Table 1.
Summary of the sham-controlled studies performed with non-invasive brain stimulation in motor recovery after stroke.
| Number of patients | Cortical/subcortical | Ischemic/hemorrhagic | Severity of stroke | Stroke duration | Motor assessments and outcomes | Concomitant therapy | Study design | NIBS Intervention | Number of sessions | Follow-ups | Result | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rTMS | ||||||||||||
| Khedr et al. (2005) | 52 | Cortico-subcortical | Ischemic | Moderate to severe | 5–10 days | SSS, NIHSS, BI | Standard physical therapy | Randomized, parallel groups | 3 Hz rTMS over iM1 | 10 days | 10 days | Pos |
| Mansur et al. (2005) | Stroke 10, healthy 6 | Cortico-subcortical | Ischemic | Mixed | <12 months | sRT, cRT, PP, FT | NA | Randomized, cross-over | 1 Hz rTMS over cM1 and cPM | One | NA | Pos |
| Takeuchi et al. (2005) | 20 | Subcortical | Ischemic | Mixed | 26.95 months | FM, PA | NA | Randomized, parallel groups | 1 Hz rTMS over cM1 | One | NA | Pos |
| Fregni et al. (2006) | 15 | Cortical 1, subcortical 13, cortico-subcortical 1 | Ischemic | Mild to moderate | 44.05 months | MRC, ASS, JTT, sRT, cRT, PPT | NA | Randomized, parallel groups | 1 Hz rTMS over cM1 | 5 days | 2 weeks | Pos |
| Kim et al. (2006) | 15 | Cortical 5, subcortical 10 | Ischemic 12, hemorrhagic 3 | Mild to moderate | 16.7 months | PP, GF, FT | FT | Randomized, cross-over | 10 Hz rTMS over iM1 | One | NA | Pos |
| Liepert et al. (2007) | 12 | Subcortical (2 pons) | NM | Mild | 7.3 days | MRC, GF, NHPT | NA | Randomized, cross-over | 1 Hz rTMS over cM1 | One | NA | Pos |
| Malcolm et al. (2007) | 20 | Cortico-subcortical | Hemorrhagic 1 | Mixed | 45.6 months | WMFT, BBT, MAL | CIT | Randomized, parallel groups | 20 Hz rTMS over iM1 | 10 days | 6 months | Neg |
| Talelli et al. (2007) | 6 | Cortical 3, subcortical 3 | Ischemic | Mild to moderate | 31 months | BI, NIHSS, ARAT, 9HP, GF, sRT, cRT | NA | Randomized, cross-over | iTBS over iM1, cTBS over cM1 | One | NA | Pos |
| Dafotakis et al. (2008) | 12 | Subcortical | Ischemic | Mild | 1.88 months | MRC (4–5), NIHSS, ARAT, grip-lift task | Grasping and lifting | Randomized, cross-over | 1 Hz rTMS over cM1 | One | NA | Pos |
| Mally and Dinya (2008) | 64 | Cortical, large | Ischemic, hemorrhagic 18 | Severe | 129.6 months | Spasticity score | NA | Randomized, parallel groups | 1 Hz rTMS over cM1 and iM1 | 7 days | 3 months | Pos |
| Nowak et al. (2008) | 15 | Subcortical | Ischemic | Mild | 1.93 months | ARAT, MRC (4–5), FT, reach to grasp | NA | Randomized, cross-over | 1 Hz rTMS over cM1 | One | NA | Pos |
| Takeuchi et al. (2008) | 20 | Subcortical | Ischemic | Mixed | 29.9 months | FM, acceleration and PF | PF training | Randomized, parallel groups | 1 Hz rTMS over cM1 | One | 1 week | Pos |
| Ameli et al. (2009) | 29 | Cortical 13, subcortical 16 | Ischemic | Mild to moderate | 5.5 months | MRC, ARAT, mRS, NIHSS, index finger and hand tapping | NA | Randomized, cross-over | 10 Hz rTMS over iM1 | One | NA | Mix |
| Khedr et al. (2009) | 36 | Cortical 19, subcortical 17 | Ischemic | Mild to moderate | 0.57 months | MRC, NIHSS, BI, tapping, PP | NA | Randomized, parallel groups | 1 Hz rTMS over cM1, 3 Hz over iM1 | Five | 3 months | Pos |
| Takeuchi et al. (2009) | 30 | Subcortical | Ischemic | Mixed | 28.8 months | FM, acceleration and PF | Motor training (pinching task) | Randomized, parallel groups | 1 Hz rTMS over cM1, 10 Hz over iM1, bilateral rTMS | One | 1 week | Pos |
| Chang et al. (2010) | 28 | Cortical 11, subcortical 17 | NM | Moderate to severe | 13.4 days | MI, FM, GF, BB | Reaching and grasping exercises | Randomized, parallel groups | 10 Hz over iM1 | 10 | 3 months | Pos |
| Emara et al. (2010) | 60 | Cortical 43, subcortical 17 | Ischemic | Mild to moderate | >1 month | FT, mRS, AI | Standard physical therapy | Randomized, parallel groups | 5 Hz rTMS over iM1, 1 Hz rTMS over cM1 | Ten | 12 weeks | Pos |
| Grefkes et al. (2010) | 11 | Subcortical | Ischemic | Mild | 1.91 months | MRC (4–5), ARAT, NIHSS, whole hand fist task | NA | Randomized, cross-over | 1 Hz rTMS over cM1 | One | NA | Pos |
| Avenanti et al. (2012) | 30 | Cortical 3, cortico-subcortical 1, subcortical 26 | Ischemic 20, hemorrhagic 10 | Mild | 31.47 months | JTT, NHPT, BB, PF | Standard physical therapy | Randomized, parallel groups | 1 Hz rTMS over cM1 | 10 | 3 months | Pos |
| Chang et al. (2012) | 17 | Cortical 2, subcortical 15 | Ischemic 14, hemorrhagic 3 | Mild to moderate | >3 months | JTT, SFTT | SFTT | Randomized, parallel groups | 10 Hz rTMS over iM1 | 10 | 1 month | Pos |
| Conforto et al. (2012) | 30 | Subcortical 16, cortical 14 | Ischemic | Mild to severe | 0.92 months | MRC, NIHSS, JTT, PF | Standard physical therapy | Randomized, parallel groups | 1 Hz rTMS, over cM1 | 10 | 1 month | Pos |
| Seniow et al. (2012) | 40 | Cortical 16, subcortical 14 | Ischemic 35, hemorrhagic 5 | Moderate | <3 months | WMFT, NIHSS, FM | Standard physical therapy | Randomized, parallel groups | 1 Hz over cM1 | 3 weeks | 3 months | Neg |
| Wang et al. (2012) | 28 | NM | NM | Moderate | >6 months | FM, WP | Task-oriented training | Randomized, parallel groups | 1 Hz rTMS over cM1 | Ten | NA | Pos |
| Etoh et al. (2013) | 18 | Cortical 1, subcortical 17 | Ischemic 13, hemorrhagic 5 | Severe | 29.9 months | FM, ARAT, MAS | Physical or occupational therapy | Randomized, cross-over | 1 Hz rTMS over cM1 | Ten | 4 weeks | Pos |
| Higgins et al. (2013) | 11 | NM | NM | Mild to severe | >3 months | BB, WMFT, MAL, GF, PF, SIS | Task-Oriented Training | Randomized, parallel groups | 1 Hz TMS over cM1 | Eight | NA | Neg |
| Sasaki et al. (2013) | 29 | Subcortical | Ischemic 13, hemorrhagic 16 | Mild to moderate | 0.58 months | NIHSS, GF, FT | Standard physical therapy | Randomized, parallel groups | 10 Hz rTMS over iM1, 1 Hz rTMS over cM1 | Five | NA | Pos |
| Sung et al. (2013) | 54 | Cortical 35, subcortical 19 | Ischemic 35, hemorrhagic 19 | Severe | 3–12 months | GF, FM, WMST, RT | NA | Randomized, parallel groups | 1 Hz rTMS over cM1/iTBS over iM1 | 20 | NA | Pos |
| Brodie et al. (2014) | 15 | Cortico-subcortical 5, subcortical 9 | NM | Mild to moderate | >6 months | STT, 2PD, WMFT, BB, GF | STT | Randomized, parallel groups | 5 Hz rTMS over iS1 | Five | 1 day | Mix |
| Rose et al. (2014) | 19 | NM | Ischemic | Moderate | >6 months | WMFT, FM, ARAT, GF, PF, MAS, MAL | Functional Task Practice | Randomized, parallel groups | 1 Hz rTMS over cM1 | 16 | 30 days | Neg |
| Motamed Vaziri et al. (2014) | 12 | NM | NM | Severe | >2 months | BI, FM | Standard physical therapy | Randomized, parallel groups | 1 Hz rTMS over cM1 | 10 | NA | Pos |
| Wang et al. (2014) | 44 | Cortical 16, subcortical 28 | Ischemic 29, hemorrhagic 15 | Moderate to severe | 3–12 months | MRC, FM, WMFT | Standard physical and occupational therapy | Randomized, parallel groups | 1 Hz rTMS over cM1, 1 Hz rTMS over cPMd | 10 | NA | Pos |
| tDCS | ||||||||||||
| Fregni et al. (2005) | 6 | Cortico-subcortical | NM | Mild to moderate | 27.1 months | MRC, ASS, JTT | NA | Randomized, double-blinded, cross-over | ctDCS over cM1 and atDCS over iM1 | One | NA | Pos |
| Hummel et al. (2005) | 6 | Subcortical 5, cortico-subcortical 1 | Ischemic | Mild | 44.4 months | MRC, FM, ASS, JTT | NA | Randomized, double-blinded, cross-over | atDCS over iM1 | One | 10 days | Pos |
| Hummel et al. (2006) | 11 | Subcortical | Ischemic | Mild to moderate | 41.8 months | MRC, FM, ASS, sRT, PF | NA | Randomized, double-blinded, cross-over | atDCS over iM1 | One | NA | Pos |
| Boggio et al. (2007) | 9 | Subcortical | NA | Mild to moderate | 40.9 months | MRC, JTT, ASS | NA | Randomized, double-blinded, cross-over | ctDCS over cM1 and atDCS over iM1 | 5 days | 2 weeks | Pos |
| Kim et al. (2010) | 18 | Cortical 5, subcortical 9, cortico-subcortical 4 | Ischemic | Mixed | 25.6 days | MRC (2–5) and FM (16–60), FM, BI | Occupational therapy | Randomized, parallel groups | ctDCS over cM1, atDCS over iM1 | 10 | 6 months | Mix |
| Lindenberg et al. (2010) | 20 | Cortico-subcortical | Ischemic | Severe | 35.4 months | FM (20–56), WMF | Occupational therapy | Randomized, parallel groups | Bilateral tDCS | Five | 1 week | Pos |
| Bolognini et al. (2011) | 14 | Cortical 9, cortico-subcortical 5 | Ischemic 12, hemorrhagic 2 | Moderate to severe | 35.21 months | FM, BI, JTT, HG, MAL | CIT | Randomized, parallel groups | Bilateral tDCS | 10 | 4 weeks | Pos |
| Hesse et al. (2011) | 96 | Mixed cortico-subcortical | Ischemic | Severe | 0.93 months | BI, FM (<18), BB, MAS, MRC | Robot-assisted arm training | Randomized, parallel groups, multicenter | ctDCS over cM1 and atDCS over iM1 | 30 (6 weeks) | 3 months | Neg |
| Madhavan and Stinear (2011) | 9 | Cortico-subcortical | NA | Lower extremity | 130.8 months | FM-LE, dorsiflexion and plantar flexion movements | Tracking dorsiflexion and plantar flexion task | Randomized, cross-over | atDCS over iM1, atDCS over cM1 | One | NA | Pos |
| Nair et al. (2011) | 14 | Cortical 9, subcortical 5 | NA | Moderate to severe | 31 months | FM (30.1) | Occupational therapy | Randomized, parallel groups | ctDCS over cM1 | Five | 1 week | Pos |
| Tanaka et al. (2011) | 8 | Subcortical | NA | Mixed, lower extremity | 21.1 months | SIAS, knee extension, GF | Force knee extension | Randomized, cross-over | atDCS over iM1 | One | NA | Pos |
| Stagg et al. (2012) | 17 | Cortical and subcortical | Ischemic 16, hemorrhagic 1 | Mixed | 37.9 months | FM, GF, response time task | NA | Randomized, double-blinded, cross-over | ctDCS over cM1 and atDCS over iM1 | One | NA | Pos |
| Zimerman et al. (2012) | 12 | Subcortical | Ischemic | Mild | 30 months | MRC, FM, ASS, FT | SFTT | Randomized, double-blinded, cross-over | ctDCS over cM1 | One | 3 months | Pos |
| Danzl et al. (2013) | 8 | NM | Ischemic 6, hemorrhagic 2 | Moderate | 1.1– 11.6 years | 10 MWT, TUG, BBS, FAC, SIS | RGO-locomotor training | Randomized, double-blind, sham-controlled | atDCS over iM1 | 12 | 1 month | Pos |
| Giacobbe et al. (2013) | 12 | NM | NM | Moderate | >6 months | MRC | Robotic motor practice | Block-randomized, sham-controlled | atDCS over iM1 | Four | NA | Mix |
| Khedr et al. (2013) | 40 | Cortical 18, cortico-subcortical 8, subcortical 14 | Ischemic | Moderate | Anodal 13.8 ± 5.8, cathodal 12.3 ± 4.4, sham 12.6 ± 4.6 days | NIHSS, OMCASS, BI, MRC | Occupational therapy within 1 h after stimulation | Single-center, randomized, double-blind, sham-controlled | atDCS over iM1, ctDCS over cM1 | 6 days | 1–3 months | Pos |
| Lefebvre et al. (2012) | 18 | Cortical 11, subcortical 7 | Ischemic 16, hemorrhagic 2 | Moderate | 2.6 ± 1.5 years | PP, GF | Visuomotor learning task | Randomized, cross-over, sham-controlled, double-blind | Dual-tDCS | One | 1 week | Pos |
| Rossi et al. (2013) | 50 | Cortical 3, cortico-subcortical 35, subcortical 12 | Ischemic | Moderate to severe | 2 days | FM, NIHSS | NA | Single-center, randomized, double-blind, sham-controlled | atDCS over iM1 | Five | 5 days, 3 months | Neg |
| Sohn et al. (2013) | 11 | Subcortical | Ischemic 4, hemorrhagic 7 | Severe | 63.00 ± 17.27 days | Static postural stability, isometric strength | NA | Randomized, cross-over, sham-controlled | atDCS over iM1 | Two | NA | Mix |
| Au-Yeung et al. (2014) | 10 | NM | Ischemic 8, hemorrhagic 2 | Mild to moderate | 8.3 ± 3.2 years | PP, Stroop test | NA | Double-blind, sham-controlled, randomized, cross-over | atDCS over iM1, ctDCS over cM1 | Three | NA | Mix |
| Fusco et al. (2014) | 11 | NM | Ischemic | Mixed | <30 days | CNS, BI, 9HPT, FM, TUG, 10MWT, 6MWT, RMI, FAC | Rehabilitative training | Double-blind, randomized, sham-controlled | ctDCS over cM1 | 10 | 30, 75–110 days | Neg |
| Lefebvre et al. (2014) | 19 | Cortical 8, subcortical 11 | Ischemic 17, hemorrhagic 2 | Moderate | 4 ± 2 years | PP, PG | NA | Randomized, cross-over, sham-controlled, double-blind | Dual-tDCS | One | NA | Pos |
| O’Shea et al. (2014) | 13 | Cortical 6, subcortical 7 | Ischemic 12, hemorrhagic 1 | Moderate | 1.5–5.8 years | sRT, FM, WMFT | NA | Cross-over, sham-controlled, single-blind | atDCS over iM1, ctDCS over cM1, Dual-tDCS | One | NA | Mix |
| Tahtis et al. (2014) | 14 | Cortical 6, subcortical 8 | Ischemic | Moderate | 2–8 weeks | TUG | NA | Double-blinded, sham-controlled, parallel design | Bi-cephalic tDCS | One | NA | Mix |
| Viana et al. (2014) | 20 | NM | Ischemic 19, hemorrhagic 1 | Moderate | Anodal 31.9 ± 18.2, sham 35 ± 20.3 months | FM, WMFT, ASS, GF | Virtual reality therapy | Randomized, double-blind, sham-controlled | atDCS over iM1 | 15 | 5 weeks | Neg |
10MWT, 10 Meter Walk Test; 2PD, 2-point discrimination; 6MWT, Six-Minute Walking Test; 9HP, 9-holepeg Test; AI, Activity Index score; ARAT, Action Research Arm Test; ASS, Ashworth Spasticity Scale; BB, Box and Block Test; BBS, Berg Balance Scale; BI, Barthel Index; CIT, constrain-induced therapy; cM1, contralesional motor cortex; CNS, Canadian Neurological Scale; cPM, contralesional premotor cortex; cRT, choice reaction time task; FAC, functional ambulation category; FM, Fugl–Meyer Scale; FT, finger-tapping task; GF, grip force; iM1, ipsilesional motor cortex; JTT, Jebsen–Taylor Hand Function Test; MAL, motor activity log; MAS, Modified Ashworth Spasticity Scale; MI, motoricity index; Mix, mixed result; MRC, Medical Research Council; mRS, modified Ranking Scale; NA, not applicable; Neg, negative result; NIHSS, NIH Stroke Scale; NM, not mentioned; OMCASS, Orgogozo’s MCA scale; PA, pinch acceleration; PF, pinch force; PG, precision grip; Pos, positive result; PP, Purdue Pegboard Test; RMI, Rivermead Mobility Index; S1, primary sensory cortex; SFTT, sequential finger-tapping task; SIAS, Stroke Impairment Assessment Set; SIS, Stroke Impact Scale 16; sRT, simple reaction time task; SSS, Scandinavian Stroke Scale; STT, serial tracking task; TUG, Timed Up and Go Test; WMFT, Wolf Motor Function Test; WP, walking performance.