Epilepsia
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Generalized epilepsy involves abnormally synchronized activity in large-scale neuronal networks. Burst firing of action potentials is a potent mechanism for increasing neural synchrony and is thought to enhance cortical and thalamic rhythmic network activity. Absence seizures, a form of generalized epilepsy, occur in children as brief 5- to 10-s periods of behavioral arrest associated with massive 3- to 4-Hz spike-wave discharges in cortical and thalamic networks. ⋯ Can enhanced burst firing in one region of the nervous system, such as the cortex, transform the entire thalamocortical network from normal activity to spike-and-wave seizures? Enhanced burst firing in corticothalamic neurons may increase gamma-aminobutyric acid-B (GABAB) receptor activation in the thalamus, leading to the slower, more synchronous oscillations seen in spike-and-wave seizures. Does "generalized" spike-wave activity homogeneously involve the entire brain, or are there crucial nodes that are more important than others for the generation and behavioral manifestations of generalized seizures? Animal and human data suggest that so-called generalized seizures involve selective thalamocortical networks while sparing others. A greater understanding of these molecular and network mechanisms will ultimately lead to improved targeted therapies for generalized epilepsy.
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Long-term antiepileptic drug (AED) therapy is the reality for the majority of patients diagnosed with epilepsy. One AED will usually be sufficient to control seizures effectively, but a significant proportion of patients will need to receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the treatment of concomitant disease. ⋯ In recent years, a more rational approach has been taken with regard to metabolic drug interactions because of our enhanced understanding of the cytochrome P450 system that is responsible for the metabolism of many drugs, including AEDs. The review briefly discusses the mechanisms of drug interactions and then proceeds to highlight some of the more clinically relevant drug interactions between AEDs and between AEDs and non-AEDs. Understanding the fundamental principles that contribute to a drug interaction may help the physician to better anticipate a drug interaction and allow a graded and planned therapeutic response and, therefore, help to enhance the management of patients with epilepsy who may require treatment with polytherapy regimens.
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New continuous infusion antiepileptic drugs (cIV-AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients. ⋯ Despite the inherent limitations of a systematic review, our results suggest that treatment with PTB, or any cIV-AED infusion to attain EEG background suppression, may be more effective than other strategies for treating RSE. However, these interventions also were associated with an increased frequency of hypotension, and no effect on mortality was seen. A prospective randomized trial comparing different agents and titration goals for RSE with obligatory continuous EEG monitoring is needed.
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Continuous EEG (CEEG) monitoring allows uninterrupted assessment of cerebral cortical activity with good spatial resolution and excellent temporal resolution. Thus, this procedure provides a means of constantly assessing brain function in critically ill obtunded and comatose patients. ⋯ Clinical examples of CEEG use, including monitoring of status epilepticus, assessment of ongoing therapy for treatment of seizures in critically ill patients, and monitoring for cerebral ischemia, are presented. Areas requiring further development of CEEG monitoring techniques and indications are discussed.
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Epilepsy and developmental disabilities (DD) often occur together but affect individuals differently and have a complex causal relationship. Most epilepsy in the population with DD is partial or symptomatic generalized. Seizures and antiepileptic drugs (AEDs) can further delay development, and the DD can complicate treatment and adjustment to epilepsy. ⋯ Studies have shown some success with oxcarbazepine (for partial and generalized epilepsy) and with adjunctive lamotrigine. For those on medication regimens, perhaps taking combinations of drugs for numerous years, queries about earlier attempts to reduce AEDs and gradual efforts to substitute less toxic mediations are worthwhile. Vagus nerve stimulation and epilepsy surgery for those with medically refractory epilepsy may be options after careful evaluation.