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Motor unit changes in children with symptomatic spinal muscular atrophy treated with nusinersen
  1. Didu Kariyawasam1,2,
  2. Arlene D'Silva2,
  3. James Howells3,
  4. Karen Herbert4,
  5. Peter Geelan-Small5,
  6. Cindy Shin-Yi Lin3,
  7. Michelle Anne Farrar1,2
  1. 1 Neurology, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia
  2. 2 School of Women's and Children's Health, UNSW Medicine, University of New South Wales, Sydney, New South Wales, Australia
  3. 3 Central Clinical School, Faculty of Medicine and Health, Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
  4. 4 Physiotherapy, Syndey Children's Hospital, Randwick, Sydney, New South Wales, Australia
  5. 5 Mark Wainwright Analytical Centre, University of New South Wales, Sydney, New South Wales, Australia
  1. Correspondence to Dr Didu Kariyawasam, Neurology, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia; Didu.Kariyawasam{at}


Objectives To elucidate the motor unit response to intrathecal nusinersen in children with symptomatic spinal muscular atrophy (SMA) using a novel motor unit number estimation technique.

Methods MScanFit MUNE studies were sequentially undertaken from the abductor pollicis brevis muscle after stimulation of the median nerve in a prospective cohort of symptomatic children with SMA, undergoing intrathecal treatment with nusinersen at a single neuromuscular centre from June 2017 to August 2019. Electrophysiological measures included compound muscle action potential (CMAP), motor unit number estimation (MUNE), motor unit number contributing to 50%–100% of CMAP (N50) and measures of collateral reinnervation including largest single motor unit potential (LSMUP) and amplitude of the smallest unit contributing to N50 (A50).

Results Twenty children (median age 99 months, range 4–193) were followed for a median of 13.8 (4–33.5) months. Therapeutic intervention was an independent and significant contributor to an increase in CMAP (p = 0.005), MUNE (p = 0.001) and N50 (p = 0.04). The magnitude of this electrophysiological response was increased in children with shorter disease durations (p<0.05). Electrophysiological changes delineated children who were functionally stable from those who attained clinically significant gains in motor function.

Interpretation Nusinersen therapy facilitated functional innervation in SMA through recovery of smaller motor units. Delineation of biomechanisms of therapeutic response may be the first step in identifying potential novel targets for disease modification in this and other motor neuropathies. MScanFit MUNE techniques may have a broader role in establishing biomarkers of therapeutic response in similar adult-onset diseases.

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  • Contributors DK and MAF planned the manuscript. MAF, DK, AD and CS-YL collated electrophysiological and clinical parameters during the study. DK and AD executed and prepared the first and subsequent drafts of the manuscript. KH completed all functional motor assessments. PG-S, AD and DK completed statistical analysis of the data. JH, CS-YL and MAF contributed to figures and interpretation of results. DK, MAF, AD, CS-YL, PG-S and KH contributed to manuscript revision. All authors read and approved the submitted version.

  • Funding DK acknowledges funding from the RTP Scholarship, University of New South Wales and The Freedman Family Foundation Scholarship, Sydney Children’s Hospital Foundation Trust. AD acknowledges funding from the Sydney Children’s Hospital Foundation.

  • Competing interests MAF has previously received compensation as a member of the scientific advisory board for Biogen, who manufactures the medication that is tested in this study. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  • Patient consent for publication Parental/guardian consent obtained.

  • Ethics approval The study was approved by the Sydney Children’s Hospital Network and South Eastern Sydney and Illawarra Area Health Service Human Research Ethics Committee (HREC/18/SCHN/373).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The data central to this study is available on request from suitably qualified researchers.

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