Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Bai, 2019

SR and meta-analysis of RCTs and cross-over studies.

Literature search up to January 2019

A: Mazzoleni, 2017

B: Figlewski, 2017

C: Straudi, 2016

D: Hesse, 2011

E: Allman, 2016

F: Hamoudi, 2018

I: Saeys, 2015

Study design:

A: RCT

B: RCT

C: RCT

D: RCT

E: RCT

G: RCT
I: Crossover

Setting and Country:

Department of Radiology and Imaging Institute of Rehabilitation and Development of Brain Function, The Second Clinical Medical College of North Sichuan Medical College Nanchong Central Hospital, Nanchong, China

Source of funding and conflicts of interest:

The authors declare that they have no conflicts of interest.

Inclusion criteria SR:

(1) all patients were adults (≥18 years)

and were diagnosed with a first stroke; (2) the articles were

focused on the effect of tDCS on the recovery of motor function

in stroke patients; (3) the stimulation sites were located

in the primary motor cortex (M1); (4) all experiments were

randomized control trials including crossover and parallel

design; (5) ≥5 patients were enrolled, and all control groups

were sham tDCS; (6) all included articles were peer reviewed

and published in English; and (7) the results were

measured with scales.

Exclusion criteria SR:

(1) patients who had other diseases that could cause motor

dysfunction; (2) articles that had been published but did

not provide raw data, such as reviews, meta-analysis, or case

reports; (3) animal experiments; and (4) results that were not

expressed as mean ± standard deviation or mean ± standard

error, but as median or interquartile range.

29 studies included

Important patient characteristics at baseline:

N, mean age

A: 24 patients, 72.6 yrs

B: 44 patients, 60.5 yrs

C: 23 patients, 58.2 yrs

D: 95 patients, 65.5 yrs

E: 24 patients, 63.5 yrs.

F: 22 patients, 63.4 yrs.

G: 36 patients, 61.8 yrs

yrs.
I: 31 patients, 63.2 yrs

Groups comparable at baseline?

Describe intervention:

A: wrist robot assisted therapy + tDCS (0.057 mA/cm²)

B: training + anodal tDCS (0.043 mA/cm²)

C: robot assisted training + tDCS (0.029 mA/cm²)

D: arm robot therapy + tDCS (0.057 mA/cm²) Anodal & Cathodal

E: tDCS (anodal, 0.029 mA/cm²) + motor training

G: tDCS (0.04 mA/cm²)

I: tDCS (0.043 mA/cm²)

Describe control:

A: wrist robot assisted therapy + tDCS

B: training + sham tDCS (1.5mA)

C: Robot Assisted training + Sham tDCS

D: Arm robot therapy + sham tDCS

E: Sham tDCS + motor training

G: Sham tDCS

I: Sham tDCS

End-point of follow-up:

A: after treatment (30 sessions)

B: after treatment (9 sessions)

C: one week after treatment (10 sessions)

D: after treatment and 3 months after treatment (30 sessions)

E: Day 10 / 1 Week / 1 Month / 3 Month (9 sessions)

G: n.r.

I: 4 weeks / 8 weeks after treatment (5 sessions)

For how many participants were no complete outcome data available?

(intervention/control)

A: n.r.

B: 3/1

C: 0

D: 4/3/4

E: 1/1

G: n.r.

I: n.r.

Treatment ≤ 3 months

Upper Limb motor function

Effect measure: standardized mean difference (95% CI):

Anodal

A: 0.17 (-0.63 – 0.97)

B: n.r.

C: n.r.

D: n.r.
E: n.r.
G: n.r.
I: n.r.

Upper limb synergy

Effect measure: standardized mean difference (95% CI):

Anodal

A: -0.39 (-0.53 – 0.31)
B: n.r.
C: n.r.
D: -0.39 (-1.20 -0.42)
E: n.r.
G: n.r.
I: n.r.

Pooled effect (random effects model): -0.11 (95% CI: -0.53 to 0.31) favoring sham

Heterogeneity (I²): 0%

Cathodal

A: n.r.
B: n.r.
C: n.r.
D: -0.02 (-0.51 – 0.47)
E: n.r.
G: n.r.
I: n.r.

Strength

A: n.r.

B: n.r.

C: n.r.

D: n.r.
E: n.r.
G: n.r.
I: n.r.

Activities of daily living

Effect measure: mean difference (95% CI):

Anodal

A: n.r.

B: n.r.

C: n.r.

D: -2.7 (-11.62 – 6.22)
E: n.r.
G: n.r.
I: n.r.

Cathodal

A: n.r.

B: n.r.

C: n.r.

D: 2.90 (-5.63 – 11.43)
E: n.r.
G: n.r.
I: n.r.

Treatment > 3 months

Upper Limb motor function

Effect measure: standardized mean difference (95% CI):

Anodal

A: n.r.

B: n.r.

C: n.r.

D: n.r.
E: 0.17 (-0.64 – 0.97)
G: n.r.
I: n.r.

Cathodal

A: n.r.

B: 0.07 (-0.52 – 0.66)

C: n.r.

D: n.r.
E: n.r.
G: n.r.
I: n.r.

Bihemispheric

A: n.r.

B: n.r.

C: 0.27 (-0.55 – 1.09)

D: n.r.
E: n.r.
G: n.r.
I: n.r.

Upper limb synergy

Effect measure: standardized mean difference (95% CI):

Anodal

A: n.r.

B: n.r.

C: n.r.

D: n.r.
E: 0.35 (-0.46 – 1.16)
G: n.r.
I: n.r.

Bihemispheric

A: n.r.

B: n.r.

C: n.r.

D: n.r.
E: 0.35 (-0.46 – 1.16)
G: n.r.
I: n.r.

Strength

Effect measure: mean difference (95% CI):

Cathodal

A: n.r.

B: 1.40 (-4.56 – 7.36

C: n.r.

D: n.r.
E: n.r.
G: n.r.
I: n.r.

Activities of daily living

A: n.r.

B: n.r.

C: n.r.

D: n.r.
E: n.r.
G: n.r.
I: n.r.

Facultative:

tDCS is effective for the recovery of stroke patients with limb dysfunction after the first unilateral stroke, but the optimal parameters of tDCS for the upper and lower limbs are different. tDCS has a great impact on the recovery of upper limb function in chronic stroke patients. In addition, stroke

patients with upper limb hemiplegia recover better by using anode or cathode tDCS with above 0.029mA/cm2 current density and ≤10 sessions of treatment. But for the recovery of lower limb function, subacute stroke patients benefit more

from bilateral tDCS.

Tien, 2020

SR and meta-analysis of  RCTs and cross-over studies.

Literature search up to January 2019

A: Chang, 2015
B: Manji, 2018

Study design:

A: RCT
B: Crossover

Setting and Country:
Department of Physical Therapy, Far Eastern Memorial Hospital, New Taipe City.

Source of funding and conflicts of interest:

There are no conflicts of interest.

Inclusion criteria SR:

(1) application of tDCS in patients with stroke who were over 18 years of age; (2) outcome assessments including gait parameters, walking speed and endurance, functional mobility test or questionnaire for walking ability and balance; (3) pre-post and randomized controlled clinical study design; (4) active tDCS versus sham tDCS and could combine other  rehabilitation

treatments in two groups; (5)  published in English or Chinese language.

Exclusion criteria SR:

(1) patients had other types of neurological or musculoskeletal diseases or subjects were non-human subjects; (2) treatment combined other types of stimulation; (3) the articles were non-clinical trials including review, case report, editorial comment, and meta-analysis.

14 studies included

Important patient characteristics at baseline:

N, mean age

A: 24 patients, 62,8 yrs.
B: 30 patients, 63.0 yrs

Stroke type
Ischaemic/Hemiparetic

A: 24/0
B: 17/13

Groups comparable at baseline?

Yes

Describe intervention:

A: 10 sessions of anodal tDCS and conventional physical therapy.
B: Combined therapy body weight-supported treadmill training (BWSTT) and tDCS (anode: front of Cz, cathode: inion, 1 mA, 20 min).

Describe  control:

A: Sham group, in which patients received 10 sessions of sham stimulation and conventional physical therapy.
B: sham stimulation

End-point of follow-up:

A: after treatment
B: n.r.

For how many participants were no complete outcome data available?

(intervention/control)

A: 0
B: n.r.

Treatment ≤ 3 months
Walking ability
Defined as FAC

Effect measure: mean difference (95% CI):

Anodal
A: 0.42 (-0.05 – 0.89)
B: n.r.

Standing balance
Defined as BBS

Effect measure: mean difference (95% CI):

Anodal
A: -2.50 (-6.07 – 1.07)
B: n.r.

Strength and Muscle Synergy
Defined as FMA-LE

Effect measure: mean difference (95% CI):

Anodal
A: 2.20 (-0.17 – 4.57)
B: n.r.

Siting balance
n.r.

Sitting and standing balance
n.r.

Walking distance
n.r.

Walking speed
Defined as the speed during gait analysis (m/s)

Effect measure: mean difference (95% CI):

Anodal
A: 0.05 (-0.15 – 0.25)
B: n.r.

Falling
n.r.

Treatment > 3 months
Walking ability
n.r.

Standing balance
n.r.

Strength and Muscle Synergy
n.r.

Sitting Balance
n.r.

Sitting and standing balance
Defined as TUG

Effect measure: mean difference (95% CI):

Anodal
A: n.r.
B: -0.90 (6.34 – 4.54)

Walking distance
Defined was 10MWT

Effect measure: mean difference (95% CI):

Anodal
A: n.r.
B: 1 wk: 2.30 (-6.17 – 1.57)
2 wk: 1.20 (-4.64 – 2.24)

Walking speed
n.r.

Facultative:

In conclusion, this meta-analysis suggests that tDCS improves walking ability with an exception of walking speed and endurance in patients with stroke. Both anodal and dual- hemispheric tDCS exert positive effects on promoting walking-related performances after stroke. However, difficulty in improving balance performance by tDCS may limit the effects of tDCS on walking speed and/or walking distance.

Level of evidence: PEDro scale (per study)
A: Excellent
B: Good

Elsner, 2019

SR and meta-analysis of RCTs

Literature search up to July 2018

A: Fridriksson, 2018

B: Meinzer, 2016

C: Spielmann, 2018

Study design:

A: RCT
B: RCT
C: Multi-centre RCT

Setting and Country:

A: USA
B: Germany
C: the Netherlands

Source of funding and conflicts of interest:

A: None
B: None
C: This work was funded by Erasmus MC Cost-Effectiveness Research and the Dutch Brain Foundation. No conflicts of interests present.

(commercial / non-commercial / industrial co-authorship)

Inclusion criteria SR:

- RCTs, cross-over trials

Exclusion criteria SR:

- Quasi-randomised controlled trials

- Aged 18 years or above

- Stroke patients (WHO definition)

- tDCS alone or with SLTH

21 studies included

Important patient characteristics at

N, mean age

A: 74, 59.8y
B: 26. 60y
C: 58, 58y

Sex:

A: 69.7% Male
B: 69.2% Male
C: 69.0% Male

Groups comparable at baseline?

Describe intervention:

A: A-tDCS (1 mA) for 20 minutes over the left scalp over the individually most active cortex region identified by naming tasks fMRI during 45 minutes of computerised naming treatment

B: A-tDCS over the leftM1 (1 mA for 20 minutes) at the beginning of computer-assisted

naming treatment session with the ’vanishing cues’ approach (2 times for 90 minutes a day, 4 days per week for 2 weeks)

C: A-tDCS for 1 mA for the first 20 minutes and word-finding therapy for 45minutes per day on 5 consecutive sessions; 225 minutes per week.

Describe control:

A: S-tDCS for 20minutes over the left scalp over the individually most active cortex region identified by naming tasks fMRI during 45 minutes of computerised naming treatment

B: S-tDCS over the leftM1 (1 mA for 30 seconds) at the beginning of computer-assisted

naming treatment session with the ’vanishing cues’ approach (2 times for 90 minutes a day, 4 days per week for 2 weeks)

C: S-tDCS for the first 20 minutes and word-finding therapy for 45minutes per day on 5 consecutive

sessions; 225 minutes per week.

End-point of follow-up:

A: 1 week after treatment

B: After treatment and after 6 months follow-up

C: After treatment and after 6 months follow-up

For how many participants were no complete outcome data available?

(intervention/control)

A: n.r.

B: n.r.

C: n.r.

Treatment ≤ 3 months

Functional communication

Measured with ANELT (0-50). Effect measure: MD (95% CI)

Anodal:

A: n.r.
B: n.r.
C: 1.00 (-5.15 to 7.15) in favour of tDCS.

Verbal comprehension

n.r.

Expressive naming

Measured with the BNT (60 items)

Effect measure: SMD (95% CI)

Anodal:
A: n.r.
B: n.r.
C: -0.99 (-1.54 to -0.44) in favour of sham.

Treatment >3 months

Functional communication

Measured with the CETI

Effect measure: MD (95% CI):

Anodal:

A: n.r.

B:  9.40 (-6.18 to 24.98) in favour of tDCS.

C: n.r.

Verbal comprehension

n.r.

Expressive naming

Measured with naming ability of trained and untrained items or the picture naming test. Effect measure SMD (95% CI):

Anodal:

A: 0.41 (-0.06 to 0.87) in favour of tDCS.

B: 0.69 (-0.10 to 1.49) in favour of tDCS.

C: n.r.

Pooled effect (random effects model:
0.48 (95% CI 0.08 to 0.88) favoring tDCS

Heterogeneity (I²): 0%

Risk of Bias:
A: Unclear (selective reporting)

B: Unclear (allocation concealment)

C: High (selective reporting)

D: Unclear (allocation concealment, blinding, elective outcome reporting), High (incomplete outcome data)

Author’s conclusion

There is no evidence of the effectiveness of tDCS (A-tDCS, CtDCS, Dual-tDCS) versus control (S-tDCS) for improving functional

communication in people with aphasia (low quality of evidence), accuracy in naming verbs (very low quality of evidence), and cognition in stroke patients with aphasia at the present time. However, tDCS improves the accuracy in naming nouns (moderate

quality of evidence), measured at the end of the intervention period and possibly also at follow-up (moderate quality of

evidence). Current evidence does not support the routine use of tDCS for aphasia after stroke.

Van Lieshout, 2019

SR and meta-analysis of  RCTs, cross-over design trials, case studies and mixed design studies.

Literature search up to January 2018

A: Ládavas, 2015

B: Yun, 2015

Study design:

A: RCT
C: RCT

Setting and Country:

A: Italy
B: Korea

Source of funding and conflicts of interest:

The authors declared no potential conflicts of interest with respect

to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support

for the research, authorship, and/or publication of this article: This

work was supported by the Netherlands Organization for Scientific

Research (VICI 016.130.662).

Inclusion criteria SR: 1) patients

with ischaemic or haemorrhagic stroke; (2) age ≥ 18 years;

(3) the use of NIBS (TMS, TBS, or tDCS); (4) objective,

standardized tests or test batteries for assessment of cognitive

function; and (5) baseline measurement and posttreatment

measurement(s)

Exclusion criteria SR:

(1) nonhuman

studies and (2) studies that only tested effects on motor, language

functions and perception.

40 studies included

Important patient characteristics at baseline:

N, mean age

A: 30 patients, 68.9 yrs

B: 30 patients, 62.1 yrs

C: 45 patients, 62.8 yrs

Sex:

A: 53.3% Male

B: 70% Male

C: 44.4% Male

Stroke
A: n.r.

B: n.r.

C: n.r.

comparable at baseline?

Yes

Describe intervention:

A: a-tDCS + prism adaptation, c-tDCS + prism adaptation, 20 minutes x 10 sessions, x5/wk, 2 weeks.

B: a-tDCS + cognitive rehabilitation, 30 minutes x 15 sessions, x5/wk x 3 wks

Describe  control:

A: Sham a/c tDCS + prism adaptation, 20 minutes x 10 sessions, x5/wk, 2x weeks.

B: sham tDCS + cognitive rehabilitation, 30 minutes, x 15 sessions, x 5/wk, x3 weeks.

End-point of follow-up:

A: first week after PA treatment.

B: Post-treatment

For how many participants were no complete outcome data available?

(intervention/control)

A: n.r.

B: n.r.

Treatment ≤ 3 months

Visual and spatial attention

n.r.

Global cognitive functioning

Defined by the Korean version of the MMSE test (B¹=left side; B²=right side)

Effect measure: Mean difference (95% Confidence Interval):
Anodal

A: n.r.
B¹: 2.20 (-1.20 – 5.60) in favour of tDCS

B²: 1.40 (-1.87 – 4.67 in favour of tDCS)

Memory

Defined by the ViLT-R/VeLT-R (B¹=left side; B²=right side).

Effect measure: Mean difference (95% Confidence Interval):
Anodal

A: n.r.
B¹: 4.50 (-9.40 – 18.40) favouring tDCS / -0.10 (-13.67 – 13.47) favouring sham

B²: 1.80 (-11.91 – 15.51) favouring tDCS / -2.70 (-14.31 – 8.91) favouring sham.

Executive functioning

n.r.

Treatment ≤ 3 months

Visual and spatial attention

Defined by the behavioral inattention test.

Effect measure:

Mean Difference (95% Confidence Interval).

Anodal
A: 9.00 (2.64 – 15.36) in favour of tDCS
B: n.r.

Global cognitive functioning

n.r.

Memory

n.r.

Executive functioning

n.r.

Author’s conclusion:

Our review suggests that NIBS is

able to alleviate neglect after stroke. However, the results are still inconclusive and preliminary for the effect of NIBS on other cognitive domains. A standardized core set of outcome measures of cognition, also at the level of daily life activities and participation, and international agreement on treatment protocols, could lead to better evaluation of the efficacy of NIBS and comparisons between studies.

Risk-of-bias:

A: n.r.

B: n.r.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Sik, 2015

Type of study:

Double-Blind Sham-Controlled Study

Setting and country:

Physical

Medicine and Rehabilitation (PMR) Department of Baskent

University Faculty of Medicine, Turkey

Funding and conflicts of interest:

This study was approved by Baskent University Institutional

Review Board and Ethics Committee (Project no: KA15/271)

and supported by Baskent University Research Fund. The authors have no financial conflicts of interest.

Inclusion criteria:

Patients with a history

of subacute or chronic stroke (disease duration of at least three months) and

hand-wrist dorsiflexion of at least 10 degrees (90 degrees wrist palmar flexion posture) due to involvement of the middle

cerebral artery were included in our study.

Exclusion criteria:

Patients with severe cognitive deficits, history of epileptic convulsion, severe depression, neglect syndrome, aphasia,

severe spasticity, static deformity in the upper

extremity, non-ambulated, cerebellar or anterior cerebral artery involvement, brain stem

involvement, basal ganglia involvement, intracranial metallic implant, cardiac

pacemaker, significant visual loss, significant hearing loss, complex regional pain syndrome in plegic upper extremity,

uncontrolled systemic problems, and application of botulinum A toxin to the plegic upper extremity in the past 6 months

were excluded from the study.

N total at baseline:

Anodal tDCS: 12

Bihemispheric tDCS: 12

Sham: 12

Important prognostic factors²:

Age: mean (25-75 percentile)

A: 62,0 (54,8–70,0)
B: 58,5 (53,8–66,0)
S: 60,0 (55,0–67,0)

Sex:

A: 60%

B: 40%

S: 72.7%

Groups comparable at baseline?

Yes

In addition to a conventional physiotherapy and

occupational therapy program, anodal tDCS application was used in one group (A) for 20 minutes and 15 sessions in 3 weeks, bihemispheric anodal/cathodal tDCS

application in another group (B) for 40 minutes and 15 sessions in 3 weeks. The anodal tDCS application involved the placement of the active electrode to the C3-C4 area of the affected hemisphere and the reference electrode to the opposite supraorbital

region. The application of bihemispheric anodal-cathodal tDCS was performed by the placement of the active electrode to the C3-C4 area of the unaffected hemisphere in addition to its anodal application, and the placement of the reference electrode to

the opposite supraorbital region with the reversal of the current against the anodal tDCS

In addition to a conventional physiotherapy and

occupational therapy program, sham tDCS application in the third group (S). In the sham tDCS group, electrodes

were placed as in the anodal group, with

the first tingling sensation (1 min) achieved by turning on the device followed

by interruption of the current, performed

carefully so that the patient did not notice.

Length of follow-up:

6 months.

Loss-to-follow-up:

A: 2 (16.7%)
B: 2 (16.7%)
S: 1 (8.3%)

Reasons: Did not continue study because of social reasons.

Incomplete outcome data:

A: 0
B: 0
S: 0

Treatment ≤ 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

Effect measure: standardized mean difference (95% Confidence Interval)

0.47 (-0.56 – 0.97)

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

In conclusion, tDCS is an important non-invasive

brain stimulation technique that can provide additional benefits to plegic upper extremity motor function when coadministered

with a rehabilitation program.

Alisar, 2020

Type of study:

prospective, randomized, sham-controlled study

Setting and country:

Physical Medicine and Rehabilitation, Department of Physical Medicine and Rehabilitation

Haydarpaşa Numune Educatıon and Research Hospital İstanbul, Turkey

Funding and conflicts of interest:

n.r.

Inclusion criteria:

(1) age 18-75 years (2) first time stroke

sufferer (3) stroke of vascular aetiology as determined

by computerised tomography or magnetic resonance

imaging (4) at least 3 months since stroke onset (5) mini

mental state examination score 23 6) stable medical condition.

Exclusion criteria:

(1) presence of sensory

aphasia/neglect/significant hearing or visual loss/significant

spasticity (modified Ashworth scale grade 3-4) (2)

history of epilepsy/brain tumour/cranial surgery (3)

presence of a pacemaker/intracranial metallic implant.

N total at baseline:

Intervention: 16

Control: 16

Important prognostic factors²:

For example

age ± SD:

I: 63.56 ± 10.19

C: 63.50 ± 12.60

Sex:

I: 38% M

C: 44% M

Groups comparable at baseline?

Yes

tDCS was applied using a double channelled direct current stimulator (ZMI Electronics Ltd. Taiwan 2012). The consistency of the direct current was constantly monitored

and determined by the direct current stimulator.

The current was applied using 5.5 cm £ 4 cm (22 cm2) rectangular electrodes.

The electrodes were placed using the same method in the

sham group and the stimulator switched on and current

increased until the patient felt the typical ''tingling'' sensation

on their scalp for a duration of 30 seconds. It is well

known that tDCS does not elicit auditory or somatosensory

perceptions beyond the initial minute of its application,12

therefore, the stimulation was gradually reduced and

switched off after approximately a minute. The electrodes

remained in situ for 30 minutes during the OT session.

Length of follow-up:

After treatment (15^th)

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 2 (11.1%)

Control: 4 (20%)

Reasons: Did not receive allocated intervention.

Treatment ≤ 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

n.r.

Upper limb synergy

Effect measure: standardized mean difference (95% Confidence Interval)

0.30 (-0.39 – 1.00)

Strength

n.r.

Activities of daily living

Effect measure: Mean difference (95% Confidence Interval):

29.82 (11.83 – 47.81)

In this double-blind randomized controlled study, bihemispheric

tDCS therapy combined with OT and conventional

rehabilitation methods were found to be effective in

improving upper extremity motor functions and ADL in

stroke patients. Functional improvement was greater in

chronic stroke sufferers who received tDCS.

In order for tDCS to routinely enter stroke rehabilitation

practice; optimum duration and intensity of tDCS, ideal

time since stroke onset, and lesion location should be

identified. With this in mind, randomized controlled clinical

trials in larger patient populations with longer follow-up

periods should be conducted.

Nicolo, 2018

Type of study:

Double-blinded, randomized, placebo-controlled study.

Funding and conflicts of interest:

n.r.

Inclusion criteria:

(1) ischaemic or haemorrhagic

stroke, (2) <10 weeks after stroke, (3) unilateral lesion in the

territory of the middle cerebral artery, and (4) first-ever appearance

of upper extremity motor impairment based on the Fugl-

Meyer upper extremity scale (score<50).

Exclusion criteria:

Participants were

excluded if they met any of the following criteria: epileptic seizures,

presence of metallic objects in the brain, skull breach after

craniectomy, presence of implants or neural stimulators, pregnancy,

sleep deprivation, recent traumatic brain injury, delirium or

disturbed vigilance, inability to participate in 1-hour treatment

sessions, severe language comprehension deficits, new stroke lesions

during rehabilitation, or medical complications.

N total at baseline:

Intervention: 14

Control: 13

Important prognostic factors²:

For example

age ± SD:

I: 68.5 ± 10.8

C: 64.3 ± 17.1

Sex:

I: 57.1% M

C: 61.5% M

Groups comparable at baseline?

Yes

tDCS was applied for 25 minutes at an intensity of 1mA38 using a

constant-current electrical stimulator. Two 35-cm2 electrodes with sponge surfaces were placed over the ipsilesional supraorbital

region (anodal electrode) and the contralesional M1 (cathodal electrode) using the positions of C3 or C4 electrodes of the international 10-20 electroencephalography system.

For sham stimulation, the current was ramped up for 30 seconds and then slowly tapered down to zero. This modus operandi has been used to prevent participants from differentiating between real and sham stimulation. Physical therapy was started after approximately

minutes of tDCS.

Length of follow-up:

After intervention.

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 0

Control: 0

Treatment ≤ 3 months

Upper limb motor function

Effect measure: Standardized mean difference (95% Confidence Interval):

0.55 (-0.22 – 1.32)

Upper limb synergy

Effect measure: Standardized mean difference (95% Confidence Interval):

-0.19 (-0.95 – 0.57)

Strength

Effect measure: Mean Difference (95% Confidence Interval):

0.00 (-4.99 -4.99)

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

This study demonstrates that tDCS and rTMS can target different aspects of stroke plasticity. An inhibition of the contralesional M1or a reduction of interhemispheric interactions did not lead to

improved motor recovery in our sample. Conversely, exploratory subgroup analyses suggest that motor recovery might be enhanced by early interventions that seek to increase FC of ipsilesional

motor nodes. This hypothesis will need to be confirmed in future

trials applying tDCS within the first 4 weeks after stroke.

Shahweiwola, 2018

Type of study:

Randomized Controlled Study.

Funding and conflicts of interest:

This work was supported by the National Natural Science

Foundation of China (No. 51475292, No. 61761166006), and the Shanghai Municipal Commission of Health and Family lanning

(No. 2017ZZ01006). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could

be construed as a potential conflict of interest.

Inclusion criteria:

(1) age between 35

and 70 years; (2) cerebral haemorrhage or cerebral infraction for the first time; (3) confirmed by head CT or MRI; (4) at least 6 months since stroke onset and an ipsilateral arm Brunnstrom

recovery at stages 0–3; (5) conscious and able to communicate; and (6) able to sign informed consent himself/herself or with the

help of his/her immediate family member.

Exclusion criteria:

(1) sequelae after lacunar cerebral infraction; (2) peripheral neuropathy in upper limbs; (3)

unconsciousness, sensory aphasia or mental disorders, that may

lead to failures in coordinating examination and treatment; (4) history of seizure. (5) serious illnesses, such as heart, liver or kidney diseases, or serious coagulation disorders; (6) history of

cognitive disorder, neuropsychiatric disorder, drug or alcohol abuse; (7) organ failure, carcinoma or terminal stroke that

seriously affect quality of life beyond hand dysfunction; (8)

inability to complete basic course, to persist treatment, or difficult

to follow-up; (9) with metal implants or skull defect; (10) existence of skin rash, allergy or wounds at the locations where stimulation electrodes would be placed.

N total at baseline:

Intervention: 15

Control: 15

Important prognostic factors²:

For example

age ± SD:

I: 49.3 ± 9.4

C: 51.9 ± 11.0

Sex:

I: 93.3% M

C: 86.7% M

Groups comparable at baseline?

Yes

The active tDCS protocol (intensity: 2.0 mA, time

of ramp-up: 10 s, time of ramp-down: 10 s). We placed the anode electrode (5 cm×5 cm) of tDCS over the hot spot on the lesioned hemisphere and the cathode electrode (5 cm×5 cm) on the contralateral symmetrical area of non-lesioned hemisphere. If MEPs could not be detected on the paralyzed arm,

the hot spot for APB on the non-lesioned hemisphere was first

determined, and then the symmetrical area on the contralateral

hemisphere was regarded as the APB hot spot corresponding

to the paralyzed arm. tDCS intervention was delivered for 20

min via a pair of sponge electrodes moistened with 0.9% NaCl solution. To deliver the FES therapy, we used the Bio-feedback Neuromuscular

Stimulator (MyoNet-BOW-III, NCC Medical Co., LTD, China), a parameter-adjustable transcutaneous stimulator that used selfadhesive surface electrodes. The amplitude of the electric current and the tasks were selected based on patients’ needs and adjusted weekly.

the sham protocol was programmed by a dedicated computer software package and saved on the device ahead of the usage. Regular parameters of tDCS were chosen based on pilot study prior to the

experiment. To deliver

the FES therapy, we used the Bio-feedback Neuromuscular

Stimulator (MyoNet-BOW-III, NCC Medical Co., LTD, China),

a parameter-adjustable transcutaneous stimulator that used selfadhesive surface electrodes. The amplitude of the electric current and the tasks were selected based on patients’ needs and adjusted weekly.

Length of follow-up:

After intervention (4 weeks)

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 0

Control: 0

Treatment ≤ 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

Effect measure: Standardized mean difference (95% Confidence Interval):

0.49 (-0.24 – 1.22)

Upper limb synergy

Effect measure: Standardized mean difference (95% Confidence Interval):

0.28 (-1.25 – 0.79)

Strength

n.r.

Activities of daily living

n.r.

Our results suggest new trials with combined intervention in both the central nervous system and

the peripheral nervous system. In terms of limitations, since only

stroke patients with unilateral arm paralysis were recruited and

tested, more types and cases of stroke are needed. In addition, due to the demographics of the patients that were available for the study, both groups were skewed toward males. To further investigate in the interaction between the tDCS treatment and

the FES therapy in the protocol, more clinical trials with various intervention conditions and more diverse demographics are also needed.

Salazar, 2020

Type of study:

A double-blind randomized controlled trial

Funding and conflicts of interest:

This study received financial support from Conselho Nacional de

Pesquisa (CNPq, Brazil) - grant universal 461254/2014-0) and from the

Coordenac¸a˜o de Aperfeic¸oamento de Pessoal de Nı´vel Superior (CAPES,

Brazil) - finance code 001). The authors declare that they have no competing interest.

Inclusion criteria
We included

individuals with ischaemic or haemorrhagic chronic stroke confirmed

by head CT or MRI at least 6 months before recruitment,

aged between 18 and 80 years, with moderate (32-47/66) or severe

hemiparesis (9-31/66) according to the Fugl–Meyer score

(17). Participants had to have minimal cognitive ability on the

Mini Mental State Examination (> 20/30 points (illiterate) or > 24/

30 points (literate) (18) and no history of seizures. Furthermore,

participants had to be able to reach forward with both ULs.

Exclusion criteria

Individuals who presented shoulder pain, adhesive capsulitis or

glenohumeral luxation and any contraindications for electrical

stimulation were excluded.

N total at baseline:

Intervention: 15

Control: 15

Important prognostic factors²:

For example

age ± SD:

I: 49.3 ± 9.4

C: 51.9 ± 11.0

Sex:

I: 93.3% M

C: 86.7% M

Groups comparable at baseline?

Yes

This group underwent 10 sessions of concurrent tDCS and FES during 30 min, 5 times a week

for 2 weeks (excluding weekends). Before each stimulation session,

participants underwentscapular, shoulder, elbow, wrist and finger

passive mobilization for approximately 10 min.

This group underwent 10 sessions of placebo tDCS (sham tDCS) and FES during 30 min, 5 times a week

for 2 weeks (excluding weekends). Before each stimulation session,

participants underwentscapular, shoulder, elbow, wrist and finger

passive mobilization for approximately 10 min.

Length of follow-up:

After intervention (2 weeks)

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 0

Control: 0

Treatment ≤ 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

n.r.

Upper limb synergy

Effect measure: Standardized mean difference (95% Confidence Interval):

-1.34 (-2.14 - -0.54)

Strength

n.r.

Activities of daily living

n.r.

Concurrent bi-cephalic tDCS and FES slightly improved reaching motor performance and

handgrip force of chronic post-stroke individuals with moderate and severe UL impairment.

Yao, 2020

Type of study:

a randomized controlled trial.

Funding and conflicts of interest:

This work was supported by Shanghai Jiao Tong University School of Medicine

- Institute of Neuroscience, Chinese Academy of Sciences, Leading Startup

Project of Brain Diseases Clinical Research Center (2017NKX002). The funders

had no role in study design, data collection and analysis, decision to publish, or

preparation of the manuscript. The authors declare that they have no competing interests.

Inclusion criteria
aged 18–80 years; had a first-ever ischaemic

stroke (silent infarct is allowed) as diagnosed by computed

tomography or magnetic resonance imaging image

scans; had their first ischaemic stroke between 2 weeks to

12 months; can induce motor evoked potential (MEP) of

contralesional first dorsal interossei muscle (FDI) using

Transcranial magnetic stimulation.

Exclusion criteria
intracranial or

orbital metallic implants, pacemakers or artificial cochlea;

previous seizure history; previous history of brain

neurosurgery or cerebral trauma; aphasia, unilateral neglect

or cognitive deficits (Mini-Mental State Examination

score < 20); refused to sign informed consent.

N total at baseline:

Intervention: 22

Control: 20

Important prognostic factors²:

For example

age ± SD:

I: 63 ± 7.5

C: 66.2 ± 6.2

Sex:

I: 70% M

C: 85% M

Groups comparable at baseline?

Yes

The electrical stimulation device was a transcranial direct

current stimulation model IS300 manufactured by

Sichuan Intelligent Company of China. Its two conductive

rubber electrodes were placed in a saline-soaked

sponge (5 × 7 cm 2) when used. The cathodal electrode

was placed over the patients’ scalp which corresponded

to the primary motor cortex (M1) of the unaffected

hemisphere, and the region was determined by the induction

of stable MEP response in the FDI using transcranial

magnetic stimulation. The reference electrode

was placed above the contralateral supraorbital region.

The current of the experimental group was constant 2

mA for 20 min. he duration of the

VR therapy was 20 min.

For the control group, the current was

rapidly increased to 2 mA in the beginning and then

slowly tapered down to 0. At the end of the experiment,

the current again rapidly ramp up to 2 mA and then

slowly ramp-down to 0. It created a scalp sensation to

blind the subject. he duration of the

VR therapy was 20 min.

Length of follow-up:

After treatment (2 weeks)

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 2

Control: 0

Reasons: Discontinued intervention.

Treatment ≤ 3 months

Upper limb motor function

Effect measure: Standardized mean difference (95% Confidence Interval):

0.33 (-0.07 – 0.90)

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Our proof-of-concept single-centre phase II study

showed that c-tDCS combined with VR can reduce

motor impairment, improve function, increase ADL in

the affected upper limb in patients with subacute or

chronic ischaemic stroke than VR alone. This study provides

critical preliminary data to plan a future multicentre

clinical trial to systematically investigate the efficacy

of combined intervention.

Edwards, 2019

Type of study:

randomized controlled trial

Funding and conflicts of interest:

This study was supported by NICHD of the NIH,

under award number R01HD069776. Dr. A. Pascual-

Leone was partly supported by the Sidney R. Baer Jr.

Foundation, the Football Players Health Study at Harvard

University, and Harvard Catalyst | The Harvard

Clinical and Translational Science Centre (NCRR

and the NCATS NIH, UL1 RR025758). Dr. L. Gerberwas

partly supported by the Clinical Translational

Science Center, grant number UL1-TR000457-06.

Dr. B.T. Volpe and J. Chang were supported by the

Feinstein Medical Research Foundation.

Inclusion criteria

a) a first unilateral

ischaemic lesion; b) cognitive function sufficient to

understand the experiments and follow instructions;

and c) Motor Power score 1-4/5 (neither hemiplegic

nor fully recovered motor function in the muscles

of the shoulder and/or elbow and/or wrist).

Exclusion criteria

n.r.

N total at baseline:

Intervention: 41

Control: 41

Important prognostic factors²:

For example

age (mean):
67.8

Sex:

61% M

Groups comparable at baseline?

No, not in age and cortical versus subcortical stroke.

For participants in the RobottDCS group, a 2mA

current was delivered by a battery driven, constant

current stimulator (1×1 tDCS device, Soterix

Medical, New York) using surface rubber-carbon

electrodes (35cm2) with surrounding saline soaked

sponges (0.9% NaCl). Participants received stimulation

for 20 minutes while seated (immediately

prior to robot-assisted motor training), with the anode

centered 5 cm lateral to the vertex (Fig. 3), and

the cathode on the contralateral supraorbital area

(Allman et al., 2016).

Participants in the RobotSham

group had a comparable set-up to RobottDCS, with

the stimulation comprising a 30 sec current ramp to

2 mA, then 30 sec ramp down to 0 mA, repeated after

20 mins.

Length of follow-up:

After treatment

Loss-to-follow-up:

Intervention: 3

Control: 5

Reasons: unrelated illness, death to spouse, transportation issue.

Incomplete outcome data:

Intervention: 4

Control: 1

Reasons: unrelated illness, botox treatment, illness of relative.

Treatment ≤ 3 months

Upper limb motor function

n.r.

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

Treatment > 3 months

Upper limb motor function

Effect measure: Standardized mean difference (95% Confidence Interval):

0.03 (-0.44 – 0.51)

Upper limb synergy

n.r.

Strength

n.r.

Activities of daily living

n.r.

We conclude that; 1. Robot-assisted arm training is an effective form of rehabilitation for

chronic post-stroke hemiparesis, 2. Supplementary

ipsilesional-anode tDCS as performed in our

study sample although well tolerated, did not augment

training effects, and 3. Residual corticospinal

integrity (motor evoked potential presence) in the

chronic stroke hemiparetic arm, can be a predictor of

clinically important response to intensive arm rehabilitation.

Andrade, 2017

Type of study:

sham-controlled, double-blinded, parallel clinical

trial.

Setting and Country: Cognitive Neuroscience and Behavior Program, Department of Psychology, Federal University of Paraíba, João Pessoa, Brazil; Nursing. Department, State University of Paraíba, Campina Grande, Brazil.

Funding and conflicts of interest:

No potential conflict of interest was reported by the authors.

Inclusion criteria:

(a) between 18 and 75 years of age; (b) diagnosis

of unilateral, non-recurring, acute ischaemic stroke, as defined by the International Classification of Diseases (ICD-10) through Computed Tomography or Magnetic Resonance conducted by neurologists; (c) able to walk 10 m independently (with or without a mobility aid); (d) high risk of falling (fall during hospital admission, leg score on the Step Test lower than 7, or Berg Balance Scale (BBS) score of less than 49).

Exclusion criteria:

(a) score between 25 and 32 points on the National Institute of Health Stroke Scale (11) and degree 5 according to the Rankin Scale (12); (b) Mini Mental State Examination score lower than 20.

N total at baseline:
A: 15
B: 15
C: 15
D: 15

Important prognostic factors²:

Age: mean (SD)
A: 68.86 ± 4.66
B: 69.06 ± 4.43

C: 70.40 ± 2.32
D: 68.00 ± 1.46

Sex (% Male):
A: 53,3%
B: 60%
C: 53,3%
D: 66,7%

Groups comparable at baseline?

Yes

Group A
Patients received 10 sessions (five consecutive

days for two weeks) of anodal tDCS stimulation at 2 mA intensity and current density equivalent to 0.05 A/m2. the active electrode was placed on the affected hemisphere.

Group B
Patients received 10 sessions (five consecutive days for two weeks) of cathodal tDCS stimulation at 2 mA intensity and current density equivalent to 0.05 A/m2. the active electrode was placed on the unaffected hemisphere.

Group C
Patients received 10 sessions (five consecutive days for two weeks) of cathodal tDCS stimulation at 2 mA intensity and current density equivalent to 0.05 A/m2. the active electrode was placed on the unaffected hemisphere. The cathode and anode were positioned as active electrodes in the same way described above.

All participants received the same physical rehabilitation program (1 h daily, three times per week). Therapy included individualized motor task training and activities of daily living training, emphasizing active participation of the affected and  unaffected hemispheres.

For sham stimulation, the current was ramped up over 30 seconds and then turned off (15). The current was delivered through two saline-soaked sponge surface electrodes (5 × 7 cm) using a battery-driven constant current stimulator (Trans Cranial Technologies®, Hong Kong, China).

Length of follow-up:

1 day after treatment, one-month and three-month follow-up.

Loss-to-follow-up (3 months)

N=3
Reasons: Drop out

Incomplete outcome data:
n.r.

Walking ability
n.r.

Standing balance
Defined as BBS

Effect measure: mean difference (95% CI):

Anodal
3.50 (3.32 – 3.68)

Cathodal
4.70 (4.52 – 4.88)

Bihemispheric
9.30 (1.07 – 7.30)

Pooled effect (random effects model): 5.83 (95% CI 2.37 to 9.30) favoring tDCS. Heterogeneity (I²): 100%

Strength and Muscle Synergy
n.r.

Sitting balance
n.r.

Sitting and standing balance
Defined as STS (% change)

Effect measure: mean difference (95% CI):

Anodal:
13.5 (12.16 – 14.84)

Cathodal
9.5 (8.34 – 10.65)

Bihemispheric
24.5 (22.96 – 26.04)

Walking distance
Defined as 6MWT (% change)

Effect measure: mean difference (95% CI):

Anodal
28l3 (27.26 – 29.24)

Cathodal
27 (26.12 – 27.88)

Bihemispheric
33.5 (32.51 – 34.49)

Pooled effect (random effects model): 29.6 (95% CI 27.7 0 – 33.46) favoring tDCS. Heterogeneity (I²): 98%

Falling
Defined as FES-I (% change)

Effect measure: mean difference (95% CI):

Anodal
8 (7.32 – 8.68)

Cathodal
6.3 (5.70 – 6.98)

Bihemispheric
20.7 (19.84 – 21.50)

Pooled effect (random effects model): 11.7 (95% CI 3.50 – 18.80) favoring tDCS. Heterogeneity (I²): 100%

This is the first trial to report the effects of different electrode’s setups in reducing the risk of falls and lower limb function in acute stroke. tDCS resulted in significant motor recovery sustained at least three months beyond the intervention. A consensus on what is the best montage is yet to come (26,29) although studies that investigate the long-term effects can contribute to the experimental point of view, proposing systematic study protocols, as well as provide clinical applicability evidence of tDCS in following these patients.

Cattagni, 2019

Type of study:

sham-controlled, double-blinded, parallel clinical

trial.

Setting and Country: Cognitive Neuroscience and Behavior Program, Department of Psychology, Federal University of Paraíba, João Pessoa, Brazil; Nursing. Department, State University of Paraíba, Campina Grande, Brazil.

Funding and conflicts of interest:

No potential conflict of interest was reported by the authors.

Inclusion criteria:

male or female aged 18 years or older, hemiparesis following uni-lateral hemispheric cerebral lesions of vascular origin more than 6 months previously, able to walk for 10 minutes non-stop without gait aids and able to provide informed consent.

Exclusion criteria:

presence of cardiac pacemaker, aphasia or cognitive difficulties that could interfere with comprehension of instructions, neuro-orthopedic surgery to the lower limbs less than 6 months previously, concomitant progressive disease, one or more epileptic seizures within the year prior to the date of inclusion, an intracerebral metal clip, non-affiliation to the social security regime or being under guardianship.

N total at baseline:
24

Important prognostic factors²:

Age: mean (SD)
57 (13)

Sex (% Male):
79,2%

Groups comparable at baseline?

Yes

Anodal tDCS was administered using a constant current electrical stimulator (Eldith DC-stimulator, Ilmenau, Ger-many). Rectangular electrodes (35 cm2; 7 × 5 cm) covered by a saline-soaked sponge were used for the anode and cathode. The anode was placed over the leg area of the motor cortex on the affected side with the medial border of electrode placed laterally to Cz on the international electroencephalogram 10—20 system (30) (Fig. 2A). The cathode was placed above the contralateral orbit. The stimulation intensity was set at 2 mA for 30 minutes. This intensity was reached progressively over a period of 8 seconds at the beginning of tDCS and was reduced to 0 mA over the last 8seconds. A current density of 0.06 mA cm − 2 (2 mA/35 cm2)was used in order to remain below the threshold that can lead to tissue damage.

The electrodes were placed in the same position as for anodal tDCS and the same stimulation procedure as for the effective anodal tDCS was respected (Fig. 2A). However, a current was only delivered for 120 seconds at the begin-ning of the application to reproduce the sensation of an increase in current intensity. This stimulation duration was chosen because it is below the 180 seconds that Nitsche andPaulus (46) showed to be required to induce anodal tDCS post-effects. This sham tDCS administration has been shown to be indistinguishable from effective tDCS (18). To ensure that the session was blinded, an independent physician set-up the tDCS equipment in either anodal or placebo mode; this person was uninvolved in data recording, col-letting or processing.

Length of follow-up:

Directly after treatment.

Loss-to-follow-up (3 months)

n.r.

Incomplete outcome data:
n.r.

Walking ability
n.r.

Standing balance
n.r.

Strength and Muscle Synergy
n.r.

Sitting Balance
n.r.

Sitting and standing balance
n.r.

Walking distance
n.r.

Walking speed
Defined was gait speed (cm/second)

Effect measure: mean difference (95% CI)

0.20 (-20.88 – 21.28)

Falling
n.r.

Although a single session of anodal tDCS has been shown pre-viously to modify the excitability of neurons in the leg motor area, in the present study it was not found to alter muscle activity patterns during gait in patients with chronic stroke, regardless of their BDNF genotype (Val66Met versus Val66Val).There is currently no evidence for the use of a single session of anodal tDCS on the leg motor cortex of patients with chronic stroke to alter leg muscle activities during gait and improve the gait pattern. Nevertheless, because the current study only focused on the acute effects of anodal tDCS on gait parameters in individuals with chronic stroke, any potential chronic effects of tDCS (i.e., effects following repeated sessions of anodal tDCS) cannot be ruled out.

Zumbansen, 2020

Type of study:

three-armed sham-controlled blinded prospective

proof-of-concept study

Setting and country:

Jewish General Hospital, Lady Davis Institute for Medical Research,

Department of Neurology & Neurosurgery, McGill University, Montreal,

Quebec

Funding and conflicts of interest:

The author(s) disclosed receipt of the following financial support

for the research, authorship, and/or publication of this

article: This trial was supported by research grants from the

Canadian Institutes for Health Research (CIHR,

MOP#125954), W.-D. Heiss Foundation, and the Lady

Davis Institute at the JGH (CLIPP#2014). AZ was funded

by a CIHR postdoctoral fellowship.

The author(s) declared no potential conflicts of interest with

respect to the research, authorship, and/or publication of this

article.

Inclusion criteria:

stroke patients presenting with speech or

language problems.

Exclusion criteria:

Withdrawal of consent, patients with very severe aphasia (who most likely

exclusively depend on the right hemisphere) were

excluded from the study.

N total at baseline:

Intervention: 24

Control: 19

Important prognostic factors²:

For example

age ± SD:

I: 65.3 ± 13.2

C: 67.4 ± 11.7

Sex:

I: 58.3% M

C: 36.8% M

Groups comparable at baseline?

Yes

ctDCS was applied with 5-cm2 sponge electrodes

placed over the target area (cathode) and the forehead

over the right eye (anode). Stimulation with a 2-mA

current started immediately before and lasted throughout

the ST session

For sham stimulation, the current

was turned on for 30 s to elicit a typical skin sensation

and then turned off.

Length of follow-up:

After treatment and after one month follow-up.

Loss-to-follow-up (after treatment)

Intervention: 1

Control: 1

Reasons: Withdrew before starting treatment.

Incomplete outcome data:

n.r.

Treatment ≤ 3 months

Functional communication

n.r.

Verbal comprehension

Measured with the standardized Z-scores of the token test post-intervention. Effect measure: MD (95% CI):

Cathodal:

-0.07 (-1.12 to 0.98) in favour of sham tDCS.

Expressive naming

Measured with the standardized Z-scores of the BNT post intervention. Effect measure: MD (95% CI)

Cathodal:

0.29 (95% CI -0.34 to 0.92)

Treatment > 3 months

n.r.

Contralesional NIBS is a safe add-on therapy for poststroke

aphasia. Low frequency rTMS improved

naming recovery one month after a 10-day treatment

course. ctDCS effect was not significantly different

from sham stimulation. Our results raise the possibility

that inhibitory NIBS over the right pars triangularis may have negative effects in patients where Broca’s

Area is affected, supporting the view that NIBS presently

should not be applied outside clinical trials.

Future trials should specifically investigate individual

factors for patient stratification (e.g., lesion location)

and include longer-term follow-up outcome measures

(>6months).

Wang, 2019

Type of study: A Randomized Sham-Controlled Study

Setting and country:

Department of Rehabilitation, Wangjing Hospital of China Academy

of Chinese Medical Science, Beijing, China

Funding and conflicts of interest:

The authors have declared that no competing interests existed at the time

of publication.

Inclusion criteria
(a) 1–4 months after the onset

of a single left hemispheric stroke; (b) absence of a previous

brain injury; (c) a lesion that affected the left frontal lobe;

(d) slow speech, laborious pronunciation; and (e) inability or difficulty in word repetition (monosyllabic and disyllabic

word repetition score < 5/10 (test scores/total scores) to

avoid ceiling effect after treatment).

Exclusion criteria:

(a) severely impaired auditory verbal comprehension

(auditory word–picture identification < 6/30), (b) a history

of seizures within 12 months until present hospitalization,

and (c) psychiatric disease or dementia.

N total at baseline

A-tDCS-M1: 18
A-tDCS-Broca: 18

S-tDCS: 16

Important prognostic factors²:

Mean age

A-tDCS-M1: 52.6 yrs

A-tDCS-Broca: 56.1 yrs
S-tDCS: 52.3 yrs

Sex:

A-tDCS-M1: 77.8% Male

A-tDCS-Broca: 61.1% Male
S-tDCS: 75% Male

Groups comparable at baseline?

Yes

A-tDCS-M1

the location of the lip region of M1 for

the tDCS treatment was selected according to transcranial

magnetic stimulation. The transcranial magnetic stimulation

was administered using a rapid magnetic stimulator

(Magstim Company, P/N: 3013-00) with a figure-of-eight

coil (diameter, 7 cm), a peak intensity of stimulation at 2 T,

and a pulse duration of 250 s. The coil was moved over the

scalp in order to determine the optimal site from which

maximal amplitude motor evoked potentials were elicited

in the unaffected orbicularis oris muscle. Then, the left homologous

area was determined as the A-tDCS site.

A-tDCS-Broca
The left Broca’s area was defined in the frontotemporal

region as the crossing point between T3-Fz and F7-Cz according

to the international 10–20 system (Friederici, Hahne,

& von Cramon, 1998). This crossing point was known as left Broca’s point (LBP). The cathodal electrode was placed

over the right shoulder.

For sham stimulation, the stimulator was turned off after 30 s. For both active and sham tDCS treatments,

the intensity of the current was gradually increased and

decreased. The anodal electrode of the S-tDCS group was placed similarly to that of the A-tDCS-M1 group. This

procedure blinded the subjects to the stimulation conditions.

tDCS was delivered immediately before the 30-min speech training.

Length of follow-up:

After treatment.

Loss-to-follow-up (after treatment)

A-tDCS-M1: 0

A-tDCS-Broca: 0

S-tDCS: 0

Reasons: Withdrew before starting treatment.

Incomplete outcome data:

n.r.

Treatment ≤ 3 months

n.r.

Treatment > 3 months

Functional communication

n.r.

Verbal comprehension

n.r.

Expressive naming

Measured with the picture naming test. Effect measure: SMD (95% CI)

Anodal:

Broca
-0.04 (-0.87 to 0.79) in favour of sham tDCS.

M1

0.08 (-0.76 to 0.91) in favour of tDCS.

In summary, our study provides the first evidence for the application of tDCS over the left lip region of M1,

improving the articulation performance in patients with

poststroke aphasia and AoS. tDCS, with its potential to enhance cortical activation and network connectivity, offers an exciting novel strategy for recovery from AoS.

Hosseinzadeh, 2018

Type of study:

RCT

Setting and country:

Iran

Funding and conflicts of interest:

This work was supported by Kerman Neuroscience

Research Center, Kerman, Iran and Kavoush Research

Center for Behavioral, Cognitive and Addiction,

Guilan University of Medical Sciences, Rasht,

Iran. Also, we thanks the Prof. Vahid Sheibani,

Dr. Mohammad Shabani for those kindness, assistance

and considerations (Ethics code number:

IR.KMU.REC.1395.23).

The authors declare no conflict of interest.

Inclusion criteria:

All subjects were patients

with chronic ischaemic stroke who were admitted at the Tolou Clinic, Rasht, Iran. Magnetic resonance

imaging (MRI) was performed to confirm both

lesion locations.

Exclusion criteria:

Patients with other types of stroke were not included to reduce the heterogeneity of the study population.

N total at baseline:

Anodal: 25

Cathodal: 25

Sham: 25

Important prognostic factors²:

age ± SD:

Anodal 58±8

Cahodal: 64±7

Sham: 59±7

Sex:

Anodal: 52% M

Cathodal: 48% M

Sham: 48%M

Stroke type:
100% ischaemic

Groups comparable at baseline?

Yes

tDCS was applied by a battery-powered, constant current electrical stimulator (at 2-mA intensity using a pair of surface saline-soaked 35-cm2sponge electrodes

(5 7 cm), for 3 times a week for 1 month, for 30 min per session and at an electric current of 2 mA. We used two different electrode  montages, including an anode and a cathode.

In anodal tDCS,

2842 5Department of Psychiatry, Guilan University of Medical Sciences, Shafa Hospital, Rasht, Iran 6Department of Neuroscience, Neuroscience Research Center, Guilan University of Medical Sciences, Rasht, Iran 7Razi Herbal Medicines Research

Center, Lorestan University of Medical Sciences, Khorramabad, Iran

University of Medical sciences, Rasht, Iran

Biomedical Research and Therapy,  (11):2841-2849

the anode electrode was mounted on the left superior temporal gyrus, while the cathode was placed over the contralateral superior region (cp5). The current

was run through the brain and other tissues of the

head, from the anode to the cathodal electrode.

In cathodal tDCS, the cathode was used for placement symmetrical to the left gyrus (cp6), while the anode was placed at the contralateral supraorbital region.

All patients received the same protocol, 3 times a week for 30 min per session for 1

month. Then, all of these evaluation tests were applied for the patients at 3 months after ending the tDCS sessions

tDCS was applied by a battery-powered, constant current electrical stimulator (at 2-mA intensity using a pair of surface saline-soaked 35-cm2sponge electrodes

(5 7 cm), for 3 times a week for 1 month, for 30 min per session and at an electric current of 2 mA. We used two different electrode  montages, including an anode and a cathode.

In sham tDCS, the anode was placed over the left superior temporal gyrus and cathode was placed on the contralateral supraorbital region, but no current was

applied.

All patients received the same protocol, 3 times a week for 30 min per session for 1 month. Then, all of these evaluation tests were applied

for the patients at 3 months after ending the tDCS sessions

Length of follow-up:

3 months after the intervention.

Loss-to-follow-up:

n.r.

Incomplete outcome data:

n.r.

Outcome measures and effect size (include 95%CI and p-value if available):

Our results demonstrate that anodic tDCS is beneficial

and safe method for increasing the rehabilitation

of movement and life–related functions in chronic

stroke patients, while cathodic tDCS can enhance executive

memory. The ability of anodic tDCS to modulate

cortical excitability becomes useful, and exploring

the preference indication of the anodic and cathodic

tDCS abilities requires further investigation.

One of the limitations of this study was the number

of patients needed to conduct the research trial,

which took a lot of research time. Among other constraints/

factors were the predictable high cost, and the

provision of help and assistance from various agencies,

such as the Kerman Neuroscience Research Center,

Kerman, Iran and Kavoush Research Center for

Behavioral, Cognitive and Addiction, Guilan University

of Medical Sciences, Rasht, Iran. Moreover, while

the introduction of the tDCS method for patients and

neurologists has garnered greater attention, more research

is necessary to fully explore the advantages of this method.

Shaker, 2018

Type of study:

RCT

Setting and country:

the outpatient clinic of  Faculty of Physical Therapy, Cairo University, and neurology

outpatient clinic of Cairo University Hospitals.

Funding and conflicts of interest:

The authors declare that they have no competing interests (financial and non-financial). We declare that the research was conducted in absence of any commercial relationships that could be constructed as a potential conflict

of interest.

Inclusion criteria:

Included in this study were patients with ischaemic cerebrovascular

stroke in the domain of carotid system diagnosed

clinically and confirmed by CT and/or MRI of the brain, their age ranged from 40 to 60 years old to

minimize the effect of age on cognition, duration of illness

at least 6 months from stroke onset, educated patients

at least 10 years of formal education, degree of

spasticity was 1 and 1+ according to Modified Ashworth

Scale, grade of muscle power was 3 according to manual

muscle test, mini mental state examination score ranged

from 19 to 24 (mild cognitive impairment), functional

independence measure score ranged from 84 to 99, Beck

depression inventory score from 0–9, and normal hearing and vision.

Exclusion criteria:

Excluded from this study were patients with recurrent

cerebrovascular stroke or concomitant neurological disorders

that may affect cognition, psychiatric disorders,

drug or alcohol abuse, and seizure disorders; patients receiving drugs that may affect cognitive functions (anti-

depressants, anti-epileptics, sedatives, muscle relaxants);

and patients with medical illness that may affect

cognitive functions (thyroid, renal or hepatic disorder)

and a presence of wounds in the skin of the skull.

N total at baseline:

Intervention: 20

Control: 20

Important prognostic factors²:

age ± SD:

I: 54.45 ± 4.68

C: 53.05 ± 6.32

Sex:

100% Male

Stroke type:
100% ischaemic

Groups comparable at baseline?

Yes

in group A, patients received

treatment for 1 month, three sessions per week (every

other day). The duration of each session was 60 min, divided

into 30 min of tDCS (2 mA) application followed

by 30 min of RehaCom training.

All patients received RehaCom for cognitive training: RehaCom is a

computerized program instituted in the

International Neurological Restoration Center for

rehabilitation of brain injury.

In group B, patients

received sham tDCS and the same cognitive training

program as group A. In sham tDCS, real stimulation

was applied for 5 s; then, stimulation was turned off.

All patients received RehaCom for cognitive training: RehaCom is a

computerized program instituted in the

International Neurological Restoration Center for

rehabilitation of brain injury.

Length of follow-up:

End of treatment

Loss-to-follow-up:

n.r.

Incomplete outcome data:

n.r.

Outcome measures and effect size (include 95%CI and p-value if available):

In view of the results of this study, it could be concluded

that tDCS is a safe and effective neurorehabilitation

modality that improves cognitive functions in several domains

including attention and concentration, figural

memory, logical reasoning, and reaction behavior. Moreover,

tDCS has a positive impact on performance of daily

activities. So, it is recommended to use it in the rehabilitation

of post stroke cognitive dysfunctions.

Bai, 2019

Yes

Yes

No

Yes

Not applicable

Yes

Yes

Yes

Yes

Tien, 2020

Yes

Yes

No

Yes

Not applicable

Yes

Yes

Yes

Yes

Elsner, 2019

Yes

Yes

Yes

Yes

Not applicable

Yes

Unclear

Yes

Yes

Van Lieshout, 2019

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

Yes

Yes

Study reference

(first author, publication year)

Was the allocation sequence adequately generated? ^a

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?^b

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?^c

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?^d

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?^e

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?^f

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure^g

LOW

Some concerns

HIGH

Alisar, 2020

Definitely yes;

Reasons: Patients were allocated a number and randomised into 1 of 2 treatment groups

using the Random Allocation Software programme.

Definitely yes;

Reasons: The patients and PMR trainee who performed all patient evaluations were blind

to the treatment received

Definitely no;

Reasons: The occupational therapist and PMR specialist involved in the study were not blind to the

treatment received.

Definitely yes;

Reasons: There were no dropouts.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably no;

Reasons: Limitations

of the study include the heterogeneity in lesion location

and the short post treatment follow-up.

Some concerns

Sik, 2015

No information;

Reasons: No information was provided about the allocation sequence.

No information;

Reasons: No information was provided abaut the concealment of the allocation sequence.

Probably yes;

Reasons: The evaluation of

WMFT and KFET was conducted by an

experienced physiotherapist who was blinded to the therapy, but no information was provided about the blinding of patients and data collectors.

Definitely yes;

Reasons: Missing outcome data was infrequent.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably yes;

Reasons: No other problems noted.

LOW

Nicolo, 2018

Definitely yes;

Reasons: Randomization was stratified for initial motor impairment and

stroke lateralization, with an allocation sequence based on a block size of 3, generated with a computer random number generator

Definitely yes;

Reasons: The allocation sequence was generated by

a researcher not involved in recruitment.

Probably no;

Reasons: Subjects

were blinded with respect to the true or sham stimulation

conditions; Motor function was assessed by a trained therapist who was blinded to treatment allocation; The researcher administering

NIBS was unblinded.

Definitely yes;

Reasons: Missing outcome data was infrequent.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably yes;

Reasons: No other problems noted.

LOW

Shaheiwola, 2018

No information;

Reasons: No information was provided about the allocation sequence.

No information;

Reasons: No information was provided about the allocation concealment.

Probably yes;

Reasons: To ensure the reliability of results, there was a baseline

observation period of 4 weeks before the intervention period; No information was provided about the blinding of the patients, data collectors and data analysts.

Definitely yes;

Reasons: No patients were excluded from the analysis or lost to follow-up.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably no;

Reasons: Only

stroke patients with unilateral arm paralysis were recruited and

tested.

Some concerns

Salazar, 2020

Definitely yes;

Reasons: Randomization was done by using a

computer-generated random number of sequences (http://www.

random.com). Concealed randomization was performed in blocks

of 4 to 6 individuals.

Probably yes;

Reasons: An investigator who was not involved in the

assessment, treatment or statistical analysis conducted the

randomization.

Definitely yes;

Reasons: A trained physiotherapist

delivered the treatment to both groups. The same blinded

examiners performed all assessments; To assess the effective blinding of participants, they were asked

to answer whether they were aware of receiving real or sham tDCS. Participants were allowed to answer only YES or NO. This

assessment was performed at the end of the last evaluation

session; A blinded assessor asked all

participants if they noticed some improvement, no change or

deterioration after the treatment.

Definitely yes;

Reasons: Missing outcome data was infrequent.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably yes;

Reasons: No other problems noted.

LOW

Yao, 2020

Definitely yes;

Reasons: The

study used a computer to generate a random number table. The physician designated the random numbers in

the random number table as the experimental group or

the control group according to odd or even numbers.

Definitely yes;

Reasons: The generated random distribution sequence was put into the sequentially coded, sealed and opaque envelope.

Definitely no;

Reasons: Only the

patients were blinded to the stimulation condition by creating a scalp sensation to the subjects receiving sham stimulation.

Definitely yes;

Reasons: No patients were excluded from the analysis.

Definitely yes;

Reasons: All relevant outcomes were reported

Definitely no;

Reasons: As the study was conducted in the rehabilitation

inpatient facility in real-world practice, and all of the patients likely received additional rehabilitation

therapy outside of the clinical-trial setting. We could not quantify and control these therapies which may pose

biases to the study.

Some concerns

Edwards, 2019

Definitely yes;

Reasons: The randomization was block stratified to ensure our two comparison groups were balanced with respect to this potential prognostic factor.

Definitely yes;

Reasons: The allocation was concealed by a predetermined sealed envelope method. Both the patient and tDCS administrator were blind to the randomization.

Probably yes;

Reasons: Patients, evaluating therapists, and analysts were

blind to the tDCS randomization.

Probably no;

Reasons: 8/77 patients were lost to follow-up due to unrelated illness, botox treatment or illness of relative.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably yes;

Reasons: No other problems noted.

LOW

Andrade, 2017

Definitely yes;

Reasons: Randomization was conducted with randomly permuted blocks, through an online program (www. random.org). After completion of baseline measures.

Definitely yes;

Reasons: Blind allocation in the ratio of 1:1:1:1 was carried out with sequentially numbered and sealed opaque envelopes.

Definitely yes;

Reasons: Blinding was extended from the person responsible for randomization, allocation, outcome assessing, and trialists

to those who analyzed the data.

Probably yes;

Reasons: 2/60 patients were lost to follow-up, which was infrequent and balanced.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably yes;

Reasons: No other problems noted.

LOW

Cattagni, 2019

Probably yes;

Reasons: The order of sessions was randomized in order to ensure that equal numbers (12) of participants began with each type of session (effective anodal tDCS or sham tDCS).

No information;

Reasons: Reasons: No information was provided about the concealment of the allocation sequence.

Definitely yes;

Reasons: To ensure that the session was blinded, an independent physician set-up the tDCS equipment in either anodal or placebo mode; this person was uninvolved in data recording, collecting or processing.

No information;

Reasons: No information was provided about lost to follow-up.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably yes;

Reasons: No other problems noted.

Some concerns

Zumbansen, 2020

Definitely yes;

Reasons: Computer-generated, non-restricted randomization by

site was performed through an online system located at

the Department of Clinical Epidemiology at the JGH

(Montreal).

Definitely yes;

Reasons: Only the technician performing the stimulation

had access to the randomization information when logging into the study platform, on the first day of treatment.

Definitely yes;

Reasons: Patients, therapist, principal investigators and

research personnel assessing clinical outcomes were

blinded to the treatment assignment. Therapists did

not attend rTMS sessions and had no access to the tDCS device settings.

Probably yes;

Reasons: 1/63 patients were lost to follow-up at the first day after the intervention, which was infrequent.

Definitely yes;

Reasons: All relevant outcomes were reported

Definitely no;

Reasons: Patient characteristics were not balanced (in terms of language variability), the recruitment goal was not reached, assessment tools lack validation.

LOW

Wang, 2019

Definitely yes;

Reasons: The subjects were assigned to the groups using a

computer-generated randomization list by a single investigator.

Definitely yes;

Reasons: The subjects were assigned to the groups using a

computer-generated randomization list by a single investigator.

The assigned random number was input into the stimulator device by the same investigator who did not

participate in other sections of the study.

Definitely yes;

Reasons: All subjects

and speech-language therapists were blinded to the design.

Definitely yes;

Reasons: No patients were lost to follow-up.

Definitely yes;

Reasons: All relevant outcomes were reported

Probably no;

Reasons: the inclusion criteria for brain lesion involved in the left frontal lobe, but most participants’ lesion was far beyond the site.

LOW

Hosseinzadeh, 2018

Definitely yes;

Reasons: The research groups (of patients) were based on the random selection of envelopes.

Definitely yes;

Reasons: In order to observe the double blindness of the research, the patients chose closed envelopes for the rhombus, in which specific codes were inserted. The patients and tDCS-conducting technicians

did not know the content of the envelopes, thus providing a satisfactory classification of the four groups.

Definitely yes;

Reasons: In order to observe the double blindness of the research, the patients chose closed envelopes for the rhombus, in which specific codes were inserted.

Probably yes;

Reasons: Loss to follow-up was not reported.

Definitely yes;

Reasons: All relevant outcomes were reported.

Probably yes;

Reasons: No other problems noted.

LOW

Shaker, 2018

No information;

Reasons: No information was provided about the generation of the allocation sequence.

No information;

Reasons: No information was provided about allocation concealment.

Definitely no;

Reasons: The study was single-blinded but did not specify who was blinded.

Probably yes;

Reasons: Loss to follow-up was not reported.

Definitely yes;

Reasons: All relevant outcomes were reported.

Probably yes;

Reasons: No other problems noted.

Some concerns