Cerebral infarction is a major contributor to childhood morbidity and mortality in sickle cell anemia (SCA). We propose a prospective study aimed at the early detection and treatment of cerebral vascular disease prior to irreversible brain injury in young children with SCA. We will test the hypotheses that these subjects experience a variable period of asymptomatic progressive CNS vasculopathy prior to cerebral infarction; that pre-infarct CNS vasculopathy can be identified by non-invasive imaging techniques:MRI, magnetic resonance angiography (MRA), and transcranial Doppler (TCD); and that therapeutic intervention at this stage of the disease can significantly reduce the subsequent occurrence of cerebral infarction. MRI, MRA, TCD, and standardized neurologic and psychometric examinations will be performed yearly in a cohort of homozygous Hb SS children enrolled at 2-4 years of age. Subjects without MRI evidence of cerebral infarction who have significant cerebral vasculopathy (cerebral arterial stenosis on MRA and/or elevated blood flow velocity on TCD) will be randomized to receive either no therapy or chronic transfusion therapy, in order to determine the risk of subsequent cerebral infarction in untreated subjects with these abnormalities, and the extent to which transfusion therapy can significantly reduce the risk. Subjects with evidence of prior cerebral infarction on MRI, whether symptomatic or asymptomatic, will be randomized to receive either chronic transfusion therapy alone (""""""""standard therapy"""""""") or chronic transfusion therapy plus ticlopidine, in order to determine whether ticlopidine can significantly increase the efficacy of standard therapy in preventing recurrent cerebral infarction in SCA. Subjects with prior cerebral infarction will also be offered the option of bone marrow transplantation if an HLA-identical non-SS sibling donor is available.
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