Abstracts

RATIONALE: Febrile seizures affect 2-5% of the pediatric population and though simple febrile seizures are currently thought to be benign studies have shown that 40-60% of patients with intractable temporal epilepsy (MTLE) have a history of prolonged febrile seizures. In models of febrile seizures induced in the immature rat it has been demonstrated that it is prolonged hyperthermia induced convulsions that are associated with long-term changes in hippocampal excitability resulting in reduced seizure thresholds in adult subjects. Studies of specimens obtained from patients surgically treated for MTLE have demonstrated that between 10-80% had a cortical dysplastic lesion of the temporal lobe along with mesial temporal sclerosis. We therefore hypothesized that children with focal cortical dysplasia are more likely to have reduced seizure thresholds and febrile seizures that are prolonged or atypical.
METHODS: Pregnant Sprague Dawley rats were conditioned one week prior to parturition so as to minimize mortality due to post-operative neglect of the offspring. Surgical freeze lesions were induced in the neo-cortex of pups at P1 by applying a frozen probe, previously cooled in liquid nitrogen, to the exposed calvarium of anesthetized subjects. Convulsions were then induced at P10. Pups were placed into a large plexi-glass container and were exposed to a stream of moderately heated dry air until they had generalized convulsions evidenced by tonic/clonic movements of the upper and lower limbs with loss of the righting reflex. The core temperatures of all subjects were continually monitored throughout the period of hyperthermia. The threshold temperature and latency to jaw myoclonus (JMC), hind-limb clonus (HLC) and generalized convulsions (GC) were recorded including the duration of the post-ictal phase. Comparisons were made between lesioned, sham operated and naive control subjects.
RESULTS: Baseline temperatures at P10 were 35.0 [plusminus] 0.91[degree] C with no differences between the groups. Seizures were induced in 100% of subjects exposed to hyperthermia. The seizures were characterized by episodes of freezing interspersed with periods of hyperkinesis followed at higher temperatures by JMC with tonic neck and forelimb flexion, HLC then GC successively. This was followed by a period of post ictal depression characterized by prolonged immobility, hypo reactivity and reduced exploratory behavior. Lesioned pups exhibited reduced threshold temperatures to HLC, 36.91.41 C vs. controls 38.8[plusminus]1.71 (p[lt]0.05) and GC, 40.4[plusminus]1.86 C vs. controls 42.3[plusminus]0.95 C (p[lt]0.001); reduced latencies to: HLC, 127.90s[plusminus]81.9 vs. controls 290.61[plusminus]166.25s (p[lt]0.05) and GC, 403.1[plusminus] 29.44s vs. controls 525.8 [plusminus] 30.33s (p[lt]0.05); and a prolonged period of post-ictal depression 938.7[plusminus] 96.91s vs. controls 461.8[plusminus] 52.22s (p[lt]0.001).
CONCLUSIONS: Febrile seizures in the presence of focal cortical dysplasia occur at lower threshold temperature and shorter latency followed by post-ictal depression of a longer duration than that seen in controls. These findings demostrate that febrile seizures in the presence of cortical dysplasia are atypical and hence may contribute to the progression to MTLE.
[Supported by: The Saint Justine Research Foundation, Saint Justine Hospital, Montreal, Quebec, Canada]