The prognostic value of CSF neurofilaments in multiple sclerosis at 15-year follow-up

Neurofilament proteins have been established as one of the most reliable body fluid biomarkers for neurodegeneration in multiple sclerosis.1 ,2 One key feature is that neurofilaments are specific for neurons and axons.3 Recent literature reviews consistently showed that elevated body fluid neurofilament protein levels are a poor prognostic sign.4 ,5 A common limitation of these studies was the relative short clinical follow-up period. Therefore, the aim of the present study was to test the long-term prognostic value of cerebrospinal fluid (CSF) neurofilament protein levels in a previously described cohort.6 More specifically, it was tested if high CSF neurofilament heavy chain (NfH) levels predicted a clinically relevant increase of disability as assessed by progression on the Expanded Disability Status Scale (EDSS) and its functional systems. Setting: a chart and database review of 51 patients from a previously reported cohort6 who were followed up clinically. Patient recruitment started in 1996 and the last clinical follow-up was in 2013. Clinical assessment and assays were as described.7 Of note, the longitudinal CSF NfH data on 29 of the 51 patients who also had undergone a second lumbar puncture were reported before,7 but the baseline CSF NfH data from the entire cohort subject to this study have not been published before. Descriptive statistics and non-parametric analyses were performed as described earlier, using SAS (V.9.4).7 Owing to non-Gaussian distribution, the median values and the 25–75% IQR were shown. Analyses of covariance (ANCOVA) were applied to test if elevated CSF NfH levels were of long-term prognostic value. The cut-off value …