Efficacy and Safety of Ischemic Preconditioning Therapy Versus Optimal Medical Therapy in Reducing the Recurrence of Ischemic Events in Symptomatic Moyamoya Disease

This clinical trial aims to investigate whether remote ischemic conditioning (RIC) can reduce the risk of cerebral ischemic events, delay clinical progression, and improve long-term outcomes in patients with symptomatic Moyamoya disease (Moyamoya syndrome). The primary research questions include: Does RIC lower the incidence of cerebral ischemic events (e.g., stroke, transient ischemic attack) compared to standard care? Does RIC slow disease progression, as measured by neuroimaging markers (e.g., cerebral blood flow, collateral vessel development) and clinical assessments? Does RIC improve long-term functional outcomes (e.g., modified Rankin Scale, quality of life) in this patient population? Study Design This is a multicenter, prospective, double-blind, randomized controlled trial (RCT). Eligible participants who provide informed consent and complete baseline evaluations will be dynamically randomized (1:1) via a central randomization system using the minimization method to either the intervention group or the control group. Intervention Group: Patients will receive RIC therapy (using an automated device) in addition to optimal medical treatment (OMT). RIC will be administered twice daily for 6 months, with each session consisting of 5 cycles of bilateral upper-limb cuff inflation (5 min at a preset high pressure) followed by deflation (5 min), totaling \~45 min per session. OMT includes antiplatelet agents, antihypertensives, antidiabetics, and lipid-lowering drugs as clinically indicated. Control Group: Patients will receive a sham RIC procedure (using the same device but with cuffs inflated to a fixed low pressure of 60 mmHg) alongside identical OMT. The frequency, duration, and cycling protocol will match those of the intervention group.

Inclusion Criteria: 1. The patient is aged between 18 and 70 years old; 2. There is evidence from MRA, CTA or DSA, and the patient is professionally diagnosed with moyamoya disease or moyamoya syndrome; 3. The patient has ischemic symptoms related to moyamoya vasculopathy, including transient ischemic attack (TIA) and cerebral infarction (limb weakness, hemiplegia, paresthesia, speech disorder, etc. The symptoms may recur in the unilateral limb, or progress to bilateral attacks or alternating bilateral attacks); 4. After clinical evaluation, non-surgical treatment strategies such as drug therapy and risk factor management are planned to be adopted currently, and the patient is not planned to undergo cerebral blood flow revascularization within 6 months after randomization during screening; 5. The patient has signed the informed consent form. Exclusion Criteria: 1. History of intracranial hemorrhage (such as subarachnoid hemorrhage, cerebral parenchymal hemorrhage and intraventricular hemorrhage) and other cerebrovascular diseases (such as intracranial aneurysm, cerebral arteriovenous malformation, arteriovenous fistula, etc.); 2. History of brain tumor, severe craniocerebral trauma, encephalitis, meningitis and other central nervous system inflammatory diseases, or other major craniocerebral diseases, any form of invasive brain treatment history and radiotherapy history; 3. Presence of severe or uncontrolled systemic diseases, or vital organ dysfunction that the investigator judges may significantly increase the subject's research risk or affect the completion of follow-up, including but not limited to severe cardiac insufficiency (ejection fraction \ 2 times the upper limit of normal value), severe renal insufficiency (such as serum creatinine \> 3 mg/dL), severe or uncontrolled respiratory diseases, severe non-cardiovascular comorbidities with expected survival time \180 mmHg and/or diastolic blood pressure \>110 mmHg after drug treatment; 6. Severe hemostatic disorder or severe coagulation dysfunction; 7. Contraindications to RIC treatment: (1) Combined with upper extremity peripheral vascular disease or those judged by the investigator to be unsuitable for upper arm cuff compression, especially vascular lesions that may increase the risk of upper extremity ischemia, including known moderate to severe stenosis or occlusion of the subclavian artery, axillary artery, brachial artery, radial artery or ulnar artery, subclavian steal syndrome, and obvious symptoms of upper extremity ischemia; (2) There are local upper extremity conditions that may affect the safe implementation of RIC, including severe skin or soft tissue infection, skin breakage, unhealed wounds, recent upper extremity trauma or fracture, obvious hematoma, severe edema or lymphedema, arteriovenous fistula or hemodialysis access, PICC or other vascular access not suitable for compression, recent upper extremity deep vein thrombosis or thrombophlebitis, etc.; (3) Known history of allergy to RIC equipment or its constituent materials 8. Patients who refuse follow-up or cannot communicate due to severe mental illness; 9. Unfit for taVNS wearing due to skin breakage, infection, redness and swelling at the wearing site; 10. Pregnant and lying-in women; 11. Participate in other studies at the same period.