Department of Clinical Neurosciences, Service of Neurology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
CNS Drugs. 2023 Aug;37(8):725-731. doi: 10.1007/s40263-023-01024-5. Epub 2023 Jul 19.
Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown.
The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients.
We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment.
Patients had a mean valproate intravenous loading dose of 34.5 mg/kg and a mean maintenance dose of 15.3 mg/kg/d (1078 mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p = 0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone).
Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases.
丙戊酸诱导的脑病（VIE）在接受长期癫痫治疗的患者中发生率为 0.1%至 2.5%。然而，在癫痫持续状态（SE）的成年患者中，其频率和特征尚不清楚。
本研究旨在描述成年 SE 患者中 VIE 的发生率和临床生物学特征。
我们回顾了 2021 年 11 月至 2023 年 2 月期间纳入我院 SE 登记处的所有接受 SE 治疗的患者，并确定了 39 例接受丙戊酸钠治疗 SE 的患者。急性 VIE 的定义为意识恶化导致丙戊酸钠停药，以及在急性住院治疗期间停药后 96 小时内意识改善。
患者的丙戊酸钠静脉负荷剂量平均为 34.5mg/kg，维持剂量平均为 15.3mg/kg/d（1078mg/d）。有 4 例测量了血氨的患者出现高血氨。我们确定了符合急性 VIE 标准的 4 例（10%）患者。从给予丙戊酸钠到发生 VIE，以及停药后 VIE 缓解的中位时间均为 2 天。4 例 VIE 患者中有 3 例无相关高血氨。发生 VIE 的患者更常患有肝病（p=0.023），且年龄更小，但其他临床变量与无 VIE 的患者无显著差异，包括丙戊酸钠负荷剂量或维持剂量、SE 病因、持续时间或严重程度、其他同时使用的抗癫痫药物（无患者使用托吡酯、苯巴比妥或扑米酮）。
在更大规模的研究中，SE 中的 VIE 似乎相对常见且难以预测；即使没有高血氨，也必须对症状保持临床警惕，并考虑在疑似病例中停用丙戊酸钠。
