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. 2025 Jul 17;18(2):e5. doi: 10.12786/bn.2025.18.e5

Effects of Repetitive Transcranial Magnetic Stimulation on Upper and Lower Limb Motor Function and Spasticity After Stroke: A Meta-Analysis

Hoo Young Lee 1, Byungju Ryu 2,✉
PMCID: PMC12438566  PMID: 40963946

Abstract

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has emerged as a potential adjunct to conventional rehabilitation though findings remain inconsistent. This study investigated the efficacy of rTMS combined with conventional rehabilitation in improving motor function and spasticity after stroke through a systematic review and meta-analysis. MEDLINE, Embase, and the Cochrane Library were comprehensively searched through February 2022. Sixty-eight randomized controlled trials were included based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias and certainty of evidence were assessed using the Cochrane tool and Grading of Recommendations Assessment, Development and Evaluation methodology. rTMS significantly improved upper limb motor outcomes including Fugl-Meyer assessment scores (mean difference [MD], 3.04; 95% confidence interval [CI], 1.16 to 4.92; p = 0.002), hand function (standardized MD, 0.28; 95% CI, 0.04 to 0.52; p = 0.02), and grip strength (MD, 3.61; 95% CI, 1.20 to 6.03; p = 0.003), with low-certainty evidence. It also significantly reduced upper limb spasticity (MD, −0.48; 95% CI, −0.64 to −0.33; p < 0.00001), with low-certainty evidence. No significant effects were observed for lower limb motor outcomes, and evidence for lower limb spasticity was insufficient. These findings suggest that rTMS may be considered as an adjunct to to enhance upper limb motor function and reduce spasticity in stroke rehabilitation. However, its use for lower limb recovery should be individualized based on neurological status. Further studies are needed to establish optimal protocols and long-term effects.

Keywords: Stroke, Transcranial Magnetic Stimulation, Motor Activity, Muscle Spasticity, Randomized Controlled Trials as Topic

Graphical Abstract

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Highlights

  • • Repetitive transcranial magnetic stimulation (rTMS) improves upper limb function.

  • • rTMS alleviates upper limb spasticity after stroke.

  • • rTMS showed no clear benefit for lower limb function or spasticity after stroke.

INTRODUCTION

Stroke remains one of the leading causes of death and disability worldwide, with approximately 80% of patients experiencing motor impairments in the upper or lower limbs [1]. These impairments significantly hinder daily functioning and social participation [2]. While 80% of patients with mild paresis recover functional ability, only around 20% of those with severe paresis achieve similar outcomes [1]. Among those with initial upper limb paralysis, only half show partial recovery within 6 months, and 70% of patients with lower limb involvement cannot walk independently; even with rehabilitation, only half regain walking ability [3].

Motor deficits and spasticity are major predictors of long-term recovery after stroke. Post stroke spasticity typically develops within 1 to 6 weeks and peaks between 1 to 3 months, affecting 17%–40% of patients within the first year [4,5]. Spasticity may further impair motor function, cause pain, and lead to secondary complications.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that delivers magnetic pulses to the cerebral cortex to induce neuronal depolarization [6,7]. By modulating cortical excitability and promoting neuroplasticity, rTMS has been investigated as an adjunct to conventional rehabilitation therapy.

Initial Cochrane reviews concluded that evidence supporting rTMS in stroke rehabilitation was insufficient [8]. Although later reviews reported potential benefits for upper limb function and activities of daily living (ADL), evidence quality was generally low [9]. Guidelines remain cautious: the 2016 Korean Clinical Practice Guideline conditionally recommends rTMS for selected patients with upper limb dysfunction, gait disturbances, or spasticity [10]. Subsequent studies and reviews, including those by Xie et al. [11], provided moderate-quality evidence supporting low-frequency rTMS (LF-rTMS) for upper limb recovery in the subacute phase. However, evidence for high-frequency rTMS (HF-rTMS) and for chronic stroke patients remains inconsistent, often limited by small sample sizes and heterogeneity in protocols [11,12,13,14,15,16,17,18,19].

Findings on lower limb recovery are also mixed. Some systematic reviews suggest improvements in mobility and balance with rTMS, but the overall quality of evidence is low [14,20]. Similarly, while several studies report reduced upper and lower limb spasticity with rTMS, robust evidence from high-quality randomized controlled trials (RCTs) is still lacking [21,22]. rehabilitation strategies.

Given the variability in results, rapid accumulation of new studies, and evolving clinical guidelines, an updated synthesis is essential. This systematic review and meta-analysis aims to evaluate the effects of rTMS combined with conventional rehabilitation on motor recovery and spasticity after stroke, providing evidence to inform clinical decision-making and personalized rehabilitation strategies.

MATERIALS AND METHODS

Study protocol and eligibility criteria

This study followed the research protocol established during the development of the Clinical Practice Guideline for Stroke Rehabilitation (2022) – Part 1: Rehabilitation for Motor Function [23]. The review was conducted using the Population, Intervention, Comparator and Outcomes (PICO) framework. The key question was: In stroke patients aged ≥ 18 years (P), does rTMS combined with conventional rehabilitation (I), compared to conventional rehabilitation alone (C), improve (1) upper limb motor function, (2) lower limb motor function, (3) upper limb spasticity, and (4) lower limb spasticity (O), without restrictions on measurement tools (e.g., Fugl-Meyer assessment for upper limb (FMA-UL), grip strength, hand function, ADL, Fugl-Meyer assessment for lower limb (FMA-LL), walking speed, Modified Ashworth Scale [MAS])?

Search strategy

A comprehensive literature search was conducted in MEDLINE, Embase, and the Cochrane Library for studies published up to February 28, 2022, following Cochrane Collaboration guidelines [24]. A manual search of reference lists was also performed. The detailed search strategy is provided in Supplementary Table 1. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the study selection process is outlined in Fig. 1.

Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. Among the 68 randomized controlled trials included in the quantitative synthesis, 2 studies on lower limb motor function overlapped with those on upper limb motor function. In addition, 3 studies on upper limb spasticity overlapped with upper limb motor function studies, and 2 overlapped with those on lower limb motor function.

Fig. 1

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Study selection and risk of bias assessment

Only RCTs comparing rTMS plus conventional rehabilitation with conventional rehabilitation alone were included, provided both groups received equivalent intensity and frequency of rehabilitation, with ≥5 participants per group. Two reviewers (HYL and BJR) independently screened titles/abstracts and reviewed full texts. Outcomes extracted included: (1) upper limb motor function (e.g., FMA-UL, hand function tests including Jebsen-Taylor Hand Function Test, Action Research Arm Test, and Wolf Motor Function Test, ADL scales including Barthel Index, Modified Barthel Index (MBI), Korean version of MBI, and Functional Independence Measure); (2) lower limb motor function (e.g., FMA-LL, walking speed); and (3) upper/lower limb spasticity (MAS). The primary outcomes for upper and lower limb motor function were defined as the FMA-UL and FMA-LL, respectively. The FMA, based on Brunnstrom’s stages of motor recovery, is designed to evaluate motor and sensory function in stroke patients and remains the most widely used quantitative measure of post-stroke motor impairment.

Studies were excluded if data were not extractable or if published only as abstracts, reviews, editorials, or conference proceedings. Risk of bias was independently assessed using the Cochrane Risk of Bias 1.0 tool, covering sequence generation, allocation concealment, blinding, incomplete data, selective reporting, and other biases. Discrepancies were resolved through discussion.

Data extraction

Two reviewers independently extracted study characteristics: design, sample size, intervention parameters, follow-up duration, and outcome measures. Analyses were based on data collected immediately after the final rTMS session. Subgroup analyses were conducted based on stroke duration (≤ 6 months vs. > 6 months).

Statistical analysis

Meta-analyses were conducted using RevMan 5.2 (Nordic Cochrane Center, Copenhagen, Denmark) with random-effects models and inverse variance estimation. Mean differences (MDs) were used for continuous outcomes (e.g., grip strength, walking speed, spasticity), and standardized mean differences (SMDs) for hand function and ADL, all with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic, with values > 50% indicating substantial heterogeneity. For upper and lower limb motor function, subgroup analysis was stratified by stroke phase: recovery (< 6 months) and chronic (≥ 6 months). A p value < 0.05 was considered statistically significant.

Certainty of evidence

The certainty of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, considering risk of bias, inconsistency, indirectness, imprecision, and publication bias [25]. Two authors (HYL and BJR) independently rated the certainty, resolving any disagreements through discussion.

RESULTS

Study selection and characteristics

From 7,317 screened studies, 68 RCTs were included in the systematic review, of which 32 were eligible for meta-analysis. For upper limb motor function, 45 RCTs were initially identified. However, 21 studies were excluded for the following reasons: absence of post-intervention values (n = 5), lack of both pre- and post-intervention data (n = 4), insufficient data for calculating means (e.g., only median without range; n = 4), use of outcome measures not included in this review (n = 7), and substantial baseline differences between groups that could introduce bias (n = 1). The remaining 24 studies were included in the meta-analysis for upper limb outcomes. Interventions varied across studies and included LF-rTMS [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43], HF-rTMS [29,34,37,39,44,45,46], intermittent theta burst stimulation (iTBS) [47], continuous theta burst stimulation (cTBS) [33], or combined stimulation protocols [48,49]. Eight RCTs investigated lower limb motor function; 2 overlapped with upper limb studies. The interventions included LF-rTMS [37,50,51,52], HF-rTMS [45,53], and iTBS [54,55]. Five RCTs focused on spasticity, 3 of which also evaluated upper limb outcomes. The interventions in these studies included LF-rTMS [27,30,33,56], iTBS [57], and cTBS [33]. Intervention details are summarized in Supplementary Table 2, and risk of bias results are presented in Figs. 2, 3, 4.

Fig. 2. Summary of risk of bias for studies included in the analysis of upper limb motor function.

Fig. 2

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Fig. 3. Summary of risk of bias for studies included in the analysis of lower limb motor function.

Fig. 3

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Fig. 4. Summary of risk of bias for studies included in the analysis of upper and lower limb spasticity.

Fig. 4

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Additional effects of rTMS on motor impairment in stroke

Upper limb motor function

Meta-analysis showed that rTMS combined with conventional rehabilitation significantly improved FMA-UL scores compared to conventional therapy (MD, 3.04; 95% CI, 1.16 to 4.92; p = 0.002) (Fig. 5). This effect was particularly evident in patients less than 6 months post stroke; however, substantial heterogeneity was observed within this subgroup. All RCTs included in the meta-analysis of grip strength were conducted in patients within 6 months of stroke onset and showed significant improvement (MD, 3.61; 95% CI, 1.20 to 6.03; p = 0.003) (Fig. 6). Hand function also improved significantly in the combined group (SMD, 0.28; 95% CI, 0.04 to 0.52; p = 0.02), with a similar effect in early-phase patients (SMD, 0.29; 95% CI, 0.02 to 0.57; p = 0.03) (Fig. 7). For ADL, no overall significant improvement was observed (SMD, 0.25; 95% CI, −0.01 to 0.50; p = 0.06) (Fig. 8). However, subgroup analysis showed a significant benefit in chronic stroke patients (≥ 6 months) (SMD, 0.59; 95% CI, 0.07 to 1.10; p = 0.03).

Fig. 5. Forest plot and risk of bias for Fugl-Meyer assessment of the upper limb as an outcome measure of upper limb motor function.

Fig. 5

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SD, standard deviation; IV, inverse variance; CI, confidence interval.

Fig. 6. Forest plot and risk of bias for grip strength as an outcome measure of upper limb motor function.

Fig. 6

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SD, standard deviation; IV, inverse variance; CI, confidence interval.

Fig. 7. Forest plot and risk of bias for hand function as an outcome measure of upper limb motor function.

Fig. 7

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SD, standard deviation; IV, inverse variance; CI, confidence interval.

Fig. 8. Forest plot and risk of bias for activities of daily living as an outcome measure of upper limb motor function.

Fig. 8

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SD, standard deviation; IV, inverse variance; CI, confidence interval.

Lower limb motor function

rTMS showed no significant additional benefit on FMA-LL in all patients (MD, 0.66; 95% CI, −0.37 to 1.69; p = 0.21), or in subgroups < 6 months (MD, 0.57; p = 0.32) and ≥ 6 months post-stroke (MD, 0.66; p = 0.21) (Fig. 9). Walking speed also did not significantly differ between groups (MD, −1.27; 95% CI, −9.80 to 7.26; p = 0.77).

Fig. 9. Forest plot and risk of bias for (A) Fugl-Meyer assessment of the lower limb and (B) walking speed as an outcome measure of upper limb motor function.

Fig. 9

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SD, standard deviation; IV, inverse variance; CI, confidence interval.

Spasticity

Certainty of evidence among the 14 eligible RCTs, 5 studies on upper limb spasticity were included in the meta-analysis, while no RCTs were available that evaluated the effects of rTMS on lower limb spasticity. rTMS combined with rehabilitation significantly reduced upper limb spasticity compared to control (MD, −0.48; 95% CI, −0.64 to −0.33; p < 0.00001) (Fig. 10).

Fig. 10. Forest plot and risk of bias for Modified Ashworth Scale as an outcome measure of upper limb spasticity.

Fig. 10

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rTMS, repetitive transcranial magnetic stimulation; SD, standard deviation; IV, inverse variance; CI, confidence interval.

Certainty of evidence

According to the GRADE rating, ADL was considered important but not critical (importance score: 5), in contrast to measures such as FMA-UL, grip strength, hand function, FMA-LL, walking speed, and spasticity (importance score: 7–9). Although upper limb motor impairment is known to significantly impact post-stroke handicap levels, lower limb deficits often show a stronger correlation with overall disability. Unlike impairment measures that focus on the motor function of the affected limb, ADL assessments capture the performance of functional tasks involving both affected and unaffected limbs. Therefore, ADL was not treated as a primary measure of upper limb motor function in our analysis [58].

The certainty of evidence was low for FMA-UL and ADL due to risk of bias and inconsistency. Grip strength and hand function also had low certainty, affected by imprecision and risk of bias. For upper limb spasticity, certainty remained low, though no concerns were found in inconsistency or publication bias.

Due to the very low certainty and inconclusive nature of the current evidence, we were unable to make a recommendation regarding the use of rTMS as an adjunct to conventional rehabilitation for lower limb motor function. Therefore, this combined intervention is recommended only in the context of clinical research.

Recommendation

Based on these findings, we conditionally recommend adding rTMS to conventional rehabilitation therapy to improve upper limb motor function and spasticity in stroke patients. The overall certainty of the evidence is rated as low, as detailed in Table 1. This recommendation considers individual patient factors, such as lesion location, severity, and time since stroke onset.

Table 1. Evidence summary of primary outcomes: upper limb motor function and spasticity.

Primary outcomes Importance Number of participants (studies) Certainty of evidence (GRADE) Statistical method Effect size
Motor function (FMA) 8 1,037 (19) Low MD (IV, Random, 95% CI) 3.04 (1.16, 4.92)
Grip strength 7 203 (6) Low MD (IV, Random, 95% CI) 3.61 (1.20, 6.03)
Hand function 7 300 (6) Low SMD (IV, Random, 95% CI) 0.28 (0.04, 0.52)
Spasticity (MAS) 9 114 (5) Low MD (IV, Random, 95% CI) −0.48 (−0.64, −0.33)
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FMA, Fugl-Meyer assessment; MAS, Modified Ashworth Scale; GRADE, Grading of Recommendations Assessment, Development and Evaluation; MD, mean difference; IV, inverse variance; CI, confidence interval; SMD, standardized mean difference.

DISCUSSION

This systematic review and meta-analysis included 68 RCTs to evaluate whether rTMS combined with conventional rehabilitation provides greater benefits than conventional rehabilitation alone in improving motor function and spasticity in stroke patients. Our meta-analysis demonstrated that rTMS, when applied as an adjunct to conventional rehabilitation, significantly improved upper limb motor outcomes, including FMA-UL scores, grip strength, and hand function, and also significantly reduced upper limb spasticity. These findings suggest a potential therapeutic role for rTMS in enhancing upper limb recovery after stroke. In particular, the improvement in FMA-UL was statistically significant (MD, 3.04; 95% CI, 1.16 to 4.92; p = 0.002). However, the clinical relevance of this finding should be interpreted with caution. Prior research indicates that the minimal clinically important difference (MCID) for FMA-UL is approximately 9–10 points in the subacute phase and 4.25–7.25 points in the chronic phase [59,60]. Given that the observed MD in our analysis falls below these thresholds, the improvement, while statistically significant, may not be perceived by patients as a meaningful functional gain in daily life. Further studies are warranted to clarify the long-term clinical impact of rTMS, particularly whether these improvements translate into tangible functional benefits across different phases of stroke recovery and patient subgroups.

Moreover, we recommend that rTMS may be selectively applied by experienced clinicians to enhance upper limb recovery, considering each patient’s clinical and neurological status. This meta-analysis included diverse rTMS protocols, including unilateral stimulation (e.g., LF-rTMS over the contralesional hemisphere and HF-rTMS or iTBS over the ipsilesional hemisphere) and dual-hemispheric approaches. Since cortical excitability of the ipsilesional primary motor cortex (M1) is typically reduced post-stroke, facilitatory stimulation (e.g., HF-rTMS or iTBS) and inhibitory stimulation over the contralesional hemisphere (e.g., LF-rTMS) aim to restore interhemispheric balance and promote functional recovery. However, growing evidence suggests that patient-specific factors significantly influence treatment response. Recent studies indicate that the role of the contralesional hemisphere may differ according to stroke severity. For instance, Lin et al. [61] demonstrated that interhemispheric inhibition from the contralesional to the ipsilesional hemisphere correlated negatively with motor impairment in patients with mild upper limb deficits, but positively in those with more severe deficits. In addition, patients with better preserved hand function or larger posterior limb volumes of the internal capsule were more responsive to LF-rTMS over the contralesional M1 [62]. Conversely, patients with more severe motor deficits may benefit more from excitatory stimulation over the contralesional hemisphere, as inhibitory stimulation in this population could impair contralateral motor performance [37,63]. These findings align with the bimodal balance–recovery model proposed by Di Pino et al. [64], which suggests that the role of the contralesional hemisphere may vary depending on stroke severity. Therefore, we suggest that clinicians carefully consider individual factors—such as motor severity, lesion location, and corticospinal tract integrity—when selecting rTMS targets and protocols. Thus, our recommendation for selective application of rTMS by experienced clinicians is grounded in the protocol heterogeneity and differential responses observed in the included studies, as well as the broader neurophysiological evidence.

Meanwhile, the additive effect of rTMS on upper limb spasticity, when combined with conventional rehabilitation, demonstrated a significant improvement in our analysis (MD, −0.48; 95% CI, −0.64 to −0.33; p < 0.00001). Notably, this MD aligns with the proposed MCID for the MAS, which has been estimated to be approximately 0.48 when the effect size corresponds to 0.5 standard deviations [65]. Therefore, this finding suggests that the reduction in upper limb spasticity observed with rTMS may be not only statistically significant but also clinically meaningful in both clinical and daily functional contexts.

In addition to motor-specific impairment measures, we also examined disability measures related to daily living. Although the meta-analysis of all stroke patients revealed no statistically significant improvement in ADL from rTMS combined with conventional rehabilitation (SMD, 0.25; 95% CI, −0.01 to 0.50; p = 0.06), subgroup analysis indicated a significant benefit in patients in the chronic phase (≥ 6 months post-stroke) (SMD, 0.59; 95% CI, 0.07 to 1.10; p = 0.03). These findings, too, require careful interpretation. Disability measures such as ADL assessments typically reflect the performance of functional tasks involving both upper and lower extremities, including transfers, walking, and stair climbing. Because ADL performance is influenced by a variety of motor components, it may not be sufficiently sensitive to changes in upper limb function alone. Moreover, in the early phase of stroke recovery, lower limb dysfunction tends to predominate and may have a disproportionate impact on ADL scores. Therefore, the lack of significant improvement in overall stroke patients should not be construed as evidence that rTMS is ineffective for enhancing upper limb-related daily functioning—particularly in early-stage patients. A more nuanced interpretation is warranted, taking into account the multifactorial and phase-dependent nature of functional recovery after stroke.

While rTMS significantly improved upper limb motor function and spasticity, it did not show a significant additive effect on lower limb motor recovery when combined with conventional rehabilitation. Given the limited number and heterogeneity of available studies, we were unable to draw firm conclusions regarding its efficacy for lower limb motor improvement. Similarly, a meta-analysis on lower limb spasticity was not feasible due to the scarcity of eligible RCTs. Although 2 relevant trials were identified, considerable heterogeneity and insufficient extractable data precluded quantitative synthesis [66,67]. Therefore, no formal recommendation can be made at this time. However, the lack of significant effects of rTMS on lower limb function or spasticity may be due to anatomical and methodological limitations rather than true inefficacy. Thus, the results warrant further discussion. In contrast to the relatively large body of literature investigating the effects of rTMS on upper limb recovery after stroke, studies focusing on lower limb motor function remain limited. One possible explanation lies in the neuroanatomical characteristics of the leg motor area, which make it more difficult to target effectively using conventional rTMS coils. The limited understanding of interhemispheric dynamics related to leg representation also contributes to the difficulty in establishing robust protocols for lower limb stimulation. Furthermore, only one RCT in our analysis employed a double-cone coil, which is considered more suitable for deeper and more intense stimulation and may be better suited for activating the lower limb M1. Most RCTs used figure-of-eight coils. This methodological variation may have contributed to the lack of significant pooled effects in our analysis. The limited evidence on the effects of rTMS on lower limb spasticity may also stem from similar technical and conceptual challenges. The effects of rTMS on spasticity are thought to result from direct or indirect modulation of cortical excitability in the affected hemisphere, depending on the stimulation protocol, leading to changes in descending corticospinal activity. Future RCTs that employ deeper stimulation techniques, such as double-cone coils, and investigate the underlying neurophysiological mechanisms may help clarify the role of rTMS in the recovery of lower limb motor function and spasticity.

rTMS has generally been reported as safe and well tolerated, with skin irritation and headaches being the most common adverse events. And discomfort from stimulation noise and facial muscle contractions may occur. Although rare, seizures are a potential adverse event associated with rTMS. Recent data estimate the incidence to be approximately 0.31 per 10,000 sessions and 0.71 per 1,000 individuals [68]. Given that theta burst stimulation (TBS) delivers very high-frequency stimulation, exceeding the individual's motor threshold may increase the risk of seizure. Therefore, it is recommended that TBS intensity be calibrated based on the motor threshold measured directly before stimulation. To ensure accuracy and safety, motor threshold should preferably be determined using surface electromyography rather than observation [69].

Our subgroup analysis shows more pronounced effects of rTMS during the recovery phase (< 6 months post-stroke) than in the chronic phase. This is consistent with findings by previous studies which suggest enhanced plasticity and cortical reorganization early post-stroke [70,71]. In contrast, the chronic phase may be less responsive due to stabilized neural circuitry, limiting the impact of neuromodulation. Thus, the timing of intervention is a key consideration, and our findings suggest that rTMS may offer greater benefits when initiated during the recovery period. However, evidence in the chronic phase remains limited and inconsistent, emphasizing the need for further research targeting this population.

Among the 32 RCTs included in the meta-analysis, 5 studies reported the use of neuronavigation. Neuronavigation can enhance the accuracy and reproducibility of stimulation by ensuring precise localization of the target cortical area. This may be particularly valuable when stimulating the affected hemisphere, especially in patients where motor evoked potentials cannot be elicited from the paretic hand. In such cases, defining the motor hotspot based on the contralesional hemisphere's mirror location may be necessary, and neuronavigation can support optimal and consistent targeting across sessions.

Several recent reviews have conducted multidimensional analyses of RCTs to evaluate the effects of rTMS on motor function recovery after stroke. In particular, the meta-analysis by Xie et al. [11] performed subgroup analyses based on stroke stage (< 1 month, 1–6 months, and > 6 months since onset) and stimulation frequency (e.g., 1 Hz, 3 Hz, 10 Hz). Their findings showed that moderate- to high-quality evidence supports the use of 1 Hz rTMS over the contralesional M1 during the acute and subacute phases (within 6 months), with moderate improvements in motor function and independence in ADLs. However, the effectiveness of HF-rTMS in post-stroke motor rehabilitation remains inconclusive and warrants further investigation. Bai et al. [72] further investigated the physiological effects of 4 rTMS protocols—LF-rTMS, HF-rTMS, iTBS, and cTBS—on cortical excitability measures such as resting/active motor thresholds, motor evoked potentials, and intracortical inhibition/facilitation. Except for cTBS, which had limited data, the other protocols were effective in modulating cortical excitability post-stroke. Moreover, a recent network meta-analysis comparing multiple neuromodulation techniques—including rTMS, transcranial direct current stimulation (tDCS), TBS, and transcutaneous auricular vagus nerve stimulation (taVNS)—demonstrated that taVNS, anodal tDCS, HF-rTMS, and LF-rTMS were all more effective than sham stimulation in improving upper limb motor function and ADL performance in patients with acute or subacute stroke [73]. Notably, taVNS was identified as the most effective intervention in this early phase. In contrast, for patients in the chronic phase, iTBS, anodal tDCS, and dual tDCS showed greater benefits than sham stimulation, with iTBS emerging as the most effective modality for enhancing upper limb motor recovery. Taken together with the updated results of our meta-analysis focusing on clinical outcomes, these evolving and increasingly stratified review methodologies are expected to support the development of more individualized neuromodulation protocols based on clinical and neurological characteristics.

The strengths of this study include the inclusion of recently published RCTs, strict adherence to the guidelines for systematic reviews and meta-analyses, and the implementation of a rigorous and conservative quality assessment. Limitations include heterogeneity existed in stimulation parameters (e.g., site, frequency, intensity, coil type, duration, and combinations of LF/HF/TBS) as well as in prognostic factors (e.g., lesion location, stroke type and severity, recovery phase, and cognitive status) [74]. More precise control of these factors could enhance the homogeneity of study populations and enhance the detectability of rTMS-induced therapeutic effects. While animal studies suggest rTMS may induce long-term potentiation and cortical remodeling, its sustained functional benefits remain unclear in clinical settings [75]. Future trials should address the durability of rTMS effects over time.

This systematic review and meta-analysis provides evidence that rTMS, when combined with conventional rehabilitation, yields statistically significant benefits for upper limb motor function and spasticity in stroke patients, with some effects approaching or meeting clinical relevance thresholds. However, its effects on lower limb function remain inconclusive, likely due to methodological and neuroanatomical limitations. To fully elucidate the role of rTMS in promoting motor recovery after stroke, future high-quality RCTs with improved population homogeneity, optimized stimulation protocols, and extended follow-up periods are needed.

Footnotes

Funding: None.

Conflict of Interest: The authors have no potential conflicts of interest to disclose.

Author Contributions:
  • Conceptualization: Lee HY, Ryu B.
  • Data curation: Lee HY, Ryu B.
  • Formal analysis: Lee HY, Ryu B.
  • Investigation: Lee HY, Ryu B.
  • Methodology: Lee HY, Ryu B.
  • Project administration: Lee HY, Ryu B.
  • Resources: Lee HY, Ryu B.
  • Software: Lee HY, Ryu B.
  • Supervision: Lee HY, Ryu B.
  • Validation: Lee HY, Ryu B.
  • Visualization: Lee HY, Ryu B.
  • Writing - original draft: Lee HY, Ryu B.
  • Writing - review & editing: Lee HY, Ryu B.

SUPPLEMENTARY MATERIALS

Supplementary Table 1

Search terms and strategies

bn-18-e5-s001.xls (53KB, xls)
Supplementary Table 2

Characteristics of included studies

bn-18-e5-s002.xls (141.5KB, xls)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Table 1

Search terms and strategies

bn-18-e5-s001.xls (53KB, xls)
Supplementary Table 2

Characteristics of included studies

bn-18-e5-s002.xls (141.5KB, xls)

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