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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. [ABSTRACT FROM AUTHOR]

Background: There is limited information on neurochemical markers being used to support and monitor the affection of motoneurons in patients with spinal muscular atrophy (SMA). The objective of this study was to examine neurochemical markers in cerebrospinal fluid (CSF) under treatment with the antisense-oligonucleotide (ASO), nusinersen. Methods: We measured markers of axonal degeneration [neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)] along with basic CSF parameters in 25 adolescent and adult SMA type 2 and 3 patients at baseline and after four intrathecal injections of nusinersen. Neurochemical markers were compared with controls. In addition, neurochemical markers in SMA patients were related to the Hammersmith Functional Rating Scale Expanded (HFMSE). Results: No significant difference in neurofilament (Nf) values was observed between SMA and control group, neither at baseline nor after four injections of nusinersen. NfL, protein and quotients of albumin (Qalb) increased slightly in SMA patients after the fourth injection. The slight increase of NfL could be related to the development of mild CSF flow change. No relations were observed between changes in Nf and HFMSE. Conclusion: We assume that Nf levels in CSF in these patients may result from slow disease progression in this stage of disease, pre-existing loss of motoneurons due to long disease duration besides affection of the LMN only. Therefore, we conclude that Nf levels in CSF do not seem useful as diagnostic and monitoring markers in adolescent and adult SMA type 2 and 3 patients. [ABSTRACT FROM AUTHOR]