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Effects of Transcranial Direct Current Stimulation on Poststroke Dysphagia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Open AccessPublished:March 21, 2022DOI:https://doi.org/10.1016/j.apmr.2022.03.004

      Abstract

      Objective

      This review aimed to systematically evaluate the effect of transcranial direct current stimulation (tDCS) on poststroke dysphagia.

      Data Sources

      PubMed, Cochrane Library (CENTRAL), Web of Science, VIP, CNKI, and Wanfang databases were systematically searched up to June 2021.

      Study Selection

      Randomized controlled trials (RCTs) on the effects of tDCS on poststroke dysphagia.

      Data Extraction

      The extracted data included the author, country of publication, time of publication, key elements of bias risk assessment (such as RCTs and blind methods), sample size and basic information (age, course of disease, stroke location), intervention measures, treatment methods of tDCS (stimulation location, intensity, duration), relevant outcome indicators, and relevant data (SDs).The Cochrane Risk of Bias Assessment Tool and Physiotherapy Evidence Database Scale were used to assess the risk of bias.

      Data Synthesis

      Sixteen RCTs were included in this meta-analysis. Overall, the results revealed a large and statistically significant pooled effect size (0.80; confidence interval [CI], 0.45-1.14; P<.001). The subgroup that explored the course of the disease yielded a large and significant effect size for the chronic phase group (0.80; CI, 0.43-1.16; P<.001). For the stimulation intensity, 1 mA and 1.6 mA showed a moderate and significant effect sizes (0.47; CI, 0.13-0.81; P=.006 vs 1.39; CI, 0.69-2.08; P<.001). In the subgroup analyses, the affected (0.87; CI, 0.26-1.48; P=.005) vs unaffected (0.61; CI, 0.23-0.99; P=.002) hemisphere showed a significant result, and stimulation of the affected hemisphere had a more obvious effect. Subgroup analysis of stroke location showed that tDCS was effective for dysphagia after unilateral hemispheric stroke, bulbar paralysis, and brainstem stroke but not for dysphagia after ataxic and basal ganglia stroke. However, the subgroup analysis of stroke location revealed a significant result (0.81; CI, 0.44-1.18; P<.001).

      Conclusions

      This meta-analysis demonstrated the height and significant beneficial effect of tDCS on improving poststroke dysphagia.

      Keywords

      List of abbreviations:

      CI (confidence interval), PEDro (Physiotherapy Evidence Database), SMD (standardized mean difference), tDCS (transcranial direct current stimulation)
      Dysphagia is a common complication of stroke, which can lead to cough while drinking water and increase the incidence of aspiration pneumonia,
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      The effect of reclining position on swallowing function in stroke patients with dysphagia.
      It has been reported that the incidence of dysphagia after acute stroke is 78%,
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      Dysphagia in acute stroke: incidence, burden and impact on clinical outcome.
      and the risk of aspiration pneumonia is 3 times higher and the mortality rate is 5.4 times higher in patients with dysphagia after stroke than that in patients without.
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      The effect of reclining position on swallowing function in stroke patients with dysphagia.
      Poststroke dysphagia not only seriously affects the recovery process and quality of life in patients but also imposes a huge economic burden on families. At present, there is no evidence-based basis for rehabilitation treatment methods used in clinical practice. It is necessary to conduct randomized controlled trials (RCTs) to confirm their effects.
      Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technology, is used as a nondrug intervention treatment for some neurologic or mental diseases because of its noninvasiveness, safety, and portability.
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      Transcranial direct current stimulation (tDCS): a promising treatment for major depressive disorder?.
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      Transcranial direct current stimulation potentiates improvements in functional ability in patients with chronic stroke receiving constraint-induced movement therapy.
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      Bihemispheric-tDCS and upper limb rehabilitation improves retention of motor function in chronic stroke: a pilot study.
      The tDCS regulates the transmembrane potential of neurons to produce hyperpolarization or depolarization by transmitting weak currents through the skull, thus changing the plasticity of the stimulated cerebral cortex.
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      Timing-dependent modulation of associative plasticity by general network excitability in the human motor cortex.
      According to different anode and cathode stimulations, tDCS can increase or decrease cortical excitability, respectively,
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      How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?.
      ,
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      Transcranial direct current stimulation: state of the art 2008.
      and thereby affect a series of behavioral measures.
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      tDCS polarity effects in motor and cognitive domains: a meta-analytical review.
      ,
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      Effects of transcranial electrical stimulation on cognition.
      Studies have reported the beneficial effects of tDCS on language performance,
      • Holland R
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      • et al.
      Speech facilitation by left inferior frontal cortex stimulation.
      learning process,
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      • Paulus W.
      Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human.
      working memory function,
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      • Fitzgerald PB.
      Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex.
      and multitasking ability
      • Andrews SC
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      • Fitzgerald PB.
      Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex.
      of healthy adults.
      Studies have confirmed that tDCS can cause motor function and psychophysiological changes related to the targeted stimulation of brain regions.
      • Stagg CJ
      • Antal A
      • Nitsche MA.
      Physiology of transcranial direct current stimulation.
      When the anodic electrode is placed in the pharyngeal motor cortex or the functional brain area related to swallowing, the resting membrane potential of neurons can be depolarized, and the spontaneous discharge of neurons can be increased, thus increasing cortical excitability.
      • Doeltgen SH
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      • Cock C
      • Omari T.
      Effects of cortical anodal transcranial direct current stimulation on swallowing biomechanics.
      ,
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      • Wollbrink A
      • et al.
      Magnetoencephalographic evidence for the modulation of cortical swallowing processing by transcranial direct current stimulation.
      In addition, tDCS regulates the synaptic microenvironment by inducing long-term neurochemical changes in the N-methyl-D-aspartate receptor or gamma-aminobutyric acid activity and thus plays a role in regulating synaptic plasticity.
      • Nitsche MA
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      Catecholaminergic consolidation of motor cortical neuroplasticity in humans.
      • Kim S
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      tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study.
      • Zhao XJ
      • Ding J
      • Pan HJ
      • et al.
      Anodal and cathodal tDCS modulate neural activity and selectively affect GABA and glutamate syntheses in the visual cortex of cats.
      It has also been suggested that tDCS may involve transient changes in the protein channel density located at the stimulating electrode. Cortical excitability can be modulated by altering the local oxygenated hemoglobin concentration and blood flow.
      • Sun Y
      • Lipton JO
      • Boyle LM
      • et al.
      Direct current stimulation induces mGluR5-dependent neocortical plasticity.
      A series of neurophysiological and behavioral results suggests that tDCS has a positive effect on the plasticity of cortical neurons and swallowing function.
      • Suntrup S
      • Teismann I
      • Wollbrink A
      • et al.
      Magnetoencephalographic evidence for the modulation of cortical swallowing processing by transcranial direct current stimulation.
      ,
      • Bolognini N
      • Vallar G
      • Casati C
      • et al.
      Neurophysiological and behavioral effects of tDCS combined with constraint-induced movement therapy in poststroke patients.
      ,
      • Vasant DH
      • Mistry S
      • Michou E
      • Jefferson S
      • Rothwell JC
      • Hamdy S.
      Transcranial direct current stimulation reverses neurophysiological and behavioural effects of focal inhibition of human pharyngeal motor cortex on swallowing.
      This review aimed to evaluate the clinical effects of tDCS on poststroke dysphagia using a meta-analysis.

      Methods

      Search strategy

      We searched the following 6 electronic databases from their inception to June 2021: PubMed, Cochrane Library (CENTRAL), Web of Science, VIP, CNKI, and Wanfang. Additionally, literature was identified by citation tracking in reference lists from the identified articles. We restricted the search to studies published in English and Chinese.
      The following English search terms were used: (transcranial direct current stimulation OR tDCS OR brain stimulation OR non-invasive brain stimulation) AND (dysphagia OR post-stroke dysphagia OR swallowing disorders OR swallowing difficulty) AND (stroke OR ischemic stroke OR hemorrhagic stroke OR cerebral apoplexy OR acute cerebral accident OR cerebrovascular accident OR brainstem stroke).

      Selection criteria

      Inclusion criteria

      According to the principle of Population, Intervention, Comparator, Outcomes, and Study Designs, the following inclusion criteria were determined: (1) the participants were all patients with stroke that was confirmed by computed tomography or magnetic resonance imaging; (2) tDCS was used as the intervention; (3) the article included at least 1 of the following standardized, validated dysphagia scales: Modified Mann Assessment of Swallowing Ability, Standardized Swallowing Assessment, Functional Oral Intake Scale, Dysphagia Outcome Severity Scale, Functional Dysphagia Scale, and Video Fluoroscopic Swallowing Study; (4) the study was clinical RCT of tDCS for the treatment of dysphagia after stroke.

      Exclusion criteria

      (1) The article was not an RCT; (2) the article was a repetitive literature, review, and nonpublic literature, such as a conference paper; (3) swallowing dysfunction in the article was caused by other diseases, such as craniocerebral trauma and Parkinson disease; (4) poor rating on the Physiotherapy Evidence Database (PEDro) Scale (0-3 of 10); (5) incomplete data.

      Process of identification

      Two researchers individually screened the literature, extracted the data, and carried out cross-checks to select the literature that was consistent with the content of this study. Ambiguous titles and abstracts were sent for full-text review to avoid erroneous exclusion of potential studies; notably, if the participants received a therapeutic intervention (that is, a combination of neuromuscular electrical stimulation and another secondary intervention), the study was not excluded. There is an ethical obligation to provide patients with alternative treatments; however, noninvasive brain stimulation is rarely used alone and often includes paired stimuli that increase the sample size and allow for greater generalization.

      Data extraction

      Data were extracted from each article for the meta-analysis. The extracted data included the author, country of publication, time of publication, key elements of bias risk assessment (such as RCTs and blind methods), sample size and basic information (age, course of disease, stroke location), intervention measures, treatment methods of tDCS (stimulation location, intensity, duration), relevant outcome indicators, and relevant data (SDs). We defined current intensity >1mA as “high-intensity” and ≤1 mA as “low-intensity.” Table 1 presents basic information on the included studies.
      Table 1Characteristics of included trials investigating tDCS in patients with poststroke dysphagia
      StudyCountryStroke TypeSample Size N1/N2Mean Age (y) n1/n2Time Post Stroke (mo)Other InterventionsStimulation SiteDosageDuration of TreatmentMain OutcomeMeasure
      Kumar et al
      • Kumar S
      • Wagner CW
      • Frayne C
      • et al.
      Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.
      USUnilateral hemispheric ischemic stroke7/770/79.70.13/0.11Concurrent standardized swallowing maneuvers

      Anodal to unaffected hemisphere Pharyngeal motor cortex2 mA30 min/5 dDOSS
      Yang et al
      • Yang EJ
      • Baek SR
      • Shin J
      • et al.
      Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia.
      South KoreaUnilateral cerebral apoplexy7/970.57/

      70.44
      0.90/0.84compensatory methods, behavioral maneuvers oromotor exercise, thermal tactile stimulationAnodal to affected hemisphere Pharyngeal motor cortex1 mA20 min/10 dFDS
      Shigematsu et al
      • Shigematsu T
      • Fujishima I
      • Ohno K.
      Transcranial direct current stimulation improves swallowing function in stroke patients.
      JapanStroke10/1064.7/66.93.02/3.22Ingestion training, indirect therapy, pushing exercises, supraglottic swallowing, shaker exercise, et alAnodal to affected hemisphere Pharyngeal motor cortex1 mA20 min/10 dDOSS
      Yuan et al
      • Yuan Y
      • Wang J
      • Wu D
      • Huang X
      • Song W.
      Effect of transcranial direct current stimulation on ataxic dysphagia after stroke.
      ChinaCerebellar and pontine arm apoplexy15/1557.4/60.71.95/1.92Peripheral percutaneous electrical stimulation therapyAnodal to body surface projection area of left/right cerebellar hemispheres1 mA20 min/20 timesMMASA
      Ahn et al
      • Ahn YH
      • Sohn HJ
      • Park JS
      • et al.
      Effect of bihemispheric anodal transcranial direct current stimulation for dysphagia in chronic stroke patients: a randomized clinical trial.
      South KoreaUnilateral cerebral apoplexy13/1366.38/61.6111.62/12.27Compensatory methods, behavioral maneuvers oromotor exercise, thermal tactile stimulationAnodal to unaffected hemisphere Pharyngeal motor cortex1 mA20 min/10 dDOSS
      Wang et al
      • Wang Z
      • Bai Y
      • Zhou J
      • Gao W
      • Shen X.
      Effect of transcranial direct current stimulation on dysphagia after cerebral apoplexy.
      ChinaUnilateral cerebral apoplexy12/1264.1/63.71.65/1.59Peripheral percutaneous electrical stimulation therapyAnodal to affected hemisphere Pharyngeal sensorimotor cortex1mA20 min/ 20 timesMMASA
      He et al
      • He H
      • Fan H
      • Wang T
      • Lu F
      • Li L
      • Ao L.
      Effect of transcranial direct current stimulation on dysphagia after stroke.
      ChinaUnilateral cerebral apoplexya/b/c

      7/7/8
      a/b/c

      62.29/61.86/60.25
      a/b/c

      1.62/1.8/1.98
      Neuromuscular electrical stimulation, ingestion training, motor and sensory training, breath traininga: Anodal to unaffected hemisphere Pharyngeal sensorimotor cortex;

      b: Anodal to affected hemisphere Pharyngeal sensorimotor cortex
      1.4 mA20 min/10 dMMASA
      Pingue et al
      • Pingue V
      • Priori A
      • Malovini A
      • Pistarini C.
      Dual transcranial direct current stimulation for poststroke dysphagia: a randomized controlled trial.
      ItalyUnilateral cerebral apoplexy20/2068.5/63.5conventional swallowing rehabilitation therapyAnodal to affected hemisphere Pharyngeal motor cortex,

      Cathodal to unaffected hemisphere Pharyngeal motor cortex
      2mA30 min/ 10 daysDOSS
      Wang et al
      • Wang S
      • Shen X
      • Mo D
      • Xu J
      • Tian J
      • Sun L.
      Clinical effect of transcranial direct current stimulation combined with swallowing training on swallowing dysfunction after cerebral apoplexy.
      ChinaBasal ganglia apoplexy20/2060.8/64.81.60/1.71Swallowing training, glottic closure training, feeding trainingAnodal to unaffected hemisphere Pharyngeal cortex1.5 mA20 min/10 dMMASS
      Suntrup et al
      • Suntrup-Krueger S
      • Ringmaier C
      • Muhle P
      • et al.
      Randomized trial of transcranial direct current stimulation for poststroke dysphagia.
      GermanyAcute ischemic stroke30/2967.3/68.90.16/0.16Swallowing exercises

      Anodal to unaffected hemisphere Pharyngeal cortex1 mA20 min/4 dFOIS
      Wang et al
      • Wang ZY
      • Chen JM
      • Lin ZK
      • Ni GX.
      Transcranial direct current stimulation improves the swallowing function in patients with cricopharyngeal muscle dysfunction following a brainstem stroke.
      ChinaBrainstem stroke14/1462.00/

      61.43
      2.25/2.22Catheter balloon dilatation and conventional swallowing therapyAnodal to the bilateral hemispheres esophageal cortical area1 mA20 min/20 dFOIS
      Chen et al
      • Chen S
      • Hu R
      • Deng X
      • Yu X.
      Effect analysis of transcranial direct current stimulation (tDCS) in the treatment of dysphagia in stroke patients.
      ChinaUnilateral cerebral apoplexy41/4356.32

      /54.31
      3.21/3.22Routine swallowing rehabilitation training, motor and sensory training, Mendelssohn swallowing and feeding trainingAnodal to affected hemisphere projection area of oropharyngeal cortex1.2 mA20 min/10 dMMASA
      Li et al
      • Li X
      • Ou Y
      • Yu T
      • Huang W
      • Chen Y
      • Yang H.
      Effect of transcranial direct current stimulation on dysphagia after brainstem stroke.
      ChinaBrainstem stroke24/2363.38/62.871.08/0.70Basic treatment, swallowing rehabilitation training, acupuncture therapyAnodal to sensory area of oropharyngeal cortex1.4 mA20 min/15 dVFSS
      Mao et al
      • Mao HW
      • Lyu Y
      • Li Y
      • et al.
      Clinical study on swallowing function of brainstem stroke by tDCS.
      ChinaBrainstem stroke20/2062.25/59.83.60/3.25Routine swallowing rehabilitation training, motor and sensory training, breath training, external laryngeal electrical stimulation, balloon dilatationAnodal to unaffected hemisphere Pharyngeal sensorimotor cortex1.6 mA20 min/48 dDOSS
      Yang et al
      • Yang C
      • Zhang J
      • Sun F
      • Du Q
      • Tian S.
      Effect of transcranial direct current stimulation on dysphagia of true pseudobulbar paralysis after cerebral apoplexy.
      ChinaStroke with bulbar paralysisa: 30/30

      b: 30/30
      b: 59.10/54.93

      a: 60.3/59.7
      b: 1.24/1.35

      a: 1.30/1.19
      Cold pharyngeal stimulation and empty swallowing, pronunciation training, tongue aspirator training, vibration training, neuromuscular electrical stimulationAnodal to affected functional regions of the brain associated with the mouth and tongue1-2 mA20 min/12 dFOIS
      Liu et al
      • Liu J
      • Wang X
      • Hua H.
      Analysis of clinical treatment effect of dysphagia after stroke.
      ChinaUnilateral cerebral apoplexy25/2554.92/55.822 wk-3moCold stimulation, soft palate lifting training, feeding trainingAnodal to affected projection area of oropharyngeal cortex1.2 mA20 min/10 dVFSS
      NOTE. n1 was the control group and n2 was the intervention group; a represents the contralateral stimulation group and the pseudobulbar paralysis group; b represents the affected side stimulation group and the true bulbar paralysis group; c is for control group.
      Abbreviations: DOSS, Dysphagia Outcome Severity Scale; FDS, Functional Dysphagia Scale; FOIS, Functional Oral Intake Scale; MMASA, Modified Mann Assessment of Swallowing Ability; VFSS, Video Fluoroscopic Swallowing Study.

      Quality assessment

      Two investigators independently evaluated the full texts of these studies for quality assessment and study eligibility using the PEDro Scale.
      • Maher CG
      • Sherrington C
      • Herbert RD
      • Moseley AM
      • Elkins M.
      Reliability of the PEDro Scale for rating quality of randomized controlled trials.
      ,
      • Moseley AM
      • Herbert RD
      • Sherrington C
      • Maher CG.
      Evidence for physiotherapy practice: a survey of the Physiotherapy Evidence Database (PEDro).
      Any disagreements were resolved in a consensus meeting. The PEDro Scale is intended to identify the internal validity of clinical studies and sufficient statistical data to guide clinical decisions, with scores ranging from 0-10, with ≤3 considered poor, 4-5 fair, 6-8 good, and 9-10 excellent.
      • Foley NC
      • Teasell RW
      • Bhogal SK
      • Speechley MR.
      Stroke rehabilitation evidence-based review: methodology.
      This review only included studies with scores of ≥4. We also used the Cochrane bias risk assessment tool to assess the risk bias of the RCTs included in the literature and carried out bias risk assessment from 6 aspects: selection bias, implementation bias, measurement bias, follow-up bias, reporting bias, and other bias.

      Statistical analyses

      All statistical analyses were performed using Reviewer Manager Software 5.4.

      The Cochrane Collaboration. Review Manager. Available at: https://training.cochrane.org. Accessed September 21, 2020.

      ,a A meta-analysis was performed for standardized mean difference (SMD) between the stimulation and control groups across the whole and predefined subgroups (stimulation site, current intensity, course of stroke, site of stroke). The data we extracted from the included studies included group sizes, group mean differences, and pooled SDs. For studies that reported median and IQR, the mean and SDs were estimated using methods previously described.
      • Luo D
      • Wan X
      • Liu J
      • Tong T.
      Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range.
      ,
      • Wan X
      • Wang WQ
      • Liu JM
      • Tong TJ.
      Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.
      Pooled SD was calculated using the following equation
      • Cohen J.
      Statistical power analysis for the behavioral sciences.
      :
      SDpooled=(npre1)SDpre2+(npost1)SDpost2npre+npost2


      For dichotomous outcomes, the odds ratios were first calculated and then converted to SMD using the equation below, as previously described48:
      SMD=3πlnoddsratio


      For each study, the SMD was calculated and synthesized into an effect size using Hedges’ g. SMD eliminates not only the effect of weights and measures on the results but also the effect of the absolute value size. Hedges’ g is a variation of Cohen's d and corrects for biases due to the small sample sizes.
      • Madden LV
      • Piepho HP
      • Paul PA.
      Statistical models and methods for network meta-analysis.
      The SMD scale was used to explain the effect size value: <0.4 was considered small, 0.40-0.69 was considered moderate, and ≥0.70 was considered large.

      Higgins JPT, Thomas J, Chandler J, et al, editors. Cochrane handbook for systematic reviews of interventions version 6.1 (updated September 2020). Available at: www.training.cochrane.org/handbook. Accessed April 15, 2021.

      In the interpretation of the combined effect size, a P value ≤.05 was considered statistically significant.
      This meta-analysis used the random-effects model, which allows within- and between-study variances (unlike fixed-effects that ignore between-study variance) and is, hence, more conservative when dealing with heterogeneity.
      • Chen H
      • Manning AK
      • Dupuis J.
      A method of moments estimator for random effect multivariate meta-analysis.
      The I2 statistic, which is useful in suggesting the effect of heterogeneity by describing the percentage of variation across studies, was used to assess statistical heterogeneity. Here, I2<25%, 25%-75%, and >75% were regarded as low, moderate, and high, respectively.
      • Higgins JP
      • Thompson SG
      • Deeks JJ
      • Altman DG.
      Measuring inconsistency in meta-analyses.

      Results

      Search results

      The search across all databases yielded a total of 273 studies. Using the duplicate finder tool in EndNote X9,

      Thomson ResearchSoft. Endnote. Available at: https://endnote.com. Accessed April 15, 2021.

      ,b we removed 100 duplicate titles. Of the remaining 173 articles, 66 were excluded by reading titles and abstracts, including reviews, conference papers, and more, and 62 articles unrelated to the research content were excluded. The remaining 45 studies were evaluated. Among them, 3 studies were excluded because of poor quality of literature, 9 studies were excluded because of repeated publication and inconformity of outcome indicators, 3 studies were excluded because of lack of available data, and 14 studies were excluded because of inconformity of inclusion criteria. The remaining 16 RCTs were included in the present study. The literature retrieval and screening process is shown in figure 1.

      Quality assessment

      Criterion 2 (hidden allocation) from the PEDro scale was disputed among the 2 raters who independently evaluated all studies. However, all differences were resolved through consultation, and consensus was reached. All the trials ranged from 5-9, with a mean internal validity score of 6.12. This indicated that the overall quality of the included RCTs was high. No study was excluded because of poor PEDro scores. We also used the Cochrane bias risk assessment tool to assess the risk bias of RCTs included in the literature (Fig 2, Fig 3). Additionally, we tested for publication bias using a simple funnel plot. Funnel plots should appear symmetrical because asymmetrical plots indicate publication bias, which is usually positive.
      • Egger M
      • Davey SG
      • Schneider M
      • Minder C.
      Bias in meta-analysis detected by a simple, graphical test.
      In our study, dots were symmetrically scattered around the size of the aggregation effect (vertical line), which indicates that there was no publication bias in this review (fig 4).
      Fig 4
      Fig 4Assessment of bias. The funnel plot assesses publication bias in the 18 included trials.

      Description of studies

      Study characteristics

      Of the 16 included RCTs, 10 were conducted in China, 2 in South Korea, and 1 each in the United States, Japan, Italy, and Germany. The trials were reported between the beginning of 2011 and beginning of 2021. The distribution of dysphagia types was as follows: 8 included studies were unilateral hemisphere poststroke dysphagia, 3 were brainstem dysphagia, 1 was stroke with bulbar palsy dysphagia, 1 was ataxia dysphagia, and 1 was basal ganglia dysphagia. The other 2 studies did not specify the location of the stroke, but both had dysphagia after stroke. The course of disease in the 3 included cases was less than 1 month, and that in the 13 was more than 1 month.

      Outcomes

      The outcome measures used differed across the trials. Five of the included RCTs in this meta-analysis used the Dysphagia Outcome and Severity Scale
      • O'Neil KH
      • Purdy M
      • Falk J
      • Gallo L.
      The Dysphagia Outcome and Severity Scale.
      as their outcome measure, 5 articles used the Modified Mann Assessment of Swallowing Ability
      • Antonios N
      • Carnaby-Mann G
      • Crary M
      • et al.
      Analysis of a physician tool for evaluating dysphagia on an inpatient stroke unit: the modified Mann Assessment of Swallowing Ability.
      , and the remaining 6 studies used the Functional Dysphagia Scale,
      • Han TR
      • Paik NJ
      • Park JW.
      Quantifying swallowing function after stroke: a functional dysphagia scale based on videofluoroscopic studies.
      Functional Oral Intake Scale,
      • Crary MA
      • Mann GD
      • Groher ME.
      Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients.
      or Video Fluoroscopic Swallowing Study.
      • Schoeppe F
      • Sommer WH
      • Haack M
      • et al.
      Structured reports of videofluoroscopic swallowing studies have the potential to improve overall report quality compared to free text reports.
      More than 1 outcome measure was used in 11 of the included 16 studies. Wherever the directionality of the scales differed, that is, greater number means improvement vs greater number means decline, the effect sizes were multiplied by −1 to make the scales uniform in direction across all trials. Excluding the effect of treatment prior to baseline assessment (prior to tDCS treatment), we found the duration of treatment was between 4 days and 8 weeks. In this study, our analysis was limited between baseline and post-treatment results, and we did not assess long-term efficacy owing to the variability of the study and lack of information.

      Stimulation protocols

      All included RCTs were performed using anode tDCS, and 1 study was a 3-arm trial. Five of them were on the unaffected hemisphere, 7 on the affected hemisphere, and 3 included bihemispheric stimulation (anodal tDCS to both affected and unaffected hemispheres). One trial used dual stimulation (anodal tDCS to the affected and cathodal tDCS to the unaffected); details of the stimulation parameters are shown in table 1.

      Synthesized data analyses

      Overall summary effect

      Overall, results from all included trials, including two 3-arm trials, a total of 18 RCTs revealed a height and statistically significant pooled effect size in favor of tDCS on poststroke dysphagia (g=0.8; 95% confidence interval [CI], 0.45-1.14; P<.001). The I2 value, which is a measure of statistical heterogeneity, was 77%, indicating high heterogeneity between trials. Five trials had a small negative effect. Thirteen trials had moderate to large positive effect sizes, ranging from 0.40-4.09, but only 7 trials were considered statistically significant (fig 5A and table 2).
      Fig 5
      Fig 5(A) Meta-analysis forest plot of the overall effects of tDCS on poststroke dysphagia. Data derived from a random-effects model. (B) Affected vs unaffected hemisphere. Subgroup analysis that shows the effect sizes for affected vs unaffected hemisphere stimulation. (C) Acute vs chronic. Subgroup analysis that shows the effect sizes for stimulation during the acute vs chronic stroke phase. (D) Stimulation intensity. Subgroup analysis that shows the effect sizes for stimulation intensity. (E) Stroke location. Subgroup analysis that shows the effect sizes for stroke location.
      Fig 5
      Fig 5(A) Meta-analysis forest plot of the overall effects of tDCS on poststroke dysphagia. Data derived from a random-effects model. (B) Affected vs unaffected hemisphere. Subgroup analysis that shows the effect sizes for affected vs unaffected hemisphere stimulation. (C) Acute vs chronic. Subgroup analysis that shows the effect sizes for stimulation during the acute vs chronic stroke phase. (D) Stimulation intensity. Subgroup analysis that shows the effect sizes for stimulation intensity. (E) Stroke location. Subgroup analysis that shows the effect sizes for stroke location.
      Fig 5
      Fig 5(A) Meta-analysis forest plot of the overall effects of tDCS on poststroke dysphagia. Data derived from a random-effects model. (B) Affected vs unaffected hemisphere. Subgroup analysis that shows the effect sizes for affected vs unaffected hemisphere stimulation. (C) Acute vs chronic. Subgroup analysis that shows the effect sizes for stimulation during the acute vs chronic stroke phase. (D) Stimulation intensity. Subgroup analysis that shows the effect sizes for stimulation intensity. (E) Stroke location. Subgroup analysis that shows the effect sizes for stroke location.
      Table 2Calculated SMDs of included studies and their magnitude
      StudyEffect Size95% CIMagnitude
      Kumar et al
      • Kumar S
      • Wagner CW
      • Frayne C
      • et al.
      Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.


      Yang et al
      • Yang EJ
      • Baek SR
      • Shin J
      • et al.
      Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia.


      Shigematsu et al
      • Shigematsu T
      • Fujishima I
      • Ohno K.
      Transcranial direct current stimulation improves swallowing function in stroke patients.


      Yuan et al
      • Yuan Y
      • Wang J
      • Wu D
      • Huang X
      • Song W.
      Effect of transcranial direct current stimulation on ataxic dysphagia after stroke.


      Ahn et al
      • Ahn YH
      • Sohn HJ
      • Park JS
      • et al.
      Effect of bihemispheric anodal transcranial direct current stimulation for dysphagia in chronic stroke patients: a randomized clinical trial.


      Pingue et al
      • Pingue V
      • Priori A
      • Malovini A
      • Pistarini C.
      Dual transcranial direct current stimulation for poststroke dysphagia: a randomized controlled trial.


      He et al
      • He H
      • Fan H
      • Wang T
      • Lu F
      • Li L
      • Ao L.
      Effect of transcranial direct current stimulation on dysphagia after stroke.
      b

      He et al
      • He H
      • Fan H
      • Wang T
      • Lu F
      • Li L
      • Ao L.
      Effect of transcranial direct current stimulation on dysphagia after stroke.
      a

      Wang et al
      The 95% confidence interval of effect size doesn't include 0.


      Wang et al
      • Wang S
      • Shen X
      • Mo D
      • Xu J
      • Tian J
      • Sun L.
      Clinical effect of transcranial direct current stimulation combined with swallowing training on swallowing dysfunction after cerebral apoplexy.


      Suntrup et al
      • Suntrup-Krueger S
      • Ringmaier C
      • Muhle P
      • et al.
      Randomized trial of transcranial direct current stimulation for poststroke dysphagia.


      Wang et al
      The 95% confidence interval of effect size doesn't include 0.


      Chen et al
      The 95% confidence interval of effect size doesn't include 0.


      Li et al
      The 95% confidence interval of effect size doesn't include 0.


      Yang et al
      • Yang C
      • Zhang J
      • Sun F
      • Du Q
      • Tian S.
      Effect of transcranial direct current stimulation on dysphagia of true pseudobulbar paralysis after cerebral apoplexy.
      b

      Yang et al
      • Yang C
      • Zhang J
      • Sun F
      • Du Q
      • Tian S.
      Effect of transcranial direct current stimulation on dysphagia of true pseudobulbar paralysis after cerebral apoplexy.
      a
      The 95% confidence interval of effect size doesn't include 0.


      Liu et al
      The 95% confidence interval of effect size doesn't include 0.


      Mao et al
      The 95% confidence interval of effect size doesn't include 0.


      Pool
      0.86

      −0.31

      0.64

      0.40

      0.15

      0.20

      0.08

      0.58

      0.89

      0.57

      0.30

      1.26

      0.97

      0.66

      0.45

      0.99

      4.09

      1.39

      0.80
      −0.25 to 1.97

      −1.31 to 0.68

      −0.26 to 1.55

      −0.32 to 1.12

      −0.62 to 0.92

      −0.42 to 0.82

      −0.94 to 1.09

      −0.47 to 1.62

      0.04 to 1.73

      −0.06 to 1.2

      −0.21 to 0.81

      0.44 to 2.09

      0.52 to 1.42

      0.07 to 1.25

      −0.06 to 0.96

      0.45 to 1.53

      3.09 to 5.10

      0.69 to 2.08

      0.45 to 1.14
      Large

      Small

      Moderate

      Moderate

      Small

      Small

      Small

      Moderate

      Large

      Moderate

      Small

      Large

      Large

      Moderate

      Moderate

      Large

      Large

      Large
      low asterisk The 95% confidence interval of effect size doesn't include 0.

      Affected vs unaffected hemispheres

      The tDCS on the affected vs unaffected hemisphere revealed a moderate and significant pooled effect size for both (g=0.87; CI, 0.26-1.48; P=.005 vs g=0.61; CI, 0.23-0.99; P=.002). The measure of heterogeneity was much lower for the unaffected group than for the affected group (I2=35% vs 85%). Three studies were excluded from this analysis because they used bihemispheric stimulation (see fig 5B).

      Patients with acute vs chronic stroke

      The chronicity of stroke was classified as acute (0-14 days) and chronic (beyond 15 days). Similarly, the application of tDCS in the acute vs chronic stroke phase yielded a moderate and significant effect size for both groups (g=0.40; CI, −0.07 to 0.86; P=.09 vs g=0.80; CI, 0.43-1.16; P<.001). The I2 values for the 2 groups were 0% and 76%, respectively (see fig 5C).

      Stimulation intensity

      The 2 high-intensity stimulation studies that used 2 mA showed a small, nonsignificant effect size of 0.36 (CI, −0.19 to 0.91; P=.20). The statistical heterogeneity of this group was small, with an I2 value of 2%. Application of 1 mA current strength for 20 min/d, as in the 7 RCTs, revealed a moderate, significant effect size of 0.47 (CI, 0.13-0.81; P=.006). This group was homogenous (27%). The 2 studies that used 1.4 mA and 1 study that used 1.6 mA showed a moderate, significant effect size of 0.53 (CI, 0.07-0.99; P=.02) and 1.39 (CI, 0.69-2.08; P<.001). Two studies that used 1.2 mA showed a large but nonsignificant effect size of 2.50 (CI, −0.56 to 5.56; P=.11). One study that used 1.5 mA showed a moderate but nonsignificant effect size of 0.57 (CI, −0.06 to 1.20; P=.08). The last study was excluded from this analysis because its current intensity was unclear (see fig 5D).

      Stroke location

      Nine trials using tDCS to the unilateral hemisphere demonstrated a large and significant pooled effect size of 0.82 (CI, 0.11-1.53; P=.02) (see fig 5E). Three studies on the brainstem demonstrated a large and significant pooled effect size (1.06, CI 0.58-1.53; P<.001), as shown in fig 5B. Studies using tDCS to the bulbar paralysis demonstrated a large and significant pooled effect size of 0.71 (CI, 0.18-1.25; P=.008). Two studies on the cerebellum and basal ganglia showed a small, nonsignificant effect size of 0.40 (CI, −0.32 to 1.12; P=.28) and 0.57 (CI, −0.06 to 1.20; P=.08).

      Safety and adverse events

      Three studies

      Higgins JPT, Thomas J, Chandler J, et al, editors. Cochrane handbook for systematic reviews of interventions version 6.1 (updated September 2020). Available at: www.training.cochrane.org/handbook. Accessed April 15, 2021.

      reported slight tingling or itching at the beginning of tDCS treatment, but no serious adverse events occurred. No cases of shedding due to tDCS treatment were reported in any of the studies (table 3).
      Table 3Safety and adverse events included in the study
      StudySecurity
      Kumar et al
      • Kumar S
      • Wagner CW
      • Frayne C
      • et al.
      Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.
      No adverse events.
      Yang et al
      • Yang EJ
      • Baek SR
      • Shin J
      • et al.
      Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia.
      The electrodes were placed in a slightly prickling position at the beginning of the stimulation.
      Shigematsu et al
      • Shigematsu T
      • Fujishima I
      • Ohno K.
      Transcranial direct current stimulation improves swallowing function in stroke patients.
      There was 1 case of abscission, which was not related to tDCS.
      Yuan et al
      • Yuan Y
      • Wang J
      • Wu D
      • Huang X
      • Song W.
      Effect of transcranial direct current stimulation on ataxic dysphagia after stroke.
      No adverse events, good tolerance No adverse events, good tolerance.
      Ahn et al
      • Ahn YH
      • Sohn HJ
      • Park JS
      • et al.
      Effect of bihemispheric anodal transcranial direct current stimulation for dysphagia in chronic stroke patients: a randomized clinical trial.
      No adverse events, good tolerance.
      Pingue et al
      • Pingue V
      • Priori A
      • Malovini A
      • Pistarini C.
      Dual transcranial direct current stimulation for poststroke dysphagia: a randomized controlled trial.
      No adverse reactions.
      He et al
      • He H
      • Fan H
      • Wang T
      • Lu F
      • Li L
      • Ao L.
      Effect of transcranial direct current stimulation on dysphagia after stroke.
      Slight prickling occurred at the beginning of the stimulation.
      Wang et al
      • Wang ZY
      • Chen JM
      • Lin ZK
      • Ni GX.
      Transcranial direct current stimulation improves the swallowing function in patients with cricopharyngeal muscle dysfunction following a brainstem stroke.
      Not described.
      Wang et al
      • Wang S
      • Shen X
      • Mo D
      • Xu J
      • Tian J
      • Sun L.
      Clinical effect of transcranial direct current stimulation combined with swallowing training on swallowing dysfunction after cerebral apoplexy.
      Not described.
      Suntrup et al
      • Suntrup-Krueger S
      • Ringmaier C
      • Muhle P
      • et al.
      Randomized trial of transcranial direct current stimulation for poststroke dysphagia.
      No adverse events, good tolerance.
      Wang et al
      • Wang ZY
      • Chen JM
      • Lin ZK
      • Ni GX.
      Transcranial direct current stimulation improves the swallowing function in patients with cricopharyngeal muscle dysfunction following a brainstem stroke.
      No adverse events, good tolerance.
      Chen et al
      • Chen S
      • Hu R
      • Deng X
      • Yu X.
      Effect analysis of transcranial direct current stimulation (tDCS) in the treatment of dysphagia in stroke patients.
      Not described.
      Li et al
      • Li X
      • Ou Y
      • Yu T
      • Huang W
      • Chen Y
      • Yang H.
      Effect of transcranial direct current stimulation on dysphagia after brainstem stroke.
      Not described.
      Yang et al
      • Yang C
      • Zhang J
      • Sun F
      • Du Q
      • Tian S.
      Effect of transcranial direct current stimulation on dysphagia of true pseudobulbar paralysis after cerebral apoplexy.
      Not described. No serious complications, only a slight itching or ant walking sensation at the beginning of the stimulation.
      Liu et al
      • Liu J
      • Wang X
      • Hua H.
      Analysis of clinical treatment effect of dysphagia after stroke.
      No adverse events, good tolerance.
      Mao et al
      • Mao HW
      • Lyu Y
      • Li Y
      • et al.
      Clinical study on swallowing function of brainstem stroke by tDCS.
      No adverse events, good tolerance.

      Discussion

      The treatment of poststroke dysphagia is expensive and potentially fatal. Studies have shown that at least 1 in every 2 patients with stroke has dysphagia. Many studies have explored whether tDCS can be used to treat dysphagia. At present, there are few RCTs investigating transcranial direct current in the treatment of stroke-related dysphagia, so there is no reliable evaluation of the therapeutic effect. In this context, a systematic review would be helpful for synthesizing the results of these trials. This meta-analysis aimed to evaluate the effect of tDCS on the improvement of poststroke dysphagia.
      Sixteen RCTs met the inclusion criteria for this review. Two trials contained 2 eligible treatment arms performed on independent participants. Therefore, 18 trials were included in this study. The synthesized findings demonstrate that the use of transcranial direct facilitated recovery in poststroke dysphagia. When the 18 trials were combined, a large and significant pooled effect size emerged (0.80; 95% CI, 0.45-1.14; P<.001).
      This meta-analysis builds on the findings of an earlier meta-analysis.
      • Marchina S
      • Pisegna JM
      • Massaro JM
      • et al.
      Transcranial direct current stimulation for post-stroke dysphagia: a systematic review and meta-analysis of randomized controlled trials.
      The pooled effect size was only 0.31. Similarly, in another meta-analysis by Pisegna et al,
      • Pisegna JM
      • Kaneoka A
      • Pearson WJ
      • Kumar S
      • Langmore SE.
      Effects of non-invasive brain stimulation on post-stroke dysphagia: a systematic review and meta-analysis of randomized controlled trials.
      a moderate effect size of 0.55 (CI, 0.17-0.93; P=.004) of noninvasive brain stimulation on poststroke dysphagia was demonstrated. Both of these meta-analyses included tDCS as well as transcranial magnetic stimulation studies. The tDCS subgroup analysis did not reach statistical significance. A meta-analysis of noninvasive brain stimulation compared with sham stimulation in patients with dysphagia after stroke was also performed previously.
      • Yang SN
      • Pyun SB
      • Kim HJ
      • Ahn HS
      • Rhyu BJ.
      Effectiveness of non-invasive brain stimulation in dysphagia subsequent to stroke: a systemic review and meta-analysis.
      The effect size of 1.08 seems substantial; however, the CIs are exceedingly large, which signals caution in interpretation. Wang
      • Wang T
      • Dong L
      • Cong X
      • et al.
      Comparative efficacy of non-invasive neurostimulation therapies for poststroke dysphagia: a systematic review and meta-analysis.
      and Cheng
      • Cheng I
      • Sasegbon A
      • Hamdy S.
      Effects of neurostimulation on poststroke dysphagia: a synthesis of current evidence from randomized controlled trials.
      and colleagues conducted a meta-analysis of the effects of neurostimulation on poststroke dysphagia, including repetitive transcranial magnetic stimulation, tDCS, surface neuromuscular electrical stimulation, and pharyngeal electrical stimulation; however, only 5-7 studies on tDCS have been included. Our study, based on a large sample size from all RCTs, showed that tDCS improves swallowing function in patients with poststroke dysphagia.
      The effectiveness of tDCS stimulation on the affected hemisphere in improving dysphagia after stroke may be related to the bilateral cortical representation of swallowing. The study also analyzed other factors that appeared in the trial results, which are discussed below.

      Affected vs unaffected

      The issue of which hemisphere to stimulate is an important factor. Our study found that the excitatory stimulation of tDCS on both the unaffected and affected sides was statistically significant in the improvement of poststroke dysphagia.
      From the perspective of anatomic structure, the swallowing cortex and neural network structure of the affected cerebral hemisphere were destroyed after stroke, while stimulation of the unaffected cerebral hemisphere was minimally affected by nerve loss or tissue injury. Remodeling of the unaffected cerebral hemisphere is the basis for the spontaneous recovery of swallowing disorders after stroke.
      • Antonios N
      • Carnaby-Mann G
      • Crary M
      • et al.
      Analysis of a physician tool for evaluating dysphagia on an inpatient stroke unit: the modified Mann Assessment of Swallowing Ability.
      However, it is probable that stimulation of the affected hemispheres would increase the chance of stimulating the infarct volume. We applied tDCS to the affected hemisphere in 1 case. Yang et al
      • Yang EJ
      • Baek SR
      • Shin J
      • et al.
      Effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia.
      found increased glucose metabolism in the postcentral gyrus of the unaffected hemisphere and believed that tDCS might activate a large area of the cortical network engaged in swallowing recovery rather than activate the only stimulated area under the electrode. In addition, some functional neuroimaging studies suggested that affected motor regions could be targeted because the reactivation of intact portions of the affected motor cortex is associated with better outcomes after stroke.
      • Cramer SC
      • Mark A
      • Barquist K
      • et al.
      Motor cortex activation is preserved in patients with chronic hemiplegic stroke.
      Our results also showed that stimulation of the affected hemisphere had a larger and more significant pooled effect size than stimulation of the unaffected hemisphere (see fig 4). The effect size of the affected hemisphere (0.87, P=.005) was much higher than that of the unaffected hemisphere (0.61, P=.002), but the heterogeneity of the affected side stimulus was higher (I2=85%, 0.87). A sensitivity analysis was conducted. Because of the differences between the outcome indicators adopted by Liu et al and other included studies, after eliminating the study by Liu
      • Liu J
      • Wang X
      • Hua H.
      Analysis of clinical treatment effect of dysphagia after stroke.
      a random-effect model was used for meta-analysis, and I2=37% (0.58). The research of Liu has a great influence on the heterogeneity of the articles. This may be because of an advantage in the age of the participants included in the study compared with other studies and a large gap in the course of disease among the participants included.
      Some scholars believe that the ipsilateral cortex is more important in swallowing function because the lesion site of patients with dysphagia may be more concentrated on the dominant side of swallowing.
      • Hamdy S
      • Aziz Q
      • Rothwell JC
      • et al.
      The cortical topography of human swallowing musculature in health and disease.
      Therefore, the role of the dominant cortex in swallowing should not be ignored. This idea was also confirmed by Khedr et al,
      • Khedr EM
      • Abo-Elfetoh N
      • Rothwell JC.
      Treatment of post-stroke dysphagia with repetitive transcranial magnetic stimulation.
      who demonstrated improvement in dysphagia after stroke by stimulating the swallowing cortex of the affected hemisphere using repetitive transcranial magnetic stimulation. The results of this review suggest that stimulation of both the affected and unaffected hemispheres with tDCS may improve dysphagia after a stroke. More RCTs will help further understand the mechanism of tDCS in the treatment of dysphagia after stroke.

      Patients with acute vs chronic stroke

      While numerous studies have investigated the use of tDCS in the chronic phase of stroke and have shown that it is safe and effective in improving function, data on safety and, more importantly, efficacy in acute stroke remains sparse. The spontaneous recovery process during the acute phase is presumed to be related to cortical reorganization and an increase in pharyngeal motor representation in the contralesional motor cortex.
      • Hamdy S
      • Aziz Q
      • Rothwell JC
      • et al.
      Recovery of swallowing after dysphagic stroke relates to functional reorganization in the intact motor cortex.
      ,

      Hamdy S, Rothwell JC, Aziz Q, Thompson DG. Organization and reorganization of human swallowing motor cortex: implications for recovery after stroke. Clin Sci (Lond) 200;99:151-157.

      Hence, it may be advantageous to facilitate this course using neuromodulatory techniques such as tDCS.
      In the subgroup analysis, we found that tDCS improved swallowing function in patients with stroke in the convalescent stage but not in the acute phase, which may be related to the small number of studies included in the acute phase. This review did not retrieve clinical trials within 72 hours of the onset of stroke and 1.5 years after the onset of stroke, and at present, there is no conclusion on when patients with dysphagia after stroke should receive tDCS after the attack of stroke.

      Stimulation intensity

      In the present review, the 9 RCTs in the high stimulation group (>1mA) used a larger current, higher current density, and longer stimulation duration than the trials in the low-stimulation group (=1mA) (see table 1); however, in the high-stimulation group, only the current intensity of 1.6 mA showed a moderate and significant effect. Despite the overall high stimulation intensity, the effect size was very small. In contrast, the low-intensity stimulation group showed moderate and significant results. Notably, variables that might have confused outcomes were not accounted for: stroke period, age, severity of stroke, dysphagia at baseline, or when swallowing treatment was performed.

      Stroke location

      This meta-analysis showed that tDCS has a good therapeutic effect on dysphagia after unilateral hemisphere stroke and brainstem stroke, but it is not obvious for dysphagia after stroke in the basal ganglia and cerebellum. The recovery of swallowing function depends on the development of plasticity in the swallowing motor cortex. Most studies suggest that the recovery of deglutition after unilateral cerebral apoplexy depends on the functional remodeling of the deglutition motor cortex in the healthy hemisphere.
      • Kumar S
      • Wagner CW
      • Frayne C
      • et al.
      Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.
      ,
      • He H
      • Fan H
      • Wang T
      • Lu F
      • Li L
      • Ao L.
      Effect of transcranial direct current stimulation on dysphagia after stroke.
      ,
      • Suntrup-Krueger S
      • Ringmaier C
      • Muhle P
      • et al.
      Randomized trial of transcranial direct current stimulation for poststroke dysphagia.
      However, some studies suggest that enhancing the plasticity of the undamaged motor cortex around the affected hemisphere is also beneficial to the recovery of swallowing function. The basal ganglia include a group of cell bodies located under the cortex of the brain, whose function is to regulate muscle tone and maintain stability of movement. Basal ganglia function injury leads to high or low muscle tone and aimless movement tDCS is performed by placing anodic electrodes in the pharyngeal motor cortex or in functional areas of the brain related to swallowing to depolarize the resting membrane potential of neurons and increase the spontaneous discharge of neurons, thereby increasing the excitability of the cortex. It may not target the basal ganglia or cerebellum.
      Treatment of dysphagia is closely related to neural injury mechanisms. Swallowing function involves the primary motor sensory cortex, insular lobe, cingulate gyrus, prefrontal cortex, temporal lobe, parietooccipital region, and other brain regions, which constitute the central network of cortical swallowing. These brain regions participate in the swallowing process together.

      Study limitations

      There are several limitations that must be addressed. First, the included studies were heterogeneous in treatment protocols and outcome measurements. One study, in particular, Liu et al,
      • Liu J
      • Wang X
      • Hua H.
      Analysis of clinical treatment effect of dysphagia after stroke.
      might have shown such a large effect size owing to several factors influencing the precision of their results. When excluding this study from the analysis, the I2 dropped from 77% to 44% and the pooled effect size dropped from 0.80 to 0.64, but the results were still considered moderate and remained significant (P<.001).
      Second, patients in different studies had different characteristics. Stroke location (unilateral hemisphere and brainstem), stroke type (ischemic and hemorrhagic), and time post onset (acute and chronic stroke) are just a few of the diverse variables that could have confounded the results. However, regardless of the lesion type, it is presumed that the cases of dysphagia were neurogenic and therefore should have benefitted from interventions that promoted neuroplasticity.
      Third, some studies combined noninvasive brain stimulation with other methods (such as, neuromuscular electrical stimulation and Mendelsohn maneuver). This review did not exclude any RCTs in which paired stimulation was provided. Certainly, by combining stimulation with another form of intervention, a confounding variable comes into play: the type and strength of secondary action. Although some studies have shown that multiple stimulation work better than 1 stimulus alone, this does not negate the importance of neurostimulation.
      • Celnik P
      • Paik NJ
      • Vandermeeren Y
      • Dimyan M
      • Cohen LG.
      Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke.
      ,
      • Michou E
      • Mistry S
      • Jefferson S
      • Singh S
      • Rothwell J
      • Hamdy S.
      Targeting unlesioned pharyngeal motor cortex improves swallowing in healthy individuals and after dysphagic stroke.
      Future research should continue to investigate how, and which, paired interventions work optimally in recovering the swallowing function in patients.
      Fourth, more clinically relevant endpoints have been studied and achieved much more rarely.
      • Dziewas R
      • Michou E
      • Trapl-Grundschober M
      • et al.
      European Stroke Organization and European Society for Swallowing Disorders guideline for the diagnosis and treatment of post-stroke dysphagia.
      Only one of the included studies
      • Mao HW
      • Lyu Y
      • Li Y
      • et al.
      Clinical study on swallowing function of brainstem stroke by tDCS.
      assessed patients' nutrition-related indicators and infection indicators and found that there were statistically significant differences in nutrition-related indexes and infection indexes between the 2 groups before and after tDCS treatment (P<.05). More clinical studies are needed to confirm the effects of tDCS on mortality, pneumonia, quality of life, and length of hospital stay in patients with poststroke dysphagia.
      Finally, under normal circumstances, meta-analysis should be based on individual data; however, because of the lack of individual data, this method is not feasible. In addition, although all recent studies on this topic were retrieved, the number of trials and participants included in the trials were relatively small.

      Conclusions

      The systematic evaluation results showed that anode tDCS had a better effect on poststroke dysphagia. Although these methods have been tested in a number of studies and in different patient populations of late, larger multicenter RCTs with clinically relevant endpoints are needed for a final assessment of their respective effectiveness.

      Suppliers

      • a.
        Review Manager; Cochrane Collaboration.
      • b.
        EndNote X9; Thomson Reuters, Clarivate, Niles Software.

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