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Publications

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Epublish 23 citations

PubMed: 31651270 DOI: 10.1186/s12887-019-1758-2

Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study.

BMC Pediatr 19(1):381

Authors: Nancy S Green, Deogratias Munube, Paul Bangirana, Linda Rosset Buluma, Bridget Kebirungi, Robert Opoka, Ezekiel Mupere, Philip Kasirye, Sarah Kiguli, Annet Birabwa, Michael S Kawooya, Samson K Lubowa, Rogers Sekibira, Edwards Kayongo, Heather Hume, Mitchell Elkind, Weixin Peng, Gen Li, Caterina Rosano, Philip LaRussa, Frank J Minja, Amelia Boehme, Richard Idro

Affiliations

  • Department of Pediatrics, Columbia University Vagelos Medical Center, 630 West 168 St. Black Building 2-241, Box 168, New York, NY, USA.
  • Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
  • Department of Psychiatry, Makerere University College of Health Sciences, Kampala, Uganda.
  • Department Radiology, Makerere University College of Health Sciences, Kampala, Uganda.
  • Department of Paediatrics, CHU Sainte-Justine, University of Montreal, Montreal, Canada.
  • Departments of Neurology, Epidemiology and Biostatistics, Columbia University Vagelos Medical Center, New York, NY, USA.
  • Department of Biostatistics, Mailman School of Public Health, Columbia University Vagelos Medical Center, New York, NY, USA.
  • Epidemiology and of Clinical and Translation Science, University of Pittsburgh, Pittsburgh, PA, USA.
  • Department of Pediatrics, Columbia University Vagelos Medical Center, New York, NY, USA.
  • Department of Radiology, Yale University, New Haven, CT, USA.
  • Department of Neurology, Columbia University Vagelos Medical Center, New York, NY, USA.

Abstract

BACKGROUND

Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited.

METHODS

We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1-12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second).

RESULTS

Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5-12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23-1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ -2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01-1.86, p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95-24.3, p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30, p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected.

CONCLUSIONS

The high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.

MeSH

Cells, Research Design, Hemoglobins, Cross-Sectional Studies, Stroke, Anemia, Sickle Cell, Anemia, Brain, Pediatrics, Child

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