Imaging increased glutamate in children with Sturge–Weber syndrome: Association with epilepsy severity

BACKGROUND:Sturge-Weber syndrome (SWS) is strongly associated with epilepsy. Brain tissue studies have suggested that epileptic activity in SWS is driven by glutamatergic synaptic activity. Here, we used proton magnetic resonance spectroscopic imaging (MRSI) to test if glutamate (GLU) concentrations are increased in the affected hemisphere and if such increases are associated with severity of epilepsy in children with SWS. We also studied the metabolic correlates of MRSI abnormalities, using glucose positron emission tomography (PET) imaging. METHODS:3T MRI and glucose PET were performed in 10 children (age: 7-78 months) with unilateral SWS and a history of epilepsy. MRSI data were acquired from the affected (ipsilateral) and non-affected (contralateral) hemispheres. GLU, N-acetyl-aspartate (NAA) and creatine (Cr) were quantified in multiple voxels; GLU/Cr and NAA/Cr ratios were calculated and compared to seizure frequency as well as glucose PET findings. RESULTS:The highest GLU/Cr ratios were found in the affected hemisphere in all children except one with severe atrophy. The maximum ipsilateral/contralateral GLU/Cr ratios ranged between 1.0 and 2.5 (mean: 1.6). Mean ipsilateral/contralateral GLU/Cr ratios were highest in the youngest children and showed a strong positive correlation with clinical seizure frequency scores assessed at the time of the scan (r=0.88, p=0.001) and also at follow-up (up to 1 year, r=0.80, p=0.009). GLU increases in the affected hemisphere coincided with areas showing current or previous increases of glucose metabolism on PET in 5 children. NAA/Cr ratios showed no association with clinical seizure frequency. CONCLUSIONS:Increased glutamate concentrations in the affected hemisphere, measured by MRSI, are common in young children with unilateral SWS and are associated with frequent seizures. The findings lend support to the role of excess glutamate in SWS-associated epilepsy.