Central nervous system abnormalities in asymptomatic young patients with Sβ‐thalassemia

Zafeiriou, Dimitrios I.; Prengler, Mara; Gombakis, N.; Kouskouras, Konsantinos; Economou, Marina; Kardoulas, Achileas; Tsantali, Chaido; Dimitriadis, Athanasios; Athanasiou, M; Kirkham, Fenella J.

doi:10.1002/ana.20104

Cited by 36 publications

(33 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…15 Similar observations were reported for an unselected cohort of 132 children with SCA in Créteil, France undergoing brain MRI as part of routine medical care 2 and in other studies. 4,5,17,18 SCI in SCA are typically smaller in size compared with overt strokes. In the CSSCD participants, 83% of the children with overt strokes, but only 16% of those with SCI, had lesions that were at least 1.5 cm.…”

Section: Clinical Significance Of Scismentioning

confidence: 99%

“…15 SCI is most common in patients with hemoglobin SS but may also be identified in individuals with heterozygous genotypes including sickle ␤-thalassemia and hemoglobin SC (HbSC) disease. Approximately 3% to 38% of patients with sickle ␤-thalassemia, 17,18,20,21 and 5% to 31% of those with HbSC disease, 15,22 will have SCI. However, limited sample size allows no significant inferences about the rate of progression or potential benefit of therapy.…”

Section: Clinical Significance Of Scismentioning

confidence: 99%

See 1 more Smart Citation

Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia

DeBaun

Armstrong

McKinstry

et al. 2012

Blood

Self Cite

289

292

View full text Add to dashboard Cite

Silent cerebral infarct (SCI) is the most common form of neurologic disease in children with sickle cell anemia (SCA). SCI is defined as abnormal magnetic resonance imaging (MRI) of the brain in the setting of a normal neurologic examination without a history or physical findings associated with an overt stroke. SCI occurs in 27% of this population before their sixth, and 37% by their 14th birthdays. In adults with SCA, the clinical history of SCI is poorly defined, although recent evidence suggests that they too may have ongoing risk of progressive injury. Risk factors for SCI include male sex, lower baseline hemoglobin concentration, higher baseline systolic blood pressure, and previous seizures. Specific morbidity associated with SCI includes a decrement in general intellectual abilities, poor academic achievement, progression to overt stroke, and progressive SCI. In addition, children with previous stroke continue to have both overt strokes and new SCI despite receiving regular blood transfusion therapy for secondary stroke prevention. Studies that only include overt stroke as a measure of CNS injury significantly underestimate the total cerebral injury burden in this population. In this review, we describe the epidemiology, natural history, morbidity, medical management, and potential therapeutic options for SCI in SCA. IntroductionOne of the most devastating medical complications of sickle cell anemia (SCA) is cerebral injury, which limits the full potential of the developing child and adult. The most common neurologic injury in SCA is silent cerebral infarct (SCI). Although there are few studies, SCI occurs in approximately one-quarter of children with SCA before their sixth birthday 1 and approximately one-third before their 14th birthday. 2 The first evidence that SCI had clinical significance was published in a cross-sectional computed tomography (CT) scan study of 25 patients. Five had cerebral infarcts but only 4 had a focal neurologic deficit (overt stroke). 3 The investigators referred to the fifth patient as having a covert stroke, 3 a term also used by others. 4 The term SCI or silent stroke has gained widespread use to describe this condition because the Cooperative Study of Sickle Cell Disease (CSSCD) used standard clinical magnetic resonance imaging (MRI) to define the radiologic parameters. 5 Subsequently, only a few studies of SCI have been completed. Until recently, the clinical importance of identifying SCI did not seem to justify the expense of MRI requiring sedation or anesthesia in preschool children, particularly in the absence of an effective intervention. Despite being the most common type of cerebral injury among children and adults with SCA, relatively little is known about the cause and optimal therapy of SCI. We will review the current literature on definition, epidemiology, natural history, clinical significance, medical management, and potential therapeutic options for the treatment of SCI in SCA. Definition of SCI in children with SCAThe largest longitudinal cohort study to a...

show abstract

Section: Clinical Significance Of Scismentioning

confidence: 99%

Section: Clinical Significance Of Scismentioning

confidence: 99%

Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia

DeBaun

Armstrong

McKinstry

et al. 2012

Blood

Self Cite

289

292

View full text Add to dashboard Cite

show abstract

“…21,22 Although the etiology of SCI is unknown, the consistent finding that anemia is a risk factor strongly implicates cerebral hemodynamic insufficiency as a central component. All patients with chronic anemia have a compensatory mechanism in the brain (auto-regulation) that occurs with vasodilation of the cerebral vasculature and manifests initially as increased cerebral blood flow.…”

Section: Risk Factors For Silent Infarcts In Sca 3687mentioning

confidence: 99%

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure

DeBaun

Sarnaik

Rodeghier³

et al. 2012

Blood

Self Cite

190

144

View full text Add to dashboard Cite

The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbS␤°thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P ‫؍‬ .018), and male sex (P ‫؍‬ .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761. IntroductionSilent cerebral infarcts (SCIs) have been recognized by neuroimaging in neurologically normal older adult populations since 1981 1 and were documented in sickle cell anemia (SCA) soon afterward. 2 As with overt stroke, SCIs represent a clinical finding that is common in older adults without SCD, but they appear during early childhood in persons with SCA. SCIs are defined as an MRI signal abnormality visible on 2 views on the T2-weighted images (axial and coronal) that must measure at least 3 mm in one dimension; further, the person deemed to have an SCI must have an absence of focal neurologic deficit compatible with the anatomic location of the brain lesion. 3 SCI is the most common form of neurologic injury among children with SCA, occurring in at least 27% before 6 years of life 4 and 37% by 14 years of life. 5 SCIs in children with SCA are associated with increased risk of future overt strokes and new or progressive SCIs. 6,7 In addition, children with SCA and SCI have been found to have poorer cognitive function The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. 3684BLOOD, 19 APRIL 2012 ⅐ VOLUME 119, NUMBER 16For personal use only. on March 28, 2019. by guest www.bloodjournal.org From than children with SCA with normal MRI of the brain 8-10 or sibling controls. 10,11 Clinical and laboratory risk factors for SCI have been evaluated only sparingly. In the most rigorous study to date, the investigators from the Cooperative Study for Sickle Cell Disease (CSSCD) described risk factors associated with SCI in 42 participants, comparing them with 188 controls with ...

show abstract

“…Few studies in patients with HbS-b thalassemia have been reported and the results are inconclusive [21][22][23][24]. The effectiveness of HU for the prevention of silent cerebral infarction has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Cerebrovascular events in sickle cell‐beta thalassemia treated with hydroxyurea: A single center prospective survey in adult Italians

et al. 2013

View full text Add to dashboard Cite

Stroke is a common cause of morbidity and mortality in sickle cell disease (SCD) and silent cerebral infarction is the most common form of neurologic injury. The frequency and risk factors for new silent cerebral infarction are incompletely understood. Moreover, no recommended treatment has been established. Although hydroxyurea (HU) is recommended for SCD, concerns remain regarding its role in the prevention of cerebrovascular events, including silent cerebral infarction. A single center population of 104 Italian patients with HbS-ß thalassemia treated with HU has been followed for a mean of 11 years. Clinical evaluation and brain imaging by Magnetic Resonance Imaging were done before and during HU treatment. During follow-up, the number of sickle cell crises (86%, 7.8 6 6.9 vs. 1.2 6 0.5 per year, P < 0.0001), hospitalizations (2.5 6 2.9 vs. 0.3 6 1.5 per year, P < 0.0001), and days in the hospital (22.4 6 21.9 vs. 0.361.5 per year, P < 0.0001) decreased significantly and HbF increased from a mean of 8-20.8%. Cerebral infarcts occurred in 37.5% of patients. Among these, 6.7% had overt strokes, while 30% had new or progressive silent cerebral infarction. Stroke and silent cerebral infarction were not related to clinical hematologic or HbF response to HU. These findings suggest that in adults, HU treatment does not prevent new cerebrovascular events or the progression of existent silent cerebral infarcts in HbS-b thalassemia. A major benefit of HU is the increase in HbF; the association of high HbF and reduced cerebrovascular disease has been weak. New treatment strategies should be developed for the prevention of sickle cerebrovascular disease. Am. J. Hematol. 88:E261-E264,

show abstract

Central nervous system abnormalities in asymptomatic young patients with Sβ‐thalassemia

Cited by 36 publications

References 33 publications

Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia

Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure

Cerebrovascular events in sickle cell‐beta thalassemia treated with hydroxyurea: A single center prospective survey in adult Italians

Contact Info

Product

Resources

About