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Understanding the Epilepsy in POLG Related Disease

Epilepsy is common in polymerase gamma (POLG) related disease and is associated with high morbidity and mortality. Epileptiform discharges typically affect the occipital regions initially and focal seizures, commonly evolving to bilateral convulsive seizures which are the most common seizure types i...

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Autores principales: Hikmat, Omar, Eichele, Tom, Tzoulis, Charalampos, Bindoff, Laurence A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618494/
https://www.ncbi.nlm.nih.gov/pubmed/28837072
http://dx.doi.org/10.3390/ijms18091845
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author Hikmat, Omar
Eichele, Tom
Tzoulis, Charalampos
Bindoff, Laurence A.
author_facet Hikmat, Omar
Eichele, Tom
Tzoulis, Charalampos
Bindoff, Laurence A.
author_sort Hikmat, Omar
collection PubMed
description Epilepsy is common in polymerase gamma (POLG) related disease and is associated with high morbidity and mortality. Epileptiform discharges typically affect the occipital regions initially and focal seizures, commonly evolving to bilateral convulsive seizures which are the most common seizure types in both adults and children. Our work has shown that mtDNA depletion—i.e., the quantitative loss of mtDNA—in neurones is the earliest and most important factor of the subsequent development of cellular dysfunction. Loss of mtDNA leads to loss of mitochondrial respiratory chain (MRC) components that, in turn, progressively disables energy metabolism. This critically balanced neuronal energy metabolism leads to both a chronic and continuous attrition (i.e., neurodegeneration) and it leaves the neurone unable to cope with increased demand that can trigger a potentially catastrophic cycle that results in acute focal necrosis. We believe that it is the onset of epilepsy that triggers the cascade of damage. These events can be identified in the stepwise evolution that characterizes the clinical, Electroencephalography (EEG), neuro-imaging, and neuropathology findings. Early recognition with prompt and aggressive seizure management is vital and may play a role in modifying the epileptogenic process and improving survival.
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spelling pubmed-56184942017-09-30 Understanding the Epilepsy in POLG Related Disease Hikmat, Omar Eichele, Tom Tzoulis, Charalampos Bindoff, Laurence A. Int J Mol Sci Review Epilepsy is common in polymerase gamma (POLG) related disease and is associated with high morbidity and mortality. Epileptiform discharges typically affect the occipital regions initially and focal seizures, commonly evolving to bilateral convulsive seizures which are the most common seizure types in both adults and children. Our work has shown that mtDNA depletion—i.e., the quantitative loss of mtDNA—in neurones is the earliest and most important factor of the subsequent development of cellular dysfunction. Loss of mtDNA leads to loss of mitochondrial respiratory chain (MRC) components that, in turn, progressively disables energy metabolism. This critically balanced neuronal energy metabolism leads to both a chronic and continuous attrition (i.e., neurodegeneration) and it leaves the neurone unable to cope with increased demand that can trigger a potentially catastrophic cycle that results in acute focal necrosis. We believe that it is the onset of epilepsy that triggers the cascade of damage. These events can be identified in the stepwise evolution that characterizes the clinical, Electroencephalography (EEG), neuro-imaging, and neuropathology findings. Early recognition with prompt and aggressive seizure management is vital and may play a role in modifying the epileptogenic process and improving survival. MDPI 2017-08-24 /pmc/articles/PMC5618494/ /pubmed/28837072 http://dx.doi.org/10.3390/ijms18091845 Text en © 2017 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/).
spellingShingle Review
Hikmat, Omar
Eichele, Tom
Tzoulis, Charalampos
Bindoff, Laurence A.
Understanding the Epilepsy in POLG Related Disease
title Understanding the Epilepsy in POLG Related Disease
title_full Understanding the Epilepsy in POLG Related Disease
title_fullStr Understanding the Epilepsy in POLG Related Disease
title_full_unstemmed Understanding the Epilepsy in POLG Related Disease
title_short Understanding the Epilepsy in POLG Related Disease
title_sort understanding the epilepsy in polg related disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618494/
https://www.ncbi.nlm.nih.gov/pubmed/28837072
http://dx.doi.org/10.3390/ijms18091845
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