Abstract
Sickle cell disease (SCD) is a chronic hemoglobinopathy characterized by recurrent vaso-occlusive events and significant neurological morbidity. While ischemic and hemorrhagic strokes are well-known complications, reversible diffusion-restricting white matter lesions are exceedingly rare and underreported. We present the case of an 18-year-old male with homozygous SCD (HbSS) who developed acute neurological deterioration during a vaso-occlusive pain crisis. MRI revealed symmetric areas of restricted diffusion and FLAIR hyperintensities in the splenium of the corpus callosum and periventricular white matter, typically associated with cytotoxic edema and irreversible injury. Remarkably, the patient experienced near-complete neurological recovery with aggressive disease-targeted therapy, including hydroxyurea, voxelotor, and serial exchange transfusions. Follow-up MRI at 4 months showed complete resolution of the prior abnormalities. This case underscores the importance of recognizing potentially reversible diffusion-restricting lesions in SCD and challenges the conventional interpretation of restricted diffusion as a marker of permanent injury. Early recognition, comprehensive management, and serial neuroimaging may improve neurological outcomes in similar cases. Clinicians should maintain a high index of suspicion for reversible white matter injury when evaluating patients with sickle cell disease presenting with acute neurological symptoms. Incorporating serial neuroimaging and a multidisciplinary treatment approach is essential for timely diagnosis and optimizing neurological recovery in this vulnerable population.