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Journal of Neurology
Published in: Journal of Neurology 1/2020

01-01-2020 | Amyotrophic Lateral Sclerosis | Original Communication

Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen

Authors: Claudia D. Wurster, Petra Steinacker, René Günther, Jan C. Koch, Paul Lingor, Zeljko Uzelac, Simon Witzel, Kurt Wollinsky, Benedikt Winter, Alma Osmanovic, Olivia Schreiber-Katz, Rami Al Shweiki, Albert C. Ludolph, Susanne Petri, Andreas Hermann, Markus Otto, the MND-Net

Published in: Journal of Neurology | Issue 1/2020

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Abstract

Objective

To determine the diagnostic and monitoring value of serum neurofilament light chain (NfL) in spinal muscular atrophy (SMA).

Methods

We measured serum NfL in 46 SMA patients at baseline and over 14 months of treatment with the antisense-oligonucleotide (ASO) nusinersen using the ultrasensitive single molecule array (Simoa) technology. Serum NfL levels of SMA patients were compared to controls and related to cerebrospinal fluid (CSF) NfL, blood-CSF barrier function quantified by the albumin blood/CSF ratio (Qalb) and motor scores (Hammersmith Functional Motor Scale Expanded, HFMSE; Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, ALSFRS-R).

Results

Serum NfL levels of SMA patients were in the range of controls (p = 0.316) and did not correlate with CSF NfL (ρ = 0.302, p = 0.142) or Qalb (ρ = − 0.160, p = 0.293). During therapy, serum NfL levels were relatively stable with notable concentration changes in single SMA patients, however, within the control range. Higher NfL levels were associated with worse motor performance in SMA (baseline: HFMSE ρ = − 0.330, p = 0.025, ALSFRS-R ρ = − 0.403, p = 0.005; after 10 months: HFMSE ρ = − 0.525, p = 0.008, ALSFRS-R ρ = − 0.537, p = 0.007), but changes in motor scores did not correlate with changes in serum NfL.

Conclusion

Diagnostic and monitoring performance of serum NfL measurement seems to differ between SMA subtypes. Unlike to SMA type 1, in adolescent and adult SMA type 2 and 3 patients, neurodegeneration is not reflected by increased NfL levels and short-term therapeutic effects cannot be observed. Long-term follow-up has to be performed to see if even low levels of NfL might be good prognostic markers.
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Metadata
Title
Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen
Authors
Claudia D. Wurster
Petra Steinacker
René Günther
Jan C. Koch
Paul Lingor
Zeljko Uzelac
Simon Witzel
Kurt Wollinsky
Benedikt Winter
Alma Osmanovic
Olivia Schreiber-Katz
Rami Al Shweiki
Albert C. Ludolph
Susanne Petri
Andreas Hermann
Markus Otto
the MND-Net
Publication date
01-01-2020
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 1/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-019-09547-y

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