Epilepsy research
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Randomized Controlled Trial Multicenter Study Clinical Trial
Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy.
The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. ⋯ The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.
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Data are available on the yield of a single EEG recording in patients with epilepsy but there is little information on EEG findings as an aid in supporting the diagnosis of an epileptic event in patients presenting with a first-ever event suspected of being an unprovoked seizure. We retrieved files of patients above the age of 15 years admitted through the emergency room during 1991-1995 with presumed first-ever unprovoked seizure. There were 91 patients (age 50+/-24; 52 males), of whom 66% had a presumed seizure of unknown origin and 34% had presumed remote symptomatic seizures. ⋯ Epileptiform activity was most common in younger patients with seizures of unknown origin, compared with older individuals with symptomatic seizures (34, 38 vs. 27%, 7%, P=0.001). We conclude that following a single unprovoked presumed seizure, adults commonly exhibit abnormalities in an EEG recorded close in time to the event. The EEG is particularly helpful in supporting the epileptic nature of the event in younger patients and in those with seizures of unknown origin.
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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.