The role of the thalamus in neuro-cognitive dysfunction in early unilateral hemispheric injury: a multimodality imaging study of children with Sturge-Weber syndrome

Abstract

Background: Sturge-Weber syndrome (SWS) with unilateral hemispheric involvement is a clinical model of early onset, chronic, often progressive hemispheric injury, resulting in variable neuro-cognitive impairment.

Aims: To evaluate if abnormal diffusion and metabolism of the thalamus, a central relay station with extensive cortical connections, may serve as a simple imaging marker of neuro-cognitive dysfunction in SWS.

Methods: We obtained both diffusion tensor imaging and FDG PET in 20 children (11 girls; age range: 3-12.4 years) with unilateral SWS. Diffusion parameters as well as FDG uptake were measured in thalami, compared to normal control values, and correlated with the extent of cortical hypometabolism, deep venous abnormalities and cognitive (IQ) as well as fine motor functions.

Results: Children with SWS had significantly higher thalamic glucose metabolic asymmetry than controls (p=0.001). Thalamic metabolic asymmetries correlated positively with the asymmetry of thalamic diffusivity (p=0.001) and also with the extent of cortical hypometabolism (p<0.001). Severe thalamic asymmetries of glucose metabolism and diffusion were strong predictors of low IQ (metabolism: p=0.002; diffusivity: p=0.01), even after controlling for age and extent of cortical glucose hypometabolism in children with left hemispheric involvement. Ipsilateral thalamic glucose hypometabolism was also associated with impairment of fine motor functions (p=0.002).

Conclusions: Both diffusion and glucose metabolic abnormalities of the thalamus are closely related to cognitive functions, independent of age and cortical metabolic abnormalities, in children with unilateral SWS. Thalamic metabolic asymmetry is a robust but simple imaging marker of neuro-cognitive outcome in children with early unilateral hemispheric injury caused by Sturge-Weber syndrome.

Figure 1

Representative images showing the ROI definition in one plane of the thalamus (patient 9). ROIs were defined on the non-diffusion weighted images (i.e., b0 series) of the DTI sequences (A) and then superimposed on the FA, MD maps (B; C) as well as on the co-registered FDG PET images (D). The rectangular shaped ROIs were drawn on 4 consecutive planes (where the thalamus was clearly identifiable). ROIs of the same size were used on both thalami. L=left, R=right.

Figure 2

FDG PET images of two patients with Sturge-Weber syndrome, with mild (A) and severe (B) left posterior (parietal, occipital, temporal) cortical involvement (solid arrows). (A) The image of a 4 years old boy (patient 4) shows minimal thalamic hypometabolism (dashed arrows; measured AI: −5.2%) on the left side. This patient had normal IQ (full-scale IQ: 110). (B) The image of an 8 years old girl (patient 5) shows severe thalamic hypometabolism (dashed arrow; AI: −23.7%). This patient`s cognitive functions were severely impaired (full-scale IQ: 55). L=left, R=right.

Figure 3

Partial regression plot of glucose metabolic asymmetry of the thalamus vs. full-scale IQ, after controlling for age and the extent of hypometabolic cortex, in the subgroup of 13 children with left hemispheric involvement. The values represent residuals from regressing asymmetry and full-scale IQ on age and extent of hypometabolic cortex. Full-scale IQ showed a strong negative correlation with glucose metabolic AI of the thalamus even after controlling for other predictors.