Epilepsia
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Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. In addition, pregabalin has been shown to be a highly effective adjunctive therapy for partial seizures in clinical trials. Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. ⋯ Therefore, pregabalin is unlikely to cause, or be subject to, pharmacokinetic drug-drug interactions--an expectation that has been confirmed in clinical pharmacokinetic studies. However, dose adjustment may be necessary in patients with renal insufficiency. Thus, the pharmacological and pharmacokinetic profiles of pregabalin provide a predictable basis for its use in clinical practice.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Pregabalin as adjunctive therapy for partial seizures.
The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been studied in three randomized, double-blind, placebo-controlled trials involving 1,052 patients. Patients (> or =12 years of age) participating in the trials were highly refractory to treatment, experiencing at least six seizures and no 4-week seizure-free period during the 8-week baseline phase, even though 73% received at least two antiepileptic drugs and 23% received three. Each fixed-dose study was 12 weeks in duration. ⋯ The most commonly reported adverse events were CNS related, and either mild or moderate in intensity and generally self limiting. Few patients (< or =5% in any treatment group) discontinued due to lack of efficacy. These results indicate that pregabalin is highly effective as adjunctive therapy in the treatment of patients with partial seizures with or without secondary generalization.
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Tuberous sclerosis complex (TSC) is associated with medically refractory seizures and developmental delay in children. These epilepsies are often resistant to antiepileptic drugs (AEDs), may be quite severe, and usually have a negative impact on the child's neurological and cognitive development. It is believed that functional outcome is improved if seizures can be controlled at an early age. ⋯ Multiple or bilateral seizure foci are not necessarily a contraindication to surgery in selected TSC patients. Long-term follow-up will determine whether this approach has durable effects. We await better methods for identifying the epileptogenic zone, both noninvasive and invasive.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures.
To evaluate pregabalin (PGB), 150 mg/day, and PGB, 600 mg/day, as an add-on treatment for patients with refractory partial seizures concurrently treated with one to three anticonvulsants (AEDs). ⋯ PGB, 150 mg/day and 600 mg/day, is highly effective and well-tolerated add-on therapy in patients with partial seizures.
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Magnetoencephalography (MEG)-also known as magnetic source imaging when combined with magnetic resonance imaging-has developed to the point that it has now entered routine clinical application. Epilepsy MEG studies show that it can accurately localize spike sources--both ictal and interictal--as compared to both direct (intracranial EEG) and indirect (imaging abnormalities) measures. ⋯ Magnetoencephalography not only provides a novel tool to localize and characterize epileptiform disturbances, it also has an important role in determining the significance of abnormalities seen on both structural and functional imaging. Combined with mapping of normal or eloquent brain function, MEG should ultimately play a major role in the totally noninvasive epilepsy surgery evaluation.