Abstract
Background Silent infarcts are associated with impaired cognitive functioning and have been shown to be predictors of stroke (Miller ST J Pediatr 2001). Until now, reported risk factors for silent infarcts were low pain event rate, history of seizures, high leukocyte count and Sen bS haplotype (Kinney TR Pediatrics 1999). Here, we seek to define the prevalence and risk factors of silent infarcts in the Créteil SCA pediatric cohort comprising patients assessed at least yearly by transcranial doppler (TCD) since 1992, and by MRI/MRA.
Methods This study retrospectively analyzed data from the Créteil cohort stroke-free SS/Sb0 children (280; 134 F, 146 M), according to institutional review board. Time-averaged mean of maximum velocities higher than 200 cm/sec were considered as abnormal, resulting in initiation of a transfusion program (TP). A switch to hydroxyurea was proposed to patients with normalized velocities (< 170 cm/sec) and normal MRA on TP, although TP was re-initiated in case of abnormal velocities recurrence. Patients with “conditional” velocities (170–199 cm/sec) were assessed by TCD 4 times yearly. Alpha genes and beta-globin haplotypes were determined. Baseline biological parameters (G6PD activity; WBC, PMN, Reticulocytes, Platelets counts; Hemoglobin, Hematocrit, HbF, LDH levels; MCV; SpO2) were obtained a minimum of 3 months away from a transfusion, one month from a painful episode, after 12 months of age, before the first TCD, and always before therapy intensification.
Results. Patients were followed for a total of 2139 patient-years. Alpha-Thal was present in 114/254 patients (45%) and 27/241 (11.2%) had G6PD deficiency. Beta genotype, available in 240 patients, was BaBa in 102 (42.5%), BeBe in 54 (22.5%), SeSe in 19 (7.9%) and “other” in 65 (27.1%); TCD was abnormal in 52 of 280 patients (18.6%). MRA showed stenoses in 30 of 226 evaluated patients (13.3%) while MRI demonstrated presence of silent infarcts in 81/280 patients (28.9%). Abnormal TCD (p<0.001), G6PD deficiency (p=0.008), high LDH (p=0.03), and low Hb (p=0.026) were significant risk factors for stenoses by univariate analysis while multivariate analysis retained only abnormal TCD as a significant risk factor for stenoses ([OR= 10.6, 95% CI (4.6–24.4)]; p<0.001). Univariate logistic regression analysis showed that the risk of silent infarcts was not related to alpha-Thal, beta genotype, abnormal TCD, WBC, PMN, platelets, reticulocyte counts, MCV, LDH level, HbF %, pain or ACS rates but was significantly associated with stenoses detected by MRA (p<0.001), gender (male; p=0.04), G6PD deficiency (p=0.05), low Hb (p=0.016) and Hct (p=0.012). Multivariate logistic regression analysis showed that gender ([OR= 2.1, 95% CI (1.03–4.27)]; p=0.042), low Hb ([OR= 1.4, 95% CI (1.0–1.1)]; p=0.05) and stenoses ([OR= 4.8, 95% CI (1.88–12.28)]; p=0.001) were all significant independent risk factors for silent infarcts. The presence of stenoses was the only significant risk factor for silent infarcts in patients with a history of abnormal TCD ([OR= 5.9, 95% CI (1.6–21.7)]; p=0.008).
Conclusion We recently showed that G6PD deficiency, absence of alpha-Thal, and hemolysis are independent significant risk factors for abnormal TCD in stroke-free SCA patients (Bernaudin et al, Blood, 2008, in press). Here, we report that an abnormal TCD is the most significant risk factor for stenoses and, expanding previous studies, we demonstrate that stenoses, low Hb and gender are significant independent risk factors for silent infarcts.
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