Effects of repetitive transcranial magnetic stimulation on lower extremity motor function and optimal parameters in stroke patients with different stages of stroke: a systematic evaluation and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS), as an emerging non-invasive neuromodulation technique, is now widely employed in rehabilitation therapy. The purpose of this paper is to comprehensively summarize existing evidence regarding rTMS intervention for lower limb motor function in patients at different stages of stroke. A systematic search was conducted to identify randomized controlled trials (RCTs) assessing the efficacy of rTMS for treating lower limb motor dysfunction after stroke. Multiple databases, including China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, PubMed, Embase, Web of Science, and Cochrane Library, were searched. The search period extended from the inception of the libraries to June 2024. Literature information was extracted, and methodological quality was evaluated using the risk of bias assessment tool in the Cochrane Handbook. Meta-analysis was performed using Stata 17.0 software. Overall, 49 appropriate studies (including 3,558 stroke subjects) were found. Meta-analysis results demonstrated that rTMS effectively improved lower limb motor function across all stages of stroke. The intervention was particularly more effective in patients in the subacute stage than in the acute or chronic stages. Subgroup analysis revealed that, for acute-stage patients, low-frequency stimulation targeting the M1 or DLPFC brain regions on the unaffected side with 20-40 sessions significantly improved FMA-LE scores. In subacute-phase patients, low-frequency stimulation targeting the M1 brain regions on the unaffected side with 18 sessions significantly improved FMA-LE scores. The results demonstrated that HF-rTMS was more effective than LF-rTMS in improving walking speed, with the greatest efficacy observed at 20 sessions. While for enhancing gait balance in stroke patients, LF-rTMS with the best therapeutic effect was observed at a frequency of 20-40 treatments. This study demonstrates the efficacy of rTMS in improving lower limb motor function, balance, and walking speed in stroke patients at various stages. The findings provide a valuable reference for the development of optimized rTMS treatment plans in clinical practice.Systematic review registration: PROSPERO: CRD42023466094.

Fan S ，Yan L ，Zhang J ，Qian Y ，Wang M ，Yang L ，Yu T ... -  《Frontiers in Neurology》

The effect and optimal parameters of repetitive transcranial magnetic stimulation on lower extremity motor function in stroke patient: a systematic review and meta-analysis.

Zhang W ，Dai L ，Liu W ，Li X ，Chen J ，Zhang H ，Chen W ，Duan W ... -  《-》

Comparative Efficacy of Different Repetitive Transcranial Magnetic Stimulation Protocols for Stroke: A Network Meta-Analysis.

Although repetitive transcranial magnetic stimulation (rTMS) has been proven to be effective in the upper limb motor function and activities of daily living (ADL), the therapeutic effects of different stimulation protocols have not been effectively compared. To fill this gap, this study carried out the comparison of the upper limb motor function and ADL performance of patients with stroke through a network meta-analysis. Randomized controlled trials (RCTs) on the rTMS therapy for stroke were searched from various databases, including PubMed, web of science, Embase, Cochrane Library, ProQuest, Wanfang database, the China National Knowledge Infrastructure (CNKI), and VIP information (www.cqvip.com). The retrieval period was from the establishment of the database to January 2021. Meanwhile, five independent researchers were responsible for the study selection, data extraction, and quality evaluation. The outcome measures included Upper Extremity Fugl-Meyer Assessment (UE-FMA), Wolf Motor Function Test (WMFT), Modified Barthel Index (MBI), the National Institute of Health stroke scale (NIHSS), and adverse reactions. The Gemtc 0.14.3 software based on the Bayesian model framework was used for network meta-analysis, and funnel plots and network diagram plots were conducted using Stata14.0 software. Ninety-five studies and 5,016 patients were included ultimately. The intervention measures included were as follows: placebo, intermittent theta-burst stimulation (ITBS), continuous theta-burst stimulation (CTBS),1 Hz rTMS,3-5 Hz rTMS, and ≥10 Hz rTMS. The results of the network meta-analysis show that different rTMS protocols were superior to placebo in terms of UE-FMA, NIHSS, and MBI outcomes. In the probability ranking results, ≥10 Hz rTMS ranked first in UE-FMA, WMFT, and MBI. For the NIHSS outcome, the ITBS ranked first and 1 Hz rTMS ranked the second. The subgroup analyses of UE-FMA showed that ≥10 Hz rTMS was the best stimulation protocol for mild stroke, severe stroke, and the convalescent phase, as well as ITBS was for acute and subacute phases. In addition, it was reported in 13 included studies that only a few patients suffered from adverse reactions, such as headache, nausea, and emesis. Overall, ≥10 Hz rTMS may be the best stimulation protocol for improving the upper limb motor function and ADL performance in patients with stroke. Considering the impact of stroke severity and phase on the upper limb motor function, ≥10 Hz rTMS may be the preferred stimulation protocol for mild stroke, severe stroke, and for the convalescent phase, and ITBS for acute and subacute phases. https://www.crd.york.ac.uk/prospero/, identifier [CRD42020212253].

Xia Y ，Xu Y ，Li Y ，Lu Y ，Wang Z ... -  《Frontiers in Neurology》

A Meta-Analysis: Whether Repetitive Transcranial Magnetic Stimulation Improves Dysfunction Caused by Stroke with Lower Limb Spasticity.

To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving lower limb spasticity after stroke. The PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) disc, China Science and Technology Journal Database (VIP), and Wanfang databases were searched online from their inception to May 2021 for randomized controlled trials (RCTs) involving repetitive transcranial magnetic stimulation for lower extremity spasticity after stroke. Valid data were extracted from the included literature, and the quality evaluation was conducted with the Cochrane Handbook for Systematic Reviews of Interventions along with the Physiotherapy Evidence Database scale (PE-Dro scale). The data that met the quality requirements were systematically analysed using Review Manager 5.4 software. A total of 554 patients from seven articles (nine studies) were quantitatively analysed. Outcomes included the Modified Ashworth Scale (MAS), Fugl-Meyer Assessment of Lower Extremity (FMA-LE), Modified Barthel Index (MBI), and Timed Up and Go (TUG), measured as the effect of rTMS compared with controls conditions after treatment. The systematic review showed that rTMS reduced MAS and increased MBI scores, respectively (SMD = -0.24, 95% CI [-0.45, -0.03], P = 0.02; MD = 6.14, 95% CI [-3.93,8.35], P ＜ 0.00001), compared with control conditions. Low-frequency rTMS (LF-rTMS) significantly improved FMA-LE scores (SMD = 0.32, 95% CI [0.13, 0.51], P = 0.001). However, there was no significant difference in FMA-LE scores when using high-frequency rTMS (HF-rTMS) (P > 0.1) and in TUG times (P > 0.1) between the treatment and control groups. rTMS was effective in improving spasticity and activities of daily living. LF-rTMS has positive clinical effects on enhancing motor function in patients who experience lower extremity spasticity after stroke. To better validate the above conclusions, more multicentre, high-quality, and double-blind randomized controlled trials are needed.

Liu Y ，Li H ，Zhang J ，Zhao QQ ，Mei HN ，Ma J ... -  《-》

Comparative efficacy of different repetitive transcranial magnetic stimulation protocols for lower extremity motor function in stroke patients: a network meta-analysis.

Lower extremity motor dysfunction is one of the most severe consequences after stroke, restricting functional mobility and impairing daily activities. Growing evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can improve stroke patients' lower extremity motor function. However, there is still controversy about the optimal rTMS protocol. Therefore, we compared and analyzed the effects of different rTMS protocols on lower extremity motor function in stroke patients using network meta-analysis (NMA). We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases (from origin to 31 December 2023). Randomized controlled trials (RCTs) or crossover RCTs on rTMS improving lower extremity motor function in stroke patients were included. Two authors independently completed article screening, data extraction, and quality assessment. RevMan (version 5.4) and Stata (version 17.0) were used to analyze the data. A total of 38 studies with 2,022 patients were eligible for the NMA. The interventions included HFrTMS-M1, LFrTMS-M1, iTBS-Cerebellum, iTBS-M1, dTMS-M1, and Placebo. The results of NMA showed that LFrTMS-M1 ranked first in FMA-LE and speed, and HFrTMS-M1 ranked first in BBS, TUGT, and MEP amplitude. The subgroup analysis of FMA-LE showed that HFrTMS-M1 was the best stimulation protocol for post-stroke time > 1 month, and LFrTMS-M1 was the best stimulation protocol for post-stroke time ≤ 1 month. Considering the impact of the stroke phase on the lower extremity motor function, the current research evidence shows that HFrTMS-M1 may be the preferred stimulation protocol to improve the lower extremity motor function of patients for post-stroke time > 1 month, and LFrTMS-M1 for post-stroke time ≤ 1 month. However, the above conclusion needs further analysis and validation by more high-quality RCTs.Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier (CRD42023474215).

Wang C ，Zhang Q ，Zhang L ，Zhao D ，Xu Y ，Liu Z ，Wu C ，Wu S ，Yong M ，Wu L ... -  《Frontiers in Neuroscience》