Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia

Abstract

Key Points• Baseline hemoglobin levels lower than 7 g/dL, acute anemia, and extracranial internal carotid stenosis are significant and independent risk factors for SCI in SCA.Early transcranial Doppler (TCD) screening of the Créteil sickle cell anemia (SCA)-newborn cohort, and rapid initiation of transfusion programs, resulted in successful prevention of overt strokes, but a high cumulative risk of silent cerebral infarcts (SCI) remained, suggesting that TCD screening does not identify all patients with SCA at risk for SCI. We hypothesized that episodes of hypoperfusion/hypoxia, as observed during acute chest syndromes or acute anemic events (AAE), and extracranial internal carotid artery (eICA) stenoses, detectable via submandibular Doppler sonography and cervical magnetic resonance angiography (MRA), could also be risk factors for SCI. This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is a highly significant predictive risk factor for SCI (hazard ratio, 2.97; 95% CI, 1.43-6.17; P 5 .004). Furthermore, we show that AAE rate (odds ratio, 2.64 per unit increase; 95% CI, 1.09-6.38; P 5 .031) and isolated eICA stenosis (odds ratio, 3.19; 95% CI, 1.18-8.70; P 5 .023) are significant and independent risk factors for SCI. (Blood. 2015;125(10):1653-1661

Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease

“…The prevalence of WMCs in our cohort of adults (49%) was higher than that reported for cohorts of children, 8,15,20,[24][25][26][27] but it was highly consistent with the findings of a recent study reporting a prevalence of silent infarcts of 53% in a cohort of adult patients with SCD with a median age of 30 years. 28 However, caution is required when studies are compared directly because of differences among studies in definitions; brain imaging techniques; and population characteristics, particularly concerning cerebrovascular history.…”

“…28 However, caution is required when studies are compared directly because of differences among studies in definitions; brain imaging techniques; and population characteristics, particularly concerning cerebrovascular history. A steady increase in the prevalence of brain lesions with age was clearly demonstrated in children, in a recent study by Bernaudin et al 24 The cumulative risk of silent cerebral infarcts was found to increase from 19.2% at age 8 years, to 32.4% at age 14 years and 39.1% at age 18 years. In our study, the most common location of WMCs was the frontal area, and half of the patients had focal lesions only, which were consistent with findings with pediatric cohorts.…”

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography

“…The etiology of SCI is complex and likely multifactorial (Debaun, Derdeyn, & McKinstry, 2006;Dowling, Quinn, Rogers, & Buchanan, 2010), but recent research has proposed a strong association with tissue-level hypoperfusion (Bernaudin et al, 2015). As such, the lack of relationship between SCI and TCD measurements potentially arises from an inability to detect changes in tissue-level cerebral blood flow (CBF) using TCD measures of BFV MCA .…”

Anemia and ischemia: how low can you go?

“…1 SCIs refer to permanent brain lesions, usually small, that do not produce obvious focal neurologic deficits. These smaller strokes are often not "silent" and can cause neurocognitive impairment and poor academic performance, as well as portend overt stroke.…”

“…Bernaudin et al hypothesized that common clinical complications associated with hypoperfusion and hypoxemia, such as AAEs and acute chest syndrome, as well as extracranial ICA stenosis, were associated with SCIs. 1 Recall, the risk for overt stroke is routinely assessed in SCA by ultrasonography of intracranial arteries. The study population was a contemporary (1992-2010) and aggressively treated cohort of children with SCA followed longitudinally by magnetic resonance imaging and angiography.…”