Epilepsia
-
Comparative Study
Rapamycin has paradoxical effects on S6 phosphorylation in rats with and without seizures.
Accumulating data have demonstrated that seizures induced by kainate (KA) or pilocarpine activate the mammalian target of rapamycin (mTOR) pathway and that mTOR inhibitor rapamycin can inhibit mTOR activation, which subsequently has potential antiepileptic effects. However, a preliminary study showed a paradoxical exacerbation of increased mTOR pathway activity reflected by S6 phosphorylation when rapamycin was administrated within a short period before KA injection. In the present study, we examined this paradoxical effect of rapamycin in more detail, both in normal rats and KA-injected animals. ⋯ These data indicate the complexity of S6 regulation and its effect on epilepsy. Paradoxical effects of rapamycin need to be considered in clinical applications, such as for potential treatment for epilepsy and other neurologic disorders.
-
Models of temporal lobe epilepsy are commonly utilized to study focal epileptogenesis and ictogenesis. The criteria that define animal models representative of human mesial temporal lobe may vary in different laboratories. We describe herein a focal epilepsy model of mesial temporal (hippocampal) origin that relies on the analysis of interictal and ictal electroencephalography (EEG) patterns and on their correlation with seizure symptoms and neuropathologic findings. The study is based on guinea pigs, a species seldom utilized to develop chronic epilepsy models. ⋯ We demonstrate that a model of hippocampal (mesial temporal lobe) epilepsy can be developed in the guinea pig by intrahippocampal injection of KA. Seizure events in this model show little behavioral signs and may be overlooked without extensive video-EEG monitoring. The establishment of a chronic epileptic condition correlates with the extension of the hippocampal damage (mainly cell loss and gliosis) and not with the intensity of the initial SE.
-
Long-lasting activation of glia occurs in brain during epileptogenesis, which develops after various central nervous system (CNS) injuries. Glia is the cell source of the biosynthesis and release of molecules that play a role in seizure recurrence and may contribute to epileptogenesis, thus representing a putative biomarker of epilepsy development and severity. In this study, we set up an in vivo longitudinal study using (1) H-magnetic resonance spectroscopy (MRS) to measure metabolite content in the rat hippocampus that could reflect the extent and the duration of glia activation. Our aim was to explore if glia activation during epileptogenesis, or in the chronic epileptic phase, can be used as a biomarker of tissue epileptogenicity (i.e., a measure of epilepsy severity). ⋯ (1) H-MRS is a valuable in vivo technique for determining the extent and temporal profile of glia activation after an epileptogenic injury. S100β levels measured in the epileptic tissue may represent a biomarker of seizure frequency, whereas GSH levels during epileptogenesis could serve as a predictive marker of seizure frequency. Both mIns and GSH levels measured before the onset of spontaneous seizures predict the extent of neuronal cell loss in epileptic tissue. These findings highlight the potential of serial (1) H-MRS analysis for searching epilepsy biomarkers for prognostic, diagnostic, or therapeutic purposes.
-
Comparative Study
Screening for depression in epilepsy clinics. A comparison of conventional and visual-analog methods.
Depression is an important but underdiagnosed complication of epilepsy. This study compares potentially suitable screening tools head-to-head. ⋯ We suggest that the six-item NDDI-E or seven-item HADS-D should be considered if a conventional scale is preferred and that the revised ET4 be considered if a visual-analog method is required. Follow-up examination and intervention, where indicated, are necessary in all those who screen positive on any measure as these are not intended as diagnostic tools.
-
Surgery in frontal lobe epilepsy (FLE) has a worse prognosis regarding seizure freedom than anterior lobectomy in temporal lobe epilepsy. The current study aimed to assess whether intracranial interictal and ictal EEG findings in addition to clinical and scalp EEG data help to predict outcome in a series of patients who needed invasive recording for FLE surgery. ⋯ Widespread epileptogenicity as indicated by rapid onset of spread of ictal activity likely explains lack of seizure freedom following frontal resective surgery. The negative prognostic effect of surgery on the left hemisphere is less clear. Future study is needed to determine if neuronal network properties in this hemisphere point to intrinsic interhemispheric differences or if neurosurgeons are restrained by proximity to eloquent cortex.