Evolution of Extracranial Internal Carotid Artery Disease in Children With Sickle Cell Anemia

Abstract

Background: Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. Methods: Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. Results: Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1–9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT ( P =0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and −0.18 (0.55) with CTT ( P =0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. Conclusions: Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.

Incidence, kinetics, and risk factors for intra- and extracranial cerebral arteriopathies in a newborn sickle cell disease cohort early assessed by transcranial and cervical color Doppler ultrasound

“…Thus, the authors suggested that systematic detection of extracranial stenosis may have limited clinical utility in patients with SCD ( 27 ). However, Verlhac et al ( 28 ) recently reported in the Debré, Paris, cohort the presence of eICA stenosis in 48 children with SCA, of whom eight had a history of stroke; importantly, five of eight had isolated eICA stenosis, confirming the clinical utility to systematically assess the extracranial part of the internal carotid artery.…”

Stroke without cerebral arteriopathy in sickle cell disease children: causes and treatment

“…Overt stroke is mainly related to chronic stenosis and occlusion of large cerebral arteries in the anterior circulation resulting from intimal thickening 4,5 , described as cerebral arteriopathy related to SCD (SCD-CA). The internal carotid, including its extracranial part 6 , middle cerebral, and anterior cerebral arteries are often involved in ischemic stroke 7,8 and up to 71% of SCA patients with a history of overt stroke have been reported to have large-vessel arteriopathy in the anterior circulation territories 9 . Without secondary prevention based on a long-term transfusion program, the recurrence rate after a first ischemic stroke is very high, reaching 67% for a mean observation time of 9 years in Powars study, with 50% of the events occurring within 2 years after the initial event 10 .…”

Analysis of structural effects of sickle cell disease on brain vasculature of mice using three-dimensional quantitative phase imaging

“… 1 These imaging modalities can provide a broad view of patients’ symptoms and can help localize strokes and ischemia; however, they lack critical histology-grade information that can lead to a better understanding of the underlying mechanisms of blood cell adhesion, stroke, and more. 5 – 10 Recently, optical imaging methods have been employed; these methods have the advantage of providing higher spatial resolution to view these tissue structures in greater detail. Studies have used fluorescence-based methods to study, for instance, the interactions between brain endothelial cells and RBCs exposed to oxidative stress in vitro 11 or to monitor SCD treatments in vivo using a dorsal skin-fold window chamber model.…”