White Matter Integrity in Tanzanian Children With Sickle Cell Anemia

Abstract

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 Oxygen Metabolic Stress, Microstructural Injury, and Infarction in Adults With Sickle Cell Disease

“…With a goal of identifying cerebral ischemic injury at its earliest stages, diffusion tensor imaging (DTI) has allowed the assessment of white matter microstructural integrity in SCD. 10 - 12 Microstructural impairment in patients with SCD has been associated with slower processing speed, independent of infarcts. 13 , 14 Likewise, several studies in non-SCD sporadic cerebral small vessel disease have shown that changes in microstructure may predict progression of white matter hyperintensities and cognitive decline.…”

MRI detection of brain abnormality in sickle cell disease

“…Although this allows understanding in the context of previous experience with digital subtraction angiography, unless surgery is contemplated, this invasive imaging technique is rarely used now for ischemic stroke, even in symptomatic patients with SCD, so there are few data for comparison. Alternatively, signal dropout or turbulence on MRA may be graded as none (grade 0), mild (grade 1), moderate (grade 2), or severe with or without collaterals (grade 3) ( Figure 5 ) [ 11 , 13 , 24 , 45 ], or even as normal or abnormal [ 35 ]. The available data suggest that even mild abnormality is associated with tissue compromise [ 24 , 35 ]; this may be a useful research strategy given that studies comparing MRA with digital subtraction angiography would be unethical in asymptomatic patients.…”

“…Alternatively, signal dropout or turbulence on MRA may be graded as none (grade 0), mild (grade 1), moderate (grade 2), or severe with or without collaterals (grade 3) ( Figure 5 ) [ 11 , 13 , 24 , 45 ], or even as normal or abnormal [ 35 ]. The available data suggest that even mild abnormality is associated with tissue compromise [ 24 , 35 ]; this may be a useful research strategy given that studies comparing MRA with digital subtraction angiography would be unethical in asymptomatic patients.…”

“…A recent U.S. study examining specific white matter tracts similarly observed reduced integrity in SCD patients, with decreases in FA in the corpus callosum significantly associated with measures of processing speed, working memory, and executive function [ 95 ]. A fourth study in Tanzanian children with SCD found that, compared with those without SCI, those with SCI exhibited increased RD in multiple regions [ 24 ]. MD and AD were higher when hemoglobin was lower.…”

“…MD and AD were higher when hemoglobin was lower. Compared with SCA patients without vasculopathy, patients with vasculopathy exhibited reduced FA in widespread regions, including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts [ 24 ]. Interestingly, the posterior cerebral arterial territory had a higher mean MD and mean RD than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in vessels supplying this area [ 24 ].…”