Epilepsy research
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Pregabalin (Lyrica) is a novel amino acid compound that binds with high affinity to the alpha2-delta (alpha2-delta) auxiliary protein of voltage-gated calcium channels. In vivo, it potently prevents seizures, pain-related behaviors and has anxiolytic-like activity in rodent models. The present studies were performed to determine the profile of pregabalin anticonvulsant activity in a variety of mouse and rat models. ⋯ Pregabalin caused ataxia and decreased spontaneous locomotor activity at dosages 10-30-fold higher than those active to prevent seizures. These findings suggest that pregabalin has an anticonvulsant mechanism different from the prototype antiepileptic drugs and similar to that of gabapentin except with increased potency and bioavailability. In summary, our results show that pregabalin has several properties that favor treatment of partial seizures in humans.
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Different approaches to clinical trials are taken by government-sponsored (NIH, VA, MRC) and industry-sponsored clinical trials. Each sector has a different perspective and funding capacity. ⋯ Studies of drug use as monotherapy, direct comparisons among drugs, and comparisons between categories of drugs often are more important to prescribers and payors, thereby requiring government funding. The challenge to clinician-investigators is to now find ways to fund comparison trials to determine evidence-based guidelines so patients receive the best treatment both in the short- and long-term, and the health care system gets the best value.
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Status epilepticus (SE), defined as recurrent epileptic seizures without complete recovery between seizures, is one of the most serious manifestations of epilepsy. Generalized convulsive status epilepticus (GCSE) is the most common and most life-threatening form of SE, and aging increases the mortality risk. In a recent study of treatment of GCSE, 226 of 518 evaluable patients (43.6%) were of age 65 or older. ⋯ The diagnosis can be challenging, particularly in the elderly, as overlapping clinical features and electroencephalogram patterns can be seen in SE and in a variety of encephalopathic conditions. There is a suggestion that aggressive treatment of elderly patients with nonconvulsive SE may worsen prognosis. Clearly, there is a need for more data to better understand management of elderly patients with both convulsive and nonconvulsive SE.
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Treatment of elderly patients with epilepsy may present unique challenges to physicians. Co-morbid conditions and drugs to treat such conditions are common in elderly patients, possibly complicating epilepsy therapies that are dependent on drugs alone. For this reason, surgical intervention may be an attractive option for elderly patients with epilepsy, particularly for medically intractable patients with key disease features, such as lateralization and precisely localized epileptic foci. ⋯ When a curative surgical procedure is not an option, palliative procedures, including vagus nerve stimulation and deep brain stimulation, may be viable options. Vagus nerve stimulation has been reported to reduce seizure rates and improve quality of life in elderly patients with epilepsy. Currently, widespread therapeutic application of deep brain stimulation is limited by risks, costs, and pending studies.
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To identify clinical features related to seizure frequency after epilepsy surgery in patients with recurrent seizures. ⋯ Some preoperative clinical features correlate with postoperative seizure frequency in patients with recurrent seizures after epilepsy surgery. This has implications for the surgical decision making process and early postoperative management.