Abstracts

Rationale: To study the relation between intelligence and diffusion tensor imaging (DTI) characteristics of normal appearing white matter (NAWM) in children with tuberous sclerosis complex (TSC). Methods: In 26 children with clinically definite TSC intelligence quotients (IQ) or developmental quotients were related to DTI characteristics of NAWM. Whole brain tractography was performed, and fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD) and axial diffusivity (AD) were calculated for well-defined segments of white matter tracts. Neuropsychological examination was performed, closely in time to the MRI, to assess intelligence or developmental quotients. Results: Corrected for age, a significant inverse correlation (p<0.01) was found between IQ and ADC in mesiotemporal, frontal and occipital NAWM tracts. In addition, IQ correlated positively with FA in corpus callosum and fronto-occipital tracts. In all supratentorial commissural and association tracts RD was inversely correlated with IQ (p<0.01). In summary, DTI characteristics of infratentorial tracts and ascending or descending projection fibers showed no correlation with intelligence, as compared with supratentorial association and commissural fibers. Conclusions: DTI characteristics of supratentorial NAWM tracts are related to intelligence in children with TSC. These findings suggest that cognitive dysfunction is, at least partly, related to a disturbed integrity of the NAWM in TSC, reflecting widespread microstructural abnormalities of white matter that are not visible on conventional MRI. Thus, white matter architecture, and not tuberload alone, is an important determinant for intelligence, adding to our understanding of the underlying pathogenesis in TSC.