Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis.

Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy to promote recovery of the upper limb after stroke. According to the regulation of cortical excitability, rTMS can be divided into excitatory rTMS and inhibitory rTMS, and excitatory rTMS includes high-frequency rTMS (HF-rTMS) or intermittent theta-burst stimulation (iTBS). We aimed to evaluate the effects of excitatory rTMS over the ipsilesional hemisphere on upper limb motor recovery after stroke. Databases of PubMed, Embase, ISI Web of Science, and the Cochrane Library were searched for randomized controlled trials published before 31 December 2021. RCTs on the effects of HF-rTMS or iTBS on upper limb function in patients diagnosed with stroke were included. Two researchers independently screened the literature, extracted the data, and assessed quality. The meta-analysis was performed by using Review Manager Version 5.4 software. Fifteen studies with 449 participants were included in this meta-analysis. This meta-analysis found that excitatory rTMS had significant efficacy on upper limb motor function (MD = 5.88, 95% CI, 3.32-8.43, P < 0.001), hand strength (SMD = 0.53, 95% CI, 0.04-1.01, P = 0.03), and hand dexterity (SMD = 0.76, 95% CI, 0.39-1.14, P < 0.001). Subgroup analyses based on different types of rTMS showed that both iTBS and HF-rTMS significantly promoted upper limb motor function (iTBS, P < 0.001; HF-rTMS, P < 0.001) and hand dexterity (iTBS, P = 0.01; HF-rTMS, P < 0.001) but not hand strength (iTBS, P = 0.07; HF-rTMS, P = 0.12). Further subgroup analysis based on the duration of illness demonstrated that applying excitatory rTMS during the first 3 months (<1 month, P = 0.01; 1-3 months, P = 0.001) after stroke brought significant improvement in upper limb motor function but not in the patients with a duration longer than 3 months (P = 0.06). We found that HF-rTMS significantly enhanced the motor evoked potential (MEP) amplitude of affected hemisphere (SMD = 0.82, 95% CI, 0.32-1.33, P = 0.001). Our study demonstrated that excitatory rTMS over the ipsilesional hemisphere could significantly improve upper limb motor function, hand strength, and hand dexterity in patients diagnosed with stroke. Both iTBS and HF-rTMS which could significantly promote upper limb motor function and hand dexterity, and excitatory rTMS were beneficial to upper limb motor function recovery only when applied in the first 3 months after stroke. HF-rTMS could significantly enhance the MEP amplitude of the affected hemisphere. High-quality and large-scale randomized controlled trials in the future are required to confirm our conclusions. www.crd.york.ac.uk/prospero/, identifier: CRD42022312288.

Tang Z ，Han K ，Wang R ，Zhang Y ，Zhang H ... -  《Frontiers in Neurology》

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》

The effectiveness of intermittent theta burst stimulation for upper limb motor recovery after stroke: a systematic review and meta-analysis of randomized controlled trials.

Intermittent theta burst stimulation (iTBS) is a promising noninvasive therapy to restore the excitability of the cortex, and subsequently improve the function of the upper extremities. Several studies have demonstrated the effectiveness of iTBS in restoring upper limb function and modulating cortical excitability. We aimed to evaluate the effects of iTBS on upper limb motor recovery after stroke. The purpose of this article is to evaluate the influence of intermittent theta-burst stimulation on upper limb motor recovery and improve the quality of life. A literature search was conducted using PubMed, EMBASE, MEDLINE, The Cochrane Library, Web of Science, and CBM, including only English studies, to identify studies that investigated the effects of iTBS on upper limb recovery, compared with sham iTBS used in control groups. Effect size was reported as standardized mean difference (SMD) or weighted mean difference (WMD). Ten studies were included in the meta-analysis. The results of the meta-analysis indicated that when compared to the control group, the iTBS group had a significant difference in the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT) (WMD: 3.20, 95% CI: 1.42 to 4.97; WMD: 3.72, 95% CI: 2.13 to 5.30, respectively). In addition, there was also a significant improvement in the modified Ashworth scale (MAS) compared to the sham group (WMD: -0.56; 95% CI: -0.85 to -0.28). More evidence is still needed to confirm the effect of Barthel Index (BI) scores after interventions. However, no significant effect was found for the assessment of Motor Evoked Potential (MEP) amplitude and MEP latency (SMD: 0.35; 95% CI: -0.21 to 0.90; SMD: 0.35, 95% CI: -0.18 to 0.87; SMD: 0.03, 95% CI: -0.49 to 0.55; respectively). Our results showed that iTBS significantly improved motor impairment, functional activities, and reduced muscle tone of upper limbs, thereby increasing the ability to perform Activities of Daily Living (ADL) in stroke patients, while there were no significant differences in MEPs. In conclusion, iTBS is a promising non-invasive brain stimulation as an adjunct to therapy and enhances the therapeutic effect of conventional physical therapy. In the future, more randomized controlled trials with large sample sizes, high quality, and follow-up are necessary to explore the neurophysiological effects. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392739.

Chen S ，Zhang S ，Yang W ，Chen Y ，Wang B ，Chen J ，Li X ，Xie L ，Huang H ，Zeng Y ，Tian L ，Ji W ，Wei X ，Lan Y ，Li H ... -  《Frontiers in Neuroscience》

Efficacy of coupling intermittent theta-burst stimulation and 1 Hz repetitive transcranial magnetic stimulation to enhance upper limb motor recovery in subacute stroke patients: A randomized controlled trial.

Meng Y ，Zhang D ，Hai H ，Zhao YY ，Ma YW ... -  《-》

Comparative efficacy of different noninvasive brain stimulation protocols on upper-extremity motor function and activities of daily living after stroke: a systematic review and network meta-analysis.

Li LL ，Wu JJ ，Li KP ，Jin J ，Xiang YT ，Hua XY ，Zheng MX ，Xu JG ... -  《-》