Chronic low-dose corticosterone supplementation enhances acquired epileptogenesis in the rat amygdala kindling model of TLE.

Mesial temporal lobe epilepsy (MTLE) is associated with high rates of depression and anxiety. A bidirectional causal relationship has been suggested, with these psychiatric comorbidities themselves enhancing epileptogenesis, possibly via hypercortisolemia. We examined the effects on epileptogenesis of chronic supplementation with low-dose corticosterone (CS) in the electrical amygdala kindling rat model. Adult Wistar rats were ovariectomized and implanted with bipolar electrodes into the left amygdala. After 1 week recovery, one group (n=7) had CS (3 mg/100 ml--approx. 4.5 mg/kg/day) and a control group saline (n=7) added to their drinking water, and both groups underwent twice daily electrical stimulations. Rats were culled 2 weeks after reaching the fully kindled state. A stereological optical fractionator technique was used to estimate the number of CA1 pyramidal cells in the hippocampus ipsilateral to the stimulations. Fewer stimulations were required in the CS-supplemented rats than in controls to reach the fully kindled state (32 vs 81, p<0.03, Student's t-test) and the first Class V seizure (14 vs 57, p<0.05). The mean after-discharge length was greater in the CS group (p=0.03, repeated measures analysis of variance). There was no difference in the mean number of CA1 neurons (1.05 x 10(5) vs 1.04 x 10(5), p=0.98). These data demonstrate that low-dose CS enhances epileptogenesis in this model of MTLE. This provides support for the hypothesis that chronic hypercortisolemia, as a result of stress, anxiety, and/or depression, may facilitate the development and progression of epilepsy in patients with MTLE. The lack of difference in hippocampal CA1 neurons indicates that the mechanism does not primarily involve pyramidal cell loss.

Depression in temporal lobe epilepsy surgery patients: an FDG-PET study.

PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. METHODS: We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p<0.001 for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.