Abstract
Objectives: Elevated neurofilament light chain (NFL) levels within the cerebrospinal fluid (CSF) are a biomarker representing axonal neurodegeneration in rapid progressive neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). It is unclear to what extent the levels of NFL increase in the CSF (CSF-NFL) in a chronic neuroinflammatory process with axonal neurodegeneration, as found in primary progressive multiple sclerosis (PPMS).Methods: We used a multicenter approach to statistically compare CSF-NFL levels between PPMS patients (n = 50), ALS patients (n = 50), and healthy controls (n = 50). Clinical findings, including disease duration, expanded disability status scale (EDSS), electrophysiological recordings such as visual evoked potentials or spinal and cerebral MRI, and previously administered treatment were selected as experimental parameters retrospectively.Results: Median [range] CSF-NFL concentrations in PPMS patients were significantly higher than in the controls [1724 (799–4275) pg/ml vs. 1202 (612–2934) pg/ml, p = 0.015], and significantly lower compared to ALS patients [1724 (799–4275) pg/ml vs. 10238 (2610–35138) pg/ml, p < 0.001]. There was no correlation between CSF-NFL and disease duration (p = 0.5), EDSS (p = 0.2) or treatment (p = 0.3).Conclusion: We conclude that CSF-NFL may mirror the proposed slow axonal degeneration in PPMS, but does not reflect the disease severity.
Highlights
The pattern underlying the concentrations of neurofilament light chain (NFL) in the cerebrospinal fluid (CSF), referred to as CSF-NFL, in diseases with slow progressive axonal degeneration, including primary progressive multiple sclerosis (PPMS), are not clear
Mean [SD] disease duration was significantly longer in PPMS [86 [952] months] compared to amyotrophic lateral sclerosis (ALS) [15 [17] months, p < 0.001]
The PPMS patients recruited from the three different University centers did not differ with respect to age, sex, CSF protein, oligoclonal band positivity, median expanded disability status scale (EDSS) or disease duration
Summary
The pattern underlying the concentrations of neurofilament light chain (NFL) in the cerebrospinal fluid (CSF), referred to as CSF-NFL, in diseases with slow progressive axonal degeneration, including primary progressive multiple sclerosis (PPMS), are not clear. PPMS and CSF-NFL neurodegenerative diseases with a predominant affection of the central motor system such as amyotrophic lateral sclerosis (ALS), result in a clear pathological increase of the CSF-NFL levels [1,2,3]. Reasons may be the small sample sizes selected for these PPMS studies [6, 8] or the inclusion of patients with partially acute inflammatory disease activity and only occasional motor impairment, not the typical long-standing chronic disease progression [12]. We conducted a cross-sectional multicenter study measuring the CSF levels of the stable protein NFL [1] in patients suffering from mainly long-standing PPMS without acute inflammatory disease activity, and compared them to the CSF levels in ALS patients and disease controls
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call