Effect of neurofilament analysis on the diagnostic delay in amyotrophic lateral sclerosis

AIMS: The aim of this study was to investigate whether neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in cerebrospinal fluid (CSF), sampled prior to referral to a neuromuscular reference center (NMRC), shorten the diagnostic delay in patients with amyotrophic lateral sclerosis. METHODS: In this retrospective study, patients with ALS were included with (i) determination of neurofilaments (Nfs) before referral to the NMRC (preC‐Nfs ALS, n = 58), (ii) determination of Nfs at the NMRC (C‐Nfs, n = 54) or (iii) with no determination of Nfs (C‐No Nfs, n = 180). Fifty‐six disease controls were included. RESULTS: The preC‐Nfs cohort had CSF sampled 2.2 months (range: 0.6–12.0 months) before referral to the NMRC. In this cohort, the diagnostic delay was significantly shorter [median (range): 8.24 (2.37–49.7) months] than in the C‐Nfs cases [median (range): 11.4 (2.93–86.5) months; p < 0.05], but not in the C‐No Nfs cases. When including the disease progression rate and the presence of a genetic mutation as covariates, the difference ceased to exist (p = 0.14). pNfH and NfL levels in the preC‐Nfs cohort were significantly higher than in disease controls (p < 0.0001). Both Nfs showed a similar discriminating performance. CONCLUSIONS: CSF Nfs assessed before the diagnosis of ALS at a NMRC decreased the diagnostic delay in specific cases by 3 months and only when other covariates were not taken into account.