Epileptic disorders : international epilepsy journal with videotape
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A brief survey of cortical development is presented, focusing on neuronal migration and its alterations. Corticogenesis is achieved through ordered temporospatial steps, via the formation of transient structures, and successive waves of cell proliferation and migration (followed by cell differentiation and maturation), and apoptotic cell death. The appearance of the proliferative ventricular zone and marginal zone, and of the superficial primordial plexiform layer, is followed by the formation of the prospective layer I, of the subplate, whose neurons are destined to die, and of the cortical plate that will give rise to layers II-VI. ⋯ Disorders of this complex process lead to a wide range of alterations, and focal derangements of cortical organization have been grouped under the term focal cortical dysplasia (FCD). As the result of a neuropathological revision of FCD cases with intractable epilepsy, a novel classification comprising three subgroups of FCD has been introduced, and is supported by electroclinical and neuroimaging data, as well as by the postsurgical outcome of patients: i). architectural dysplasia, characterized by altered cortical lamination; ii). cytoarchitectural dysplasia, with the occurrence of giant neurons besides cortical dyslamination; iii). Taylor-type cortical dysplasia, in which altered cortical lamination is consistently associated with the occurrence of giant, dysmorphic and ectopic neurons, and frequently with the so-called balloon cells.
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Review Comparative Study
Alternative surgical procedures to help drug-resistant epilepsy - a review.
The concepts of pathophysiology of epilepsy which underly the non-resective surgical treatment of epilepsy are reviewed. The available techniques, lesioning, disconnection and stimulation are described and reviewed critically. Stereotactic lesioning, popular in the 1950's has been largely abandoned but stereotactic radiosurgery emerges as a useful technique, especially in the treatment of mesial temporal sclerosis. ⋯ Vagus nerve stimulation(VNS) is an accepted method of treatment with low morbidity and mortality, which improves seizure control in at least 30% of patients, together with concomitant improvements in QOL and economic advantages. Stimulation of deep brain targets in the thalamus, subthalamus and mesial temporal structures is practical. There are indications that this improves seizure control in groups of patients previously un helped by surgery, and this methodology has enormous potential.
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Review
The ideal pharmacokinetic properties of an antiepileptic drug: how close does levetiracetam come?
The pharmacokinetic properties of a drug are the primary deter-minant of the extent and duration of drug action, and influence susceptibility to clinically important drug interactions. Most of the older-generation antiepileptic drugs (AEDs) are far from ideal in terms of pharmacokinetics and interaction potential. ⋯ One of the most recently developed of these drugs, levetiracetam, comes especially close to fulfilling the desirable pharmacokinetic characteristics for an AED: (1) it has a high oral bioavailability, which is unaffected by food; (2) it is not significantly bound to plasma proteins; (3) it is eliminated partly in unchanged form by the kidneys and partly by hydrolysis to an inactive metabolite, without involvement of oxidative and conjugative enzymes; (4) it has linear kinetics; and (5) it is not vulnerable to important drug interactions, nor does it cause clinically significant alterations in the kinetics of concomitantly administered drugs. Although its half-life is relatively short (6 to 8 hours), its duration of action is longer than anticipated from its pharmacokinetics in plasma, and a twice-daily dosing regimen is adequate to produce the desired response.
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The search for antiepileptic drugs (AEDs) using drug screens that test for the ability to suppress paroxysmal events has primarily resulted in the discovery of AEDs that inhibit neuronal excitability. While profoundly reducing expression of epileptic seizures, current pharmacologic treatments have not been able to completely control seizures in all patients, and can impair normal neuronal excitation underlying cognition. A new approach to drug screening, including the process of epileptogenesis, may yield new classes of drugs that not only suppress seizures but also specifically act to protect against the neurobiological changes that contribute to the development of epilepsy. ⋯ One new AED with potential antiepileptogenic properties is levetiracetam, which was discovered using non-conventional drug screens. It markedly suppresses kindling development at doses devoid of adverse effects, with persistent suppression of kindled seizures even after termination of treatment. Further design and implementation of antiepileptogenic drug screens are needed for the discovery of other novel disease-modifying agents.