Umesh Vivekananda1, Simona Balestrini2,3,4, Angeliki Vakrinou1,5, Elaine Murphy6, Sanjay M Sisodiya1,5. 1. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK. 2. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK. s.balestrini@ucl.ac.uk. 3. Chalfont Centre for Epilepsy, Gerrards Cross, SL9 0RJ, UK. s.balestrini@ucl.ac.uk. 4. Neuroscience Department, Children's Hospital Meyer-University of Florence, Florence, Italy. s.balestrini@ucl.ac.uk. 5. Chalfont Centre for Epilepsy, Gerrards Cross, SL9 0RJ, UK. 6. Charles Dent Metabolic Unit, The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Abstract
BACKGROUND: Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear. OBJECTIVE: To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes. METHODS: We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia. RESULTS: We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment. CONCLUSIONS: Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.
BACKGROUND: Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear. OBJECTIVE: To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes. METHODS: We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia. RESULTS: We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment. CONCLUSIONS: Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.
Authors: Cátia C P Aires; Arno van Cruchten; Lodewijk Ijlst; Isabel Tavares de Almeida; Marinus Duran; Ronald J A Wanders; Margarida F B Silva Journal: J Hepatol Date: 2010-12-13 Impact factor: 25.083
Authors: Wendy Smith; Priya S Kishnani; Brendan Lee; Rani H Singh; William J Rhead; Lisa Sniderman King; Michael Smith; Marshall Summar Journal: Crit Care Clin Date: 2005-10 Impact factor: 3.598