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Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

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Abstract

Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 μmol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes.

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References

  1. Altunbasak S, Baytok V, Tasouji M et al (1997) Asymptomatic hyperammonemia in children treated with valproic acid. J Child Neurol 12:461–463

    CAS  PubMed  Google Scholar 

  2. Lee WL, Yang CC, Deng JF, Chen YF, Lin HD, Wang PH (1998) A case of severe hyperammonemia and unconsciousness following sodium valproate intoxication. Vet Hum Toxicol 40:346–348

    CAS  PubMed  Google Scholar 

  3. Barrueto F Jr, Hack JB (2001) Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy. Acad Emerg Med 8:999–1001

    PubMed  Google Scholar 

  4. Feil D, Chuang K, Sultzer DL (2002) Valproate-induced hyperammonemia as a cause of altered mental status. Am J Geriatr Psychiatry 10:476–478

    Article  PubMed  Google Scholar 

  5. Spiller HA, Krenzelok EP, Klein-Schwartz W et al (2000) Multicenter case series of valproic acid ingestion: serum concentrations and toxicity. J Toxicol Clin Toxicol 38:755–760

    Article  CAS  PubMed  Google Scholar 

  6. Duarte J, Macias S, Coria F, Fernandez E, Claveria LE (1993) Valproate-induced coma: case report and review of the literature. Ann Pharmacother 27:582–583

    CAS  PubMed  Google Scholar 

  7. Guérit JM, de Tourtchaninoff M, Soveges L, Mahieu P (1993) The prognostic value of three-modality evoked potentials (TMEPs) in anoxic and traumatic comas. Neurophysiol Clin 23:209–226

    CAS  PubMed  Google Scholar 

  8. Sztajnkrycer MD (2002) Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol 40:789–801

    Article  CAS  PubMed  Google Scholar 

  9. Ratnaike RN, Schapel GJ, Purdie G, Rischbieth RH, Hoffmann S (1986) Hyperammonaemia and hepatotoxicity during chronic valproate therapy: enhancement by combination with other antiepileptic drugs. Br J Clin Pharmacol 22:100–103

    CAS  PubMed  Google Scholar 

  10. Hamer HM, Knake S, Schomburg U, Rosenow F (2000) Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology 54:230–232

    Article  CAS  PubMed  Google Scholar 

  11. Dupuis RE, Lichtman SN, Pollack GM (1990) Acute valproic acid overdose: clinical course and pharmacokinetic disposition of valproic acid and metabolites. Drug Saf 5:65–71

    CAS  Google Scholar 

  12. Khoo SH, Leyland MJ (1992) Cerebral edema following acute sodium valproate overdose. J Toxicol Clin Toxicol 30:209–214

    CAS  PubMed  Google Scholar 

  13. Triggs WJ, Gilmore RL, Millington DS, Cibula J, Bunch TS, Harman E (1997) Valproate-associated carnitine deficiency and malignant cerebral edema in the absence of hepatic failure. Int J Clin Pharmacol Ther 35:353–356

    CAS  PubMed  Google Scholar 

  14. Baganz MD, Dross PE (1994) Valproic acid-induced hyperammonemic encephalopathy: MR appearance. Am J Neuroradiol 15:1779–1781

    CAS  PubMed  Google Scholar 

  15. Ziyeh S, Thiel T, Spreer J, Klisch J, Schumacher M (2002) Valproate-induced encephalopathy: assessment with MR imaging and 1H MR spectroscopy. Epilepsia 43:1101–1105

    Article  PubMed  Google Scholar 

  16. Schaefer PW, Grant PE, Gonzalez RG (2000) Diffusion-weighted MR imaging of the brain. Radiology 217:331–345

    CAS  PubMed  Google Scholar 

  17. Wieshmann UC, Symms MR, Shorvon SD (1997) Diffusion changes in status epilepticus. Lancet 350:493–494

    CAS  Google Scholar 

  18. Collins RM Jr, Zielke HR, Woody RC (1994) Valproate increases glutaminase and decreases glutamine synthetase activities in primary cultures of rat brain astrocytes. J Neurochem 62:1137–1143

    CAS  PubMed  Google Scholar 

  19. Blindauer KA, Harrigton G, Morris GL III, Ho KC (1998) Fulminant progression of demyelinating disease after valproate-induced encephalopathy. Neurology 51:292–295

    CAS  PubMed  Google Scholar 

  20. Rovira A, Cordoba J, Raguer N, Alonso J (2002) Magnetic resonance imaging measurement of brain edema in patients with liver disease: resolution after transplantation. Curr Opin Neurol 15:731–737

    Article  PubMed  Google Scholar 

  21. Dolman CL, Clasen RA, Dorovini-Zis K (1988) Severe cerebral damage in ornithine transcarbamylase deficiency. Clin Neuropathol 7:10–15

    CAS  PubMed  Google Scholar 

  22. Mirowitz SA, Saitor K, Prensky AJ, Gado M, Hodges FJ (1991) Neurodegenerative diseases of childhood: MR and CT evaluation. J Comput Assist Tomogr 15:210

    Google Scholar 

  23. Mamourian AC, du Plessis A (1991) Urea cycle defect: a case with MR and CT findings resembling infarct. Pediatr Radiol 21:594–595

    CAS  PubMed  Google Scholar 

  24. Takanashi J, Barkovich J, Cheng S, Kostiner D, Baker J, Packman S (2003) Brain MR imaging in acute hyperammonemic encephalopathy arising from late-onset ornithine transcarbamylase deficiency. Am J Neuroradiol 24:390–393

    PubMed  Google Scholar 

  25. Chen YF, Huang YC, Liu HM, Hwu WL (2001) MRI in a case of adult-onset citrullinemia. Neuroradiology 43:845–847

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Philippe Hantson.

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Hantson, P., Grandin, C., Duprez, T. et al. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma. Eur Radiol 15, 59–64 (2005). https://doi.org/10.1007/s00330-004-2338-9

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  • DOI: https://doi.org/10.1007/s00330-004-2338-9

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