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PLoS One. 2018 Jun 26;13(6):e0199657. doi: 10.1371/journal.pone.0199657. eCollection 2018.

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

Author information

1
Departments of Neurology, Columbia University Medical Center, New York, NY, United States of America.
2
Rehabilitation and Regenerative Medicine, Columbia University Medical Center, New York, NY, United States of America.
3
Department of Neurology, University of Rochester, Rochester, NY, United States of America.
4
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, United States of America.
5
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
6
Department of Physical Therapy and Occupational Therapy Services, Boston Children's Hospital, Boston, MA, United States of America.
7
Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Rome, Italy.
8
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
9
Department of Physical Therapy, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
10
Departments of Neurology and Pediatrics, Stanford University School of Medicine, Stanford, CA, United States of America.
11
Nemours Children's Hospital, Orlando, FL, United States of America.
12
Departments of Neurology, Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States of America.

Abstract

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.

PMID:
29944707
PMCID:
PMC6019250
DOI:
10.1371/journal.pone.0199657
[Indexed for MEDLINE]
Free PMC Article

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