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

Schlotman, Alyssa; Donahue, Manus J.; Kassim, Adetola A.; Lee, Chelsea A.; Waddle, Spencer; Pruthi, Sumit; Davis, L. Taylor; Rodeghier, Mark; DeBaun, Michael R.; Jordan, Lori C.

doi:10.1016/j.pediatrneurol.2020.10.006

Cited by 14 publications

(16 citation statements)

References 20 publications

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“…The high prevalence of silent infarcts on MRI in children with SCD compared with children with non-sickle stroke [ 192 ] probably at least in part reflects the chronicity of the vascular compromise in this population. Silent infarction may be associated with intracranial cerebrovascular disease, such as stenosis or moyamoya syndrome [ 193 , 194 ] but many patients with SCI have normal TCD and MRA and alternative mechanisms include embolus associated with right-to-left shunting [ 195 ].…”

Section: Abnormalities Detectable On Cross-sectional Neuroimaging In Asymptomatic Patientsmentioning

confidence: 99%

“…Ectasia of the basilar and intracranial circulations has also been documented and is associated with low haematocrit [ 206 , 207 ]. Extracranial ICA stenosis and occlusion in children with sickle cell anaemia have been reported [ 208 ]; pathogenesis is unclear but some may be secondary to extracranial dissection while others appear to be associated with intracranial stenosis [ 194 ]. There is controversy over whether extracranial stenosis is associated with SCI [ 191 , 194 ].…”

Section: Abnormalities Detectable On Cross-sectional Neuroimaging In Asymptomatic Patientsmentioning

confidence: 99%

“…Extracranial ICA stenosis and occlusion in children with sickle cell anaemia have been reported [ 208 ]; pathogenesis is unclear but some may be secondary to extracranial dissection while others appear to be associated with intracranial stenosis [ 194 ]. There is controversy over whether extracranial stenosis is associated with SCI [ 191 , 194 ]. Extracranial carotid artery occlusion or dissection should be considered in children with sickle cell anaemia presenting with symptoms of stroke and imaging of the neck vessels should be part of the investigation of these patients in the acute phase [ 208 ].…”

Section: Abnormalities Detectable On Cross-sectional Neuroimaging In Asymptomatic Patientsmentioning

confidence: 99%

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Epidemiology of Stroke in Sickle Cell Disease

Kirkham

Lagunju

2021

JCM

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Sickle cell disease is the most common cause of stroke in childhood, both ischaemic and haemorrhagic, and it also affects adults with the condition. Without any screening or preventative treatment, the incidence appears to fall within the range 0.5 to 0.9 per 100 patient years of observation. Newborn screening with Penicillin prophylaxis and vaccination leading to reduced bacterial infection may have reduced the incidence, alongside increasing hydroxyurea prescription. Transcranial Doppler screening and prophylactic chronic transfusion for at least an initial year has reduced the incidence of stroke by up to 10-fold in children with time averaged mean of the maximum velocity >200 cm/s. Hydroxyurea also appears to reduce the incidence of first stroke to a similar extent in the same group but the optimal dose remains controversial. The prevention of haemorrhagic stroke at all ages and ischaemic stroke in adults has not yet received the same degree of attention. Although there are fewer studies, silent cerebral infarction on magnetic resonance imaging (MRI), and other neurological conditions, including headache, epilepsy and cognitive dysfunction, are also more prevalent in sickle cell disease compared with age matched controls. Clinical, neuropsychological and quantitative MRI screening may prove useful for understanding epidemiology and aetiology.

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Section: Abnormalities Detectable On Cross-sectional Neuroimaging In Asymptomatic Patientsmentioning

confidence: 99%

Section: Abnormalities Detectable On Cross-sectional Neuroimaging In Asymptomatic Patientsmentioning

confidence: 99%

Section: Abnormalities Detectable On Cross-sectional Neuroimaging In Asymptomatic Patientsmentioning

confidence: 99%

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Epidemiology of Stroke in Sickle Cell Disease

Kirkham

Lagunju

2021

JCM

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“…2,3 Vasculopathy seen on brain magnetic resonance angiography (MRA) is also common in individuals with SCA and is associated with SCI 4,5 and future strokes. 6 SCI progresses over time with additional lesions in patients with or without previous overt strokes. [7][8][9][10][11][12] Progression of SCI is observed both in the pediatric and adult SCA populations; however, most data regarding the longitudinal development of brain parenchymal or vascular lesions are derived from pediatric cohorts with relatively short prospective follow-up.…”

Section: Introductionmentioning

confidence: 99%

Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia

Champlin

Hwang

Heitzer

et al. 2021

Exp Biol Med (Maywood)

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Silent cerebral infarcts and arteriopathy are common and progressive in individuals with sickle cell anemia. However, most data describing brain lesions in sickle cell anemia are cross-sectional or derive from pediatric cohorts with short follow-up. We investigated the progression of silent cerebral infarct and cerebral vessel stenosis on brain MRI and MRA, respectively, by describing the incidence of new or worsening lesions over a period of up to 25 years among young adults with sickle cell anemia and explored risk factors for progression. Forty-four adults with sickle cell anemia (HbSS or HbSβ0thalassemia), exposed to chronic transfusions ( n = 12) or hydroxyurea ( n = 32), median age 19.2 years (range 18.0–31.5), received a screening brain MRI/MRA and their results were compared with a clinical exam performed during childhood and adolescence. We used exact log-rank test to compare MRI and MRA progression among any two groups. The hazard ratio (HR) and 95% confidence interval (CI) were calculated from Cox regression analyses. Progression of MRI and MRA occurred in 12 (27%) and 4 (9%) young adults, respectively, relative to their pediatric exams. MRI progression risk was high among participants with abnormal pediatric exams (HR: 11.6, 95% CI: 2.5–54.7) and conditional or abnormal transcranial Doppler ultrasound velocities (HR: 3.9, 95% CI: 1.0–15.1). Among individuals treated with hydroxyurea, high fetal hemoglobin measured in childhood was associated with lower hazard of MRI progression (HR: 0.86, 95% CI: 0.76–0.98). MRA progression occurred more frequently among those with prior stroke (HR: 8.6, 95% CI: 1.2–64), abnormal pediatric exam ( P = 0.00084), and elevated transcranial Doppler ultrasound velocities ( P = 0.004). Brain MRI/MRA imaging in pediatrics can identify high-risk patients for CNS disease progression in young adulthood, prompting consideration for early aggressive treatments.

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“…MRI does not require exogenous contrast or ionizing radiation and therefore is well suited for surveillance imaging or therapy response evaluation. MRI is used frequently in both children and adults for infarct [5][6][7] and vasculopathy [8,9] assessment, to evaluate iron loading and accumulation [10,11], and studies have also reported evidence of acute infarcts visible on MRI in a small subset of children with SCD, which occurred with or without recent clinical symptoms [12,13].…”

Section: Introductionmentioning

confidence: 99%

Safety of 3 Tesla Magnetic Resonance Imaging in Patients with Sickle Cell Disease

Justice

Jordan

Lee

et al. 2021

Radiology Research and Practice

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Sickle cell disease (SCD) is a well-characterized hemoglobinopathy affecting more than 20 million individuals worldwide and carries an increased risk of cerebral vasculopathy, cerebral infarct, and stroke. As mechanisms of cerebral infarction in SCD are partly attributable to microvascular vaso-occlusive crises, manifesting as altered cerebral blood flow and associated impaired oxygen delivery, magnetic resonance imaging (MRI) methods that can quickly provide a comprehensive perspective on structural and functional disease status, without exogenous contrast administration or ionizing radiation, have emerged as crucial clinical tools for surveillance. However, early ex vivo MRI work in suspended erythrocytes containing hemoglobin S at 0.35 Tesla (T) suggested that sickled erythrocytes can orient preferentially in the presence of an external magnetic field, and as such, it was suggested that MRI exams in sickle cell hemoglobinopathy could induce vaso-occlusion. While this observation has generally not impacted clinical imaging in individuals with SCD, it has led to resistance for some sickle cell studies within the engineering community among some imaging scientists as this early observation has never been rigorously shown to be unconcerning. Here, we performed MRI at the clinical field strength of 3 T in 172 patients with SCD, which included standard anatomical and angiographic assessments together with gold standard diffusion-weighted imaging (DWI; spatial resolution = 1.8 × 1.8 × 4 mm; b-value = 1000 s/mm2) for acute infarct assessment (performed approximately 20 min after patient introduction to the field isocenter). The presence of vasculopathy, as well as chronic and acute infarcts, was evaluated by two independent board-certified radiologists using standard clinical criteria. In these patients (52.3% female; mean age = 19.6 years; age range = 6–44 years), hematocrit (mean = 25.8%; range = 15–36%), hemoglobin phenotype (87.8% HbSS variant), presence of silent infarct (44.2%), and overt chronic infarct (13.4%) were consistent with a typical SCD population; however, no participants exhibited evidence of acute infarction. These findings are consistent with 3 T MRI not inducing acute infarction or vaso-occlusion in individuals with SCD and suggest that earlier low-field ex vivo work of erythrocytes in suspension is not a sufficient cause to discourage MRI scans in patients with SCD.

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

Cited by 14 publications

References 20 publications

Epidemiology of Stroke in Sickle Cell Disease

Epidemiology of Stroke in Sickle Cell Disease

Progression of central nervous system disease from pediatric to young adulthood in sickle cell anemia

Safety of 3 Tesla Magnetic Resonance Imaging in Patients with Sickle Cell Disease

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