Antiepileptic treatment and blood lactate level alteration in patients with myoclonic epilepsy with ragged-red fi bers (MERRF) syndrome in a Chinese family

Background: Myoclonic epilepsy with ragged-red fi bers (MERRF) is a type of mitochondrial encephalomyopathy, clinical experience with the antiepileptic treatment for myoclonus in MERRF is still limited. Myoclonus appears to be intractable, and some antiepileptic drugs may change the blood lactate level. Objective: In this study, we report on two patients, a girl and her mother, both with MERRF in a Chinese family. We aimed to study their myoclonus attack, response to AEDs and blood lactate level. Methods: The diagnosis was based on muscle biopsies and a genetic test. We recorded their myoclonus and detected alterations of blood lactate when the patients received antiepileptic drugs. Results: The patients displayed substantial differences in their responses to antiepileptic drugs. The mother exhibited a good response to valproic acid, although valproic acid is not recommended for mitochondrial disease; however, her daughter was refractory to many antiepileptic drugs until she received a combination treatment of levetiracetam and topiramate. We did not fi nd valproic acid, levetiracetam or topiramate affected the blood lactate levels. Conclusion: These fi ndings imply that not all MERRF patients are resistant to antiepileptic drugs, and for those who are intractable, combination treatment involving levetiracetam and topiramate may be effective for treating myoclonus in MERRF and does not worsen lactic acidosis. Neurology Asia 2013; 18(1) : 47 – 51 Address correspondence to: Dr. Xuefeng Wang, Department of Neurology, The First Affi liated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 You Yi Road, Chongqing 400016, China (tel.: 86 23 89012878; fax: 86 23 68708697; e-mail: [email protected]). INTRODUCTION Myoclonic epilepsy with ragged-red fibers (MERRF) is a type of mitochondrial encephalomyopathy; its clinical features include myoclonic epilepsy, ataxia, weakness, hearing loss, lactic acidosis and ragged-red fibers discovered in muscle. Short stature, optic atrophy and cardiomyopathy are also found in MERRF, as in other mitochondrial encephalomyopathies. Approximately 80% of patients with MERRF have a family history of the disease, and the mode of inheritance is compatible with maternal inheritance, although not all maternal relatives were affected, and not all those who were affected exhibit the same symptoms. The use of antiepileptic drugs (AEDs) for the treatment for myoclonus and seizures is an important symptomatic therapy for the management of MERRF. However, AED treatment of MERRF is challenging because it has not been investigated in randomized controlled study. Therefore, its underlying biochemical mechanisms are not well understood, and the treatment of myoclonus in MERRF is largely based on anecdotal evidence. Previous studies have demonstrated the poor efficacy of valproic acid (VPA), phenytoin (PHT), phenobarbital (PB) and clonazepam in myoclonus in MERRF. Thus, myoclonus appears to be intractable to conventional treatments. In addition, many drugs, including PB, VPA and PHT, have negative effects on mitochondrial function. VPA can inhibit carnitine uptake and induce fulminant liver failure. Studies have also shown that VPA can worsen epilepsy due to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Recently, levetiracetam (LEV) was reported to be effective against seizures that resulted from MERRF. However, small samples of patients were recruited in those studies, and not all of the patients exhibited satisfactory response to LEV. Lactic acidosis is one of the key features of MERRF and is toxic to all types of cells; therefore, any medication that causes or increases lactic acidosis may be detrimental to the body. However, in vivo and in vitro studies have shown that many AEDs, including carbamazepine (CBZ), PB, and VPA, could lead to changes in the blood Neurology Asia March 2013 48 lactate level. An overdose of lamotrigine or VPA can also increase the lactate level. Hence, in this study, we aimed to investigate the lactate levels in a MERRF pedigree in response to VPA, topiramate (TPM) and LEV. Our study subjects consisted of 2 patients with MERRF in a Chinese family, a girl and her mother. The diagnosis was based on muscle biopsies and genetic test. We report here the response of the myoclonus to the different AEDs, and the effect of the AEDs on blood lactate level.