Brain volume in Tanzanian children with sickle cell anaemia: A neuroimaging study.

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5-20 years; 74 male) and sibling controls (n = 53; aged 5-17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non-SCA children may be vulnerable to contemporaneous anaemia.

Effect of age, cerebral infarcts, vasculopathy and haemoglobin on cognitive function, in Tanzanian children with sickle cell anaemia.

BACKGROUND: Developmental difficulties in many cognitive domains are common in children with sickle cell anaemia (SCA). Children with stroke are most affected but delayed or atypical cognitive function has been reported in children with SCA and silent infarcts (SCI), vasculopathy, and normal brain MRI. However, very few studies of cognition have been conducted in Africa, a continent with 75% of the SCA burden. We therefore investigated cognitive profiles in Tanzanian children with SCA and examined the impact of age, SCI, vasculopathy, and haemoglobin concentration (Hb). METHODS: Children aged 6-16 years with and without SCA were eligible for this cross-sectional study. Cognitive assessment was performed using Raven's Matrices, assessing fluid, non-verbal intelligence and subtests from the Wechsler Intelligence Scales for Children (WISC-IV), assessing processing speed (PS), perceptual reasoning (PR), and working memory (WM) as these tests are less culture-bound. Magnetic resonance imaging (MRI) and angiography (MRA) were also completed to assess the presence of SCI and vasculopathy. Hb was collected in both SCA children and their non-SCA siblings. RESULTS: Seventy-three children with SCA and 71 healthy siblings (Meanages 11.9, SD = 2.8 and 11.1, SD = 2.9 years respectively) were recruited. Compared with healthy siblings, children with SCA had lower PS (Meandiff 7.35 points; p = .002). Older children had higher performance scores on all tests in relation to their ages. Lowest cognitive scores were observed on the PS subtest, where patients with SCI (SCI+) had lowest mean values as compared to children with no SCI (SCI-) and healthy siblings (i.e., SCI+ < SCI- < healthy siblings, p = .028). On post-hoc analysis the difference was between SCI+ and healthy siblings SCI+ < non-SCA siblings (p = .015); there was no difference between SCI+ and SCI- patient groups. PS was significantly lower in SCA patients with no vasculopathy as compared to healthy siblings. The mean difference from healthy siblings was -8.352 and -0.752 points for VASC- and VASC + respectively (p = .004). There was a significant positive effect of Hb on PSI (p = .001) in both patients and controls and a trend level significant positive effect of Hb on PR (p = .050) and WM (p = .051). CONCLUSION: In this Tanzanian study, cognitive performance was reduced in children with SCA with or without SCI on MRI or vasculopathy. Cognitive performance improved with increasing age. Lower Hb was associated with lower cognitive performance in both patients with SCA and their non-SCA siblings. SCI and vasculopathy do not appear to have an impact on cognitive function.

Magic Dr.T? Tuberculous brain lesions in an immunocompetent patient-A case report.

Tuberculomas in the form of multiple ring-enhancing brain lesions is an uncommon occurrence in immunocompetent patient. Central nervous system tuberculosis may manifest as meningitis, tuberculoma, or abscess and can even occur in patients with or without active respiratory tract infection. In the case of active infection, specific antibiotic combinations and dosing duration are required, and respiratory isolation/precautionary measures must be taken by the health care workers and members of the family. Most literature has reported Central nervous system tuberculosis in patients with immunosuppression such as from HIV infection or solid organ transplantation; however, in endemic areas, CNS tuberculoma should be a differential consideration even for immunocompetent patients presenting with ring enhancing lesion (s). Our case highlights the importance of maintaining this clinical suspicion. Early diagnosis and management of our patient helped prevent potentially serious neurological sequelae.

White Matter Integrity in Tanzanian Children With Sickle Cell Anemia: A Diffusion Tensor Imaging Study.

Background and Purpose- Widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether white matter integrity differs across arterial territories. Methods- Sixty two children with sickle cell anemia aged 6 to 19 years were prospectively studied at Muhimbili National Hospital, Tanzania. SCI± and VSC± were identified on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) scans by 2 neuroradiologists. Tract-based spatial statistics tested for voxel-wise differences in diffusion tensor imaging metrics (ie, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between SCI± and VSC± groups, with correlations between diffusion tensor imaging metrics and Hb. In tract-based spatial statistics analyses, potentially mediating factors (ie, age, sex, as well as Hb, SCI, and/or vasculopathy) were covariates. Differences in mean diffusion tensor imaging metrics across regions of interest in arterial territories were explored. Results- Compared with SCI- patients (n=45), SCI+ patients (n=17) exhibited increased radial diffusivity in multiple regions; negative relationships were observed between mean diffusivity, axial diffusivity, and Hb (P<0.005). Compared with VSC- patients (n=49), mild (n=6) or moderate (n=7) VSC+ patients exhibited reduced fractional anisotropy in widespread regions (P<0.05) including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts. Overall, the posterior cerebral arterial territory had higher mean mean diffusivity and mean radial diffusivity than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in this area. There was an interaction between territory and vasculopathy. Conclusions- SCI, vasculopathy, and Hb are independent risk factors, and thus treatment targets, for diffuse white matter injury in patients with sickle cell anemia. Exacerbation of hemodynamic stress may play a role.

Cerebral Infarcts and Vasculopathy in Tanzanian Children With Sickle Cell Anemia.

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.

A Massive Extradural Hematoma in Sickle Cell Disease and the Importance of Rapid Neuroimaging.

Sickle cell disease (SCD) is an inherited hemoglobinopathy leading to several serious organ complications and early death. It is mostly found in equatorial countries like Tanzania. Extradural hematoma (EDH) is a rare, but serious complication to SCD and may have debilitating consequences. Hitherto, there is no report of EDH in SCD where neuroimaging has been available before, during, and after such an event. Here, we describe a young female SCD patient who developed EDH that required surgical evacuation. She had made full recovery after three months. Neuroimaging performed two years prior to this event was unremarkable except for multiple small cerebral infarcts. On admission, neuroimaging revealed a subgaleal hematoma, possibly indicating disruption of the skull cortex due to increased hematopoiesis. Three months after evacuation of the hematoma, neuroimaging showed evidence of brain atrophy and the previously reported cerebral infarcts and multifocal bone infarction, but no vasculopathy. Possibly, disruption of the skull cortex with subsequent bleeding caused the EDH. As the differential diagnoses of neurological complications in SCD are many and some complications are reversible, neuroimaging should be performed without delay.