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 (NfH^SMI35) correlate with disability, disease activity, or specific stages of MS.

Methods:

An electrochemiluminescence immunoassay was used to retrospectively measure NfH^SMI35 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 NfH^SMI35 increased with age in controls (r_s = 0.50, p < 0.0001) and CIS (r_s = 0.50, p < 0.0001); this effect was less pronounced in RRMS (r_s = 0.35, p = 0.027) and absent in SPMS/PPMS. After age correction, NfH^SMI35 levels were found to be higher in all disease stages compared to control. Relapses were associated with higher CSF NfH^SMI35 values compared with stable disease. NfH^SMI35 levels correlated with EDSS scores in patients with CIS and RRMS (r_s = 0.33, p = 0.001), and during relapse (r_s = 0.35, p = 0.01); the correlation was most prominent in RRMS during relapse (r_s = 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 NfH^SMI35 suggests that this loss accelerates over time. For MS, increased NfH^SMI35 levels reflect the superimposed presence of further neurodegenerative processes. Evaluation of NfH^SMI35 levels is likely to provide a useful surrogate for measuring the rate of neurodegeneration in MS. Furthermore, the dissociation of NfH^SMI35 levels with biomarkers of inflammation suggests that the mechanisms responsible for their production are at least partly independent.

	Year	Citations

Abstract

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