Mahmut Bilal ÇAMAN, Ayşe Özlem AKGÜN, Semai BEK, Gülnihal KUTLU

Hiperammonemi Olmaksızın Valproik Asit ile İlişkili Ensefalopati Olgusu

Valproik asit antiepileptik ajan olarak kullanılan dallı zincirli karboksilik asit yapısında bir ajandır. Yan etkileri; bulantı, kusma, alopesi, kilo alımı, asemptomatik olarak karaciğer fonksiyon testlerinde artış, fulminan hepatit, sedasyon, ataksi, tremor, pankreatit, kardiyak aritmi, trombositopeni, hiperammonemi ve ensefalopati tablosu olarak sıralanabilir. Valproat ile ilişkili ensefalopati sıklıkla bilinç durumunda bozulma, apati, sinirlilik, konfüzyon, karaciğer fonksiyonlarında bozulma ile karakterize bir tablodur. Bu tabloya kan amonyak düzeyinde yükseklik sıklıkla eşlik eder. Daha nadir olarak ise hiperammonemi görülmeden ve serum valproat düzeyine bağlı olmaksızın da ensefalopati tablosu ortaya çıkabilir. Bildirmiş olduğumuz bu olguda tipik klinik bulgular; EEG kayıtları ile desteklenmiş, hastamızda serum amonyak düzeyi normal bulunmuştur ve Hiperammonemi olmaksızın Valproat Ensefalopatisi tanısına ulaşılmıştır. Sonrasında valproat tedavisinin kesilmesinin ardından görülen klinik iyileşme, yine EEG bulgularıyla da ortaya konmuş, tanı desteklenmiştir.

Anahtar Kelimeler:

Encephalopathy, Epilepsy, Non-hyperammonemia, Valproic acid

A Case of Valproic Acid-Associated Encephalopathy without Hyperammonemia

Valproic acid is a branched-chain carboxylic acid construct used as an antiepileptic agent. Side effects can be listed as nausea, vomiting, alopecia, weight gain, asymptomatic increase in liver function tests, fulminant hepatitis, sedation, ataxia, tremor, pancreatitis, cardiac arrhythmia, thrombocytopenia, hyperammonemia and encephalopathy. Valproate-associated encephalopathy is often characterized by impairment in change of consciousness, apathy, irritability, confusion, and impaired liver function. This table is accompanied with a high level of ammonia in the blood. Rarely, encephalopathy may occur without hyperammonemia and irrespective of serum valproate level. Typical clinical findings in this case report were supported by EEG records and serum ammonia level was found to be normal in our patient. Valproate Encephalopathy without Hyperammonemia was diagnosed. Clinical improvement after cessation of valproate treatment was also demonstrated by EEG findings and the diagnosis was supported.

Keywords:

Encephalopathy, Epilepsy, Non-hyperammonemia, Valproic Acid,

PDF

___

1. Perucca E. Pharmacological and therapeutic properties of valproate. Cns Drugs. 2002;16(10):695–714.
2. Blackford MG, Do ST, Enlow TC, Reed MD. Valproic acid and topiramate ınduced hyperammonemic encephalopathy in a patient with normal serum carnitine. J Pediatr Pharmacol Ther. 2013;18(2):128–36.
3. Twilla JD, Pierce AS. Hyperammonemic encephalopathy due to valproic acid and topiramate interaction. Case Rep Psychiatry. 2014;2014:410403.
4. Moore K, Dixit D, Wagner M. Topiramate-related hyperammonemia. J Pharm Technol. 2016;32(1):34– 6.
5. Sin O, Batterink J. Encephalopathy induced by combination theraphy with valproic acid and topiramate: challenging the utility of serum ammonia measurement. Can J Hosp Pharm. 2015;68(1):54-6.
6. Chopra A, Kolla BP, Mansukhani MP, Netzel P, Frye MA. Valproate-induced hyperammonemic encephalopathy: an update on risk factors, clinical correlates and management. Gen Hosp Psychiatry. 2012;34(3):290-8.
7. Raja M, Azzoni A. Valproate-induced hyperammonaemia. J Clin Psychopharmacol. 2002;22(6):631-3.
8. Hamer HM, Knake S, Schomburg U, Rosenow F. Valproate-induced hyperammonemic encephalopathy in the presence of topiramate. Neurology. 2000;54(1):230–2.
9. Deutsch SI, Burket JA, Rosse RB. Valproate-induced hyperammonemic encephalopathy and normal liver functions: possible synergism with topiramate. Clin Neuropharmacol. 2009;32(6):350-2.
10. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-45.
11. Shapira Y, Gutman A. Muscle carnitine deficiency in patients using valproic acid. J Pediatr. 1991;118(4 pt 1):646-9.