This is a multicenter, randomized, double-blind, sham-controlled, investigator-initiated clinical study, to evaluate the clinical efficacy and safety of LF-rTMS in rescuing the ischemic penumbra, reducing disability rate and improving functional outcome in patients with acute ischemic stroke receiving early endovascular recanalization (bridging or direct endovascular therapy)

The target population of this study was patients with acute ischemic stroke of the anterior circulation diagnosed clinically. The site of acute occlusion of the responsible vessel was located in the intracranial segment of the internal carotid artery, T-type bifurcation or M1 segment of the middle cerebral artery, planning for bridging therapy (bridging intravascular therapy after intravenous thrombolysis with alteplase) or direct intravascular therapy, the time from stroke onset to the start of the trial intervention was less than 24 hours (when the exact time of onset was unknown, the patient's"Last apparent normal time" was defined as the time of onset).

Enrolled patients were randomly assigned in a 1:1 ratio to the"LF-rTMS group" or the"Sham Stimulation Group" and received:

1. LF-rTMS group: using "8" coil,1-Hz rTMS to stimulate the M1 region of the ipsilateral hemisphere, the stimulation intensity was RMT 100%, 1200pulses/session, two sessions (2400 pulses)/day (interval ≥ 2 hours), lasting 3 days (total 6 sessions, 7200pulses);
2. Sham stimulation group: the sham stimulation coil was used to stimulate the same site, duration and sound as the LF-rTMS group, ensuring no effective stimulation, twice a day for 3 days.

All patients received endovascular therapy (bridging therapy or direct endovascular therapy).

All patients were followed up until the 90th day after randomization to evaluate the clinical efficacy and safety of LF-rTMS in rescuing the ischemic penumbra, reducing disability rate and improving functional outcome in patients with acute ischemic stroke receiving early endovascular recanalization (bridging or direct endovascular therapy)

Inclusion Criteria:

1. 18 - 80 years, male or female;

2. Clinically diagnosed as acute anterior ischemic stroke, artery occlusion occurred at the terminal of the intracranial carotid artery, T-shaped bifurcation or M1 segment of the middle cerebral artery;

3. Within 24 hours of stroke onset;

4. Eligible for other imaging indications for bridging therapy or direct mechanical thrombectomy:

   ASPECTS ≥6 certified by the latest brain CT imaging; Patients within 6-16 hours after stroke onset should meet the mismatch criteria, which was defined as infarction core volume <70 ml, mismatch ratio ≥1.8 and the ischemic volume > 15 ml (DEFUSE-3 Criteria); or NIHSS score ≥ 10 with infarction -core volume < 31 cm3, or NIHSS score ≥ 20 with infarction core volume ≤ 51 cm3 (DAWN Criteria); Patients within 16-24 hours after stroke onset should meet the mismatch criteria, which was defined as NIHSS score ≥ 10 with infarction-core volume < 31 cm3, or NIHSS score ≥ 20 with infarction-core volume ≤ 51 cm3 (DAWN Criteria);

5. Planned to receive bridging therapy (endovascular therapy after intravenous alteplase) or direct endovascular therapy;

6. Pre-morbid modified Rankin Scale ≤1;

7. 6 ≤ NIHSS ≤ 25 before endovascular therapy;

8. Signed informed consent from subjects or legally authorized representatives

Exclusion Criteria:

1. TMS contraindications include metallic foreign bodies in the head, pacemaker, implantable drug pumps, cochlear implants, etc.
2. Epilepsy or history of epilepsy, intracranial hypertension, tumor and other serious neurological disorders;
3. Midline displacement and brain parenchymal mass effect seen in head CT and other images;
4. Head CT or MRI showed bilateral acute cerebral infarction;
5. CT or MRI showed a large area of infarction (> 1/3 of the area supplied by middle cerebral artery);
6. Evidence of acute intracranial hemorrhage;
7. Before the bridging therapy, other thrombolytic drugs besides alteplase or tenecteplase were used;
8. A history of congenital or acquired hemorrhagic disease, coagulation factor deficiency, or thrombocytopenia disease;
9. After blood pressure control, the systolic blood pressure was still ≥180 mmHg or the diastolic blood pressure was ≥110 mmHg;
10. Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (EGFR) < 60 mL/min;
11. Patients during pregnancy or lactation and within 90 days of planned pregnancy;
12. Patients with severe mental disorders or dementia who can not cooperate with informed consent and follow-up;
13. Patients with malignancy or severe systemic disease and expected survival of less than 90 days;
14. Participants in other clinical intervention studies within 30 days before randomization or who were participating in other clinical intervention studies.

In order to ensure the blind method, the sham stimulation coil was used, which had the same parameters (including location, stimulation frequency, time, etc.) as the LF-rTMS group, and had the same stimulation sound to ensure no effective stimulation, to ensure the blind state is maintained during the test. Investigators and patients who participated in the study treatment or involved in the clinical evaluation of patients were blinded to treatment grouping.