TY - JOUR
T1 - Ambulatory function in spinal muscular atrophy
T2 - Age-related patterns of progression
AU - Montes, Jacqueline
AU - McDermott, Michael P
AU - Mirek, Elizabeth
AU - Mazzone, Elena S
AU - Main, Marion
AU - Glanzman, Allan M
AU - Duong, Tina
AU - Young, Sally Dunaway
AU - Salazar, Rachel
AU - Pasternak, Amy
AU - Gee, Richard
AU - De Sanctis, Roberto
AU - Coratti, Giorgia
AU - Forcina, Nicola
AU - Fanelli, Lavinia
AU - Ramsey, Danielle
AU - Milev, Evelin
AU - Civitello, Matthew
AU - Pane, Marika
AU - Pera, Maria Carmela
AU - Scoto, Mariacristina
AU - Day, John W
AU - Tennekoon, Gihan
AU - Finkel, Richard S
AU - Darras, Basil T
AU - Muntoni, Francesco
AU - De Vivo, Darryl C
AU - Mercuri, Eugenio
PY - 2018/6/26
Y1 - 2018/6/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85049168252&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0199657
DO - 10.1371/journal.pone.0199657
M3 - Article
C2 - 29944707
SN - 1932-6203
VL - 13
SP - e0199657
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0199657.
ER -