Clinical use of ictal SPECT in secondarily generalized tonic-clonic seizures

Abstract

Partial seizures produce increased cerebral blood flow in the region of seizure onset. These regional cerebral blood flow increases can be detected by single photon emission computed tomography (ictal SPECT), providing a useful clinical tool for seizure localization. However, when partial seizures secondarily generalize, there are often questions of interpretation since propagation of seizures could produce ambiguous results. Ictal SPECT from secondarily generalized seizures has not been thoroughly investigated. We analysed ictal SPECT from 59 secondarily generalized tonic-clonic seizures obtained during epilepsy surgery evaluation in 53 patients. Ictal versus baseline interictal SPECT difference analysis was performed using ISAS (http://spect.yale.edu). SPECT injection times were classified based on video/EEG review as either pre-generalization, during generalization or in the immediate post-ictal period. We found that in the pre-generalization and generalization phases, ictal SPECT showed significantly more regions of cerebral blood flow increases than in partial seizures without secondary generalization. This made identification of a single unambiguous region of seizure onset impossible 50% of the time with ictal SPECT in secondarily generalized seizures. However, cerebral blood flow increases on ictal SPECT correctly identified the hemisphere (left versus right) of seizure onset in 84% of cases. In addition, when a single unambiguous region of cerebral blood flow increase was seen on ictal SPECT, this was the correct localization 80% of the time. In agreement with findings from partial seizures without secondary generalization, cerebral blood flow increases in the post-ictal period and cerebral blood flow decreases during or following seizures were not useful for localizing seizure onset. Interestingly, however, cerebral blood flow hypoperfusion during the generalization phase (but not pre-generalization) was greater on the side opposite to seizure onset in 90% of patients. These findings suggest that, with appropriate cautious interpretation, ictal SPECT in secondarily generalized seizures can help localize the region of seizure onset.

Figure 1

Ictal SPECT injected during the pre-generalization period, with CBF increases including but not limited to the correct localization. Patient had right temporal neocortical epilepsy confirmed by intracranial EEG (Patient 12, Table 1, see also Supplementary Table 1). (A) Three dimensional rendering. (B) Coronal views with results superimposed on the SPM MRI template. Ictal SPECT scan was background subtracted using the patient's interictal SPECT, and the difference was then compared with a database of normal SPECT pairs using ISAS (see Methods section). CBF increases are shown as warm colours, and decreases are shown as cool colours; colour bars indicate t-values. The most significant hyperperfusion cluster was localized to the right temporal and occipital lobes (cluster-level significance P < 0.0001 corrected for multiple comparisons, Z-score of most significant voxel = 6.48, cluster size, k = 29 663 voxels). Extent threshold, k = 125 voxels (voxel dimensions 2 × 2 × 2 mm), voxel-level height threshold, P = 0.01.

Figure 2

Ictal SPECT injected during the generalization period, with CBF increases involving multiple lobes in the hemisphere of seizure onset, and CBF decreases in the contralateral hemisphere. Patient had right hemisphere seizure onset (Patient 15, Table 1, see also Supplementary Table 2). (A) Three-dimensional rendering. (B) Coronal views with results superimposed on the SPM MRI template. The most significant hyperperfusion cluster was localized to the right frontal, temporal and parietal lobes (cluster-level significance P < 0.0001 corrected for multiple comparisons, Z-score of most significant voxel = 5.09, cluster size, k = 27 513 voxels). Hypoperfusion was greatest in the left hemisphere, contralateral to seizure onset (hypoperfusion asymmetry index = 0.91, Patient 15, Table 3). Ictal–interictal SPECT difference images were analysed using ISAS (see Methods section). CBF increases are shown as warm colours, and decreases are shown as cool colours; colour bars indicate t-values. Extent threshold, k = 125 voxels (voxel dimensions 2 × 2 × 2 mm), voxel-level height threshold, P = 0.01.

Figure 3

Ictal SPECT injected during the post-ictal period was not useful for seizure localization. Patient had a left medial parietal localization based on MRI, PET and surgical pathology (Patient 49, Table 2, see also Supplementary Table 2). (A) Three-dimensional rendering. (B) Coronal views with results superimposed on the SPM MRI template. The most significant hyperperfusion cluster was localized to the right temporal lobe (cluster-level significance P < 0.0001 corrected for multiple comparisons, Z-score of most significant voxel = 4.32 cluster size, k = 6298 voxels), and a second large hyperperfusion cluster was present in the left temporal lobe (cluster-level significance P = 0.002 corrected for multiple comparisons, Z-score of most significant voxel = 4.80 cluster size, k = 2958 voxels). Hypoperfusion changes were also bilateral (hypoperfusion assymetery index = −0.03, Patient 49, Table 4). Ictal–interictal SPECT difference images were analysed using ISAS (see Methods section). CBF increases are shown as warm colours, and decreases are shown as cool colours; colour bars indicate t-values. Extent threshold, k = 125 voxels (voxel dimensions 2 × 2 × 2 mm), voxel-level height threshold, P = 0.01.