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.

New Ways to Detect Pediatric Sickle Cell Retinopathy: A Comprehensive Review

“…For example, improved detection of vascular pathology and its sequellae could be compared to effects of SCD vasculopathy in other organs, such as those appreciated through MRI evaluation of pediatric sickle vasculopathy in pediatric central nervous systems. [27, 80]…”

Sickle cell disease: a natural model of acute and chronic pain

“…Clinical manifestations of SCD include severe acute and chronic pain[6; 46; 51; 59], pulmonary pathology[21; 66], splenic impairment resulting in life-threatening pneumococcal infections[37; 38], strokes resulting in motor and cognitive impairments[15], renal failure[42], vision loss[34], bony infarcts, joint osteonecrosis[36], priapism[3], and leg ulcers. [40] The mean age of death for patients with HbSS disease is 38 for males and 42 for females (55 years for all SCD genotypes).…”

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

“…[3][4][5] Further, the completion of 4 major randomized clinical trials since the 1990s has provided evidenced-based guidelines for primary and secondary stroke prevention in SCD. 6 Survival in children has improved to an extent that the mortality rate is now 0.5 per 100 000 persons. 7 In contrast, survival is lower in adults, with a mortality rate exceeding 2.5 per 100 000 persons.…”