University of Hertfordshire

From the same journal

From the same journal

Ambulatory function in spinal muscular atrophy: Age-related patterns of progression

Research output: Contribution to journalArticlepeer-review


  • Jacqueline Montes
  • Michael P McDermott
  • Elizabeth Mirek
  • Elena S Mazzone
  • Marion Main
  • Allan M Glanzman
  • Tina Duong
  • Sally Dunaway Young
  • Rachel Salazar
  • Amy Pasternak
  • Richard Gee
  • Roberto De Sanctis
  • Giorgia Coratti
  • Nicola Forcina
  • Lavinia Fanelli
  • Danielle Ramsey
  • Evelin Milev
  • Matthew Civitello
  • Marika Pane
  • Maria Carmela Pera
  • And 8 others
  • Mariacristina Scoto
  • John W Day
  • Gihan Tennekoon
  • Richard S Finkel
  • Basil T Darras
  • Francesco Muntoni
  • Darryl C De Vivo
  • Eugenio Mercuri
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Original languageEnglish
Article numbere0199657.
Pages (from-to)e0199657
JournalPLoS ONE
Publication statusPublished - 26 Jun 2018


Individuals with spinal muscular atrophy (SMA) type 3 are able to walk but they have weakness, gait impairments and fatigue. Our primary study objective was to examine longitudinal changes in the six-minute walk test (6MWT) and to evaluate whether age and SMA type 3 subtype are associated with decline in ambulatory function. Data from three prospective natural history studies were used. Seventy-three participants who performed the 6MWT more than once, at least 6 months apart, were included; follow-up ranged from 0.5-9 years. Only data from patients who completed the 6MWT were included. The mean age of the participants was 13.5 years (range 2.6-49.1), with 52 having disease onset before age 3 years (type 3A). At baseline, type 3A participants walked a shorter distance on average (257.1 m) than type 3B participants (390.2 m) (difference = 133.1 m, 95% confidence interval [CI] 71.8-194.3, p < 0.001). Distance walked was weakly associated with age (r = 0.25, p = 0.04). Linear mixed effects models were used to estimate the mean annual rate of change. The overall mean rate of change was -7.8 m/year (95% CI -13.6 --2.0, p = 0.009) and this did not differ by subtype (type 3A: -8.5 m/year, type 3B: -6.6 m/year, p = 0.78), but it did differ by age group (< 6: 9.8 m/year; 6-10: -7.9 m/year; 11-19: -20.8 m/year; ≥ 20: -9.7 m/year; p = 0.005). Our results showed an overall decline on the 6MWT over time, but different trajectories were observed depending on age. Young ambulant SMA patients gain function but in adolescence, patients lose function. Future clinical trials in ambulant SMA patients should consider in their design the different trajectories of ambulatory function over time, based on age.

ID: 15037924