Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency

- Generalized seizures are common in Glut1 DS, often present with absence and myoclonic seizures.
- Milder clinical phenotypes of Glut1 DS may present without clinical seizures.
- Visual analysis and the quantitative analysis of FDG-PET data demonstrate that the glucose hypometabolism is prominent in thalamus, cerebellum and neocortex.
- Glucose hypometabolism in thalamus is spared in the milder clinical phenotype of Glut 1 DS.
- In Glut1 DS, the epileptic network most likely involves thalamo neocortical connection.

SummaryRationale18F fluorodeoxyglucose positron emission tomography (18F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using 18F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism.Methods18F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results.ResultsVisual analysis of the 18F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score.ConclusionQuantitative analysis of 18F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy.

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