Mboka Jacob1, Dawn E Saunders2, Raphael Z Sangeda3, Magda Ahmed4, Hilda Tutuba5, Frank Kussaga4, Balowa Musa4, Bruno Mmbando6, April E Slee2, Jamie M Kawadler2, Julie Makani7, Fenella J Kirkham2. 1. Department of Radiology & Imaging, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania. Electronic address: mbokajacob@gmail.com. 2. Developmental Neurosciences Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. 3. Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania. 4. Department of Radiology & Imaging, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania. 5. Department of Heamatology and Blood Transfusion, Muhimbili Sickle Cell Program, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania. 6. Department of Heamatology and Blood Transfusion, Muhimbili Sickle Cell Program, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania; Department of Heamatology and Blood Transfusion, Muhimbili Sickle Cell Program, Muhimbili University of Health and Allied Sciences & National Institute for Medical Research, Tanga Center, Tanga, Tanzania. 7. Department of Heamatology and Blood Transfusion, Muhimbili Sickle Cell Program, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania; Muhimbili Sickle Cell Program & Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania.
Abstract
BACKGROUND: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia. METHODS: We prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin. RESULTS: Prevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170<200 cm/s) in one. Vasculopathy grades 2 (stenosis) and 3 (occlusion) occurred in 16 (7%) and two (1%), respectively; none had grade 4 (moyamoya). SCI was associated with vasculopathy on MRA (odds ratio 2.68; 95% confidence intervals [95% CI] 1.32 to 5.46; P = 0.007) and mean prior indirect bilirubin (odds ratio 1.02, 95% CI 1.00 to 1.03, P = 0.024; n = 83) but not age, sex, non-normal TCD, or contemporaneous hemoglobin. Vasculopathy was associated with mean prior values for hemoglobin (odds ratio 0.33, 95% CI 0.16 to 0.69, P = 0.003; n = 87), oxygen content (odds ratio 0.43, 95% CI 0.25 to 0.74, P = 0.003), reticulocytes (odds ratio 1.20, 95% CI 1.01-1.42, P = 0.041; n = 77), and indirect bilirubin (odds ratio 1.02, 95% CI 1.01 to 1.04, P = 0.009). CONCLUSIONS: SCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy.
BACKGROUND: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia. METHODS: We prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin. RESULTS: Prevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170<200 cm/s) in one. Vasculopathy grades 2 (stenosis) and 3 (occlusion) occurred in 16 (7%) and two (1%), respectively; none had grade 4 (moyamoya). SCI was associated with vasculopathy on MRA (odds ratio 2.68; 95% confidence intervals [95% CI] 1.32 to 5.46; P = 0.007) and mean prior indirect bilirubin (odds ratio 1.02, 95% CI 1.00 to 1.03, P = 0.024; n = 83) but not age, sex, non-normal TCD, or contemporaneous hemoglobin. Vasculopathy was associated with mean prior values for hemoglobin (odds ratio 0.33, 95% CI 0.16 to 0.69, P = 0.003; n = 87), oxygen content (odds ratio 0.43, 95% CI 0.25 to 0.74, P = 0.003), reticulocytes (odds ratio 1.20, 95% CI 1.01-1.42, P = 0.041; n = 77), and indirect bilirubin (odds ratio 1.02, 95% CI 1.01 to 1.04, P = 0.009). CONCLUSIONS: SCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy.
Authors: Richard Idro; Amelia K Boehme; Michael Kawooya; Samson K Lubowa; Deogratias Munube; Paul Bangirana; Robert Opoka; Ezekiel Mupere; Angela Lignelli; Philip Kasirye; Nancy S Green; Frank J Minja Journal: J Stroke Cerebrovasc Dis Date: 2022-02-11 Impact factor: 2.136
Authors: Grace Champlin; Scott N Hwang; Andrew Heitzer; Juan Ding; Lisa Jacola; Jeremie H Estepp; Winfred Wang; Kenneth I Ataga; Curtis L Owens; Justin Newman; Allison A King; Robert Davis; Guolian Kang; Jane S Hankins Journal: Exp Biol Med (Maywood) Date: 2021-08-18