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Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen.
J Neurol 2020; 267(1):36-44JN

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.

Authors+Show Affiliations

Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany. claudia.wurster@uni-ulm.de.Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.Department of Neurology, Technische Universität Dresden, Dresden, Germany. German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany.Department of Neurology, University Medicine Göttingen, Göttingen, Germany.Department of Neurology, Klinikum Rechts Der Isar der Technischen Universität München, Munich, Germany.Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.Department of Anesthesiology, RKU, University and Rehabilitation Clinics, Ulm University, Ulm, Germany.Department of Pediatrics, Ulm University, Ulm, Germany.Department of Neurology, Hannover Medical School, Hannover, Germany.Department of Neurology, Hannover Medical School, Hannover, Germany.Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany. German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany.Department of Neurology, Hannover Medical School, Hannover, Germany.Translational Neurodegeneration Section "Albrecht-Kossel", Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany. German Center for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany.Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31552549

Citation

Wurster, Claudia D., et al. "Neurofilament Light Chain in Serum of Adolescent and Adult SMA Patients Under Treatment With Nusinersen." Journal of Neurology, vol. 267, no. 1, 2020, pp. 36-44.
Wurster CD, Steinacker P, Günther R, et al. Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen. J Neurol. 2020;267(1):36-44.
Wurster, C. D., Steinacker, P., Günther, R., Koch, J. C., Lingor, P., Uzelac, Z., ... Otto, M. (2020). Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen. Journal of Neurology, 267(1), pp. 36-44. doi:10.1007/s00415-019-09547-y.
Wurster CD, et al. Neurofilament Light Chain in Serum of Adolescent and Adult SMA Patients Under Treatment With Nusinersen. J Neurol. 2020;267(1):36-44. PubMed PMID: 31552549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen. AU - Wurster,Claudia D, AU - Steinacker,Petra, AU - Günther,René, AU - Koch,Jan C, AU - Lingor,Paul, AU - Uzelac,Zeljko, AU - Witzel,Simon, AU - Wollinsky,Kurt, AU - Winter,Benedikt, AU - Osmanovic,Alma, AU - Schreiber-Katz,Olivia, AU - Al Shweiki,Rami, AU - Ludolph,Albert C, AU - Petri,Susanne, AU - Hermann,Andreas, AU - Otto,Markus, AU - ,, Y1 - 2019/09/24/ PY - 2019/08/15/received PY - 2019/09/16/accepted PY - 2019/09/13/revised PY - 2019/9/26/pubmed PY - 2019/9/26/medline PY - 2019/9/26/entrez KW - Antisense-oligonucleotide KW - Neurofilaments KW - Nusinersen KW - SMA SP - 36 EP - 44 JF - Journal of neurology JO - J. Neurol. VL - 267 IS - 1 N2 - 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. SN - 1432-1459 UR - https://www.unboundmedicine.com/medline/citation/31552549/Neurofilament_light_chain_in_serum_of_adolescent_and_adult_SMA_patients_under_treatment_with_nusinersen_ L2 - https://dx.doi.org/10.1007/s00415-019-09547-y DB - PRIME DP - Unbound Medicine ER -