Metabolic Brain Disease

, 22:105 | Cite as

Valproic Acid Aggravates Epilepsy due to MELAS in a Patient with an A3243G Mutation of Mitochondrial DNA

  • Chih-Ming Lin
  • Peterus Thajeb
Original Paper


Epilepsy is one of the most common presentations of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is typically caused by an A-to-G substitution at nucleotide position 3243 of mitochondrial DNA. Valproic acid, a common anticonvulsant, can actually increase the frequency of seizures in individuals with MELAS. Here, we report a single case-study of a 38-year-old man who presented with focal seizures and had MELAS Syndrome due to the A3243G mitochondrial DNA mutation. Manifestation of epilepsia partialis continua was aggravated by use of valproic acid. Convulsions abated after discontinuation of valproic acid. Our experience suggests that valproic acid should be avoided for the treatment of epilepsy in individuals with mitochondrial disease.


Epilepsy Mitochondrial disease Valproate Valproic acid MELAS 


  1. Altrup U, Gerlach G, Reith H, Said MN, Speckmann EJ (1992) Effects of valproate in model nervous system (buccal ganglia of Helix pomatia): I. Antiepileptic actions. Epilepsia 33:743–752PubMedCrossRefGoogle Scholar
  2. Altrup U, Reith H, Speckmann EJ (1992) Effects of valproate in a model nervous system (buccal ganglia of Helix pomatia): II. Epileptogenic actions. Epilepsia 33:753–759PubMedCrossRefGoogle Scholar
  3. Aure K, Jardel C, Lombes A (2005) Mitochondrial diseases: Molecular mechanisms, clinical presentations and diagnosis investigations. Ann Pathol 25:270–281PubMedGoogle Scholar
  4. Chabrol B, Mancini J, Chretien D, Rustin P, Munnich A, Pinsard N (1994) Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency. Eur J Pediatr 153:133–135PubMedGoogle Scholar
  5. Chinnery PF, Howell N, Lightowlers RN, Tumball DM (1997) Molecular pathology of MELAS and MERRF: The relationship between mutation load and clinical phenotypes. Brain 120:1713–1721PubMedCrossRefGoogle Scholar
  6. Dimauro S, Davidzon G (2005) Mitochondrial DNA and disease. Ann Med 37:222–232PubMedCrossRefGoogle Scholar
  7. Krahenbuhl S, Brandner S, Kleinle S, Liechti S, Straumann D (2000) Mitochondrial diseases represent a risk factor for valproate-induced fulminant liver failure. Liver 20:346–348PubMedCrossRefGoogle Scholar
  8. Kunz WS (2002) The role of mitochondria in epileptogenesis. Curr Opin Neurol 15:179–184PubMedCrossRefGoogle Scholar
  9. Lam CW, Lau CH, Williams JC, Chan YW, Wong LJ (1997) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy. Eur J Pediatr 156:562–564PubMedCrossRefGoogle Scholar
  10. Liou CW, Huang CC, Chee EC, Jong YJ, Tsai JL, Pang CY, Lee HC, Wei YH (1994) MELAS Syndrome: Correlation between clinical features and molecular genetic analysis. Acta Neurol Scand 90:354–359PubMedCrossRefGoogle Scholar
  11. Morris AA (1999) Mitochondrial respiratory chain disorders and the liver. Liver 19:357–368PubMedCrossRefGoogle Scholar
  12. Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP (1984) Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: A distinctive clinical syndrome. Ann Neurol 16:481–488PubMedCrossRefGoogle Scholar
  13. Ponchaut S, Van Hoof F, Veitch K (1992) Cytochrome aa3 depletion is the cause of the deficient mitochondrial respiration induced by chronic valproate administration. Biochem Pharmacol 43:644–647PubMedCrossRefGoogle Scholar
  14. Ponchaut S, Van Hoof F, Veitch K (1995) Valproate and cytochrome c oxidase deficiency. Eur J Pediatr 154:79PubMedCrossRefGoogle Scholar
  15. Scaglia F, Northrop JP (2006) The mitochondrial myopathy encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome: A review of treatment options. CNS Drugs 20:443–464PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of NeurologyMackay Memorial HospitalTaipeiTaiwan

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