The management of MMD includes medical treatment and surgical treatment. Platelet aggregation inhibitors [[i]]or calcium channel blockers [22,[ii]] may generate excellent but transient effects, could be only applied to mild cases [18] or acute phase of stroke [11].Surgical treatment is considered to be the most effective method to treat MMD, especially for MMD, manifesting as a cerebral ischemic symptom [11].However, few studies focus on the surgical treatment of epileptic type MMD, and there is a lack of randomized controlled studies and meta-analysis. Thus, we reviewed the current literature and summarized the efficacy of surgical treatment for epileptic type MMD.
We calculated an overall pooled postoperative incidence of seizure in pediatric patients with epileptic type MMD, which was 23.44%. Most of the patients with epileptic type MMD suffered seizures after surgery could be controlled by anti-epileptic drugs [15,17,18], and only very few patients deteriorated or without improvement after surgery [2,19]. We also calculated the overall pooled postoperative incidence of cerebral infarction in pediatric patients with epileptic type MMD, which was 9.12%. The data suggest that surgical revascularization is a secure intervention for pediatric epileptic type MMD and most treated patients could gain symptom improvement [[iii]].
The risk factors for epilepsy and ischemic event after cerebral revascularization in pediatric patients with epileptic type MMD were various. Age of patients, course of clinical symptoms, and severity of clinical presentations may all affect the prognosis of operation [6,19,20]. Only one study [19] explored the risk factor of seizure recurrence in epileptic type MMD. They identified the duration of epilepsy as an independent risk factor for recurrent seizure after surgery in pediatric patients with epileptic type MMD. Nevertheless, the intervals between onset of clinical symptoms and surgery in our study were not consistent, it is particular important to group analysis by different course in the future. In addition, age less than 1 year and severe abnormal imageological findings correlate with poor prognosis of epileptic type MMD [3], infantile onset and sever clinical manifestations are more likely to have recurrent seizures or cerebral infarction after surgery. In our study, although the age range and angiographic characteristics were not be consistent among the included studies, the pooled rates still showed low heterogeneity. Hence group analysis should be considered according to different ages and severity of clinical presentations in the future.
Most scholars believed that seizure could be associated with ischemia [20]. Among the studies included in our meta-analysis, it is hard to identify whether the preoperative seizures came from ischemia events, due to epilepsy and ischemic event always exist together and has an analogical progression in most of the patients with MMD [16]. Choi et al. [2] reported that surgery could prevent epileptic seizures and obtained more approving clinical outcomes when applied to patients with epileptic type MMD compared to ischemic type MMD, but there were no differences in postoperative neuroimaging and hemodynamic changes between the two groups. Yang et al. [20] didn’t consider the presence of epileptic symptoms before surgery is a risk factor for postoperative epileptic recurrence. The different outcomes between epileptic type and ischemic type need more future studies.
Different operation procedures (indirect, direct, or combined) may affect the prognosis of MMD. Indirect revascularization is widely used in pediatric patients because of its simple procedure and few complications [[iv],[v],[vi]]. Many studies confirmed the effectiveness of this modality. But direct revascularization can improve cerebral blood flow perfusion immediately as its advantage [26,27]. Therefore, more and more surgeons chose combined revascularization to treat patients with MMD [[vii],[viii]], just as most of the included studies [16,17,19,20] in our meta-analysis. However, in our analysis, different modalities didn’t show obvious different postoperative incidences of seizure and cerebral infarction, which was in line with the finding of Ma Y et al.[19], who believed that the surgical modalities would not affect the outcome of the surgery. Further research on the effect of the different operation techniques is needed.
There are many possible causes of postoperative seizure in MMD patients: ischemic events, intracranial hemorrhage, hyperperfusion syndrome, poor scalp healing and infection, surgical procedure [[ix]]. Seldom studies could identify where the postoperative seizure came from. No postoperative hyperperfusion mentioned in the included studies. Only two included studies described the postoperative complications of patients with epileptic type MMD. In the study by Sainte-Rose C, et al.[15], one patient suffered subcutaneous cerebrospinal fluid effusions, and had a single seizure five months postoperatively. Due to such a long interval and no infection occurred, this seizure was unlikely caused by subcut effusion. In the study by Caldarelli M, et al. [18], one patient experienced epidural bleeding during the surgery, and died six months later. This patient presented seizure post operation, but controlled by medication well. It is hard to say whether the seizure was induced by this postoperative complication. But omitting this study won’t change the pooling results in our analysis.
There were several limitations in our study: the numbers of patients and studies were all tiny, and all of these studies were retrospective and nonrandomized. That may because the incidence of epileptic type MMD is relatively low, and few scholars focus on this type of MMD. Follow-up periods were not consistent among individuals, ranging from 0.2 to 25 years, which implies that the observational time of some patients may not be sufficient. Most of the studies didn’t describe the detail of the clinical feature of this type of patients, which results in the difficulty of distinguishing whether ischemic events or other reasons cause the patient’s preoperative and postoperative seizures. In a word, future studies should focus on the epileptic type MMD in large-scale randomized controlled clinical studies.