Epilepsy research
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New treatments are needed to control prolonged status epilepticus given the high failure rate of current therapies. In an animal model of status epilepticus based on electrical stimulation of the hippocampus, rats demonstrate at least 5 five-hours of seizure activity following stimulation. Phenobarbital (70 mg/kg) administered 15 min after stimulation effectively controlled seizures in 66% of animals (n=6). ⋯ The ketamine dose response (fraction of seizure free rats) data were fit to a sigmoid curve to derive an ED(50) of 58 mg/kg. These findings suggest that prolonged status epilepticus becomes refractory to phenobarbital but can be effectively controlled by ketamine. For patients experiencing prolonged status epilepticus that is refractory to phenobarbital, ketamine may be an alternative to general anesthesia.
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Electroconvulsive therapy, which is used to treat refractory major depression in humans increases seizure threshold and decreases seizure duration. Moreover, the expression of brain derived neurotrophic factor induced by electroshocks (ECS) might protect hippocampal cells from death in patients suffering from depression. As temporal lobe epilepsy is linked to neuronal damage in the hippocampus, we tested the effect of repeated ECS on subsequent status epilepticus (SE) induced by lithium-pilocarpine and leading to cell death and temporal epilepsy in the rat. ⋯ Finally, while 11 out of the 12 sham-pilo rats developed spontaneous recurrent seizures after a silent period of 40+/-27 days, only two out of the 10 ECS-pilo rats became epileptic, but after a prolonged latency of 106 and 151 days. One ECS-pilo rat developed electrographic infraclinical seizures and seven did not exhibit any seizures. Thus, the extensive neuronal damage occurring in the entorhinal and perirhinal cortices of the ECS-pilo rats seems to prevent the establishment of the hyperexcitable epileptic circuit.
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We evaluated the anticonvulsant efficacy of the new antiepileptic drugs (AEDs) gabapentin and levetiracetam in amygdala kindled rats that had been preselected with respect to their response to phenytoin. Anticonvulsant response was tested by determining the afterdischarge threshold (ADT), i.e. a sensitive measure for drug effects on focal seizure activity. By repeated testing with the phenytoin prodrug fosphenytoin, three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (phenytoin responders), rats which showed no anticonvulsant response (phenytoin nonresponders), and rats with variable responses (variable phenytoin responders). ⋯ In phenytoin responders, gabapentin tended to be more efficacious in increasing ADT and GST than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. In contrast to gabapentin, levetiracetam was more efficacious in increasing ADT in nonresponders than in responders. The data of this study substantiate that phenytoin nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.
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Repetitive high intensity (110 dB) sound stimulation induces a forebrain-kindling phenomenon in animals predisposed to sound induced seizures. Wistar audiogenic rats (WARs) have been reported to develop a mixed brainstem-limbic seizure pattern, after more than five to ten stimuli. Besides the original brainstem wild running and tonic-clonic seizures, new behavioral patterns appear resembling those of electrical amygdala kindling. ⋯ All animals showed very similar polyspike-wave activity in the amygdala, after behavioral seizure patterns (Racine's scale) occurred. The morphology of such epileptiform EEG activity is very similar to that reported for electrical amygdala kindling. Also, when audiogenic kindling continued, both inferior colliculus and cortical electrodes presented high amplitude and synchronized epileptiform polyspike activity.
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Comparative Study
Absence of simple partial seizure in temporal lobe epilepsy: its diagnostic and prognostic significance.
The diagnostic and prognostic significance of the absence of simple partial seizures (SPS) immediately preceding complex partial seizures (CPS) was examined in patients with temporal lobe epilepsy. The status of self-reported SPS in 193 patients with temporal lobe epilepsy who had surgical therapy more than 2 years ago was reviewed. Before surgery, 37 patients never experienced SPS before CPS (Group A), 156 patients either always or occasionally had SPS before CPS (Group B). ⋯ The surgical outcome did not differ between the two groups. The findings suggest that temporal lobe seizures without preceding SPS tend to originate in the language-dominant temporal lobe that contains a pathologic etiology other than MTS, especially in the lateral temporal lobe. The surgical outcome in patients without SPS is similar to that in patients with SPS.