Silent brain infarcts are rare in Kuwaiti children with sickle cell disease and high Hb F

Adekile, Adekunle; Yacoub, Fadi; Gupta, Renu; Sinan, Tariq; Haider, M.Z.; Habeeb, Yousif; Al-Bloushi, M.; Moosa, A.

doi:10.1002/ajh.10143

Cited by 38 publications

(27 citation statements)

References 32 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A few years ago, we started a prospective brain MRI study of children with SCD to document the prevalence of silent infarcts. Among 30 patients screened, only one, a 10 1 ⁄2-year-old male SS patient, had evidence of small infarcts, giving a prevalence of 3.3%, which is much lower than that reported for American patients [17]. We …”

Section: Introductionmentioning

confidence: 47%

Silent brain infarcts in adult Kuwaiti sickle cell disease patients

et al. 2003

Self Cite

View full text Add to dashboard Cite

Although overt stroke is a common complication of sickle cell disease (SCD), its incidence is very low in Kuwaiti patients. On the other hand, the prevalence of silent brain infarcts, which is reported to be about 17-20% in American patients, has not been documented in adult Kuwaiti patients. This is a 1-year study of consecutive, asymptomatic SCD patients seen in the hematology clinic of Mubarak Al-Kabeer Hospital. Patients with a past history of seizure or any other neurological abnormality were excluded. The patients' charts were reviewed for frequency of hospitalizations, any documented complications, and steady-state CBC. MRI was done with a 1.5-Tesla unit with super-conducting magnet. T1-and T2-weighted sagittal and axial sections and proton-density axial images were obtained in 5-mm-thick sections. Thirty-five patients were studied, made up of 25 SS and 10 S␤ 0 Thal, aged between 17 and 44 years, with a mean age of 26.9 ± 9.3 years. MRI findings consistent with infarcts were found in 7 (20.0%) patients-6 SS and 1 S␤ 0 thalwith a mean age of 31.8 ± 8.2 years, which was significantly higher (P < 0.05) than the mean age of the unaffected group (25.1 -9.0 years). There were also no differences in the mean Hb, Hb F, or any other hematological parameter in the two groups. Among the affected 6 SS, 2 had co-existent ␣-thal trait. It is interesting that, while silent infarcts are prevalent in young American patients, it is in the older age group that they occur in Kuwaiti patients. Further studies are needed to investigate the factors modulating this heterogeneity. Am. J. Hematol. 73:240-243, 2003.

show abstract

Section: Introductionmentioning

confidence: 47%

Silent brain infarcts in adult Kuwaiti sickle cell disease patients

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because metHb F does not bind Aβ1-42 as avidly as metHb A, the interaction of metHb F with Aβ may be less toxic than the interaction of metHb A with Aβ resulting in less RBC lysis and damage to the vascular epithelium. Evidence for the contribution of the XmnI polymorphism in the protective role of Hb F against vascular damage has been observed in patients with sickle cell disease [1,66,94]. These results suggest that further investigation into the effects of the XmnI polymorphism upon Hb F levels in AD subjects may provide additional evidence supporting this hypothesis.…”

Section: Discussionmentioning

confidence: 70%

“…Additionally, with hematological stress (e.g. Sickle Cell disease, Beta Thalasemia, hemolysis, pregnancy), the XmnI polymorphism has been shown to be at least partly responsible for an even greater increase in total Hb F and F cell levels [1,7,18,25,33,60,66,94,98].…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Perry

Gearhart

Wiener

et al. 2008

Neurobiology of Aging

View full text Add to dashboard Cite

From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (Hb F) as a protein that bound strongly to Aβ1-42. We showed the oxidized form 1 These authors are co-corresponding authors for all stages of refereeing and publication and contributed equally to this work. Rodney T. Perry; Rm. 210H, 1665 University Blvd.; University of Alabama at Birmingham, Birmingham, USA; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement:I so state for myself and on behalf of the other authors on the manuscript, Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease, that we have no conflicts and sources of funding that influence the results of this paper, the data is not published or submitted elsewhere, and that appropriate approval and procedures were used concerning human subjects. I also verify that all authors on this manuscript have reviewed the contents of the manuscript, approve of its contents, and validate the accuracy of the data. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of adult Hb (metHb A) binds with greater affinity to Aβ1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C→T) at −158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n=489) in families, with at least two affected and one unaffected sibling (p=0.006), with an age of onset >50 years (p=0.010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with Aβ and may protect against the development of AD.

show abstract

“…CNS infarction is a particularly intriguing complication. In contrast to the rarity of OS or SBI in Kuwaiti children with SCD [10], AVNFH is particularly common [8]. Why the cerebral vasculature is protected from vasculopathy and the osseous vasculature is not, still needs to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore the most common complication among our SCD patients. Overt stroke (OS) is exceedingly rare in patients with the IA haplotype; silent brain infarcts (SBI) were seen in only 3.3% of the children [10].…”

Section: Introductionmentioning

confidence: 99%

HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head

2005

Self Cite

View full text Add to dashboard Cite

Strong associations have been established between various HLA alleles and different complications of sickle cell disease (SCD). Recently, the HLA-DRB1*03 allele was shown to be associated with susceptibility to stroke while the HLA-DRB1*02 allele may be protective. While stroke and silent brain infarcts (SBI) are unusual in Kuwaiti children with SCD, avascular necrosis of the femoral head (AVNFH) is quite common. The modulatory association factors must still be elucidated. An investigation of HLA-DRB1 alleles was carried out in a group of 68 Kuwaiti SS patients, of age 7-44 years, of whom 20 (29.4%) had AVNFH, confirmed by magnetic resonance imaging. A group of 167 apparently healthy age-and sex-matched individuals served as controls. Comparison of the HLA alleles between the whole SS group and the controls showed a significant over-representation of DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) in the patient group. No significant differences in the allele frequencies in the SS patients with or without AVNFH were observed. It therefore appears that the HLA-DRB1 locus does not play a significant role in the pathogenesis of AVNFH Kuwaiti patients. Am.

show abstract

Silent brain infarcts are rare in Kuwaiti children with sickle cell disease and high Hb F

Cited by 38 publications

References 32 publications

Silent brain infarcts in adult Kuwaiti sickle cell disease patients

Silent brain infarcts in adult Kuwaiti sickle cell disease patients

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head

Contact Info

Product

Resources

About