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

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.

Extracranial carotid arteriopathy in stroke-free children with sickle cell anemia: detection by submandibular Doppler sonography.

BACKGROUND: Cerebral vasculopathy is a serious complication of sickle cell anemia. Overt strokes are largely due to intracranial arteriopathy, detected by routine transcranial Doppler and largely prevented through chronic transfusions. As extracranial internal carotid artery arteriopathy was considered rare, it has not been routinely assessed in sickle cell anemia. Recent cases of overt strokes associated with stenosis/occlusion of the extracranial portion of the internal carotid artery prompted us to include extracranial internal carotid artery assessment to our transcranial Doppler sonography protocol. OBJECTIVE: The aim of the study was to perform a cross-sectional study in children with sickle cell anemia to evaluate Doppler flow patterns of the extracranial internal carotid arteries and to assess potential associated factors. MATERIALS AND METHODS: Between June 2011 and April 2012, 435 consecutive stroke-free children with sickle cell anemia (200/235 M/F, median age: 7.9 years) were assessed for extracranial internal carotid artery using a 2-MHz transcranial Doppler sonography probe via a submandibular window during routine transcranial Doppler sonography visits. The course of both extracranial internal carotid artery was assessed by color Doppler mapping, and the highest flow velocity was recorded after insonation of the entire length of the artery and analyzed. Intra- and extracranial MR angiographies were available in 104/435 subjects for comparison. RESULTS: Mean (SD) extracranial internal carotid artery time-averaged mean of maximum velocity was 96 (40) cm/s. Extracranial internal carotid artery tortuosities were echo-detected in 25% cases and were more frequent in boys (33% vs.18%; P < 0.001). Velocity ≥160 cm/s in at least one extracranial internal carotid artery was found in 45 out of 435 patients with sickle cell anemia (10.3%) and was highly predictive of MR angiography stenosis. Simultaneous abnormal intracranial velocity (≥200 cm/s) was recorded in 5/45 patients, while 40 patients had isolated extracranial internal carotid artery velocity ≥160 cm/s. Low hemoglobin (odds ratio: 1.9/g/dL, 95% confidence interval (CI): 1.3-2.9; P = 0.001) and tortuosities (odds ratio: 19.2, 95% CI: 7.1-52.6; P < 0.001) were significant and independent associated factors for isolated extracranial internal carotid artery velocities ≥160 cm/s. CONCLUSION: Adding extracranial internal carotid artery evaluation via the submandibular window to transcranial Doppler sonograpy allowed us to detect 10.3% patients at risk for extracranial internal carotid arteriopathy. Further studies are needed to evaluate the prognosis of these anomalies.