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

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.

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.

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.

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.