Neurofilament heavy chain in CSF correlates with relapses and disability in multiple sclerosis
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Abstract
Objective: Neurodegeneration is now accepted as a pathologic hallmark of multiple sclerosis (MS). We sought to discover whether CSF levels of neurofilament heavy chain protein (NfHSMI35) correlate with disability, disease activity, or specific stages of MS.
Methods: An electrochemiluminescence immunoassay was used to retrospectively measure NfHSMI35 in CSF of patients with clinically isolated syndrome (CIS) (n = 63), relapsing-remitting multiple sclerosis (RRMS) (n = 39), secondary progressive multiple sclerosis (SPMS) (n = 25), primary progressive multiple sclerosis (PPMS) (n = 23), or controls (n = 73). Cell count and CSF levels of immunoglobulin and albumin were also measured.
Results: CSF levels of NfHSMI35 increased with age in controls (rs = 0.50, p < 0.0001) and CIS (rs = 0.50, p < 0.0001); this effect was less pronounced in RRMS (rs = 0.35, p = 0.027) and absent in SPMS/PPMS. After age correction, NfHSMI35 levels were found to be higher in all disease stages compared to control. Relapses were associated with higher CSF NfHSMI35 values compared with stable disease. NfHSMI35 levels correlated with EDSS scores in patients with CIS and RRMS (rs = 0.33, p = 0.001), and during relapse (rs = 0.35, p = 0.01); the correlation was most prominent in RRMS during relapse (rs = 0.54, p = 0.01). This was not the case for any of the other CSF markers examined.
Conclusions: Neuronal loss is a feature of aging, and the age-dependent increase of CSF NfHSMI35 suggests that this loss accelerates over time. For MS, increased NfHSMI35 levels reflect the superimposed presence of further neurodegenerative processes. Evaluation of NfHSMI35 levels is likely to provide a useful surrogate for measuring the rate of neurodegeneration in MS. Furthermore, the dissociation of NfHSMI35 levels with biomarkers of inflammation suggests that the mechanisms responsible for their production are at least partly independent.
Footnotes
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Study funding: Supported by the Swiss Multiple Sclerosis Society.
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Editorial, page 1200
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Supplemental data at www.neurology.org
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- CI
- confidence interval
- CIS
- clinically isolated syndrome
- ECL
- electrochemiluminescence
- EDSS
- Expanded Disability Status Scale
- Ig
- immunoglobulin
- MS
- multiple sclerosis
- Nf
- neurofilament
- OCB
- oligoclonal IgG band
- PPMS
- primary progressive multiple sclerosis
- RRMS
- relapsing-remitting multiple sclerosis
- SPMS
- secondary progressive multiple sclerosis.
- Received June 26, 2010.
- Accepted October 25, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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