Abstracts

RATIONALE: Modern imaging techniques have demonstrated that chronically epileptic tissue is hypometabolic and energetically impaired interictally. The degree of hypometabolism, however, does not correlate absolutely with the extent of cell loss noted in patients with medial temporal lobe epilepsy. We tested the hypothesis that the degree of energetic impairment would correlate with a change in the ability of neurons to respond to repetitive synaptic stimulation.
METHODS: PCr/ATP ratios determined from 31P MR spectroscopic images of the hippocampal body were used as a measure of bioenergetic impairment. Intracellular recordings from dentate granule cells in hippocampal slices prepared from tissue resected from patients with temporal lobe epilepsy were used to examine the ability of neurons to respond to repetitive synaptic stimulation at 5 and 10 Hz (10 s trains; stimulus intensity 2.5 times action potential threshold). The synaptic response was assessed as the time-voltage interval.
RESULTS: In cells from comparison material (temporal lobe patients whose hippocampi showed no synaptic reorganization or extensive cell loss) there was a slight potentiation of the synaptic response (14.9 [plusminus] 6.1%; mean [plusminus] SEM) which peaked at one second and recovered over the course of the ten second train to control levels (n=7). By contrast, in cells from patients with [dsquote]classical[dsquote] mesial temporal lobe epilepsy (MTLE) there was a significant depression at one second (-20 [plusminus] 2.5%) which only recovered to -6.3 [plusminus] 3.1% of baseline at the end of the train (n=18). Baseline was set at 0 for these comparisons. These values were significantly different at both the 1 and 10 second time points (p[lt]0.002; 0.02 respectively). Comparable results were obtained when the data were analyzed by patient as well as by cell. No significant depression was seen in either patient group at lower frequencies (0.5-2 Hz). We noted that the degree of synaptic depression at both the 1 and 10 second time points correlated significantly with the degree of bioenergetic impairment measured pre-operatively (p[lt]0.03; n=8). This effect was also seen with the 5 Hz trains, although the data approached, but did not reach significance.
CONCLUSIONS: These data suggest that one consequence of the observed energetic impairment in this tissue is an inability to sustain prolonged periods of synaptic activation. Possible underlying mechanisms are currently being investigated.
Support: NIH Grant PO139092 to AW, HH and DDS and AG00795 to PRP