Department of Neurology, Konkuk University School of Medicine, Seoul, the Republic of Korea.
Department of Neurology, Konkuk University School of Medicine, Seoul, the Republic of Korea.
Clin Neurol Neurosurg. 2023 Oct;233:107962. doi: 10.1016/j.clineuro.2023.107962. Epub 2023 Sep 6.
Hyperammonemia can occur after acute overdose or chronic use of valproic acid (VPA). Although VPA-related hyperammonemic encephalopathy (VHE) is a rare complication of VPA therapy, early recognition of VHE and identifying its risk factors are important because VHE can lead to loss of consciousness and increased seizure frequency.
The purpose of our study is to evaluate the risk factors of hyperammonemia in epilepsy patients during treatment with VPA therapy.
We reviewed the medical records of 1084 adult patients with epilepsy and enrolled 116 patients with VPA therapy who had results of blood levels of ammonia over a 3-year period. Hyperammonemia was defined as a blood ammonia level exceeding 80 µg/dL. Correlations of blood levels of ammonia with dosages and blood levels of VPA were evaluated. We further performed univariate and multivariate linear regression analyses to identify risk factors for hyperammonemia in epilepsy patients treated with VPA therapy.
Blood levels of ammonia were well correlated with dosages of VPA (p = 0.036), but not with blood levels of VPA (p = 0.463). Hyperammonemia was more common in patients with higher VPA dosage and higher total drug loads of concurrent antiseizure medications (ASMs). Hyperammonemia was also associated with the use of topiramate and phenobarbital. In multivariate analysis, we identified total drug load of ASMs (p = 0.003) and use of topiramate (p = 0.007) as independent predictors of hyperammonemia. Four patients (4/116, 3.4 %) had clinical symptoms of VHE. Three of them had hyperammonemia while the other patient had normal blood level of ammonia with a high blood level of VPA.
Our study shows that higher total drug loads of concurrent ASMs and use of topiramate were independent risk factors of hyperammonemia in epilepsy patients with VPA therapy. Although the incidence of VHE was not high in our study, clinicians should be aware of this potential adverse effect of VPA therapy, especially in patients with polytherapy of ASMs including topiramate.
急性过量或慢性使用丙戊酸（VPA）后可能会发生高血氨症。尽管 VPA 相关高氨血症性脑病（VHE）是 VPA 治疗的罕见并发症，但早期识别 VHE 并确定其危险因素很重要，因为 VHE 可导致意识丧失和癫痫发作频率增加。
本研究旨在评估 VPA 治疗中癫痫患者高氨血症的危险因素。
我们回顾了 1084 例成年癫痫患者的病历，并纳入了 116 例 VPA 治疗期间血氨水平超过 3 年的患者。高血氨症定义为血氨水平超过 80μg/dL。评估了血氨水平与 VPA 剂量和血药浓度的相关性。我们进一步进行了单变量和多变量线性回归分析，以确定 VPA 治疗的癫痫患者高氨血症的危险因素。
血氨水平与 VPA 剂量呈良好相关性（p=0.036），但与 VPA 血药浓度无关（p=0.463）。高 VPA 剂量和更高的合并抗癫痫药物（ASM）总药物负荷的患者更常发生高氨血症。高氨血症也与托吡酯和苯巴比妥的使用有关。多变量分析中，我们确定 ASM 总药物负荷（p=0.003）和托吡酯的使用（p=0.007）是高氨血症的独立预测因素。4 名患者（4/116，3.4%）出现 VHE 的临床症状。其中 3 名患者发生高氨血症，而另 1 名患者血氨水平正常但 VPA 血药浓度升高。
本研究表明，更高的合并 ASM 总药物负荷和使用托吡酯是 VPA 治疗癫痫患者高氨血症的独立危险因素。尽管本研究中 VHE 的发生率不高，但临床医生应意识到 VPA 治疗的这种潜在不良反应，尤其是在包括托吡酯在内的 ASM 多药治疗的患者中。
