Neurostimulation in People with Oropharyngeal Dysphagia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials—Part II: Brain Neurostimulation
by
, , , , , , and
Renée Speyer
1,2,3,*
,
Anna-Liisa Sutt
4,5,
Liza Bergström
6,7,
Shaheen Hamdy
8,
Timothy Pommée
9,
Mathieu Balaguer
9
,
Anett Kaale
1,10 and
Reinie Cordier
2,11 1
Department Special Needs Education, University of Oslo, 0318 Oslo, Norway
2
Curtin School of Allied Health, Faculty of Health Sciences, Curtin University, Perth, WA 6102, Australia
3
Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Centre, 1233 ZA Leiden, The Netherlands
4
Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD 4032, Australia
5
School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia
6
Remeo Stockholm, 128 64 Stockholm, Sweden
7
Speech Therapy Clinic, Danderyd University Hospital, 182 88 Stockholm, Sweden
8
Faculty of Biology, GI Sciences, School of Medical Sciences, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
9
IRIT, CNRS, Université Paul Sabatier, 31400 Toulouse, France
10
Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias, Oslo University Hospital, 0424 Oslo, Norway
11
Department of Social Work, Education and Community Wellbeing, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon the Tyne NE7 7XA, UK
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2022, 11(4), 993; https://doi.org/10.3390/jcm11040993
Submission received: 7 December 2021
/
Revised: 9 February 2022
/
Accepted: 11 February 2022
/
Published: 14 February 2022
(This article belongs to the Special Issue Advances in Management of Voice and Swallowing Disorders)
Abstract
:Objective. To assess the effects of brain neurostimulation (i.e., repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) in people with oropharyngeal dysphagia (OD). Methods. Systematic literature searches were conducted in four electronic databases (CINAHL, Embase, PsycINFO, and PubMed) to retrieve randomised controlled trials (RCTs) only. Using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2), the methodological quality of included studies was evaluated, after which meta-analysis was conducted using a random-effects model. Results. In total, 24 studies reporting on brain neurostimulation were included: 11 studies on rTMS, 9 studies on tDCS, and 4 studies on combined neurostimulation interventions. Overall, within-group meta-analysis and between-group analysis for rTMS identified significant large and small effects in favour of stimulation, respectively. For tDCS, overall within-group analysis and between-group analysis identified significant large and moderate effects in favour of stimulation, respectively. Conclusion. Both rTMS and tDCS show promising effects in people with oropharyngeal dysphagia. However, comparisons between studies were challenging due to high heterogeneity in stimulation protocols and experimental parameters, potential moderators, and inconsistent methodological reporting. Generalisations of meta-analyses need to be interpreted with care. Future research should include large RCTs using standard protocols and reporting guidelines as achieved by international consensus.
1. Introduction
Oropharyngeal dysphagia (OD) or swallowing problems is highly prevalent among stroke patients, people with progressive neurological diseases, patients with head and neck cancer, and in frail older persons [1,2]. Prevalence estimates of OD may vary depending on underlying medical diagnoses, but have been reported as high as 80% in stroke and Parkinson’s disease [3], and 70% in oncological populations [4]. OD is associated with dehydration, malnutrition, aspiration pneumonia, and increased mortality [5,6,7], but also leads to decreased health-related quality of life [8].
Treatment and management of OD may vary widely. However, apart from traditional compensatory and rehabilitative strategies including diet modifications, postural adjustments, oromotor training and swallow manoeuvres [9], recent studies report on the possible beneficial effects of non-invasive brain stimulation. Brain neurostimulation aims to modulate cortical excitability and include techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). rTMS uses electromagnetic induction resulting in depolarisation of postsynaptic connections, whereas tDCS uses direct electrical current shifting the polarity of nerve cells [10]. Neurostimulation protocols may vary greatly per study, including different neurostimulation sites, frequencies, stimulation duration and number of different outcome measures are used to objectify treatment effects, and individual responses to stimulation are highly variable [10,11,12].
Aspiring to improved treatment efficacy in OD management, non-invasive brain stimulation has achieved growing interest over the past decade. Several reviews have been published on rTMS and tDCS [10,12,13,14,15,16,17,18], each publication having different inclusion and exclusion criteria and methodology. All previous reviews targeted brain neurostimulation interventions in post-stroke populations except for one review that included patients with acquired brain injury [16]; to date, all reviews on brain stimulation set criteria based on medical diagnoses. Moreover, not all reviews performed meta-analysis [14] and as several neurostimulation trials have only been published recently, earlier reviews will have identified fewer studies.
This is the second paper (Part II) of two companion papers on treatment effects of neurostimulation in people with OD. The first systematic review (Part I) reported on the effects of pharyngeal electrical stimulation (PES) and neuromuscular electrical stimulation (NMES).
The aim of this systematic review (Part II) is to determine the effects of brain neurostimulation (i.e., rTMS and tDCS) in people with OD without excluding populations based on medical diagnoses. Only randomised controlled trials (RCTs) will be included being the highest level of evidence. Meta-analyses will be conducted to summarise results and report on possible moderators of treatment effects.
2. Methods
The methodology and reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and checklist (Supplementary Tables S1 and S2) [19,20]. Adhering to the PRISMA statement and checklist ensures essential and transparent reporting of systematic reviews. The protocol for this review was registered with PROSPERO, the international prospective register of systematic reviews (registration number: CRD42020179842).
2.1. Information Sources and Search Strategies
An electronic database search for extant literature was conducted on 6 March 2021, using the following four databases: CINAHL, Embase, PsycINFO, and PubMed. Publications dates included in the search were 1937–2021, 1902–2021, 1887–2021, and 1809–2021, respectively. Generally, search strategies consisted of combinations of terms related to ‘dysphagia’ and ‘randomised controlled trial’. Both subject headings (e.g., MeSH and Thesaurus terms) and free text terms were used to search databases. The full list of electronic search strategies for each database can be found in Table 1. To identify literature not found utilising these strategies, the reference lists of eligible articles were checked.
2.2. Inclusion and Exclusion Criteria
To be eligible for inclusion in this systematic review, studies had to meet the following criteria: (1) participants had a diagnosis of oropharyngeal dysphagia; (2) the study included non-invasive neurostimulation interventions aimed at reducing swallowing or feeding problems; (3) the study included a control group or comparison intervention group; (4) participants were randomly assigned to one of the study arms or groups; and (5) the study was published in English language.
Interventions such as non-electrical peripheral stimulation (e.g., air-puff or gustatory stimulation), pharmacological interventions and acupuncture, were considered out of scope of this review, thus were excluded. Invasive techniques and/or those that did not specifically target OD (e.g., deep-brain stimulation studies after neurosurgical implementation of a neurostimulator) were also excluded. Conference abstracts, doctoral theses, editorials, and reviews were excluded.
2.3. Systematic Review
Methodological Quality and Risk of Bias. The Revised Cochrane risk-of-bias tool for randomised trials (RoB 2) [21] was used to assess the methodological quality of the included studies. The RoB 2 tool identifies domains to consider when assessing where bias may have been introduced into a randomised trial: (1) bias arising from the randomisation process; (2) bias due to deviations from intended interventions; (3) bias due to missing outcome data; (4) bias in measurement of the outcome; and (5) bias in selection of the reported result. For each domain, a series of signalling questions are answered to give a judgement (i.e., “low risk of bias”, “some concerns”, or “high risk of bias”), which can then be assessed in aggregate to determine a study’s overall risk of bias [21].
Data Collection Process. Data were extracted from the included studies using a data extraction form created for this purpose. This form allowed for extraction of data under several categories, relevant to meta-analyses, including participant diagnosis, inclusion and exclusion criteria, sample size, age, gender, intervention goal, intervention agent/delivery/dosage, outcome measures, and treatment outcomes.
Data, Items and Synthesis of Results. Titles and abstracts of included studies were reviewed for eligibility by two independent reviewers. Next, the same two reviewers assessed the selected original articles at a full-text level to determine their eligibility. To ensure rating accuracy, a random selection of one hundred records were scored and discussed over two consecutive group sessions prior to rating the remaining records. Any disagreement between the first two reviewers was resolved by consulting a third reviewer. Assessment of methodology study quality followed an equivalent process. None of the reviewers had formal or informal affiliations with any of the authors of the included studies.
Extracted data were extrapolated and synthesised within the following categories to allow for comparison: participant characteristics, inclusion criteria, intervention conditions, outcome measures and intervention outcomes. Effect sizes and significance of findings were used to assess treatment outcomes.
2.4. Meta-Analysis
Using the extracted data, effect sizes were compared for the following: (1) pre-post outcome measures of OD and (2) mean difference in outcome measures from pre- to post-intervention scores between neurostimulation and comparison controls. Control groups either received no treatment, sham stimulation and/or traditional dysphagia therapy (DT; e.g., compensatory and rehabilitative strategies including diet modifications, postural adjustments, oromotor training and swallow manoeuvres). Only studies using instrumental assessment (e.g., videofluoroscopic swallow study [VFSS] or fiberoptic endoscopic evaluation of swallowing [FEES]) to confirm OD were included.
When selecting what data points to extract, data collected using outcome measures based on visuoperceptual evaluation of instrumental assessment were preferred over clinical non-instrumental assessments. Oral intake measures were only included if no other clinical data were available, whereas screening tools and patient self-report measures were excluded entirely. When selecting outcome measures for meta-analyses, reducing heterogeneity between studies was given priority. Consequently, measures other than the authors’ primary outcomes may have been preferred if these measures contributed to greater homogeneity.
Comprehensive Meta-Analysis Version 3.3.070 [22] software was used to complete the meta-analysis, allowing comparison of sample size, effect size, group means and standard deviations of pre- and post-measurements. In the case that no parametric data were available, the reported non-parametric data (i.e., medians, interquartile ranges) were converted into parametric data for meta-analysis purposes. Studies with multiple intervention groups were analysed separately for each experimental-control comparison. If studies included the same participants, only one study was included in the meta-analysis. Where reported data were insufficient, attempts were made to contact authors of individual studies and request additional data.
Using Comprehensive Meta-Analysis, a random-effects model was used to calculate effect sizes. This was due to variations in participant characteristics, sampling, interventions, and measurement, which suggested a low likelihood that studies would have similar true effects. Heterogeneity was estimated using the Q statistic to determine the spread of effect sizes about the mean and I2 was used to estimate the ratio of true variance to total variance. I2-values of less than 50%, 50% to 74%, and higher than 75% denote low, moderate, and high heterogeneity, respectively [23]. Effects sizes were generated using the Hedges’ g formula for standardised mean difference with a confidence interval of 95%. Effects sizes were interpreted using Cohen’s d convention as follows: d ≤ 0.2 as no or negligible effect; 0.2 < d ≤ 5 as small effect; 0.5 < d ≤ 0.8 as moderate effect; and d > 0.8 as large effect [24].
Forest plots of effect sizes for OD outcome scores were generated for both types of neurostimulation (i.e., rTMS and tDCS): (1) pre-post neurostimulation and (2) neurostimulation interventions versus comparison groups. Subgroup analyses were conducted to compare effect sizes as a function of different moderators and neurostimulation types including: outcome measures, total treatment duration, total neurostimulation time, and stimulation characteristics (e.g., pulse range, stimulation current, and stimulation site). To take into consideration the possibility of spontaneous recovery during the intervention period, only between-subgroup meta-analyses were conducted using post-intervention data.
Utilising Comprehensive Data Analysis software, publication bias was evaluated as per the Begg and Muzumdar’s rank correlation test and the Fail-safe N test. Begg and Muzumdar’s rank correlation test provides information on the rank correlations between standardised effect size and the ranks of their variances [25]. In addition to a tau value, a two-tailed p value is also generated. Where the analysis results in a value of zero, it can be concluded that there is unlikely to be an association between the effect size and ranks of variance. Conversely, the closer to one the tau or p values, the more likely there is to be an association between the effect size and ranks of variance. Therefore, high standard error would be connected to higher effect sizes if publication bias was the result of asymmetry. If larger effects are represented by low values, tau would be over zero; conversely tau would be negative if larger effects are represented by high values.
The Fail-safe N test is a calculation of the quantity of studies with zero effect size that could be incorporated into the meta-analysis prior to the result losing statistical significance, that is, the quantity of excluded studies that would result in the effect being nullified [26]. Results should be treated with care where the fail-safe N is relatively small, however, when it is large, conclusions can be confidently drawn that the treatment effect, while potentially raised by the removal of some studies, is not nil.
3. Results
3.1. Study Selection
A total of 8059 studies were retrieved through the subject heading and free text searches (CINAHL: n = 239, Embase: n = 4550, PsycINFO: n = 231, and PubMed: n = 3039). Following removal of duplicates at a title and abstract level (n = 1113), a total of 6946 records remained. A total of 261 original articles were assessed at a full-text level, with articles grouped according to type of intervention. At this stage, no studies were excluded based on type of intervention (e.g., behavioural intervention, neurostimulation). Of these, 58 articles on neurostimulation were identified that satisfied the inclusion criteria. Four additional studies were found through reference checking of the included articles. This process resulted in a final number of 24 included studies. Figure 1 presents the flow diagram of the overall reviewing process according to PRISMA.
3.2. Description of Studies
Table 2 and Table 3 report detailed descriptions of all included studies. Table 2 includes data on study characteristics including methodological study quality, inclusion and exclusion criteria, and details on participant groups. Information is provided for all study groups (control and intervention groups), medical diagnosis, sample size, age and gender. Table 3 reports on intervention characteristics, including goals, intervention components, outcome measures, intervention outcomes, as well as main conclusions.
Brain stimulation Interventions (Table 2). Across the 24 included studies, eleven studies reported on rTMS and nine studies reported on tDCS. Four studies used another type of neurostimulation (i.e., NMES) in addition to rTMS, either within the same group or over different treatment groups.
Participants (Table 2). The 24 studies included a total of 728 participants (mean 30.3; SD 13.4). The sample sizes ranged from the smallest sample of 14 participants [27] to the largest sample of 64 participants [28]. By intervention type, samples were characterised as follows: rTMS total 280, mean 25.5, SD 7.6, range 15–40; tDCS total 283, mean 31.4, SD 14.6, range 14–59; and combined neurostimulation total 165, mean 41.3, SD 19.3, range 18–64. The mean age of participants across all studies was 64.6 years (SD 5.8), ranging from 51.8 years [29] to 74.9 years [27]. By intervention group, the mean age of participants was: rTMS 63.6 (4.8), tDCS 66.2 (SD 6.9), and combined neurostimulation 66.5 years (SD 4.4).
Across all studies 59.6% (SD 12.7) participants were male and two studies did not report gender distribution [29,30]. Percentage of males by intervention group was rTMS 61.9% (SD 12.8), tDCS 57.5% (SD 10.9), and other/combined 65.4% (SD 12.3). Most studies included stroke patients (n = 21), with other diagnoses by intervention group reported as: presbyphagia due to central nervous system disorder (n = 1) [31] in tDCS; Parkinson’s disorder (n = 1) [30] and brain injury (n = 1) [32] in rTMS. All 24 studies used VFSS to confirm participants’ diagnosis of OD. The studies were conducted across 12 countries, with the highest number of studies conducted in Korea (n = 6), Egypt (n = 4), China (n = 3), Italy (n = 2) and Japan (n = 2).
Outcome Measures (Table 3). Outcomes measures varied greatly across all studies included in the review, covering several domains within the area of OD. The Penetration Aspiration Score (PAS) was the most reported outcome measure (8 studies), followed by the Dysphagia Outcome and Severity Scale (DOSS; 7 studies), Functional Oral Intake Scale (FOIS; 3 studies) and Degree of Dysphagia (DD; 3 studies).
rTMS Intervention (n = 11:Table 2 and Table 3). All but one of the rTMs studies [33] compared rTMS stimulation with sham rTMS. One single study compared rTMS with rTMS combined with DT, and DT only [33]. Three more studies included three arms; two studies compared rTMS using different frequencies versus sham rTMS [32,34], and one study compared bilateral and unilateral rTMS versus sham rTMS [35].
tDCS Intervention (n = 9:Table 2 and Table 3). Eight studies compared tDCS with sham tDCS [27,29,31,36,37,38,39,40,41], and one study compared tDCS with theta-burst stimulation (TBS) [31]. All but one study (31) combined both study arms with DT. In one study both groups received simultaneous catheter balloon dilatation in addition to DT [40].
Combined Neurostimulation Interventions (n = 4: seeTable 2 and Table 3). Three studies in the combined intervention group compared three different treatments. Of these, one compared rTMS, PES and paired associative stimulation (PAS) [42], a second compared DT, rTMS combined with DT, and NMES combined with DT [43], and a third compared rTMS, PES and capsaicin stimulation [44]. A fourth study combined NMES stimulation with sham rTMS or rTMS stimulating different hemispheres (ipsilesional, contralesional or bilateral) [45].
Table 2.
Study characteristics of studies on rTMS and tDCS interventions for people with oropharyngeal dysphagia.
Table 2.
Study characteristics of studies on rTMS and tDCS interventions for people with oropharyngeal dysphagia.
Study
| Inclusion/Exclusion Criteria | Sample (n)
| Group Descriptives (Mean ± SD) Age, Gender, Medical Diagnoses | Procedure, Delivery and Dosage per Intervention Group a |
|---|---|---|---|---|
| repetitive Transcranial Magnetic Stimulation (rTMS)—n = 11 | ||||
Cheng et al. (2017) [46]
|
| n = 15
| Treatment group: Age = 65.1 ± 8.3 Male = 64% Sham group: Age = 63.3 ± 7.8 Male = 100% NS difference between groups in age or post-stroke duration. | Procedure: rTMS (Magstim Rapid) daily for 10 days over 2 weeks
|
Du et al. (2016) [34]
|
| n = 40
| Treatment group 1: Age 58.2 ± 2.8 87% male Location of lesion: cortical (1), subcortical (10), massive (4) Treatment group 2: Age 57.9 ± 2.5 54% male Location of lesion: cortical (0), subcortical (9), massive (4) Sham group: Age 58.8 ± 3.4 50% male Location of lesion: cortical (2), subcortical (5), massive (5) NS differences between groups. | Procedure:
|
Khedr et al. (2009) [47]
|
| n = 26
| Treatment group: Age 58.9 ± 11.7 Sham group: Age 56.2 ± 13.4 No group specific descriptors given. Overall, 38.5% male. 14 with right-sided hemiplegia and 12 patients with left-sided hemiplegia. NS difference between groups. | Procedure:
|
Khedr and Abo-Elfetoh (2010) [48]
|
| n = 22
| Group statistics given based on infarction type divided into treatment versus sham. Lateral medullary infarction group: Treatment group (6): Age 56.7 ± 16 100% male Sham (5): Age: 58 ± 17.5 100% male Other brainstem infarction group: Treatment group (5): Age: 55.4 ± 9.7 40% male Sham (6): Age: 60.5 ± 11 50% male NS difference between groups. | Procedure:
|
Khedr et al. (2019) [30]
|
| n = 30
| Treatment group: Age 60.7 ± 8.8 duration of illness 5.7 +/− 3.9 Hoehn and Yahr 3.1 +/− 1.1 Sham group: Age 57.4 ± 10.0 duration of illness 6.5 +/− 3.7 Hoehn and Yahr 3.5 +/− 1.0 Gender distribution not given. NS difference between groups. | Procedure:
|
Kim et al. (2011) [32]
|
| n = 30
| Treatment group 1: Age: 69.8 ± 8.0 50% male Stroke (9), TBI (1) Treatment group 2: Age: 66.4 ± 12.3 66.6% maleStroke (10), TBI (0) Sham group: Age: 68.2 ± 12.6 66.6% male Stroke (9), TBI (1) NS difference between groups. | Procedure:
|
Momosaki et al. (2014) [49]
|
| n = 20
| Treatment group: Age 61 ± 22 80% male Duration post-stroke 19 +/− 8 months Lesion: cerebrum 2, cerebellum 2, brainstem 5, mixed 1 Sham group: Age 66 ± 9 60% male Duration post-stroke 21 +/− 8 months Lesion: cerebrum 1, cerebellum 3, brainstem 2, mixed 4. NS difference between groups. | Procedure:
Same parameters with the coil held on its lateral side |
Park et al. (2013) [50]
|
| n = 18
| Treatment group: Age 73.7 ± 3.8 56% male Infarct = 7, haemorrhage = 2Right lesion = 6 Sham group: Age 68.9 ± 9.354% male Infarct = 8, haemorrhage = 1Right lesion = 5 NS difference between groups. | Procedure: rTMS (Magstim Rapid2)
Same rTMS dosage, however Magstim coil positioned at 90 degree tilt (same noise, no motor cortical stimulation) |
Park et al. (2017) [35]
|
| n = 33
| Treatment group 1: Age 60.2 ± 13.8 73% male Infarct = 7, haemorrhage = 4 Treatment group 2: Age 67.5 ± 13.4 73% male Infarct = 9, haemorrhage = 2 Sham group: 69.6 ± 8.6 64% male Infarct = 7, haemorrhage = 4 NS difference between groups. | Procedure: rTMS (Magstim Rapid 2) to cortical representation of the mylohyoid muscle, identified by EMG. Applied 10 Hz and 90% of RMT for 5 s with a 55 s inter-train interval.
|
Tarameshlu et al. (2019) [33]
|
| n = 18
| Treatment group 1: Age 55.33 ± 19.55 67% male 67% cortical stroke, 33% subcortical Treatment group 2: Age 74.67 ± 5.92 17% male 83% cortical stroke, 17% subcortical Treatment group 3: Age 66 ± 5.55 67% male 67% cortical stroke, 33% subcortical NS difference between groups. | Treatment group 1: rTMS (Magstim super-rapid stimulator).
|
Ünlüer et al. (2019) [51]
|
| n = 28
| Treatment group: Age 67.80 ± 11.88 60% male 7% haemorrhage, 93% ischaemic stroke Sham group: Age 69.31 ± 12.89 46% male 8% haemorrhage, 92% ischaemic stroke NS difference between groups. | Procedure: DT for 30–45 min, 3 days/week (+2 days home exercises) for 4 weeks
|
| transcranial Direct Current Stimulation (tDCS)—n = 9 | ||||
Ahn et al. (2017) [36]
|
| n = 26
| Treatment group: Age 61.6 ± 10.3 69.2% male 38.5% infarction, 61.5% haemorrhage Sham group: Age 66.4 ± 10.7 46.2% male 84.6% infarction, 15.4% haemorrhage Statistical difference between groups = NR | Procedure:
|
Cosentino et al. (2020) [31]
|
| n = 40
Both groups crossed over to sham treatment, also. Order randomised. | Treatment group 1: Age 71.5 ± 5.2 53% male 70.5% primary presbydysphagia, 72.4% secondary presbydysphagia Treatment group 2: Age 75.2 ± 4.8 (p = 0.025) 57% male 76.4% primary presbydysphagia, 74.0% secondary presbydysphagia Statistical difference between groups = NR | Procedure:
|
Kumar et al. (2011) [27]
|
| n = 14 (pilot study)
| Treatment group: Average age 79.7 43% male Average NIHHS score 13.6Sham group: Average age 70 57% male Average NIHHS score 13.1Statistical difference between groups = NR | Procedure:
Treatment parameters not described in detail |
Pingue et al. (2018) [37]
|
| n = 40
| Treatment group: Age 63.5 (range = 54.5–75.25) 40% male Infarct = 11, haemorrhage = 11 (NB. Note numeral errors reported here, n= 20, not 22) Sham group: Age 68.5 (range = 62–73) 40% male Infarct = 4, haemorrhage = 16 NS difference between groups. | Procedure: tDCS by a battery-driven constant current stimulator (HDCkit Newronika, Italy). Stimulation targeted the pharyngeal motor cortex (site location method not described).
2 mA of anodal tDCS over the lesioned hemisphere and cathodal stimulation to the contralesional hemisphere. Sham + DT: Same protocol except current was delivered for only 30 s through 2 electrodes, producing initial tingling sensation but no cortical excitability. |
Sawan et al. (2020) [29]
|
| n = 40
| Treatment group: Age 53.3 ± 5.0 50% unilateral stroke, 50% bilateral stroke Sham group: Age 50.3 ± 5.2 50% unilateral stroke, 50% bilateral stroke NS difference between groups. | Procedure:
Group 1 (unilateral hemispheric stroke) anode placed on healthy hemisphere with reference electrode over contralateral supraorbital region.Group 2 (bilateral hemispheric stroke) stimulation first applied to the dominant hemisphere, then non-dominant hemisphere. Sham + DT: Same protocol producing tingling sensation but no cortical excitability. |
Shigematsu et al. (2013) [38]
|
| n = 20
| Treatment group: Age: 66.9 ± 6.3 70% male; Time post-stroke: 12.9 ± 7.8 Site of lesion: 20% putamen; 20% medulla oblongata; 10% corona radiata; 10% frontotemporal; 10% frontoparietal; 10% pons; 10% thalamus; 10% internal capsule Sham group: Age 64.7 ± 8.9 70% male Time post-stroke: 12.1 ± 9.0 Site of lesion: 40% pons; 20% frontoparietal; 10% putamen; 10% thalamus; 10% internal capsule; 10% caudate nucleus NS difference between groups. | Procedure: stimulation by DC stimulator (NeuroConn)
|
Suntrup-Krueger et al. (2018) [39]
|
| n = 59
| Treatment group: Age 68.9 ± 11.5 58.6 % male 72.4% supratentorial stroke 27.6% infratentorial stroke Sham group: Age 67.2 ± 14.5 56.7 % male 80.0% supratentorial stroke 20.0% infratentorial stroke NS difference between groups. | Procedure: tDCS stimulation delivered by battery-driven constant current stimulator (NeuroConn)
|
Wang et al. (2020) [40]
|
| n = 28
| Treatment group: Age 61.43 ± 11.24 79% male Time post-stroke: 66.79 ± 38.62 days Sham group: Age 62.00 ± 10.46 71% male Time post-stroke: 67.50 ± 47.62 days NS difference between groups. | Procedure: anodal tDCS + catheter balloon dilatation + standard swallow therapy (based on VFSS, details not described)
|
Yang et al. (2012) [41]
|
| n = 16
| Treatment group: Age 70.44 ± 12.59 66.7% male 44.4% right lesion, NIHSS = 9.7 ± 5.4 Sham group: Age 70.57 ± 8.46 42.9% male 57.1% right lesion, NIHSS = 13.9 ± 6.3 NS differences between groups. | Procedure: anodal tDCS (Phoresor II)
|
| Combined Neurostimulation Interventions—n = 4 | ||||
Cabib et al. (2020) [44]
|
| n = 36
| Treatment group 1: Age 70.0 ± 8.6 75% male 0% haemorrhage, 100% infarction Treatment group 2: Age 74.3 ± 7.8 58% male 8% haemorrhage, 92% infarction Treatment group 3: Age 70.0 ± 14.2 92% male 25% haemorrhage, 75% infarction NS differences between groups, except shorter time since stroke for capsaicin group. | Procedure: All patients received both treatment and sham, cross-over active/sham in visits 1 week apart (randomised). Assessment occurred immediately prior to treatment and within 2 h post-treatment.Treatment group 1: rTMS (Magstim rapid stimulator)
Treatment group 3: PES via two-ring electrode naso-pharyngeal catheter (Gaeltec Ltd.)
|
Lim et al. (2014) [43]
|
| n = 47
| Treatment group 1: Age 62.5 ± 8.2 60% male 34% haemorrhage, 66% infarction Treatment group 2: Age 59.8 ± 11.8 43% male 71% haemorrhage, 29% infarction Treatment group 3: Age 66.3 ± 15.4 67% male 66% haemorrhage, 44% infarction NS difference between groups. | Procedure:
|
Michou et al. (2014) [42]
|
| n = 18
| Treatment group: Avg age 60.3 83% male Treatment group 2: Avg age 67.3 100% male Treatment group 3: Avg age 67.8 66.7% male Overall 63 +/− 15 weeks post-stroke with 7.6 +/− 1 on NIHHS Statistical difference between groups = NR | Procedure:
|
Zhang et al. (2019) [45]
|
| n = 64
| Treatment group 1: Age 55.9 ± 8.9 43% male 61.5% subcortical, 38.5% brainstem Treatment group 2: Age 56.8 ± 9.7 54% male 30.8% subcortical, 69.2% brainstem Treatment group 3: Age 56.5 ± 10.1 50% male 58.3% subcortical, 41.7% brainstem Treatment group 4: Age 53.1 ± 10.6 31% male 61.5% subcortical, 38.5% brainstem All data given on participants that finished the trial and follow-up period (n = 52) | Procedure:
10-Hz real rTMS was delivered to the hot spot for the mylohyoid muscle at the ipsilesional hemisphere followed by 1-Hz sham rTMS over the corresponding position of the contralesional hemisphere. Treatment group 3: Contralateral rTMS + NMES 10-Hz sham rTMS was delivered to the hot spot for the mylohyoid muscle at the ipsilesional hemisphere followed by 1-Hz real rTMS over the corresponding position of the contralesional hemisphere. Treatment group 4: Bilateral rTMS + NMES 10-Hz real rTMS was delivered to the hot spot for the mylohyoid muscle at the ipsilesional hemisphere followed by 1-Hz real rTMS over the corresponding position of the contralesional hemisphere. |
a Where information was available on how stimulation site was located and mapped, and whether stimulation was applied ipsilateral or contralateral to the lesion site, it was included. Note. NMES is at motor stimulation level unless explicitly mentioned. Notes. CP—cerebral palsy; CT—computed tomography; DOSS—dysphagia outcome and severity scale; DT—dysphagia therapy; EMG—electromyography; FEES—fiberoptic endoscopic evaluation of swallowing; FOIS—functional oral intake scale; MEP—motor-evoked potentials; MMSE—Mini-Mental State Exam; MRI—magnetic resonance imaging; MS—multiple sclerosis; MT—Motor Threshold; NIHSS—National Institutes of Health Stroke Scale; NMES—neuromuscular electrical stimulation; NR—not reported; NS—not significant; OD—oropharyngeal dysphagia; OST—oral sensorimotor treatment; PAS—penetration—aspiration scale; PES—pharyngeal electrical stimulation; rTMS—repetitive transcranial magnetic stimulation; SLT—Speech and Language Therapist; TBI—traumatic brain injury; tDCS—transcranial direct current stimulation; TOR-BSST—Toronto Bedside Swallowing Screening test; VFSS—videofluoroscopic swallowing study.
Table 3.
Outcome of rTMS and tDCS for people with oropharyngeal dysphagia.
| Study | Intervention Goal | Outcome Measures | Intervention Outcomes &Conclusions |
|---|---|---|---|
| repetitive Transcranial Magnetic Stimulation (rTMS)—n = 11 | |||
| Cheng et al. (2017) [46] | To investigate the short-(2-months) and long-term (6 and 12 months) effects of 5 Hz rTMS on chronic post-stroke dysphagia | Primary outcomes: Maximum tongue strength, VFSS (oral transit time, stage transit time, pharyngeal transit time, pharyngeal constriction ratio), and SAPP [52]. Assessed: 1 week pre-, and 2, 6 and 12 months post-intervention. |
|
| Du et al. (2016) [34] | To investigate the effects of high-frequency versus low-frequency rTMS on poststroke dysphagia during early rehabilitation | Primary outcome: SSA [53]. Secondary outcomes: WST [54], DD [55], NIHSS score [56], BI [57], mRS, measures of mylohyoid MEPs evoked from both hemispheres before and after treatment. Assessed: before treatment, after 5th rTMS session, and at 1-, 2-, and 3-months post-treatment. | Primary outcomes:
|
| Khedr et al. (2009) [47] | To investigate the therapeutic effect of rTMS on post-stroke dysphagia | Primary outcome: Dysphagia rating scale [58] (swallowing questionnaire + bedside examination). Secondary outcomes: Motor power of hand grip, BI [57], measures of oesophageal MEPs from both hemispheres. Assessed: before and immediately after treatment, and at 1- and 2-months post-treatment. |
|
| Khedr and Abo-Elfetoh (2010) [48] | To assess the effect of rTMS on dysphagia in patients with acute lateral medullary or other brainstem infarction | Primary outcome: DD [55] Secondary outcomes: Hand grip strength, NIHHS [56] and BI [57]. Assessed: before treatment, after 5th rTMS session, and at 1- and 2-months post-treatment. | Results given based on infarction type divided into treatment versus sham. rTMS and lateral medullary infarction
|
| Khedr et al. (2019) [30] | To investigate the therapeutic effect of rTMS on dysphagia with Parkinson’s Disease | Primary outcomes: Hoen and Yahr staging [59], UPDRS [60] part III, IADL [61], Self-Assessment Scale [62], SDQ [63], Arabic-DHI [64]. VFSS was conducted on 9 rTMS and 6 sham group patients. Assessed: before treatment, post treatment, and at 1-, 2-, and 3-months post-treatment. |
|
| Kim et al. (2011) [32] | To investigate the effect of rTMS on dysphagia recovery in patients with brain injury | Primary outcomes: FDS [65], PAS [66] and ASHA-NOMS [67] before and after treatment Assessed: before and after treatment, times unspecified. |
|
| Momosaki et al. (2014) [49] | To assess the effectiveness of a single functional magnetic stimulation session on post-stroke dysphagia | Primary outcomes: Timed WST [54] before and after stimulation Secondary outcome: N/R |
|
| Park et al. (2013) [50] | To find the therapeutic effect of high-frequency repetitive TMS on a contra-lesional intact pharyngeal motor cortex inpost-stroke dysphagic patients | Primary outcome: VDS [68], PAS [66] (as per VFSS), pre- and post- treatment. 2 and 4 weeks from baseline. Secondary outcomes: Oral and pharyngeal components of VDS | Treatment group:
|
| Park et al. (2017) [35] | to investigate the effects of high-frequency rTMS at the bilateral motor cortices over the cortical representation of the mylohyoid muscles in the patients with post-stroke dysphagia. | Primary outcomes: Immediately post-treatment and 3 weeks post-treatment: using CDS [69], DOSS [58], PAS [66], and VDS [68]. Secondary outcome: N/R |
|
| Tarameshlu et al. (2019) [33] | To compare the effects of standard swallow therapy (DT), rTMS and a combined intervention (CI)on swallowing function in patients with poststroke dysphagia | Primary outcome: MASA [70]. Secondary outcomes: FOIS [71] assessed (a) before treatment, (b) after 5th session and after 10th, 15th and 18th session. | Primary outcome: MASA
|
| Ünlüer et al. (2019) [51] | To identify whether applying low-frequency rTMS can enhance the effect of conventional swallowing treatment and quality of life of chronic (2–6 months) stroke patients suffering from dysphagia | Primary outcome: PAS [66], pre-post treatment, 1 and 3 months post-treatment. Secondary outcomes: VFSS parameters (including oral parameters, tongue retraction, hyolaryngeal elevation, delayed swallow reflex, residue, nutritional status, SWAL-QOL). |
|
| transcranial Direct Current Stimulation (tDCS)—n = 9 | |||
| Ahn et al. (2017) [36] | To investigate the effect of bihemispheric anodal tDCS with conventional dysphagia therapy on chronic post-stroke dysphagia | Primary outcome: DOSS [58] score based on VFSS pre- and post-treatment Secondary outcome: N/R |
|
| Cosentino et al. (2020) [31] | To investigate the therapeutic potential of tDCS and theta-burst stimulation on primary or secondary presbydysphagia | Primary outcomes: DOSS [58] based on bedside assessment and FEES. Similarity Index based on Electrokinesiographic/electromyographic Study (EES) for Laryngeal-pharyngeal Mechanogram (LPM) and electromyographic activity of the submental/suprahyoid muscles complex (SHEMG). Secondary outcome: N/R Outcomes assessed at baseline, 1 month and 3 months post-treatment |
|
| Kumar et al. (2011) [27] | To investigate whether anodal tDCS in combination with swallowing manoeuvres facilitates dysphagia recovery in stroke patients during early stroke convalescence | Primary outcome: DOSS [58]. Secondary outcome: N/R | Treatment group had significantly improved DOSS scores compared to sham group (p = 0.019). |
| Pingue et al. (2018) [37] | To evaluate whether anodal tDCS over the lesioned hemisphere and cathodal tDCS to the contralateral one during the early stage of rehabilitation can improve poststroke dysphagia | Primary outcome: DOSS [58], PAS [66] post-treatment. Secondary outcome: N/R |
|
| Sawan et al. (2020) [29] | To assess the effect of tDCS on improving dysphagia in stroke patients | Primary outcomes: DOSS [58]; Oral Transit Time; laryngeal and hyoid elevation; oesophageal sphincter spasm; aspiration Secondary outcome: N/R |
|
| Shigematsu et al. (2013) [38] | To investigate if the application of tDCS to the ipsilateral cortical motor and sensory pharyngeal areas can improve swallowing function in poststroke patients | Primary outcome: DOSS [58] immediately post-treatment and 1 month post-treatment Secondary outcomes: PAS [66], oral intake status. |
|
| Suntrup-Krueger et al. (2013) [39] | To evaluate the efficacy of a pathophysiologically reasonable tDCS protocol to improve stroke-related OD, via a randomized controlled trial (RCT) in a sufficiently large patient sample with objective clinical outcome measures alongside functional neuroimaging | Primary outcome: Improved FEDSS 4 days post-treatment Secondary outcomes: DSRS [72]; final FEDSS, and FOIS [71] scores prior to discharge; pneumonia rate until discharge; length of stay (in hospital). Activation changes in the swallowing network as measured with MEG. | Primary outcome:
|
| Wang et al. (2020) [40] | To investigate the effects of tDCS combined with conventional swallowing training on the swallowing function in brainstem stroke patients with cricopharyngeal muscle dysfunction. | Primary outcome: FDS [65] (before and immediately after intervention). Secondary outcomes: FOIS [71], MBSImp [73], PESO measurement [74]. | Primary outcomes: Statistical difference between the groups at endpoint not reported.
|
| Yang et al. (2012) [41] | To investigate the effects of anodal tDCS combined with swallowing training for post-stroke dysphagia. | Primary outcome: FDS [65] immediately post-treatment and at 3 months Secondary outcomes: Oral Transit Time, Pharyngeal Transit Time and total transit time. |
|
| Combined Neurostimulation Interventions—n = 4 | |||
| Cabib et al. (2020) [44] | To investigate the effect of rTMS of the primary sensory cortex (A), oral capsaicin (B) and intra-pharyngeal electrical stimulation (IPES; C) on post-stroke dysphagia | Primary outcomes: Effect size pre-post treatment for neurophysiological variables (pharyngeal and thenar RMT and MEP). Secondary outcomes: Effects on the biomechanics of swallow (PAS [66], impaired efficiency + more) VFSS before and after treatment |
|
| Lim et al. (2014) [43] | To investigate the effect of low-frequency rTMS and NMES on post-stroke dysphagia. | Primary outcomes: VFSS baseline, 2- + 4-weeks post-treatment (for semi-solids and liquids): FDS [65], PAS [66], Pharyngeal Transit Time. Secondary outcome: N/R |
|
| Michou et al. (2014) [42] | To compare the effects of a single application of one of three neurostimulation techniques (PES, paired stimulation, rTMS) on swallow safety and neurophysiological mechanisms in chronic post-stroke dysphagia. | Primary Outcome: VFSS before and after treatment Secondary outcomes: Percentage change in cortical excitability; Oral Transit Time, pharyngeal response time, Pharyngeal Transit Time, airway closure time and upper oesophageal opening time as per VFSS | Treatment group 1 (PES): significant excitability increase immediately post-Tx in the unaffected hemisphere (real vs. sham p = 0.043) and in the affected hemisphere 30 min post-Tx (real vs. sham p = 0.04).
Corticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, Paired Stimulation and to a lesser extent by rTMS. |
| Zhang et al. (2019) [45] | To determine whether rTMS NMES effectively ameliorates dysphagia and how rTMS protocols (bilateral vs. unilateral) combined with NMES can be optimized. | Primary outcome: Cortical excitability(amplitude of the motor evoked potential) Secondary outcomes: SSA [53] and DD [55]. | Compared with group 2 or 3 in the affected hemisphere, group 4 displayed a significantly greater percentage change (p.0.017 and p.0.024, respectively). All groups displayed significant improvements in SSA and DD scores after treatment and at 1-month follow-up. The percentage change in cortical excitability increased over time in either the affected or unaffected hemisphere in treatment groups 1, 2 and 4 (p < 0.05). In Group 3, the percentage change in cortical excitability in the unaffected hemisphere significantly decreased after the stimulation course (p < 0.05). Change in SSA and DD scores in group 4 was markedly higher than that in the other three groups at the end of stimulation (p.0.02, p.0.03, and p.0.005) and still higher than that in group 1 at the 1-month follow-up (p.0.01). |
Note. NMES is at motor stimulation level unless explicitly mentioned. Notes. ASHA-NOMS—American speech-language-hearing association national outcome measurement system; BI—Barthel index; CDS—clinical dysphagia scale; CT—computed tomography; DD—degree of dysphagia; DOSS—dysphagia outcome and severity scale; DSRS—dysphagia severity rating scale; DT—dysphagia therapy; EES— electrokinesiographic/electromyographic study of swallowing; EQ-5D—European Quality of Life Five Dimension; FDS—functional dysphagia scale; FEDSS—fiberoptic endoscopic dysphagia severity scale; FEES—fiberoptic endoscopic evaluation of swallowing; FOIS—functional oral intake scale; HNCI—head neck cancer inventory; IADL—instrumental activities of daily living; ICU—intensive care unit; LCD—laryngeal closure duration; LPM—laryngeal-pharyngeal mechanogram; MASA—Mann assessment of swallowing ability; MBS—modified barium swallow; MBSImp—modified barium swallow impairment profile; MDADI—M.D. Anderson dysphagia inventory; MEG—magnetoencephalography; MEP—motor evoked potentials; MMSE—mini-mental state exam; MRI—magnetic resonance imaging; mRS—modified rankin scale; MS—multiple sclerosis; NEDS—neurological examination dysphagia score; NIHSS—National Institutes of Health Stroke Scale; NMES—neuromuscular electrical stimulation; NS—not significant; OD—oropharyngeal dysphagia; OPSE—oropharyngeal swallow efficiency; OST—oral sensorimotor treatment; PAS—penetration—aspiration scale; PES—pharyngeal electrical stimulation; PESO— pharyngoesophageal segment opening; RMT— resting motor thresholdS; rTMS—repetitive transcranial magnetic stimulation; SAPP—swallowing activity and participation profile; SDQ—swallowing disturbance questionnaire; SFS—swallow function score; SHEMG— electromyographic activity of the submental/suprahyoid muscles complex; SLT—speech and language therapist; SSA—standardised swallowing assessment; SWAL-QOL—swallowing quality of life; TBI—traumatic brain injury; tDCS—transcranial direct current stimulation UPDRS—unified Parkinson’s disease rating scale; VFSS—videofluoroscopic swallowing study; WST—water swallow test.
3.3. Risk of Bias Assessment and Methodological Quality
The Begg and Mazumdar rank correlation procedure produced a tau of −0.036 (two-tailed p = 0.902) and 0.178 (two-tailed p = 0.536) for rTMS and tDCS, respectively. The rTMS meta-analysis incorporates data from 8 studies, which yield a z-value of 2.348 (two-tailed p-value = 0.019). The fail-safe N is 4. This means that 4 ‘null’ studies need to be located and included for the combined two-tailed p-value to exceed 0.050. That means there would be need to be 0.5 missing studies for every observed study for the effect to be nullified. The tDCS meta-analysis incorporates data from 8 studies yielding a z-value of 4.857 (two-tailed p-value < 0.001). The fail-safe N is 42 indicating 42 ‘null’ studies need to be located and included for the combined two-tailed p-value to exceed 0.050; there would be need to be 5.3 missing studies for every observed study for the effect to be nullified. Both of these procedures (i.e., Begg and Mazumdar rank correlation and fail-safe N test) indicate the absence of publication bias.
Figure 2 and Figure 3 present, respectively, the risk of bias summary per domain for all included studies combined and for individual studies, assessed using the Revised Cochrane Collaboration tool for assessing risk of bias (RoB 2) [21]. The majority of studies had low risk of bias with very few exceptions.
3.4. Meta-Analysis: Effects of interventions
3.4.1. rTMS Meta-Analysis
Eight studies using rTMS [32,33,35,42,43,44,50,51] were included in the meta-analysis. Of these, three studies provided data for two different interventions groups [32,35,36]. Six studies were excluded as OD was not confirmed by instrumental assessment and one study was excluded as rTMS was combined with NMES.
Overall within-group analysis. Pre-post intervention effect sizes ranged from 0.085 to 2.068 (Figure 4) with seven studies showing large effect sizes (Hedges’ g > 0.8). Pre-post interventions produced a significant, large effect size (Hedges’ g = 1.038).
Overall between-group analysis. A significant, small post-intervention between-group total effect size was calculated in favour of rTMS (random-effects model: z(7) = 2.338, p = 0.019, Hedges’ g = 0.355, and 95% CI = 0.057–0.652; Figure 5). Between-study heterogeneity was non-significant (Q(7) = 6.763, p = 0.454).
Between-subgroup analyses. Subgroup analyses were conducted to compare time between pre- and post-intervention measurement, stimulation sites (bilateral, contra-lesional and ipsi-lesional sites), pulse ranges (low: ≤600; medium; >600 and <10,000; high: ≥10,000 pulses), stimulation frequencies (1, 5 and 10 Hz), and optional behavioural training (rTMS versus rTMS + DT; Table 4). No subgroup comparisons for outcome measures were conducted as all but one study used PAS. Studies including a longer time span between pre- and post-interventions (indicating longer stimulation times) showed increased positive effect sizes compared to one-day interventions, which showed negligible effect sizes. When comparing stimulation sites, non-significant, positive effect sizes were obtained for all three stimulation groups with large ranges in effect sizes within groups. Pulse range comparisons indicated an increased significant, positive effect for higher pulse ranges. Effect sizes were only significant for large numbers of pulses delivered. Sub-analyses comparing stimulation frequencies did not indicate obvious tendencies between groups. rTMS in combination with DT showed non-significant, small positive effect sizes in one study, whereas DT alone showed similar significant, small effects sizes.
3.4.2. tDCS Meta-Analysis
A total of eight studies using tDCS in stroke patients were included in the meta-analysis [27,29,36,37,38,39,40,41]. One study was excluded as having too few data for meta-analysis [31].
Overall within-group analysis. The overall pre-post intervention effect size was 1.385, with effect sizes ranging from 0.432 (small effect) to 3.365 (high effect; Figure 6). Studies showed small (n = 2), moderate (n = 1), and high effect sizes (n = 5).
Overall between-group analysis. A moderate but significant post-intervention between-group total effect size in favour of tDCS was found using a random-effects model (z(7) = 3.332, p = 0.001, Hedges’ g = 0.655, and 95% CI = 0.270–1.040; Figure 7). Between-study heterogeneity was significant (Q(7) = 15.034, and p = 0.036), with I2 showing that heterogeneity accounted for 53.4% of variation in effect sizes across studies.
Between subgroup analyses. Subgroup analyses were conducted comparing time between pre- and post-intervention measurements, outcome measures, total stimulation times and stimulation current (Table 4). Increasing the number of days between pre- and post-intervention showed a strong tendency towards increased positive effect sizes, with significant effect sizes for two and four-week periods. Comparisons between measures resulted in significant, large positive effect sizes for visuoperceptual evaluation of instrumental assessment, but negligible effects when using an oral intake measure. Effect sizes for comparisons between total stimulation times indicated increased effects when using longer stimulation times. Significant, large effects were demonstrated for stimulation times of 300 min and longer. Additionally, higher stimulation currents resulted in increased significant, large positive effect sizes.
4. Discussion
This systematic review (Part II) aimed to determine the effects of rTMS and tDCS in people with OD. This systematic review and meta-analysis of RCT studies were completed in accordance with PRISMA procedures [19,20]. No populations were excluded based on medical diagnoses.
4.1. Systematic Review Findings
Like the systematic review on effects of NMES and PES in people with OD (Part I) [75], methodological problems were identified relating to unclear definitions of OD and differences in methods of confirming the presence of OD (i.e., using instrumental assessment, patient self-report or clinical assessment). Consequently, to reduce heterogeneity in participant characteristics between RCTs, only studies using instrumental assessment to confirm diagnosis of OD were included in meta-analyses. As most studies included stroke patients only, no meta-analysis could be performed to determine effects per medical diagnosis.
With the exception of one study [33], all rTMS studies included in the meta-analysis used the PAS to evaluate intervention effects. For the tDCS studies, as heterogeneity in outcome measures was larger, data on three different clinical outcome measures were used when conducting the meta-analysis. All rTMS studies used sham stimulation as a comparison group with the exception of one study which included a rTMS plus DT group [33]. For the tDCS studies, all but one study [31] combined neurostimulation with simultaneous DT. When comparing the degree of heterogeneity in study designs between brain neurostimulation (i.e., rTMS and tDCS) and peripheral neurostimulation (i.e., NMES and PES), those in the peripheral neurostimulation group were more diverse, creating greater challenges for conducting meta-analyses. Non-invasive brain stimulation studies tended to recruit smaller sample populations compared to peripheral studies [75].
4.1.1. rTMS
This review prioritised reducing heterogeneity for purposes of meta-analysis. In contrast to previously published reviews that did not confirm OD by instrumental assessment, those studies were excluded from this meta-analysis. With the exception of Bath, Lee [13], earlier reviews identified significant beneficial effects of rTMS. Therefore, even though comparing the current meta-analysis with analyses from previous reviews may be challenging due to the inclusion of different outcome data, the findings from these studies seem in line with each other and this review.
4.1.2. tDCS
Fewer RCTs were identified for tDCS compared with rTMS. Eight out of nine studies were eligible for meta-analysis, with one study excluded due to insufficient data; this was the only study to include non-stroke patients (presbydysphagia) [31]. Again, as previous reviews on tDCS [10,12,13,16,17,18] applied different criteria for inclusion and study methodology (e.g., differences in selection of electronic databases and publication years), final numbers of studies used for these meta-analyses ranged between two and seven publications, with reviews published before 2020 including four or fewer studies. When comparing the present results with the two most recent reviews [10,18] (both including seven studies), the beneficial effects of tDCS identified by this review were confirmed by significant, small-to-moderate effects in favour of tDCS.
4.1.3. Moderators
Several factors may have had an impact on conducting meta-analyses and results. Comparing previous reviews, different decisions were made concerning criteria for meta-analyses. For example, Bath, Lee [13] excluded comparison groups with active treatment components and Chiang, Lin [12] excluded chronic stroke patients. Chronicity of stroke has shown to influence effect sizes [10,18], but selecting different primary outcomes may also result in deviating findings. For instance, Bath, Lee [13] did not find any positive effects for either rTMS or tDCS on primary outcome measures defined as death or dependency at the end of trials. Additionally, underlying medical diagnoses of OD are expected to affect meta-analyses. However, no conclusions could be drawn as very few studies of non-stroke patients were included in this review, thus no meta-analysis differentiating between diagnoses was conducted.
Similar reasons for hindering comparisons between RCTs are present in the current review, for example, spontaneous recovery and stroke severity, as were identified in the systematic review on effects of NMES and PES in people with OD (Part I) [75]. To account for the possibility of spontaneous recovery in participants, only between-subgroup meta-analyses were conducted using post-intervention data. However, the effects of stroke severity linked to OD severity remains unclear as RCTs usually did not report on the severity of stroke in sufficient detail.
Lastly, brain neurostimulation between RCTs may differ with respect to stimulation protocols (e.g., stimulation site, number and duration of treatment sessions and period) and technical parameters (e.g., frequency or number of pulses). The relatively low numbers of RCTs included in this review meant that meta-analysis could not incorporate all potential moderators. However, many of the included studies lacked sufficient details on technical parameters to allow further comparisons.
4.2. Limitations
Although this review followed PRISMA guidelines and aimed at reducing bias, some limitations may have had an impact on the results as presented. Only RCTs published in English were eligible in this review. Thus, some RCTs may have been excluded based on language criteria when their findings could have contributed to the current meta-analysis. Moreover, the high degree of heterogeneity between included studies hampered meta-analyses. Therefore, the results of meta-analyses and generalisations made should be interpreted with care.
5. Conclusions
The results of this systematic review suggest that both rTMS and tDCS show promising effects in people with OD. Meta-analysis for RCTs identified large pre-post intervention effect sizes for both types of brain neurostimulation. In addition, this analysis found significant, small and moderate post-intervention between-group effects in favour of rTMS and tCDS, respectively. However, comparisons between studies remain uncertain and challenging due to high heterogeneity in stimulation protocols and experimental parameters, potential moderators of stimulation effects, small samples sizes, and inconsistent methodological reporting.
These findings suggest that there is a need for RCTs including larger sample sizes to support future meta-analyses that will be able to adequately account for the presence of moderators. In addition, international consensus on standardised study protocols and reporting guidelines is required to support comparisons between studies.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm11040993/s1, Table S1: PRISMA 2020 for Abstracts Checklist, Table S2: PRISMA 2020 Checklist.
Author Contributions
Conceptualization: R.S., R.C., A.-L.S., L.B. and S.H., Formal analysis: R.S., R.C., Methodology: R.S. and R.C., Project administration: R.S. and R.C.; Validation: R.S. and R.C.; Writing—review & editing: R.S., R.C., A.-L.S., L.B., S.H., T.P., M.B. and A.K. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1.
Flow diagram of the reviewing process according to PRISMA.
Figure 2.
Risk of bias summary for all included studies (n = 24) in accordance with RoB 2 [21].
Figure 2.
Risk of bias summary for all included studies (n = 24) in accordance with RoB 2 [21].
Figure 3.
Risk of bias summary for individual studies (n = 24) in accordance with RoB 2 [21,27,28,29,30,31,32,33,34,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]. Note. If one or more yellow circles (domains) have been identified for a particular study, the Overall score (last column) shows an exclamation mark, indicating that the study shows some concerns (yellow circle with exclamation mark).
Figure 3.
Risk of bias summary for individual studies (n = 24) in accordance with RoB 2 [21,27,28,29,30,31,32,33,34,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]. Note. If one or more yellow circles (domains) have been identified for a particular study, the Overall score (last column) shows an exclamation mark, indicating that the study shows some concerns (yellow circle with exclamation mark).
Figure 4.
rTMS within intervention group pre-post meta-analysis [32,33,35,42,43,44,50,51]. Notes. Kim et al. (2011a): high frequency, Kim et al. (2011b): low frequency; Park et al. (2017a): unilateral stimulation, Park et al. (2017b): bilateral stimulation; Tarameshu et al. (2019a): rTMS, Tarameshu et al. (2019b): rTMS plus DT.
Figure 4.
rTMS within intervention group pre-post meta-analysis [32,33,35,42,43,44,50,51]. Notes. Kim et al. (2011a): high frequency, Kim et al. (2011b): low frequency; Park et al. (2017a): unilateral stimulation, Park et al. (2017b): bilateral stimulation; Tarameshu et al. (2019a): rTMS, Tarameshu et al. (2019b): rTMS plus DT.
Figure 5.
rTMS between group post meta-analysis [32,34,35,37,47,49]. Notes. Kim et al. (2011a): high frequency versus sham, Kim et al. (2011b): low frequency versus sham; Park et al. (2017a): unilateral stimulation versus sham, Park et al. (2017b): bilateral stimulation versus sham.
Table 1.
Search strategies.
| Database and Search Terms | Number of Records |
|---|---|
| Cinahl: ((MH “Deglutition”) OR (MH “Deglutition Disorders”)) AND (MH “Randomized Controlled Trials”) | 239 |
| Embase: (swallowing/OR dysphagia/) AND (randomization/or randomized controlled trial/OR “randomized controlled trial (topic)”/OR controlled clinical trial/) | 4550 |
| PsycINFO: (swallowing/OR dysphagia/) AND (RCT OR (Randomised AND Controlled AND Trial) OR (Randomized AND Clinical AND Trial) OR (Randomised AND Clinical AND Trial) OR (Controlled AND Clinical AND Trial)).af. | 231 |
| PubMed: (“Deglutition” [Mesh] OR “Deglutition Disorders” [Mesh]) AND (“Randomized Controlled Trial” [Publication Type] OR “Randomized Controlled Trials as Topic” [Mesh] OR “Controlled Clinical Trial” [Publication Type] OR “Pragmatic Clinical Trials as Topic” [Mesh]) | 3039 |
Table 4.
Between subgroup meta-analyses per type of neurostimulation comparing intervention groups of included studies.
Table 4.
Between subgroup meta-analyses per type of neurostimulation comparing intervention groups of included studies.
| Neurostimulation | Subgroup | Hedges’ g | Lower Limit CI | Upper Limit CI | Z-Value | p-Value |
|---|---|---|---|---|---|---|
| rTMS | Time between pre-post (days) | |||||
| 1 (n = 2) | 0.082 | −0.541 | 0.704 | 0.257 | 0.797 | |
| 5 (n = 1) | 0.257 | −0.467 | −0.981 | 0.696 | 0.486 | |
| 14 (n = 5) | 0.491 | 0.054 | 0.929 | 2.202 | 0.028 * | |
| Stimulation site | ||||||
| Bilateral (n = 2) | 0.523 | −0.730 | 1.776 | 0.818 | 0.413 | |
| Contra-lesional (n = 3) | 0.315 | −0.141 | 0.771 | 1.353 | 0.176 | |
| Ipsi-lesional (n = 3) | 0.272 | −0.251 | 0.795 | 1.020 | 0.308 | |
| Pulse range | ||||||
| Low [≤ 600] (n = 2) | 0.082 | −0.541 | 0.704 | 0.257 | 0.797 | |
| Medium [> 600 and < 10000] (n = 3) | 0.248 | −0.213 | 0.710 | 1.054 | 0.292 | |
| High [≥ 10000] (n = 3) | 0.660 | 0.014 | 1.306 | 2.004 | 0.045 * | |
| Stimulation frequency (Hz) | ||||||
| 1 (n = 2) | 0.492 | −0.067 | 1.052 | 1.726 | 0.084 | |
| 5 (n = 4) | 0.180 | −0.257 | 0.617 | 0.809 | 0.419 | |
| 10 (n = 2) | 0.552 | −0.555 | 1.658 | 0.978 | 0.328 | |
| Behavioural training | ||||||
| rTMS + DT (n = 1) | 0.257 | −0.467 | 0.981 | 0.696 | 0.486 | |
| rTMS (n = 7) | 0.375 | 0.031 | 0.720 | 2.135 | 0.033 * | |
| tDCS | Time between pre-post (days) | |||||
| 4 (n = 1) | 0.193 | −0.312 | 0.697 | 0.747 | 0.455 | |
| 5 (n = 1) | 0.654 | −0.356 | 1.664 | 1.269 | 0.205 | |
| 10 (n = 1) | 0.432 | −0.192 | 1.037 | 1.348 | 0.178 | |
| 14 (n = 4) | 0.784 | 0.056 | 1.512 | 2.112 | 0.035 * | |
| 28 (n = 1) | 1.024 | 0.256 | 1.791 | 2.614 | 0.009 * | |
| Outcome measures | ||||||
| DOSS (n = 5) | 0.753 | 0.195 | 1.311 | 2.644 | 0.008 * | |
| DSRS (n = 1) | 0.193 | −0.312 | 0.697 | 0.747 | 0.455 | |
| FDS (n = 2) | 0.764 | 0.147 | 1.381 | 2.428 | 0.015 * | |
| Total stimulation time (min) | ||||||
| 80 (n = 1) | 0.193 | −0.312 | 0.697 | 0.747 | 0.455 | |
| 150 (n = 1) | 0.654 | −0.356 | 1.664 | 1.269 | 0.205 | |
| 200 (n = 4) | 0.419 | 0.039 | 0.799 | 2.161 | 0.031 * | |
| 300 (n = 1) | 1.796 | 1.072 | 2.519 | 4.862 | <0.001 * | |
| 400 (n = 1) | 1.024 | 0.256 | 1.791 | 2.614 | 0.009 * | |
| Stimulation current (mA) | ||||||
| 1 (n = 6) | 0.430 | 0.148 | 0.712 | 2.985 | 0.003 * | |
| 2 (n = 2) | 1.281 | 0.168 | 2.395 | 2.256 | 0.024 * |
Note. * Significant. Notes. CI—confidence interval; DOSS—dysphagia outcome and severity scale; DSRS—dysphagia severity rating scale; DT—dysphagia therapy; FDS—functional dysphagia scale; rTMS—repetitive transcranial magnetic stimulation.
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Speyer, R.; Sutt, A.-L.; Bergström, L.; Hamdy, S.; Pommée, T.; Balaguer, M.; Kaale, A.; Cordier, R. Neurostimulation in People with Oropharyngeal Dysphagia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials—Part II: Brain Neurostimulation. J. Clin. Med. 2022, 11, 993. https://doi.org/10.3390/jcm11040993
AMA Style
Speyer R, Sutt A-L, Bergström L, Hamdy S, Pommée T, Balaguer M, Kaale A, Cordier R. Neurostimulation in People with Oropharyngeal Dysphagia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials—Part II: Brain Neurostimulation. Journal of Clinical Medicine. 2022; 11(4):993. https://doi.org/10.3390/jcm11040993
Chicago/Turabian StyleSpeyer, Renée, Anna-Liisa Sutt, Liza Bergström, Shaheen Hamdy, Timothy Pommée, Mathieu Balaguer, Anett Kaale, and Reinie Cordier. 2022. "Neurostimulation in People with Oropharyngeal Dysphagia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials—Part II: Brain Neurostimulation" Journal of Clinical Medicine 11, no. 4: 993. https://doi.org/10.3390/jcm11040993
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