Dataset Information

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

ABSTRACT:

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.

SUBMITTER: De Schaepdryver M

PROVIDER: S-EPMC9804063 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

De Schaepdryver Maxim M Masrori Pegah P Van Damme Philip P Poesen Koen K

CNS neuroscience & therapeutics 20220901 1

<h4>Aims</h4>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.<h4>Methods</h4>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) determina ...[more]

PMID: 36047371

Similar Datasets

Project description:ImportanceA clearer definition of the role of neurofilament light chain (NFL) as a biomarker in amyotrophic lateral sclerosis (ALS) is needed.ObjectivesTo assess the ability of NFL to serve as a diagnostic biomarker in ALS and the prognostic value of cerebrospinal fluid NFL in patients with ALS.Design, setting, and participantsIn this single-center, retrospective, longitudinal study, disease progression was assessed by the ALS Functional Rating Score-Revised and the ALS Milano-Torino Staging system at baseline and 6, 12, 24, and 36 months. Cerebrospinal fluid samples were obtained from 176 patients admitted to the Department of Neurosciences of the University of Padua, Padova, Italy, from January 1, 2010, through February 29, 2016. Patients with ALS underwent ambulatory follow-up at the same department.Main outcomes and measuresLevels of NFL.ResultsThe study included 94 patients with ALS (64 men [36.4%] and 30 women [17.0%]; median age, 62.5 years), 20 patients with frontotemporal dementia (FTD) (8 men [4.5%] and 12 women [6.8%]; median age, 65 years), 18 patients with motor neuropathies (14 men [8.0%] and 4 women [2.3%]; median age, 63 years), and 44 controls (24 men [13.6%] and 20 women [11.4%]; median age, 54 years). Log-transformed NFL (log[NFL]) concentrations were higher in the ALS and FTD groups compared with the motor neuropathies and control groups (hazard ratio [HR], 2.45; 95% CI, 1.66-3.61; P < .001). Patients with typical ALS (HR, 1.0 [reference]), progressive bulbar palsy (HR, 1.48; 95% CI, 0.58-3.75; P = .41), and upper motor neuron dominant ALS (HR, 0.12; 95% CI, 0.02-0.61; P = .01) had higher levels of NFL than did those with flail arm or leg syndrome (HR, 0.28; 95% CI, 0.08-0.10; P = .049) and progressive muscular atrophy (HR, 0.17; 95% CI, 0.22-1.36; P = .10). There was an inverse correlation between log[NFL] concentration and overall survival (HR, 2.45; 95% CI, 1.66-3.61; P < .001). There was no evidence of different log[NFL] concentrations and survival in genetic ALS.Conclusions and relevanceThis study confirms the role of NFL as a biomarker in ALS. Elevation in NFL levels in patients with upper motor neuron involvement and FTD might reflect the corticospinal tract degeneration. Low NFL levels in patients with lower motor neuron signs might be a prognostic indicator of milder phenotypes of disease.

Project description:Abstract A biomarker specific for the diagnosis of amyotrophic lateral sclerosis must be sensitive across a spectrum of clinical heterogeneity. Neurofilament light chain levels in amyotrophic lateral sclerosis correlate with the rate of disability progression. Previous attempts to establish a diagnostic role for neurofilament light chain have been limited to comparison with healthy individuals or controls with alternative diagnoses unlikely to be confused with amyotrophic lateral sclerosis in real-world clinical practice. In a tertiary amyotrophic lateral sclerosis referral clinic, at first visit, serum was taken for neurofilament light chain measurement after prospectively recording the clinical diagnosis as ‘amyotrophic lateral sclerosis’, ‘primary lateral sclerosis’, ‘alternative’ or ‘currently uncertain’. Of 133 referrals, 93 patients were diagnosed with amyotrophic lateral sclerosis (median neurofilament light chain 218.1 pg/ml, interquartile range 130.7–311.9), three primary lateral sclerosis (65.6, 51.5–106.9) and 19 alternative diagnoses (45.2, 13.5–71.9) at first visit. Of 18 initially uncertain diagnoses, eight were subsequently diagnosed with amyotrophic lateral sclerosis (98.5, 45.3–300.1). Neurofilament light chain ≥110.9 pg/ml had a positive predictive value of 0.92 for amyotrophic lateral sclerosis; <110.9 pg/ml had a negative predictive value of 0.48. In a specialized clinic, neurofilament light chain is largely confirmatory to clinical judgement in diagnosing amyotrophic lateral sclerosis and has limited ability to exclude alternative diagnoses. The current, important, value of neurofilament light chain is its potential to stratify patients with amyotrophic lateral sclerosis by disease activity and as a biomarker in therapeutic trials. To consider any added value of serum neurofilament light chain to the routine amyotrophic lateral sclerosis diagnostic pathway, Davies et al. prospectively analysed tertiary clinic referrals. In this setting, neurofilament light was neither a reliable rule-in nor rule-out test for amyotrophic lateral sclerosis or any alternative diagnosis. Graphical Abstract Graphical abstract

Dataset Information

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

Aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets