Moyamoya Syndrome in Children with Sickle Cell Disease: A 10-Year Single-Center Experience

Background: Moyamoya syndrome (MMS) is a relatively uncommon vascular complication of sickle cell disease (SCD) characterized by progressive stenosis of the supraclinoid carotid arteries and development of typical collaterals. MMS confers a significant lifetime risk of ischemic stroke, and frequently results in multiple cerebrovascular events leading to poor outcomes. Management of MMS in this population is challenging, and to date no clinical trials have evaluated the long-term neurologic outcome of treatment with chronic transfusion versus surgical intervention [Encephaloduroarteriosynangiosis (EDAS) or Encephalomyoarteriosynangiosis (EMAS)]. Determination of efficacy and safety of various interventions and information about long-term progression could guide treatment decisions and potentially support the establishment of treatment guidelines. We report clinical and radiographic characteristics and neurological outcomes in children with SCD and MMS treated at our center over the last 10 years.

Methods: We conducted a retrospective chart review of all patients with SCD who were diagnosed with MMS at our center from 2006 to 2016. Cases were identified utilizing radiology data mining software (MONTAGE^TM Search and Analytics). The radiological images and reports of potential MMS cases were independently reviewed by a hematologist, a radiologist and a neurologist to confirm the diagnosis of MMS. Relevant clinical data were collected and summarized using descriptive statistics.

Results: During the study period, 542 unique patients with SCD required neuroimaging at our institution. Indications for neuroimaging included concerns for stroke, abnormal TCD, headaches or follow up imaging. Out of the 542 patients, 23 patients (4%) [18 males] were diagnosed with MMS. The median age at time of diagnosis of MMS was 6 years [Interquartile range (IQR) 4-8]. The genotype was SS in 20 patients, S-beta⁰ thalassemia in 2, and SC in 1. Of the 23 patients with MMS, 16 patients (70%) were diagnosed with MMS after initially presenting with a clinically overt ischemic stroke, while 7 patients (30%) were diagnosed following an abnormal or conditional surveillance Transcranial Doppler (TCD) study. MMS was bilateral in 16 patients (70%) and unilateral in the remaining 7 patients (30%). Prior to diagnosis, baseline laboratory values were (median and IQR): hemoglobin (Hb) 7.5 g/dL [IQR 6.7-8]; absolute reticulocyte count 333 k/mL [IQR 227-414]; white blood cell count 14.6 k/mL [IQR 12-18]; platelet count 371 k/mL [IQR 282-424]; total bilirubin 3.25 mg/dL [ IQR 2-4.45]; lactate dehydrogenase 522 u/L [IQR 426-862]; and HbF 6.6% [IQR 3.4-17.1]. Of the 16 patients who presented with clinically overt ischemic stroke, 11 patients (69%) experienced recurrent ischemic events (mean 2 strokes/patient). After diagnosis of MMS, 19/23 patients (82%) were started on chronic monthly transfusions aimed at maintaining HbS level below 30%. Nine patients (39%) were treated with indirect surgical revascularization procedure performed at a median of 17 months [IQR3.5-36] after MMS diagnosis. Two patients received matched sibling bone marrow transplantation. Two patients died after suffering a massive stroke.

Conclusion: Children with SCD who develop MMS are at significant risk of recurrent strokes and poor neurologic outcomes. Optimal management remains unclear but should include consideration for urgent surgical revascularization procedures. The most effective treatment as well as the optimal time for revascularization procedure should be addressed by a large multi-center trial. Future studies should also evaluate mechanisms underlying MMS.