Abstracts

Rationale: Status epilepticus is a neurological emergency associated with neuronal injury, lasting behavioral disturbance, and a high rate of mortality if not treated promptly. Levetiracetam (LEV) is a recently developed antiepileptic drug that has been approved to treat partial, generalized and myoclonic seizures. An intravenous preparation of LEV has recently been approved for use in the hospital setting. To investigate the potential of LEV as a first line treatment for status epilepticus, we examined the effect of intravenous LEV in a rat model of status epilepticus induced by systemic treatment with lithium and pilocarpine.Methods: Ten or 30 minutes after the onset of behavioral status epilepticus, animals were treated with LEV (200-1200 mg/kg i.v.) administered in a single bolus. All animals were observed and behavioral responses recorded. Selected animals had continuous extracranial EEG recording prior to, during and after the administration of LEV. A subset of animals was sacrificed 24 h after the experiment and processed for histochemical assessment of neuronal injury. Results: When administered 30 minutes after the onset of behavioral epileptic seizure, transient attenuation of seizure activity was observed in animals treated with 800 mg/kg or more of LEV.. The duration of seizure attenuation increased sharply as the dose rose to 1000 mg/kg or higher, from 4 minutes to at least 23.6 minutes. When administered 10 minutes after seizure onset, 400 mg/kg of LEV resulted in transient seizure attenuation, and higher doses caused relatively longer periods of attenuation. Pretreatment with LEV prior to pilocarpine injection also delayed the onset of seizures. EEG study of surface and depth recordings from hippocampus showed modest attenuation of ictal discharge that did not correlate strongly with observed behavioral changes induced by LEV. By contrast, TUNEL staining demonstrated less neuronal injury in the hippocampii and other limbic structures in animals that responded behaviorally to LEV.Conclusions: Intravenous levitiracetam may have a role in the treatment of status epilepticus.