Infantile spasms are characterized by age-specific expression of epileptic spasms, hypsarrhythmia and often result in significant cognitive impairment. Other epilepsies or autism often ensue especially in symptomatic IS (SIS). Cortical or subcortical damage, including white matter, have been implicated in the pathogenesis of SIS. To generate a model of SIS, we recreated this pathology by injecting rats with lipopolysaccharide and doxorubicin intracerebrally at postnatal day (P) 3 and with p-chlorophenylalanine intraperitoneally at P5. Spasms occurred between P4-13 and were associated with ictal EEG correlates, interictal EEG abnormalities and neurodevelopmental decline. After P9 other seizures, deficits in learning and memory, and autistic-like behaviors (indifference to other rats, increased grooming) were observed. Adrenocorticotropic hormone (ACTH) did not affect spasms. Vigabatrin transiently suppressed spasms at P5. This new model of SIS will be useful to study the neurobiology and treatment of SIS, including those that are refractory to ACTH.

The atypical febrile seizure has important clinical implications because of its association with the mesial temporal lobe epilepsy syndrome, which is the most common of the intractable epilepsies. However, whether a causal relation exists between these conditions is currently unknown. We have previously shown that a focal cortical lesion induced in the neonatal rat predisposes to the development of atypical hyperthermic seizures. We show here that 86% of the lesion plus hyperthermia group experience development of spontaneous recurrent seizures recorded from the amygdala ipsilateral to the lesion. Control rats did not have spontaneous recurrent behavioral or electrographic seizures. Lesioned rats with hyperthermic seizures also showed an impaired performance on the Morris water maze when compared with naive control rats, suggesting mild deficits in learning and memory. These findings support a link between the atypical febrile seizure and mesial temporal lobe epilepsy, and at the same time establish a new model for this condition through which new preventative and therapeutic strategies can be tested.

The aetiology and prognosis of infantile spasms is evolving. To improve outcome, we need to reduce the delay to diagnosis and develop prospective double-blind randomized clinical trials looking at not only the epileptic outcome but also cognitive outcome of these children.

Summary:Purpose: To determine the effects of focal cortical dysplasia on the behavioral and electrographic features of hyperthermia-induced seizures (HSs) in rats.Methods: 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.Results: 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• C, n = 24, vs. 42.0 ± 0.2 • 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.Conclusions: 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.