Abstracts

Rationale: Impaired cortical venous drainage can lead to hypoxic brain damage in children with Sturge-Weber syndrome (SWS). Cortical hypoxia can trigger excessive release and extracellular accumulation of glutamate (Glu), thus potentially inducing seizures. Recent tissue studies also suggested that epileptiform activity in SWS cortex is driven by glutamatergic synapses (Tyzio et al., Ann Neurol, 2009;66:209-18). Based on these, we hypothesized that proton magnetic resonance spectroscopic imaging (MRSI) may detect elevated Glu levels in the epileptogenic hemisphere in children with SWS, and we also tested if such Glu increases are related to seizure severity and intractibility. Methods: Using a 3-Tesla MR scanner, conventional MRI was supplemented by MRSI in 9 children (age: 1.1 - 6.5 years) with SWS-associated seizures and unilateral hemispheric involvement. A chemical shift imaging sequence, using STEAM, was employed to acquire 2D MRSI data in the interictal state (parameters: TR = 1500 ms, TE=40ms, TM=8ms, voxel size= 20mm x 20mm x 15mm, NA=16, total acquisition time = 10'48"). Glu (separated from glutamine and gamma-aminobutyric acid; as described by Hu et al., J Magn Reson, 2007;185:204-13), N-acetyl aspartate (NAA) and Creatine (Cr) were quantified in multiple voxels in axial brain slices positioned at levels showing typical MRI signs of SWS. Glu/Cr ratios, measured in voxels showing maximal Glu values, were compared between regions ipsi- (affected hemisphere) vs. contralateral (homotopic region in the unaffected hemisphere) to the leptomeningel angioma. NAA/Cr ratios were also measured in the same regions. Glu/Cr and NAA/Cr asymmetries (using ipsilateral/contralateral ratios) were correlated with clinical variables: age, age at epilepsy onset, duration of epilepsy and seizure frequency. Results: The highest Glu values were found in the affected hemisphere in all 9 children: the maximum ipsilateral/contralateral Glu/Cr ratios ranged between 1.11 and 2.50 (median: 1.63). In the same regions, NAA/Cr ratios showed variable abnormalities: either decreases or mild increases (ipsilateral/contralateral ratios ranging between 0.75 to 1.19, median: 0.99). High Glu/Cr ratios in the affected hemisphere were associated with high seizure frequency scores (Spearman's rho: 0.79, p=0.01). The three SWS children with the highest Glu/Cr ratios (≥75% increase on the affected side) had the most severe, intractable seizures: one had weekly clusters of infantile spasms, while the other two had intractable partial seizures requiring resective surgery after the scan. NAA/Cr asymmetries showed no correlation with any clinical variables. Conclusions: These data suggest a role of increased cortical Glu levels in epileptogenesis associated with SWS. The maximum level of Glu increases, detected by MRSI in the affected hemisphere, may be an imaging marker of seizure severity. Glutamate levels with 75% or greater increase, as compared to the contralateral homotopic region, may be associated with severe, intractable seizures in children with unilateral SWS.