Freeze lesion-induced focal cortical dysplasia predisposes to atypical hyperthermic seizures in the immature rat.

Abstract

To determine the effects of focal cortical dysplasia on the behavioral and electrographic features of hyperthermia-induced seizures (HSs) in rats. A right sensorimotor cortex freeze lesion was induced in postnatal day 1 (P1) rat pups, and HSs were provoked at P10 under continuous monitoring of core temperature; EEGs were recorded from the right amygdala during and after hyperthermia. Controls included both sham-operated at P1 and naïve rats. HSs began with jaw myoclonus, followed by hindlimb clonus and generalized convulsions (GCs), and terminated by a period of posthyperthermia depression. The threshold temperature and latency of jaw myoclonus were similar across the groups. However, both the threshold temperature and latency of GCs were significantly lower in lesioned pups than in controls (40.5 +/- 0.5 degrees C, n = 24, vs. 42.0 +/- 0.2 degrees C, n = 21; p < 0.001; 6.7 +/- 0.6 min, n = 20, vs. 8.4 +/- 0.6 min, n = 22; p < 0.05). In lesioned pups, the threshold and latencies for jaw myoclonus and hindlimb clonus were similar, whereas in controls, the progression from one to the other was marked by significant differences in both parameters. Posthyperthermia depression was longer in lesioned (13.3 +/- 1.2 min, n = 21) than in control (8.0 +/- 0.8 min, n = 20; p < 0.0001) pups. Ictal EEG activity was recorded during both behavioral seizures and posthyperthermia depression. An HS in rats with a localized freeze lesion results in lower threshold GC and prolonged ictal manifestations, thus supporting a pathophysiologic link between focal cortical dysplasia and atypical febrile seizures, conditions that have a high prevalence in children with mesial temporal lobe epilepsy.