Ambulatory function in spinal muscular atrophy: Age-related patterns of progression.
Ambulatory function in spinal muscular atrophy: Age-related patterns of progression.
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DOI：
10.1371/journal.pone.0199657
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Mercuri E
中科院分区：
文献类型：
--
作者：
Montes J;McDermott MP;Mirek E;Mazzone ES;Main M;Glanzman AM;Duong T;Young SD;Salazar R;Pasternak A;Gee R;De Sanctis R;Coratti G;Forcina N;Fanelli L;Ramsey D;Milev E;Civitello M;Pane M;Pera MC;Scoto M;Day JW;Tennekoon G;Finkel RS;Darras BT;Muntoni F;De Vivo DC;Mercuri E
脊髓性肌萎缩症(SMA)3型患者能够行走，但他们有虚弱、步态障碍和疲劳。我们的主要研究目标是检查6分钟步行试验(6MWT)的纵向变化，并评估年龄和SMA 3型亚型是否与步行功能下降有关。使用了三项前瞻性自然历史研究的数据。73名参与者进行了一次以上的6MWT，间隔至少6个月；随访时间为0.5-9年。只有完成6MWT的患者的数据才包括在内。参与者的平均年龄为13.5岁(范围2.6-49.1)，其中52人在3岁之前发病(3A型)。在基线时，3A型参与者的平均步行距离(257.1米)比3B型参与者(390.2米)短(差异=133.1米，95%可信区间[CI]71.8-194.3，p<；0.001)。步行距离与年龄的相关性较弱(r=0.25，p=0.04)。采用线性混合效应模型估计年平均变化率。总体平均变化率为-7.8m/年(95%CI-13.6--2.0p=0.009)，这在亚型上没有差异(3A型：-8.5m/年，3B型：-6.6m/年，p=0.78)，但它确实因年龄组而不同(<；6：9.8m/年；6-10：-7.9m/年；11-19：-20.8m/年；≥20：-9.7m/年；P=0.005)。我们的结果显示，随着时间的推移，6MWT总体上呈下降趋势，但根据年龄的不同，观察到了不同的轨迹。年轻的SMA患者获得了功能，但在青春期，患者失去了功能。未来对非卧床SMA患者的临床试验应在设计中考虑基于年龄的随时间变化的不同的步行功能轨迹。
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.
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影响因子：
158.5
作者：
Mercuri, E.;Darras, B. T.;Kim, Hyuna
通讯作者：
Kim, Hyuna
影响因子：
9.9
作者：
Karaa A;Haas R;Goldstein A;Vockley J;Weaver WD;Cohen BH
通讯作者：
Cohen BH
影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
3.2
作者：
Bartels, Bart;de Groot, Janke F.;Terwee, Caroline B.
通讯作者：
Terwee, Caroline B.
影响因子：
9.9
作者：
Montes, J.;McDermott, M. P.;Finkel, R. S.
通讯作者：
Finkel, R. S.