Takeuchi first described the clinical features of moyamoya disease in 1957. Suzuki and Takaku named it MMD by examining the imaging features of MMD in 1969 (6). MMD was discovered more than 60 years ago, but its etiology remains unclear. Due to this, there are no definite and effective treatments that can stabilize or reverse MMD, let alone prevent its occurrence (10, 12, 16). Ischemic MMD is most common in children and can be classified into TIA and cerebral infarction, which based on the duration of the ischemic attack and the presence or absence of imaging changes (14, 17).
Variations in clinical manifestations may be related to the location of the ischemic attack. Ischemia of the left cerebral hemisphere may result in aphasia, while ischemia near the motor and sensory areas leads to limb hemiplegia or numbness and fatigue. Patients with hemiplegia are the most common in patients with cerebral infarction, limb weakness is more common present in pediatric with TIA. According to the follow-up of these cases, some patients had both TIA and cerebral infarction, and TIA occurred first and forebrain infarction later, suggesting a correlation between progression and transformation. The relevant literature documented that crying will cause children to hyperventilate, resulting in vasospasm and cerebral ischemia (13, 18). However, no correlation analysis between precipitating factors and ischemic attacks in children with ischemic MMD. There were obvious predisposing factors for ischemic attacks in 74.1% of children with MMD. Previous studies suggest that the cerebral infarction and frequent TIAs may be an indicator of the instability of cerebral hemodynamics condition in both adult and pediatric patients (19, 20). And speculated the rate of ischemic attacks in patients with MMD may be associated with the reduced ability of patients to cope with external stimuli after long-term vascular stenosis and reduced cerebral vascular reserve function. Vascular ischemia can occur when external factors affect vasomotor function (21). The most common predisposing factor was fever, accounting for 41.3% (26/63) of all predisposing factors. In comparing the differences in the predisposing factors between the TIA and cerebral infarction, fever was the main predisposing factor. In addition to affecting brain tissue metabolism, fever may also affect the invisible evaporation of water and lead to a reduction in blood volume, thereby causing irreversible cerebral ischemia. In TIA type of MMD, hyperventilation is often triggered by crying and irritating food. This may be due to a short period of ischemic attack following the quick removal of the underlying cause. Importantly, crying was identified to be independent risk factors for inducing TIA in pediatrics with ischemic MMD, which indicated that TIA can be effectively reduced by avoiding crying. In this study, vigorous exercise, diarrhea, and cold stimulation were identified as the predisposing factors for ischemic events occurred in pediatrics with ischemic MMD, although these factors without significantly difference between cerebral infarction and TIA. But the diarrhea may be directly related to hypovolemia, the vigorous exercise can cause the hyperventilation and hypovolemia, and cold stimulation can stimulate vasospasm which are associated with the cerebral ischemia attack. Moreover, we also found that the stress and lack of sleep trigger the cerebral ischemia attack in adult rather than pediatric in clinical. In the perioperative management of MMD, hemodynamic changes caused by these predisposing factors are mentioned, such as maintaining normal body temperature, normal partial pressure of carbon dioxide, and normal blood volume(10, 19, 20).
Previous studies have found some significant factors, such as younger age, higher Suzuki grade and frequent TIA before surgery and posterior circulation artery (PCA) involvement was associated with the postoperative cerebral ischemic complication(11, 13, 20, 22). In our study, we found that pediatric MMD patients with younger age and posterior circulation artery (PCA) involvement were more likely to present with infarction at diagnosis. These results indicated that younger age and PCA involvement were the important factors in the cause of hemodynamic instability in MMD.
Therefore, by analyzing the predisposing factors for ischemic events in children and clarifying the correlation between each predisposing factor and each subtype of an ischemic event, they may be able to guide patients to avoid the occurrence of predisposing factors. Managing inducing factors can reduce the incidence of ischemic events and assist in guiding during the perioperative period. In addition, it could be used as a reference for treatment and it might be possible to prevent ischemic attacks before a patient undergoes surgery or before the blood supply has improved sufficiently after surgery. Thus, we hope that reduce cerebral ischemic attack by avoiding these inducing factors, and provide guidance for perioperative management of MMD.
This study has some limitations. Firstly, we only focused the pediatric patients in this study. The patterns of inducing factors in adults could be different. Second, this is a retrospective analysis, and further prospective and case-validation analyses are needed to provide a more accurate reference for clinical diagnosis and treatment. Thirdly, this is a study based on a single center of a tertiary hospital, selection bias is unavoidable.