Evaluating Antiplatelet and Physical Therapy for Slowing Progression in Mild Moyamoya Disease.

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease characterized by progressive stenosis or occlusion at the terminal portion of the internal carotid artery, with formation of an abnormal vascular network at the base of the brain. Moyamoya syndrome (MMS) has the same cerebrovascular imaging and clinical manifestations as moyamoya disease, but it is accompanied by other systemic comorbidities. Moyamoya disease and moyamoya syndrome are collectively referred to as moyamoya-like cerebrovascular disease. They are highly prevalent in East Asia, and China has a large patient population. In 2018, the incidence was 1.6 per 100,000 person-years, and the disease is a major cause of stroke in children, adolescents, and young adults [1]. This group of diseases often causes severe complications such as stroke and cognitive impairment, leading to poor prognosis and reduced ability to live independently [2]. Among patients who do not receive effective treatment, the risk of severe neurological deficit or death is as high as 75%, and approximately 60% of patients with moyamoya disease develop cognitive impairment [3]. Therefore, moyamoya disease (moyamoya syndrome) is a major health problem that seriously affects the health of the Chinese population.

At present, several urgent problems remain in the clinical diagnosis and treatment of moyamoya disease (moyamoya syndrome). First, the epidemiological characteristics and disease susceptibility of this condition in the Chinese population are not yet fully clear. Second, reliable clinical assessment tools and standardized risk prediction models for moyamoya disease are lacking, and there is still no clear basis for identifying which patients need timely intervention. Third, a systematic precision treatment pathway for moyamoya disease has not yet been established, and high-quality evidence is still lacking regarding the role of pharmacological and physical therapy in delaying disease progression. Therefore, systematic research to clarify the efficacy of different treatment approaches in moyamoya disease is of great significance for promoting the establishment of an integrated diagnostic and therapeutic system for this disease.

[Add a paragraph introducing ischemic conditioning and its role in stroke and MMD.] Systematic treatment is an important means to improve the prognosis of moyamoya disease. Current major treatment options include revascularization surgery and pharmacological therapy. Previous studies have shown that revascularization surgery can improve cerebral blood flow and reduce the risk of stroke; however, for asymptomatic or early-stage patients, surgery is not the only option [4]. In terms of pharmacological therapy, nonsurgical treatments such as antiplatelet therapy and intensive lipid-lowering therapy may delay disease progression, but high-quality clinical evidence remains lacking. In addition, emerging physical therapies such as ischemic conditioning have been shown to improve the tolerance of brain tissue to ischemia and have demonstrated potential therapeutic value in patients with stroke [5]. However, the safety and efficacy of these treatment approaches in patients with moyamoya disease require further study and validation.

Therefore, this study proposes to conduct a multicenter, prospective randomized controlled clinical trial to systematically evaluate the efficacy and safety of aspirin therapy and ischemic conditioning therapy in delaying the progression of moyamoya disease, and to provide evidence-based support for nonsurgical treatment strategies for patients with moyamoya disease.

[The following content was moved from the study rationale section and should be integrated with the research background.] Even when patients with moyamoya disease (moyamoya syndrome) have not yet developed definite symptoms of cerebral infarction, their cerebral hemodynamics may already be in a compensated or critical state. They are often prone to nonspecific symptoms such as headache and dizziness, subjective cognitive decline, and TIA attacks, and they have a potential risk of progression to symptomatic stroke. Microembolus formation and vascular endothelial dysfunction may further reduce flow reserve and aggravate hypoperfusion, thereby leading to adverse events. For such mildly affected patients, early intervention has important clinical value for delaying disease progression and preventing cerebrovascular events.

Aspirin irreversibly inhibits cyclooxygenase-1 and blocks thromboxane A2 production, thereby inhibiting platelet aggregation. In the pathological process of moyamoya disease (moyamoya syndrome), microcirculatory changes and vascular intimal injury may activate platelets and promote microthrombus formation, which may aggravate ischemia-induced stroke. Therefore, aspirin may reduce the risk of ischemic events by inhibiting platelet aggregation. Ischemic conditioning is a noninvasive physical therapy that activates systemic endogenous protect