Epilepsy research
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Observational studies may provide important information on the long-term effects of treatments for epilepsy, but systematic reviews of observational studies may be more prone to heterogeneity and biases. These issues were investigated in a systematic review of non-randomised add-on anti-epileptic drug studies. ⋯ Reports of observational anti-epileptic studies give limited information on patient selection and characteristics. Systematic reviews of observational studies are prone to significant heterogeneity and bias which cannot adequately be explained by reported study characteristics. Reporting standards for observational studies of anti-epileptic drugs could be improved by following guidelines for reporting non-randomised studies of interventions.
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Acute brain insults, such as traumatic brain injury, status epilepticus, or stroke are common etiologies for the development of epilepsy, including temporal lobe epilepsy (TLE), which is often refractory to drug therapy. The mechanisms by which a brain injury can lead to epilepsy are poorly understood. It is well recognized that excessive glutamatergic activity plays a major role in the initial pathological and pathophysiological damage. ⋯ The amygdala, a temporal lobe structure that is most well known for its central role in emotional behavior, also plays a key role in epileptogenesis and epilepsy. In this article, we review the current knowledge on the pathology of the amygdala associated with epileptogenesis and/or epilepsy in TLE patients, and in animal models of TLE. In addition, because a derangement in the balance between glutamatergic and GABAergic synaptic transmission is a salient feature of hyperexcitable, epileptic neuronal circuits, we also review the information available on the role of the glutamatergic and GABAergic systems in epileptogenesis and epilepsy in the amygdala.
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In recent years, surgery has become a treatment option for some patients with intractable epilepsy, particularly those with temporal lobe epilepsy. Psychiatric disturbances may complicate the postsurgical outcome in some patients and de novo psychiatric symptoms have been reported. In many but not all epilepsy surgical centres, a psychiatric assessment is included as part of the presurgical evaluation of potential candidates for surgery. ⋯ Whilst there are no absolute psychiatric contraindications to surgery, certain pre-existing psychiatric conditions may need careful consideration as there may be a risk of postsurgical psychiatric complications. Routine pre- and postsurgical psychiatric evaluations in patients undergoing epilepsy surgery are recommended. Clinicians involved in the care of surgical candidates should be aware of the possible psychiatric complications following surgery and ensure that the psychiatric risks are discussed with the patient and family.
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Pregabalin (Lyrica) is a new antiepileptic drug that is active in animal seizure models. Pregabalin is approved in US and Europe for adjunctive therapy of partial seizures in adults, and also has been approved for the treatment of pain from diabetic neuropathy or post-herpetic neuralgia in adults. Recently, it has been approved for treatment of anxiety disorders in Europe. ⋯ Several studies indicate that the pharmacology of pregabalin requires binding to alpha2-delta subunits, including structure-activity analyses of compounds binding to alpha2-delta subunits and pharmacology in mice deficient in binding at the alpha2-delta Type 1 protein. The preclinical findings to date are consistent with a mechanism that may entail reduction of abnormal neuronal excitability through reduced neurotransmitter release. This review addresses the preclinical pharmacology of pregabalin, and also the biology of the high affinity binding site, and presumed site of action.
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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.