Discussion:
This study represents, to our knowledge, the largest retrospective cohort of pediatric patients with SCD-MMS analyzing the effectiveness and safety of surgical revascularization compared to conservative therapy. After initiation of treatment, no strokes were observed in the ten patients who underwent surgical revascularization, while three of the seven patients who underwent conservative therapy experienced a stroke during the course of the average 7.4 year follow-up despite having less severe cerebral vasculopathy. No significant complications of surgery were observed.
Hankinson et al. examined 12 pediatric SCD-MMS patients who underwent surgical revascularization for an average of 46.8 months follow-up and found no strokes post-operatively and no major surgical complications.9 Only four of the patients were compliant with CTT protocol throughout the study; patients who received conservative treatment only were not included. Greissenhauer et al. examined a similar cohort of 14 pediatric SCD-MMS patients on CTT who underwent surgical revascularization.7 There was one observed stroke in the cohort and a reported 5-fold reduction risk in stroke compared to pre-surgical risk. Our group recently published a systematic review of the literature available on surgical revascularization for children with sickle cell disease and moyamoya syndrome. We found an overall rate of ischemic stroke free survival of 94.3% with only 1.8% intraprocedural complications.2
A study comparing conservative and surgical treatment was published by Yang et al. who examined 15 pediatric SCD-MMS patients.17 Seven patients underwent surgical revascularization and eight patients underwent conservative therapy. The authors observed no strokes in the surgical revascularization group and four strokes in the conservative treatment group with an average follow-up of 11.6 years equating to a 2.3% risk of stroke per year. The results of our study showed very similar results to these studies. We observed a stroke risk of 3.0% per year in SCD-MMS patients undergoing conservative therapy alone and no risk of stroke in patients who underwent surgical revascularization. When considering the differences in average vasculopathy scores and observing a statistically significant difference between the two groups, the evidence of more severe vasculopathy in the surgical group supports the protective nature of the surgery treatment in regards to stroke.
Although our study does not show a statistically significant difference between treatment options, there is a clear trend towards a clinically significant reduction of stroke risk associated with surgical revascularization. By combining our data with published data from the Yang et al. study17 and the Hall et al. study8 (the only studies with similar cohorts of patients and detailed outcomes), the pooled data showed a statistically significant difference (p=0.001) in the stroke rates between the conservative (n=30) and surgical (n=29) groups. Figure 4 shows the difference in survival curves with the surgical group showing superior results.
The major limitations of our study are the lack of statistical power due to small sample size and the lack of equivalent long-term follow-up in the surgical revascularization group. Furthermore, the two treatment groups are not likely to differ only in the surgical therapy due to the retrospective design of the study. A multi-center, retrospective study is currently underway to accrue a larger patient sample in order to better detect a difference in stroke outcome between conservative treatment and surgical revascularization.