Relationship of Mitochondria and Epilepsy Effect of Mitochondrial Disorders on Epilepsy

1071-9091/13/ http://dx.doi.or of Neurology, r's Hospital fo adelphia, PA. reprint reque hristopher'sH ail: divya.khur Epilepsy is themost common neurologic disorder worldwide and is characterized by recurrent unprovoked seizures. Themitochondrial (mt) respiratory chain is thefinal commonpathway for cellular energy production through the process of oxidative phosphorylation. As neurons are terminally differentiated cells that lack significant regenerative capacity andhave a high energy demand, they are more vulnerable to mt dysfunction. Therefore, epileptic seizures have been well described in several diseases such asmt encephalomyopathy, lactic acidosis, and strokelike episodes and myoclonic epilepsy and ragged red fibers, which are caused by gene mutations inmtDNA, among others.Mutations in nuclear DNA regulatingmt function are also being described (eg, POLG gene mutation). The role of mitochondria (mt) in acquired epilepsies, which account for about 60% of all epilepsies, is equally important but less well understood. Oxidative stress is one of the possible mechanisms in the pathogenesis of epilepsy resulting frommtdysfunctiongradually disrupting the intracellularCa2þ homeostasis, which modulates neuronal excitability and synaptic transmission, making neurons more vulnerable to additional stress, and leading to energy failure and neuronal loss in epilepsy. Antiepileptic drugs (AEDs) also affectmt function in severalways. Theremust be cautionwhen treating epilepsy in patients with known mt disorders as some AEDs are toxic to the mt. This reviewsummarizes our current knowledgeof the effect ofmt disorders onepilepsy, of epileptic seizures onmt, and of AEDsonmt function and the implications of all these interactions for the management of epilepsy in patients with or without mt disease. Semin Pediatr Neurol 20:176-187 C 2013 Elsevier Inc. All rights reserved.