In most children with Sturge-Weber syndrome (SWS) only one hemisphere of the brain is involved. For Csaba Juhasz, Ph.D., an assistant professor of pediatrics and neurology at Wayne State University in Detroit, and colleagues, this provided an opportunity to use magnetic resonance imaging (MRI) to assess cortical gray matter and hemispheric white matter volumes and any possible relationships with global intellectual function in a prospective study, with the unaffected hemisphere serving as an internal control for each child (Arch. Neurol. 2007;64:1169–74).
The researchers used MRI to study 21 children (13 girls) with SWS plus a history of partial seizures, which are common in this disorder. The children ranged in age from 18 months to 10.3 years (mean age 5.3 years). Most of the children (18) were on daily antiepileptic medication, either mono- or polytherapy with oxcarbazepine, valproate semisodium, levetiracetam, carbamazepine, phenobarbital, and/or topiramate.
The children underwent neuropsychologic testing 1 day prior to scanning. Those aged 18–36 months were assessed using the Bayley Scales of Infant Development, which yielded the Mental Developmental Index. Children aged 3–6 years were assessed using the Wechsler Preschool and Primary Scales of Intelligence, third edition. Children older than 6 years were assessed using the Wechsler Intelligence Scales for Children, third edition. Both indices yielded the full-scale IQ. The Mental Developmental Index and the full-scale IQ are highly correlated. Verbal and nonverbal intellectual functions were available for a subgroup of 15 children. Manual dexterity scores were also obtained using age-appropriate tests.
MRI was performed using a 1.5-T scanner. Researchers calculated volumetric measurements using findings from an axial three-dimensional T1-weighted scan.
The volumetric MR images were processed using statistical parametric mapping software. Dr. Juhasz and colleagues created a study-specific template using the brains of the children in this study because most software only includes an adult template. The template is used to spatially normalize the volumetric images of individual children.
By comparing the new template to each child's MRI, researchers produced three new volumetric maps with voxel values between 0 and 1, allowing them to assess volumes of gray matter, white matter, and cerebrospinal fluid.
Left and right hemispheric regions of interest were defined in all supratentorial image planes to derive cortical gray matter and hemispheric white matter volumes. The researchers calculated cortical gray matter and hemispheric white matter volumes for each hemisphere ipsilateral and contralateral to the angioma.
White matter volume in the affected hemisphere was a major predictor of cognitive impairment. Multivariate regression analysis showed a strong correlation between ipsilateral hemispheric white matter volume and full-scale IQ. Age was negatively correlated with full-scale IQ; cortical gray matter volumes showed no link with full-scale IQ. Ipsilateral white matter volumes correlated significantly for both verbal and nonverbal IQ. “The implication is that the white matter has to be preserved or targeted by some kind of treatment in the future,” he added. Currently, SWS is treated primarily with seizure drugs. “There is no rational therapy right now to somehow protect or preserve white matter, but it looks like that would be important.”
Given the findings, abnormal development or loss of white matter may be a critical factor of cognitive decline in SWS. It may be that incomplete maturation or disruption of fiber tracts that connect various cortical and subcortical structures may lead to loss of functional connectivity, impaired efficiency of information processing, and abnormal cognitive development.
The researchers are also using diffusion tensor imaging (DTI) to view tracts of fiber. Susceptibility-weighted imaging (SWI) allows for visualization of small vessel abnormalities. In SWS, vessel abnormalities typically start in the parietal and occipital regions. The frontal lobe becomes involved as the disease progresses. Preliminary DTI appears to show more extensive diffusion changes than would be expected from conventional MR images, said Dr. Juhasz.
“We are trying to figure out why for many of these children their brain involvement looks quite limited on conventional MR imaging but the neurocognitive outcomes are very variable,” said Dr. Juhasz.
Mismatch between the brain's large metabolic demands in the first few years of life and the limited blood supply in children with SWS may provide one answer. Dr. Juhasz and Dr. Harry T. Chugani, (director of the PET center at the Children's Hospital of Michigan, Detroit) and their colleagues also recently studied children with SWS using [18F]-2-fluoro-deoxy-D-glucose (FDG) PET imaging. They showed major metabolic progression in children with SWS occurs in the first 3–4 years of life, coinciding with a huge increase of metabolic demand as the brain develops.
A major aim of the larger (MRI and PET) longitudinal study is to find imaging markers to flag children with SWS who need aggressive therapy. Currently, there are not many treatment options. Aspirin is sometimes used; it may diminish the effects of ischemia. “The bottom line is that it only works if we can catch the patients early,” he said.