Epilepsy research
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Clinical Trial
Levetiracetam in newly diagnosed late-onset post-stroke seizures: a prospective observational study.
Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F, 71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures occurring at least 2 weeks after an ischemic stroke) in a prospective open-label study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%) at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke seizures.
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A 22-year-old woman with mitochondriopathy and pre-existing epilepsy developed status epilepticus (SE) not responding to benzodiazepines, phenytoin, thiopental, and propofol. SE was terminated within days after supplemental administration of continuous ketamine infusion to midazolam. The case suggests strong anticonvulsant properties of ketamine even after failure of GABAergic anesthetics, likely due to increased NMDA receptor expression with ongoing seizure activity. Thus, ketamine should be incorporated into therapeutic regimens for difficult-to-treat SE.
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Comparative Study
Isoflurane exacerbates electrically evoked seizures in amygdala-kindled rats during recovery.
Neuroexcitatory effects of isoflurane during or following anesthesia are controversial, particularly in epileptic patients. In contrast, halothane is generally considered to be highly anticonvulsant. Kindling is an animal model of epilepsy suitable for studying the effects of anesthetic agents on the epileptic brain. ⋯ Total seizure duration and clonus duration were significantly (P<0.05) increased 30 min after isoflurane but not halothane exposure relative to pre-treatment control. These results are the first to demonstrate that isoflurane exacerbates electrically evoked secondarily generalized seizures in fully kindled animals during recovery. These results also show that the kindling paradigm is useful for evaluating the mechanism of anesthetic agents that may be proconvulsant in epileptic subjects.
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Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. ⋯ Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.