Moyamoya Syndrome Treated with Encephaloduroarteriosynangiosis Followed by Hematopoietic Cell Transplantation in Patients with Sickle Cell Disease

Patients with sickle cell disease (SCD) have a high risk of intracranial large vessel vasculopathy, leading to a proliferation of microvasculature at the base of the brain known as moyamoya syndrome. This confers a high risk of intraventricular hemorrhage and permanent neurologic deficits. Moyamoya syndrome can be treated surgically with a revascularization procedure called encephaloduroarteriosynangiosis (EDAS), which has been shown to decrease but not eliminate the risk of stroke. Hematopoietic cell transplantation (HCT) from a compatible sibling is the most effective way of preventing central nervous system (CNS) complications in SCD patients at risk for CNS events. There have been several reports of patients with SCD and moyamoya syndrome undergoing EDAS successfully; however, there have been no reports of these patients undergoing EDAS followed by HCT. We report six pediatric cases of patients with SCD who developed moyamoya syndrome, all of whom underwent EDAS followed by HCT. All patients underwent EDAS procedure successfully. One patient experienced a stroke less than a month after EDAS. Another patient developed a foot-drop post-EDAS, though imaging did not show any new areas of infarct. All patients underwent HLA-matched sibling-donor HCT. The chronic transfusion therapy was successfully discontinued in the two patients who had been on it prior to treatment. Post-transplant, one patient developed seizures, with imaging consistent with possible infarct; the patient was placed on antiepileptics and has not had subsequent seizures. In all follow-up imaging, there has been no progression of the patients' moyamoya syndrome.Table 1Supplemental Patient DataPatientPresenting Symptoms of Initial CNS EventAge at Diagnosis of Moyamoya SyndromeAge at EDAS ProcedureAge at HCTPost-HCT Complications1Seizures11 years 6 months12 years 2 months12 years 8 monthsSeizure, Possible Left Middle Cerebral Artery Infarct2Visual changes13 years 2 monthsTwo-Step Procedure: 13 years 4 months and 13 years 7 months13 years 9 monthsNone3Seizures2 years 6 months4 years 6 months5 years 6 monthsNone4Left-Sided Hemiparesis3 years6 years 6 months8 years 6 monthsNone5Seizures, Personality Changes7 years 6 monthsTwo-Step Procedure: 8 years 10 months and 8 years 11 months13 yearsNone6Eye pain6 years11 years 9 months13 years 6 monthsNone Open table in a new tab These are the first reported cases of EDAS successfully followed by HCT in patients with SCD and moyamoya syndrome. Five of the six patients had no further CNS events, and all remained neurologically stable, with no progression of their moyamoya syndrome. HCT is the standard of care in patients with SCD at risk for CNS complications, leading to excellent stroke-free survival rates. Patients with moyamoya syndrome and SCD are at high risk of developing CNS complications. Transplant-eligible SCD patients who develop moyamoya syndrome may benefit from EDAS prior to HCT in order to minimize CNS complications. Further investigation by way of an international, multicenter prospective study is needed to determine the long-term outcome and potential benefits of this therapeutic combination.