Metabolic Crisis Induced by Antiepileptic Drugs in Patients with Mitochondrial Epilepsy : The Effect of Valproic Acid, Topiramate and Propofol on Mitochondrial Function

Abstract: Mitochondria are important cytosolic organelles present in nearly all eukaryotic cells. The main function of mitochondria are to generate the vast majority of ATP through the process of oxidative phosphorylation. Mitochondria have key roles regarding other systems in the body as well, such as regulation of apoptosis, calcium homeostasis, reactive oxygen production etc. Mitochondrial diseases are caused by impaired mitochondrial function, originating from mutations in either the mitochondrial DNA or the nuclear DNA. Epilepsy is a common symptom of mitochondrial disease, especially in children. The pathophysiology behind mitochondrial epilepsy is primarily based on ATP deficit, leading to a negative effect on a range of different nervous system related functions that in the end leads to seizures. The study aimed to investigate the effect on mitochondrial respiration of two commonly used antiepileptic drugs, namely valproic acid and Topiramate, and the anesthesic drug propofol, commonly used in case of refractory status epilepticus. The three drugs were titrated in different concentrations in a high-resolution respirometer from Oroboros Instruments (n=6). Propofol seemed especially inhibiting of mitochondrial function, and both propofol and topiramate had a significant decrease in mitochondrial respiration within the clinical concentrations. The result of the study supported research stating that propofol should be used with caution in patients with a mitochondrial disease, but further research should be done regarding all three drugs in order to draw definite conclusions.