Quantitative brain surface mapping of an electrophysiologic/metabolic mismatch in human neocortical epilepsy

Abstract

The spatial relationship between an intracranial EEG-defined epileptic focus and cortical hypometabolism on glucose PET has not been precisely described. In order to quantitatively evaluate the hypothesis that ictal seizure onset and/or rapid seizure propagation, detected by subdural EEG monitoring, commonly involves normometabolic cortex adjacent to hypometabolic cortical regions, we applied a novel, landmark-constrained conformal mapping approach in 14 children with refractory neocortical epilepsy. The 3D brain surface was parcellated into finite cortical elements (FCEs), and hypometabolism was defined using lobe- and side-specific asymmetry indices derived from normal adult controls. The severity and location of hypometabolic areas vs. ictal intracranial EEG abnormalities were compared on the 3D brain surface. Hypometabolism was more severe in the seizure onset zone than in cortical areas covered by non-onset electrodes. However, similar proportions of the onset electrodes were located over and adjacent to (within 2 cm) hypometabolic regions (46% vs. 41%, respectively), whereas rapid seizure spread electrodes preferred these "adjacent areas" rather than the hypometabolic area itself (51% vs. 22%). On average, 58% of the hypometabolic regions had no early seizure involvement. These findings strongly support that the seizure onset zone often extends from hypometabolic to adjacent normometabolic cortex, while large portions of hypometabolic cortex are not involved in seizure onset or early propagation. The clinical utility of FDG PET in guiding subdural electrode placement in neocortical epilepsy could be greatly enhanced by extending grid coverage to at least 2 cm beyond hypometabolic cortex, when feasible.

Figure 1

Determination of electrode locations. The intraoperative digital photos (A and B) show the cortical surface before and after subdural grid placement in a 3-year-old girl (patient 1). The skull X-ray (C) with the three fiducial markers [two ipsilateral (solid line arrows), one contralateral (dotted line arrow)] was used for initial co-registration of the lateral electrode grids with the 3D MRI. Electrode grids placed to anatomically hidden areas, such as the interhemispheric grid seen on the X-ray, were not used for analyses in this study. The intraoperative photos were used to verify and refine the location of electrodes on the surface rendered 3D MRI image based on some readily identifiable landmarks (e.g., central sulcus, Sylvian fissure) delineated on the images (dotted black lines). Seizure onset (red) electrodes were located in the left frontal lobe and overlapped partially with the corresponding hypometabolic area. Rapid seizure spread could be identified in electrodes posterior to the onset zone (yellow electrodes). Green circles represent electrodes with no early ictal involvement (blue triangles, D).

Figure 2

Definition of the “adjacent area” surrounding hypometabolism. Intracranial electrodes and decreased glucose metabolism are displayed on the three-dimensional, parcellated MRI surface of an 8-year-old girl (patient 13). Hypometabolic cortex is marked with blue color. Triangles outlined with magenta represent the adjacent area around the hypometabolism. Seizure onset (red) and spread (yellow) electrodes in this case did not overlap with the glucose PET abnormality; however, the most of them were located in the adjacent area.

Figure 3

Partial mismatch between the onset zone and the hypometabolic cortex. The original transaxial FDG PET images (A) of a 15-year-old girl with refractory partial seizures (patient 7) show extensive glucose hypometabolism in the left hemisphere including all four lobes (red arrows). Hypometabolic cortex is marked with blue color on the parcellated 3D surface display (B). Although the hypometabolic cortex was not covered completely with subdural electrodes, the detected onset zone (red electrodes) overlapped only partially with the hypometabolic cortex. Several electrodes over the hypometabolic cortex did not show seizure onset or rapid propagation (green electrodes). On the other hand, all seizure onset and most propagation electrodes were located over hypometabolic or adjacent cortical areas.