Claudia D Wurster1, Petra Steinacker2, René Günther3,4, Jan C Koch5, Paul Lingor6, Zeljko Uzelac2, Simon Witzel2, Kurt Wollinsky7, Benedikt Winter8, Alma Osmanovic9, Olivia Schreiber-Katz9, Rami Al Shweiki2, Albert C Ludolph2,10, Susanne Petri9, Andreas Hermann11,12, Markus Otto2. 1. Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany. claudia.wurster@uni-ulm.de. 2. Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081, Ulm, Germany. 3. Department of Neurology, Technische Universität Dresden, Dresden, Germany. 4. German Center for Neurodegenerative Diseases (DZNE) Dresden, Dresden, Germany. 5. Department of Neurology, University Medicine Göttingen, Göttingen, Germany. 6. Department of Neurology, Klinikum Rechts Der Isar der Technischen Universität München, Munich, Germany. 7. Department of Anesthesiology, RKU, University and Rehabilitation Clinics, Ulm University, Ulm, Germany. 8. Department of Pediatrics, Ulm University, Ulm, Germany. 9. Department of Neurology, Hannover Medical School, Hannover, Germany. 10. German Center for Neurodegenerative Diseases (DZNE) Ulm, Ulm, Germany. 11. Translational Neurodegeneration Section "Albrecht-Kossel", Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany. 12. German Center for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany.
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.
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 SMApatients 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 SMApatients 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 SMApatients 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 SMApatients, 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.
Entities:
Keywords:
Antisense-oligonucleotide; Neurofilaments; Nusinersen; SMA
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