Dataset Information

A prospective longitudinal brain morphometry study of children with sickle cell disease.

ABSTRACT:

Background and purpose

Age-related changes in brain morphology are crucial to understanding the neurobiology of sickle cell disease. We hypothesized that the growth trajectories for total GM volume, total WM volume, and regional GM volumes are altered in children with sickle cell disease compared with controls.

Materials and methods

We analyzed T1-weighted images of the brains of 28 children with sickle cell disease (mean baseline age, 98 months; female/male ratio, 15:13) and 28 healthy age- and sex-matched controls (mean baseline age, 99 months; female/male ratio, 16:12). The total number of MR imaging examinations was 141 (2-4 for each subject with sickle cell disease, 2-3 for each control subject). Total GM volume, total WM volume, and regional GM volumes were measured by using an automated method. We used the multilevel-model-for-change approach to model growth trajectories.

Results

Total GM volume in subjects with sickle cell disease decreased linearly at a rate of 411 mm(3) per month. For controls, the trajectory of total GM volume was quadratic; we did not observe a significant linear decline. For subjects with sickle cell disease, we found 35 brain structures that demonstrated age-related GM volume reduction. Total WM volume in subjects with sickle cell disease increased at a rate of 452 mm(3) per month, while the trajectory of controls was quadratic.

Conclusions

There was a significant age-related decrease in total GM volume in children with sickle cell disease. The GM volume reduction was spatially distributed widely across the brain, primarily in the frontal, parietal, and occipital lobes. Total WM volume in subjects with sickle cell disease increased at a lower rate than for controls.

SUBMITTER: Chen R

PROVIDER: S-EPMC6598682 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundSickle cell disease is the most common severe monogenic disorder in humans. In Africa, 50-90% of children born with sickle cell disease die before they reach their fifth birthday. In this study, we aimed to describe the comparative incidence of specific clinical outcomes among children aged between birth and 5 years with and without sickle cell disease, who were resident within the Kilifi area of Kenya.MethodsThis prospective cohort study was done on members of the Kilifi Genetic Birth Cohort Study (KGBCS) on the Indian Ocean coast of Kenya. Recruitment to the study was facilitated through the Kilifi Health and Demographic Surveillance System (KHDSS), which covers a resident population of 260 000 people, and was undertaken between Jan 1, 2006, and April 30, 2011. All children who were born within the KHDSS area and who were aged 3-12 months during the recruitment period were eligible for inclusion. Participants were tested for sickle cell disease and followed up for survival status and disease-specific admission to Kilifi County Hospital by passive surveillance until their fifth birthday. Children with sickle cell disease were offered confirmatory testing and care at a dedicated outpatient clinic.Findings15 737 infants were recruited successfully to the KGBCS, and 128 (0·8%) of these infants had sickle cell disease, of whom 70 (54·7%) enrolled at the outpatient clinic within 12 months of recruitment. Mortality was higher in children with sickle cell disease (58 per 1000 person-years of observation, 95% CI 40-86) than in those without sickle cell disease (2·4 per 1000 person-years of observation, 2·0-2·8; adjusted incidence rate ratio [IRR] 23·1, 95% CI 15·1-35·3). Among children with sickle cell disease, mortality was lower in those who enrolled at the clinic (adjusted IRR 0·26, 95% CI 0·11-0·62) and in those with higher levels of haemoglobin F (HbF; adjusted IRR 0·40, 0·17-0·94). The incidence of admission to hospital was also higher in children with sickle cell disease than in children without sickle cell disease (210 per 1000 person-years of observation, 95% CI 174-253, vs 43 per 1000 person-years of observation, 42-45; adjusted IRR 4·80, 95% CI 3·84-6·15). The most common reason for admission to hospital among those with sickle cell disease was severe anaemia (incidence 48 per 1000 person-years of observation, 95% CI 32-71). Admission to hospital was lower in those with a recruitment HbF level above the median (IRR 0·43, 95% CI 0·24-0·78; p=0·005) and those who were homozygous for α-thalassaemia (0·07, 0·01-0·83; p=0·035).InterpretationAlthough morbidity and mortality were high in young children with sickle cell disease in this Kenyan cohort, both were reduced by early diagnosis and supportive care. The emphasis must now move towards early detection and prevention of long-term complications of sickle cell disease.FundingWellcome Trust.

Project description:Developmental dyscalculia (DD) is a learning disability affecting the acquisition of numerical-arithmetical skills. Affected people show persistent deficits in number processing, which are associated with aberrant brain activation and structure. Reduced gray matter has been reported in DD for the parietal cortex including the intraparietal sulcus (IPS), but also the frontal and occipito-temporal cortex. Furthermore, dyscalculics show white matter differences for instance in the inferior (ILF) and superior longitudinal fasciculus (SLF). However, the longitudinal development of these structural differences is unknown. Therefore, our goal was to investigate the developmental trajectory of gray and white matter in children with and without DD. In this longitudinal study, neuropsychological measures and T1-weighted structural images were collected twice with an interval of 4 years from 13 children with DD (8.2-10.4 years) and 10 typically developing (TD) children (8.0-10.4 years). Voxel-wise estimation of gray and white matter volumes was assessed using voxel-based morphometry for longitudinal data. The present findings reveal for the first time that DD children show persistently reduced gray and white matter volumes over development. Reduced gray matter was found in the bilateral inferior parietal lobes including the IPS, supramarginal gyri, left precuneus, cuneus, right superior occipital gyrus, bilateral inferior and middle temporal gyri, and insula. White matter volumes were reduced in the bilateral ILF and SLF, inferior fronto-occipital fasciculus (IFOF), corticospinal tracts, and right anterior thalamic radiation (ATR). Behaviorally, children with DD performed significantly worse in various numerical tasks at baseline and follow-up, corroborating persistent deficits in number processing. The present results are in line with the literature showing that children with DD have reduced gray and white matter volumes in the numerical network. Our study further sheds light on the trajectory of brain development, revealing that these known structural differences in the long association fibers and the adjacent regions of the temporal- and frontoparietal cortex persist in dyscalculic children from childhood into adolescence. In conclusion, our results underscore that DD is a persistent learning disorder accompanied by deficits in number processing and reduced gray and white matter volumes in number related brain areas.