Supplementary Table 1.

Summary of studies included in the systematic review: Part I

Study ID Population

n Gender Age Etiology Injury phase

1st Author, Year Design
Total EG-1 EG-2 GC EG-1 EG-2 CG EG-1 EG-2 CG
Ada, 2013 RCT 68 34 34 34 (M:24, F:10) (M:28 ,F:6) (M:19, F:15) 70 64 63 Stroke Chronic
Aguiar, 2020 RCT 22 11 11 - (M:8, F:3) (M:8, F:3) - 52 48 - Stroke Chronic
Aidar, 2007 RCT 31 16 - 15 (M:10, F:6) - (M:9, F:4) 50 - 53 Stroke Chronic
Aidar, 2016 RCT 24 11 - 13 (M:6, F:5) - (M:9, F:4) 51 - 53 Stroke Chronic
Askim, 2018 RCT 380 186 - 194 (M:104, F:82) - (M:127, F:67) 72 - 72 Stroke Chronic
Chen, 2015 RCT 24 12 12 - (M:7, F:5) (M:6, F:6) - 64 67 - Stroke Subacute
Chu, 2004 RCT 12 7 5 - (M:6, F:1) (M:5) - 62 63 - Stroke Chronic
Curcio, 2020 RCT 20 10 - 10 (M:4, F:6) - (M:5, F:5) 37 - 43 TBI Chronic
Dean, 2018 RCT 45 23 - 22 (M:16, F:7) - (M:14, F:8) 70 - 71 Stroke Subacute, Chronic
Gjellesvik, 2021 RCT 70 36 - 34 (M:21, F:15) - (M:20, F:14) 58 - 59 Stroke Chronic
Gordon, 2013 RCT 188 64 - 64 (M:29, F:35) - (M:29, F:35) 63 - 65 Stroke Chronic
Han, 2017 RCT 20 10 10 - (M:4, F:6) (M:4, F:6) - 59 62 - Stroke Subacute
Holmgren, 2010 RCT 34 15 - 19 (M:9, F:6) - (M:12, F:7) 78 - 79 Stroke Subacute
Jin, 2012 RCT 193 68 65 - (M:48, F:20) (M:46, F:19) - 57 56 - Stroke Chronic
Kim, 2015 RCT 22 11 - 11 (M:7, F:4) - (M:6, F:5) 54 - 55 Stroke Chronic
Knox, 2018 RCT 96 51 45 48 (M:25, F:26) (M:25, F:20) (M:22, F:26) 51 51 48 Stroke Subacute
Lamberti, 2017 RCT 35 17 18 - (M:13, F:4) (M:14, F:4) - 67 69 - Stroke Chronic
Langhammer, 2014 RCT 37 19 18 - (M:-, F:-) (M:-, F:-) - 78 72 - Stroke Subacute, Chronic
Lorenz, 2017 SG 14 - - - (M:12, F:2) - - 45 - - ABI Chronic
Macko, 2005 RCT 59 32 - 29 (M:22, F:10) - (M:21, F:8) 63 - 64 Stroke Chronic
Marigold, 2005 RCT 48 22 26 - (M:17, F:5) (M:18, F:8) - 68 68 - Stroke Chronic
Martins, 2020 RCT 36 18 - 18 (M:8, F:10) - (M:8, F:10) 56 - 55 Stroke Chronic
Marzolini, 2018 RCT 68 33 35 - (M:22, F:11) (M:22, F:13) - 62 66 - Stroke Chronic
May, 2013 RCT 87 43 44 - (M:34, F:9) (M:26, F:18) - 68 68 - Stroke Subacute
Meester, 2018 RCT 50 26 24 - (M:15, F:11) (M:11, F:13) - 61 62 - Stroke Chronic
Moore, 2015 RCT 40 20 20 - (M:18, F:2) (M:16, F:4) - 68 70 - Stroke Chronic
Munari, 2018 RCT 15 8 7 - (M:7, F:1) (M:7) - 61 62 - Stroke Chronic
Nave, 2019 RCT 20 105 - 95 (M:60, F:45) - (M:59, F:36) 69 - 70 Stroke Subacute
Pérez-de la Cruz, 2020 RCT 28 13 13 15 (M:8, F:5) (M:7, F:6) (M:7, F:8) 61 64 63 Stroke Chronic
Pérez-Rodríguez, 2021 CT 62 34 - 28 (M:22, F:12) - (M:13, F:15) 50 - 52 ABI Subacute, Chronic
Qurat, 2018 RCT 30 15 15 - (M:16, F:14) - 52 54 - Stroke Subacute, Chronic
Reynolds, 2021 RCT 20 10 10 - (M:10) (M:8, F:2) - 55 60 - Stroke Chronic
Soh, 2020 RCT 36 18 - 18 (M:13, F:5) - (M:12, F:6) 56 - 57 Stroke Chronic
Stuart, 2009 RCT 78 40 - 38 (M:25, F:15) - (M:29, F:9) 67 - 70 Stroke Chronic
Taricco, 2014 RCT 229 126 - 103 (M:85, F:41) - (M:62, F:41) 72 70 Stroke Subacute
Vahlberg, 2017 RCT 67 34 - 33 (M:27, F:7) - (M:24, F:9) 73 - 74 Stroke Chronic
Wise, 2012 SG 40 40 - - (M:15, F:25) - - 40 - - TBI Chronic
Yeh, 2019 RCT 30 15 15 - (M:8, F:7) (M:13, F:2) - 51 60 - Stroke Chronic
Abbreviations: n, Sample; GC, Control Group; EG, Experimental Group; RCT, Randomized Controlled Clinical Trial; CT, Non-randomized Controlled Clinical Trial; SG, Single
Group; M, Male; F, Female; TBI, Traumatic Brain Injury ; ABI, Acquired Brain Injury
Supplementary Table 2. Summary of studies included in the systematic review: Part II
Intervention

Exercise Duration Frequency Time

1st Author, Year CG
EG-1 EG-2 (weeks) (sessions/week) (minutes/session)

Ada, 2013 Aerobic Aerobic 16 3 30 Usual treatment

Aguiar, 2020 Aerobic Aerobic 12 1 40 -
Aidar, 2007 Multicomponent - 12 2 45-60 Usual treatment
Aidar, 2016 Strength - 12 3 45-60 Usual treatment
Askim, 2018 Multicomponent - 72 3 45-60 Usual treatment
Chen, 2015 Multicomponent Multicomponent 4 5 5x3 -
Chu, 2004 Multicomponent Multicomponent 8 3 60 -
Curcio, 2020 Multicomponent - 4 3 45 Usual treatment
Dean, 2018 Multicomponent - 24 2 120 Usual treatment
Gjellesvik, 2021 Aerobic - 8 3 30 Usual treatment
Gordon, 2013 Aerobic - 12 3 30 Usual treatment
Han, 2017 Multicomponent Aerobic 6 5 30 -
Holmgren, 2010 Multicomponent - 5 6 45 Usual treatment
Jin, 2012 Aerobic Aerobic 8 5 - -
Kim, 2015 Multicomponent - 6 2 60 Usual treatment
Usual treatment and educational
Knox, 2018 Multicomponent Strength 12 1 60
sessions
Lamberti, 2017 Multicomponent Multicomponent 8 3 60 -
Langhammer, 2014 Multicomponent Multicomponent 48 2 45-60 -
Lorenz, 2017 Multicomponent - 6 4 60-90 -
Macko, 2005 Aerobic Multicomponent 24 3 40 -
Marigold, 2005 Multicomponent Multicomponent 10 3 60 -
Usual treatment and educational
Martins, 2020 Multicomponent - 12 1 60
sessions
Marzolini, 2018 Multicomponent Aerobic 24 5 - -
May, 2013 Multicomponent Multicomponent 12 7 30 -
Meester, 2018 Aerobic Aerobic 10 2 30 -
Moore, 2015 Multicomponent Stretching 19 3 45-60 -
Munari, 2018 Aerobic Aerobic 12 3 50-60 -
Regular treatment and relaxation
Nave, 2019 Aerobic - 4 5 50
sessions
Pérez de la Cruz, 2020 Multicomponent Multicomponent 12 2 60 Usual treatment
Pérez-Rodríguez, 2020 Multicomponent - 18 2 30 Usual treatment
Qurat, 2018 Aerobic Aerobic 6 3 45 -
Reynolds, 2021 Aerobic Aerobic 12 2 30 -
Soh, 2020 Multicomponent - 12 3 30 Usual treatment
Stuart, 2009 Multicomponent - 24 3 60 Usual treatment
Taricco, 2014 Multicomponent - 8 2 60 Usual treatment
Valhberg, 2017 Multicomponent - 12 2 75 Usual treatment
Wise, 2012 Aerobic - 10 1 60 -
Yeh, 2019 Multicomponent Multicomponent 12 1 60 -
Abbreviations: n, Sample; GC, Control Group; EG, Experimental Group; RCT, Randomized Controlled Clinical Trial; CT, Non-randomized Controlled Clinical Trial; SG, Single
Group; M, Male; F, Female; TBI, Traumatic Brain Injury ; ABI, Acquired Brain Injury
Supplementary Table 3. Quality of Evidence
n Participants Mean difference
Variable Risk of bias Inconsistency Indirectness Imprecision Other considerations Certainty of evidence
(n Studies) (95% IC)
554 ⨁⨁◯◯ 2.35
SF-36 (PCS) Very serious c Serious b Not serious Not serious Strong association
(8) (Low) (1.01 – 3.70)
554 ⨁⨁◯◯ 1.80
SF-36 (MCS) Very serious c Serious c Not serious Not serious Strong association
(8) (Low) (0.63 – 2.98)
All plausible residual
1119 confounding would ⨁⨁⨁⨁ 27.5
6MWT Not serious Not serious Not serious Serious a
(9) reduce the (High) (8.52 – 46.49)
demonstrated effect
All plausible residual
485 confounding would ⨁⨁⨁⨁ 0.12
10MWT Not serious Not serious Not serious Not serious
(5) reduce the (High) (0.08 – 0.16)
demonstrated effect
328 0.16
TUG Not serious Not serious Not serious Serious a None ⨁⨁⨁◯ (Moderate)
(4) (0.06 – 0.38)
All plausible residual
544 confounding would ⨁◯◯◯ 1.24
BBS Not serious Very serious b Not serious Very serious a
(5) reduce the (Very low) (4.06 – 6.54)
demonstrated effect
a. Large CI; b. High heterogeneity; c. Most information from studies at high risk of bias; d. Moderate heterogeneity
Abbreviations: n, number; CI, Confident Interval; SF-36, 36-item Short Form Health Survey; PCS, Physical Component Score; MCS, Mental Component Score; 6MWT, Six Minutes
Walk Test; 10MWT, Ten Meter Walk Test; TUG, Timed Up and Go test; BBS, Berg Balance Scale.
Supplementary Table 4. Exercise effects on functional capacity and balance: subgroup’s analysis
Between-group
n n Random IV,95% CI a Heterogeneity
Z (p) differences
Groups Participants [Lower; Upper]
2
p I χ2 (p)
Functional Capacity: Walking Endurance (6MWT)
Injury phase
Subacute 8 419 47.17 [20.65; 73.69] 3.49 (<0.001) 0.010 61%
0.15 (0.700)
Chronic 20 573 40.59 [19.79; 61.39] 3.83 (<0.001) <0.001 72%
Type of component
Aerobic 16 555 48.39 [21.54; 75.24] 3.53 (<0.001) <0.001 79%
Strength 1 45 75.00 [27.49; 122.51] 3,09 (0.002) N/A N/A
3,61 (0.310)
Multicomponent 11 408 31.96 [16.05; 47.87] 3.94 (<0.001) 0,230 23%
Stretching 1 20 22.00 [-56.40; 100.40] 0.55 (0.580) N/A N/A
Program Frequency (Sessions/Week)
1 6 151 50.16 [21.93; 78.39] 3.48 (<0.001) 0,110 45%
2 2 160 26.70 [6.31; 47.08] 2.34 (0.020) 0,710 0%
5.80 (0.120)
3 14 339 57.56 [27.51; 87.62] 3.75 (<0.001) 0,001 62%
>3 7 378 20.06 [-1.79; 41.91] 1.80 (0.070) 0,020 62%
Functional Capacity: Walking Speed (10MWT)
Injury phase
Subacute 2 96 0.28 [0.17; 0.40] 4.80 (<0.001) 0.450 0%
11.57 (<0.001)
Chronic 17 342 0.07 [0.02; 0.11] 2.74 (0.005) 0.800 0%
Type of component
Aerobic 10 193 0.06 [-0.01; 0.14] 1.57 (0.120) 0.870 0%
Strength 1 45 0.24 [0.08; 0.40] 2.95 (0.003) - -
5.06 (0.170)
Multicomponent 7 180 0.17 [0.04; 0.29] 2.26 (0.008) 0.010 63%
Stretching 1 20 0.10 [-0.09; 0.29] 1.05 (0.290) - -
Program Frequency (Sessions/Week)
1 4 118 0.17 [-0.00; 0.34] 1.95 (0.050) 0.060 60%
2 4 65 0.10 [-0.02; 0.23] 1.59 (0.110) 1.000 0% 1.93 (0.500)
3 11 255 0.07 [0.02; 0.12] 2.52 (0.010) 0.440 0%
Mobility (TUG)
Injury phase
Subacute 8 250 -5.21 [-9.28; -1.14] 2.51 (0.002) 0.020 58%
0.79 (0.370)
Chronic 7 104 -3.15 [-5.13; -1.17] 3.11 (0.002) 0.330 13%
Type of component
Aerobic 5 81 -2.34 [-5.19; 0.52] 1.61 (0.110) 0.050 58%
Strength 1 45 -7.30 [-15.08; 0.48] 1.84 (0.070) - - 2.16 (0.340)
Multicomponent 9 228 -4.49 [-6.71; -2.28] 3.97 (<0.001) 0.470 0%
Program Frequency (Sessions/Week)
1 2 96 -9.60 [-15.68; -3.52] 3.09 (0.002) 0.350 0%
18.15 (<0.001)
2 5 131 -3.60 [-6.42; -0.79] 2.51 (0.010) 0.690 0%
 3 5 99 -0.76 [-2.23; 0.70] 1.02 (0.310) 0.840 0%
>3 4 54 -7.20 [-10.69; -3.71] 4.04 (<0.001) 0.570 0%
Balance (BBS)
Injury phase
Subacute 7 365 1.40 [-1.22; 4.03] 2.35 (0.020) <0.001 82%
0.03 (0.860)
Chronic 16 428 3.78 [1.92; 5.64] 3.99 (<0.001) <0.001 94%
Type of component
Aerobic 4 163 6.03 [1.47; 10.59] 2.59 (0.010) <0.001 95%
Strength 1 45 6.00 [2.28; 9.72] 3.16 (0.002) - -
3.54 (0.310)
Multicomponent 16 527 3.54 [2.20; 4.88] 5.18 (<0.001) <0.001 72,5%
Stretching 1 20 2.00 [-1.29; 5.29] 1.19 (0.230) - -
Program Frequency (Sessions/Week)
1 2 96 7.47 [4.53; 10.41] 4.98 (<0.001) 0.270 18%
2 4 231 3.60 [1.15; 6.04] 2,88 (0.004) 0.260 25%
5.16 (0.160)
3 10 193 4.20 [3.17; 5.23] 8.00 (<0.001) 0.070 43%
>3 6 235 3.36 [0.24; 6.48] 2.11 (0.030) <0.001 93%
a
Inverse variance random effects method
Abbreviations: 6MWT, Six Minutes Walk test; 10MWT, Ten Meter Walk Test; TUG, Timed Up and Go test; BBS, Berg
Balance Scale.
Supplementary Table 5. Exercise effects on quality of life: subgroup’s analysis
Between-group
n n Random IV,95% CI a Heterogeneity
Z (p) differences
Groups Participants [Lower; Upper]
2
p I χ2 (p)
Health-Related Quality of Life: SF 36 (PCS)
Injury phase
Subacute 5 188 3.28 [1.57; 5.00] 3.75 (<0.001) 0.530 0%
5.50 (0.020)
Chronic 13 236 5.79 [4.59; 6.99] 9.48 (<0.001) 0.090 20%
Type of component
Aerobic 9 175 6.20 [4.57; 7.83] 7.45 (<0.001) 0.200 28%
3.60 (0.060)
Multicomponent 9 249 4.19 [2.91; 5.47] 6.41 (<0.001) 0.390 5%
Program Frequency (Sessions/Week)
2 6 195 4.29 [2.73; 5.84] 5.41 (<0.001) 0.270 22%
3 9 190 5.87 [4,08; 7.65] 6.44 (<0.001) 0.100 41% 2.05 (0.360)
>3 3 39 3.36 [-1.89; 8.62] 1.25 (0,210) 0.640 0%
Health-Related Quality of Life: SF 36 (MCS)
Injury phase
Subacute 5 188 3.28 [1.25; 5.31] 3.17 (0,002) 0.430 0%
0.62 (0.430)
Chronic 11 186 2.32 [1.03; 3.61] 4.45 (<0.001) 0.250 21%
Type of component
Aerobic 6 115 5.02 [2.56; 7.48] 4.00 (<0.001) 0.530 0%
5.94 (0.010)
Multicomponent 10 259 1.81 [1.03; 2.60] 4.52 (<0.001) 0.540 0%
Program Frequency (Sessions/Week)
2 6 195 2.07 [0.57; 3.56] 2.71 (0,007) 0.110 44%
3 7 140 4.14 [1.94; 6.34] 3.69 (<0.001) 0.570 0% 2.36 (0.310)
>3 3 39 2.32 [-3.11; 7.75] 0.84 (0.400) 0.830 0%
a
Inverse variance random effects method
Abbreviations: n, Sample; CI, Confident Interval; SF-36, 36-item Short Form Health Survey; PCS, Physical Component
Score; MCS, Mental Component Score
Supplementary Table 6. Exercise effects on functional capacity and balance: meta-regression analysis
Intercept Covariates Heterogeneity
df Effect Effect R²
Z p Z p I² p
[Lower; Upper] [Lower; Upper]
Functional capacity: 6MWT
Age 28 40.61 [-103.21; 184.43] 0.55 0.580 -0.00 [-2.32; 2.31] -0.00 0.997 73.45% <0.001 0%
Program duration 29 15.24 [-22.29; 52.77] 0.80 0.426 1.90 [-0.80; 4.59] 1.38 0.168 69.98% <0.001 9%
Number of sessions 29 39.05 [13.08; 65.03] 2.95 0.003 0.01 [-0.50; 0.53] 0.05 0.960 72.83% <0.001 0%
Time per session 25 46.98 [-16.47; 110.42] 1.45 0.147 -0.06 [-1.32; 1.21] -0.09 0.931 69.29% <0.001 0%
Functional capacity: 10MWT
Age 17 0.22 [-0.28; 0.73] 0.87 0.384 -0.00 [-0.01; 0.01] -0.33 0.742 24.87% 0.456 0%
Program duration 18 0.27 [0.11; 0.43] 3.36 <0.001 -0.01 [-0.02; -0.00] -2.10 0.035 12.56% 0.570 72%
Number of sessions 18 0.22 [0.12; 0.33] 4.24 <0.001 -0.00 [-0.00; 0.00] -2.46 0.014 6.71% 0.596 86%
Time per session 18 -0.05 [-0.26; 0.16] -0.47 0.641 0.00 [-0.00; 0.01] 1.67 0.096 28.08% 0.432 29%
Functional capacity / Mobility: TUG
Age 14 -13.78 [-31.59; 4.03] -1.52 0.129 0.17 [-0.13; 0.46] 1.11 0.266 45.36% 0.033 0%
Program duration 14 -4.16 [-7.19; -1.13] -2.69 0.007 0.04 [-0.16; 0.24] 0.37 0.709 46.17% 0.026 0%
Number of sessions 14 -5.14 [-8.73; -1.55] -2.81 0.005 0.05 [-0.05; 0.15] 0.94 0.346 44.22% 0.033 0%
Time per session 12 .14 [-6.95; 7.22] 0.04 0.970 -0.06 [-0.19; 0.07] -0.96 0.336 31.88% 0.124 16%
Balance: BBS
Age 20 18.90 [4.32; 33.47] 2.54 0.011 -0.24 [-0.46; -0.01] -2.03 0.043 87.61% <0.001 17%
Program duration 20 3.43 [0.30; 6.57] 2.15 0.032 0.04 [-0.16; 0.24] 0.43 0.664 90.33% <0.001 0%
Number of sessions 20 6.03 [2.78; 9.27] 3.64 <0.001 -0.05 [-0.12; 0.02] -1.48 0.140 88.73% <0.001 12%
Time per session 18 3.41 [-5.64; 12.46] 0.74 0.460 0.02 [-0.14; 0.18] 0.23 0.822 86.75% <0.001 0%
Abbreviations: gl, Degrees of Freedom; 6MWT, Six Minutes Walk test; 10MWT, Ten Meter Walk Test; TUG, Timed Up and Go test;
BBS, Berg Balance Scale.
Supplementary Table 7. Exercise effects on quality of life: meta-regression analysis
Intercept Covariates Heterogeneity
df Effect Effect R²
Z p Z p I² p
[Lower; Upper] [Lower; Upper]
Health-Related Quality of Life: SF-36 (PCS)
Age 17 17.24 [5.13; 29.36] 2.79 0.005 -0.18 [-0.37; 0.00] -1.94 0.053 0.00% 0.166 100%
Program duration 17 3.71 [0.17; 7.24] 2.06 0.040 0.10 [-0.14; 0.34] 0.79 0.431 33.71% 0.103 0%
Number of sessions 17 3.05 [0.13; 5.97] 2.05 0.040 0.06 [-0.02; 0.13] 1.48 0.138 26.26% 0.163 14%
Time per session 15 8.96 [6.01; 11.92] 5.94 <0.001 -0.07 [-0.12; -0.02] -2.66 0.008 13.87% 0.240 73%
Health-Related Quality of Life: SF-36 (MCS)
Age 15 -12.28 [-26.82; 2,27] -1.66 0.098 0.22 [-0.00; 0.45] 1.94 0.052 0.00% 0.444 100%
Program duration 15 3.36 [-0.69; 7.40] 1.63 0.104 -0.05 [-0.36; 0.26] -0.32 0.750 39.25% 0.233 0%
Number of sessions 15 1.76 [-2.31; 5.84] 0.85 0.396 0.03 [-0.10; 0.16] 0.51 0.614 39.22% 0.244 0%
Time per session 13 4.98 [1.44; 8.51] 2.76 0.006 -0.04 [-0.11; 0.02] -1.38 0.169 44.40% 0.173 0%
Abbreviations: df, Degrees of Freedom; SF-36, 36-item Short Form Health Survey; PCS, Physical Component Score; MCS,
Mental Component Score.