Table I.
Summary of relevant articles
| Study | Methods | Participants | Interventions | Relevant outcome measures | Relevant findings |
|---|---|---|---|---|---|
| Arias et al. 2010 (26) | Double-blind RCT. ATP: Baseline, postintervention, 1-week follow-up | Parkinson’s Disease. n = 18 Hoehn-Yahr stage 2–4 Sex: NA Age: NA | Active rTMS 10 sessions (Mon–Fri for 2 weeks) over the vertex with a 90-mm round coil. 100 pulses per session (1 Hz, 2 trains of 50 pulses @ 90% RMT, 50 s on/5 min off) Sham Identical treatment protocol. Stimulation parameters unavailable. Inactive coil held on the scalp. A second, active coil placed perpendicularly to the first. |
Gait velocity during non-standard gait analysis | There was no significant difference between pre- or post-intervention in either group ON or OFF medication. Similarly, there was no significant difference in effect between groups in either medication phase. |
| Benito et al. 2012 (27) | Double-blind RCT. ATP: Baseline, postintervention, 2-week follow-up | Spinal cord injury. n = 17 Tetraplegia (n = 7) and paraplegia (n = 10). AIS: D. Sex (M/F): 13/4 Age: 37.3±14.1 years | Active rTMS 15 sessions (Mon–Fri for 3 weeks) over leg motor cortex with a double cone coil. 1,800 pulses per session (20 Hz, 45 trains of 40 pulses @ 90% RMT, 2 s on/28 s off) Sham Identical treatment protocol. Stimulation parameters unavailable. Inactive coil held on the scalp. A second, active coil placed below the pillow, discharging into the couch. |
LEMS, 10MWT, MAS, TUG, WISCIII | LEMS and 10MWT velocity increased and MAS decreased significantly for REAL but not for SHAM. For both groups, TUG performance increased significantly at post and at 2-week follow-up. WISCI scores did not change for either group. |
| Benninger et al. 2011 (38) | Double-blind RCT. ATP: Baseline, postintervention, 1-month follow-up | Parkinson’s Disease. n = 26 Hoehn-Yahr stage 2–4 Sex (M/F, active|sham): 7/6 | 11/2 Age (active|sham): 62.1±6.9 | 65.6±9.0 years | Active rTMS (iTBS) 8 sessions over 2 successive weeks, a session/day for 4 consecutive days/week, over hand M1 and DLPFC bilaterally with a 90 mm circular coil 600 pulses per session (3 pulses at 50 Hz repeated at 200 ms intervals (5 Hz) for 2 s (10 bursts) @ 80% AMT. These 2-s trains were repeated 20 times every 10 s) Sham Identical protocol. Sham coil. |
10MWT | rTMS had no effects on gait in ON or OFF state. |
| Benninger et al. 2012 (46) | Double-blind RCT. ATP: Baseline, postintervention, 1-month follow-up | Parkinson’s Disease. n = 26 Hoehn-Yahr stage 2–4 Sex (M/F, active|sham): 11/2 | 9/4 Age (active|sham): 62.5±9.1 | 63.7±8.3 years | Active rTMS 8 sessions over 2 successive weeks, a session/day for 4 consecutive days/week, over bilateral hand M1 with a 90-mm circular coil 600 pulses per session (50 Hz in 6-s trains @ 80% AMT) Sham Identical protocol. Inactive coil held on the scalp. A second, active coil placed perpendicularly to the first. |
10MWT | rTMS had no effects on gait in ON or OFF state. |
| Chang et al. 2010 (47) | Double-blind RCT. ATP: Baseline, postintervention, 3-month follow-up | Stroke. n = 28 Post-onset duration <1 month Sex (M/F, active|sham): 11/7 | 6/4 Age (active|sham): 56.4±11.2 | 57.0±14.5 years | Active rTMS 10 sessions over 2 weeks over lesional hemisphere hand M1 with a figure-of-eight coi 1,000 pulses per session (10 Hz, 50 trains @ 90% RMT, 5 s on/55 s off). Hand motor training between trains (50 s active/5 s rest). Sham Identical protocol. Active coil rotated perpendicularly to the scalp. | MI-L, FMA-LL, FAC | MI-L, FMA-LL and FAC scores increased significantly for both groups, with no significant difference in effect between groups. |
| Cohen et al. 2018 (48) | Double-blind RCT. ATP: Baseline, postintervention | Parkinson’s Disease. n = 42 Hoehn-Yahr stage 2–4 Sex (M/F, active|sham): 17/4 | 15/6 Age (active|sham): 64.4±6.8 | 66.8±8.1 years | Active rTMS 24 sessions over 3 months (3/week in the first month, 2/week in the second, and 1/week in the third) over hand M1 and PFC with an H-coil 1,700 pulses per session [900 for M1 and then 800 for PFC] (M1: 1 Hz for 900 s @ 110% RMT | PFC: 10 Hz, 40 trains of 20 pulses @ 100% RMT, 2 s on/20 s off). Sham Identical protocol. Sham coil. |
TUG, Foot tapping | TUG and foot tapping (most affected side) performance increased significantly for both groups, with no significant difference in effect between groups. |
| El-Tamawy et al. 2013 (49) | Double-blind RCT. ATP: Baseline, 2-month follow-up | Parkinson’s Disease. n = 16 Hoehn-Yahr stages 2.5–4 Sex (M/F): 11/5 Age: 67±7.32 years | Active rTMS 12 sessions over 4 weeks over leg M1 contralateral to the more affected side with a figure-of-eight coil 500 pulses per session (1 Hz, 10 trains of 50 pulses @ 90% RMT, 50 s on/20 s off) Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
Frequency of FOG episodes, FOG-Q, Turn time | ”Freezing episodes statistically decreased in patients subjected to the active rTMS stimulation relative to the placebo arm. FOG Q showed marked improvement after the sessions. Significant decrease in turn time was detected.” |
| Forogh et al. 2017 (50) | Double-blind RCT. ATP: Baseline, postintervention, 3-week, 12-week follow-up | Stroke. n = 26 Post-onset duration >1 month Sex (M/F): 16/10 Age: range 53–79 years | Active rTMS 5 sessions over 5 consecutive days over hand contralesional motor cortex with a figure-of-eight coil 1,200 pulses per session (1 Hz for 1,200 s) Sham Identical protocol. A speaker replayed stimulation sound from the handle of the coil. |
MRC scale, BBS, Postural stability | For all relevant outcome measures, no improvement was seen at post-intervention; only REAL showed significant improvements at 3- and 12- week follow-up, compared with baseline, and the improvements were significantly greater compared with SHAM. |
| Guan et al. 2017 (51) | Double-blind RCT. ATP: Baseline, post-intervention, 1-month, 3-month, 6-month, 1-year follow-up | Stroke. n = 42 Post-onset duration <1 week Sex (M/F, active|sham): 16/5 | 14/7 Age (active|sham): 59.7±6.8 | 57.4±14.0 years | Active rTMS 10 sessions over 10 consecutive days over ipsilesional motor cortex with a figure-of-eight coil 1,000 pulses per session (5 Hz, 50 trains of 20 pulses @ 120% contralesional RMT, 2 s on/2 s off) Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
FMA-LL | There was no significant difference from baseline at any time-point in either group. Similarly, there was no significant difference in effect between groups at any time-point. |
| Hamada et al. 2009 (52) | Double-blind RCT. ATP: Baseline, 4-week follow-up | Parkinson’s Disease. n = 99 Hoehn-Yahr stage 2.8±0.6 (active) and 2.9±0.7 (sham) Sex (M/F, active|sham): 29/26 | 25/18 Age (active|sham): 65.3±8.9 | 67.4±8.5 years | Active rTMS 8 sessions over 8 consecutive weeks over SMA with a figure-of-eight coil 1,000 pulses per session (5 Hz, 20 trains of 50 pulses @ 110% AMT, 10 s on/50 s off) Sham Identical protocol. Inactive coil held over the scalp. Active coil discharged near the participants head, while scalp electrodes produced cutaneous electrical currents. |
UPDRS-Gait, UPDRS-Chair rise, Postural stability | For all relevant outcome measures, no significant differences in improvement were seen between groups. |
| Huang et al. 2018 (28) | Double-blind RCT. ATP: Baseline, postintervention, 3-month follow-up | Stroke. n = 38 Post-onset duration 10–90 days Sex (M/F, active|sham): 10/8 | 13/7 Age (active|sham): 62.2±10.4 | 61.2±9 years | Active rTMS 15 sessions over 3 weeks over contralesional leg M1 with a double-cone coil 900 pulses per session (1 Hz continuously for 15 min @ 120% AMT), followed by 45 min physical therapy Sham Identical protocol. Sham coil. |
TUG, FMA-LL, PASS | Both groups achieved significant improvement in all relevant outcome measures. No differences between groups were seen. |
| Ji et al. 2014 (29) | RCT. ATP: Baseline, post-intervention | Stroke. n = 29 Post-onset duration <1 year Sex (M/F, active|sham): 9/6 | 8/6 Age (active|sham): 49.0±11.0 | 44.28±8.5 years | Active rTMS 18 sessions over 6 weeks (3 sessions/week) over the hotspot of the ipsilesional hemisphere with a figure-of-eight coil 1,500 pulses per session (10 Hz, 15 trains of 100 pulses, 10 s on/50 s off. Stimulation intensity information unavailable) and 15 min motor imagery practice Sham Identical protocol. Sham procedure information unavailable. |
Gait velocity during non-standard gait analysis | Both groups achieved significant improvement. REAL improved significantly more than SHAM. |
| Ji et al. 2015 (30) | RCT. ATP: Baseline, post-intervention | Stroke. n = 39 Post-onset duration <3 months Sex (M/F, active|sham): 11/9 | 12/7 Age (active|sham): 55.7±9.0 | 56.4±10.4 years | Active rTMS 20 sessions over 4 weeks (5 sessions/week) over the hotspot of the ipsilesional hemisphere with a figure-of-eight coil 2,000 pulses per session (10 Hz, 20 trains of 100 pulses, 10 s on/50 s off. Stimulation intensity information unavailable) Sham Identical protocol. Sham procedure information unavailable. |
Gait velocity during non-standard gait analysis | Both groups achieved significant improvement. REAL improved significantly more than SHAM. |
| Khedr et al. 2003 (31) | Double-blind RCT. ATP: Baseline, after the first, fifth, 10th session, 1-month follow-up | Parkinson’s Disease. n = 36 Hoehn-Yahr stage 2-3 Sex (M/F, active|sham): 14/5 | 10/7 Age (active|sham): 57.8±9.2 | 57.5±8.4 years | Active rTMS 10 sessions over 10 consecutive days over bilateral leg and hand motor cortex with a figure-of-eight coil 2000 pulses per session [1,000 pulses per hemisphere, 500 pulses per location] (5 Hz, 1000 trains of 2 pulses @ 120% RMT) Sham Identical protocol. Active coil elevated and angled away from the head. |
TUG-25 m | Only REAL increased walking speed at post-intervention, and the change was significantly greater than for SHAM. |
| Kim et al. 2014 (32) | Double-blind RCT. ATP: Baseline, postintervention, 1-month follow-up | Ataxic stroke. n = 32 Post-onset duration <3 months Sex (M/F, active|sham): 11/11 | 6/4 Age (active|sham): 67.4±7.8 | 64.8±11.7 years | Active rTMS 5 sessions over 5 consecutive days over cerebellum ipsilateral to the ataxic side 900 pulses per session (1 Hz continuously for 15 min @ 100% RMT) Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
10MWT, BBS | Gait velocity increased significantly for REAL but not for SHAM. Both groups increased BBS scores significantly. There were no differences between groups in either outcome. |
| Kumru et al. 2016 (33) | Double-blind RCT. ATP: Baseline, postintervention, 1-month follow-up | Spinal cord injury. n = 31 Tetraplegia (n = 14) and paraplegia (n = 17). All AIS C or D Sex (M/F): 24/7 Age: range 23–68 years | Active rTMS 20 sessions over 4 weeks (Mon–Fri) over the vertex with a double cone coil 1,800 pulses per session (20 Hz, 45 trains of 40 pulses @ 90% RMT, 2 s on/28 s off) followed by 30–45 min body-weight-assisted treadmill training Sham Identical protocol. Inactive coil held on the scalp. A second, active coil placed below the pillow, discharging into the couch. |
10MWT, WISCI-II, LEMS | For 10MWT, a trend for more participants being able to complete the test was seen in REAL compared with SHAM at post-intervention and at followup. WISCI change scores were similar between groups at both time-points. LEMS increased significantly for both groups at both time-points, but change score for REAL was significantly greater than for SHAM at both time-points. |
| Lin 2015 (34) | Double-blind RCT. ATP: Baseline, postintervention | Stroke. n = 32 Post-onset duration 10–90 days Sex (M/F, active|sham): 10/6 | 11/5 Age (active|sham): 58.3±10.8 | 62.3±11.7 years | Active rTMS 15 sessions over 15 consecutive days over contralesional leg motor cortex with a figure-of-eight coil 900 pulses per session (1 Hz continuously for 15 min @ 130% AMT) followed by 45 min physical therapy Sham Identical protocol. Sham coil. |
TUG, PASS, FMA-LL | Significantly more participants were able to complete the TUG at post-intervention in REAL compared with SHAM. For PASS and FMA-LL, both groups improved significantly, but for PASS there was significantly greater improvement in REAL. |
| Lin et al. 2019 (35) | Double-blind RCT. ATP: Baseline, postintervention | Stroke. n = 20 Post-onset duration >6 months Sex (M/F, active|sham): 9/1 | 8/2 Age (active|sham): 60.8±8.1 | 61.1±9.7 years | Active rTMS (iTBS) 10 sessions over 5 weeks (2 sessions/week) over the midline of the scalp with a figure-of-eight coil 1,200 pulses per session (10 pulses at 35 Hz repeated at 200 ms intervals (5 Hz) for 2 s @ 100% AMT. These 2-s trains were repeated every 10 s for a total of 40 trains.) Sham Identical protocol. Sham coil. |
TUG, 10MWT, FMALL, BBS | There was no change in TUG or 10MWT for both groups. In FMA-LL only REAL improved significantly, but there was no difference between groups. Both groups improved significantly in BBS, with no difference between groups. |
| Lomarev et al. 2006 (36) | Double-blind RCT. ATP: Baseline, after each session, 1-month follow-up | Parkinson’s disease. n = 18 Hoehn-Yahr stage 2–4 Sex (M/F, active|sham): 7/2 | 8/1 Age (active|sham): 63±10 | 66±10 years | Active rTMS 8 sessions over 4 weeks over bilateral hand motor cortex and DLPFC with a solid core coil 1,200 pulses per session [300 pulses each location] (25 Hz @ 100% RMT. No other information given.) Sham Identical protocol. Active coil rotated 180°. | 10MWT | Only REAL significantly improved time-to-complete, and the improvement was significantly greater than for SHAM. |
| Ma 2019 et al. (37) | Double-blind RCT. ATP: Baseline, after the 1st, 5th session, post-intervention, 2-week, 4-week follow-up | Parkinson’s Disease. n = 28 Sex (M/F, active|sham): 8/10 | 5/5 Age (active|sham): 59.9±9.2 | 66.0±8.6 years | Active rTMS 10 sessions over 2 weeks (Mon–Fri) over bilateral leg SMA with a figure-of-eight coil 1,000 pulses per session (10 Hz, 20 trains of 50 pulses @ 90% RMT, 5 s on/55 s off) Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
Gait velocity during non-standard gait analysis, FOG-Q | Only REAL showed significant improvements for both outcome measures, and the improvements were significantly greater than for SHAM. |
| Mi 2019 et al. (39) | Double-blind RCT. ATP: Baseline, after the 5th session, postintervention, 2-week, 4-week follow-up | Parkinson’s Disease. n = 30 Hoehn-Yahr stage 2.60±0.85 (active) and 2.35±0.91 (sham) Sex (M/F, active|sham): 9/11 | 5/5 Age (active|sham): 62.7±10.6 | 65.6±8.7 years | Active rTMS 10 sessions over 2 weeks (Mon–Fri) over bilateral leg SMA with a figure-of-eight coil 1,000 pulses per session (10 Hz, 20 trains of 50 pulses @ 90% RMT, 5 s on/55 s off) Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
TUG-7 m, FOG-Q | For TUG, time-to-complete significantly improved at all time-points for REAL, and REAL improved significantly more compared with SHAM. Similar developments were seen for FOG-Q. |
| Mor et al. 2010 (40) | Double-blind RCT. ATP: Baseline, after the 7th session, postintervention, 1-week, 2-week, 3-week, 4-week follow-up | Multiple Sclerosis. n = 20 Relapsing-remitting MS and spasticity Sex (M/F): 7/13 Age: 44.3±12.5 years | Active rTMS (iTBS) 14 sessions over 14 consecutive days over leg M1 contralateral to the affected side with a figure-of-eight coil 600 pulses per session (10 bursts, each burst composed of 3 stimuli at 50 Hz, repeated at a theta frequency of 5 Hz every 10 s @ 80% AMT) Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
MAS, H-reflex | Compared with baseline, REAL displayed significant decreases in (a) MAS scores on the stimulated target limb at postintervention and 1-week follow-up and (b) H/M ratio at post-7th session, postintervention and 1- and 2-week follow-up. There was no change in SHAM. |
| Sasaki et al. 2017 (41) | Double-blind RCT. ATP: Baseline, postintervention | Stroke. n = 21 Post-onset duration 10.9±6.6 days Sex (M/F, active|sham): 8/3 | 5/5 Age (active|sham): 66.5±16.6 | 62.4±10.3 years | Active rTMS 10 sessions over 5 consecutive days (2 sessions/day) over bilateral leg motor cortex with a double-cone coil 1000 pulses per session (10 Hz, 10 trains of 100 pulses @ 90% RMT, 10 s on/50 s off) Sham Inactive coil held over scalp. Speaker playing recording from 10 Hz stimulation. |
BRS-LL | BRS for the lower limb significantly improved in REAL but did not change in the sham stimulation group. |
| Wang et al. 2012 (42) | Double-blind RCT. ATP: Baseline, postintervention | Stroke. n = 24 Post-onset duration >6 months Sex (M/F, active|sham): 7/5 | 8/4 Age (active|sham): 64.9±12.4 | 63.0±10.9 years | Active rTMS 10 sessions over 10 consecutive days over contralesional leg motor cortex with a figure-of-eight coil 600 pulses per session (1 Hz continuously for 10min @ 90% RMT) followed by 30 min taskoriented training Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
Gait velocity during non-standard gait analysis, FMA-LL | Gait velocity and FMA-LL scores increased significantly more for REAL compared with SHAM. |
| Wang et al. 2019 (43) | Double-blind RCT. ATP: Baseline, postintervention, 1-month follow-up | Stroke. n = 14 Post-onset duration >6 months Sex (M/F, active|sham): 7/1 | 4/2 Age (active|sham): 53.5±13.7 | 54.7±12.2 years | Active rTMS 9 sessions over 3 weeks (3 sessions/week) over ipsilesional leg motor cortex with a figure-of-eight coil 900 pulses per session (5 Hz, 15 trains of 60 pulses @ 90% RMT, 12 s on/48 s off) followed by treadmill training Sham Identical protocol. Active coil rotated perpendicularly to the scalp. |
Gait velocity during non-standard gait analysis, FMA-LL | Gait velocity and FMA-LL scores increased significantly for REAL at post-intervention and follow-up (only gait), and increased significantly more than for SHAM. |
| Yang et al. 2013 (44) | Double-blind RCT. ATP: Baseline, postintervention | Parkinson’s Disease. n = 20 Hoehn-Yahr stage 2.30±0.42 (active) and 2.35±0.41 (sham) Sex (M/F, active|sham): 5/5 | 7/3 Age (active|sham): 65.2±11.1 | 67.0±13.2 years | Active rTMS 12 sessions over 4 weeks (3 sessions/week) over leg motor cortex contralaterally to the more affected side with a figure-ofeight coil 1200 pulses per session (5 Hz, 24 trains of 50 pulses @ 100% RMT, 10 s on/5 s off) followed by treadmill training Sham Identical protocol. Active coil rotated 45° to the scalp. |
10MWT, TUG | Gait velocity for ”fast” and ”comfortable” walking speed in the 10MWT increased significantly in both groups, but ”fast” increased significantly more for REAL. Time-to-complete the TUG decreased significantly in both groups, but decreased significantly more in REAL. |
| Zanette et al. 2008 (45) | RCT ATP: Baseline, post-intervention, 2-week follow-up | Amyotrophic lateral sclerosis. n = 10 Disease duration 11.4±3.0 (active) and 12.2±4.0 (sham) months Sex (M/F, active|sham): 4/1 | 3/2 Age (active|sham): 59.4±9.2 | 60.2±8.7 years | Active rTMS 10 sessions over 2 weeks over left and right hand and bilateral leg motor cortex with a figure-of-eight (hand) and circular (leg) coil 900 pulses per session [300 pulses each location] (5 Hz, 20 trains of 15 pulses @ 110% RMT, 3 s on/60 s off (each location)) Sham Identical protocol. Sham coil. |
MRC scale, Isokinetic dynamometry | There were no changes in MRC scores in either group. Lower limb muscle power increased significantly for REAL at post-intervention (but not at follow-up), and the increase was significantly greater compared with SHAM. |
10MWT: 10-metre walking test; AIS: ASIA Impairment Scale; AMT: active motor threshold; ATP: assessment time-points; BBS: Berg Balance Scale; BRS-LL: Brunnstrom Recovery Stages Lower Limb; DLPFC: dorsolateral prefrontal cortex; FAC: Functional Ambulatory Category; FMA-LL: Fugl-Meyer Assessment Lower Limb; FOG-Q: Freezing of Gait Questionnaire; iTBS: Intermittent Theta Burst Stimulation; LEMS: Lower Extremity Motor Score; MAS: Modified Ashworth Scale; MBI: Modified Barthel Index; MI-L: Motricity Index Leg; MRC: Medical Research Council; PASS: Postural Assessment Scale for Stroke Patients; RMT: Resting Motor Threshold; SMA: Supplementary Motor Area; TUG: Timed Up-and-Go test; WISCI: Walking Index for Spinal Cord Injury.