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      Experimental Therapeutic Strategies in Epilepsies Using Anti-Seizure Medications

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          Abstract

          Epilepsies are among the most common neurological problems. The disease burden in patients with epilepsy is significantly high, and epilepsy has a huge negative impact on patients’ quality of life with epilepsy and their families. Anti-seizure medications are the mainstay treatment in patients with epilepsy, and around 70% of patients will ultimately control with a combination of at least two appropriately selected anti-seizure medications. However, in one-third of patients, seizures are resistant to drugs, and other measures will be needed. The primary goal in using experimental therapeutic medication strategies in patients with epilepsy is to prevent recurrent seizures and reduce the rate of traumatic events that may occur during seizures. So far, various treatments using medications have been offered for patients with epilepsies, which have been classified according to the type of epilepsy, the effectiveness of the medications, and the adverse effects. Medications such as Levetiracetam, valproic acid, and lamotrigine are at the forefront of these patients’ treatment. Epilepsy surgery, neuro-stimulation, and the ketogenic diet are the main measures in patients with medication-resistant epilepsies. In this paper, we will review the therapeutic approach using anti-seizure medications in patients with epilepsy. However, it should be noted that some of these patients still do not respond to existing treatments; therefore, the limited ability of current therapies has fueled research efforts for the development of novel treatment strategies. Thus, it seems that in addition to surgical measures, we should look for more specific agents that have less adverse events and have a greater effect in stopping seizures.

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          Most cited references179

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          The Epidemiology of Epilepsy

          Epilepsy is a chronic disease of the brain characterized by an enduring (i.e., persisting) predisposition to generate seizures, unprovoked by any immediate central nervous system insult, and by the neurobiologic, cognitive, psychological, and social consequences of seizure recurrences. Epilepsy affects both sexes and all ages with worldwide distribution. The prevalence and the incidence of epilepsy are slightly higher in men compared to women and tend to peak in the elderly, reflecting the higher frequency of stroke, neurodegenerative diseases, and tumors in this age-group. Focal seizures are more common than generalized seizures both in children and in adults. The etiology of epilepsy varies according to the sociodemographic characteristics of the affected populations and the extent of the diagnostic workup, but a documented cause is still lacking in about 50% of cases from high-income countries (HIC). The overall prognosis of epilepsy is favorable in the majority of patients when measured by seizure freedom. Reports from low/middle-income countries (LMIC; where patients with epilepsy are largely untreated) give prevalence and remission rates that overlap those of HICs. As the incidence of epilepsy appears higher in most LMICs, the overlapping prevalence can be explained by misdiagnosis, acute symptomatic seizures and premature mortality. Studies have consistently shown that about one-half of cases tend to achieve prolonged seizure remission. However, more recent reports on the long-term prognosis of epilepsy have identified differing prognostic patterns, including early and late remission, a relapsing-remitting course, and even a worsening course (characterized by remission followed by relapse and unremitting seizures). Epilepsy per se carries a low mortality risk, but significant differences in mortality rates are expected when comparing incidence and prevalence studies, children and adults, and persons with idiopathic and symptomatic seizures. Sudden unexplained death is most frequent in people with generalized tonic-clonic seizures, nocturnal seizures, and drug refractory epilepsy.
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            Understanding and using sensitivity, specificity and predictive values

            In this article, we have discussed the basic knowledge to calculate sensitivity, specificity, positive predictive value and negative predictive value. We have discussed the advantage and limitations of these measures and have provided how we should use these measures in our day-to-day clinical practice. We also have illustrated how to calculate sensitivity and specificity while combining two tests and how to use these results for our patients in day-to-day practice.
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              Seizures and epilepsy: an overview for neuroscientists.

              Epilepsy is one of the most common and disabling neurologic conditions, yet we have an incomplete understanding of the detailed pathophysiology and, thus, treatment rationale for much of epilepsy. This article reviews the clinical aspects of seizures and epilepsy with the goal of providing neuroscientists an introduction to aspects that might be amenable to scientific investigation. Seizures and epilepsy are defined, diagnostic methods are reviewed, various clinical syndromes are discussed, and aspects of differential diagnosis, treatment, and prognosis are considered to enable neuroscientists to formulate basic and translational research questions.
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                Author and article information

                Journal
                J Exp Pharmacol
                J Exp Pharmacol
                jep
                jexpharm
                Journal of Experimental Pharmacology
                Dove
                1179-1454
                11 March 2021
                2021
                : 13
                : 265-290
                Affiliations
                [1 ]Molecular Medicine and Bioinformatics, Research Center of Thalassemia & Hemoglobinopathy, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
                [2 ]Department of Pediatrics, Division of Pediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
                [3 ]Education Development Center (EDC), Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
                [4 ]Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
                [5 ]Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
                Author notes
                Correspondence: Mehdi Sayyah Education Development Center (EDC), Ahvaz Jundishapur University of Medical Sciences , Ahvaz, IranTel/Fax +986133367652 Email sayahbargard@gmail.com
                Author information
                http://orcid.org/0000-0002-2857-4562
                http://orcid.org/0000-0001-5423-6375
                Article
                267029
                10.2147/JEP.S267029
                7959000
                33732031
                1d380982-786f-4649-a76c-e7e74bb058f8
                © 2021 Rahim et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 28 October 2020
                : 10 February 2021
                Page count
                Figures: 2, Tables: 5, References: 179, Pages: 26
                Categories
                Review

                seizure,epilepsy,experimental therapeutic,drug strategies

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