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      Treatment, Therapy and Management of Metabolic Epilepsy: A Systematic Review

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          Abstract

          Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect. After applying our inclusion and exclusion criteria as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed a total of 43 articles. Based on the reviewed articles, we summarized the methods used for the treatment, therapy and management of metabolic epilepsy. These methods were tailored to address the root causes of the metabolic disturbances rather than targeting the epilepsy phenotype alone. Diet modification and dietary supplementation, alone or in combination with antiepileptic drugs, are used in tackling the different types of metabolic epilepsy. Identification, treatment, therapy and management of the underlying metabolic derangements can improve behavior, cognitive function and reduce seizure frequency and/or severity in patients.

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          Most cited references52

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          Genetics and molecular basis of human peroxisome biogenesis disorders.

          Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of autosomal recessive disorders comprised of two clinically distinct subtypes: the Zellweger syndrome spectrum (ZSS) disorders and rhizomelic chondrodysplasia punctata (RCDP) type 1. PBDs are caused by defects in any of at least 14 different PEX genes, which encode proteins involved in peroxisome assembly and proliferation. Thirteen of these genes are associated with ZSS disorders. The genetic heterogeneity among PBDs and the inability to predict from the biochemical and clinical phenotype of a patient with ZSS which of the currently known 13 PEX genes is defective, has fostered the development of different strategies to identify the causative gene defects. These include PEX cDNA transfection complementation assays followed by sequencing of the thus identified PEX genes, and a PEX gene screen in which the most frequently mutated exons of the different PEX genes are analyzed. The benefits of DNA testing for PBDs include carrier testing of relatives, early prenatal testing or preimplantation genetic diagnosis in families with a recurrence risk for ZSS disorders, and insight in genotype-phenotype correlations, which may eventually assist to improve patient management. In this review we describe the current status of genetic analysis and the molecular basis of PBDs. Copyright © 2012 Elsevier B.V. All rights reserved.
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            The etiologic classification of epilepsy.

            The etiology of epilepsy is a major determinant of clinical course and prognosis, yet the current classifications of epilepsy do not list etiology in any detail. In this article, a classification (database) of the etiologies of epilepsy is proposed. In this scheme, the etiology of epilepsy is divided into four categories: idiopathic, symptomatic, provoked, and cryptogenic. These are defined and subcategories are proposed. A commentary addressing the following points is included: problems associated with assigning causation, symptomatic versus idiopathic epilepsy, focal versus generalized epilepsy, acquired epilepsy, acute symptomatic epilepsy, risk factor analysis, provoked epilepsy genetic and developmental epilepsy, and epilepsy as a disease not a symptom. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
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              Glucose transporter type I deficiency syndrome: epilepsy phenotypes and outcomes.

              Glut 1 deficiency syndrome (DS) is defined by hypoglycorrhachia with normoglycemia, acquired microcephaly, episodic movements, and epilepsy refractory to standard antiepileptic drugs (AEDs). Gold standard treatment is the ketogenic diet (KD), which provides ketones to treat neuroglycopenia. Our purpose is (1) to describe epilepsy phenotypes in a large Glut 1 DS cohort, to facilitate diagnosis; and (2) to describe cases in which non-KD agents achieved seizure freedom (SF), highlighting potential adjunctive treatments.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                15 March 2018
                March 2018
                : 19
                : 3
                : 871
                Affiliations
                Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia; vanessa.lee1@ 123456monash.edu (V.L.L.L.); brandon.choo@ 123456monash.edu (B.K.M.C.); chung.yinsir@ 123456monash.edu (Y.-S.C.); uday.kundap@ 123456monash.edu (U.P.K.); yatinesh.kumari@ 123456monash.edu (Y.K.)
                Author notes
                [* ]Correspondence: farooq.shaikh@ 123456monash.edu ; Tel.: +60-355-14-4483
                Author information
                https://orcid.org/0000-0002-4873-5706
                https://orcid.org/0000-0003-4791-4646
                Article
                ijms-19-00871
                10.3390/ijms19030871
                5877732
                29543761
                aeb6bf49-f13a-4ded-a1c5-d01c3cbe9094
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 February 2018
                : 13 March 2018
                Categories
                Review

                Molecular biology
                metabolic epilepsy,metabolic disorders,antiepileptic drugs,dietary therapy,seizures,cognitive function

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