1076 Background: Sickle cell anemia (SCA) has been associated with impairments in general cognitive functioning as measured by IQ scores and other neurocognitive measures. Children with SCA and overt stroke are the most affected, but those with silent infarcts (SI) on brain magnetic resonance imaging (MRI) also have cognitive impairment. Transcranial doppler ultrasonography (TCD) screening has allowed identification of individuals at high risk for stroke, in whom institution of prophylactic transfusion therapy produces a dramatic reduction in the incidence of primary stroke. Elevated TCD velocities have been reported to predict neurocognitive impairment in patients with SCA. We hypothesize that children with SCA with normal TCD velocities and no overt stroke or SI on brain MRI will have normal cognitive performance when compared with normal-matched controls. We investigated the academic achievement and cognitive function among children with SCA with normal brain MRI and normal TCD velocities, and compared their results with normal age and race matched controls. Methods: School age children with SCA who had normal MRI and TCD exams were evaluated. Controls (classmates and siblings) were matched for race, age, and social-economic status. SCA patients receiving chronic transfusion therapy or with a history of prior overt stroke were not eligible. All participants were followed at Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO). All patients and controls underwent MRI examination (to document the absence of stroke and SI) and cognitive testing. In addition, SCA subjects underwent TCD testing and had hematologic laboratory testing. SCA subjects were not experiencing pain or any other complication during study evaluations. The WISC-III was obtained as a measure of intellectual function, and achievement scores in reading, writing, and arithmetic were used to evaluate school performance. Comparisons among patients and controls were made using the Mann-Whitney test. This study was approved by the HEMORIO Ethics committee and all participants signed informed consent. Results: SCA patients had significantly lower total IQ and academic achievement than healthy controls (Table). Discussion: This is the first report showing cognitive dysfunction in children with SCA with both normal MRI and TCD examination. Early neurocognitive deficits are known to occur in children with SCA. In general, a patient with SCA in Brazil has a low socioeconomic status, low educational level, and poor access to health services, placing these children at higher risk of neurocognitive complications from the disease. Our study shows that children with SCA perform worse on measures of key cognitive function when compared with healthy matched controls, even without evidence of elevated velocities in the main cerebral arterial vessels or radiological insult to the brain. There was a significant difference in total IQ and school achievement among SCA patients and controls; however this was not true for verbal or executive IQ, suggesting that the cognitive compromise in this population is global. Cognitive dysfunction may occur long before lesions are observed on the MRI (ischemic insult) or on the TCD (vasculopathy), underscoring the need for preemptive screening and treatment of cognitive dysfunction in children with SCA. Disclosures: Off Label Use: Hydroxyurea for prevention of neuropsychological changes in SCD.

4623 INTRODUCTION Sickle cell disease (SCD) is the most frequent cause of stroke in children. It is possible that cognitive dysfunction occurs in the absence of identifiable stroke due to silent cerebrovascular disorders. OBJECTIVE To evaluate SCD compromises cognitive functions of patients with no radiological nor clinical evidence of stroke. METHODS Thirty eutrophic children with SCD, with normal neurological examination and imaging (brain CT) and without past cerebrovascular disease were submitted to neuropsychological assessment between 2002 and 2008. The neuropsychological battery included the following tests: WISC-III, BTN (battery of neuropsychological tests, assessing laterality), Rey complex figure (visual perception and memory), and behavioral screening for ADHD, learning disorders and antisocial behavior. RESULTS 66.7% of patients were male. The average age of patients was 9.6 years (6 - 15 years). The mean total IQ was 78.8 (50 - 105) and the executive IQ was 77.9 (47 - 108), both at the borderline limit. The verbal IQ mean was 84.9 (55 - 113), on lower average. Verbal comprehension verbal was on average 87.4 (58 - 115). The results of visual memory was at the lower limit of normal (mean percentile 16 to 18). There was no correlation between the rates of behavior disorders (inattention, hyperactivity, learning difficulties and conduct disturbance) and IQ results. There was no statistically significant difference between the results of males and females or between age groups. 40% of the sample had not developed manual preference. CONCLUSION The subjects of this sample showed significant cognitive impairment in the absence of clinical or radiological evidence of cerebrovascular disease. The study has limitations as the sample size, the imaging technique used and neuropsychological battery comprehensiveness, but the results are quite suggestive of a relationship between SCD and cognitive impairment. The research group is developing a study with a larger sample (100 patients) to clarify the correlations between these findings. This will be important to outline earlier neuroprotective measures, which will provide improvements in neurodevelopment, learning, quality of life and social inclusion. Disclosures: No relevant conflicts of interest to declare.

4614 Brazil is characterized by free miscegenation of populations of African and Mediterranean ancestry. On the basis of surveys and hospital-based series, the Brazilian Ministry of Health has recently estimated that approximately 2 million individuals carry the gene for HbS and nearly 8 thousand people having homozygous SCD. Given the burden of SCD in Brazil, this group of disorders has been declared a public health problem, and a strategy of awareness, diagnosis and prevention of complications is currently ongoing under the auspices of the Brazilian Ministry of Health. OBJECTIVES Standardize TCD examination of children with SCD in three Sickle Cell Units in Brazil, to assess TAMMV in consecutive children with SCD, to allow treatment decisions for such children, based on TCD results and to estimate the prevalence of neurological complications in Brazilian children with SCD (before and after newborn screening). METHODS All of the pediatric patients with SCD from newborn screening, who underwent a TCD examination between 2 and 11 y.o. were included. Consecutive patients seen at three tertiary-care hematology centers (HEMORIO, HEMOPE and HEMOMINAS) made TCD screening, with determination of blood flow-velocity. This study begun in January, 2008. Legal representatives of patients assigned the informed consent TCD procedures followed the technique used in STOP study (Adams et al 1998). Identical equipment and software were used (2-MHz pulsed Doppler- Nicolet EME) in the three Sickle Cell Units and investigators studied transtemporal and transforaminal windows and recorded the highest time-averaged mean of the maximun velocity (TAMMV) in middle cerebral artery (MCA), distal internal carotid artery (ICA), anterior cerebral artery (ACA) and biffurcation (BIF). All TCD studies were performed by one physician of each Sickle Cell Unit (ACC Leite – HEMORIO, C Silva – HEMOMINAS and R Azevedo – HEMOPE). Data were collected and stored in EPIDATA and exported to SPSS for Statistical analysis. RESULTS From January 2008 to July 2009 (18 months) the three centers followed about one thousand children with HbSS or SB-thalassemia, who underwent at least one TCD examination. There is no difference about gender. The mean age of the first TCD was 3.2 yo (HEMOPE), 5.8 (HEMRIO and 6.8 (HEMOMINAS). The main genotype was SS (95%). In the study of acute preliminary event there was high prevalence of acute chest syndrome and dactilitis in the three hemocenters and statisitical significant correlation between ACS and dactilitis versus abnormal TCD. The principal compromised artery was media cerebral (MCA). When we performed MRA and MRI in patients with abnormal TCD we found significant number of silent infarcts. CONCLUSIONS TCD screening has had a substantial impact to prevent primary stroke in SCD patients. The transfusions were efficacious but discontinuation resulted in new events. Long term therapy is needed (HU?). In patients with conditional TCD and comorbidities (ACS and dactilitis) the risk to develop stroke is higher than in patients with normal TCD and then, the use of hydroxiurea should be considered. The patient number of inadequate TCD is still significant. Since the cost of MRI in Brazil is high we suggest TCD imaging as screening if suspect of severe arterial disease. Disclosures: No relevant conflicts of interest to declare.