Reduced ventral cingulum integrity and increased behavioral problems in children with isolated optic nerve hypoplasia and mild to moderate or no visual impairment

Abstract

Objectives: To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified.

Patients and methods: Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed.

Results: Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = -0.52, p<0.02, r = -0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores.

Conclusions: Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.

Figure 1. The difference in Fractional Anisotropy (FA) between children with Isolated Optic Nerve Hypoplasia (ONH) and normal controls (Tract Based Spatial Statistics Analysis comparing ONH to controls).

The difference in white matter skeleton fractional anisotropy (FA) between children with isolated optic nerve hypoplasia (ONH) and controls (Tract Based Spatial Statistics Analysis comparing ONH to controls). Mean FA skeleton overlaid on the mean FA map. Regions of the mean FA skeleton in green represent areas where there were no significant differences in FA values in the ONH children compared to controls. Areas in red/yellow are regions where the FA was significantly lower in the ONH group, and can be observed bilaterally in the (a) optic radiation, (b) corpus callosum, and (c) ventral cingulum. Colour map indicates the degree of significance for red and yellow regions.

Figure 2. Correlations between child behavior checklist performance and ventral cingulum fractional anisotropy.

Ventral cingulum fractional anisotropy (FA) was extracted from the tract based spatial statistics analysis. FA was significantly lower in the ventral cingulum in children with ONH as compared to controls. Partial correlations were used to assess the relationships between scores on the child behavioral checklist (CBCL) and right ventral cingulum FA (controlled for age at scan and sex). Higher scores on the CBCL indicate more behavioral problems. FA correlated significantly with the total (A. r = −0.52, p<0.02) and externalising score on the CBCL (B. r = −0.46, p<0.049).