Valproate Acid (Depakote) Induced Hyperammonemic Encephalopathy in the Pediatric Populations

Abstract

Valproate acid (Depakote) (VPA) is very effective in the treatment of various illnesses including: seizure disorders, migraine headache prophylaxis, neuralgia, and bipolar disorder. The use of VPA frequently results in elevated plasma levels of ammonia. This is seen despite normal baseline liver function test results in such patients.In this case report, we describe two instances of VPA-induced hyper ammonemic encephalopathy in patients who had supra therapeutic levels of VPA. Family physicians, Child Neurologists, Child Psychiatrists and Pediatricians should be aware of this potential complication, and it is highly recommended to check ammonia levels in patients taking VPA who present with a change in mental status. With a rise in off-label use it is even more important that physicians are made aware of this potential complication. Treatment of VPA-induced hyperammonemic encephalopathy is still under investigation. As of yet, administration of L-carnitine is postulated to have a potential benefit in some cases.VPA has numerous drug interactions and toxicities, including pancreatitis, thrombocytopenia, hepatitis and hyperammonemia. Here are we list two case reports of VPA induced hyperammonemic encephalopathy both occurring in patients with no history of any underlying liver pathologies. In both two cases, both patients were under stable conditions, no comatose. In both 2 cases of patients we described, they all have normal or sub therapeutic level of VPA. Because of the wide spectrum of symptoms associated with Valproate Acid induced Hepatic Encephalopathy (VHE), clinician should be aware of hyperammonenia in differential diagnosis with other common symptoms.Keywords: Seizure disorders; Migraine headache prophylaxis; Child neurologists; Neuralgia Case Report 1A 6 year old girl is brought to the physician due to recent altered mental status. Her immunizations are up to date. The patient's past medical history is unremarkable except for generalized seizure, and she has been generally healthy. The girl has no fever, vomiting or joint pains. She has had no travel, animal exposures or sick contacts. Her medications include Topiramate and Depakote for seizure. Topiramate and Depakote were given within the normal dosing, and both under regular formulation. In the ER, she was nonresponsive to verbal or painful stimuli, her vital signs were normal. Her pupils were equal at 5 mm and her ammonia level was 230 mmol/L (normal value is 10-47), her VPA level was 120 mcg/mL (normal value is 50-100), her AST=18 IU/L, and ALT=20 IU/L. Both level of VPA and Ammonia were performed by high-performance liquid chromatography method (HPLC) with ultraviolet-visible (UV-Vis). The remainder of lab test including hematology panel and urinalysis were normal. For the first 24 hours, the patient remained nonresponsive, after discontinuing VPA and maintenance IV fluid, Ammonia level dropped to 160 mmol/L. Generalized Tonic-Clonic Seizure (GTC) is the diagnosis. Accordingly, EEG showed generalized spikes or sharp waves. Pediatrician wa...

High Blood Ammonia Levels Associated with Long-term Valproic Acids Therapy in Epileptic Children

“…However, although VPA is highly effective in controlling seizure in children, it also has several adverse effects such as fatigue, gastrointestinal disturbances, weight gain, muscle tremors, hair loss, thrombocytopenia, and an increase in hepatic enzymes. 1,2 Other than that, VPA also increases blood ammonia concentrations (hyperammonemia) in adults [3][4][5][6][7] and children [8][9][10][11][12][13][14][15] . The actual increases in blood ammonia concentrations depend on the dose of VPA 4,8 and the use of long-term therapy with VPA 5 .…”