{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:26:15Z","timestamp":1791516375297,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T00:00:00Z","timestamp":1360800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,6]]},"abstract":"Summary<\/jats:title>Purpose<\/jats:title>To identify risk factors for hyperammonemia in pediatric patients with epilepsy.<\/jats:p><\/jats:sec>Methods<\/jats:title>A total of 2,944 pediatric patients (ages 0\u201315\u00a0years) were classified into the following three groups: a group without drug treatment (n\u00a0=\u00a0445, group I<\/jats:styled-content>), a group receiving antiepileptic drugs other than valproic acid (VPA<\/jats:styled-content>) (n\u00a0=\u00a0673, group II<\/jats:styled-content>), and a VPA<\/jats:styled-content>\u2010treated group (n\u00a0=\u00a01,826, group III<\/jats:styled-content>). Hyperammonemia was defined as a plasma ammonia level exceeding 100\u00a0\u03bcg\/dl with reference to the standard range and previous reports.<\/jats:p><\/jats:sec>Key Findings<\/jats:title>The mean ammonia level of groups I, II<\/jats:styled-content>, and III<\/jats:styled-content> was 36.0, 56.0, and 86.8\u00a0\u03bcg\/dl, respectively, and the incidence of hyperammonemia was 1.6%, 7.7%, and 31.7%, respectively. In each group, the mean ammonia level of patients aged 3\u00a0years or younger was significantly higher than that of patients aged 4\u201315\u00a0years. In group II<\/jats:styled-content>, concomitant use of topiramate and zonisamide were risk factors for hyperammonemia (adjusted odds ratio [OR<\/jats:styled-content>] 3.9, 95% confidence interval [CI<\/jats:styled-content>] 1.7\u20139.2, and OR<\/jats:styled-content> 3.5, 95% CI<\/jats:styled-content> 1.9\u20136.5, respectively). In group III<\/jats:styled-content>, the ammonia level increased in a VPA<\/jats:styled-content> dose\u2013dependent manner. At a VPA<\/jats:styled-content> dose of 30\u00a0mg\/kg, there was 4.3\u2010fold increase in the incidence of hyperammonemia. The other significant risk factors identified were female gender (OR<\/jats:styled-content> 1.3, 95% CI<\/jats:styled-content> 1.0\u20131.6), symptomatic generalized epilepsy (OR<\/jats:styled-content> 1.4, 95% CI<\/jats:styled-content> 1.1\u20131.8), and the concomitant use of phenytoin (OR<\/jats:styled-content> 4.7, 95% CI<\/jats:styled-content> 3.3\u20136.9), phenobarbital (OR<\/jats:styled-content> 2.2. 95% CI<\/jats:styled-content> 1.6\u20133.2), acetazolamide (OR<\/jats:styled-content> 6.6, 95% CI<\/jats:styled-content> 2.5\u201317.2), topiramate, or zonisamide.<\/jats:p><\/jats:sec>Significance<\/jats:title>A young age and concomitant use of carbonic anhydrase inhibitors are associated with an increased risk of hyperammonemia regardless of whether the patient is taking VPA<\/jats:styled-content>. In patients receiving VPA<\/jats:styled-content>, concomitant use of phenytoin and\/or phenobarbital enhances the risk of hyperammonemia. An increase in ammonia can be caused by multiple factors. Our results may help clinicians to avoid problems of hyperammonemia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12125","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T17:25:55Z","timestamp":1360862755000},"page":"983-989","source":"Crossref","is-referenced-by-count":49,"title":["Risk factors for hyperammonemia in pediatric patients with epilepsy"],"prefix":"10.1111","volume":"54","author":[{"given":"Yoshiaki","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Clinical Research National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka Japan"},{"name":"Department of Clinical Pharmaceutics Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukitoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Research National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Clinical Research National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Clinical Research National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Yazawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Genetics Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka 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