This is a multicenter, open-label, evaluator-blinded, investigator-initiated, randomized clinical trial, to evaluate the clinical efficacy and safety of LF-rTMS in reducing infarct size, reducing disability rate and improving functional outcome in patients with acute ischemic stroke within 48 hours after stroke onset.

The target population of this study was patients with clinically diagnosed AIS who had an acute occlusion of the responsible vessel in the anterior circulation and were not scheduled for intravenous thrombolysis and/or endovascular therapy, the time from stroke onset to the start of study intervention was less than 48-hours.

Enrolled patients were randomly assigned in a 1:1 ratio to either the"LF-rTMS group" or the"Control group" to receive:

1. LF-rTMS group: H 4 Coil (stimulation site: prefrontal cortex, insular lobe),1-Hz rTMS, stimulation intensity RMT 100%,1200 pulses/session, two sessions (2400 pulses)/day (interval ≥2 hours), lasting about half an hour each time, the total duration of treatment was 3 days (6 sessions,7200 pulses).
2. Control group: received routine treatment.

All the above therapeutic interventions were conducted by trained TMS operators. Except for the study intervention, the subjects in both groups received clinical routine diagnosis and treatment which were not affected by the intervention.

All patients were followed up until the 90th day after randomization to evaluate the clinical efficacy and safety of LF-rTMS in reducing infarct size, reducing disability rate and improving functional outcome in patients with acute ischemic stroke within 48 hours after stroke onset.

Inclusion Criteria:

1. Age 18-80 years, gender is not limited;
2. Acute ischemic stroke of anterior circulation was diagnosed clinically
3. mRS 0-1 score before onset;
4. 6 ≤ NIHSS ≤25 at randomization;
5. Within 48 hours of stroke onset;
6. No thrombolysis therapy or thrombectomy is planned;
7. Obtain informed consent signed by the patient himself or by his legal authorized representative.

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, brainstem infarction, or insular infarction;
5. Evidence of acute intracranial hemorrhage;
6. A history of congenital or acquired hemorrhagic disease, coagulation factor deficiency, or thrombocytopenia disease;
7. After blood pressure control, the systolic blood pressure was still ≥180 mmHg or the diastolic blood pressure was ≥110 mmHg;
8. Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (EGFR) < 60 mL/min;
9. Patients during pregnancy or lactation and within 90 days of planned pregnancy;
10. Patients with severe mental disorders or dementia who can not cooperate with informed consent and follow-up;
11. Patients with malignancy or severe systemic disease and expected survival of less than 90 days;
12. Participants in other clinical intervention studies within 30 days before randomization or who were participating in other clinical intervention studies.

The investigators involved in the clinical evaluation of the patients remained blinded to treatment grouping.