Cortical and subcortical networks in human secondarily generalized tonic–clonic seizures

Abstract

Generalized tonic-clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus and basal ganglia. Post-ictally, there was a marked progressive CBF increase in the cerebellum which spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus and cingulate gyrus during and following seizures, similar to the 'default mode' regions reported previously to show decreased activity in seizures and in normal behavioural tasks. Analysis of patient behaviour during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that are most consistently involved in secondarily generalized tonic-clonic seizures. Abnormal increased activity in subcortical structures (cerebellum, basal ganglia, brainstem and thalamus), along with decreased activity in the association cortex may be crucial for motor manifestations and for impaired consciousness in tonic-clonic seizures. Understanding the networks involved in generalized tonic-clonic seizures can provide insights into mechanisms of behavioural changes, and may elucidate targets for improved therapies.

Functional Networks in Temporal-Lobe Epilepsy: A Voxel-Wise Study of Resting-State Functional Connectivity and Gray-Matter Concentration

“…Using ictal and interictal single-photon-emission computed tomography, Blumenfeld et al (2009) successfully mapped the temporal evolution of generalized tonic-clonic seizure-related perfusion changes. While the thalamus plays a key role as described above during generalization of the seizure, post-ictally, the bilateral frontal regions near the postcentral gyrus, the precuneus, and the midcingulate region all showed significant hypoperfusion.…”

Right parietal source in Mahjong‐induced seizure: a system epilepsy of focal origin

“…In the partial seizure without generalization, CBF often decreases postictally both within and around the seizure focus 10. In contrast, in the secondary generalized partial seizure, CBF tends to increase in multiple lobes ipsilateral to the seizure focus with relatively decreased CBF in the contralateral hemisphere 11. In the present case, postictal SPECT showed localized hypoperfusion in the parietal lobe of the right hemisphere, that is, the side of seizure focus.…”

“…Another important factor to modify the sensitivity and specificity of ictal SPECT is the timing of tracer injection. Whether CBF change is identified in the cases of partial seizure depends on the generalization and the timing of tracer injection, namely, either (i) pregeneralization period (during the partial seizure phase prior to generalization), (ii) during the generalization period, or (iii) postictal period 10, 11. In the partial seizure without generalization, CBF often decreases postictally both within and around the seizure focus 10.…”

MRI Characterization of Progressive Brain Alterations After Experimental Traumatic Brain Injury: Region Specific Tissue Damage, Hemodynamic Changes and Axonal Injury

“…Our study did not yield any correlations between CBF changes and memory and learning impairment, but poor performance in the Morris water maze was found to correlate with enhanced thalamic vessel density (r = -0.81, p < 0.01). The thalamus is often found to be damaged in moderate and severely injured TBI patients as well as in animal models (Pierce et al 1998, Maxwell et al 2004, Tollard et al 2009, Little et al 2010, but the role of the thalamic pathology in epileptogenesis after acquired etiologies like TBI is poorly understood (Bonilha et al 2004, Blumenfeld et al 2009). We also found that a high vessel density in the ipsilateral thalamus was associated with increased CBF and enhanced seizure susceptibility in injured rats.…”

“…We also found that a high vessel density in the ipsilateral thalamus was associated with increased CBF and enhanced seizure susceptibility in injured rats. A recent clinical report measured increased thalamic CBF during secondary generalization of focal onset seizures (Blumenfeld et al 2009). Still, one must be cautious with the interpretation of such clinical and preclinical correlations and keep in mind that in most of the cases it is still unclear whether the cerebrovascular sequelae is the cause or the consequence of abnormal neural activity.…”