Focal White Matter Abnormalities Related to Neurocognitive Dysfunction: An Objective Diffusion Tensor Imaging Study of Children With Sturge-Weber Syndrome

Abstract

White matter (WM) loss is associated with cognitive impairment in Sturge-Weber syndrome (SWS). In this study, we evaluated if cognitive and fine motor abnormalities are associated with impaired microstructural integrity in specific WM regions in SWS. Fifteen children with unilateral SWS (age: 3-12.4 years) and 11 controls (age: 6-12.8 years) underwent diffusion tensor imaging. Tract Based Spatial Statistics was used for objective comparisons of WM fractional anisotropy (FA) and mean diffusivity (MD) between the two groups. In the SWS group, WM FA and MD values were correlated with IQ and fine motor scores, with age as a co-variate. Bilateral, multilobar WM areas showed decreased FA, while significant MD increases were confined to small ipsilateral posterior regions in SWS children. IQ in the SWS group (range: 47-128) was positively correlated with FA in the ipsilateral prefrontal WM and inversely associated with MD in the ipsilateral posterior parietal WM. A negative correlation between fine motor function and MD was found in ipsilateral frontal WM encompassing motor pathways. Microstructural WM abnormalities occur not only ipsi- but also contralateral to the angioma in unilateral SWS. Nevertheless, cognitive and fine motor functions are related to diffusion abnormalities in specific ipsilateral, mostly frontal, WM regions.

What Does Diffusion Tensor Imaging Reveal About the Brain and Cognition in Fetal Alcohol Spectrum Disorders?

“…Nonetheless, with a clear understanding of the limitations of the technique, it remains evident that DTI is a promising tool that has now become a staple in the investigation of a wide range of neurodevelopmental conditions (Alkonyi et al 2010;Cykowski et al 2010;Filippi et al 2003;Groen et al 2010;Kao et al 2010;Kumar et al 2010;Mullen et al 2010;Radua et al 2010;Shukla et al 2010;Utsunomiya 2010;Wozniak et al 2011b;Yoshida et al 2010). Ultimately, DTI's primary advantage lies in its sensitivity: to neurodevelopmental abnormalities, to normal developmental changes (reviewed below), to changes in disease status including progression and recovery (Teipel et al 2010;Wu et al 2010), and to the effects of both biological and behavioral treatments Keller and Just 2009;Schweder et al 2010;Trivedi et al 2008).…”

Quantitative Assessment of Brain Networks in Children With Sturge-Weber Syndrome Using Resting State Functional Magnetic Resonance Imaging (MRI)

“…Our recent studies have also suggested that both grey matter and white matter injury may contribute to Sturge-Weber syndrome related neurocognitive deficits 4,6,9,10 . Early onset white matter damage may lead to disruptions in brain connectivity thus leading to abnormalities that impact the development of intrinsic resting-state brain networks 11,12 (such as default mode, visual, sensory-motor, and language networks), which are present in the human brain both during task performance and rest, across degrees of consciousness.…”

“…All three children took antiepileptic drugs (levetiracetam and/or oxcarbazepine) at the time of the evaluation. All three children underwent a neurological examination on the day of the MRI scans, and all three children underwent detailed neuro-psychological or (one year old) developmental and behavioral assessments, as described previously 9,10 .…”

“…Sedation was performed with pentobarbital (3 mg/kg) followed by fentanyl (1μg/kg) (for the 3-year old, induced after resting state functional MRI acquisition) or pentobarbital (3 mg/kg) followed by a booster dose of pentobarbital (1.5 mg/kg, 1-year old child, induced before any MRI acquisition). Additional MR sequences, including pre-and post-contrast T1-weighted, pre-contrast fluid attenuated inversion recovery, T2, susceptibility weighted sequences and MR venography were acquired, as described previously 8–10 .…”

“…Advanced neuroimaging techniques have improved the detection of vascular and brain tissue abnormalities in Sturge-Weber syndrome, identified imaging markers associated with specific neurocognitive complications, and discovered mechanisms of brain damage and reorganization 4–10 . Our recent studies have also suggested that both grey matter and white matter injury may contribute to Sturge-Weber syndrome related neurocognitive deficits 4,6,9,10 .…”