Early detection and management of extracranial arteriopathy reduces the incidence of silent cerebral infarcts in sickle cell anemia: a long-term prospective cohort study.

Previous reports about the Creteil newborn cohort (1988/April 2007) showed that the risk of silent cerebral infarcts (SCI) remained high (37.1%) at the age of 14 years in children with sickle cell anemia (SCA) and intracranial time-averaged mean maximum velocity (TAMMV) ≥200 cm/second (s), despite chronic transfusion. Systematic assessment of extracranial internal carotid artery (eICA) since June 2011 revealed that SCI risk is associated with chronic or acute anemia and eICA stenosis. Based on these results, SCA children with eICA TAMMV ≥200 cm/s or eICA stenosis were placed on chronic transfusion and considered for allogeneic stem cell transplantation (alloSCT). SCA children with 160-199 cm/s eICA TAMMV were maintained on hydroxyurea (HU). We hypothesized that detection/management of eICA arteriopathy and wider use of HU could reduce SCI incidence. Comparison between the new cohort (May 2007/December 2014; eICA-assessed before 4 years of age) with wider but not systematic use of HU and the earlier cohort (1988/April 2007; never eICA-assessed until the 2008 update) revealed a significant reduction in SCI risk (Log Rank: P=0.009) associated with eICA assessment but not with wider use of HU. eICA TAMMV ≥160 cm/s, even with no eICA stenosis, was a risk factor for SCI, suggesting that all SCA children with eICA TAMMV ≥160 cm/s should be placed on chronic transfusion. HU initiation at an early age was associated with lower intracranial arteriopathy incidence, but not with lower eICA arteriopathy or SCI incidence. In the overall cohort (1988-2014), including 332 SCA children, all assessed/managed for eICA arteriopathy after 2011, the cumulative SCI incidence by the age of 14 years was 25.0% (95%CI: 19.0-31.0%). SCI risk was associated with being older at first neck magnetic resonance angiography and having high mean corpuscular volume on HU. While the impact of HU on SCI incidence remains unclear, making controlled trials necessary, eICA arteriopathy management by intensive therapy is effective at improving SCI prevention.