Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort

Abstract

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Cré teil newborn SCA cohort (n ‫؍‬ 217 SS/ S␤ 0 ), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigengenoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L ؋ 10 9 /L increase, 95% CI 1.000-1.006; P ‫؍‬ .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P ‫؍‬ .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention. (Blood. 2011;117(4):1130-1140)

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Silent cerebral infarction (SCI) is the most common permanent neurological injury in children and, possibly, adults with SCD [80]. A SCI is not associated with obvious neurological impairment or abnormalities on neurological examination.…”

Transcranial Doppler in children

“…Conditional velocities are more likely to become abnormal when the child is younger and when velocities are close to 200 cm/s [14,30]. In the French cohort, conditional TCD occurred in 58/217 patients and became abnormal in 20/58 patients (34.5% conversion rate).…”

“…Maximum values in children with sickle cell anaemia are recorded at age 3-6 years [14]. Velocities are slightly higher in pubertal girls than in boys [11].…”

“…In Memphis, the stroke rate decreased from 0.46 to 0.18 per 100 person-years after the TCD screening rate reached 99% [25]. In a newborn SCA-cohort of Creteil, France, including 217 SS/Sβ0 thalassaemia patients, early and annually screened with TCD since 1992, the cumulative stroke risk by age 18 was 1.9% (95% CI, 0.6-5.9) [14,26,27]. In Philadelphia, the incidence of overt stroke in the post-TCD period was 0.06 per 100 patient-years, compared with 0.67 per 100 patient-years in the pre-TCD period [28].…”

“…In a French cohort [14], TCD was abnormal in 21% of SCA-patients at a median age of 3.2 years (range, 1.3-8.3). In 44% of these, conditionally abnormal TCD had been observed earlier.…”