Epilepsy research
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Clinical Trial
EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness.
Subtypes of status epilepticus (SE) without tonic-clonic convulsions (nontonic-clonic SE) present as altered consciousness sometimes with subtle motor activity and are important to consider in the differential diagnosis of patients with unexplained altered consciousness. Other patients may have altered consciousness with intermittent ictal activity on electroencephalography (EEG) that represents probable SE, but have other medical conditions that may be contributing to altered consciousness. EEG is the only reliable way to make the diagnosis of nontonic-clonic SE and we make emergency EEG available on a 24-h basis at our hospital. ⋯ Contrary to other reports, we found no relationship between duration of SE and EEG pattern. Subtle generalized SE occurred most commonly in the setting of a diffuse brain injury rather than evolving from convulsive SE. This study demonstrates that nontonic-clonic SE is a common finding in patients with unexplained altered consciousness and EEG is necessary in the evaluation of these patients.
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Randomized Controlled Trial Multicenter Study Clinical Trial
The long-term safety and efficacy of gabapentin (Neurontin) as add-on therapy in drug-resistant partial epilepsy. The US Gabapentin Study Group.
This is the 2-year interim report of results from a multicenter, open-label study evaluating the long-term efficacy and safety of gabapentin (Neurontin) as add-on therapy in patients with refractory partial seizures who had had a therapeutic response to gabapentin in a preceding 12-week double-blind trial or 12-week open-label extension. A total of 240 patients continued to receive gabapentin as add-on therapy at dosages of 600-2400 mg/day for an average of 342 days (range 10-784 days). Efficacy analyses compared seizure frequency during consecutive 12-week treatment periods with seizure frequency during the 12-week baseline. ⋯ No consistent changes in clinical laboratory values were associated with gabapentin. Gabapentin as add-on therapy at dosages up to 2400 mg/day is safe during long-term treatment in patients with refractory partial seizures. Subgroup analyses of patients who remained in the study over the long term confirmed that gabapentin maintained efficacy for up to 2 years.
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Extracellular levels of aspartate, glutamate and glutamine were monitored by microdialysis in the dorsal hippocampus of freely moving rats following the administration of a convulsant dose of pilocarpine (400 mg/kg, i.p.). Rats were either pretreated with the glutamate uptake inhibitor, 1-trans-pyrrolidine-2,4-dicarboxylic acid (PDC, 1 mM in the perfusion medium, -25 min), or received pilocarpine directly. All rats injected with pilocarpine (with or without PDC pretreatment) developed limbic seizures (latency 15.4 +/- 2.4 min). ⋯ Aspartate and glutamate levels were not significantly increased (relative to PDC controls) during seizures. The conditions for pilocarpine-induced increases in aspartate and glutamate release were established in parallel groups of anaesthetised rats where pilocarpine was administered via a microdialysis probe in the dorsal hippocampus. Following the infusion of 10 mM pilocarpine there were large and rapid increases in the levels of aspartate (143%) and glutamate (179%), which were completely abolished by the absence of calcium in the perfusion medium, or by the presence of atropine (20 mM) or tetrodotoxin (1 microM).
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Historical Article
A brief history of epilepsy and its therapy in the Western Hemisphere.
The history of epilepsy and its treatment in the western world dates back at least 4 millennia to the ancient civilization of the middle east. Past and present treatments have been empirical, usually reflecting the prevailing views of epilepsy, be they medical, theological or superstitious. Ancient physicians relied on clinical observation to distinguish between epileptic syndromes and infer their cause. ⋯ The idea that focal irritation may cause seizures came about from clinical and experimental work, and was supported by the successful control of seizures by the (sedative) bromides and barbiturates in the late 19th century. The introduction of phenytoin showed that non-sedative drugs could be effective in controlling seizures as well, and the development of in vivo seizure models widened the scope of pharmaceutical agents tested for their efficacy against epilepsy. Increasing knowledge of the cellular mechanisms of epilepsy will, hopefully, allow the development and introduction of drugs with increasing specificity against seizure activity and the development of epilepsy.
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Thirteen drug-resistant epilepsy patients received loreclezole as add-on therapy. The trial lasted 6 months. Loreclezole was dosed to reach a target plasma concentration between 1 and 3 mg/l. ⋯ A reduction of 50% or more was observed in four patients. These effects are most likely related to loreclezole, as doses and plasma levels of the associated anti-epileptic drugs remained unchanged during the study. Loreclezole was tolerated well and no changes in haematological or biochemical parameters were observed.