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Table 1 Review papers including disease, author, study type, sample age and size, outcome measures and main findings

From: Walking and weakness in children: a narrative review of gait and functional ambulation in paediatric neuromuscular disease

DiseaseStudy type
Author
Sample sizeAge
years
mean (SD)
Outcome measuresGait speed
m/s
mean (SD)
6MWD
m
mean (SD)
10 m walk/run
s
mean (SD)
Other assessments
CMTCross-sectional, observational
Estilow et al. 2019 [13]
CMT n = 52010.9 (4.4)Balance (BOT-2)   ↓ balance
Mean (SD)
z-score − 3.25 (2.9)
Cross-sectional, case-controlled observational Kennedy et al. 2019 [14]CMT n = 50
TD n = 50
CMT 12.5 (3.9)
TD 12.5 (3.9)
6MWT
Balance (BOT-2)Walk-12
 ↓ 6MWD
CMT 507.7 (137.3)
TD 643.3 (75.6);
p < 0.001
Norm to height
CMT 341.9 (95.7)
TD 429.4 (56.0);
p < 0.001
 ↓ balance (BOT-2 /37) median (IQR)
CMT 19 (9)
TD 32 (3)
p < 0.001
Walk-12 mean score 24.7% (SD 19) 95% CI [19.3, 30.2]
n = 49
Longitudinal observational Baptista et al. 2019 [15]CMT n = 40
TD n = 49
CMT 11.45 (3.50)
TD 10.62 (3.10)
10 m walk test
(baseline)
  Slower 10 m walk
Median (25th; 75th)
CMT 7.90 (6.67;8.92)
TD 7.25 (5.60; 8.56);
p ≤ 0.05
 
Cross-sectional, case-controlled observational Kennedy et al. 2018 [11] b1CMT n = 30
TD n = 30
CMT 11.5 (3.7)
TD 11.5 (3.7)
Gait speed
6MWT
10 m walk/run (n = 26)
Balance (BOT-2)
Slower speed
CMT 1.19 (0.16)
TD 1.32 (0.14);
p < 0.001
↓ 6MWD
CMT 557 (73)
TD 615 (71);
p < 0.001
Slower 10 m walk/run
CMT 3.8 (1.0)
TD 2.9 (0.3);
p < 0.001
↓ balance (BOT-2 /37) Median (IQR)
CMT 25.5 (4–34)
TD 32 (26–35)
p < 0.001
Longitudinal cohort Kennedy et al. 2017 [16] b1CMT n = 27Baseline 11.1 (3.7)
12 months 12.2 (3.7)
Gait speed non−/norm
6MWT non−/norm
Balance (BOT-2)
Functional mobility scale (FMS)
Slower norm speed over 12 months
Baseline 1.18 (0.16)
12 months 1.15 (0.14);
p = 0.22
Baseline 0.43 (0.07)
12 months 0.41 (0.05); p = 0.04
↓ norm 6MWD over 12 months
Baseline 556 (73.7)
12 months 555 (80.2);
p = 0.91
Baseline 720 (117)
12 months 690 (121); p = 0.006
 No change in balance over 12 months (BOT-2 /37)
Baseline 22.6 (9.4)
12 months 23.3 (8.7)
p = 0.76
FMS 78% reported reduced ambulatory function
Cross-sectional, observational cohort
Cornett et al. (2016) [17]
CMT n = 52010.9 (4.4)6MWT ↓ 6MWD in CMT genotypes
6MWD z-scores reduced in CMT2A, CMT1B, CMT4C compared with CMT1A and CMTX1;
p < 0.05
6MWD z-scores reduced in CMT2A and CMT4C compared with CMT1B; p < 0.05
  
Systematic review
Kennedy et al. (2016) [18]
7 eligible studiesMean 13
Range 2–52
Gait speedSlower speed
Range 0.50–1.25
   
Cross-sectional, observational
Ounpuu et al. (2013) [19]
CMT n = 33
TD database
CMT 11.9 (3.6)
TD 12.0 (3.0)
Gait speedSlower speed dependent on gait dysfunction
CMT toe walker 1.17 [0.21]
CMT “typical” 1.11 [0.16]a
CMT foot drop 1.03 [0.21]a
TD control 1.27 [0.11];
p < 0.001 a compared with TD
   
Longitudinal Ferrarin et al. (2013) [20] b2CMT n = 1613.2 (2.9)Gait speedNon-significant changes in speed with large inter-subject variability   
Cross-sectional, case-controlled observational
Ferrarin et al. (2012) [21] b2
CMT n = 21
TD n = 18
CMT 11.9 (2.8) yo
TD 11.0 (3.3) yo
Gait speedSlower norm speed
CMT1A foot drop and push-off deficit 69 [9]
TD 77 [7];
p < 0.05
Norm to height
   
Cross-sectional observational
Pagliano et al. (2011) [22]
n = 2111.9 (2.8) range 6–17Walk-12   Walk-12
Mean 12.4% (SD 9.5) Range 0–33
RCT
Rose et al. (2010) [23] a
CMT treatment group n = 15
CMT placebo group n = 15
CMT treatment 10 [4] yo
CMT placebo 11 [3] yo
Gait speedCMT treatment group 0.50 [0.10]
CMT placebo group
0.60 [0.50]
   
RCT
Burns et al. (2009a) [24] b3
n = 81
[n = 53 for gait data; n = 65 for 6MWT data]
8.3 (3.5)Gait speed
6MWT
Baseline
CMT treatment group 1.19 (0.16)
CMT placebo group 1.24 (0.19)
Baseline
CMT treatment group 519 (86)
CMT placebo group
521 (98)
  
Cross-sectional, observational
Burns et al. (2009b) [25] b3
n = 81
[n = 53 for gait data; n = 65 for 6MWT data]
8.3 (3.5)Gait speed
6MWT
CMT 2–6 yo 1.13 (0.25)
CMT 7–11 yo 1.25 (0.12)
CMT 12–16 yo 1.23 (0.14)
CMT 2–6 yo 494.3 (70.6) 385–640
CMT 7–11 yo 526.8 (83.1) 250–640
CMT 12–16 yo 518.7 (150.2) 110–710
  
Cross-sectional, observational
Newman et al. (2007) [26] a
n = 16
TD database n = 40
CMT 20.1 (13)
TD 18.4 (8.5)
Gait speedSlower speed
CMT 1.12 (0.17)
TD controls 1.31 (0.13);
p < 0.001
   
DMDLongitudinal
Fowler et al. (2018) [27]
n = 427.9 (2.9)
Range 4.1–16.1
10 m walk/run test
StepWatch Activity monitoring
Baseline speed 1.71 (0.68) m/s as measured by 10 m walk/run Baseline 5.85 s derived from reported gait speedSignificant ↓ average strides per day with ↑ age; per age group average strides per day ↑ for 4-7yo, plateau for 8-10yo and ↓ >10yo
Systematic review of gait
Goudriaan et al. (2018) [28]
9 eligible studies Gait speed calculated from 6 studiesSlower speed compared to TD
Standardised mean difference (effect size) ranging from 1.26 to 3.20
   
RCT
Victor et al. (2017) [29]
n = 3319.6 (1.92)6MWT
10 m walk/run
 Baseline
329.6 (55.47)
Baseline
6.8 (1.97)
 
Cross-sectional observational
case controlled
Alfano et al. (2017) [30]
DMD n = 72
TD n = 599
DMD range 4–12
TD range 4–14
100 m timed test   Slower timed 100 m across all ages compared to TD; p < 0.01
DMD times improve up to 6 years and then decline from 7 years
Cross-sectional, observational case controlled
Ropars et al. (2016) [31]
DMD n = 16
TD n = 15
DMD 8.67 (2.04)
TD 9.39 (2.21)
Gait speedSlower speed compared to TD
DMD 0.78 (0.18)
TD 1.21 (0.13);
p < 0.001
   
Cross-sectional observational case-controlled
Davidson et al. (2015) [32]
DMD n = 16
TD n = 13
DMD 9.0 (2.1)
TD 9.0 (2.4)
6MWT
StepWatch Activity monitoring
 ↓ 6MWD compared to TD
DMD 387 (86)
TD 598 (63);
p < 0.005
 ↓ steps and high activity time and ↑ inactive time compared to TD
Steps
DMD 5138 (2500)
TD 7239 (2621);
p = 0.044
High activity time
DMD 25 (17)
TD 53 (34) min
p = 0.018
Inactive time
DMD 1103 (134) min
TD 1016 [33] min;
p = 0.036
Longitudinal observational
Pane et al. (2014) [34] b4
n = 96Baseline
8.3 (2.3)
6MWT ↓ 6MWD 3 years
− 15.8 (77.3) at 12 months, − 58.9 (125.7) at 24 months and − 104.22 (146.2) at 36 months
  
Longitudinal observational
Mazzone et al. (2013) [35] b4
n = 1138.2
4.1–17.0
6MWT ↓ 6MWD 2 years
 22.7 (SD 81.0) 1st year − 64.7 (SD 123.1) 2nd year
  
Longitudinal observational
Henricson et al. (2013a) [36]
n = 340Baseline range
2–28
10 m walk/run  Slower 10 m walk/run with ↑ age
No participant aged > 18 years able to walk
 
Longitudinal observational, case-controlled
Henricson et al. (2013b) [37]
DMD n = 24
TD n = 36
1 year
DMD n = 13
TD n = 18
DMD 7.9 (2.3)
TD 8.7 (2.6)
6MWT
10 m walk/run
 Baseline ↓ 6MWD
DMD 369.5 (79.3)
TD 613.3 (73.6) p < 0.001
MCID 26.4 m
1 year change DMD > MCID
DMD − 53.67 (SE 25.96) p = 0.027
TD 16.5 (SE 11.46)
Baseline ↓time
DMD 1.68 (0.56)
TD 3.32 (0.36)
p < 0.001
MCID 0.19 s
1 year change DMD > MCID
DMD − 0.25 (SE 0.68) p = 0.007
TD 0.33 (SE 0.07) p < 0.001
 
Observational study McDonald et al. (2013a) [38]n = 1748.5 (2.6)6MWT
10 m walk/run
 358 (95)
MCID 28.5–31.7 m
7.4 (4.3)
MCID 2.3–1.4 s
 
Longitudinal observational study
McDonald et al. (2013b) [39]
n = 578.3 (2.33)6MWT
10 m walk/run
 ↓ 6MWD 48 weeks
Baseline 361.1 (87.5)
Week 48,317.4 (152.3)
Slower 10 m walk/run with ↑ age
Baseline
< 7yo 4.8 (0.86)
> 7yo 7.1 (2.80)
 
Longitudinal observational study
Bello et al. (2012) [40]
n = 80
2 genotypes
Group 1 = 57
Group 2 = 23
8.3 (2.7)6MWT ↓ 6MWD 12 months, associated with age (r = − 0.38 p = 0.013), baseline 6MWD (r = 0.73, p < 0.001) and genotype (p = 0.029)
Baseline
Gp 1368 (86)
Gp 2387 (67)
12 months
Gp 1360 (98)
Gp 2343 (124)
  
Cross-sectional, observational case controlled
Doglio et al. (2011) [41]
DMD n = 15
TD n = 9
DMD 6.1 (0.7)
TD 7.5 (1.2)
Gait speed
10 m walk
Speed in younger boys with DMD does not differ to TD
DMD 1.06 (0.17)
TD 1.07 (0.18)
NS
 Slower 10 m walk
DMD 4.4 (3.2)
TD 3.4 (0.6)
p < 0.05
 
Longitudinal observational study
Mazzone et al. (2011) [42] b4
n = 106
(n = 100 10 m walk/run)
Baseline
8.3 (2.3)
10 m walk/run
6MWT
 ↓ 6MWD 12 months, > in older boys
≤ 7 yo − 7.8 (63.9)
> 7 yo − 42.3 (73.9)
All − 25.8 (74.3);
p = 0.01
(≤7yo vs > 7yo)
Slower 10 m walk/run in older boys
≤ 7 yo 0.3 (3.1)
> 7 yo 1.3 (3.5)
All 1.0 (3.4)
p = 0.11 ≤ 7yo vs >7yo
 
Cross-sectional observational study
Mazzone et al. (2010) [43]
n = 1128.18 (2.3)10 m walk/run
6MWT
 Range 127–560.6Range 3–15 
Cross-sectional observational case controlled
McDonald et al. (2010) [44]
DMD n = 21
TD n = 34
Median [range]
DMD 8 [5–12]
TD 9 [4–12]
6MWT ↓ 6MWD compared to TD
DMD 366 (83)
TD 621 (68);
p < 0.001
  
Cross-sectional observational case controlled
Gaudreault et al. (2010) [8]
DMD n = 11
TD n = 14
DMD 9.2 (2.6)
TD 9.7 (1.9)
Gait speedSlower speed
DMD 0.62 (0.12)
TD 1.02 (0.13)
p < 0.001
   
Cross-sectional, observational case controlled
D’Angelo et al. (2009) [45]
DMD n = 21
TD n = 10
DMD 7.0 (2.4)
TD 7.4 (1.2)
Gait speedTrend to slower norm speed
DMD 0.81 (0.14)
TD 0.90 (0.13)
norm to height; NS
   
RCT
Skura et al. (2008) [46]
n = 15Baseline
8.4 (1.46)
30 ft timed walk/run test  Baseline 30 ft timed run
5.6 (1.3)
 
 RCT
Beenakker et al. (2005) [47]
n = 16Baseline
6.25 (0.93)
Range 5–8
9 m run  Baseline speed 1.78 m/s
= 5.06 s over 9 m
 
SMAPilot study
Bartels et al. (2019) [48]
n = 426.2; range 10–37Endurance shuttle walk test (ESWT)   ESWT feasible measure of fatigability during walking in SMA3
Longitudinal, observational
Montes et al. (2018) [10]
n = 7313.5 (12.4) range 2.6–49.16MWT Baseline SMA3a 257.1 (107.3)
SMA3b 390.2 (144.0)
Mean rate of change − 7.8 m/year; p = 0.009
Age affects rate of change
<  6 yrs.: 9.8 m/ year; 6–10 yrs.: − 7.9 m/year; 11–19 yrs.: − 20.8 m/year; > 20 yres: − 9.7 m/year; p = 0.005
  
Cross-sectional, observational
Montes et al. (2014) [49]
n = 1031.2; range, 9–496MWT 273.4 (45.7); range, 53–492  
Dunaway et al. (2014) [50]n = 1528.7; range 10–4910 m walk/run
6MWT
Timed up and go (TUG)
 362.13 (29.22)7.44 (0.84)TUG
12.97 (2.49) s;
Moderate to good correlation between TUG and 10 m walk/run (r = 0.691; p = 0.009) and 6MWT (r = − 0.514; p < 0.05)
Longitudinal observational study
Mazzone et al. (2013) [51]a
n = 3814.07 (12.43) 3.4–49.36MWT No change in 6MWD 12 months
Baseline 294.91 (127)
12 months 293.4 (141)
  
Cross-sectional, case controlled
Montes et al. (2011) [9]
SMA3 n = 9
TD n = 9
22
4–49 years
6MWT ↓ 6MWD
SMA3 343 m (range 267–449)
TD 601 m (range 490–733)
  
Cross-sectional observational
Montes et al. (2010) [52]
n = 1815.3(13.3)6MWT
10 m walk/run
 288.9 (161.9)
Strong correlation between 6MWT and 10 m walk/run (r = − 0.87; p < 0.0001)
Median (25th, 75th %)
8.4 (5.4,10.7)
 
CMDCross-sectional observational
Hayes et al. (2018) [53]
n = 257.76 (3.02) 3.25–13.2210 m self-selected walk speed
6MWT
StepWatch activity monitoring
0.97 (0.26) 0.52–1.36325.23 (109.85)
150–604
 ↓ physical activity
Time inactive, % 80.85 (9.15) Low steps, % 33.19 (13.11) Medium steps, % 51.15 (9.80) High steps, % 16.01 (10.27)
Cross-sectional observational case-controlled
Johnson et al. (2016) [54]
CMD n = 41
(6MWT n = 33)
TD n = 29
CMD 6.8 (3.3)
TD 9.1 (3.1)
6MWT ↓ 6MWD
CMD 258.3 m (SD 176)
TD 568.3 m (SD 73.2);
p < 0.001
  
FSHDObservational test-retest reliability study
Eichinger et al. (2017) [55]a
n = 8649.1 (15.2) 18–846MWT 404.3 (123.9); Reliability ICC = 0.99 (n = 25)
Minimal detectable change (MDC95) 34.3
  
Late onset PompeObservational cross-sectional
McIntosh et al. (2015) [56]a
n = 22
Gender age-matched reference data
48.6 (range 13–72)Gait speed
6MWT
10 m fast walk test
1.02 (0.30)Variable performance ranging from 39.4 to 110% predicted10 m fast walk
1.41 (0.42) m/s = 7.09 s
 
Collagen VILongitudinal observational
Meilleur et al. (2015) [57]a
n = 32
(n = 11 for 10 m walk/run and 6MWT)
Range 4.8–21.26MWT
10 m walk/run
 338.27 (126.65) 144–60010 m walk
8.6 (3.5) 4.0–15.8
 
NMD
(mixed)
Cross-sectional observational
Witherspoon et al. (2019) [58] c
n = 7710.1 ± 2.936MWT
2MWT
 442.1 (121.6) 2MWD = 149.8 (40.3) m
Strong correlation 2MWD and 6MWD
r = 0.90, p < 0.01
Cross-sectional observational
Kaya et al. (2015) [59]
n = 40
DMD = 20
PN d = 20
DMD 9.05 (3.1)
PN 12.95 (3.3)
6MWT
TUG
 DMD 349.70 (77.18)
PN 358.85 (75.07)
NS
 TUG
DMD 7.79 (1.54) s
PN 10.13 (2.63) s
p < 0.01
Cross-sectional observational
Montes et al. (2013) [60] a e
n = 11421.3 (range 4–64)6MWT
(% predicted of normative reference data)
 Mean 61.9%
DMD/BMD 65.1%
SMA 52.0%
myasthenia gravis 66.3%
GLUT1 deficiency/mitochondrial disorders 63.9%
  
Cross-sectional observational
Holtebekk (2013) [61] f
n = 17Median (IQR) 14.2 (3.6)6MWT
Activity monitoring SenseWear Armband
 Median (IQR) 485 (131) Activity monitor
Moderate physical activity
Median (IQR) 2.4 (1.9) hours/weekday
1.1 (3.3) hours/weekend day
  1. Mean and standard deviation (SD) unless otherwise stated; IQR = inter-quartile rank; Main findings in bold
  2. Abbreviations: 6MWT six-minute walk test, 6MWD six-minute walk distance, BMD Becker muscular dystrophy, BOT-2 Bruininks-Oseretsky Test, 2nd Edition, CMT Charcot-Marie-Tooth disease, CMD Congenital myotonic dystrophy, DMD Duchenne muscular dystrophy, ESWT Endurance shuttle walk test, FMS Functional Mobility Scale, FSHD fascioscapulohumeral dystrophy, LGMD limb girdle muscular dystrophy, NMD neuromuscular disease, norm norm, PN peripheral neuropathies, SMA spinal muscular atrophy
  3. aNelson - included adult participants with no sub analysis; McIntosh – 2 of 22 subjects aged ≤18 years, no sub-analysis; Mazzone - included adult participants with no sub analysis; Eichinger – one 18-year-old participant, all others adults with no sub-analysis; Meilleur - included adult participants with no sub analysis; Montes - included adult participants with no sub analysis
  4. b same data sets
  5. cCollagen VI-related dystrophy (COL6-RD), laminin alpha 2-related dystrophy (LAMA2-RD), limb-girdle muscular dystrophy (LGMD), and RYR1-related myopathies (RYR1-RM), and other
  6. dPN = peripheral neuropathies including CMT/hereditary motor and sensory neuropathy (HMSN), motor neuropathy (MN) and polyneuropathy (PNP)
  7. eSpinal muscular atrophy (n = 23), Duchenne/Becker muscular dystrophy (n = 29), myasthenia gravis (n = 12), or an energy failure syndrome (glucose transporter protein type 1 [GLUT1] deficiency/mitochondrial disorders) (n = 50)
  8. fCMT n = 4, Congenital myopathy n = 2, LGMD 2I n = 8, BMD n = 1, Unspecified n = 2