethodsNfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.ResultsCSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = - 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.ConclusionsThe observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.

Project description:BACKGROUND:Neurofilament light chain is a marker of axonal damage and is of interest as a biofluid biomarker for PD. The objective of this study was to investigate whether CSF or serum neurofilament contributes to a combination of CSF biomarkers in defining the optimal biomarker panel for discriminating PD patients from healthy controls. In addition, we aimed to assess whether CSF and/or serum neurofilament levels are associated with clinical measures of disease severity. METHODS:We measured neurofilament light chain levels in CSF and/or serum of 139 PD patients and 52 age-matched healthy controls. We used stepwise logistic regression analyses to test whether neurofilament contributes to a biomarker CSF panel including total, oligomeric, and phosphorylated ?-synuclein and Alzheimer's disease biomarkers. Measures of disease severity included disease duration, UPDRS-III, Hoehn & Yahr stage, and MMSE. RESULTS:After correcting for age, CSF neurofilament levels were 42% higher in PD patients compared with controls (P?<?0.01), whereas serum neurofilament levels were 37% higher (P = 0.08). Combining CSF neurofilament, phosphorylated-/total ?-synuclein, and oligomeric-/total ?-synuclein yielded the best-fitting model for discriminating PD patients from controls (area under the curve 0.92). The discriminatory potential of serum neurofilament in the CSF biomarker panel was similar (area under the curve 0.90). Higher serum neurofilament was associated with a lower MMSE score. There were no other associations between CSF and/or serum neurofilament levels and clinical disease severity. CONCLUSIONS:CSF neurofilament contributes to a panel of CSF ?-synuclein species in differentiating PD patients from healthy controls. Serum neurofilament may have added value to a biofluid biomarker panel for differentiating PD patients from controls. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS.

Publications

Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS.

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