Understanding the Epilepsy in POLG Related Disease
Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway
Department of Clinical Medicine (K1), University of Bergen, 5020 Bergen, Norway
K.G. Jebsen Center for Research on Neuropsychiatric Disorders, University of Bergen, 5009 Bergen, Norway
Department of Biological and Medical Psychology, University of Bergen, 5009 Bergen, Norway
Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(9), 1845; https://doi.org/10.3390/ijms18091845
Received: 21 July 2017 / Revised: 18 August 2017 / Accepted: 21 August 2017 / Published: 24 August 2017
(This article belongs to the Special Issue Commemorative Issue in Honor of Professor Uwe Heinemann: Metabolic Epilepsies)
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.