Interictal Spikes Increase Cerebral Glucose Metabolism and Blood Flow: A PET Study

Abstract

Summary:Purpose: In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges.Methods. To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood-flow tracer ['50]H,0 and with [ iXF]tluorodeoxyglucose in a patient with fixation-off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively.Results: The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: -36, y: -71, z: 39; t = 4.5; p < 0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10-mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 pmo1/100 g/min with eyes open and 44. I pmo1/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto-occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone.Conclusions: Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism. Key Words: Epilepsy -1nterictal spikes-PET-Glucose-Ener g y .The energy requirements of interictal spike discharges remain incompletely understood. In the majority of cases of adult temporal lobe epilepsy, interictal ["F]fluorodeoxyglucose (FDG) uptake is reduced (1-S), despite the presence of interictal spikes. However, a number of patients with increased focal glucose metabolism during interictal spike activity have now been reported (2,9,10). Additionally, in some animal models, interictal spikes have been shown to increase the regional metabolic rate for glucose (rCMRglc; 11). In general, it is difficult to study the metabolic effects of interictal spike discharges in humans because spike frequency can rarely be manipulated to suit a scanning schedule.We describe a patient with fixation-off epilepsy in whom interictal spike frequency was modulated by eye closure. Positron emission tomography (PET) was used

Significance of FDG-PET Hypermetabolism in Children with Intractable Focal Epilepsy

“…The presence of localized PET hypometabolism is correlated with a good seizure outcome after epilepsy surgery [24,27]. Interictal hypermetabolism on FDG-PET has been correlated with very frequent or continuous epileptiform discharges [24,[28][29][30][31][32][33][34][35][36]. Infrequent reports of interictal SPECT hyperperfusion also support these findings [19,37,38].…”

“…A high spike count was also reported in other studies although the calculation was different [29,31]. Bansal et al [24] found FCD in all cases.…”

“…Despite being uncommon, one study used ictal PET-MRI coregistration to determine the EZ and to help with epilepsy surgery planning [33], while another ictal PET study showed that complex partial seizures are associated with bilaterally increased cerebral blood flow in the cortical areas, especially the temporal and frontal lobes and subcortical areas [50]. Interictal hypermetabolism on FDG-PET appears to be associated with very frequent or continuous epileptiform discharges [24,[28][29][30][31][32][33][34][35][36]. Infrequent reports of interictal SPECT hyperperfusion also support these findings [19,37,38].…”

The Relationship between Glucose Metabolism, Resting-State fMRI BOLD Signal, and GABAA-Binding Potential: A Preliminary Study in Healthy Subjects and Those with Temporal Lobe Epilepsy

“…35 Although patients with epilepsy exhibit hypometabolism in the extended epileptogenic zone, evidence suggests that even interictal discharges cause transient focal increases in both blood flow and metabolism. [36][37][38] Although purely speculative, it is conceivable that increases in metabolism after these abnormal discharges may pathologically stimulate long-range connectivity, enabling abnormal interictal discharges to propagate across the brain, resulting in seizures. Although the partial correlations we observed between GC and GABA A BP ND controlling for rMRGlu did not differ significantly between groups, this parameter only reflects correlations above and beyond those because of correlations between GC and rMRGlu or GABA A BP ND and rMRGlu.…”

Hypometabolism and Interictal Spikes during Positron Emission Tomography Scanning in Temporal Lobe Epilepsy

“…In most of adult TLE, interictal FDG-PET shows hypometabolism in epileptic temporal lobe where interictal spikes are recorded [16, 17]. However, increased regional glucose metabolism during interictal spike activity have been reported in other studies [18, 19, 20]. …”