title: Central nervous system complications and management in sickle cell disease.
abstract: With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention.
authors.affiliation: Department of Pediatrics and Medicine, Division of Hematology/Oncology, and Vanderbilt-Meharry Sickle Cell Center for Excellence, Vanderbilt University School of Medicine, Nashville, TN; and.
authors.forename: Michael R
authors.identifier: http://orcid.org/0000-0002-0574-1604
authors.initials: MR
authors.lastname: DeBaun
authors.affiliation: Developmental Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Fenella J
authors.identifier: http://orcid.org/0000-0002-2443-7958
authors.initials: FJ
authors.lastname: Kirkham
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000150:complications / Q000628:therapy*; D020520:Brain Infarction / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002908:Chronic Disease; D020773:Headache Disorders / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male