Molecular and environmental contributors to neurological complications in sickle cell disease

Abstract

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which affected hemoglobin polymerizes under hypoxic conditions resulting in red cell distortion and chronic hemolytic anemia. SCD affects millions of people worldwide, primarily in Sub-Saharan Africa and the Indian subcontinent. Due to vaso-occlusion of sickled red cells within the microvasculature, SCD affects virtually every organ system and causes significant morbidity and early mortality. The neurological complications of SCD are particularly devastating and diverse, ranging from overt stroke to covert cerebral injury, including silent cerebral infarctions and blood vessel tortuosity. However, even individuals without evidence of neuroanatomical changes in brain imaging have evidence of cognitive deficits compared to matched healthy controls likely due to chronic cerebral hypoxemia and neuroinflammation. In this review, we first examined the biological contributors to SCD-related neurological complications and then discussed the equally important socioenvironmental contributors. We then discuss the evidence for neuroprotection from the two primary disease-modifying therapies, chronic monthly blood transfusions and hydroxyurea, and end with several experimental therapies designed to specifically target these complications.

Role of Traditional Stroke Risk Factors Aiding in Prediction of Infarcts in Adult Patients With Sickle Cell Disease

“…Addressing these factors is crucial for a comprehensive approach to managing the SCD‐associated complications. 14 Approximately 25% of the patients with SCD develop stroke by the age of 45 years, 15 which appears as a devastating medical condition that contributes to the morbidity and mortality stemming from SCD. In addition, the majority of adults with SCD will experience a silent cerebral infarction (SCI).…”