Potential new roles for glycogen in epilepsy

Abstract

Seizures often originate in epileptogenic foci. Between seizures (interictally), these foci and some of the surrounding tissue often show low signals with 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in many epileptic patients, even when there are no radiologically detectable structural abnormalities. Low FDG-PET signals are thought to reflect glucose hypometabolism. Here, we review knowledge about metabolism of glucose and glycogen and oxidative stress in people with epilepsy and in acute and chronic rodent seizure models.

Interictal HFO and FDG‐PET correlation predicts surgical outcome following SEEG

“…Although it is well acknowledged that PET hypometabolism is often larger than the EZ, 39 the cause of this remains unclear. 28 Here we provide evidence showing that the hypometabolism gradient is correlated with HFO distribution and rate, and we hypothesize in agreement with Lamarche and colleagues that these may reflect common underlying pathophysiologic mechanisms of ictogenesis. 10 Subgroup analyses to control for the potential effects of vigilance state, EZ localization, and etiology helped to confirm the robust nature of the observed PET/HFO correlation.…”

“…The present results echo and extend their findings with interictal SEEG recordings. Although it is well acknowledged that PET hypometabolism is often larger than the EZ, 39 the cause of this remains unclear 28 . Here we provide evidence showing that the hypometabolism gradient is correlated with HFO distribution and rate, and we hypothesize in agreement with Lamarche and colleagues that these may reflect common underlying pathophysiologic mechanisms of ictogenesis 10 …”

“…Indeed, it has been suggested that HFO and infra‐slow activity (whether ictal or interictal) may reflect different underlying cellular activity, with HFOs reflecting a possible neuronal origin and infra‐slow activity reflecting neural‐glial interactions 27 . More granular study of correlations of these electrophysiological signatures with brain metabolic activity as measured using FDG‐PET is required, especially since the biochemical origins of altered FDG‐PET signal remain poorly understood 28 …”

“…27 More granular study of correlations of these electrophysiological signatures with brain metabolic activity as measured using FDG-PET is required, especially since the biochemical origins of altered FDG-PET signal remain poorly understood. 28 Because it has been reported that FRs are more closely associated with epileptogenicity than lower frequency HFOs, 12 we sought to compare the CCs between ripples and FRs, which proved to be stronger in the FR group. Physiological HFOs are frequently mentioned as a confounder when implementing HFO as an EZ biomarker, since they overlap in frequency range, 13,[29][30][31] whereas the FRs are mostly considered pathological.…”

“…eight patients underwent resective surgery tailored to the SEEG results after invasive evaluation; 12 of 28 (43%) were MRI negative. At a mean follow-up of 25.3 months, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] 57.1% (16/28) achieved seizure freedom (ILAE class I); worthwhile improvement (>50% reduction in seizure frequency compared with baseline) was observed in 89.3% (25/28). Clinical characteristics can be found in Table 1.…”