Table 3 Characteristics of included studies in this systematic review (continue)
ID | The area of stroke | Intervention-related adverse events | Intent-to-treat analysis | Drop off |
|---|---|---|---|---|
Abdelkader 2024 [92] | DR | DR | Yes | No one |
Aşkın 2017 [40] | DR | DR | No | No one |
Avenanti 2012 [69] | DR | DR | No | DR |
Barros 2014 [70] | DR | No adverse events were reported by any of the participants | No | Two patients (1 in each group) dropped out after the post-intervention evaluation, leaving 18 participants who completed all the study procedures |
Blesneag 2015 [41] | The region of MCA | DR | No | No one |
Chen 2023 [71] | DR | No | DR | |
Chervyakov 2018 [35] | The region of MCA | Two patients developed secondary generalized epileptic seizures. One female patient presented with seizures during single-pulse stimulation for diagnostic mapping. Nine patients withdrew from the study at different stages because they developed epileptic seizures, reported subjective “bad” or “tired” feelings after rTMS session(s) or for no cause. Thirteen participants were excluded from analysis, mainly because of incomplete data sets | No | Nine patients withdrew from the study at different stages because they developed epileptic seizures, reported subjective “bad” or “tired” feelings after rTMS session(s) or for no cause |
Chieffo 2021 [80] | DR | No serious adverse events were reported. Vital signs remained stable after treatment for all participants. Three subjects reported transitory dizziness, and one showed muscle twitches on shoulders during real rTMS. For these patients, intensity was lowered to a comfortable level (80% of RMT on average), and all subjects completed the whole treatment cycle | No | One subject (Subject 9 Table 1) attended all sessions of the first treatment but withdrew from the protocol before the second phase for personal reasons |
Conforto 2012 [42] | The region of MCA | There were no serious intervention-related adverse events. There were no significant differences in rates of sleepiness (86.7%, active and 78.6%, sham; local or nuchal pain (33.3%, active and 28.6%, sham; = 0.46; sham group, = 0.65) or headache, = 1.0) between the groups. Head or nuchal pain were mild and subsided spontaneously after a few minutes. None of the patients reported dizziness or paresthesias. No syncopes or seizures were observed. There were no significant differences in systolic (active group, blood pressure (active group, = 0.76; sham group = 0.21) or diastolic = 0.26; sham group = 0.96), and heart rate (active group = 0.32), along the ten sessions of treatment | No | 1 drop off because recurrent stroke |
Du 2016 [36] | The region of MCA | No adverse effects were observed except for three transient headaches and one tingling sensation on the head at the beginning of the stimulation | No | 7 of experimental group lost,1 of control lost |
Du 2019 [43] | The region of MCA | Fifty-three patients successfully completed the intervention protocol with no adverse effects, except for two transient headaches at the beginning of stimulation (both in HF-rTMS groups) | No | 6 of experimental group lost,3 of control lost |
Edwards 2023 [47] | Cortical/Subcortical/Cortical/subcortical/Brainstem | Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P = 0.72) | Yes | 3 lost in rTMS group, and 1lost in sham group |
El-Tamawy 2019 [45] | DR | DR | No | DR |
El-Tamawy 2020 [46] | the region of MCA | DR | No | DR |
Emara 2010 [47] | DR | No significant adverse events were observed during treatment in either group. Six patients (four active rTMS and two controls) experienced transient headache or tingling sensation in the head following the rTMS session. This resolved spontaneously within 30 min in three patients and required oral paracetamol in the other three to effectively control the symptoms | No | DR |
Fang 2024 [96] | DR | One patient reported a mild headache during rTMS, which subsided once the intervention stopped | No | 4 patients drop out |
Forogh 2017 [72] | DR | DR | No | 11 patients (5 patients in the treatment and 6 patients in Sham group) withdrew from the study |
Fregni 2006 [48] | Left basal ganglia Left internal capsule Left putamen Left internal capsule Left corona radiata Left internal capsule (posterior limb) Left internal capsule Right lentiform nucleus Right internal capsule Left somatosensory cortex Right frontal lobe Left temporofrontal Left putamen and caudate Left corona radiata Left putamen | There were few adverse events. In the active group, one patient reported a mild headache (contralateral to the side of TMS application) and one patient reported an increase in anxiety. In the sham rTMS group, one patient reported an increase in the tiredness and one patient reported a mild headache | Yes | There were no dropouts and the few missing data were considered missing at random |
Gong 2021 [37] | The region of MCA | Except for two transient headaches on the head at the beginning of the stimulation, no adverse effects were observed in this study, such as seizures | No | 2 patients drop off |
Gottlieb 2021 [73] | The region of MCA | Five patients reported a mild adverse event within 24 h after the rTMS session (headache: n = 4, pain in contralateral hand: n = 1). One patient with headache needed a low dose of an analgetic. However, the frequency of reported adverse events was equal in both groups | No | Six patients did not receive complete intervention and one patient of the sham-rTMS group had to be excluded from the analyses because the second examination could not be performed |
Guan 2017 [49] | The region of MCA | None of the patients complained of discomfort after rTMS or sham rTMS | No | 8 patients in the treatment group and 7 patients were lost to follow- up due to personal reasons |
Haghighi 2021 [74] | The region of MCA | All participants completed the study protocol without any adverse events | Yes | The treatment and assessment sessions were completed by all the participants |
Harvey 2018 [75] | Cortex, subcortical, both cortex and subcortex, brain stem, centrum semiovale, corona radiata, basal ganglia, internal capsule, and thalamus | Of the safety population (n = 196), a total of 26 serious adverse events occurred in 18 participants. Rates within treatment arms were not significantly different. The most common treatment-related adverse events were arm and hand pain, spasm or myalgia (n = 14), head discomfort (n = 11), and paresthesia (n = 6). These were transient and resolved within 24 h of onset | Yes/Missing values were imputed using the last observation carried forward principle | Because of 3 participants withdrawing before study interventions, the safety sample is 196. The per-protocol sample was 169 after removing 30 subjects with significant protocol deviations (15 active and 15 sham) |
Higgins 2013 [76] | DR | Did not experience adverse events related/No subjects reported experiencing headaches or any sort of discomfort following the rTMS or the behavioral intervention | Yes | Of the eleven subjects recruited, two subjects withdrew from the study before the post intervention evaluation. One withdrew following an adverse event during but not related to the intervention session. The subject experienced an important drop in blood pressure, having taken the wrong dose of medication on the morning of the treatment. He had completed five intervention sessions. The second participant withdrew following four intervention sessions. She had sustained a fall at home and was no longer able to travel for the study |
Hosomi 2016 [77] | Subcortex and Involvement of cortex | There were no serious adverse effects observed during or after the stimulations during the 2-week follow up period after completion of stimulations. As was previously mentioned, 1 subject withdrew from the protocol due to uncomfortableness. Incidentally, he later apparently demanded continuation of stimulations, after which he reportedly found the same stimulation pattern relaxing and enjoyable | No | Two subjects in the real stimulation group failed to complete the study. One patient did not like the stimulation sensation on the scalp after one 10-s train of stimulations on the first day of stimulations, and declined following stimulations. The other patient also temporarily refused other forms of treatment such as regular rehabilitation during the first week of the stimulation |
Huang 2018 [78] | Cortical involved subcortical only | DR | No | Four patients withdraw |
Jia 2024 [97] | DR | No adverse events were observed during the intervention period | No | Two patients were discharged early, one patient refused treatment, and one patient withdrew from treatment because of a recurrence of cerebral hemorrhage |
Juan 2022 [50] | The region of MCA | DR | No | Fourteen patients dropped out during the trial for different reasons, mainly symptom exacerbation, incompliance or poor fMRI data quality |
Ke 2020 [53] | Cortex and subcortex | Because of medical insurance complications, leading to rTMS termination. In addition, four patients were lost during follow-up: two patients in the sham group and one patient in each of the short and long ITI rTMS groups | No | Four patients (one from the sham group, two from the short ITI group, and one from the long ITI group) were discharged before the end of rTMS. because of medical insurance complications, leading to rTMS termination. In addition, four patients were lost during follow-up: two patients in the sham group and one patient in each of the short and long ITI rTMS groups |
Khedr 2005 [55] | Cortical/subcortical/massive | All patients completed the protocols, and there were no side effects of rTMS except occasional mild headache | All patients completed trail | All patients completed the protocols, and there were no side effects of rTMS except occasional mild headache |
Khedr 2009 [54] | Ischemic stroke of middle cerebral artery territory/cortical and subcortical | All the patients tolerated rTMS well without any adverse effects | All the patients tolerated rTMS well without any adverse effects | All the patients tolerated rTMS well without any adverse effects |
Khedr 2010 [56] | The region of MCA | All the patients tolerated rTMS well without any adverse effects | All the patients tolerated rTMS well without any adverse effects | Ten patients out of the 48 patients (four from the first group, three from the second group and three from the sham group) did not complete the follow-up at the end of the year. Four of them developed another stroke, two died before the end of the year and four could not attend because of family reasons |
Kim 2014 [57] | Ischemic cerebellar or brain stem stroke with symptoms of ataxia (Cerebellum Pons Medulla) | Adverse events were not reported during and after the rTMS session in both real and sham rTMS groups | Yes | Two patients in the real rTMS group and 4 in the sham rTMS group were lost to follow-up for reasons not related to the intervention |
Kim 2020 [28] | Cortical Subcortical Cortical/subcortical Brain stem | A total of 111 adverse events occurred in 48 participants and were more numerous among real rTMS: Most of the events were mild in real rTMS and 38 in sham rTMS) and only one serious adverse event (ischemic stroke recurrence) occurred in real rTMS but was determined to be unrelated to the intervention. There were 7 adverse device events for real rTMS and 2 for sham rTMS, with no statistically significant difference. No serious and unexpected ADEs were noted | Yes | One participant in the real rTMS group did not receive the intervention due to consent withdrawal. Three in the real rTMS group were lost to follow-up due to consent withdrawal before EOT. At 1 month after EOT, one participant from each group withdrew their consent |
Lin 2015 [79] | DR | A Group E patient reported dizziness, and a Group C patient reported tingling scalp pain after the intervention sessions. These symptoms were tolerable and subsided after the treatment sessions | No | One patient was transferred to another hospital for personal reasons before treatment completion |
Liang 2023 [39] | DR | DR | Yes | No one |
Long 2018 [81] | In the territory of the middle cerebral artery or supratentorial intracerebral hemorrhage (ICH) without invasion into the cerebral cortex | No patient complained of pain or discomfort immediately after rTMS or during the follow-up visits. No patient experienced any pathologic symptoms, such as seizure or deterioration of motor function in the upper limb | No | All patients completed the protocols |
Ludemann-Podubecka 2015 [82] | The region of MCA | Participants tolerated the interventions well without serious adverse events | No | No one |
Luk 2022 [83] | DR | The participants did not report any adverse events during the study period | Intention-to-treat analysis was first conducted. Any missing data would be substituted using the last-observation-carried-forward method | One participant from each group withdrew during the course of the study |
Lv 2023 [51] | DR | DR | Yes | No one |
Maclolm 2007 [84] | Middle cerebral artery, hemispheric lacunar infarcts, deep hemispheric hemorrhage, lacunar infarcts | There were no discernible adverse effects of rTMS beyond scalp discomfort | Yes | All patients completed study |
Matsuura 2015 [58] | Subcortical stroke | All patients completed their rTMS sessions and did not report any adverse effects | No | All patients completed their rTMS |
Mello 2015 [59] | Involving up to 50% of the internal carotid artery territory | In the active group, two patients reported headache or local pain (22.2%), two patients reported nuchal pain (22.2%), and five patients reported drowsiness (55.6%). In the sham group, three patients reported headache or local pain (33.3%), four patients reported nuchal pain (44.4%), and six patients reported drowsiness (66.7%) | No | One patient in the sham group had a recurrent stroke on the day before the second session of treatment and did not complete the study. Due to technical problems (malfunction of the paired-pulse TMS stimulator), cortical excitability data in 7 patients in the active group and 7 patients in the sham group were not collected. One patient in the active group coughed repeatedly during one of the TMS experiments |
Meng 2017 [60] | Cerebral infarction of the internal carotid artery that was diagnosed based on clinical symptoms and signs | None of the patients had any severe adverse reactions such as recurrent stroke or seizures. One individual in the low frequency rTMS group experienced dizziness, but the symptoms disappeared soon after treatment | No | All patients completed study |
Petruseviciene 2023 [52] | DR | DR | Yes | No one |
Qin 2021 [61] | Subcortical stroke | DR | No | 1 patient of real TMS and 6 patients of sham TMS did withdraw |
Qin 2023 [62] | The middle cerebral artery territory | DR | No | 2 patients drop off |
Rastgoo 2016 [85] | Cortex Subcortex Both cortex and subcortex | No adverse events were reported by any of the patients throughout the study | DR | DR |
Revill 2020 [63] | Ischemic infarction affecting M1 and/or corticospinal tract | DR | No | 1 patient lost to follow-up because subject declined TMS measure |
Rezaei 2023 [103] | Supratentorial/infratentorial | All patients completed the study protocol, and no adverse effect was reported | Yes | No one |
Sasaki 2017 [86] | The region of MCA | No patient experienced any pathological symptoms or deterioration of neurological symptoms | No | All patients completed the study protocol |
Sasaki 2013 [87] | The region of MCA | No patient experienced any pathologic symptoms such as seizure or any deterioration of motor function in the affected upper limb during the study period | Yes | The protocol of this study was completed by all patients |
Sengul 2023 [88] | Subcortical and cortical plus subcortical | No adverse events were observed during the intervention. In addition, no adverse events were reported to the investigators by the participants during the 3-month period after the intervention | Yes | None of the subjects dropped out of the study or analyses |
Seniow 2012 [98] | Cortical and corticosubcortical | DR | No | Four patients from the E group and 2 from the C group were lost to follow-up |
Sharma 2020 [64] | Large artery Lacunar Cardioembolic Others | One participant had seizure who was managed symptomatically | Yes | During the run-in period, 35 participants withdrew consent and 4 died after discharge from hospital. Seven participants in real rTMS were lost to follow-up |
Shim 2023 [38] | Subcortex damage | DR | No | 2 patients were excluded due to discharge, and 1 dropped out of the intervention |
Shu 2024 [93] | DR | DR | No | Six of each group withdrew midway, with 30 for each group ultimately being included in statistical analysis |
Takeuchi 2005 [65] | Subcortical infarction | Subjects did not report any adverse side effects during the course of the study | No | No one |
Takeuchi 2008 [66] | Subcortical infarction | The subjects did not report any adverse effects during the course of the study | No | No one |
Tosun 2017 [67] | DR | No adverse events were reported by any of the participants, all participants completed the trial | All patients completed trail | No one |
Wang 2014 [89] | The region of MCA | All of the patients completed the experimental protocols and assessments and exhibited no notable adverse effects | No | All of the patients completed the experimental protocols |
Wang 2022 [90] | Cortical Subcortical Brain stem | There were no severe adverse reactions such as seizures or recurrent stroke happened during all treatments. Only one patient in the HF-rTMS group experienced dizziness at the first few sessions of stimulation. No special treatment was performed, the symptom disappeared soon after intervention | Yes | All participants completed the trial |
Wang 2024 [94] | DR | without any observed adverse events during treatment | Yes | No one |
Wang 2020 [91] | The region of MCA | DR | Yes | All the patients completed treatments |
Wang C 2023 [68] | Cortical Subcortical Both | DR | Yes | All patients completed study |
Wang T 2023 [99] | DR | No | All patients completed study | |
Wu 2023 [100] | DR | No patient experienced any adverse reactions, such as epilepsy, pain, or deterioration of the condition | Yes | No one |
Yang 2021 [101] | Cortex; Subcortex; Both | Finally, thirty-nine patients completed the interventions without incident, severe side effects, or discomfort, indicating that the procedure was well tolerated | No | Five patients dropped out of the trial due to personal problems |
Yu 2022 [102] | Basal ganglia | DR | Yes | No one |
Xie 2023 [95] | Supratentorial/infratentorial | DR | No | 3 of the 10 dropouts were passive withdrawal due to hardware equipment problems, and 5 of the remaining 7 active withdrawal were from the sham group |