Managing seizures in mitochondrial disorders

Introduction: Epilepsy is a frequent CNS manifestation of syndromic as well as non-syndromic mitochondrial disorders (MIDs). Areas covered: This review summarizes and discusses established knowledge, recent findings, and future perspectives concerning the management of mitochondrial epilepsy. A literature search using appropriate search terms was carried out. Expert opinion: Treatment of epilepsy in MIDs relies on the administration of antiepileptic drugs (AEDs), epilepsy surgery, diet, vagal stimulation, and administration of supportive agents. Mitochondrion-toxic AEDs such as valproic acid (VPA), phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB) may trigger severe or even fatal adverse reactions, but the mitochondrion-toxic effect may vary considerably between patients. Antiepileptic treatment of mitochondrial epilepsy should start with AEDs carrying a low mitochondrion-toxic potential, such as zonisamide (ZNS), levetiracetam (LEV), lamotrigine (LTG), or gabapentin (GBT). In case of ineffectivity or side effects, AEDs with higher mitochondrion-toxic potential can be tried. VPA is the AED with the highest mitochondrion-toxic potential. Since VPA may exhibit deleterious effects, particularly in patients carrying POLG1-mutations or patients with MERRF syndrome, it should be avoided in these conditions. However, mitochondrion-toxic AEDs are indicated in MIDs for intractable seizures under less toxic drugs. Treatment of mitochondrial epilepsy remains a challenge but should be directed by the mitochondrion-toxicity of AEDs and supplemented by diet, antioxidants, and vitamins.