Abstract: OBJECTIVE: Upper extremity dyskinesia is the most common complication in stroke patients, mainly manifested in the peripheral limbs, while the lesions are located in the central brain. However, there is still a lack of meta-analysis of the effects of different central and peripheral interventions applied alone or in combination on the upper extremity motor function and activities of daily living in stroke patients, which imposes a certain limitation on the clinical selection of the best rehabilitation approach. Here, a network meta-analysis was conducted to assess the clinical efficacy of four commonly used central rehabilitation methods (transcranial magnetic stimulation, transcranial direct current stimulation, mirror therapy and motor imagery) and four commonly used peripheral rehabilitation methods (rehabilitation robotics, constraint-induced movement therapy, electromyography biofeedback, and functional electrical stimulation) applied alone or in combination on the motor function of the upper limbs and activities of daily living in stroke patients, thereby determining the optimal rehabilitation program. 
METHODS: A computer search of PubMed, Web of Science, Embase, The Cochrane Library, CNKI, WanFang, VIP, and the Chinese Biomedical Literature Database. The time period was from database inception to October 15, 2024. Randomized controlled trials of different central or peripheral rehabilitation methods alone or in combination on upper limb function and activities of daily living in stroke patients were collected. The risk of bias and methodological quality of the included literature were evaluated using the Cochrane Risk of Bias Assessment Tool and the revised Jadad scale. Network meta-analyses of Fugl-Meyer Assessment-Upper Extremity, Wolf motor function test and Modified Barthel index were performed using RevMan 5.4 and Stata 18. The strength of recommendation for the outcome metrics was assessed using the GRADE Level of Evidence system. 
RESULTS: (1) A total of 88 studies were included, including 82 high-quality and 6 low-quality studies, involving 5 561 stroke patients, resulting in a total of 19 rehabilitation programs. (2) The Fugl-Meyer scale results indicated that the top eight rehabilitation programs, ranked by the area under the cumulative ranking probability chart, were transcranial direct current stimulation+robot (99.4%) > motor imagery therapy+robot (84.4%) > motor imagery therapy+constraint-induced movement therapy (82.8%) > mirror therapy+electromyography biofeedback (81.2%) > motor imagery therapy+electromyography biofeedback (77.0%) > repetitive transcranial magnetic stimulation+constraint-induced movement therapy (69.9%) > transcranial direct current stimulation+electromyography biofeedback (67.1%) > repetitive transcranial magnetic stimulation+electromyography biofeedback (60.2%). (3) Wolf motor function test results indicated that the top three rehabilitation programs, ranked by the area under the cumulative ranking probability chart, were constraint-induced movement therapy+transcranial direct current stimulation (70.7%) > constraint-induced movement therapy (65.3%) > transcranial direct current stimulation (63.4%). (4) Modified Barthel index results indicated that the top eight rehabilitation programs, ranked by the area under the cumulative ranking probability chart, were transcranial direct current stimulation+robot (95.4%) > transcranial direct current stimulation+electromyography biofeedback (82.3%) > motor imagery therapy+constraint-induced movement therapy (79.7%) > repetitive transcranial magnetic stimulation+constraint-induced movement therapy (79.5%) > functional electrical stimulation (74.2%) > motor imagery therapy+electromyography biofeedback (68.6%) > mirror therapy+robot (65.1%) > mirror therapy+electromyography biofeedback (51.0%).
CONCLUSION: The moderate strength of evidence recommends transcranial direct current stimulation+robot as the optimal rehabilitation protocol to promote upper limb motor function and activities of daily living in stroke patients. The central combined with peripheral rehabilitation approach is superior to a single means of rehabilitation to improve upper limb motor function and activities of daily living in stroke patients. Higher-quality and multicentral clinical trials should be carried out in the future to validate the results of this study.

Key words: stroke, upper limb, motor function, activities of daily living, transcranial magnetic stimulation, transcranial direct current stimulation, rehabilitation robot, mirror therapy