White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts

Abstract

Background and Purpose-Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. Methods-A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age-and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Results-Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. Conclusions-These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. (Stroke. 2015;46:1793-1799.

Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients

“…Recently, decreased measures of O 2 saturation have been shown to correlate with compromised WM structure in SCD patients, supporting a role for acute-on-chronic hypoxia in white matter damage (Kawadler et al, 2015). …”

Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation

“…White matter abnormalities from sickle vasculopathy have been reported in children with SCD despite lack of infarct observed on standard clinical MRI scans. Some uncertainty may be clarified with the shift to more powerful scanner magnets and/or use of additional MRI-based sequences and analytic methodologies [34–36]. …”

Neurological Complications and MRI

“…Another TBSS study in 25 patients with no evidence of SCI showed FA significantly lower in cerebral peduncles and cerebellar white matter, whereas there were widespread increases in MD and RD across frontal and parietal lobes, corpus callosum and subcortical white matter. Furthermore, significant negative correlations were found between daytime peripheral oxygen saturation (SpO 2 ) and haemoglobin and RD in the anterior corpus callosum [96] (Figure 7). Results from a recent DTI-TBSS study [96], showing the white matter 'skeleton' (green) and significant correlations between RD and daytime peripheral oxygen saturation (blue) and haemoglobin (red).…”

“…Furthermore, significant negative correlations were found between daytime peripheral oxygen saturation (SpO 2 ) and haemoglobin and RD in the anterior corpus callosum [96] (Figure 7). Results from a recent DTI-TBSS study [96], showing the white matter 'skeleton' (green) and significant correlations between RD and daytime peripheral oxygen saturation (blue) and haemoglobin (red).…”