Int Rev Neurobiol
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Status epilepticus (SE) is a medical and neurological emergency requiring prompt and aggressive treatment, particularly for elderly individuals in whom comorbid conditions may increase the severity of consequences in SE. Generalized convulsive status epilepticus (GCSE) is the most common and life-threatening type of SE. It may be overt or subtle in its presentation. ⋯ Analysis of data on elderly patients with overt GCSE from a Veterans Affairs cooperative study revealed that success rates of first-line treatment were 71.4% for phenobarbital, 63.0% for lorazepam, 53.3% for diazepam followed by phenytoin, and 41.5% for phenytoin alone. In elderly patients with subtle GCSE, success rates for first-line treatment were 30.8% for phenobarbital, 14.3% for lorazepam, 11.8% for phenytoin, and 5.6% for diazepam followed by phenytoin. Because each drug has advantages and disadvantages, the choice of which agent to use as first-line treatment depends on individual patient characteristics.
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Understanding the importance of cortical lesions in MS pathogenesis has changed. Histopathologic studies using new immunohistochemical methods show that cortical lesions can be detected more frequently than previously reported. Newer MRI sequences also detect cortical lesions more accurately. ⋯ We observed a significant correlation between T2-LV and GM atrophy in all slice thickness (r = -0.4 to -0.48, p = 0.001-0.003) and a modest relationship between cortical and cortical-juxtacortical LVs and disability, especially at 1.5-mm slice thickness (r = 0.35, p = 0.025). Use of thinner slices (1.5 mm) on 2D-FLAIR images can significantly increase the sensitivity and precision of detecting cortical and juxtracotical lesions in patients with MS. Cortical and juxtacortical lesions contribute more to disability development than total T2-LV alone.
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Schizophrenia is a serious mental disorder that affects up to 1% of the population worldwide. As of yet, neurochemical mechanisms underlying schizophrenia remain unknown. To date, the most widely considered neurochemical hypothesis of schizophrenia is the dopamine hypothesis, which postulates that symptoms of schizophrenia may result from excess dopaminergic neurotransmission particularly in striatal brain regions, along with dopaminergic deficits in prefrontal brain regions. ⋯ As compared to dopaminergic agents, NMDA antagonists induce negative and cognitive symptoms of schizophrenia, as well as positive symptoms. Treatment studies with NMDA modulators, such as glycine, d-serine, and glycine transport inhibitors (GTIs), have yielded encouraging findings, although results remain controversial. Finally, genetic linkage and in vivo neurochemical studies in schizophrenia highlight potential etiological mechanisms giving rise to glutamatergic/NMDA dysfunction in schizophrenia.
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Stroke is a major risk factor for developing acquired epilepsy (AE). Although the underlying mechanisms of ischemia-induced epileptogenesis are not well understood, glutamate has been found to be associated with both epileptogenesis and ischemia-induced injury in several research models. This chapter discusses the development of an in vitro model of epileptogenesis induced by glutamate injury in hippocampal neurons, as found in a clinical stroke, and the implementation of this model of stroke-induced AE to evaluate calcium's role in the induction and maintenance of epileptogenesis. ⋯ The permanent epileptiform phenotype expressed as SREDs that resulted from glutamate injury was found to be dependent on the presence of extracellular calcium. The "epileptic" neurons manifested elevated intracellular calcium levels when compared to control neurons, independent of neuronal activity and seizure discharge, demonstrating that alterations in calcium homeostatic mechanisms occur in association with stroke-induced epilepsy. Findings from this investigation present the first in vitro model of glutamate injury-induced epileptogenesis that may help elucidate some of the mechanisms that underlie stroke-induced epilepsy.
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The knowledge base for treating elderly persons with epilepsy is limited. There are few known knowns, many known unknowns, and probably many unknown knowns, that is, the things we know that "ain't so." We know that the incidence and prevalence of epilepsy is higher in the elderly than any other age group, that the elderly are not a homogeneous group, that epilepsy is much more common in the nursing home population than in the community-dwelling elderly, and that antiepileptic drug (AED) use varies greatly among countries, but that in all, the older AEDs (phenytoin, phenobarbital, and carbamazepine) are the most commonly used. ⋯ Some unknown knowns (i.e., misconceptions) are that the elderly need levels of AEDs similar to those for younger adults and that AED levels do not fluctuate widely. This book is designed to help the reader understand the issues and, hopefully, to stimulate research to provide answers for the known unknowns.