Intracranial and Extracranial Vascular Stenosis as Risk Factors for Stroke in Sickle Cell Disease

Abstract

Background: Prevalence and contribution of intracranial and extracranial arterial stenosis to stroke risk were assessed prospectively in children and young adults with sickle cell disease.

Methods: In this cross-sectional study, children and young adults (mean = 19.4 years) with sickle cell disease underwent neurological examination, brain MRI, and magnetic resonance angiography of the head and neck. Two neuroradiologists independently recorded infarcts and arterial stenosis. Clinical features and stroke outcomes were compared between participants with and without stenosis and between children and young adults. Logistic regression analysis assessed the association of variables of interest with overt stroke and silent cerebral infarct.

Results: Of 167 participants (79 children and 88 young adults), 20 (12.0%) had intracranial stenosis, all in the anterior circulation, and nine had concurrent extracranial stenosis. No participants had isolated extracranial stenosis. Participants with intracranial stenosis were more likely than those without stenosis to have an overt stroke (70% vs 5%, P < 0.001) or silent cerebral infarct (95% vs 35%, P < 0.001). Logistic regression analysis indicated that intracranial stenosis was strongly associated with overt stroke when compared with participants with silent cerebral infarct alone and strongly associated with silent cerebral infarct when compared with participants with normal brain MRI; male sex and age were also significant predictors of silent cerebral infarct.

Conclusions: Intracranial stenosis was strongly associated with both overt stroke and silent cerebral infarct; prevalence of intracranial stenosis was similar to prior estimates in sickle cell disease. Extracranial stenosis without concurrent intracranial stenosis did not occur and thus could not be evaluated as an independent risk factor for stroke.

Keywords: Child; Sickle cell disease; Silent cerebral infarction; Stenosis; Stroke.

Figure 1.. Flow diagram for vascular imaging and stenosis outcomes.

Diagram shows numbers of participants that received relevant vascular imaging studies (head and/or neck magnetic resonance angiography, MRA) and presence and absence of stenosis.

Figure 2.. Representative examples of intracranial stenosis and extracranial stenosis with diffuse smooth vessel narrowing in sickle cell disease.

Panel (A) 32-year-old female with right intracranial internal carotid artery (ICA) severe stenosis seen on head magnetic resonance angiography (MRA) maximum intensity projection (MIP) and axial MRA head; neck MRA MIP demonstrates the long-segment stenosis extending continuously from the extracranial ICA to the intracranial ICA and tiny extracranial ICA is seen on axial MRA neck. Panel (B) 34-year-old male with similar but less severe intracranial and extracranial ICA stenosis as patient (A). Panel (C) 39-year-old female with right middle cerebral artery (MCA) stenosis seen on head MRA MIP, ICA is not visible on MIP due to near occlusion, and intracranial ICA stenosis seen on axial MRA head. Neck MIP and axial MRA show longitudinal and cross-sectional smooth narrowing of the extracranial ICA.