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      Neuropeptide Y affects thalamic reticular nucleus neuronal firing and network synchronization associated with suppression of spike-wave discharges

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          Most cited references 38

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          Studies in astronomical time series analysis. II - Statistical aspects of spectral analysis of unevenly spaced data

           J Scargle (1982)
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            Early identification of refractory epilepsy.

            More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.
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              Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats.

              Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy. Nonlinear association analysis revealed a consistent cortical "focus" within the peri-oral region of the somatosensory cortex. The SWDs recorded at other cortical sites consistently lagged this focal site, with time delays that increased with electrode distance (corresponding to a mean propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more complex and could not account for the observed cortical propagation pattern. Cortical and thalamic sites interacted bi-directionally, whereas the direction of this coupling could vary throughout one seizure. However, during the first 500 msec, the cortical focus was consistently found to lead the thalamus. These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spike-wave discharges characteristic for absence seizures in the rat. Instead, the results suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and that the large-scale synchronization is mediated by ways of an extremely fast intracortical spread of seizure activity. Analogous mechanisms may underlie the pathophysiology of human absence epilepsy.
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                Author and article information

                Journal
                Epilepsia
                Epilepsia
                Wiley
                00139580
                July 2018
                July 2018
                June 20 2018
                : 59
                : 7
                : 1444-1454
                Affiliations
                [1 ]Department of Medicine; The Royal Melbourne Hospital; University of Melbourne; Parkville Vic. Australia
                [2 ]Departments of Neuroscience and Neurology; Central Clinical School; The Alfred Hospital; Monash University; Melbourne Vic. Australia
                [3 ]Department of Physiology and Pharmacology; The University of New South Wales; Randwick NSW Australia
                Article
                10.1111/epi.14451
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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