The current state of cerebral complications of sickle cell disease.

Cerebral complications are among the most devastating manifestations of sickle cell disease (SCD), affecting children and adults with a spectrum that includes overt ischemic and hemorrhagic stroke, silent cerebral infarcts, vasculopathy, and long-term neurocognitive impairment. Advances in screening, primary and secondary stroke prevention, and acute stroke care have reduced risk for some patients, yet cerebrovascular injury remains common and likely underdiagnosed. The pathophysiology of cerebral injury in SCD is multifactorial, resulting from chronic hemolytic anemia, vaso-occlusion, large- and small-vessel vasculopathy, endothelial dysfunction, inflammation, and altered cerebral hemodynamics. Emerging data suggest stabilization or reduced incidence of new infarcts and preservation of neurocognitive function after successful hematopoietic cell transplantation (HCT), although some neurodevelopmental deficits may persist. This review synthesizes contemporary epidemiology, pathophysiology, diagnostic strategies, prevention and treatment, in the context of HCT. Key gaps for future research include optimizing screening strategies, quantifying neurocognitive benefit of curative therapy, and improving access to prevention in resource-limited settings.